Beta-blockers in high-risk outpatients with chronic obstructive pulmonary disease are associated with all-cause mortality – The statuette cohort study

BACKGROUND: Beta-blockers have been proposed to improve COPD-related outcomes, yet studies report conflicting results. We aimed to investigate the effect of beta blockers on time-to-first exacerbation and all-cause mortality in high-risk COPD outpatients. METHODS: All COPD outpatients managed at the Department of Respiratory Medicine, Copenhagen University Hospital – Hvidovre, Denmark in 2016 were followed for 3.5 years in this retrospective, registry-based cohort study. Outcomes were time-to-first acute exacerbation of COPD (AECOPD) or death. The association was estimated using time-varying crude and multivariable Cox proportional hazard regression adjusted for age, sex, BMI, use of COPD medication, smoking status, cardiovascular disease and COPD severity. RESULTS: The cohort comprised 950 COPD outpatients, mean age 71 (SD 11) years, and FEV(1) 44% predicted (IQR 33%; 57%). The annual exacerbation rate was 0.88 (SD 1.68) and 211 patients (22%) had a history of hospitalization requiring AECOPD within 12 months. Of the enrolled patients, 247 (26%) were prescribed beta blockers. Beta-blocker use was associated, although with borderline significance, with increased all-cause mortality (HR 1.37 (95% CI, 0.99 to 1.89, p = 0.059)). On the other hand, beta blocker use did not reduce the risk of AECOPD (HR = 0.89 (95% CI 0.71 to 1.10; p = 0.270)), which remained non-significant after stratifying for severity of exacerbations. CONCLUSION: We found an association between beta blocker use and all-cause mortality in high-risk COPD outpatients. No association was found between beta blocker use and risk of AECOPD

Inhaled corticosteroid therapy in bronchiectasis is associated with all-cause mortality:A prospective cohort study

BACKGROUND AND OBJECTIVE: Prescribing inhaled corticosteroids (ICS) for bronchiectasis (BE) in the absence of obstructive lung disease is controversial. Studies investigating ICS therapy and impact on morbidity and mortality in BE are sparse. METHODS: This study comprises all patients with BE managed at respiratory outpatient clinics at two university hospitals in the Capital Region of Denmark 2014–2015. Baseline data were obtained from patient medical records, and patients were followed until April 2020. RESULTS: Out of 264 patients, 122 (46%) were prescribed ICS with no demographic differences between users/non-users of ICS. Among patients prescribed ICS, 21% did not have a concomitant diagnosis of asthma or COPD. Patients prescribed ICS had lower lung function (median FEV(1) 65.2 vs 80.9%pred, p<0.001) and a higher symptom burden in terms of cough (p 0.028), sputum production (p <0.001) and dyspnea (p <0.001). Pseudomonas-positive sputum cultures were more common in ICS-treated patients (6.5 vs 20%, p 0.010), as were previous severe exacerbations (41% vs 21%, p <0.001). In terms of mortality, high-dose ICS use was associated with increased mortality in multivariable Cox regression adjusted for age, sex, FEV(1) and concomitant asthma/COPD (HR 4.93 [95% CI 1.73–14.0], p 0.003). CONCLUSION: In this cohort, close to one out of five patients with BE were prescribed ICS despite having no concomitant diagnosis of asthma or COPD. Overall, ICS treatment was associated with higher morbidity and mortality, though causation is difficult to establish

Hydroxychloroquine as a primary prophylactic agent against SARS-CoV-2 infection: A cohort study

Objective: Hydroxychloroquine has been proposed as a primary prophylactic agent against coronavirus disease 2019 (COVID-19). This study aimed to investigate if patients treated with hydroxychloroquine for a non-COVID-19 indication had a lower risk of verified infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) compared with matched controls. Methods: A cohort comprising all persons in Denmark collecting hydroxychloroquine prescriptions in 2020 and 2019 (i.e., both during and before SARS-CoV-2 was confirmed in Denmark), matched by age and sex with controls, was studied. Data were collected using the Danish national registries, which contain complete information on patient health data, prescriptions and microbiological test results. The main outcome was microbiologically verified SARS-CoV-2 infection. Results: In total, 5488 hydroxychloroquine users were matched with 54,486 non-users. At baseline, the groups differed in terms of diagnoses of pulmonary disease, cardiovascular disease, renal disease, gastrointestinal/metabolic disease and dementia, as well as treatment with antirheumatic drugs. The final model was adjusted for these potential confounders. Use of hydroxychloroquine for non-COVID-19 indications was not associated with any change in confirmed SARS-CoV-2 (hazard ratio 0.90, 95% confidence interval 0.76–1.07). This result was robust in the propensity-score-matched sensitivity analysis. Conclusion: This study, which is the largest to date to investigate the primary prophylactic effect of hydroxychloroquine against SARS-CoV-2, does not support any prophylactic benefit of hydroxychloroquine in the prevention of infection with SARS-CoV-2