Annals of the American Thoracic Society最新文献

Rationale: Pleural infection is associated with significant mortality, and its management is complex. Little attention has been given to care-process metrics such as management delays, pleural drainage practices, and adequacy of intrapleural therapy administration despite their potential impact on outcomes. Audits revealed gaps in those care processes in our institution. Objectives: To assess the impact of quality-improvement initiatives on pleural effusion management in adults. Methods: We performed a retrospective comparison of patients treated with intrapleural therapy for pleural infection at the McGill University Health Center before (April 2013 to April 2016; N = 109) and after interventions (June 2020 to June 2021; N = 44). Interventions included a pleural drainage policy and order set, an intrapleural therapy protocol and preprinted order, implementation of intrapleural therapy administration by nurses, local pleural infection guideline development, and an online learning module for physicians. Major outcomes (length of stay, mortality, surgical treatment) and care-process metrics (management delays, pleural drainage practices, intrapleural therapy administration) were compared between the two periods. Results: After implementation of the interventions, in-hospital mortality and length of stay were unchanged, but the incidence of surgical management went from 14% to 0% (P = 0.01). Delays in drain insertion and intrapleural therapy initiation were not significantly different. Insertion of drains smaller than 12 F decreased from 51% to 7% (P < 0.001). Drain blockage decreased from 20% to 2% (P = 0.004). The incidence of additional drain insertion went from 62% to 48% (P = 0.12). After interventions, 70% of intrapleural therapy doses were given by nurses, the intrapleural therapy protocol was more often adequately followed, fewer doses were missed, and less extended therapy was prescribed. Complications related to drain insertion and intrapleural therapy were similar between the two periods. Conclusions: After the implementation of multifaceted quality improvement interventions for pleural infection including the involvement of nurses in pleural drain flushing and intrapleural therapy, improvements were observed in intrapleural therapy administration, chest drainage practices, and need for surgery. However, length of stay, mortality, and management delays were unchanged.

Rationale: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by progressive lung disease. Pseudomonas aeruginosa is a major pathogen in this disease and is known to impact lung function. Previous genotype-phenotype studies have been limited by cross-sectional designs, isolated adult or pediatric populations, small numbers, or short follow-up durations. Objectives: We aimed to explore long-term lung function in PCD grouped by genotypes and ultrastructural defects, considering the influence of P. aeruginosa. Methods: In this retrospective observational study, we analyzed 43 years of spirometry and 20 years of microbiology data. Using linear mixed-effects models, we estimated forced expiratory volume in 1 second z-score trends and compared them at ages 10, 25, and 50 years, whereas generalized estimating equations were used to assess P. aeruginosa prevalence between groups. In a secondary analysis, we matched spirometry and microbiology samples to evaluate the influence of P. aeruginosa on lung function. Results: We included 127 genotyped patients, 6,691 spirometry measurements, and 10,082 microbiology samples. CCDC39 and CCDC40 variants showed early-onset and sustained decline in lung function, whereas DNAH11 and HYDIN variants demonstrated relative stability. Lung function in the proximity of positive P. aeruginosa cultures was on average 0.06 z-score lower. Despite this, differences between groups remained largely unaffected by P. aeruginosa. Conclusions: Long-term lung function in PCD follows discrete genotype-specific profiles and appears independent of P. aeruginosa infection. We confirm and extend previous findings of CCDC39 and CCDC40 as variants associated with early-onset severe lung function impairment persisting in the long term.

Rationale: Further evaluation of the impact of long-term exposure to the gaseous air pollutants nitrogen dioxide (NO₂) and ozone (O₃) on child lung function and of NO₂ or O₃ on eosinophilic airway inflammation is needed. Objectives: To determine whether NO₂ and O₃ are associated with lung function and fractional exhaled nitric oxide (Fe_NO) in children. Methods: We measured lung function (forced expiratory volume in 1 second [FEV₁] and forced vital capacity [FVC]) at midchildhood (mean age, 7.9 yr; n = 703), early teens (13.2 yr; n = 976), and midteens (17.6 yr; n = 624) study visits, and Fe_NO at the early and midteens study visits in Project Viva, a cohort of mother-child pairs in the Boston area. Long-term exposure to NO₂ and O₃ was estimated at the home address using geospatial models. We examined associations of home address NO₂ and O₃ exposure and proximity to roadway with lung function and Fe_NO using linear regression models, adjusting for age, sex, height, weight, season, relative humidity, temperature, parental smoking, and measures of socioeconomic status. We examined for effect modification of the midteen associations by blood eosinophil concentration, physical activity, aeroallergen sensitization, and parental atopy. Results: Median exposure to NO₂ was 33.1 ppb (interquartile range [IQR], 10.4 ppb) and to O₃ was 35.3 ppb (IQR, 3.4) in the first year of life. Exposure to NO₂ was associated with lower FEV₁ and FVC across all age groups and exposure time intervals: For example, an IQR increment of NO₂ exposure from birth through the early teen visit was associated with 189.9 ml lower FEV₁ (95% confidence interval, -273.3, -106.5) at the midteen visit. Lifetime NO₂ exposure at was associated with higher Fe_NO at the early teen visit: for example, 16.2% higher Fe_NO (95% confidence interval, 7.1-26.4%) per IQR of lifetime NO₂ through the early teen visit. O₃ exposure was not associated with lung function or Fe_NO. Aeroallergen sensitization (measured in a subset of participants) modified associations of NO₂ and O₃ with Fe_NO. Conclusions: Exposure to NO₂ was associated with lower lung function and higher Fe_NO among generally healthy children and teenagers. Because NO₂ exposure levels were within the annual U.S. Environmental Protection Agency standard, these findings suggest a need to reduce exposure to this pollutant to optimize child respiratory health.

