Withdrawal of inhaled corticosteroids in COPD: a European Respiratory Society guideline.

Inhaled corticosteroids (ICS) combined with bronchodilators can reduce the frequency of exacerbations in some patients with chronic obstructive pulmonary disease (COPD). There is evidence, however, that ICS are frequently used in patients where their benefit has not been established. Therefore, there is a need for a personalised approach to the use of ICS in COPD and to consider withdrawal of ICS in patients without a clear indication. This document reports European Respiratory Society recommendations regarding ICS withdrawal in patients with COPD.Comprehensive evidence synthesis was performed to summarise all available evidence relevant to the question: should ICS be withdrawn in patients with COPD? The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence synthesis was discussed and recommendations formulated by a committee with expertise in COPD and guideline methodology.After considering the balance of desirable and undesirable consequences, quality of evidence, and feasibility and acceptability of interventions, the guideline panel made: 1) conditional recommendation for the withdrawal of ICS in patients with COPD without a history of frequent exacerbations, 2) strong recommendation not to withdraw ICS in patients with blood eosinophil counts ≥300 eosinophils·µL-1 and 3) strong recommendation to treat with one or two long-acting bronchodilators if ICS are withdrawn.A conditional recommendation indicates that there was uncertainty about the balance of desirable and undesirable consequences of the intervention, and that well-informed patients may make different choices regarding whether to have or not have the specific intervention.

Validation of the COPD Assessment Test (CAT) as an Outcome Measure in Bronchiectasis.

BACKGROUND: Objective assessment of symptoms in bronchiectasis is important for research and in clinical practice. The COPD Assessment Test (CAT) is a short, simple assessment tool widely used in COPD. The items included in the CAT are not specific to COPD and also reflect the dominant symptoms of bronchiectasis. We therefore performed a study to validate the CAT as an outcome measure in bronchiectasis. METHODS: The CAT was administered to two cohorts of bronchiectasis patients along with other quality of life questionnaires. Patients underwent comprehensive clinical assessment. One cohort had repeated questionnaires collected before-and-after treatment of acute exacerbations. We analyzed convergent validity, repeatability, and responsiveness of the score and calculated the minimum clinically important difference (MCID) using a combination of distribution and anchor-based methods. RESULTS: In both cohorts there were positive correlations between the CAT and the St. George's Respiratory Questionnaire (r = 0.90, P < .0001 and r = 0.87, P < .0001). There was an inverse relationship between CAT and Quality of Life - Bronchiectasis Respiratory Symptoms Scale (r = -0.75, P < .0001) and Leicester Cough Questionnaire score (r = -0.77, P < .0001). Patients with more severe disease, based on the bronchiectasis severity index, had significantly higher CAT scores. CAT also correlated with FEV1 % predicted and 6-min walk distance (6MWD). CAT increased significantly at exacerbation and fell at recovery. The intraclass correlation coefficient for two measurements four-weeks apart while clinically stable was 0.88 (95% CI, 0.73-0.95, P < .0001). An MCID of 4 was most consistent. CONCLUSIONS: CAT is a valid, responsive symptom assessment tool in bronchiectasis. The MCID is estimated as 4 points.

The efficacy and safety of inhaled antibiotics for the treatment of bronchiectasis in adults: a systematic review and meta-analysis.

