Latest from Thorax

Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the {beta}2 agonist vilanterol administered once daily for 52 weeks in patients >=12 years old with asthma: a randomised trial [ASTHMA]

Sat, 1 Jun 2013 00:00:00 +0000

BackgroundThe inhaled corticosteroid fluticasone furoate (FF) in combination with the long-acting {beta}2 agonist vilanterol (VI) is in development for asthma and chronic obstructive pulmonary disease. ObjectiveTo assess the safety and tolerability of FF/VI over 52 weeks in patients with asthma. MethodsPatients (aged [≥]12 years; on inhaled corticosteroid) were randomised (2:2:1) to FF/VI 100/25 {micro}g or FF/VI 200/25 {micro}g once daily in the evening, or fluticasone propionate (FP) 500 {micro}g twice daily. Safety evaluations included adverse events (AEs), non-fasting glucose, potassium, 24-h urinary cortisol excretion, ophthalmic assessments, heart rate and pulse rate. ResultsOn-treatment AEs were similar across groups (FF/VI 66-69%; 73% FP). Oral candidiasis/oropharyngeal candidiasis was more common with FF/VI (6-7%) than FP (3%). Twelve serious AEs were reported; one (worsening hepatitis B on FP) was considered drug related. Statistically significant cortisol suppression was seen with FP compared with both FF/VI groups at Weeks 12 and 28 (ratios [95% CI] to FP ranged from 1.43 [1.11 to 1.84] to 1.67 [1.34 to 2.08]; p[≤]0.006), but not at Week 52 (ratios to FP were 1.05 [0.83 to 1.33] for FF/VI 100/25 {micro}g and 1.09 [0.87 to 1.38] for FF/VI 200/25 {micro}g). No clinically important changes in non-fasting glucose, potassium, QT interval corrected using Fridericia's formula (QTc[F]) or ophthalmic assessments were reported. Pulse rate (10 min post dose [Tmax], Week 52) was significantly increased with FF/VI versus FP (3.4 bpm, 95% CI 1.3 to 5.6; p=0.002 [FF/VI 100/25 {micro}g]; 3.4 bpm, 95% CI 1.2 to 5.6; p=0.003 [FF/VI 200/25 {micro}g]). Mean heart rate (24-h Holter monitoring) decreased from screening values in all groups (0.2-1.1 bpm FF/VI vs 5 bpm FP; Week 52). ConclusionsFF/VI (100/25 {micro}g or 200/25 {micro}g) administered once daily over 52 weeks was well tolerated by patients aged [≥]12 years with asthma. The overall safety profile of FF/VI did not reveal any findings of significant clinical concern. ClinicalTrials.govNCT01018186

Impact of the Tohoku earthquake and tsunami on pneumonia hospitalisations and mortality among adults in northern Miyagi, Japan: a multicentre observational study [EPIDEMIOLOGY]

Sat, 1 Jun 2013 00:00:00 +0000

BackgroundOn 11 March 2011, the Tohoku earthquake and tsunami struck off the coast of northeastern Japan. Within 3 weeks, an increased number of pneumonia admissions and deaths occurred in local hospitals. MethodsA multicentre survey was conducted at three hospitals in Kesennuma City (population 74 000), northern Miyagi Prefecture. All adults aged [≥]18 years hospitalised between March 2010 and June 2011 with community-acquired pneumonia were identified using hospital databases and medical records. Segmented regression analyses were used to quantify changes in the incidence of pneumonia. ResultsA total of 550 pneumonia hospitalisations were identified, including 325 during the pre-disaster period and 225 cases during the post-disaster period. The majority (90%) of the post-disaster pneumonia patients were aged [≥]65 years, and only eight cases (3.6%) were associated with near-drowning in the tsunami waters. The clinical pattern and causative pathogens were almost identical among the pre-disaster and post-disaster pneumonia patients. A marked increase in the incidence of pneumonia was observed during the 3-month period following the disaster; the weekly incidence rates of pneumonia hospitalisations and pneumonia-associated deaths increased by 5.7 times (95% CI 3.9 to 8.4) and 8.9 times (95% CI 4.4 to 17.8), respectively. The increases were largest among residents in nursing homes followed by those in evacuation shelters. ConclusionsA substantial increase in the pneumonia burden was observed among adults after the Tohoku earthquake and tsunami. Although the exact cause remains unresolved, multiple factors including population aging and stressful living conditions likely contributed to this pneumonia outbreak.

Metformin reduces airway glucose permeability and hyperglycaemia-induced Staphylococcus aureus load independently of effects on blood glucose [RESPIRATORY INFECTION]

Fri, 24 May 2013 00:00:00 +0000

BackgroundDiabetes is a risk factor for respiratory infection, and hyperglycaemia is associated with increased glucose in airway surface liquid and risk of Staphylococcus aureus infection. ObjectivesTo investigate whether elevation of basolateral/blood glucose concentration promotes airway Staphylococcus aureus growth and whether pretreatment with the antidiabetic drug metformin affects this relationship. MethodsHuman airway epithelial cells grown at air-liquid interface ({+/-}18 h pre-treatment, 30 M-1 mM metformin) were inoculated with 5x105 colony-forming units (CFU)/cm2 S aureus 8325-4 or JE2 or Pseudomonas aeruginosa PA01 on the apical surface and incubated for 7 h. Wild-type C57BL/6 or db/db (leptin receptor-deficient) mice, 6-10 weeks old, were treated with intraperitoneal phosphate-buffered saline or 40 mg/kg metformin for 2 days before intranasal inoculation with 1x107 CFU S aureus. Mice were culled 24 h after infection and bronchoalveolar lavage fluid collected. ResultsApical S aureus growth increased with basolateral glucose concentration in an in vitro airway epithelia-bacteria co-culture model. S aureus reduced transepithelial electrical resistance (RT) and increased paracellular glucose flux. Metformin inhibited the glucose-induced growth of S aureus, increased RT and decreased glucose flux. Diabetic (db/db) mice infected with S aureus exhibited a higher bacterial load in their airways than control mice after 2 days and metformin treatment reversed this effect. Metformin did not decrease blood glucose but reduced paracellular flux across ex vivo murine tracheas. ConclusionsHyperglycaemia promotes respiratory S aureus infection, and metformin modifies glucose flux across the airway epithelium to limit hyperglycaemia-induced bacterial growth. Metformin might, therefore, be of additional benefit in the prevention and treatment of respiratory infection.

Against all odds: anti-IgE for intrinsic asthma? [CHEST CLINIC]

Fri, 24 May 2013 00:00:00 +0000

For many years, pathogenetic concepts and the results of clinical trials supported the view that anti-IgE treatment is specifically effective in allergic asthma. However, there is now growing clinical and mechanistic evidence suggesting that treatment with the anti-IgE antibody omalizumab can be effective in patients with intrinsic asthma. Therefore, large and well-controlled clinical trials with anti-IgE are urgently warranted in patients with intrinsic asthma. In addition, there is a need to find new biomarkers which can identify patients with asthma who respond to anti-IgE treatment.

Asthma mortality in Australia in the 21st century: a case series analysis [RESEARCH]

Thu, 23 May 2013 00:00:00 +0000

ObjectiveAs previous asthma mortality studies were undertaken between 1986 and 1997, and treatments have evolved since that time, in order to direct future asthma interventions, we investigated the reasons for asthma deaths between 2005 and 2009. DesignWe undertook a case series analysis by searching the National Coroners' Information System using the most recent International Classification of Diseases-10 codes J45 and J46 and the keyword asthma' as the underlying cause of death. SettingRecords for 283 cases aged 70 years and under were retrieved from each Australian state and territory. Coroner's findings, autopsy, toxicology and police reports were reviewed to determine: if the team agreed the death was due to asthma and whether the death was preventable or modifiable factors existed? Owing to the likelihood of comorbidities or alternative diagnoses contributing to deaths in those over 70 years of age, this group was excluded. ResultsExamination of available data in those aged under 70 years identified risk factors associated with asthma death. These included physical barriers (rural and remote location, institutionalised care), psychosocial issues (social disengagement, mental illness, living alone, being unemployed), smoking, drug and alcohol dependence, allergies, respiratory tract infections, inadequate treatment and delay in seeking help. ConclusionsOur study provides a current assessment of death from asthma across Australia. Further reductions in the rate of asthma deaths will require interventions targeted at the personal, practice and policy levels. Asthma-related health literacy needs to be improved especially among those with episodic asthma. Reforms are also needed to address inequity in healthcare delivery to reach the unreached'. Our study points to the dangers associated with smoking, drug and alcohol use and the consequences of delay in seeking care among those with asthma.

Nocturnal sweating--a common symptom of obstructive sleep apnoea: the Icelandic sleep apnoea cohort [RESEARCH]

Tue, 14 May 2013 00:00:00 +0000

ObjectivesTo estimate the prevalence and characteristics of frequent nocturnal sweating in obstructive sleep apnoea (OSA) patients compared with the general population and evaluate the possible changes with positive airway pressure (PAP) treatment. Nocturnal sweating can be very bothersome to the patient and bed partner. DesignCase-control and longitudinal cohort study. SettingLandspitali--The National University Hospital, Iceland. ParticipantsThe Icelandic Sleep Apnea Cohort consisted of 822 untreated patients with OSA, referred for treatment with PAP. Of these, 700 patients were also assessed at a 2-year follow-up. The control group consisted of 703 randomly selected subjects from the general population. InterventionPAP therapy in the OSA cohort. Main outcome measuresSubjective reporting of nocturnal sweating on a frequency scale of 1-5: (1) never or very seldom, (2) less than once a week, (3) once to twice a week, (4) 3-5 times a week and (5) every night or almost every night. Full PAP treatment was defined objectively as the use for [≥]4 h/day and [≥]5 days/week. ResultsFrequent nocturnal sweating ([≥]3x a week) was reported by 30.6% of male and 33.3% of female OSA patients compared with 9.3% of men and 12.4% of women in the general population (p<0.001). This difference remained significant after adjustment for demographic factors. Nocturnal sweating was related to younger age, cardiovascular disease, hypertension, sleepiness and insomnia symptoms. The prevalence of frequent nocturnal sweating decreased with full PAP treatment (from 33.2% to 11.5%, p<0.003 compared with the change in non-users). ConclusionsThe prevalence of frequent nocturnal sweating was threefold higher in untreated OSA patients than in the general population and decreased to general population levels with successful PAP therapy. Practitioners should consider the possibility of OSA in their patients who complain of nocturnal sweating.

Patients' with obstructive sleep apnoea syndrome (OSAS) preferences and demand for treatment: a discrete choice experiment [POSTSCRIPT]

Wed, 1 May 2013 00:00:00 +0000

RationaleDespite its high level of effectiveness, initial acceptance of continuous positive airway pressure (CPAP) and regular use in patients with obstructive sleep apneoa syndrome (OSAS) are still an issue. Alternatively, oral appliances (OAs) can be recommended. To improve patient engagement in their treatment, physicians are advised to take into account patient preferences and to share the therapeutic decision. We aimed to determine patients' preferences for OSAS treatment-related attributes, and to predict patients' demand for both CPAP and OAs. MethodsA discrete choice experiment (DCE) was performed in 121 newly diagnosed patients consecutively recruited in a sleep unit. ResultsRegression parameters were the highest for impact on daily life and effectiveness ahead of side effects. In the French context, the demanding probabilities for CPAP and OAs were 60.2% and 36.2%, respectively. They were sensitive to the variation in the amount of out-of-pocket expenses for both CPAP and OAs. ConclusionsThis first DCE in OSAS emphasises the importance to communicate with patients before the implementation of treatment.

Fever, splenomegaly and lymphopenia in sarcoidosis [CHEST CLINIC]

Wed, 1 May 2013 00:00:00 +0000

Clinical presentation Clinical presentation Question Answer References A 42-year-old woman was referred to our department with a 5 months history of intermittent fever and fatigue. Her past medical history included a consolidated diagnosis of sarcoidosis (obtained 7 years before with a sub-carinal lymph node biopsy) and in the previous years she had been treated with steroids, hydroxychloroquine, methotrexate and azathioprine with persistent and progressive enlargement of mediastino-hilar adenopathies and bilateral nodular infiltrates. Her symptoms progressed despite a course of antibiotics prescribed for presumed community-acquired pneumonia and a course of corticosteroids. The patient lived in Italy and there was no history of travels or other additional risk factors for infections. At the time of admission, the patient had a temperature of 38.5{degrees}C and the physical ...

Which patients with chronic obstructive pulmonary disease benefit from the addition of an inhaled corticosteroid to their bronchodilator? A cluster analysis [RESEARCH]

Mon, 22 Apr 2013 00:00:00 +0000

ObjectiveTo identify subsets of chronic obstructive pulmonary disease (COPD) patients who are more protected from exacerbations with the use of an inhaled corticosteroid/long-acting {beta}2 agonist (ICS/LABA) combination, compared with the use of LABA monotherapy. DesignPost hoc cluster analysis of patients from two randomised clinical trials of salmeterol/fluticasone propionate (SFC) and salmeterol (SAL) that had primary endpoints of moderate/severe exacerbation rates. SettingCentres in North America. Participants1543 COPD patients were studied. InterventionsSFC 50/250 {micro}g or SAL 50 {micro}g, twice daily. Primary and secondary outcome measuresThe analysis identified clusters of COPD patients more responsive to SFC versus SAL with respect to the annual rate of moderate/severe exacerbations and compared their baseline clinical characteristics. ResultsOverall, SFC significantly reduced the annual rate of moderate/severe exacerbations as compared with SAL alone (rate ratio (RR)=0.701, p<0.001). Three-patient clusters were identified: COPD patients receiving diuretics (RR=0.56, p<0.001); patients not receiving diuretics but with forced expiratory volume in 1 s (FEV1) reversibility [≥]12% (RR=0.67, p<0.001) exhibited a substantial reduction in the annual rate of moderate/severe exacerbations relative to SAL. A third cluster, consisting of patients not receiving diuretics and without FEV1 reversibility, demonstrated no difference for SFC versus SAL. Patients receiving diuretics had a significantly higher prevalence of comorbid cardiovascular disease. ConclusionsCOPD patients receiving diuretics and those not receiving diuretics but with FEV1 reversibility >12% at baseline were significantly more likely to experience a reduction in COPD-associated exacerbations with SFC versus SAL alone. Trial registrationNCT00115492, NCT00144911

Daily physical activity in subjects with newly diagnosed COPD [POSTSCRIPT]

Sat, 20 Apr 2013 00:00:00 +0000

RationaleInformation about daily physical activity levels (PAL) in subjects with undiagnosed chronic obstructive pulmonary disease (COPD) is scarce. This study aims to assess PA and to investigate the associations between PA and clinical characteristics in subjects with newly diagnosed COPD. MethodsFifty-nine subjects with a new spirometry-based diagnosis of mild (n=38) and moderate (n=21) COPD (63{+/-}6 years, 68% male) were matched with 65 smoking controls (62{+/-}7 years, 75% male). PA (daily steps, time spent in moderate-to-vigorous intense physical activities (MVPA) and PAL) was measured by accelerometry. Dyspnoea, complete pulmonary function tests, peripheral muscle strength and exercise capacity served as clinical characteristics. ResultsPA was significantly lower in COPD versus smoking controls (7986{+/-}2648 vs 9765{+/-}3078 steps, 64 (27-120) vs 110 (55-164) min of MVPA, 1.49{+/-}0.21 vs 1.62{+/-}0.24 PAL respectively, all p<0.05). Subjects with COPD with either mild symptoms of dyspnoea (mMRC 1), those with lower diffusion capacity (TL,co), low 6 min walking distance (6MWD) or low maximal oxygen uptake (VO2 peak) had significantly lower PA. Multiple regression analysis identified 6 MWD and TL,co as independent predictors of PA in COPD. ConclusionsThe reduction in PA starts early in the disease, even when subjects are not yet diagnosed with COPD. Inactivity is more pronounced in subjects with mild symptoms of dyspnoea, lower levels of diffusion capacity and exercise capacity.

Maternal occupational exposure to asthmogens during pregnancy and risk of asthma in 7-year-old children: a cohort study [RESEARCH]

Thu, 11 Apr 2013 00:00:00 +0000

ObjectivesThe objective of this study was to examine whether maternal exposure to asthmogens during pregnancy is associated with the development of asthma in 7-year-old Danish children, taking atopic status and sex into consideration. DesignThe study is a prospective follow-up of a birth cohort. Setting and participantsA total of 41 724 women and their children from The Danish National Birth Cohort were categorised according to maternal occupational exposure. Exposure information was obtained by combining job title in pregnancy and 18 months after pregnancy with a commonly used asthma Job Exposure Matrix. Primary and secondary outcome measuresPrimary outcome was parent-reported asthma among their 7-year-old children in an internet-based questionnaire. Secondary outcome was asthma among the same children with or without atopic dermatitis and among boys and girls, respectively. ResultsPrenatal exposure to low molecular weight (LMW) agents was borderline associated with asthma in children with OR 1.17 (0.95 to 1.44) for children with atopic dermatitis and 1.10 (0.98 to 1.22) for children without. Maternal postnatal exposure was associated with asthma (OR 1.15 (1.04 to 1.28). After mutual adjustment,postnatal exposure (OR 1.13 (0.99 to 1.29) and the combined effects of prenatal and postnatal exposure (OR 1.34 (1.19 to 1.51)) seem to increase the risk of asthma in children. No significant associations were observed for other prenatal or postnatal exposures. The gender of the child did not modify the aforementioned associations. ConclusionsMaternal occupational exposures during pregnancy do not seem to be a substantial risk factor for the development of asthma in 7-year-old children. Maternal prenatal and postnatal exposures to LMW agents may predispose the propensity of the children to develop asthma. Future studies should prioritise the characterisation of the timing of exposure in relation to the birth.

