Annals of the American Thoracic Society最新文献

Rationale: Cannabis use is rapidly growing in the United States, but its health implications are poorly understood, particularly when compared with cigarette smoking. Previous research conducted on animal models or nonrepresentative populations with small sample sizes has yielded mixed results on the impact of marijuana use on hemoglobin concentrations, which might reflect subclinical hypoxemia and/or carbon monoxide exposure. Objectives: We evaluated the association between marijuana use and hemoglobin concentrations in a nationally representative sample of U.S. adults. Methods: This cross-sectional study included 16,038 individuals 18-59 years of age enrolled in National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. We related current and former marijuana use with measured hemoglobin concentrations, with adjustment for demographics, education, housing, and cigarette smoking status in multivariable analyses that incorporated complex survey weights. As candidate positive and negative control exposures, we used similar methods to relate cigarette smoking and benzodiazepine use, respectively, with hemoglobin concentrations. Results: Current marijuana use was associated with significantly higher hemoglobin concentrations. After multivariable adjustment, compared with never use, current marijuana use was associated with a 0.111 (95% confidence interval, 0.021 to 0.201) g/dl higher hemoglobin concentration, whereas former use was associated with a 0.047 (95% confidence interval, -0.018 to 0.113) g/dl higher concentration (linear trend P = 0.01). As hypothesized, cigarette smoking was also associated with higher hemoglobin concentrations, whereas benzodiazepine use was not. Conclusions: Among American adults, current marijuana use was associated with higher hemoglobin concentrations, as is cigarette smoking but not benzodiazepine use. These results suggest the possibility that marijuana smoking induces subclinical hypoxemia stimulating hemoglobin production. Further confirmation of this observational finding is needed in light of the increasing medical and recreational use of smoked marijuana products.

Rationale: Evaluating approaches to reduce treatment burden is a research priority among people with cystic fibrosis on highly effective modulators, including elexacaftor-tezacaftor-ivacaftor (ETI). Objectives: We sought to evaluate the impact of discontinuing both hypertonic saline (HS) and dornase alfa (DA) versus continuing both therapies among a subgroup of participants in the SIMPLIFY study who sequentially participated in trials evaluating the independent clinical effects of discontinuing HS and DA. Methods: SIMPLIFY participants ≥12 years old on ETI and constituting a subgroup using both HS and DA at study entry were randomized to the HS or DA trial and then randomized 1:1 to continue or discontinue the applicable therapy for 6 weeks. After completion of the first trial, eligible participants could enroll in the second trial beginning with a 2-week run-in. Study outcomes were compared across the duration of SIMPLIFY participation between a cohort remaining on both therapies during SIMPLIFY and a cohort that sequentially discontinued both as a result of trial randomizations. Multivariable regression models were used to estimate treatment differences, adjusted for time between trials, trial order, baseline age, sex at birth, and percent predicted forced expiratory volume in 1 second (ppFEV₁) at study entry. Results: Forty-three participants discontinued both therapies by the end of SIMPLIFY, and 63 remained on both, with overall average ppFEV₁ of 96.7% at study entry and 3.9 months as the average duration of follow-up from beginning of the first trial to completion of the second trial, including time between trials. No clinically meaningful difference in the change in ppFEV₁ from baseline to completion of the second trial was observed between those who discontinued and those who remained on both therapies (difference: 0.22% off-on; 95% confidence interval = -1.60, 2.03). Changes in lung clearance index at 2.5% starting concentration, patient-reported outcomes, and safety outcomes were also comparable. Patient-reported treatment burden, as measured by a Cystic Fibrosis Questionnaire-Revised subscale, significantly decreased in those who discontinued both therapies. Conclusions: SIMPLIFY participants who sequentially discontinued both HS and DA experienced no meaningful changes in clinical outcomes and reported decreased treatment burden as compared with those who remained on both therapies. These data continue to inform a new era of postmodulator care of people with cystic fibrosis.

Rationale: Intrapleural enzyme therapy (IET) with tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) has been shown to reduce the need for surgical intervention for complicated parapneumonic effusion/empyema (CPPE/empyema). Failure of IET may lead to delayed care, and increased length of stay.

Objective: The goal of this study was to identify risk factors for failure of IET.

Methods: We performed a multicenter, retrospective study of patients who received IET for the treatment of CPPE/empyema. Clinical and radiological variables at the time of diagnosis were included. We compared four different machine learning classifiers (L1-penalized logistic regression, support vector machine (SVM), XGBoost and LightGBM) by multiple bootstrap-validated metrics, including F-beta to demonstrate model performances.

