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Clinical Inquiry: Do inhaled steroids reduce bone mineral density and increase fracture risk?

No, except perhaps at high doses. Inhaled corticosteroids at low to medium doses (<1500 mcg beclomethasone hydrofluoroalkane per day) for asthma and chronic obstructive pulmonary disease don't increase the risk of significant bone loss or fracture at 2 to 3 years follow-up. Higher doses, however, may raise the risk of nontraumatic fracture over 1 to 4 years of follow-up.

Bronchodilator responsiveness as a phenotypic characteristic of established chronic obstructive pulmonary disease

Background

Bronchodilator responsiveness is a potential phenotypic characteristic of chronic obstructive pulmonary disease (COPD). We studied whether change in lung function after a bronchodilator is abnormal in COPD, whether stable responder subgroups can be identified, and whether these subgroups experience different clinical outcomes.

Methods

1831 patients with COPD, 285 smoking (SC) and 228 non-smoking (NSC) controls from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) cohort. Spirometric reversibility to 400 μg inhaled salbutamol was assessed on four occasions over 1 year.

Results

Forced expiratory volume in 1 s (FEV1) increase after salbutamol was similar in SC (mean 0.14 litres (SD 0.15)) and COPD (0.12 litres (0.15)) and was significantly greater than NSC (0.08 litres (0.14)). Reversibility status varied with repeated testing in parallel with the day-to-day variation in pre-bronchodilator FEV1, which was similar in control subjects and patients with COPD. Absolute FEV1 change decreased by Global initiative for chronic Obstructive Lung Disease (GOLD) stage in patients with COPD (GOLD II, mean 0.16 litres (SD 0.17); III, 0.10 litres (0.13); IV, 0.05 litres (0.08) as did chances of being classified as reversible. CT-defined emphysema was weakly related to the absolute change in FEV1 post salbutamol. Consistently reversible patients (n=227) did not differ in mortality, hospitalisation or exacerbation experience from irreversible patients when allowing for differences in baseline FEV1.

Limitations

Reversibility only assessed with salbutamol and defined by FEV1 criteria. The COPD population was older than the control populations.

Conclusions

Post-salbutamol FEV1 change is similar in patients with COPD and smoking controls but is influenced by baseline lung function and the presence of emphysema. Bronchodilator reversibility status varies temporally and does not distinguish clinically relevant outcomes, making it an unreliable phenotype.

Clinical trial registration number

NCT00292552 (http://ClinicalTrials.gov).

Bronchodilator responsiveness: interpret with caution

Bronchodilator responsiveness (BDR) is widely considered to be a key diagnostic criterion for asthma, and is used to differentiate asthma from chronic obstructive pulmonary disease (COPD). Currently, the threshold of a 12% increase in FEV1 from baseline following inhaled salbutamol, with at least a 200 ml increase in absolute terms, is recommended as a response indicative of asthma,1 although recent British guidelines recognise the poor discriminatory function of this criterion.2 Thus, despite this criterion being commonly used in clinical practice, there is uncertainty regarding its clinical utility, in particular its ability to differentiate asthma from COPD, or indeed, normal subjects.

One approach to enable a better understanding of the clinical utility of BDR is to determine the worldwide distribution of BDR in health and disease, which has been undertaken by Tan and colleagues, and reported in Thorax.3 The authors report BDR in terms of...

Volume targeted versus pressure support non-invasive ventilation in patients with super obesity and chronic respiratory failure: a randomised controlled trial

Introduction

Automatic titration modes of non-invasive ventilation, including average volume assured pressure support (AVAPS), are hybrid technologies that target a set volume by automated adjustment of pressure support (PS). These automated modes could offer potential advantages over fixed level PS, in particular, in patients who are super obese.

Methods

Consecutive patients with obesity hypoventilation syndrome were enrolled in a two-centre prospective single-blind randomised controlled trial of AVAPS versus fixed-level PS using a strict protocolised setup.

Measurements

The primary outcome was change in daytime arterial PCO2 (PaCO2) at 3 months. Body composition, physical activity (7-day actigraphy) and health-related quality of life (severe respiratory insufficiency questionnaire, SRI) were secondary outcome measures.

Results

50 patients (body mass index 50±7 kg/m2; 55±11 years; 53% men) were enrolled with a mean PaCO2 of 6.9±0.8 kPa and SRI of 53±17. 46 patients (23 AVAPS and 23 PS) completed the trial. At 3 months, improvements in PaCO2 were observed in both groups (AVAPS 0.6 kPa, 95% CI 0.2 to 1.1, p<0.01 vs PS 0.6 kPa, 95% CI 0.1 to 1.1, p=0.02) but no between-group difference (–0.1 kPa, 95% CI –0.7 to 0.6, p=0.87). SRI also improved in both groups (AVAPS 11, 95% CI 6 to 17, p<0.001 vs PS 7, 95% CI 1 to 12, p=0.02; between groups 5, 95% CI –3 to 12, p=0.21). Secondary analysis of both groups combined showed improvements in daytime physical activity that correlated with reduction in fat mass (r=0.48; p=0.01).

Conclusion

The study demonstrated no differences between automated AVAPS mode and fixed-level PS mode using a strict protocolised setup in patients who were super obese. The data suggest that the management of sleep-disordered breathing may enhance daytime activity and promote weight loss in super-obese patients. Trial registration details available at http://www.controlled-trials.com/ISRCTN63940700

Randomised controlled trial of amoxycillin clavulanate in children with chronic wet cough

Background

Despite guideline recommendations, there are no published randomised controlled trial data on the efficacy of antibiotics for chronic wet cough in children. The majority of children with chronic wet cough have protracted bacterial bronchitis (PBB), a recognised condition in multiple national guidelines. The authors conducted a parallel 1:1 placebo randomised controlled trial to test the hypothesis that a 2-week course of amoxycillin clavulanate is efficacious in the treatment of children with chronic wet cough.

Methods

50 children (median age 1.9 years, IQR 0.9–5.1) with chronic (>3 weeks) wet cough were randomised to 2 weeks of twice daily oral amoxycillin clavulanate (22.5 mg/kg/dose) or placebo. The primary outcome was ‘cough resolution’ defined as a >75% reduction in the validated verbal category descriptive cough score within 14 days of treatment compared with baseline scores, or cessation of cough for >3 days. In selected children, flexible bronchoscopy and bronchoalveolar lavage (BAL) were undertaken at baseline.

Results

Cough resolution rates (48%) were significantly higher in children who received amoxycillin clavulanate compared with those who received placebo (16%), p=0.016. The observed difference between proportions was 0.32 (95% CI 0.08 to 0.56). Post treatment, median verbal category descriptive score in the amoxycillin clavulanate group of 0.5 (IQR 0.0–2.0) was significantly lower than in the placebo group, 2.25 (IQR 1.15–2.9) (p=0.02). Pre-treatment BAL data were consistent with PBB in the majority of children, with no significant difference between groups.

Conclusion

A 2-week course of amoxycillin clavulanate will achieve cough resolution in a significant number of children with chronic wet cough. BAL data support the diagnosis of PBB in the majority of these children.

Clinical trial number

ACTRN 12605000533695.

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