Recruiting ethnic minority participants to a clinical trial: a qualitative study [RESEARCH]

Wed, 10 Apr 2013 00:00:00 +0000

ObjectivesTo compare the motives and experiences of different ethnic groups participating in a randomised double blind placebo-controlled trial of montelukast in preschool wheeze, and to assess parents' or guardians' understanding of trial procedures and their implications, including the collection of genetic material. DesignQualitative interviews with parents or guardians. SettingInterviews occurred in the homes of London children recruited to a national multicentre clinical trial following primary and secondary care attendance with wheeze. Participants42 parents (20 of Bangladeshi origin, 10 white UK, 12 other ethnicities) of preschool children enrolled in a clinical trial. ResultsBangladeshi families were relatively reluctant to participate in the qualitative study, despite strong engagement with the parent study. Anxiety related to wheezing was a common primary motive for trial enrolment. Parents viewed the trial as a route to improved treatment. Verbal delivery of trial information appeared more effective than study literature, especially for Bangladeshi families, with low parental literacy and high levels of trust in medical professionals potential contributors to this effect. All ethnic groups expressed a low understanding and/or retention of essential study concepts such as randomisation and genetic testing. ConclusionsBangladeshi families are particularly motivated to participate in clinical trials despite variable comprehension of study concepts. This motivation is more strongly contingent on strong researcher-subject rapport than on the quality of study literature. Trial teams seeking to recruit from South Asian populations should emphasise face-to-face verbal explanation of trial concepts and procedures and consider modified trial literature.

Haemodynamic and structural correlates of the first and second heart sounds in pulmonary arterial hypertension: an acoustic cardiography cohort study [RESEARCH]

Mon, 8 Apr 2013 00:00:00 +0000

ObjectiveTo examine the relationship between acoustic characteristics of the first and second heart sounds (S1 and S2) and underlying cardiac structure and haemodynamics in patients with isolated pulmonary arterial hypertension (PAH) and controls. DesignProspective multicentre cohort study. SettingTertiary referral and community hospitals. ParticipantsWe prospectively evaluated 40 PAH patients undergoing right-heart catheterisation with contemporaneous digital acoustic cardiography (intensity and complexity) and two-dimensional transthoracic echocardiography. To normalise for differences in body habitus, acoustic variables were also expressed as a ratio (S2/S1). 130 participants (55 also had haemodynamic and/or echocardiographic assessment) without clinical or haemodynamic evidence of PAH or congestive heart failure acted as controls. ResultsPatients with PAH had higher mean pulmonary artery pressure (mPA; 40{+/-}13 vs 16{+/-}4 mm Hg, p<0.0001) and pulmonary vascular resistance (9{+/-}6 vs 1{+/-}1 Wood Units, p<0.0001) compared with controls, but cardiac index and mean pulmonary capillary wedge pressure were similar. More PAH patients had evidence of right ventricular (RV) dilation (50% vs 19%) and RV systolic dysfunction (41% vs 9%) in the moderate-severe range (all p<0.05). Compared with controls, the acoustic profiles of PAH patients were characterised by increased S2 complexity, S2/S1 complexity and S2/S1 intensity (all p<0.05). In the PAH cohort, S2 complexity was inversely related to S1 complexity. mPA was the only independent multivariate predictor of S2 complexity. The severity of RV enlargement and systolic impairment had reciprocal effects on the complexity of S2 (increased) and S1 (decreased). Decreased S1 complexity was also related to evidence of a small left ventricular cavity. ConclusionsAcoustic characteristics of both S1 and S2 are related to the severity of PAH and are associated with RV enlargement and systolic dysfunction. The reciprocal relationship between S2 and S1 complexity may also reflect the underlying ventricular interaction associated with PAH.

General practitioners' prescribing behaviour as a determinant of poor persistence with inhaled corticosteroids in children with respiratory symptoms: mixed methods study [RESEARCH]

Wed, 3 Apr 2013 00:00:00 +0000

ObjectivesTo evaluate general practitioners' (GPs') prescribing behaviour as a determinant of persistence with and adherence to inhaled corticosteroids (ICS) in children. DesignProspective observational study of persistence with and adherence to ICS followed by a focus group study of the GPs prescribing this treatment. Setting7 primary care practices in the area of Zwolle, the Netherlands. Participants134 children aged 2-12 years had been prescribed ICS in the year before the study started by their 19 GPs. Main outcome measuresPatterns and motives of GPs' prescribing behaviour and the relationship with persistence with and adherence to ICS. ResultsGPs' prescribing behaviour was characterised by prescribing short courses of ICS to children with various respiratory symptoms without follow-up for making a diagnosis of asthma. This was driven by the GPs' pragmatic approach to deal with the large number of children with respiratory symptoms, and by beliefs about ICS which differed from currently available evidence. This prescribing behaviour was the main reason why 68 (51%) children did not persist with the use of ICS. In children with persistent use of ICS and a GP's advice to use ICS on a daily basis, the median (IQR) adherence was 70% (41-84%), and was similar for patients with persistent asthma and children lacking a diagnosis or symptoms of asthma. ConclusionsInappropriate prescription of ICS to children by GPs is common and drives the lack of persistence with ICS therapy in primary care. This finding should be taken into account when interpreting data from large prescription database studies. Improving primary healthcare providers' knowledge and competence in diagnosing and managing asthma in children is needed.

The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): routine screening data for central Europe from a cohort study [RESEARCH]

Wed, 3 Apr 2013 00:00:00 +0000

ObjectivesOwing to novel therapy strategies in epidermal growth factor receptor (EGFR)-mutated patients, molecular analysis of the EGFR and KRAS genome has become crucial for routine diagnostics. Till date these data have been derived mostly from clinical trials, and thus collected in pre-selected populations. We therefore screened allcomers' with a newly diagnosed non-small cell lung carcinoma (NSCLC) for the frequencies of these mutations. DesignA cohort study. SettingLung cancer centre in a tertiary care hospital. ParticipantsWithin 15 months, a total of 552 cases with NSCLC were eligible for analysis. Primary and secondary outcome measuresFrequency of scrutinising exons 18, 19 and 21 for the presence of activating EGFR mutation and secondary codon 12 and 13 for activating KRAS mutations. ResultsOf the 552 patients, 27 (4.9%) showed a mutation of EGFR. 19 of these patients (70%) had deletion E746-A750 in codon 19 or deletion L858R in codon 21. Adenocarcinoma (ACA) was the most frequent histology among patients with EGFR mutations (ACA, 22/254 (8.7%) vs non-ACA, 5/298 (1.7%); p<0.001). Regarding only ACA, the percentage of EGFR mutations was higher in women (16/116 (14%) women vs 6/138 (4.3%) men; p=0.008). Tumours with an activating EGFR mutation were more likely to be from non-smokers (18/27; 67%) rather than smoker (9/27; 33%). KRAS mutation was present in 85 (15%) of all cases. In 73 patients (86%), the mutation was found in exon 12 and in 12 cases (14%) in exon 13. Similarly, ACA had a higher frequency of KRAS mutations than non-ACA (67/254 (26%) vs 18/298 (6.0%); p<0.001). ConclusionsWe found a lower frequency for EGFR and KRAS mutations in an unselected Caucasian patient cohort as previously published. Taking our results into account, clinical trials may overestimate the mutation frequency for EGFR and KRAS in NSCLC due to important selection biases.

Influence of the 2009 financial crisis on detection of advanced pulmonary tuberculosis in Osaka city, Japan: a cross-sectional study [RESEARCH]

Wed, 3 Apr 2013 00:00:00 +0000

ObjectiveTo investigate the association between the economic recession and the detection of advanced cases of pulmonary tuberculosis in Osaka city from 2007 to 2009. DesignA repeated cross-sectional study. SettingOsaka city has been the highest tuberculosis burden area in Japan. After the previous global financial crisis, the unemployment rate in Osaka prefecture has deteriorated from 5.3% in 2008 to 6.6% in 2009. ParticipantsDuring the study period, 3406 pulmonary tuberculosis cases were enrolled: 2530 males and 876 females; 1546 elderly cases (65 years and above) and 1860 young cases (under 65 years); 417 homeless cases and 2989 non-homeless cases. Outcome measuresPatients' information included the sex, age, registry, health insurances, places of detection, sputum smear test results, patients' delay, doctors' delay and the grade of chest x-ray findings. They were statistically analysed between 2007 and 2008, two years before and just before the financial crisis, and between 2008 and 2009, just before and after the financial crisis. ResultsThe total numbers of pulmonary tuberculosis cases were 1172 in 2007, 1083 in 2008 and 1151 in 2009. In health examinations for non-homeless people, higher number of cases in 2009 were sputum smear positive, had respiratory symptoms and showed advanced disease in chest x-rays than those in 2008, with a longer patients' delay. On the contrary, in health examination for homeless people, fewer cases of advanced pulmonary tuberculosis were found in 2009 than in 2008, with a shorter patients' delay. In clinical examinations, there was no trend towards a difference between non-homeless and homeless people. ConclusionsAlthough homeless people might be protected by public assistance, tuberculosis prevention and control need to be reinforced for the non-homeless population after the financial crisis.

Safety, efficacy and convenience of colistimethate sodium dry powder for inhalation (Colobreathe DPI) in patients with cystic fibrosis: a randomised study [CYSTIC FIBROSIS]

Mon, 1 Apr 2013 00:00:00 +0000

PurposeTo assess efficacy and safety of a new dry powder formulation of inhaled colistimethate sodium in patients with cystic fibrosis (CF) aged [≥]6 years with chronic Pseudomonas aeruginosa lung infection. Study design and methodsA prospective, centrally randomised, phase III, open-label study in patients with stable CF aged [≥]6 years with chronic P aeruginosa lung infection. Patients were randomised to Colobreathe dry powder for inhalation (CDPI, one capsule containing colistimethate sodium 1 662 500 IU, twice daily) or three 28-day cycles with twice-daily 300 mg/5 ml tobramycin inhaler solution (TIS). Study duration was 24 weeks. Results380 patients were randomised. After logarithmic transformation of data due to a non-normal distribution, adjusted mean difference between treatment groups (CDPI vs TIS) in change in forced expiratory volume in 1 s (FEV1% predicted) at week 24 was -0.98% (95% CI -2.74% to 0.86%) in the intention-to-treat population (n=373) and -0.56% (95% CI -2.71% to 1.70%) in the per protocol population (n=261). The proportion of colistin-resistant isolates in both groups was [≤]1.1%. The number of adverse events was similar in both groups. Significantly more patients receiving CDPI rated their device as very easy or easy to use' (90.7% vs 53.9% respectively; p<0.001). ConclusionCDPI demonstrated efficacy by virtue of non-inferiority to TIS in lung function after 24 weeks of treatment. There was no emergence of resistance of P aeruginosa to colistin. Overall, CDPI was well tolerated. Trial Reg NoEudraCT 2004-003675-36.

Effectiveness of influenza vaccination in working-age adults with diabetes: a population-based cohort study [EPIDEMIOLOGY]

Wed, 27 Mar 2013 00:00:00 +0000

BackgroundGuidelines recommend influenza vaccinations in all diabetic adults, but there is limited evidence to support vaccinating working-age adults (<65 years) with diabetes. We examined the effectiveness of influenza vaccine in this subgroup, compared with elderly adults ([≥]65 years) for whom vaccination recommendations are well accepted. MethodsWe identified all adults with diabetes, along with a sample of age-matched and sex-matched comparison subjects without diabetes, from 2000 to 2008, using administrative data from Manitoba, Canada. With multivariable Poisson regression, we estimated vaccine effectiveness (VE) on influenza-like illnesses (ILIs), pneumonia and influenza (PI) hospitalisations and all-cause (ALL) hospitalisations during periods of known circulating influenza. Analyses were replicated outside of influenza season to rule out residual confounding. ResultsWe included 543 367 person-years of follow-up, during which 223 920 ILI, 5422 PI and 94 988 ALL occurred. The majority (58%) of adults with diabetes were working age. In this group, influenza vaccination was associated with relative reductions in PI (43%, 95% CI 28% to 54%) and ALL (28%, 95% CI 24% to 32%) but not ILI (-1%, 95% CI -3% to 1%). VE was similar in elderly adults for ALL (33-34%) and PI (45-55%), although not ILI (12-13%). However, similar estimates of effectiveness were also observed for all three groups during non-influenza control periods. ConclusionsWorking-age adults with diabetes experience similar benefits from vaccination as elderly adults, supporting current diabetes-specific recommendations. However, these benefits were also manifest outside of influenza season, suggesting residual bias. Vaccination recommendations in all high-risk adults would benefit from randomised trial evidence.

Epithelial mesenchymal transition (EMT) in small airways of COPD patients [POSTSCRIPT]

Thu, 14 Mar 2013 00:00:00 +0000

We congratulate Milara et al1 for getting a paper suggesting that epithelial mesenchymal transition (EMT) is important in the pathogenesis of chronic obstructive pulmonary disease (COPD) into a top respiratory journal. This is quite a breakthrough. In the discussion, Milara et al were somewhat dismissive of our findings on EMT markers in large airways of COPD patients;2 commenting that our study was limited by the mesenchymal protein expressions analysed (MMP-9, S100A4, vimentin) being potentially expressed by inflammatory cells. In a follow-up paper3 we excluded such confounding. Further, our study illustrated that cells in the basal epithelium, and reticular basement membrane (Rbm) in smokers/COPD double-stain for cytokeratin-(s) and the EMT marker' S100A4, confirming a likely epithelial origin of these cells. Notably, Milara et al also stained their tissue with ...

Meteorological factors and risk of community-acquired Legionnaires' disease in Switzerland: an epidemiological study [RESEARCH]

Tue, 5 Mar 2013 00:00:00 +0000

ObjectivesThe aim of this study was to identify meteorological factors that could be associated with an increased risk of community-acquired Legionnaires' disease (LD) in two Swiss regions. DesignRetrospective epidemiological study using discriminant analysis and multivariable Poisson regression. SettingWe analysed legionellosis cases notified between January 2003 and December 2007 and we looked for a possible relationship between incidence rate and meteorological factors. ParticipantsCommunity-acquired LD cases in two Swiss regions, the Canton Ticino and the Basle region, with climatically different conditions were investigated. Primary outcome measuresVapour pressure, temperature, relative humidity, wind, precipitation and radiation recorded in weather stations of the two Swiss regions during the period January 2003 and December 2007. ResultsDiscriminant analysis showed that the two regions are characterised by different meteorological conditions. A multiple Poisson regression analysis identified region, temperature and vapour pressure during the month of infection as significant risk factors for legionellosis. The risk of developing LD was 129.5% (or 136.4% when considering vapour pressure instead of temperature in the model) higher in the Canton Ticino as compared to the Basle region. There was an increased relative risk of LD by 11.4% (95% CI 7.70% to 15.30%) for each 1 hPa rise of vapour pressure or by 6.7% (95% CI 4.22% to 9.22%) for 1{degrees}C increase of temperature. ConclusionsIn this study, higher water vapour pressure and heat were associated with a higher risk of community-acquired LD in two regions of Switzerland.

Acute and chronic inflammatory responses induced by smoking in individuals susceptible and non-susceptible to development of COPD: from specific disease phenotyping towards novel therapy. Protocol of a cross-sectional study [PROTOCOL]

Fri, 22 Feb 2013 00:00:00 +0000

IntroductionChronic obstructive pulmonary disease (COPD) is a heterogeneous disease with pulmonary and extra-pulmonary manifestations. Although COPD is a complex disease, diagnosis and staging are still based on simple spirometry measurements. Different COPD phenotypes exist based on clinical, physiological, immunological and radiological observations. Cigarette smoking is the most important risk factor for COPD, but only 15-20% of smokers develop the disease, suggesting a genetic predisposition. Unfortunately, little is known about the pathogenesis of COPD, and even less on the very first steps that are associated with an aberrant response to smoke exposure. This study aims to investigate the underlying local and systemic inflammation of different clinical COPD phenotypes, and acute effects of cigarette smoke exposure in individuals susceptible and non-susceptible for the development of COPD. Furthermore, we will investigate mechanisms associated with corticosteroid insensitivity. Our study will provide valuable information regarding the pathogenetic mechanisms underlying the natural course of COPD. Methods and analysisThis cross-sectional study will include young and old individuals susceptible or non-susceptible to develop COPD. At a young age (18-40 years) 60 party smokers' will be included who are called susceptible or non-susceptible based on COPD prevalence in smoking family members. In addition, 30 healthy smokers (age 40-75 years) and 110 COPD patients will be included. Measurements will include questionnaires, pulmonary function, low-dose CT scanning of the lung, body composition, 6 min walking distance and biomarkers in peripheral blood, sputum, urine, exhaled breath condensate, epithelial lining fluid, bronchial brushes and biopsies. Non-biased approaches such as proteomics will be performed in blood and epithelial lining fluid. Ethics and disseminationThis multicentre study was approved by the medical ethical committees of UMC Groningen and Utrecht, the Netherlands. The study findings will be presented at conferences and will be reported in peer-reviewed journals. Trial registrationClinicalTrials.gov, NCT00807469 (study 1) and NCT00850863 (study 2).

Cross-sectional and prospective study of the association between lung function and prediabetes [RESEARCH]

Wed, 20 Feb 2013 00:00:00 +0000

ObjectivesA growing body of evidence suggests that there is a relationship between impaired lung function and the risk of developing diabetes mellitus (DM). However, it is not known if this reflects a causal effect of lung function on glucose metabolism. To clarify the relationship between lung function and the development of DM, we examined the incidence of newly diagnosed prediabetes (a precursor of DM) among subjects with normal glucose tolerance (NGT) at baseline. DesignPrimary analysis of an occupational cohort with both cross-sectional and longitudinal data (follow-up duration mean{+/-}SD: 28.4{+/-}6.1 months). Setting and participantsData were analysed from 1058 men in a cross-sectional study and from 560 men with NGT in a longitudinal study. Outcomes and methodsImpaired lung function (per cent predicted value of forced vital capacity (%FVC) or per cent value of forced expiratory volume 1 s/FVC (FEV1/FVC ratio)) in relation to the ratio of prediabetes or DM in a cross-sectional study and development of new prediabetes in a longitudinal study. NGT, prediabetes including impaired glucose tolerance (IGT) and increased fasting glucose (IFG) and DM were diagnosed according to 75 g oral glucose tolerance tests. Measurements and main results%FVC at baseline, but not FEV1/FVC ratio at baseline, was significantly associated with the incidences of DM and prediabetes. Among prediabetes, IGT but not IFG was associated with %FVC. During follow-up, 102 subjects developed prediabetes among those with NGT. A low %FVC, but not FEV1/FVC ratio, was predictive of an increased risk for development of IGT, but not of IFG. ConclusionsLow lung volume is associated with an increased risk for the development of prediabetes, especially IGT, in Japanese men. Although there is published evidence for an association between chronic obstructive pulmonary disease and DM, prediabetes is not associated with the early stage of COPD.

