Annals of the American Thoracic Society最新文献

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.

Rationale: Tobacco smoking is a well-established risk factor for idiopathic pulmonary fibrosis (IPF), yet the influence of early-life tobacco exposure on future IPF risk remains poorly understood.

Objectives: To test the hypothesis that early-life tobacco exposure may elevate the risk of developing IPF, with this effect potentially modified by genetic susceptibility to IPF and mediated through accelerated biological aging.

Methods: Using data from over 430,000 participants in the UK Biobank, we performed a prospective cohort study to examine the associations of maternal smoking around birth and age of smoking initiation with IPF risk. We evaluated the combined effects and interactions between early-life tobacco exposure and genetic susceptibility to IPF, quantified using polygenic risk scores. We assessed biological aging, as measured by telomere length and phenotypic age, as potential mediators in the associations between early-life tobacco exposure and IPF risk. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Maternal smoking around birth was associated with a higher risk of IPF (HR: 1.26; 95% CI: 1.11-1.43). Compared to never-smokers, individuals who initiated smoking in childhood (HR: 3.65; 95% CI: 3.02-4.41), adolescence (HR: 2.64; 95% CI: 2.28-3.05), and adulthood (HR: 2.09; 95% CI: 1.79-2.44) exhibited increased IPF risk (P for trend < 0.001). An additive interaction was observed between age of smoking initiation and genetic risk for IPF. Individuals with high genetic risk, maternal smoking exposure, and childhood smoking initiation had a 16-fold greater risk of IPF (HR: 16.47; 95% CI: 9.57-28.32), compared to those with low genetic risk and no tobacco exposure. Telomere length and phenotypic age each mediated approximately 10% of the effect of maternal smoking on IPF, with weaker mediation effects observed for later ages of smoking initiation.

Conclusion: Early-life tobacco exposure may elevate the risk of IPF, with effect modified by genetic susceptibility and partially mediated through accelerated biological aging.

Rationale: Globally, in 2019, chronic obstructive pulmonary disease (COPD) was the third leading cause of death. While tobacco smoking is the predominant risk factor, the role of long-term air pollution exposure in increasing risk of COPD remains unclear. Moreover, there are few studies that have been conducted in racial and ethnic minoritized and socioeconomically diverse populations, while accounting for smoking history and other known risk factors.

Objective: To evaluate the association for ambient air pollution and COPD in a multiethnic population in California.

Methods: Among 38,654 African American, Japanese American, Latino and White California participants in the Multiethnic Cohort study enrolled in the fee-for-service component of Medicare, we used Cox proportional hazards regression to estimate the association of time-varying ambient air pollutants: particulate matter with diameter ≤2.5 μm or 10 μm (PM_2.5, PM₁₀), nitrogen dioxide (NO₂), carbon monoxide (CO), ozone (O₃), benzene and ultrafine particles (UFP) with COPD risk (n=10,915 cases; 8.8 years of follow-up). Subgroup analyses were conducted by race and ethnicity, sex, smoking status at MEC baseline questionnaire, and neighborhood socioeconomic status (nSES).

Results: We observed positive associations for NOx (per 50 ppb) with risk of COPD (hazards ratios (HR)=1.45; 95% CI: 1.35-1.55). The associations for NO₂ (per 20 ppb), PM_2.5 (10ug/m3), PM₁₀ (10ug/m3), CO (1000 ppb), and UFP (IQR=5241.7 particles/cm3) with risk of COPD were in similar directions as these air pollutants are highly correlated with NOx. These associations were found in African American, Latino, and Japanese American participants, but not in whites (p-heterogeneity across race and ethnicity<0.04). These associations also differed by nSES with effects being stronger in racial and ethnic minoritized populations and residents of low SES neighborhoods.

Conclusion: Long-term ambient air pollutant exposure is associated with COPD risk in a multiethnic, older adult (>65 years of age), population.

Rationale: Although the guidelines generally omit routine antibiotic prophylaxis for diagnostic bronchoscopy, this recommendation is primarily based on studies with relatively small sample sizes conducted at single institutions. Moreover, the applicability of recent technical and procedural advancements to these guidelines remains uncertain.

Objectives: To evaluate whether oral prophylactic antibiotic administration for diagnostic bronchoscopy reduces post-bronchoscopy infections among non-infectious diseases in the current setting.

Methods: Using the Diagnosis Procedure Combination database, a national inpatient database in Japan, we identified patients who underwent diagnostic bronchoscopy with or without oral prophylactic antibiotics between April, 2020 and March, 2022. We employed the propensity score-stabilized inverse probability of treatment weighting and instrumental variable analyses to compare post-bronchoscopy infections between the groups. Stratified analyses were also conducted based on patient profiles and antibiotic types.

Results: A total of 68,660 eligible patients were divided into prophylaxis (N=10,426) and no prophylaxis (N=58,234) groups. Post-bronchoscopy infections were observed in 612 patients (0.89%). The stabilized inverse probability of treatment weighting analysis showed that the prophylactic group was significantly associated with a decrease in post-bronchoscopy infections (odds ratio, 0.60; 95% confidence interval, 0.45 to 0.80). The instrumental variable analysis showed similar results (odds ratio, 0.50; 95% confidence interval, 0.34-0.74). Oral antibiotic prophylaxis was associated with reduction in post-bronchoscopy infection in patients who were older than 70 years, underwent bronchoscopy for malignancy, underwent biopsy or bronchoalveolar lavage, or received aminopenicillin or fluoroquinolone for prophylaxis.

Conclusions: Our findings suggest a potential role for prophylactic antibiotics in reducing post-bronchoscopy infections among non-infectious cases. While prophylactic antibiotics may help prevent these infections, their use should be carefully considered in relation to individual patient profiles and the specific antibiotics being administered.