Abstract Background The treatment of NTM pulmonary disease is hindered by scarce therapeutic options. Bedaquiline is a diarylquinoline with activity against Mycobacterium tuberculosis and a variety of pathogenic nontuberculous mycobacteria (NTM) that could help fill this unmet need, but clinical data are needed to support its use. Methods We retrospectively reviewed the use of bedaquiline in patients with NTM pulmonary disease from National Jewish Health and the University of Texas Health Science Center Tyler between the years of 2013 and 2022. Results Eighty-seven patients were included in the study. Most patients were female (66/87, 75.8%) and the mean age was 55 years. 54% had cavitary lung disease. People with cystic fibrosis made up 26.4% of the cohort. There were 46 patients with Mycobacterium avium complex, 36 patients with Mycobacterium abscessus and five patients with other mycobacterial infections. 64% of isolates had macrolide resistance, either inducible or mutational, 31% had amikacin resistance (MIC ≥ 64 𝜇g/ml) and 21.8% had both macrolide and amikacin resistance. The mean duration of antibiotic use prior to the initiation of bedaquiline was 32.8 months (0-165 months). The most common indication for bedaquiline use was treatment failure related to intolerance or resistance to antibiotics. Mean duration of bedaquiline use was 20 months (range 1-134 mos.). Bedaquiline was well tolerated: only 10% (9/87) of patients required discontinuation of treatment related to side effects of whom 4 reported adverse events related to bedaquiline, one with a rash, one with nausea and two with transaminase elevation. None of the patients discontinued therapy related to QTc prolongation. Ten patients had to discontinue bedaquiline due to lack of insurance coverage, although the mean exposure to bedaquiline in this group was 18 months (2-43 mo.) Once on bedaquiline, 46% had sputum cultures convert to negative (defined as two negative cultures over three months) and 40% were able to discontinue all therapy with 12 months of negative cultures. Conclusion In this cohort of treatment experienced patients with drug resistance or intolerance, bedaquiline was well-tolerated and led to cure in 40% of patients.
Abstract Rationale Adherence to center-based pulmonary rehabilitation after a COPD-related hospitalization—which improves all outcomes, including survival—is only 3%. Home-based programs have been proposed as a more feasible option, but they are not systematically offered, and patient preference is unknown. Objectives and Methods This pragmatic randomized trial involving patients with COPD recently hospitalized for a COPD exacerbation, originally aimed to investigate the comparative effect two arms: The choice of a facilitated referral to a center-based outpatient pulmonary rehabilitation program or a home-based program versus a home-based program on adherence to post-hospitalization rehabilitation and disease-specific QoL measured by the Chronic Respiratory Questionnaire. The trial aimed to investigate the patient’s preference of home vs center-based rehabilitation in individuals randomized to the choice arm. Daily steps were measured by Actigraph ®. The asynchronous home-based program included weekly health coaching and daily monitoring of daily steps, symptoms, and a 20-minute daily flexibility-balance exercise routine. Results Of 1,906 patients approached, 294 (15%) were randomized and agreed to the rehabilitation options offered by the study arms (uptake); of those, 56% completed the 12-week intervention (adherence). Of the 145 randomized to the choice arm, only one patient chose center-based PR; therefore, both groups received the same intervention, and results are presented as a one-group (before–after) analysis. Compared with baseline, the home intervention significantly improved (p < 0.01) physical and emotional QoL (Chronic Respiratory Questionnaire) and increased daily steps beyond the minimal clinically important difference. Trajectory models adjusted for age, FEV1%, and mMRC (breathlessness) confirmed sustained improvements in QoL at 6 and 12 months from baseline. Conclusions When offered a choice of rehabilitation setting after a COPD-related hospital admission for an exacerbation, home-based rehabilitation is patients’ preferred option. Sustained quality-of-life improvements in 1 year may represent an opportunity to regain well-being and/or deliver primary palliative care. Our results may have important implications for clinical practice.
Rationale Chronic obstructive pulmonary disease (COPD) exacerbations, often triggered by viral infections like COVID-19, are associated with increased cardiovascular risk. We hypothesized that COVID-19-related exacerbations carry higher short-term cardiovascular and mortality risks than non-COVID-19-related exacerbations.Objectives To compare 28-day risk of stroke, pulmonary embolism (PE), acute myocardial infarction (AMI), major adverse cardiovascular events (MACE), and all-cause mortality following COVID-19-related vs non-COVID-19-related COPD exacerbations and assess variation across the pandemic.Methods Using Swedish national registers, we identified COPD with moderate (treated with oral corticosteroids with/without antibiotics) or severe (hospitalized) exacerbations from March 2020 to June 2023. Exacerbations with infection, hospitalization, or intensive care admission for COVID-19 were defined as COVID-19 related. A target trial was emulated and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated for each outcome, stratified by exacerbation severity and COVID-19 variants.Results Among 266 273 exacerbations (87.2% moderate, 12.8% severe), 5425 (2%) were COVID-19 related. COVID-19-related vs non-COVID-19-related moderate exacerbations were associated with risk of PE (aHR, 2.26 [95% CI, 1.49-3.42]), overall cardiovascular events (1.94 [1.47-2.56]), MACE (1.88 [1.28-2.76]), and mortality (4.58 [4.06-5.17]), but not significantly with AMI and stroke. Severe COVID-19-related exacerbations were only associated with higher mortality (1.46 [1.28-1.66]). Cardiovascular risks were highest during pre-Alpha and Delta for moderate exacerbations. Mortality remained elevated for both moderate and severe exacerbations, particularly during the same periods.Conclusions COVID-19-related exacerbations increased MACE, short-term cardiovascular, and mortality risks, mainly for moderate exacerbations, with attenuation during Alpha and Omicron, highlighting the need for proactive cardiovascular care during respiratory outbreaks.