'The blue one takes a battering' why do young adults with asthma overuse bronchodilator inhalers? A qualitative study [RESEARCH]

Tue, 19 Feb 2013 00:00:00 +0000

ObjectiveOveruse of short-acting bronchodilators is internationally recognised as a marker of poor asthma control, high healthcare use and increased risk of asthma death. Young adults with asthma commonly overuse short-acting bronchodilators. We sought to determine the reasons for overuse of bronchodilator inhalers in a sample of young adults with asthma. DesignQualitative study using a purposive extreme case sample. SettingA large urban UK general practice. ParticipantsTwenty-one adults with moderate asthma, aged 20-32 years. Twelve were high users of short-acting bronchodilators, nine were low users. ResultsAsthma had a major impact on respondents' lives, disrupting their childhood, family life and career opportunities. High users of short-acting bronchodilators had adapted poorly to having asthma and expressed anger at the restrictions they experienced. Overuse made sense to them: short-acting bronchodilators were a rapid, effective, cheap quick-fix' for asthma symptoms. High users had poorer control of asthma and held explanatory models of asthma which emphasised short-term relief via bronchodilation over prevention. Both high and low users held strong views about having to pay for asthma medication, with costs cited as a reason for not purchasing anti-inflammatory inhalers. ConclusionsYoung adults who were high users of short-acting bronchodilators had adapted poorly to having asthma and had poor asthma control. They gave coherent reasons for overuse. Strategies that might address high bronchodilator use in young adults include improving education to help young people accept and adapt to their illness, reducing stigmatisation and providing free asthma medication to encourage the use of anti-inflammatory inhalers.

Procalcitonin levels to guide antibiotic therapy in adults with non-microbiologically proven apparent severe sepsis: a randomised controlled trial [RESEARCH]

Thu, 14 Feb 2013 00:00:00 +0000

ObjectiveSome patients with the phenotype of severe sepsis may have no overt source of infection or identified pathogen. We investigated whether a procalcitonin-based algorithm influenced antibiotic use in patients with non-microbiologically proven apparent severe sepsis. DesignThis multicentre, randomised, controlled, single-blind trial was performed in two parallel groups. SettingEight intensive care units in France. ParticipantsAdults with the phenotype of severe sepsis and no overt source of infection, negative microbial cultures from multiple matrices and no antibiotic exposure shortly before intensive care unit admission. InterventionThe initiation and duration of antibiotic therapy was based on procalcitonin levels in the experimental arm and on the intensive care unit physicians' clinical judgement without reference to procalcitonin values in the control arm. Main outcome measureThe primary outcome was the proportion of patients on antibiotics on day 5 postrandomisation. ResultsOver a 3-year period, 62/1250 screened patients were eligible for the study, of whom 31 were randomised to each arm; 4 later withdrew their consent. At day 5, 18/27 (67%) survivors were on antibiotics in the experimental arm, versus 21/26 (81%) controls (p=0.24; relative risk=0.83, 95% CI: 0.60 to 1.14). Only 8/58 patients (13%) had baseline procalcitonin <0.25 {micro}g/l; in these patients, physician complied poorly with the algorithm. ConclusionsIn intensive care unit patients with the phenotype of severe sepsis or septic shock and without an overt source of infection or a known pathogen, the current study was unable to confirm that a procalcitonin-based algorithm may influence antibiotic exposure. However, the premature termination of the trial may not allow definitive conclusions.

Intrapleural fibrinolytic therapy (IPFT) in loculated pleural effusions--analysis of predictors for failure of therapy and bleeding: a cohort study [RESEARCH]

Thu, 31 Jan 2013 00:00:00 +0000

ObjectivesTo assess risk factors associated with failure and bleeding in intrapleural fibrinolytic therapy (IPFT) for pleural effusions. DesignRetrospective case series. SettingTwo tertiary-care centres in North America. ParticipantsWe identified 237 cases that received IPFT for the treatment of pleural effusions. Data for 227 patients were compiled including demographics, investigations, radiological findings pretherapy and post-therapy and outcomes. InterventionFibrinolytic therapy in the form of tissue plasminogen activator (t-PA) or streptokinase. Primary and secondary outcomesSuccess of therapy is defined as the presence of both clinical and radiological improvement leading to resolution. Failure was defined as persistence (ie, ineffective treatment) or complications requiring intervention from IPFT. Incidence of bleeding post-IPFT, identifying factors related to failure of therapy and bleeding. ResultsIPFT was used in 237 patients with pleural effusions; 163 with empyema/complicated parapneumonic effusions, 32 malignant effusions and 23 with haemothorax. Overall, resolution was achieved in 80% of our cases. Failure occurred in 46 (20%) cases. Multivariate analysis revealed that failure was associated with the presence of pleural thickening (>2 mm) on CT scan (p=0.0031, OR 3, 95% CI 1.46 to 6.57). Bleeding was not associated with any specific variable in our study (antiplatelet medications, p=0.08). ConclusionsPleural thickening on a CT scan was found to be associated with failure of IPFT.

Chronic lower respiratory diseases among demolition and cement workers: a population-based register study [RESEARCH]

Thu, 24 Jan 2013 00:00:00 +0000

ObjectiveTo estimate standardised hospitalisation ratios (SHR) for chronic lower respiratory diseases among demolition and cement workers in Denmark, 1995-2009. DesignThis is a population-based register study on data from the Occupational Hospitalisation Register'. SHR of chronic obstructive pulmonary disease (COPD) was calculated for both demolition and cement workers. SettingsRegister study with data from all hospitals in Denmark. Participants895 demolition workers and 5633 cement and concrete workers were included in the study and all economical active men were used as reference group. ResultsWe found a statistically significant high SHR for the cement workers, SHR=134 (95% CI 117 to 153). The SHR for demolition workers was 131 (95% CI 87 to 188). ConclusionsWe find a higher risk of being hospitalised due to COPD in cement and concrete workers (significant) and demolition workers (insignificant) compared to gainfully employed men.

Are children carrying the burden of broad-spectrum antibiotics in general practice? Prescription pattern for paediatric outpatients with respiratory tract infections in Norway [RESEARCH]

Mon, 7 Jan 2013 00:00:00 +0000

ObjectivesTo investigate the antibiotic prescription pattern and factors that influence the physicians' choice of antibiotic. DesignObservational study. SettingPrimary healthcare in Norway, December 2004 through November 2005. Participants426 general practitioners, GPs, in Norway, giving 24 888 respiratory tract infection episodes with 19 938 children aged 0-6 years. Outcome measuresAssess antibiotic prescription details and patient and GP characteristics associated with broad-spectrum and narrow-spectrum antibiotic use. ResultsOf the 24 888 episodes in the study, 26.2% (95% CI 25.7% to 26.8%) included an antibiotic prescription. Penicillin V accounted for 42% and macrolide antibiotics for 30%. The prescription rate varied among the physicians, with a mean of 25.5% (95% CI 24.2% to 26.7%). Acute tonsillitis gave the highest odds for a prescription, OR 33.6 (95% CI 25.7% to 43.9%), compared to acute respiratory tract infections and symptoms' as a reference group. GPs with a prescription rate of 33.3% or higher had the larger probability for broad-spectrum antibiotic prescriptions, OR 3.33 (95% CI 2.01% to 5.54%). Antibiotic prescriptions increased with increasing patient age. ConclusionsWe found a low antibiotic prescription rate for childhood respiratory tract infections. However, our figures indicate an overuse of macrolide antibiotics and penicillins with extended spectrum, more so than in the corresponding study including the adult population. Palatability of antibiotic suspensions and other administrative challenges affect medication compliance in children. To help combat antibiotic resistance, guidelines need to be followed, in particular for our youngest patients. Trial registration number (clinicaltrials.org)NCT00272155.

The impact of the 2011 Great East Japan Earthquake on hospitalisation for respiratory disease in a rapidly aging society: a retrospective descriptive and cross-sectional study at the disaster base hospital in Ishinomaki [RESEARCH]

Thu, 3 Jan 2013 00:00:00 +0000

ObjectiveTo investigate the impact in an aging society of the 2011 Great East Japan earthquake on hospitalisation for respiratory disease at the disaster base hospital. DesignDescriptive and cross-sectional study. SettingEmergency care in Japanese Red Cross Ishinomaki Hospital, a regional disaster base hospital in Miyagi, Japan. Participants322 emergency patients who were hospitalised for respiratory disease from 11 March to 9 May 2011, and 99 and 105 emergency patients who were hospitalised in the corresponding periods in 2009 and 2010, respectively. Main outcome measuresDescription and comparison of patient characteristics and disease distribution in terms of age, time after the disaster and activities of daily living (ADL). Results1769 patients were admitted to our hospital during the study period (compared to 850 in 2009 and 1030 in 2010), among whom 322 were hospitalised for respiratory disease (compared to 99 in 2009 and 105 in 2010). Pneumonia (n=190, 59.0%) was the most frequent cause of admission for pulmonary disease, followed by acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) (n=53, 16.5%), asthma attacks (n=27, 8.4%) and progression of lung cancer (n=22, 6.8%). Compared with the corresponding periods in 2009 and 2010, the increase in the absolute numbers of admissions was highest for pneumonia, followed by AE-COPD and asthma attacks. At hospitalisation, 195 patients were dependent' and 54 patients were partially dependent'. Respiratory admissions accompanied by deterioration of ADL after the disaster were more frequent in elderly and female patients. ConclusionsAfter the Great East Japan Earthquake, admissions for pneumonia and exacerbation of chronic respiratory disease in the elderly increased at the disaster base hospital.

Obstructive airway disease and edentulism in the atherosclerosis risk in communities (ARIC) study [RESEARCH]

Tue, 18 Dec 2012 00:00:00 +0000

ObjectivesWe examined the potential association between prior chronic obstructive pulmonary disease (COPD) and edentulism, and whether the association varied by COPD severity using data from the Dental Atherosclerosis Risk in Communities Study. DesignCross-sectional. SettingCommunity dwelling subjects from four US communities. Participants and measurementsCases were identified as edentulous (without teeth) and subjects with one or more natural teeth were identified as dentate. COPD cases were defined by spirometry measurements that showed the ratio of forced expiratory volume (1 s) to vital capacity to be less than 0.7. The severity of COPD cases was also determined using a modified Global Initiative for Chronic Obstructive Lung Disease classification criteria (GOLD stage I-IV). Multiple logistic regression was used to examine the association between COPD and edentulism, while adjusting for age, gender, centre/race, ethnicity, education level, income, diabetes, hypertension, coronary heart disease and congestive heart failure, body mass index, smoking, smokeless tobacco use and alcohol consumption. Results13 465 participants were included in this analysis (2087 edentulous; 11 378 dentate). Approximately 28.3% of edentulous participants had prior COPD compared with 19.6% among dentate participants (p<0.0001). After adjustment for potential confounders, we observed a 1.3 (1.08 to 1.62) and 2.5 (1.68 to 3.63) fold increased risk of edentulism among GOLD II and GOLD III/IV COPD, respectively, as compared with the non-COPD/dentate referent. Given the short period of time between the measurements of COPD (visit 2) and dentate status (visit 4) relative to the natural history of both diseases, neither temporality nor insight as to the directionality of the association can be ascertained. ConclusionsWe found a statistically significant association between prior COPD and edentulism, with evidence of a positive incremental effect seen with increasing GOLD classification.

Effectiveness of involving the private medical sector in the National TB Control Programme in Bangladesh: evidence from mixed methods [RESEARCH]

Tue, 18 Dec 2012 00:00:00 +0000

ObjectivesIn Bangladesh, private healthcare is common and popular, regardless of income or area of residence, making the private sector an important player in health service provision. Although the private sector offers a good range of health services, tuberculosis (TB) care in the private sector is poor. We conducted research in Dhaka, between 2004 and 2008, to develop and evaluate a public-private partnership (PPP) model to involve private medical practitioners (PMPs) within the National TB Control Programme (NTP)'s activities. Since 2008, this PPP model has been scaled up in two other big cities, Chittagong and Sylhet. This paper reports the results of this development, evaluation and scale-up. DesignMixed method, observational study design. We used NTP service statistics to compare the TB control outcomes between intervention and control areas. To capture detailed insights of PMPs and TB managers about the process and outcomes of the study, we conducted in-depth interviews, focus group discussions and workshops. SettingUrban setting, piloted in four areas in Dhaka city; later scaled up in other areas of Dhaka and in two major cities. FindingsThe partnership with PMPs yielded significantly increased case finding of sputum smear-positive TB cases. Between 2004 and 2010, 703 participating PMPs referred 3959 sputum smear-positive TB cases to the designated Directly Observed Treatment, Short-course (DOTS) centres, contributing about 36% of all TB cases in the project areas. There was a steady increase in case notification rates in the project areas following implementation of the partnership. ConclusionsThe PPP model was highly effective in improving access and quality of TB care in urban settings.

Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study [RESEARCH]

Thu, 13 Dec 2012 00:00:00 +0000

BackgroundLow serum levels of 25-hydroxyvitamin D3 are associated with an increased risk of respiratory tract infections (RTIs). Clinical trials with vitamin D3 against various infections have been carried out but data are so far not conclusive. Thus, there is a need for additional randomised controlled trials of effects of vitamin D3 on infections. ObjectiveTo investigate if supplementation with vitamin D3 could reduce infectious symptoms and antibiotic consumption among patients with antibody deficiency or frequent RTIs. DesignA double-blind randomised controlled trial. SettingKarolinska University Hospital, Huddinge. Participants140 patients with antibody deficiency (selective IgA subclass deficiency, IgG subclass deficiency, common variable immune disorder) and patients with increased susceptibility to RTIs (>4 bacterial RTIs/year) but without immunological diagnosis. InterventionVitamin D3 (4000 IU) or placebo was given daily for 1 year. Primary and secondary outcome measuresThe primary endpoint was an infectious score based on five parameters: symptoms from respiratory tract, ears and sinuses, malaise and antibiotic consumption. Secondary endpoints were serum levels of 25-hydroxyvitamin D3, microbiological findings and levels of antimicrobial peptides (LL-37, HNP1-3) in nasal fluid. ResultsThe overall infectious score was significantly reduced for patients allocated to the vitamin D group (202 points) compared with the placebo group (249 points; adjusted relative score 0.771, 95% CI 0.604 to 0.985, p=0.04). LimitationsA single study centre, small sample size and a selected group of patients. The sample size calculation was performed using p=0.02 as the significance level whereas the primary and secondary endpoints were analysed using the conventional p=0.05 as the significance level. ConclusionsSupplementation with vitamin D3 may reduce disease burden in patients with frequent RTIs.

Large-scale international validation of the ADO index in subjects with COPD: an individual subject data analysis of 10 cohorts [RESEARCH]

Wed, 12 Dec 2012 00:00:00 +0000

BackgroundLittle evidence on the validity of simple and widely applicable tools to predict mortality in patients with chronic obstructive pulmonary disease (COPD) exists. ObjectiveTo conduct a large international study to validate the ADO index that uses age, dyspnoea and FEV1 to predict 3-year mortality and to update it in order to make prediction of mortality in COPD patients as generalisable as possible. DesignIndividual subject data analysis of 10 European and American cohorts (n=13 914). SettingPopulation-based, primary, secondary and tertiary care. PatientsCOPD GOLD stages I-IV. MeasurementsWe validated the original ADO index. We then obtained an updated ADO index in half of our cohorts to improve its predictive accuracy, which in turn was validated comprehensively in the remaining cohorts using discrimination, calibration and decision curve analysis and a number of sensitivity analyses. Results1350 (9.7%) of all subjects with COPD (60% male, mean age 61 years, mean FEV1 66% predicted) had died at 3 years. The original ADO index showed high discrimination but poor calibration (p<0.001 for difference between predicted and observed risk). The updated ADO index (scores from 0 to 14) preserved excellent discrimination (area under curve 0.81, 95% CI 0.80 to 0.82) but showed much improved calibration with predicted 3-year risks from 0.7% (95% CI 0.6% to 0.9%, score of 0) to 64.5% (61.2% to 67.7%, score of 14). The ADO index showed higher net benefit in subjects at low-to-moderate risk of 3-year mortality than FEV1 alone. InterpretationThe updated 15-point ADO index accurately predicts 3-year mortality across the COPD severity spectrum and can be used to inform patients about their prognosis, clinical trial study design or benefit harm assessment of medical interventions.

Evaluation of the filter paper IP-10 tests in school children after exposure to tuberculosis: a prospective cohort study with a 4-year follow-up [RESEARCH]

Tue, 4 Dec 2012 00:00:00 +0000

ObjectivesThe prevalence of active tuberculosis (TB) is low in Finland, but outbreaks do occur. Following exposure national guidelines recommend either tuberculosis skin test or interferon-{gamma}-release assay-testing of asymptomatic children. The aim of this study was to compare QuantiFERON-TB Gold In-Tube test (QFT) and interferon-{gamma}-inducible protein (IP-10) release assay for detection of Mycobacterium tuberculosis infection following exposure to TB in a primary school. DesignA prospective cohort study. SettingSchool children in Helsinki, Finland. ParticipantsTwo siblings of the index case and 58 classmates exposed to M tuberculosis. InterventionAll the children were screened using the QFT, which was used to guide preventive treatment. All those exposed were followed up through the national TB registry. Outcome measuresIP-10 was measured in plasma supernatants from the QFT test supernatants and in plasma dried and stored for 1 year on filter paper. IP-10 test results were calculated using preset algorithms for positive and indeterminate tests. The negative predictive values of the tests were assessed. ResultsAt an initial screening 2 months after the debut of symptoms in the index case, QFT was positive in two children; 56 tests were negative; one was indeterminate and one was borderline. IP-10 showed a perfect concordance between the dried plasma spot and plasma method; two children were IP-10 positive and two were IP-10 indeterminate. There were two (3%) discordant results between the QFT and IP-10 tests. Four children converted to positive QFT at a 1-3 month follow-up. None of the QFT negative/borderline children developed TB in the 4-year period since exposure. ConclusionsWe demonstrated that IP-10 and QFT perform comparably as screening tools for infection with M tuberculosis in a contact investigation. IP-10 determined in dried plasma spots was at par with IP-10 determined in plasma, which further supports the usefulness of this alternative approach.