Results: 466 participants who received IET for pleural infection were included from five institutions across the United States. Resolution of CPPE/empyema with IET was achieved in 78% (n=365). SVM performed superior with median F-beta of 56%, followed by L1-penalized logistic regression, LGBM and XGBoost. Clinical and radiological variables were graded based on their ranked variable importance. The top two significant predictors of IET failure using SVM were the presence of an abscess/necrotizing pneumonia (17%) and pleural thickening (13%). Similarly, LightGBM identified abscess/necrotizing pneumonia (35%) and pleural thickening (26%) and XGBoost indicated pleural thickening (36%) and abscess/necrotizing pneumonia (17%) as the most significant predictors of treatment failure. Predictors identified by L1-penalized logistic regression model were pleural thickening (18%) and pleural fluid LDH (9%).

Conclusions: The presence of abscess/necrotizing pneumonia and pleural thickening consistently ranked among the strongest predictors of IET failure in all machine learning models. The difference in rankings between models may be a consequence of the different algorithms used by each model. These results indicate that the presence of abscess/necrotizing pneumonia, and pleural thickening may predict IET failure. These results should be confirmed in larger studies.

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.

Objective: To determine whether NO₂ and O₃ are associated with lung function and FeNO in children.

Methods: We measured lung function (FEV1 and FVC) at mid-childhood (mean age 7.9 years, n=703), early teens (13.2 years, n=976), and mid-teen (17.6 years, n=624) study visits, and fractional exhaled nitric oxide (FeNO) at the early and mid-teen study visits in Project Viva, a cohort of mother-child pairs in the Boston, MA area. Long-term exposure to NO₂ and O₃ was estimated at home address using geospatial models. We examined associations of home address NO₂ and O₃ exposure and proximity to roadway with lung function and FeNO 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 mid-teen associations by blood eosinophil level, 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: e.g. an IQR increment of NO₂ exposure from birth through the early teen visit was associated with 189.9 mL lower FEV1 (95% CI -273.3, -106.5) at the mid-teen visit. Lifetime NO₂ exposure at was associated with higher FeNO at the early teen visit: e.g. 16.2% higher FeNO [95% CI 7.1-26.4%) per IQR of lifetime NO₂ through the early teen visit. O₃ exposure was not associated with lung function or FeNO. Aeroallergen sensitization (measured in a subset of participants) modified associations of NO₂ and O₃ with FeNO.

Conclusions: Exposure to NO₂ was associated with lower lung function and higher FeNO among generally healthy children and teenagers. As NO₂ exposure levels were within the annual EPA standard, these findings suggest a need to reduce exposure to this pollutant to optimize child respiratory health.

Rationale: Under-perception of asthma symptoms is associated with poor asthma outcomes.

Objective: We assessed the effects of a behavioral intervention for improving perception of airflow limitation and asthma outcomes.

Methods: A two-arm randomized controlled trial compared peak expiratory flow (PEF) feedback versus supportive counseling. Latino and Black adolescents with asthma ages 10-17 years old and caregivers were recruited from hospitals in the Bronx, NY. PEF feedback sessions reviewed accuracy of PEF guesses and medication adherence data, and targeted behavior change using motivational interviewing and problem-solving skills training. Supportive counseling received emotional support related to asthma. Both groups received 3 sessions across 6 weeks. All participants were blinded to PEF while guessing PEF during pre-intervention, 1, 6, and 12-month follow-up. Children in PEF feedback saw actual PEF after guesses were locked in during the 6-week intervention. Participants and assessors were blinded to group assignment.

Measurements: The primary outcome was under-perception of airflow limitation (divergence between actual PEF and guesses) on home spirometers. Secondary outcomes included daily PEF and forced expiratory volume in 1 second (FEV₁), inhaled corticosteroid adherence measured by electronic monitors, Asthma Control Test, and emergency healthcare use for asthma.

Results: The sample comprised 354 children (M = 13.2±2.2 years; 62% Latino, 38% Black) and caregivers. PEF feedback (N = 153 analyzed) demonstrated greater improvements at 1-month follow-up on under-perception of airflow limitation (difference-in-differences, -12.64; 95% CI, -17.54 to -7.74), % personal best PEF (9.89; 95% CI, 7.13 to 12.65), % predicted FEV₁ (4.93; 95% CI, 0.95 to 8.90) and ICS adherence (16.02; 95% CI, 7.15 to 24.89) compared with supportive counseling (N = 152 analyzed). At 12-month follow-up PEF feedback maintained improvements on under-perception of airflow limitation (-13.87; 95% CI, -19.03 to -8.71), higher PEF (14.23; 95% CI, 11.37 to 17.08) and %FEV₁ (5.62; 95% CI, 1.56 to 9.67), and had smaller declines in ICS adherence (17.51; 95% CI, 7.12 to 27.89) versus pre-intervention than supportive counseling. No between-group differences existed for asthma control or healthcare use.

Conclusion: The efficacy and sustainability of PEF feedback was established in improving children's perception of airflow limitation, pulmonary function, and medication adherence. Clinical trial registration available at www.

Clinicaltrials: gov, ID: NCT02702687.