BACKGROUND: Although use of inhaled antibiotics is the standard of care in cystic fibrosis, there is insufficient evidence to support use of inhaled antibiotics in patients with bronchiectasis not due to cystic fibrosis. We aimed to assess the efficacy and safety of inhaled antibiotics for the long-term treatment of adults with bronchiectasis and chronic respiratory tract infections. METHODS: We did a systematic review and meta-analysis of all randomised controlled trials of inhaled-antibiotic use in adult patients with bronchiectasis and chronic respiratory tract infections. Eligible publications were identified by searching MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov. Randomised controlled trials of inhaled antibiotics were included if the patients were adults with stable bronchiectasis diagnosed by CT or bronchography, the trials had treatment a duration of at least 4 weeks, and their outcomes met at least one of the endpoints of interest. Studies in cystic fibrosis were excluded. Efficacy endpoints assessed were bacterial load, bacterial eradication from sputum, frequency of exacerbations, time to first exacerbation, proportion of patients with at least one exacerbation, frequency of severe exacerbations, quality of life, change in FEV1, 6-min walk distance, mortality, adherence to treatment, and sputum volume; safety endpoints were adverse events and bacterial resistance in sputum. Each study was independently reviewed for methodological quality using the Cochrane risk of bias tool. Random-effects meta-analysis was used to pool individual studies. Heterogeneity was assessed using I2. The review is registered on PROSPERO, number CRD42019122892. FINDINGS: 16 trials (n=2597 patients) were included for analysis. The mean reduction of colony forming units per g of sputum with inhaled antibiotics was -2·32 log units (95% CI -3·20 to -1·45; p<0·0001). Bacterial eradication was increased with inhaled antibiotic therapy (odds ratio [OR] 3·36, 1·63 to 6·91; p=0·0010). Inhaled antibiotics significantly reduced exacerbation frequency (rate ratio 0·81, 0·67 to 0·97; p=0·020). Time to first exacerbation was significantly prolonged with inhaled antibiotics (hazard ratio 0·83, 0·69 to 0·99; p=0·028). The proportion of patients with at least one exacerbation decreased (risk ratio 0·85, 0·74 to 0·97; p=0·015). There was a significant reduction in the frequency of severe exacerbations (rate ratio 0·43, 0·24 to 0·78; p=0·0050). The scores for neither the Quality of Life Bronchiectasis questionnaire nor St George's Respiratory Questionnaire improved above the minimal clinically important difference. The relative change in FEV1 was a deterioration of 0·87% predicted value (-2·00 to 0·26%; p=0·13). Other efficacy endpoints were reported in only few studies or had few events. There was no difference in treatment-emergent adverse effects (OR 0·97, 0·67 to 1·40; p=0·85) or bronchospasm (0·99, 0·66 to 1·48; p=0·95). Emergence of bacterial resistance was evident at the end of the treatment period (risk ratio 1·91, 1·46 to 2·49; p<0·0001). INTERPRETATION: Inhaled antibiotics are well tolerated, reduce bacterial load, and achieve a small but statistically significant reduction in exacerbation frequency without clinically significant improvements in quality of life in patients with bronchiectasis and chronic respiratory tract infections. FUNDING: British Lung Foundation through the GSK/British Lung Foundation Chair of Respiratory Research and European Respiratory Society through the EMBARC2 consortium. EMBARC2 is supported by project partners Chiesi, Grifols, Insmed, Novartis, and Zambon.

Diagnostic utility and accuracy of rapid on-site evaluation of bronchoscopic brushings.

The aim of the study was to determine the accuracy of rapid on-site examinations, performed on transbronchial brushings of peripheral pulmonary lesions, in determining final bronchoscopic diagnosis. In addition to determining if rapid on-site examination impacts procedural outcomes. A prospective cohort study of consecutive patients with peripheral pulmonary lesions, which had been located by radial endobronchial ultrasound, was undertaken. Bronchoscopy was terminated if rapid on-site examination demonstrated diagnostic malignant material. Non-diagnostic rapid on-site examination resulted in further bronchoscopic sampling, including transbronchial lung biopsy and/or sampling from different locations. 128 peripheral pulmonary lesions were located by endobronchial ultrasound in 118 patients. The final bronchoscopic diagnoses included nonsmall cell lung cancer (n=76), carcinoid (n=3), and metastatic malignancy (n=3). Procedure times were significantly shorter for procedures when rapid on-site examinations demonstrated malignancy compared to those where rapid on-site examination was non-diagnostic (19±8 min versus 31±11 min, respectively; p<0.0001). In four procedures, initial negative rapid on-site examination results prompted redirection of sampling from alternate bronchial segments, resulting in positive diagnostic tissue being obtained. Positive and negative predictive value of rapid on-site examination for a malignant bronchoscopic diagnosis was 63 (97%) out of 65, and 43 (68%) out of 63, respectively. Rapid on-site examination of brushing specimens has a very high, positive, predictive value for bronchoscopic diagnosis of cancer and shortens the bronchoscopy procedure times. It has the potential to reduce complications, improve cost-effectiveness, and may improve diagnostic performance via live feedback.