Respiratory symptoms and peripheral airways disease in a cross-sectional study on a random population sample [RESEARCH]

Tue, 27 Nov 2012 00:00:00 +0000

ObjectivesRespiratory symptoms are associated with spirometry results but more strongly with smoking history, suggesting that alterations in the lung other than those revealed by spirometry contribute to cause symptoms. Smoking may cause obstruction of peripheral airways that is poorly detected by spirometry. The slope of phase III of the single-breath nitrogen (N2) test detects smoking-induced alterations in smokers before spirometry is impaired. The aim of the present investigation was to study the association between respiratory symptoms and the slope of phase III adjusting for spirometry results and smoking history. DesignSingle-centre retrospective cross-sectional study. SettingUniversity hospital in Gothenburg, Sweden. ParticipantsA random population sample of 430 elderly men. MethodsThe presence of seven different respiratory symptoms were analysed by a multiple logistic regression model in relation to spirometry results, smoking history (pack-years) and the slope of phase III in a population sample of 430 elderly men, age span 50-67 years. Furthermore, smoking normalised values of the slope of phase III were calculated and differences between subjects reporting/not reporting symptoms were tested. ResultsThe presence of some cough symptoms was significantly associated with a steep slope of phase III also when adjusting for spirometry results and smoking history. Furthermore, smoking normalised slope of phase III was significantly steeper among subjects with cough symptoms compared to those without cough symptoms. ConclusionsCough symptoms may be an effect of abnormalities in peripheral airways at least among elderly men.

Descriptive analysis of the respiratory health status of persons exposed to Libby amphibole asbestos [RESEARCH]

Wed, 21 Nov 2012 00:00:00 +0000

ObjectiveDescribe respiratory health and quality of life in persons exposed to Libby amphibole asbestos (LAA) contaminated vermiculite. DesignCross-sectional descriptive. SettingAsbestos-related disease clinic in Libby, Montana USA. Participants329 individuals exposed to LAA; mostly men, married, between 50 and 69 years; two-thirds lived in the surrounding county; one-third lived elsewhere in the state and USA. Primary outcome measuresChest radiograph (CXR), pulmonary function data and the St George Respiratory Questionnaire (SGRQ). ResultsExposure categories included vermiculite workers=7.6%; family/household contact of vermiculite worker=32%; and environmental exposure only=60%. Of the participants, 55% had only pleural abnormalities; 5.4% had only interstitial abnormalities; nearly 21% had both abnormalities and 18% had no lung abnormality on chest x-ray. Mean forced vital capacity (FVC) 95.3% (SD=18.7); forced expiratory volume (FEV1) mean 87% (SD=20.2); ratio of FEV11/FVC 95.5% (SD=12.0); and diffusing capacity (DLCO) of 83% (SD=21.7) of the percent predicted. The mean total SGRQ (38.5; SD=22.1) indicated a lower quality of life than healthy persons and persons with other chronic conditions. SGRQ subscale means were Symptoms 52.1 (SD=24.9), activity 49.4 (SD=26.9) and impacts 27.5 (SD=21.9). Participants with normal CXR differed significantly from those with both interstitial and pleural abnormalities on total, activity and impacts scores. For activity alone, subjects with normal CXR differed significantly from those with pleural disease; no differences were found for those with interstitial disease. Significant findings were found for smoking history across all pulmonary measures, and for exposure status, radiographic findings, age and gender for select pulmonary parameters. Subjects with any smoking history had significantly worse average total and subscale scores on the SGRQ. ConclusionsOf 329 persons exposed to LAA, the majority (182) had pleural abnormalities identified on CXR. SGRQ scores for persons with abnormalities (pleural, interstitial or both) (269) differed significantly from those with a normal CXR.

Eliciting symptoms interpreted as normal by patients with early-stage lung cancer: could GP elicitation of normalised symptoms reduce delay in diagnosis? Cross-sectional interview study [RESEARCH]

Mon, 19 Nov 2012 00:00:00 +0000

ObjectivesTo investigate why symptoms indicative of early-stage lung cancer (LC) were not presented to general practitioners (GPs) and how early symptoms might be better elicited within primary care. Design, setting and participantsA qualitative cross-sectional interview study about symptoms and help-seeking in 20 patients from three south England counties, awaiting resection of LC (suspected or histologically confirmed). Analysis drew on principles of discourse analysis and constant comparison to identify processes involved in interpretation and communication about symptoms, and explain non-presentation. ResultsMost participants experienced health changes possibly indicative of LC which had not been presented during GP consultations. Symptoms that were episodic, or potentially caused by ageing or lifestyle, were frequently not presented to GPs. In interviews, open questions about health changes/symptoms in general did not elicit these symptoms; they only emerged in response to closed questions detailing specific changes in health. Questions using disease-related labels, for example, pain or breathlessness, were less likely to elicit symptoms than questions that used non-disease terminology, such as aches, discomfort or getting out of breath'. Most participants described themselves as feeling well and were reluctant to associate potentially explained, non-specific or episodic symptoms with LC, even after diagnosis. ConclusionsPatients with early LC are unlikely to present symptoms possibly indicative of LC that they associate with normal processes, when attending primary care before diagnosis. Faced with patients at high LC risk, GPs will need to actively elicit potential LC symptoms not presented by the patient. Closed questions using non-disease terminology might better elicit normalised symptoms.

Life event stress and chronic obstructive pulmonary disease (COPD): associations with mental well-being and quality of life in a population-based study [RESEARCH]

Mon, 19 Nov 2012 00:00:00 +0000

ObjectivesTo investigate whether life event stress was associated with greater psychological distress and poorer quality of life in older individuals with chronic obstructive pulmonary disease (COPD), in comparison with their counterparts without COPD. DesignCross-sectional study. ParticipantsA population-based sample (N=497) of individuals aged 65 and above with COPD (postbronchodilatation FEV1/FVC<0.70, N=136) and without COPD (N=277). MeasurementsWe measured life event stress, depressive symptoms (GDS, Geriatric Depression Scale), cognitive symptoms and function (CFQ, Cognitive Failures Questionnaire and MMSE, Mini-Mental State Examination), and physical and mental health functional status (SF36-PCS, Physical Health Component Summary and SF36-MCS, Mental Health Component Summary) in participants with and without COPD. ResultsIn two-way analysis of variance controlling for potential confounders, life event stress was associated with significant main effects of worse GDS (p<0.001), SF36-PCS (p=0.008) and SF36-MCS scores (p<0.001), and with significant interaction effects on GDS score (p<0.001), SF36-PCS (p=0.045) and SF36-MCS (p=0.034) in participants with COPD, more than in non-COPD participants. The main effect of COPD was found for postbronchodilator FEV1 (p<0.001) and cognitive symptoms (p=0.02). ConclusionsOur findings indicate that life event stress was associated with more depressive symptoms and worse quality of life in individuals with COPD, much more than in those without COPD. Further studies should explore the role of cognitive appraisal of stress, coping resources and psycho-social support in this relationship.

Risk of developing tuberculosis after brief exposure in Norwegian children: results of a contact investigation [RESEARCH]

Tue, 6 Nov 2012 00:00:00 +0000

ObjectiveProlonged exposure to adults with pulmonary tuberculosis is a risk factor for infecting children. We have studied to what extent a brief exposure may increase the risk of being infected in children. DesignObservational study of a tuberculosis contact investigation. Setting7 day-care centres and 4 after-school-care centres in Norway. Participants606 1-year-old to 9-year-old children who were exposed briefly to a male Norwegian with smear-positive pulmonary tuberculosis. Main outcome measuresNumber of children with latent and active tuberculosis detected by routine clinical examination, chest x-ray and use of a Mantoux tuberculin skin test (TST) and an interferon-{gamma} release assay (IGRA). ResultsThe children were exposed to a mean of 6.9 h (range 3-18 h). 2-3 months after the exposure, 11 children (1.8%) had a TST [≥]6 mm, 6 (1.0%) had TST 4-5 mm, and 587 (97.2%) had a negative TST result. Two children (0.3%) with negative chest x-rays who were exposed 4.75 and 12 h, respectively, had a positive IGRA test result, and were diagnosed with latent tuberculosis. None developed active tuberculosis. ConclusionsChildren from a high-income country attending day-care and after-school-care centres had low risk of being infected after brief exposure less than 18 h to an adult day-care helper with smear-positive pulmonary tuberculosis.

Furthering the understanding of olfaction, prevalence of loss of smell and risk factors: a population-based survey (OLFACAT study) [RESEARCH]

Tue, 6 Nov 2012 00:00:00 +0000

ObjectivesTo investigate olfaction in general population, prevalence of olfactory dysfunction and related risk factors. DesignCross-sectional population-based survey, distributing four microencapsulated odorants (rose, banana, musk and gas) and two self-administered questionnaires (odour description; epidemiology/health status). SettingThe survey was distributed to general population through a bilingual (Catalan, Spanish) newspaper in Catalonia (Spain), on December 2003. ParticipantsNewspaper readers of all ages and gender; 9348 surveys were analysed from the 10 783 returned. Main outcome measuresCharacteristics of surveyed population, olfaction by age and gender, smell self-perception and smell impairment risk factors. Terms normosmia, hyposmia and anosmia were used when participants detected, recognised or identified all four, one to three or none of the odours, respectively. ResultsSurvey profile was a 43-year-old woman with medium-high educational level, living in a city. Olfaction was considered normal in 80.6% (detection), 56% (recognition/memory) and 50.7% (identification). Prevalence of smell dysfunction was 19.4% for detection (0.3% anosmia, 19.1% hyposmia), 43.5% for recognition (0.2% anosmia, 43.3% hyposmia) and 48.8% for identification (0.8% anosmia, 48% hyposmia). Olfaction was worse (p<0.0001) in men than in women through all ages. There was a significant age-related smell detection decline however smell recognition and identification increased up to fourth decade and declined after the sixth decade of life. Risk factors for anosmia were: male gender, loss of smell history and poor olfactory self-perception for detection; low educational level, poor self-perception and pregnancy for recognition; and older age, poor self-perception and history of head trauma and loss of smell for identification. Smoking and exposure to noxious substances were mild protective factors for smell recognition. ConclusionsSense of smell in women is better than in men suggesting a learning process during life with deterioration in older ages. Poor self-perception, history of smell loss, head trauma and pregnancy are potential risk factors for olfactory disorders.

Time trend in hospitalised chronic lower respiratory diseases among Danish building and construction workers, 1981-2009: a cohort study [RESEARCH]

Tue, 6 Nov 2012 00:00:00 +0000

ObjectivesTo show trends in age-standardised hospital admission ratios (SHR) for chronic lower respiratory diseases, estimated for Danish construction workers over three time periods (1981-1990, 1991-2000, 2001-2009). DesignWithin consecutive cohorts of all male building and construction workers in Denmark, selected occupations: bricklayers, carpenters, electricians, painters, plumbers and other construction workers' were followed up for hospitalisation due to chronic lower respiratory diseases. SHR was calculated for each occupation and time period. Time trend was calculated for construction workers at large using Poisson regression. SettingDenmark. ParticipantsAll gainfully employed male building and construction workers aged 20 or more. Primary and secondary outcome measuresAge-standardised and gender-standardised hospitalisation ratios (SHR). ResultsThe number of hospitalised construction workers at large was reduced from 1134 in the first 10-year period to 699 in the last 9-year period. Among all Danish males, it was, however, even more reduced as reflected in the expected number that was down from 1172 to 617. Hence, SHR increased from 97 during 1981-1990, 100 during 1991-2000 to 113 during 2001-2009. It means that SHR increased with an average rate of 0.76% per year (95% CI 0.28 to 1.24) during the study period. A low SHR=72 (95% CI 60 to 87) was found among carpenters in 1981-1990. From 2001 to 2009, high SHRs were found among painters (SHR=147; 95% CI 111 to 192) and plumbers (SHR=132; 95% CI 101 to 171). In general, the selected groups of construction workers had, however, a low or average SHR due to chronic lower respiratory diseases. ConclusionsThe number of hospitalised workers, suffering from chronic lower respiratory diseases, was reduced over time for construction workers, but for all economically active men, it was reduced even more. Therefore, SHR due to chronic lower respiratory diseases increased over time in the construction industry at large.

Gene expression profiles of alveolar type II cells of chronic obstructive pulmonary disease: a case-control study [RESEARCH]

Wed, 31 Oct 2012 00:00:00 +0000

ObjectivesThe aim of this study was to identify the gene expression pattern specific in alveolar epithelial type II cells (ATII cells) isolated from patients with chronic obstructive pulmonary disease (COPD). DesignCase control. SettingTwo hospitals in Japan. ParticipantsThree patients without COPD and three patients with COPD in microarray analyses. Five smokers without COPD and nine smokers with COPD in the following analyses. Primary and secondary outcome measuredPrimary outcome included identification of differentially expressed genes and activated or inhibited pathways in ATII cells of the patients with COPD, compared to those of the patients without COPD, using Affymetrix gene expression arrays. Secondary outcome included validation of the results of microarray analyses by quantitative reverse transcription-PCR. ResultsWe isolated ATII cells from COPD and non-COPD lungs using fluorescence-activated cell sorting. We performed Affymetrix gene expression arrays on both types of ATII cells. Gene set enrichment analyses revealed that two major gene sets were enriched in ATII cells from COPD lungs: interferon-responsive gene sets and gene sets associated with cell cycle progression. Gene ontology term enrichment analyses indicated that among the interferon-stimulated genes, ATII cells in COPD expressed genes such as PSMB8, PSMB9, TAP1 and TAP2 associated with the antigen processing and presentation pathway. We validated the results of the microarray analyses using quantitative reverse transcriptase-PCR. In addition, FACS analysis indicated that the percentage of ATII cells to CD45-negative lung cells isolated from COPD lungs were significantly increased more than that from non-COPD lungs. ConclusionsOur study demonstrated that interferon-stimulated genes involved in the antigen processing and presentation pathway and genes involved in cell cycle progression were enriched in ATII cells of the patients with COPD. These pathways might alter phenotypes of ATII cells in COPD lungs.

Utilisation of a thoracic oncology database to capture radiological and pathological images for evaluation of response to chemotherapy in patients with malignant pleural mesothelioma [RESEARCH]

Fri, 26 Oct 2012 00:00:00 +0000

ObjectiveAn area of need in cancer informatics is the ability to store images in a comprehensive database as part of translational cancer research. To meet this need, we have implemented a novel tandem database infrastructure that facilitates image storage and utilisation. BackgroundWe had previously implemented the Thoracic Oncology Program Database Project (TOPDP) database for our translational cancer research needs. While useful for many research endeavours, it is unable to store images, hence our need to implement an imaging database which could communicate easily with the TOPDP database. MethodsThe Thoracic Oncology Research Program (TORP) imaging database was designed using the Research Electronic Data Capture (REDCap) platform, which was developed by Vanderbilt University. To demonstrate proof of principle and evaluate utility, we performed a retrospective investigation into tumour response for malignant pleural mesothelioma (MPM) patients treated at the University of Chicago Medical Center with either of two analogous chemotherapy regimens and consented to at least one of two UCMC IRB protocols, 9571 and 13473A. ResultsA cohort of 22 MPM patients was identified using clinical data in the TOPDP database. After measurements were acquired, two representative CT images and 0-35 histological images per patient were successfully stored in the TORP database, along with clinical and demographic data. DiscussionWe implemented the TORP imaging database to be used in conjunction with our comprehensive TOPDP database. While it requires an additional effort to use two databases, our database infrastructure facilitates more comprehensive translational research. ConclusionsThe investigation described herein demonstrates the successful implementation of this novel tandem imaging database infrastructure, as well as the potential utility of investigations enabled by it. The data model presented here can be utilised as the basis for further development of other larger, more streamlined databases in the future.

Carers' perspectives on the presentation of community-acquired pneumonia and empyema in children: a case series [RESEARCH]

Thu, 18 Oct 2012 00:00:00 +0000

ObjectiveTo describe carers' perceptions of the development and presentation of community-acquired pneumonia or empyema in their children. DesignCase series. SettingSeven hospitals with paediatric inpatient units in South Wales, UK. ParticipantsCarers of 79 children aged 6 months to 16 years assessed in hospital between October 2008 and September 2009 with radiographic, community-acquired pneumonia or empyema. MethodsCarers were recruited in hospital and participated in a structured face-to-face or telephone interview about the history and presenting features of their children's illnesses. Responses to open questions were initially coded very finely and then grouped into common themes. Cases were classified into two age groups: 3 or more years and under 3 years. ResultsThe reported median duration of illness from onset until the index hospital presentation was 4 days (IQR 2-9 days). Pain in the torso was reported in 84% of cases aged 3 or more years and was the most common cause for carer concern in this age group. According to carer accounts, clinicians sometimes misjudged the origin of this pain. Almost all carers reported something unusual about the index illness that had particularly concerned them--mostly non-specific physical symptoms and behavioural changes. ConclusionsPain in the torso and carer concerns about unusual symptoms in their child may provide valuable additional information in a clinician's assessment of the risk of pneumonia in primary care. Further research is needed to confirm the diagnostic value of these features.

Alu and LINE-1 methylation and lung function in the normative ageing study [RESEARCH]

Wed, 17 Oct 2012 00:00:00 +0000

ObjectivesTo investigate the association between methylation of transposable elements Alu and long-interspersed nuclear elements (LINE-1) and lung function. DesignCohort study. SettingOutpatient Veterans Administration facilities in greater Boston, Massachusetts, USA. ParticipantsIndividuals from the Veterans Administration Normative Aging Study, a longitudinal study of aging in men, evaluated between 1999 and 2007. The majority (97%) were white. Primary and secondary outcome measuresPrimary predictor was methylation, assessed using PCR-pyrosequencing after bisulphite treatment. Primary outcome was lung function as assessed by spirometry, performed according to American Thoracic Society/European Respiratory Society guidelines at the same visit as the blood draws. ResultsIn multivariable models adjusted for age, height, body mass index (BMI), pack-years of smoking, current smoking and race, Alu hypomethylation was associated with lower forced expiratory volume in 1 s (FEV1) ({beta}=28 ml per 1% change in Alu methylation, p=0.017) and showed a trend towards association with a lower forced vital capacity (FVC) ({beta}=27 ml, p=0.06) and lower FEV1/FVC ({beta}=0.3%, p=0.058). In multivariable models adjusted for age, height, BMI, pack-years of smoking, current smoking, per cent lymphocytes, race and baseline lung function, LINE-1 hypomethylation was associated with more rapid decline of FEV1 ({beta}=6.9 ml/year per 1% change in LINE-1 methylation, p=0.005) and of FVC ({beta}=9.6 ml/year, p=0.002). ConclusionsIn multiple regression analysis, Alu hypomethylation was associated with lower lung function, and LINE-1 hypomethylation was associated with more rapid lung function decline in a cohort of older and primarily white men from North America. Future studies should aim to replicate these findings and determine if Alu or LINE-1 hypomethylation may be due to specific and modifiable environmental exposures.