Rationale: Acetazolamide, eszopiclone, and venlafaxine may target different underlying mechanisms of obstructive sleep apnea (OSA) and individually may partially reduce OSA severity in select patients. We tested whether acetazolamide plus eszopiclone (DualRx) reduces OSA severity. We further explored whether the addition of venlafaxine (TripleRx) alleviates OSA in patients who do not fully respond to DualRx. Methods: In this double-blind crossover trial, 20 patients with OSA underwent baseline polysomnography followed by DualRx/placebo phases in random order. Subsequently, 18 patients underwent an open-label TripleRx phase. Each phase lasted 3 days and concluded with polysomnography. The primary outcome was the placebo-adjusted change in apnea-hypopnea index during supine, non-rapid eye movement sleep (AHI_NREM,supine) from baseline to DualRx. Secondary outcomes included other OSA metrics, sleep parameters, and select clinical outcomes (blood pressure, symptoms, and vigilance). Results: Participants were on average middle aged, overweight, and relatively diverse (20% women, 60% non-White), with severe OSA (median [interquartile range] AHI_NREM,supine, 32.8 [20 to 48.8] events/h). Compared with placebo, DualRx was well tolerated and improved AHI_NREM,supine (-13.8 [-24.1 to -5.2] events/h or -45% [-77% to -14%]; P_Wilcoxon = 0.003), overall AHI, hypoxic burden, and sleep architecture (P < 0.05) but not the selected clinical outcomes. TripleRx did not provide a clear benefit relative to DualRx, although some measures of OSA-related hypoxemia improved more substantially. There were no serious side effects. Conclusions: Short-term use of dual-drug therapy with DualRx substantially reduced OSA severity. Adding venlafaxine did not generally reduce OSA severity but may be beneficial for some patients. Longer term studies are needed to assess effects on clinically important outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT04639193).

Rationale: Previous studies evaluating the effect of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) on blood pressure (BP) showed variable results. Moreover, several studies recruited patients with normal or controlled BP, and compliance to antihypertensive drugs was not monitored. In addition, very few studies investigated central BP in this scenario.

Objectives: To evaluate whether OSA treatment is able to reduce central and peripheral BP in patients with uncontrolled hypertension (HTN) despite well documented use of anti-hypertensive treatment.

Methods: The MORPHEOS is a multicenter, randomized controlled trial designed to evaluate the effects of CPAP or placebo (nasal dilator strips-NDS) for 6-months in patients with moderate-to-severe OSA and uncontrolled HTN on office BP, ambulatory BP monitoring (ABPM) and central BP (co-primary endpoints). Uncontrolled HTN was defined by ≥1 abnormal parameter in ABPM after 1-month of pill count and ≥80% adherence to medication. Pill count, adherence to CPAP or NDS and office BP was determined once a week in the first month and monthly thereafter.

Results: A total of 123 patients completed the study (NDS: n=64, CPAP: n=59). The two groups were similar at baseline. Adherence to NDS (≥80%) and CPAP (≥4h/night) were 98.3% and 81.7%, respectively. As compared to NDS, office systolic BP (Δ=-10±16mmHg, p<0.001) and diastolic BP (Δ=-7±12mmHg, p=0.001) were reduced significantly in the CPAP group. Despite the BP lowering effect of CPAP did not reach statistical differences for ABPM parameters, the rate of 24-h ABPM control (<130X80mmHg) was higher in the CPAP than in the NDS group (40.7 vs 20%; p=0.024). Central diastolic BP reduced significantly (Δ=-6±9mmHg; adjusted p=0.029).

Conclusions: CPAP improves the rates of BP control in patients with OSA and uncontrolled HTN under regular use of medications. Clinical trial registration available at www.

Clinicaltrials: gov, ID: NCT02270658.