The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
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Bronchiolitis obliterans is a complication after allogeneic haematopoietic stem cell transplantation (HSCT). Management of bronchiolitis obliterans comprises intensive immunosuppression, but treatment response is poor. We investigated the effect of cyclosporine A (CsA), tacrolimus (FK506), methylprednisolone (mPRED), mycophenolate mofetil (MMF) and everolimus on the proliferation of primary lung myofibroblasts from HSCT patients with bronchiolitis obliterans syndrome (BOS). ⋯ Serial pulmonary function tests over 12 months after lung biopsy and under triple therapy demonstrated that patients with lymphocytic bronchiolitis had a significant improvement in forced expiratory volume in 1 s (FEV1), whereas FEV1 of patients with bronchiolitis obliterans was unchanged. Our data demonstrate a pro-proliferative effect of calcineurin inhibitors on primary human lung myofibroblasts obtained from patients with BOS after HSCT. In contrast, based on the observed antiproliferative capacity of MMF in vitro, MMF-based calcineurin inhibitor-free treatment strategies should be further evaluated in patients with bronchiolitis obliterans after HSCT.
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Letter Case Reports
Bedaquiline in MDR/XDR-TB cases: first experience on compassionate use.
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Randomized Controlled Trial
Umeclidinium in patients with COPD: a randomised, placebo-controlled study.
Efficacy and safety of umeclidinium administered in a dry power inhaler were evaluated in moderate-to-very-severe chronic obstructive pulmonary disease patients. This was a randomised, placebo-controlled study assessing once-daily umeclidinium 62.5 and 125 μg over 12 weeks. The primary end-point was change from baseline in trough forced expiratory volume in 1 s (FEV1) on day 85. ⋯ Significant improvements in least squares mean transitional dyspnoea index focal score for UMEC 125 mg(1.3 units; p,0.05) and change from baseline St George's Respiratory Questionnaire total score for both UMEC doses (-7.9 and -10.87 units, for UMEC 62.5 mg and 125 mg, respectively; both p,0.001) were noted compared with placebo at week 12 [DOSAGE ERROR CORRECTED]. The incidence of adverse events was low and similar across treatments. Umeclidinium 62.5 and 125 μg significantly improved lung function, dyspnoea and health status compared with placebo, and were well tolerated in chronic obstructive pulmonary disease patients over 12 weeks.
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The aim of this study was to establish which cut-off point for the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio (i.e. fixed 0.70 or lower limit of normal (LLN) cut-off point) best predicts accelerated lung function decline and exacerbations in middle-aged smokers. We performed secondary analyses on the Lung Health Study dataset. 4045 smokers aged 35-60 years with mild-to-moderate obstructive pulmonary disease were subdivided into categories based on presence or absence of obstruction according to both FEV1/FVC cut-off points. ⋯ Our study showed that FEV1 decline in subjects deemed obstructed according to a fixed criterion (FEV1/FVC <0.70), but non-obstructed by a sex- and age-specific criterion (LLN) closely resembles FEV1 decline in subjects designated as non-obstructed by both criteria. Sex and age should be taken into account when assessing airflow obstruction in middle-aged smokers.
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Multicenter Study Observational Study
Association of lung function, chest radiographs and clinical features in infants with cystic fibrosis.
The optimal strategy for monitoring cystic fibrosis lung disease in infancy remains unclear. Our objective was to describe longitudinal associations between infant pulmonary function tests, chest radiograph scores and other characteristics. Cystic fibrosis patients aged ≤24 months were enrolled in a 10-centre study evaluating infant pulmonary function tests four times over a year. ⋯ Parent-reported cough was associated with significantly diminished forced expiratory flow at 75% but not with hyperinflation. In this infant cohort in whom we previously reported worsening in average lung function, chest radiograph scores also worsened over a year. The significant associations detected between both Wisconsin chest radiograph score and S. aureus and hyperinflation, as well as between cough and diminished flows, reinforce the ability of infant pulmonary function tests and chest radiographs to detect early cystic fibrosis lung disease.