Early assisted discharge with generic community nursing for chronic obstructive pulmonary disease exacerbations: results of a randomised controlled trial [RESEARCH]

Tue, 16 Oct 2012 00:00:00 +0000

ObjectivesTo determine the effectiveness of early assisted discharge for chronic obstructive pulmonary disease (COPD) exacerbations, with home care provided by generic community nurses, compared with usual hospital care. DesignProspective, randomised controlled and multicentre trial with 3-month follow-up. SettingFive hospitals and three home care organisations in the Netherlands. ParticipantsPatients admitted to the hospital with an exacerbation of COPD. Patients with no or limited improvement of respiratory symptoms and patients with severe unstable comorbidities, social problems or those unable to visit the toilet independently were excluded. InterventionEarly discharge from hospital after 3 days inpatient treatment. Home visits by generic community nurses. Primary outcome measure was change in health status measured by the Clinical COPD Questionnaire (CCQ). Treatment failures, readmissions, mortality and change in generic health-related quality of life (HRQL) were secondary outcome measures. Results139 patients were randomised. No difference between groups was found in change in CCQ score at day 7 (difference in mean change 0.29 (95% CI -0.03 to 0.61)) or at 3 months (difference in mean change 0.04 (95% CI -0.40 to 0.49)). No difference was found in secondary outcomes. At day 7 there was a significant difference in change in generic HRQL, favouring usual hospital care. ConclusionsWhile patients' disease-specific health status after 7-day treatment tended to be somewhat better in the usual hospital care group, the difference was small and not clinically relevant or statistically significant. After 3 months, the difference had disappeared. A significant difference in generic HRQL at the end of the treatment had disappeared after 3 months and there was no difference in treatment failures, readmissions or mortality. Early assisted discharge with community nursing is feasible and an alternative to usual hospital care for selected patients with an acute COPD exacerbation. Trial registration: NetherlandsTrialRegister NTR 1129.

Prevalence of respiratory symptoms at two time points in a population of children in Manchester--a cohort study [RESEARCH]

Thu, 11 Oct 2012 00:00:00 +0000

ObjectiveAlthough the prevalence of asthma and atopy has been noted to have increased in recent decades, patterns of asthma prevalence have, traditionally, been difficult to track. Most reports on trends in childhood asthma have been cross-sectional measuring the prevalence in cohorts of similar aged children at different time points. The aim of this paper is to report on the prevalence of symptoms in the same cohort at two separate time points. DesignRetrospective cohort study. SettingCommunity-based study, Central Manchester. ParticipantsMANCAS1, study n=5086, participation n=2414. MANCAS2, study n=6338, participation n=1608. Children born in a hospital in Manchester within specified dates and still living or attending a school in Central Manchester were eligible for inclusion. Children on an at-risk' register or living with short-term carers were excluded. Outcome measuresData on respiratory symptoms were collected at two separate time points using parent completed questionnaires. ResultsResponse rate for MANCAS1 was 47.5% and 25.4% for MANCAS2. There were 801 individuals for whom a response to both studies was received. There was a significant reduction in the prevalence of night cough (29.5% vs 18.3%, McNemar <0.01) and antibiotic use for respiratory infections (9.1% vs 4.3%, McNemar <0.01) between the two study time points. The prevalence of hay fever/eczema increased (41.6% vs 46.9%, McNemar <0.01) between the two studies. There was no significant difference in the prevalence of wheeze, exercise-induced wheeze or asthma medication. ConclusionsAlthough this report of respiratory symptom prevalence in the same population at two time points over a 7-year period shows a constant burden of asthma symptoms, there is some suggestion of variability in asthma symptom prevalence within the cohort as the children matured while the burden of allergy symptoms increased.

Urban city transportation mode and respiratory health effect of air pollution: a cross-sectional study among transit and non-transit workers in Nigeria [RESEARCH]

Thu, 11 Oct 2012 00:00:00 +0000

ObjectivesTo assess the respiratory health effect of city ambient air pollutants on transit and non-transit workers and compare such effects by transportation mode, occupational exposure and sociodemographic characteristics of participants. DesignCross-sectional, randomised survey. SettingA two primary healthcare centre survey in 2009/2010 in Uyo metropolis, South-South Nigeria. ParticipantsOf the 245 male participants recruited, 168 (50 taxi drivers, 60 motorcyclists and 58 civil servants) met the inclusion criteria. These include age 18-35 years, a male transit worker or civil servant who had worked within Uyo metropolis for at least a year prior to the study, and had no history of respiratory disorders/impairment or any other debilitating illness. Main outcome measureThe adjusted ORs for respiratory function impairment (force vital capacity (FVC) and/or FEV1<80% predicted or FEV1/FVC<70% predicted) using Global Initiative for Chronic Obstructive Lung Diseases (GOLD) and National Institute for Health and Clinical Excellence (NICE) criteria were calculated. In order to investigate specific occupation-dependent respiratory function impairment, a comparison was made between the ORs for respiratory impairment in the three occupations. Adjustments were made for some demographic variables such as age, BMI, area of residence, etc. ResultsExposure to ambient air pollution by occupation and transportation mode was independently associated with respiratory functions impairment and incident respiratory symptoms among participants. Motorcyclists had the highest effect, with adjusted OR 3.10, 95% CI 0.402 to 16.207 for FVC<80% predicted and OR 1.71, 95% CI 0.61 to 4.76 for FEV1/FVC<70% predicted using GOLD and NICE criteria. In addition, uneducated, currently smoking transit workers who had worked for more than 1 year, with three trips per day and more than 1 h transit time per trip were significantly associated with higher odds for respiratory function impairment at p<0.001, respectively. ConclusionsFindings of this study lend weights to the existing literature on the adverse respiratory health effect of ambient air pollution on city transit workers globally. The role of other confounders acting synergistically to cause a more deleterious effect is obvious. In all, the effect depends on the mode and duration of exposure.

Lung function in volunteers before and after exposure to trichloramine in indoor pool environments and asthma in a cohort of pool workers [RESEARCH]

Mon, 8 Oct 2012 00:00:00 +0000

ObjectivesExposure to trichloramine (NCl3) in indoor swimming-pool environments is known to cause mucous membrane irritation, but if it gives rise to changes in lung function or asthma in adults is not known. (1) We determined lung function in volunteers before and after exposure to indoor pool environments. (2) We studied the occurrence of respiratory symptoms and asthma in a cohort of pool workers. Design/methods/participants(1) We studied two groups of volunteers, 37 previously non-exposed healthy persons and 14 pool workers, who performed exercise for 2 h in an indoor pool environment. NCl3 in air was measured during pool exposures and in 10 other pool environments. Filtered air exposures were used as controls. Lung function and biomarkers of pulmonary epithelial integrity were measured before and after exposure. (2) We mailed a questionnaire to 1741 persons who indicated in the Swedish census 1990 that they worked at indoor swimming-pools. Results(1) In previously non-exposed volunteers, statistically significant decreases in FEV1 (forced expiratory volume) and FEV% (p=0.01 and 0.05, respectively) were found after exposure to pool air (0.23 mg/m3 of NCl3). In pool workers, a statistically significant decrease in FEV% (p=0.003) was seen (but no significant change of FEV1). In the 10 other pool environments the median NCl3 concentration was 0.18 mg/m3. (2) Our nested case/control study in pool workers found an OR for asthma of 2.31 (95% CI 0.79 to 6.74) among those with the highest exposure. Exposure-related acute mucous membrane and respiratory symptoms were also found. ConclusionsThis is the first study in adults showing statistically significant decreases in lung function after exposure to NCl3. An increased OR for asthma among highly exposed pool workers did not reach statistical significance, but the combined evidence supports the notion that current workroom exposures may contribute to asthma development. Further research on sensitive groups is warranted.

Impacts of early smoking initiation: long-term trends of lung cancer mortality and smoking initiation from repeated cross-sectional surveys in Great Britain [RESEARCH]

Mon, 8 Oct 2012 00:00:00 +0000

ObjectiveTo show long-term trends of smoking initiation in Great Britain including unanalysed data and assess the impact of early smoking initiation on the lung cancer mortality in later ages focusing on birth cohorts. DesignReanalysis of repeated cross-sectional surveys conducted 13 times during 1965-1987. SettingGreat Britain. ParticipantsMen and women aged 16 years and over in each survey. Primary outcome measuresSmoking initiation for 1898-1969 birth cohorts and lung cancer mortality in 1950-2009. ResultsIn men, 1900-1925 birth cohorts showed high smoking initiation (>32%, >50% and >80% at 15, 17 and 29 years old, respectively). Correspondingly, the lung cancer mortality in these cohorts exceeded 1 per 1000 at a young age (50-54 years old). In women, smoking initiation increased clearly from the 1898 cohort to the 1925 cohort (2% to 12%, 4% to 24%, and 13% to 54% at 15, 17 and 29 years old, respectively). Correspondingly, the age at which the mortality exceeded 1 per 1000 became younger (75-79 to 60-64 years old). In both men and women, short-term decreases in initiation were seen from the late-1920s cohorts. Correspondingly, lung cancer mortality decreased. In women, initiation increased again after the mid-1930s cohorts, and mortality increased after they became 60-64 years old. ConclusionsClear relationships between smoking initiation and lung cancer mortality across birth cohorts were observed. Countries with rapid increases in initiation in teens should not underestimate the risk in the distant future. Because of the long time lags within cohorts compared with rapid changes in smoking habits across cohorts, age-specific measures focusing on birth cohorts should be monitored.

Lung Injury Prevention with Aspirin (LIPS-A): a protocol for a multicentre randomised clinical trial in medical patients at high risk of acute lung injury [PROTOCOL]

Tue, 4 Sep 2012 00:00:00 +0000

IntroductionAcute lung injury (ALI) is a devastating condition that places a heavy burden on public health resources. Although the need for effective ALI prevention strategies is increasingly recognised, no effective preventative strategies exist. The Lung Injury Prevention Study with Aspirin (LIPS-A) aims to test whether aspirin (ASA) could prevent and/or mitigate the development of ALI. Methods and analysisLIPS-A is a multicentre, double-blind, randomised clinical trial testing the hypothesis that the early administration of ASA will result in a reduced incidence of ALI in adult patients at high risk. This investigation will enrol 400 study participants from 14 hospitals across the USA. Conditional logistic regression will be used to test the primary hypothesis that early ASA administration will decrease the incidence of ALI. Ethics and disseminationSafety oversight will be under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained from the DSMB prior to enrolling the first study participant. Approval of both the protocol and informed consent documents were also obtained from the institutional review board of each participating institution prior to enrolling study participants at the respective site. In addition to providing important clinical and mechanistic information, this investigation will inform the scientific merit and feasibility of a phase III trial on ASA as an ALI prevention agent. The findings of this investigation, as well as associated ancillary studies, will be disseminated in the form of oral and abstract presentations at major national and international medical specialty meetings. The primary objective and other significant findings will also be presented in manuscript form. All final, published manuscripts resulting from this protocol will be submitted to Pub Med Central in accordance with the National Institute of Health Public Access Policy.

Factors influencing the length of hospital stay among patients resident in Blackpool admitted with COPD: a cross-sectional study [RESEARCH]

Sat, 1 Sep 2012 00:00:00 +0000

ObjectivesTo identify the differential effects of patient, health service, temporal and geographic factors on length of stay (LOS) for chronic obstructive pulmonary disease (COPD)-related admissions. DesignWe used stratified Cox proportional hazard model to evaluate the association between LOS and patient, health service, temporal and geographical factors. SettingPatients resident in Blackpool, North West England, admitted to the local hospital with COPD. ParticipantsWe used the Admitted Patient Care General Episode Commissioning Dataset for the period 1 April 2005-31 March 2010. We analysed records of admission spells among patients resident in Blackpool aged 40 years or older admitted with a primary diagnosis of COPD. ResultsThere were 2410 admissions meeting the inclusion criteria over the period. These admissions were attributed to 1172 COPD patients, an average of 2.06 admissions per patient. The median LOS was 6 days (95% CI 6 to 6) while the mean was 9.8 days (95% CI 9.1 to 10.5). Patients were 22% more likely to be discharged earlier in 2009/2010 compared with 2005/2006 (adjusted HR 1.22; p=0.0100). LOS was associated with socioeconomic deprivation with those in the most deprived areas being 35% less likely to be discharged earlier compared with those from the least deprived areas (adjusted HR 0.65; p=0.0010). ConclusionsLOS among COPD patients have reduced over the period of the study. Age, deprivation, Charlson index, specialty of admission and cause of exacerbations were independently associated with LOS. Though there were no significant associations between LOS and season of admission and distance from hospital, there were significant variations in LOS associated with these variables based on selected patient characteristics.

Understanding variation in primary medical care: a nine-country qualitative study of clinicians' accounts of the non-clinical factors that shape antibiotic prescribing decisions for lower respiratory tract infection [RESEARCH]

Wed, 22 Aug 2012 00:00:00 +0000

ObjectivesThere is a wide variation between European countries in antibiotic prescribing for patients in primary care with lower respiratory tract infection (LRTI) that is not explained by case mix and clinical factors alone. Variation in antibiotic prescribing that is not warranted by differences in illness and clinical presentation may increase selection of resistant organisms, contributing to the problem of antibiotic resistance. This study aimed to investigate clinicians' accounts of non-clinical factors that influence their antibiotic prescribing decision for patients with LRTI, to understand variation and identify opportunities for addressing possible unhelpful variation. DesignMulticountry qualitative semistructured interview study, with data subjected to a five-stage analytic framework approach (familiarisation, developing a thematic framework from interview questions and emerging themes, indexing, charting and interpretation), and with interviewers commenting on preliminary analytic themes. SettingPrimary care. ParticipantsEighty primary care clinicians randomly selected from primary care research networks based in nine European cities. ResultsClinicians' accounts identified non-clinical factors imposed by the healthcare system operating within specific regional primary care research networks, including patient access to antibiotics before consulting a doctor (Barcelona and Milan), systems to reduce patient expectations for antibiotics (Southampton and Antwerp) and lack of consistent treatment guidelines (Balatonfured and [L]od[z]). Secondly, accounts revealed factors related to specific characteristics of clinicians regardless of network (professional ethos, self-belief in decision-making and commitment to shared decision-making). ConclusionsAddressing healthcare system factors (eg, limiting patients' self-management with antibiotics before consulting in primary care, increased public awareness and provision of more consistent guidelines) may assist in reducing unhelpful variation in antibiotic prescribing. Promoting clinicians' receptivity to change, confidence in decision-making and readiness to invest in explaining prescribing decisions may also be beneficial. As factors were emphasised differently between networks, local flexibility in interventions is likely to maximise effectiveness.

A randomised cross-over cohort study of exposure to emissions from a road tunnel ventilation stack [RESEARCH]

Fri, 17 Aug 2012 00:00:00 +0000

Background and objectiveRoad tunnels are increasingly important components of urban infrastructure. However, knowledge of their health impact on surrounding communities is limited. Our objective was to estimate the short-term respiratory health effects of exposure to emissions from a road tunnel ventilation stack. MethodsWe conducted a randomised cross-over cohort study in 36 volunteers who underwent three exposure scenarios in 2006 before the road tunnel opened, and in 2007 (n=27) and 2008 (n=20) after the tunnel opened. Exposure downwind of the stack was compared to upwind of the stack and to a distant heavily trafficked location adjacent to a main road. Spirometry, exhaled nitric oxide (eNO) and symptom scores were measured repeatedly during each 2 h exposure session. ResultsDownwind locations were associated with increased reports of dry nose' (score difference 0.36; 95% CI 0.09 to 0.63) compared with the control location (2006 vs 2007/2008), but not with impaired lung function, increased airway inflammation or other symptoms. The heavily trafficked location was associated with significantly increased eNO (ratio=1.09; 95% CI 1.04 to 1.14), eye (score difference 0.05; 95% CI 0.01 to 0.10) and chest (score difference 0.21; 95% CI 0.09 to 0.33) symptoms compared to the stack locations. ConclusionsThere was no consistent evidence of adverse respiratory effects from short-term exposures downwind of the tunnel ventilation stack, except for dry nose symptoms. However, the findings of increased airway inflammation and symptoms in subjects after only 2 h exposure at the heavily trafficked location, are suggestive of detrimental effects of short-term exposures to traffic-related air pollution.

Observational follow-up study following two cohorts of children with severe pneumonia after discharge from day care clinic/hospital in Dhaka, Bangladesh [RESEARCH]

Fri, 27 Jul 2012 00:00:00 +0000

ObjectivesTo compare the features of relapse, morbidity, mortality and re-hospitalisation following successful discharge after severe pneumonia in children between a day care group and a hospital group and to explore the predictors of failures during 3 months of follow-up. DesignAn observational study following two cohorts of children with severe pneumonia for 3 months after discharge from hospital/clinic. SettingDay care was provided at the Radda Clinic and hospital care at a hospital in Dhaka, Bangladesh. ParticipantsChildren aged 2-59 months with severe pneumonia attending the clinic/hospital who survived to discharge. InterventionNo intervention was done except providing some medications for minor illnesses, if indicated. Primary outcome measuresThe primary outcome measures were the proportion of successes and failures of day care at follow-up visits as determined by estimating the OR with 95% CI in comparison to hospital care. ResultsThe authors enrolled 360 children with a mean (SD) age of 8 (7) months, 81% were infants and 61% were men. The follow-up compliance dropped from 95% at first to 85% at sixth visit. The common morbidities during the follow-up period included cough (28%), fever (17%), diarrhoea (9%) and rapid breathing (7%). During the follow-up period, significantly more day care children (n=22 (OR 12.2 (95% CI 8.2-17.8))) required re-hospitalisation after completion of initial day care compared with initial hospital care group (n=11 (OR 6.1 (95% CI 3.4-10.6))). The predictors for failure were associated with tachycardia, tachypnoea and hypoxaemia on admission and prolonged duration of stay. ConclusionsThere are considerable morbidities in children discharged following treatment of severe pneumonia like cough, fever, rapid breathing and diarrhoea during 3-month period. The findings indicate the importance of follow-up for early detection of medical problems and their management to reduce the risk of death. Establishment of an effective community follow-up would be ideal to address the problem of non-compliance with follow-up'. Trial registrationThe original randomised control trial comparing day care with hospital care was registered at http://www.clinicaltrials.gov (identifier NCT00455468).

