Background: Although inhaled corticosteroids have an established role in the treatment of asthma, studies have tended to concentrate on non-smokers and little is known about the possible effect of cigarette smoking on the efficacy of treatment with inhaled steroids in asthma. A study was undertaken to investigate the effect of active cigarette smoking on responses to treatment with inhaled corticosteroids in patients with mild asthma. Methods: The effect of treatment with inhaled fluticasone propionate (1000 μg daily) or placebo for 3 weeks was studied in a double blind, prospective, randomised, placebo controlled study of 38 steroid naïve adult asthmatic patients (21 non-smokers). Efficacy was assessed using morning and evening peak expiratory flow (PEF) readings, spirometric parameters, bronchial hyperreactivity, and sputum eosinophil counts. Comparison was made between responses to treatment in non-smoking and smoking asthmatic patients. Results: There was a significantly greater increase in mean morning PEF in non-smokers than in smokers following inhaled fluticasone (27 l/min v –5 l/min). Non-smokers had a statistically significant increase in mean morning PEF (27 l/min), mean forced expiratory volume in 1 second (0.17 l), and geometric mean PC₂₀ (2.6 doubling doses), and a significant decrease in the proportion of sputum eosinophils (–1.75%) after fluticasone compared with placebo. No significant changes were observed in the smoking asthmatic patients for any of these parameters. Conclusions: Active cigarette smoking impairs the efficacy of short term inhaled corticosteroid treatment in mild asthma. This finding has important implications for the management of patients with mild asthma who smoke.

Patients with bronchiectasis often have concurrent comorbidities, but the nature, prevalence, and impact of these comorbidities on disease severity and outcome are poorly understood. We aimed to investigate comorbidities in patients with bronchiectasis and establish their prognostic value on disease severity and mortality rate. An international multicentre cohort analysis of outpatients with bronchiectasis from four European centres followed up for 5 years was done for score derivation. Eligible patients were those with bronchiectasis confirmed by high-resolution CT and a compatible clinical history. Comorbidity diagnoses were based on standardised definitions and were obtained from full review of paper and electronic medical records, prescriptions, and investigator definitions. Weibull parametric survival analysis was used to model the prediction of the 5 year mortality rate to construct the Bronchiectasis Aetiology Comorbidity Index (BACI). We tested the BACI as a predictor of outcomes and explored whether the BACI added further prognostic information when used alongside the Bronchiectasis Severity Index (BSI). The BACI was validated in two independent international cohorts from the UK and Serbia. Between June 1, 2006, and Nov 22, 2013, 1340 patients with bronchiectasis were screened and 986 patients were analysed. Patients had a median of four comorbidities (IQR 2-6; range 0-20). 13 comorbidities independently predicting mortality rate were integrated into the BACI. The overall hazard ratio for death conferred by a one-point increase in the BACI was 1·18 (95% CI 1·14-1·23; p<0·0001). The BACI predicted 5 year mortality rate, hospital admissions, exacerbations, and health-related quality of life across all BSI risk strata (p<0·0001 for mortality and hospital admissions, p=0·03 for exacerbations, p=0·0008 for quality of life). When used in conjunction with the BSI, the combined model was superior to either model alone (p=0·01 for combined vs BACI; p=0·008 for combined vs BSI). Multimorbidity is frequent in bronchiectasis and can negatively affect survival. The BACI complements the BSI in the assessment and prediction of mortality and disease outcomes in patients with bronchiectasis. European Bronchiectasis Network (EMBARC).

Introduction: A recent pilot study noted clinical benefit of macrolide therapy in the management of six lung transplant recipients with bronchiolitis obliterans syndrome (BOS), a condition previously regarded as irreversible. Objective: To examine the effect of low-dose macrolides on lung function in lung allograft recipients with established BOS and to assess whether this benefit is sustained. Methods: We retrospectively evaluated the effect of azithromycin (250 mg alternate days) on clinical status and lung function in 20 allograft recipients with established BOS, confirmed by decline in FEV₁ or FEF_25–75; consistent high-resolution computed tomography findings; and exclusion of acute rejection, infection, or anastomatic complications. Azithromycin was introduced at mean 82 months after transplantation. BOS staging at initiation of treatment was BOS 3 (10), BOS 2 (2), BOS 1 (6), and BOS0-p (2). All patients were on maintenance immunosuppression comprising cell-cycle inhibitor, oral corticosteroids, and calcineurin inhibitor. Results: There was a significant increase in FEV₁ of median 110 ml (range, −70 to 730 ml) between baseline and 3 months of azithromycin therapy (p = 0.002). This improvement was sustained beyond 3 months in the majority of patients, who had initially benefited from azithromycin (up to 11 months follow up). Conclusions: This case series confirms the benefit of azithromycin in not only halting, but reversing the declining lung function seen in patients with BOS. This benefit appears to be maintained over time. Low-dose macrolides offer a new and exciting therapeutic strategy for the treatment of progressive BOS, and further clinical and translational mechanistic studies are required.

We explore potential dysregulation of macrophage phenotypes in COPD pathogenesis through integrated study of human small airway tissue, bronchoalveolar lavage (BAL) and an experimental murine model of COPD. We evaluated human airway tissue and BAL from healthy controls, normal lung function smokers (NLFS), and COPD subjects. Both small airways and BAL cells were immunohistochemically stained with anti-CD68 for total macrophages and with anti-CD163 for M2, and anti-iNOS for M1 macrophages. Multiplex ELISA measured BAL cytokines. Comparable cigarette smoke-induced experimental COPD mouse model was assessed for relevant mRNA profiles. We found an increase in pro-inflammatory M1s in the small airways of NLFS and COPD compared to controls with a reciprocal decrease in M2 macrophages, which remained unchanged among pathological groups. However, luminal macrophages showed a dominant M2 phenotype in both NLFS and COPD subjects. BAL cytokine skewed towards an M2 profile with increase in CCL22, IL-4, IL-13, and IL-10 in both NLFS and COPDs. The mouse-model of COPD showed similar increase in mRNA for M2 markers. Our finding suggests abnormal macrophage switching in both mucosal and luminal areas of COPD patients, that strongly associated with cytokine balance. There may be potential for beneficial therapeutic cytokine manipulation of macrophage phenotypes in COPD.