Asthma and allergies in Jamaican children aged 2-17 years: a cross-sectional prevalence survey [RESEARCH]

Thu, 12 Jul 2012 00:00:00 +0000

ObjectiveTo determine the prevalence and severity of asthma and allergies as well as risk factors for asthma among Jamaican children aged 2-17 years. DesignA cross-sectional, community-based prevalence survey using the International Study of Asthma and Allergies in Childhood questionnaire. The authors selected a representative sample of 2017 children using stratified, multistage cluster sampling design using enumeration districts as primary sampling units. SettingJamaica, a Caribbean island with a total population of approximately 2.6 million, geographically divided into 14 parishes. ParticipantsChildren aged 2-17 years, who were resident in private households. Institutionalised children such as those in boarding schools and hospitals were excluded from the survey. Primary and secondary outcome measuresThe prevalence and severity of asthma and allergy symptoms, doctor-diagnosed asthma and risk factors for asthma. ResultsAlmost a fifth (19.6%) of Jamaican children aged 2-17 years had current wheeze, while 16.7% had self-reported doctor-diagnosed asthma. Both were more common among males than among females. The prevalence of rhinitis, hay fever and eczema among children was 24.5%, 25% and 17.3%, respectively. Current wheeze was more common among children with rhinitis in the last 12 months (44.3% vs 12.6%, p<0.001), hay fever (36.8% vs 13.8%, p<0.001) and eczema (34.1% vs 16.4%, p<0.001). Independent risk factors for current wheeze (ORs, 95% CI) were chest infections in the first year of life 4.83 (3.00 to 7.77), parental asthma 4.19 (2.8 to 6.08), rhinitis in the last 12 months 6.92 (5.16 to 9.29), hay fever 4.82 (3.62 to 6.41), moulds in the home 2.25 (1.16 to 4.45), cat in the home 2.44 (1.66 to 3.58) and dog in the home 1.81 (1.18 to 2.78). ConclusionsThe prevalence of asthma and allergies in Jamaican children is high. Significant risk factors for asthma include chest infections in the first year of life, a history of asthma in the family, allergies, moulds and pets in the home.

A case-control study on risk factors associated with death in pregnant women with severe pandemic H1N1 infection [RESEARCH]

Sat, 7 Jul 2012 00:00:00 +0000

ObjectivesTo describe the risk factors associated with death in pregnant women with severe pandemic H1N1 infection. DesignCase-control study. SettingAnhui, China. ParticipantsA total of 46 pregnant women with severe pandemic H1N1 infection were studied during June 2009-April 2011. Primary and secondary outcome measuresAll the cases were confirmed by the clinicians and epidemiologists together based on the positive laboratory result. ResultsOf the seven pregnant women who died of the pandemic H1N1 infection, five (70%) cases were in their third trimester. Twenty-nine (63%) cases from the surviving group were admitted to hospital within 3 days after the onset of symptoms, while only one (2%) case from the death group took the earliest admission 2 days after the onset. There was a significant difference on how soon to be admitted between the death and the surviving groups (OR 0.09, 95% CI 0.01 to 0.68). The median time of administrating corticosteroids was 5 days after the onset in the death group and 3 days in the surviving group showing no significant difference between them (p=0.056). ConclusionsFor the pregnant women with severe p(H1N1) infection, the risk factors associated with death were as follows: the delay of antiviral treatment and being in the third trimester. The corticosteroids therapy appeared to have no effects on preventing the cases from death.

An investigation of the effects of the common cold on simulated driving performance and detection of collisions: a laboratory study [RESEARCH]

Mon, 2 Jul 2012 00:00:00 +0000

ObjectiveThe aim of the present research was to investigate whether individuals with a common cold showed impaired ability on a simulated driving task and the ability to detect potential collisions between moving objects. DesignThe study involved comparison of a healthy group with a group with colds. These scores were adjusted for individual differences by collecting further data when both groups were healthy and using these scores as covariates. On both occasions, volunteers rated their symptoms and carried out a simulated driving session. On the first occasion, volunteers also carried out a collision detection task. SettingUniversity of Leeds Institute for Transport Studies. SampleTwenty-five students from the University of Leeds. Ten volunteers were healthy on both occasions and 15 had a cold on the first session and were healthy on the second. Main outcome measuresIn the collision detection task, the main outcomes were correct detections and response to a secondary identification task. In the simulated driving task, the outcomes were speed, lateral control, gap acceptance, overtaking behaviour, car following, vigilance and traffic light violations. ResultsThose with a cold detected fewer collisions and had a higher divided attention error than those who were healthy. Many basic driving skills were unimpaired by the illness. However, those with a cold were slower at responding to unexpected events and spent a greater percentage of time driving at a headway of <2 s. ConclusionsThe finding that having a common cold is associated with reduced ability to detect collisions and respond quickly to unexpected events is of practical importance. Further research is now required to examine the efficacy of information campaigns and countermeasures such as caffeine.

Focused sonographic examination of the heart, lungs and deep veins in an unselected population of acute admitted patients with respiratory symptoms: a protocol for a prospective, blinded, randomised controlled trial [PROTOCOL]

Wed, 30 May 2012 00:00:00 +0000

IntroductionPatients admitted to hospital with acute respiratory symptoms remain a diagnostic challenge for the emergency physician. The use of focused sonography may improve the initial diagnostics, as most of the diseases, commonly seen and misdiagnosed in patients with acute respiratory symptoms, can be diagnosed with sonography. The protocol describes a prospective, blinded, randomised controlled trial that aims to assess the diagnostic impact of a pragmatic implementation of focused sonography of the heart, lungs and deep veins as a diagnostic modality in acute admitted patients with respiratory symptoms. Methods and analysisThe primary outcome of the study is the number of patients with a correct presumptive diagnosis within 4 h of admission to the emergency department. The patient is randomised to either an intervention or a control group. In the intervention group, the usual initial diagnostic work up is supplemented by focused sonographic examination of the heart, lungs and deep veins of the legs. In the control group, usual diagnostic work up is performed. The {chi}2 test, alternatively the Fischer exact test will be used, to establish whether there is a difference in the distribution of the total number of patients with a correct/incorrect 4 h' presumptive diagnosis in the control group and in the intervention group. Ethics and disseminationThis clinical trial is performed according to the Declaration of Helsinki and has been approved by the Regional Scientific Ethical Committee for Southern Denmark and the Danish Data Protection Agency. The results of the trial will be published according to the CONSORT statement with the extension for pragmatic trials. The results of the trial will be published in a peer-reviewed scientific journal regardless of the outcome. Trial registration numberThis study is registered at http://clinicaltrials.gov, registration number NCT01486394.

A new user cohort study comparing the safety of long-acting inhaled bronchodilators in COPD [RESEARCH]

Tue, 22 May 2012 00:00:00 +0000

ObjectiveTo investigate a possible increased risk observed in tiotropium clinical trials of stroke and other adverse events. DesignNew users of long-acting anticholinergic therapy (tiotropium HandiHaler(R)) were compared with new users of long-acting {beta}-agonist (LABA) monotherapy, and propensity scores were used to control confounding. SettingUK healthcare system general practitioner electronic medical record database. Participants10 840 patients newly prescribed tiotropium (n=4767) or LABA (n=6073), at least 40 years old, and not having asthma as their only respiratory illness. Primary and secondary outcome measuresIncidence rates of total stroke, myocardial infarction, angina and other adverse events. ResultsTiotropium was associated with increased rates of stroke (HR=1.49, 95% CI 0.91 to 2.45), angina (HR=1.38, 95% CI 0.88 to 2.16) and myocardial infarction (HR=1.26, 95% CI 0.72 to 2.21). Groups had similar rates of chronic obstructive pulmonary disease exacerbation (HR=0.95, 95% CI 0.80 to 1.12) and pneumonia (HR=0.96, 95% CI 0.58 to 1.58). Tiotropium was associated with a lower rate of total mortality (HR=0.70, 95% CI 0.56 to 0.89) and asthma exacerbations (HR=0.46, 95% CI 0.36 to 0.57) than users of LABA. ConclusionSmall increased risks of serious ischaemic cardiovascular events have been reported with inhaled anticholinergic medication from randomised and nonrandomized studies of ipratropium, tiotropium HandiHaler(R) and tiotropium Respimat(R). Additional research is needed to understand the full extent of cardiovascular effects of inhaled anticholinergic medications and the patients who may be most susceptible.

Do statins improve outcomes in patients with asthma on inhaled corticosteroid therapy? A retrospective cohort analysis [RESEARCH]

Tue, 22 May 2012 00:00:00 +0000

ObjectivesAnimal studies and clinical trials have examined the potential benefits of statins in asthma management with contradictory results. The objective of this study was to determine if asthma patients on concurrent statins are less likely to have asthma-related hospitalisations. DesignA retrospective cohort study using Mississippi Medicaid data for 2002-2004. ParticipantsAsthma patients [≥]18 years were identified using the ICD9 code 493.xx from 1 July 2002 through 31 December 2003. The index date for an exposed subject was any date within the identification period, 180 days prior to which the subject had at least one inhaled corticosteroid prescription and at least an 80% adherence rate to statins. Asthma patients on inhaled corticosteroids, but not on statins, were selected as the unexposed population. The two groups were matched and followed for 1 year beginning the index date. Main outcomes measuresPatient outcomes in terms of hospitalisations and ER visits were compared using conditional logistic regression. ResultsAfter matching, there were 479 exposed subjects and 958 corresponding unexposed subjects. The odds of asthma-related hospitalisation and/or emergency room (ER) visits for asthma patients on concurrent statins were almost half the odds for patients not on statins (OR=0.55; 95% CI (0.37 to 0.84); p=0.0059). Similarly, the odds of asthma-related ER visits were significantly lower for patients on statins (OR=0.48; 95% CI (0.28 to 0.82); p=0.0069). ConclusionThe findings suggest beneficial effects of statins in asthma management. Further prospective investigations are required to provide more conclusive evidence.

The International Community-Acquired Pneumonia (CAP) Collaboration Cohort (ICCC) study: rationale, design and description of study cohorts and patients [RESEARCH]

Mon, 21 May 2012 00:00:00 +0000

ObjectiveTo improve the understanding of the determinants of prognosis and accurate risk stratification in community-acquired pneumonia (CAP). DesignMulticentre collaboration of prospective cohorts. Setting6 cohorts from the USA, Canada, Hong Kong and Spain. ParticipantsFrom a published meta-analysis of risk stratification studies in CAP, the authors identified and pooled individual patient-level data from six prospective cohort studies of CAP (three from the USA, one each from Canada, Hong Kong and Spain) to create the International CAP Collaboration Cohort. Initial essential inclusion criteria of meta-analysis were (1) prospective design, (2) in English language, (3) reported 30-day mortality and transfer to an intensive or high dependency care and (4) minimum 1000 participants. Common baseline patient characteristics included demographics, history and physical examination findings, comorbidities and laboratory and radiographic findings. Primary and secondary outcome measuresThis paper reports the rationale, hypotheses and analytical framework and also describes study cohorts and patients. The authors aim to (1) compare the prognostic accuracy of existing CAP risk stratification tools, (2) assess patient-level determinants of prognosis, (3) improve risk stratification by combined use of scoring systems and (4) understand prognostic factors for specific patient groups. ResultsThe six cohorts assembled from 1991 to 2007 included 13 784 patients (median age 71 years, 54% men). Aside from one randomised controlled study, the remaining five were cohort studies, but all had similar inclusion criteria. Overall, there was 0%-6% missing data. A total of 6159 (44%) had severe pneumonia by Pneumonia Severity Index class IV/V. Mortality at 30 days was 8% (1036). Admission to intensive care or high dependency unit was also 8% (1059). ConclusionsInternational CAP Collaboration Cohort provides a pooled multicentre data set of patients with CAP, which will help us to better understand the prognosis of CAP.

A cohort study of mortality predictors and characteristics of patients with combined pulmonary fibrosis and emphysema [RESEARCH]

Tue, 15 May 2012 00:00:00 +0000

ObjectivesOur purpose was to assess the clinical data, predictors of mortality and acute exacerbation (AE) in combined pulmonary fibrosis and emphysema (CPFE) patients. DesignSingle-centre retrospective cohort study. SettingTeaching hospital in Japan. ParticipantsWe identified 93 CPFE patients with high-resolution computed tomographic (HRCT) through multidisciplinary discussion. Patients who had connective tissue disease, drug-associated interstitial lung disease and occupationally related interstitial lung disease, such as asbestosis and silicosis, were excluded. InterventionsThere were no interventions. MethodsMedical records and HRCT scans from January 2002 through December 2007 were reviewed retrospectively at our hospital. Ninety-three patients had CPFE. ResultsThe mean age of CPFE patients was 74 years. Idiopathic pulmonary fibrosis and non-specific interstitial pneumonia were observed as distinct HRCT patterns. Forty-two patients showed finger clubbing. Mean serum Krebs von den Lungen-6 (KL-6) and per cent predicted forced vital capacity (%FVC) were 1089 IU/l, 63.86%, respectively. Twenty-two patients developed AE during observation period. Baseline KL-6 was a strong predictor of AE (OR=1.0016, p=0.009). Finger clubbing (HR=2.2620, p=0.015) and per cent predicted forced expiratory volume in one second/%FVC more than 1.2 (HR=1.9259, p=0.048) were independent predictors of mortality in CPFE. ConclusionsBaseline serum KL-6 was a useful predictor of AE (cut-off =1050, receiver operator characteristic curve: 0.7720), which occurred in 24% (22/93) of the CPFE patients. Finger clubbing and per cent predicted forced expiratory volume in one second/%FVC more than 1.2 were independent predictors of mortality.

Strategies to increase influenza vaccination rates: outcomes of a nationwide cross-sectional survey of UK general practice [RESEARCH]

Fri, 11 May 2012 00:00:00 +0000

ObjectiveTo identify practice strategies associated with higher flu vaccination rates in primary care. DesignLogistic regression analysis of data from a cross-sectional online questionnaire. Setting795 general practices across England. Participants569 practice managers, 335 nursing staff and 107 general practitioners. Primary outcome measuresFlu vaccination rates achieved by each practice in different groups of at-risk patients. Results7 independent factors associated with higher vaccine uptake were identified. Having a lead staff member for planning the flu campaign and producing a written report of practice performance predicted an 8% higher vaccination rate for at-risk patients aged <65 years (OR 1.37, 95% CI 1.10 to 1.71). These strategies, plus sending a personal invitation to all eligible patients and only stopping vaccination when Quality and Outcomes Framework targets are reached, predicted a 7% higher vaccination rate (OR 1.45, 95% CI 1.10 to 1.92) in patients aged [≥]65 years. Using a lead member of staff for identifying eligible patients, with either a modified manufacturer's or in-house search programme for interrogating the practice IT system, independently predicted a 4% higher vaccination rate in patients aged [≥]65 years (OR 1.22, 95% CI 1.06 to 1.41/OR 1.20, 95% CI 1.03 to 1.40). The provision of flu vaccine by midwives was associated with a 4% higher vaccination rate in pregnant women (OR 1.19, 95% CI 1.02 to 1.40). ConclusionsClear leadership, effective communication about performance and methods used to identify and contact eligible patients were independently associated with significantly higher rates of flu vaccination. Financial targets appear to incentivise practices to work harder to maximise seasonal influenza vaccine uptake. The strategies identified here could help primary care providers to substantially increase their seasonal flu vaccination rates towards or even above the Chief Medical Officer's targets.

Grey and white matter abnormalities in chronic obstructive pulmonary disease: a case-control study [RESEARCH]

Tue, 24 Apr 2012 00:00:00 +0000

ObjectivesThe irreversible airflow limitation characterised by chronic obstructive pulmonary disease (COPD) causes a decrease in the oxygen supply to the brain. The aim of the present study was to investigate brain structural damage in COPD. DesignRetrospective case-control study. Patients with COPD and healthy volunteers were recruited. The two groups were matched in age, gender and educational background. SettingA hospital and a number of communities: they are all located in southern Fujian province, China. Participants25 stable patients and 25 controls were enrolled from December 2009 to May 2011. MethodsUsing voxel-based morphometry and tract-based spatial statistics based on MRI to analyse grey matter (GM) density and white matter fractional anisotropy (FA), respectively, and a battery of neuropsychological tests were performed. ResultsPatients with COPD (vs controls) showed decreased GM density in the limbic and paralimbic structures, including right gyrus rectus, left precentral gyrus, bilateral anterior and middle cingulate gyri, bilateral superior temporal gyri, bilateral anterior insula extending to Rolandic operculum, bilateral thalamus/pulvinars and left caudate nucleus. Patients with COPD (vs controls) had decreased FA values in the bilateral superior corona radiata, bilateral superior and inferior longitudinal fasciculus, bilateral optic radiation, bilateral lingual gyri, left parahippocampal gyrus and fornix. Lower FA values in these regions were associated with increased radial diffusivity and no changes of longitudinal diffusivity. Patients with COPD had poor performances in the Mini-Mental State Examination, figure memory and visual reproduction. GM density in some decreased regions in COPD had positive correlations with arterial blood Po2, negative correlations with disease duration and also positive correlations with visual tasks. ConclusionThe authors demonstrated that COPD exhibited loss of regional GM accompanied by impairment of white matter microstructural integrity, which was associated with disease severity and may underlie the pathophysiological and psychological changes of COPD.

Inhaled hypertonic saline in adults hospitalised for exacerbation of cystic fibrosis lung disease: a retrospective study [RESEARCH]

Thu, 19 Apr 2012 00:00:00 +0000

BackgroundInhaled hypertonic saline (HTS) improves quality of life and reduces pulmonary exacerbations when given long term in patients with cystic fibrosis (CF). While increasingly being offered for acute pulmonary exacerbations, little is known about the efficacy in this setting. ObjectivesThe authors examined the tolerability and efficacy of HTS use among adult subjects hospitalised with a CF pulmonary exacerbation and hypothesised that use of HTS would improve pulmonary function during the admission. DesignPilot retrospective non-randomised study. SettingSingle tertiary care centre. Participants45 subjects admitted to the inpatient service for acute CF pulmonary exacerbation in 2006-2007. A subset of 18 subjects who were also admitted in 2005 when HTS was not available was included in the comparative study. Primary outcomeChange in forced expiratory volume in one second from admission to discharge. Secondary outcomesChange in weight from admission to discharge and time to next exacerbation. ResultsMean age was 32.5 years, and mean length of stay was 11.5 days. HTS was offered to 33 subjects and was well tolerated for a total use of 336 days out of 364 days of hospital stay. Baseline demographics, lung function and sputum culture results were comparable in first and second visits. Use of HTS was not associated with an improvement in forced expiratory volume in one second (p=0.1), weight gain (p=0.24) or in the time to next admission (p=0.08). ConclusionsThese pilot data suggest that HTS is well tolerated during CF pulmonary exacerbation but offers no clear outcome benefits. It is possible that HTS may not have much advantage above and beyond intensive rehabilitation and intravenous antibiotics and may add to hospital costs and treatment burden.

The trajectory to diagnosis with pulmonary arterial hypertension: a qualitative study [RESEARCH]

Wed, 18 Apr 2012 00:00:00 +0000

ObjectivesTo investigate the patient's experience of the trajectory to receiving a diagnosis of pulmonary arterial hypertension (PAH) and inform the provision of care for this patient group. DesignQualitative study using in-depth one-to-one interviews and pictorial representations. Data were analysed using thematic analysis. SettingParticipants were interviewed in their own homes across England. Participants30 patients with a diagnosis of pulmonary hypertension (18 participants were women, mean age 56 and range 26-80 years and time since diagnosis ranged from a few months to more than 12 years) participated. ResultsAll participants, regardless of the time since diagnosis, vividly described the process from manifestation of symptoms to receiving a confirmed diagnosis. The authors present data using three major themes: (i) making sense of symptoms, (ii) process of elimination and (iii) being diagnosed with PAH. Making sense of symptoms represented an early period of perseverance--people tried to carry-on as usual despite unexplained breathlessness'. As time progressed, this period was punctuated by critical events that triggered seeking medical advice. Once medical contact had been made, patients described a period of elimination' and convoluted contact with the medical profession. Dyspnoea misdiagnosis was a key factor that delayed the PAH diagnosis. Diagnosis disclosure by some medical professionals was also viewed as lacking empathy. More positive experiences were relayed when the medical team disclosing the diagnosis acknowledged previous limitations. ConclusionsA lack of awareness of this illness from both the sufferer themselves and the medical profession emerged as a central theme and led to prolonged periods of being misdiagnosed. The application of a diagnostic pathway for unexplained dyspnoea that alerts practitioners to rare conditions could expedite the process of correct diagnosis.

International collaboration: a retrospective study examining the survival of Irish citizens following lung transplantation in both the UK and Ireland [RESEARCH]

Wed, 28 Mar 2012 00:00:00 +0000

ObjectivePrior to 2005, Irish citizens had exclusively availed of lung transplantation services in the UK. Since 2005, lung transplantation has been available to these patients in both the UK and Ireland. We aimed to evaluate the outcomes of Irish patients undergoing lung transplantation in both the UK and Ireland. DesignWe retrospectively examined the outcome of Irish patients transplanted in the UK and Ireland. Lung allocation score (LAS) was used as a marker of disease severity. ResultsA total of 134 patients have undergone transplantation. 102 patients underwent transplantation in the UK and 32 patients in Ireland. In total, 52% were patients with cystic fibrosis, 19% had emphysema and 15% had idiopathic pulmonary fibrosis. In Ireland, 44% of the patients suffered from idiopathic pulmonary fibrosis, 31% had emphysema and 16% had cystic fibrosis. A total of 96 double sequential transplants and 38 single transplants have been performed. LAS of all patients undergoing lung transplantation was 37.8 ({+/-}1.02). The mean LAS for patients undergoing lung transplantation in Ireland was 44.7 ({+/-}3.1), and 35 ({+/-}0.4) for patients undergoing lung transplantation in the UK (p<0.05). The 5-year survival of all Irish citizens who had undergone lung transplantation was 73%. The 5-year survival of Irish patients transplanted in the UK was 69% and in Ireland was 91% and 73% at 5.01 years. ConclusionsInternational collaboration can be achieved, as evidenced by the favourable outcomes seen in Irish citizens who undergo lung transplantation in both the UK and Ireland. Irish citizens undergoing lung transplantation in Ireland have a higher LAS score. Despite excellent outcomes, an intention-to-treat analysis of the treatment utility (transplant) indicates the limited effectiveness of lung transplantation in Ireland and emphasises the need for increased rates of lung transplantation.

A retrospective cross-sectional study of risk factors and clinical spectrum of children admitted to hospital with pandemic H1N1 influenza as compared to influenza A [RESEARCH]

Sun, 11 Mar 2012 00:00:00 +0000

ObjectiveTo compare risk factors for severe disease as measured by admission to hospital and intensive care unit (ICU) and other clinical outcomes in children with pandemic H1N1 (pH1N1) versus those with seasonal influenza. DesignRetrospective analysis of children admitted to hospital with pH1N1 versus seasonal influenza A. SettingCanadian tertiary referral children's hospital. ParticipantsAll laboratory-identified cases of pH1N1 in children younger than 18 years admitted to hospital in 2009 (n=176) and all seasonal influenza A cases admitted to hospital from influenza seasons 2004-2005 to 2008-2009 (n=200). Children with onset of symptoms more than 3 days after admission were excluded. Primary and secondary outcome measuresPrimary outcomes include admission to hospital and ICU and need for mechanical ventilation. Secondary outcomes include length of stay in hospital and duration of supplemental oxygen requirement. ResultsChildren admitted with pH1N1 were older than seasonal influenza A admissions (hospital admission: 6.5 vs 3.3 years, p<0.01; ICU admission: 7.3 vs 3.6 years, p=0.02). Children hospitalised with pH1N1 were more likely to have a pre-existing diagnosis of asthma (15% vs 5%, p<0.01); however, there was no difference in the severity of pre-existing asthma between the two groups. After controlling for obesity, asthma (OR 4.59, 95% CI 1.42 to 14.81) and age [≥]5 years (OR 2.87, 95% CI 1.60 to 5.16) were more common risk factors in admitted children with pH1N1. Asthma was a significant predictor of the need for intensive care in patients with pH1N1 (OR 4.56, 95% CI 1.16 to 17.89) but not in patients with seasonal influenza A. ConclusionWhile most pH1N1 cases presented with classic influenza-like symptoms, risk factors for severe pH1N1 disease differed from seasonal influenza A. Older age and asthma were associated with increased admission to hospital and ICU for children with pH1N1.

A survey of early health effects of the Eyjafjallajokull 2010 eruption in Iceland: a population-based study [RESEARCH]

Thu, 8 Mar 2012 00:00:00 +0000

ObjectiveTo estimate physical and mental health effects of the Eyjafjallajokull volcanic eruption on nearby residents. DesignCross-sectional study. SettingThe Icelandic volcano Eyjafjallajokull erupted on 14 April 2010. The eruption lasted for about 6 weeks and was explosive, ejecting some 8 million tons of fine particles into the atmosphere. Due to prevailing winds, the ash spread mostly to the south and south-east, first over the rural region to the south, later over the Atlantic Ocean and Europe, closing European air space for several days. ParticipantsResidents (n=207) of the most ash-exposed rural area south and east of the volcano. MethodsThe study period was from 31 May to 11 June 2010. Participants were examined by a physician. To ascertain respiratory health, standardised spirometry was performed before and after the use of a bronchodilator. All adult participants answered questionnaires about mental and physical health, their children's health and the use of protective equipment. ResultsEvery other adult participant reported irritation in eyes and upper airway when exposed to volcanic ash. Adults (n=26) and children (n=5) with pre-existing asthma frequently reported worsening of their symptoms. No serious health problems requiring hospitalisation could be attributed to the eruption. The majority of the participants reported no abnormal physical or mental symptoms to the examining physician. Compared to an age- and gender-matched reference group, the ash-exposed participants reported lower smoking rates and were less likely to have ventilation impairment. Less than 10% of the participants reported symptoms of stress, anxiety or depression. ConclusionsShort-term ash exposure was associated with upper airway irritation symptoms and exacerbation of pre-existing asthma but did not contribute to serious health problems. The exposure did not impair respiratory function compared to controls. Outdoor use of protective glasses and face masks was considered protective against irritation in eyes and upper airway.

Protocol: inspiratory muscle training for promoting recovery and outcomes in ventilated patients (IMPROVe): a randomised controlled trial [PROTOCOL]

Fri, 2 Mar 2012 00:00:00 +0000

IntroductionInspiratory muscle weakness is a known consequence of mechanical ventilation and a potential contributor to difficulty in weaning from ventilatory support. Inspiratory muscle training (IMT) reduces the weaning period and increases the likelihood of successful weaning in some patients. However, it is not known how this training affects the residual inspiratory muscle fatigability following successful weaning nor patients' quality of life or functional outcomes. Methods and analysisThis dual centre study includes two concurrent randomised controlled trials of IMT in adult patients who are either currently ventilator-dependent (>7 days) (n=70) or have been recently weaned from mechanical ventilation (>7 days) in the past week (n=70). Subjects will be stable, alert and able to actively participate and provide consent. There will be concealed allocation to either treatment (IMT) or usual physiotherapy (including deep breathing exercises without a resistance device). Primary outcomes are inspiratory muscle fatigue resistance and maximum inspiratory pressures. Secondary outcomes are quality of life (Short Form-36v2, EQ-5D), functional status (Acute Care Index of Function), rate of perceived exertion (Borg Scale), intensive care length of stay (days), post intensive care length of stay (days), rate of reintubation (%) and duration of ventilation (days). Ethics and disseminationEthics approval has been obtained from relevant institutions, and results will be published with a view to influencing physiotherapy practice in the management of long-term ventilator-dependent patients to accelerate weaning and optimise rehabilitation outcomes. Trial registration numberACTRN12610001089022.

Fibroproliferative changes on high-resolution CT in the acute respiratory distress syndrome predict mortality and ventilator dependency: a prospective observational cohort study [RESEARCH]

Thu, 1 Mar 2012 00:00:00 +0000

ObjectivesTo examine whether the extent of fibroproliferative changes on high-resolution CT (HRCT) scan influences prognosis, ventilator dependency and the associated outcomes in patients with early acute respiratory distress syndrome (ARDS). DesignA prospective observational cohort study. SettingIntensive care unit in a teaching hospital. Participants85 patients with ARDS who met American-European Consensus Conference Criteria and eligible criteria. InterventionsHRCT scans were performed and prospectively evaluated by two independent observers on the day of diagnosis and graded into six findings according to the extent of fibroproliferation. An overall HRCT score was obtained by previously published method. Primary and secondary outcomesThe primary outcome was 60-day mortality. Secondary outcomes included the number of ventilator-free days, organ failure-free days, the incidence of barotraumas and the occurrence of ventilator-associated pneumonia. ResultsHigher HRCT scores were associated with statistically significant decreases in organ failure-free days as well as ventilator-free days. Multivariate Cox proportional hazards model showed that the HRCT score remained an independent risk factor for mortality (HR 1.20; 95% CI 1.06 to 1.36; p=0.005). Multivariate analysis also revealed that the CT score had predictive value for ventilator weaning within 28 days (OR 0.63; 95% CI 0.48 to 0.82; p=0.0006) as well as for an incidence of barotraumas (OR 1.61; 95% CI 1.08 to 2.38; p=0.018) and for an occurrence of ventilator-associated pneumonia (OR 1.46; 95% CI 1.13 to 1.89; p=0.004). A HRCT score <210 enabled prediction of 60-day survival with 71% sensitivity and 72% specificity and of ventilator-weaning within 28 days with 75% sensitivity and 76% specificity. ConclusionsPulmonary fibroproliferation assessed by HRCT in patients with early ARDS predicts increased mortality with an increased susceptibility to multiple organ failure, including ventilator dependency and its associated outcomes.

The Peru Urban versus Rural Asthma (PURA) Study: methods and baseline quality control data from a cross-sectional investigation into the prevalence, severity, genetics, immunology and environmental factors affecting asthma in adolescence in Peru [RESEARCH]

Wed, 22 Feb 2012 00:00:00 +0000

ObjectivesAccording to a large-scale international survey, Peru has one of the highest prevalences of asthma worldwide; however, data from this survey were limited to participants from urban Lima. The authors sought to characterise the epidemiology of asthma in Peru in two regions with disparate degrees of urbanisation. In this manuscript, the authors summarise the study design and implementation. DesignA cross-sectional study. ParticipantsUsing census data of 13-15-year-old adolescents from two communities in Peru, the authors invited a random sample of participants in Lima (n=725) and all adolescents in Tumbes (n=716) to participate in our study. Primary and secondary outcome measuresThe authors asked participants to complete a questionnaire on asthma symptoms, environmental exposures and socio-demographics and to undergo spirometry before and after bronchodilator, skin allergy testing and exhaled nitric oxide testing. The authors obtained blood samples for haematocrit, total IgE levels, vitamin D levels and DNA in all participants and measured indoor particulate matter concentrations for 48 h in a random subset of 70-100 households at each site. ResultsOf 1851 eligible participants, 1441 (78%) were enrolled and 1159 (80% of enrolled) completed all physical tests. 1283 (89%) performed spirometry according to standard guidelines, of which 86% of prebronchodilator tests and 92% of postbronchodilator tests were acceptable and reproducible. 92% of allergy skin tests had an adequate negative control. The authors collected blood from 1146 participants (79%) and saliva samples from 148 participants (9%). Overall amounts of DNA obtained from blood or saliva were 25.8 g, with a 260/280 ratio of 1.86. ConclusionsThis study will contribute to the characterisation of a variety of risk factors for asthma, including urbanisation, total IgE levels, vitamin D levels and candidate genes, in a resource-poor setting. The authors present data to support high quality of survey, allergic, spirometric and genetic data collected in our study.

Risk of tuberculosis among people with diabetes mellitus: an Australian nationwide cohort study [RESEARCH]

Mon, 13 Feb 2012 00:00:00 +0000

ObjectivePrevious studies that have found an increased risk for tuberculosis (TB) in people with diabetes mellitus (DM) have been conducted in segments of the population and have not adjusted for important potential confounders. We sought to determine the RR for TB in the presence of DM in a national population with data on confounding factors in order to inform the decision-making process about latent tuberculosis infection (LTBI) screening in people with diabetes. DesignWhole population historical cohort study. SettingAll Australian States and Territories with a mean TB incidence of 5.8/100 000. ParticipantsCases of TB in people with DM were identified by record linkage using the National Diabetes Services Scheme Database and TB notification databases for the years 2001-2006. Primary and secondary outcome measuresPrimary outcome was notified cases of TB. Secondary outcome was notified cases of culture-confirmed TB. RR of TB was estimated with adjustment for age, sex, TB incidence in country of birth and indigenous status. ResultsThere were 6276 cases of active TB among 19 855 283 people living in Australia between 2001 and 2006. There were 271 (188 culture positive) cases of TB among 802 087 members of the DM cohort and 130 cases of TB among 273 023 people using insulin. The crude RR of TB was 1.78 (95% CI 1.17 to 2.73) in all people with DM and 2.16 (95% CI 1.19 to 3.93) in people with DM using insulin. The adjusted RRs were 1.48 (95% CI 1.04 to 2.10) and 2.27 (95% CI 1.41 to 3.66), respectively. ConclusionsThe presence of DM alone does not justify screening for LTBI. However, when combined with other risk factors for TB, the presence of DM may be sufficient to justify screening and treatment for LTBI.

Efficacy and safety of 4 weeks' treatment with combined fluticasone furoate/vilanterol in a single inhaler given once daily in COPD: a placebo-controlled randomised trial [RESEARCH]

Thu, 19 Jan 2012 00:00:00 +0000

BackgroundFluticasone furoate/vilanterol (FF/VI) is a novel once-daily (OD) inhaled corticosteroid/long-acting {beta}2 agonist combination in development for chronic obstructive pulmonary disease (COPD) and asthma. Trial designA multicentre, randomised, double-blind, parallel-group, placebo-controlled study. MethodsParticipants were patients with moderate-to-severe COPD treated with placebo or FF/VI 400/25 g OD for 4 weeks. Study objectives were to assess the safety and efficacy of FF/VI 400/25 g OD administered for 4 weeks via a novel dry powder inhaler. Co-primary end points were change from baseline in weighted mean (wm) heart rate 0-4 h postdose at day 28 and the incidence of adverse events (AEs). Secondary end points included change from baseline in trough forced expiratory volume in one second (FEV1) (23-24 h postdose; day 29) and wm FEV1 (0-4 h postdose; day 28). Patients were randomised to receive FF/VI 400/25 g or placebo in a 2:1 ratio; all patients and investigators were blinded to active or placebo treatment. Results60 patients (mean age 64 years) were randomised (FF/VI: n=40; placebo: n=20), and all contributed data to the analysis. Mean screening post-bronchodilator FEV1 per cent predicted was comparable between groups (FF/VI: 58.5%; placebo: 60.1%). The wm heart rate 0-4 h postdose was similar between groups (difference: 0.6 beats per minute; 95% CI -3.9 to 5.1). More on-treatment AEs were reported in the FF/VI group (68%) compared with the placebo group (50%). The most common drug-related AEs in the FF/VI group were oral candidiasis (8%) and dysphonia (5%). There were no clinically relevant effects on laboratory values, including glucose and potassium, or on vital signs or ECGs/Holters. The FF/VI group had statistically greater improvements compared with placebo in trough FEV1 (mean difference 183 ml) and 0-4 h postdose wm FEV1 (mean difference 236 ml). ConclusionFF/VI has a good safety and tolerability profile and improves lung function compared with placebo in patients with COPD. Trial registration numberclinical trials.gov--NCT00731822.

Addressing geographical variation in the progression of non-communicable diseases in Peru: the CRONICAS cohort study protocol [PROTOCOL]

Wed, 11 Jan 2012 00:00:00 +0000

BackgroundThe rise in non-communicable diseases in developing countries has gained increased attention. Given that around 80% of deaths related to non-communicable diseases occur in low- and middle-income countries, there is a need for local knowledge to address such problems. Longitudinal studies can provide valuable information about disease burden of non-communicable diseases in Latin America to inform both public health and clinical settings. MethodsThe CRONICAS cohort is a longitudinal study performed in three Peruvian settings that differ by degree of urbanisation, level of outdoor and indoor pollution and altitude. The author sought to enrol an age- and sex-stratified random sample of 1000 participants at each site. Study procedures include questionnaires on socio-demographics and well-known risk factors for cardiopulmonary disease, blood draw, anthropometry and body composition, blood pressure and spirometry before and after bronchodilators. All participants will be visited at baseline, at 20 and 40 months. A random sample of 100 households at each site will be assessed for 24 h particulate matter concentration. Primary outcomes include prevalence of risk factors for cardiopulmonary diseases, changes in blood pressure and blood glucose over time and decline in lung function. DiscussionThere is an urgent need to characterise the prevalence and burden of non-communicable diseases in low- and middle-income countries. Peru is a middle-income country currently undergoing a rapid epidemiological transition. This longitudinal study will provide valuable information on cardiopulmonary outcomes in three different settings and will provide a platform to address potential interventions that are locally relevant or applicable to other similar settings in Latin America.

Survival of drug resistant tuberculosis patients in Lithuania: retrospective national cohort study [RESEARCH]

Mon, 28 Nov 2011 00:00:00 +0000

ObjectiveTo establish risk factors influencing survival of patients with multidrug-resistant and extensively drug-resistant tuberculosis (MDR/XDRTB). DesignAll MDR/XDRTB cases (n=1809) reported from 2002 to 2008 in Lithuania with a known outcome were included in the survival analysis. ResultsMedian survival for MDRTB and XDRTB patients was 4.1 (95% CI 3.7 to 4.4) and 2.9 (95% CI 2.2 to 3.9) years. In a multivariable analysis adjusting for other patient characteristics, the difference in survival between MDRTB and XDRTB patients was not significant (HR=1.29 (0.91 to 1.81)). Older age (HR=4.80 (3.16 to 7.29)) for 60+ vs <30 years, rural living (HR=1.20 (1.02 to 1.40)), alcohol use (HR=1.49 (1.13 to 1.96)) for alcoholic versus moderate use, unemployment (HR=1.79 (1.31 to 2.46)), lower education levels (HR=1.50 (1.08 to 2.07)) for primary level versus tertiary level, cavitary disease (HR=1.54 (1.29 to 1.83)) and being smear positive at the time of MDR/XDRTB diagnosis (HR=1.47 (1.19 to 1.82)) were associated with poorer survival. HIV positivity significantly affected survival (HR=3.44 (1.92 to 6.19)) for HIV positive versus HIV negative; HR=1.60 (1.28 to 2.01) for HIV not tested versus HIV negative). There was no difference in survival of patients who acquired MDR/XDRTB during treatment compared with patients with primary MDR/XDRTB (HR=1.01 (0.85 to 1.19)). Treatment with a second-line drug improved survival (HR=0.40 (0.34 to 0.47)). In a subgroup with genotyped TB strains, a Beijing family of strains was associated with poorer survival (HR=1.71 (1.19 to 2.47)). ConclusionsSocial factors, rural living, HIV infection and Beijing strain family impact on survival. Survival of MDR/XDRTB patients is short. Rapid drug resistance identification, early administration of appropriate treatment and achieving high cure rates, expansion of HIV testing and antiretroviral treatment are necessary for optimal management of MDR/XDRTB.

Passive smoking and chronic obstructive pulmonary disease: cross-sectional analysis of data from the Health Survey for England [RESEARCH]

Sun, 27 Nov 2011 00:00:00 +0000

ObjectivesThere is increasing evidence that passive smoking is associated with chronic respiratory diseases, but its association with chronic obstructive pulmonary disease (COPD) requires more study. In this cross-sectional analysis of data from 3 years of the Health Survey for England, the association between passive smoking exposure and risk of COPD is evaluated. DesignCross-sectional analysis of the 1995, 1996 and 2001 Health Surveys for England including participants of white ethnicity, aged 40+ years with valid lung function data. COPD was defined using the lower limit of normal spirometric criteria for airflow obstruction. Standardised questions elicited self-reported information on demography, smoking history, ethnicity, occupation, asthma and respiratory symptoms (dyspnoea, chronic cough, chronic phlegm, wheeze). Passive smoking was measured by self-report of hours of exposure to cigarette smoke per week. ResultsIncreasing passive smoke exposure was independently associated with increased risk of COPD, with adjusted OR 1.05 (95% CI 0.93 to 1.18) for 1-19 h and OR 1.18 (95% CI 1.01 to 1.39) for 20 or more hours of exposure per week. Similar patterns (although attenuated and non-significant) were observed among never smokers. More marked dose-response relationships were observed between passive smoking exposure and respiratory symptoms, but the most marked effects were on the development of clinically significant COPD (airflow obstruction plus symptoms), where the risk among never smokers was doubled (OR 1.98 (95% CI 1.03 to 3.79)) if exposure exceeded 20 h/week. ConclusionThis analysis adds weight to the evidence suggesting an association between passive smoking exposure and COPD.

Application of impulse oscillometry for within-breath analysis in patients with chronic obstructive pulmonary disease: pilot study [RESEARCH]

Sun, 27 Nov 2011 00:00:00 +0000

BackgroundThe impulse oscillometry is increasingly used for assessing the oscillatory mechanics of the respiratory system. The within-breath behaviour of the oscillatory mechanics in chronic obstructive pulmonary disease (COPD) is a well-known physiological feature. The purpose of this study was to develop a new approach for assessing this feature using impulse oscillometry. MethodsThe oscillatory mechanics were assessed by a commercially available impulse oscillometry device. The respiratory system resistance (Rrs) and reactance (Xrs) were measured during tidal breathing in patients with COPD (n=39) and healthy subjects (n=5). Selected data, the Rrs at 5 Hz (R5), Rrs at 20 Hz (R20), Xrs at 5 Hz (X5), and resonant frequency of Xrs (Fres) every 0.2 s, were extracted from the device. These data were divided into eight time fractions during the respiratory cycle to form averaged respiratory phases. ResultsThe time courses of the R5 and X5 were notably dependent on the respiratory cycles in patients with COPD, while there was little such dependency in healthy subjects. Irrespective of respiratory phase, R5 and Fres increased, and X5 fell to a more negative level in patients with COPD in a severity-dependent fashion. The increase in the R5 and negative level in the X5 were more prominent in the middle of the expiratory phase. The severity dependence in the R20 was relatively small compared with that in the R5. ConclusionsThe results of this study suggest that impulse oscillometry can assess the within-breath behaviour of the oscillatory mechanics with high temporal resolution, which may be helpful for evaluating the severity of COPD. Further studies are needed to reveal which biomarkers obtained with this approach would be suitable for evaluating the airway obstruction.

A Phase I study evaluating the safety and immunogenicity of MVA85A, a candidate TB vaccine, in HIV-infected adults [RESEARCH]

Mon, 14 Nov 2011 00:00:00 +0000

ObjectivesControl of the tuberculosis (TB) epidemic is a global health priority and one that is likely to be achieved only through vaccination. The critical overlap with the HIV epidemic requires any effective TB vaccine regimen to be safe in individuals who are infected with HIV. The objectives of this clinical trial were to evaluate the safety and immunogenicity of a leading candidate TB vaccine, MVA85A, in healthy, HIV-infected adults. DesignThis was an open-label Phase I trial, performed in 20 healthy HIV-infected, antiretroviral-naive subjects. Two different doses of MVA85A were each evaluated as a single immunisation in 10 subjects, with 24 weeks of follow-up. The safety of MVA85A was assessed by clinical and laboratory markers, including regular CD4 counts and HIV RNA load measurements. Vaccine immunogenicity was assessed by ex vivo interferon {gamma} (IFN-{gamma}) ELISpot assays and flow-cytometric analysis. ResultsMVA85A was safe in subjects with HIV infection, with an adverse-event profile comparable with historical data from previous trials in HIV-uninfected subjects. There were no clinically significant vaccine-related changes in CD4 count or HIV RNA load in any subjects, and no evidence from qPCR analyses to indicate that MVA85A vaccination leads to widespread preferential infection of vaccine-induced CD4 T cell populations. Both doses of MVA85A induced an antigen-specific IFN-{gamma} response that was durable for 24 weeks, although of a lesser magnitude compared with historical data from HIV-uninfected subjects. The functional quality of the vaccine-induced T cell response in HIV-infected subjects was remarkably comparable with that observed in healthy HIV-uninfected controls, but less durable. ConclusionMVA85A is safe and immunogenic in healthy adults infected with HIV. Further safety and efficacy evaluation of this candidate vaccine in TB- and HIV-endemic areas is merited.

Stratified assessment of the role of inhaled hypertonic saline in reducing cystic fibrosis pulmonary exacerbations: a retrospective analysis [RESEARCH]

Fri, 2 Sep 2011 00:00:00 +0000

ObjectiveLimited data exist concerning the role of inhaled hypertonic saline (HS) in decreasing pulmonary exacerbations in cystic fibrosis (CF), especially as more advanced stages of CF lung disease were excluded in prior studies. Herein, the authors retrospectively determined the efficacy of inhaled HS in reducing CF pulmonary exacerbations when stratified according to the severity of CF lung disease. Stratification was based on the framework of the Pulmonary Therapeutics Committee's published gradation of obstructive lung physiology in CF, that is, mild (FEV1 >70%), moderate (FEV1 40-70%) and severe (FEV1 <40%) lung disease, respectively. DesignA retrospective review of the Port CF database over a 3-year period performed at an academic CF care centre. Results340 pulmonary exacerbations were identified; inhaled HS was being used in 99 of these cases. Univariate analysis demonstrated a significant reduction in pulmonary exacerbations only in mild obstruction (OR=0.09, CI 0.01 to 0.81, p=0.012); however, multivariate logistic regression that adjusted for confounding variables showed a reduction in pulmonary exacerbations across the entire spectrum of obstructive lung disease when using inhaled HS, that is, mild obstructive CF lung disease (OR=0.17, CI 0.05 to 0.58, p=0.004), moderate obstructive CF lung disease (OR=0.39, CI 0.16 to 0.93, p=0.034), as well as severe obstructive CF lung disease (OR=0.02, CI 0.001 to 0.45, p=0.015). Moreover, inhaled HS appeared reasonably well tolerated across all stages of lung-disease severity, and was discontinued in only 7% of cases (n=4) with severe lung disease. ConclusionIn this study, inhaled HS appeared to reduce pulmonary exacerbations in CF lung disease at all stages of obstruction. This underscores the importance of therapeutic inhaled HS in CF lung disease, regardless of the severity of lung obstruction.

Clinical and epidemiological profile of patients with severe H1N1/09 pandemic influenza in Australia and New Zealand: an observational cohort study [RESEARCH]

Fri, 2 Sep 2011 00:00:00 +0000

BackgroundPandemic influenza H1N1/09 emerged in April 2009 and spread widely in Australia and New Zealand. Although an unprecedented number of cases required intensive care, comparative community-based studies with seasonal influenza strains have not shown any significant differences in clinical symptoms or severity. MethodsThe authors performed active surveillance on confirmed influenza-related admissions and compared the clinical profile of patients with pandemic H1N1/09 influenza and patients with seasonal influenza at eight hospitals in Australia and one hospital in New Zealand. ResultsDuring the 1 July and 30 November 2009, 560 patients with confirmed influenza were admitted, of which 478 had H1N1/09, and 82 had other seasonal strains. Patients with H1N1/09 influenza were younger, were more likely to have fever and were more likely to be pregnant but less likely to have chronic obstructive pulmonary disease and ischaemic heart disease than patients with seasonal strains. Other clinical features and comorbidities were reported in similar proportions. Admission to intensive care was required in 22% of patients with H1N1/09 influenza and 12% in patients with other strains. Hospital mortality was 5% in patients with H1N1 influenza. ConclusionsThe clinical features of H1N1/09 influenza and seasonal strains were similar in hospitalised patients. A higher proportion of patients had comorbidities than had been reported in community-based studies. Although the overall mortality was similar, the authors found evidence that H1N1/09 caused severe disease in a higher proportion of hospitalised patients.

Heterogeneity of the efficacy of the 23-valent pneumococcal polysaccharide vaccine caused by various underlying conditions of chronic pulmonary disease in older patients: prospective cohort study [RESEARCH]

Fri, 2 Sep 2011 00:00:00 +0000

ObjectiveTo determine the ideal conditions for use of the 23-valent pneumococcal polysaccharide vaccine (PPV23) in older outpatients with chronic pulmonary diseases. DesignProspective cohort study. Participants1378 outpatients with chronic pulmonary diseases [≥]60 years of age. InterventionParticipants were educated about PPV23, and those who responded affirmatively were vaccinated between August and November 2002. The participants who chose no intervention served as controls. The prevaccine period was defined as August 2001 to August 2002. Participants were followed for 2 years from December 2002 or until death. Main outcome measuresEvents of interest included the first episode of bacterial (including pneumococcal) pulmonary infection (primary endpoint) and death of any cause (secondary endpoint). ResultsFrequent episodes of pulmonary infection during the prevaccine period significantly decreased event-free survival during the 2-year observation period (p<0.001). Chronic respiratory failure was associated with a decreased event-free survival only when the pulmonary infection episode did not occur in the prevaccine period (p<0.001). No significant differences in event-free survival were observed between the vaccinated and unvaccinated group during analysis of the entire cohort. In the Cox proportional hazards regression model, event-free survival decreased significantly when pulmonary infection occurred in the prevaccine period. In the subgroup analysis, the first episode of bacterial pulmonary infection (but not death of any cause) was reduced significantly by PPV23 only in patients with chronic respiratory failure who had no episodes of pulmonary infection during the prevaccine period (p=0.019). ConclusionThe efficacy of PPV23 against pulmonary infection and death of any cause might be unachievable if pulmonary infection occurs during the prevaccine period. PPV23 needs to be given to older patients with chronic pulmonary disease at an earlier time in which infectious complications in the lung have not yet occurred.

Phase II study of tight glycaemic control in COPD patients with exacerbations admitted to the acute medical unit [RESEARCH]

Fri, 2 Sep 2011 00:00:00 +0000

BackgroundHyperglycaemia is associated with poor outcomes from exacerbations of chronic obstructive pulmonary disease (COPD). Glycaemic control could improve outcomes by reducing infection, inflammation and myopathy. Most patients with COPD are managed on the acute medical unit (AMU) outside intensive care (ICU). ObjectiveTo determine the feasibility, safety and efficacy of tight glycaemic control in patients on an AMU. DesignProspective, non-randomised, phase II, single-arm study of tight glycaemic control in COPD patients with acute exacerbations and hyperglycaemia admitted to the AMU. Participants received intravenous, then subcutaneous, insulin to control blood glucose to 4.4-6.5 mmol/l. Tight glycaemic control was evaluated: feasibility, protocol adherence; acceptability, patient questionnaire; safety, frequency of hypoglycaemia (capillary blood glucose (CBG) <2.2 mmol/l and 2.2-3.3 mmol/l); efficacy, median CBG, fasting CBG, proportion of measurements/time in target range, glycaemic variability. Results were compared with 25 published ICU studies. Results20 patients (10 females, age 71{+/-}9 years; forced expiratory volume in 1 s: 41{+/-}16% predicted) were recruited. Tight glycaemic control was feasible (78% CBG measurements and 89% of insulin-dose adjustments were adherent to protocol) and acceptable to patients. 0.2% CBG measurements were <2.2 mmol/l and 4.1% measurements 2.2-3.3 mmol/l. The study CBG and proportion of measurements/time in target range were similar to that of ICU studies, whereas the fasting CBG was lower, and the glycaemic variability was greater. ConclusionsTight glycaemic control is feasible and has similar safety and efficacy on AMU to ICU. However, as more recent ICU studies have shown no benefit and possible harm from tight glycaemic control, alternative strategies for blood glucose control in COPD exacerbations should now be explored. Trial registration numberISRCTN: 42412334. http://Clinical.Trials.gov NCT00764556.

Yoga respiratory training improves respiratory function and cardiac sympathovagal balance in elderly subjects: a randomised controlled trial [RESEARCH]

Fri, 2 Sep 2011 00:00:00 +0000

ObjectivesSince ageing is associated with a decline in pulmonary function, heart rate variability and spontaneous baroreflex, and recent studies suggest that yoga respiratory exercises may improve respiratory and cardiovascular function, we hypothesised that yoga respiratory training may improve respiratory function and cardiac autonomic modulation in healthy elderly subjects. Design76 healthy elderly subjects were enrolled in a randomised control trial in Brazil and 29 completed the study (age 68{+/-}6 years, 34% males, body mass index 25{+/-}3 kg/m2). Subjects were randomised into a 4-month training program (2 classes/week plus home exercises) of either stretching (control, n=14) or respiratory exercises (yoga, n=15). Yoga respiratory exercises (Bhastrika) consisted of rapid forced expirations followed by inspiration through the right nostril, inspiratory apnoea with generation of intrathoracic negative pressure, and expiration through the left nostril. Pulmonary function, maximum expiratory and inspiratory pressures (PEmax and PImax, respectively), heart rate variability and blood pressure variability for spontaneous baroreflex determination were determined at baseline and after 4 months. ResultsSubjects in both groups had similar demographic parameters. Physiological variables did not change after 4 months in the control group. However, in the yoga group, there were significant increases in PEmax (34%, p<0.0001) and PImax (26%, p<0.0001) and a significant decrease in the low frequency component (a marker of cardiac sympathetic modulation) and low frequency/high frequency ratio (marker of sympathovagal balance) of heart rate variability (40%, p<0.001). Spontaneous baroreflex did not change, and quality of life only marginally increased in the yoga group. ConclusionRespiratory yoga training may be beneficial for the elderly healthy population by improving respiratory function and sympathovagal balance. Trial RegistrationCinicalTrials.gov identifier: NCT00969345; trial registry name: Effects of respiratory yoga training (Bhastrika) on heart rate variability and baroreflex, and quality of life of healthy elderly subjects.

A survey of acute self-reported infections in pregnancy [RESEARCH]

Fri, 2 Sep 2011 00:00:00 +0000

ObjectiveThe objective of this study was to estimate the weekly prevalence of self-reported recently acquired infections in women at least 20 weeks pregnant. DesignWe conducted a cross-sectional survey of pregnant women in a hospital antenatal clinic in Sydney, Australia between August 2008 and April 2009. Women were asked to report whether they had onset of a new infection in the 7 days before completing the questionnaire, and were asked for details of symptoms and medication taken. Results737 women at least 20 weeks pregnant completed the survey (94% of women approached). Five per cent of the completed questionnaires reported the onset of an infection in the 7 days prior to survey completion. When symptoms were analysed, 3.5% of women were classified as having a moderate or severe infection in the past 7 days. The most common infection reported was a cold/upper respiratory tract infection followed by gastroenteritis. Women pregnant with their first child had a lower rate of self-reported infection than women who had other children (2.9% vs 7.2%). ConclusionsThese results can be used to inform future research examining acute infection as a trigger for pregnancy complications.