Annals of the American Thoracic Society最新文献

Rationale: The pathogenicity of Aspergillus in the cystic fibrosis (CF) airway is debated, leading to unclear clinical benefit of antifungal therapy for Aspergillus infection. Objective: To determine the real-world effectiveness of antifungal use in people with CF (PwCF) with Aspergillus species in the United States. Methods: We conducted a retrospective cohort study evaluating the association of antifungal use and respiratory outcomes in PwCF and Aspergillus-positive cultures using the Cystic Fibrosis Foundation Patient Registry. Marginal structural models using inverse-probability treatment weighted estimators were used to test whether antifungal exposure was associated with forced expiratory volume in 1 second percent predicted (FEV₁pp) and pulmonary exacerbation rate while controlling for fixed and time-varying confounders. We conducted sensitivity analyses on individuals with persistent Aspergillus and without concomitant allergic bronchopulmonary aspergillosis (ABPA). Results: A total of 14,754 individuals with Aspergillus-positive cultures between 2006 and 2019 were identified. Antifungals were prescribed to 3,575 (24.2%) unique PwCF during the study period. Antifungal use was not associated with FEV₁pp (adjusted estimate = -0.96 percentage points; 95% confidence interval [CI] = -2.21, 0.29). Antifungal use was associated with 29% increased rate of pulmonary exacerbations requiring intravenous (i.v.) antibiotics (adjusted incidence rate ratio = 1.29, 95% CI = 1.22, 1.37). In sensitivity analyses limited to individuals without ABPA, antifungals were associated with 1.88 lower FEV₁pp (95% CI = -3.35, -0.41) and an increased rate of pulmonary exacerbations (adjusted incidence rate ratio = 1.30; 95% CI = 1.21, 1.40), whereas in patients with persistent Aspergillus and persistent Aspergillus without concomitant ABPA, antifungals were not associated with FEV₁pp. Conclusions: Antifungal therapy in PwCF and Aspergillus-positive cultures was not associated with improvements in FEV₁pp, suggesting no observed benefit. Although antifungal therapy was associated with increased risk for pulmonary exacerbations, this could reflect confounding by severity of disease. Randomized clinical trials examining the clinical efficacy of antifungals in Aspergillus infections in CF are warranted.

Rationale: Obstructive lung disease (OLD) pathogenesis includes inhalational (e.g., smoking) and noninhalational mechanisms (e.g., infections). Human immunodeficiency virus (HIV) has been suggested as a novel OLD risk factor. Substantial data have recently emerged about its effects on lung function and structure, especially in low- to middle-income countries and regarding longitudinal lung function. Objectives: To assess the association of HIV infection with OLD, impaired gas exchange, and emphysema. Methods: In this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science, Scopus, Cumulative Index to Nursing and Allied Health Literature, and Global Index Medicus through April 2023 for controlled and observational studies of people living with and without HIV reporting pulmonary function and/or emphysema. Primary outcomes were OLD by spirometry, gas exchange impairment by diffusing capacity of the lung for carbon monoxide, and visual emphysema by computed tomography. We performed random-effects meta-analyses using odds ratios (ORs) with 95% confidence intervals (CIs). This study was registered in PROSPERO (CRD42021268498). Results: We included 95 publications pertaining to 43 unique studies. HIV was associated with OLD (OR, 1.29; 95% CI, 1.02-1.63), impaired gas exchange (OR, 2.63; 95% CI, 0.96-7.24), emphysema (OR, 1.46; 95% CI, 1.02-2.09), and faster lung function decline. OLD risk was greatest in Africans with HIV. There were no gas exchange or emphysema data from Africa. The certainty of evidence was low to very low, primarily because of studies' observational design. Conclusions: People living with HIV have increased risk for OLD, gas exchange impairment, faster lung function decline, and emphysema. OLD risk in HIV varies regionally. We recommend that both spirometry and diffusing capacity of the lung for carbon monoxide be measured in people living with HIV and respiratory symptoms. Future studies should develop and validate HIV-specific screening and case-finding strategies for chronic lung disease.

Rationale: Intrapleural enzyme therapy (IET) with tissue plasminogen activator (tPA) and 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. Objectives: 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], extreme gradient boosting [XGBoost], and light gradient-boosting machine [LightGBM]) by multiple bootstrap-validated metrics, including F-β, to demonstrate model performances. Results: A total of 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 superiorly, with median F-β of 56%, followed by L1-penalized logistic regression, LightGBM, 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 the L1-penalized logistic regression model were pleural thickening (18%) and pleural fluid lactate dehydrogenase (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: Propofol is one of the first-line sedative-hypnotic agents for critically ill adults requiring mechanical ventilation. Although propofol can elevate triglyceride levels, and the latter is a risk factor for pancreatitis, the association between propofol and acute pancreatitis is unclear. Objectives: We sought to determine the clinical impact and potential associations between propofol infusion, hypertriglyceridemia, and acute pancreatitis. Methods: This is an observational multicenter study of adults (⩾18 yr old) who were admitted to an intensive care unit, who required mechanical ventilation and received continuous propofol infusion for at least 24 hours. The primary outcomes were the frequency of hypertriglyceridemia (>400 mg/dl) and acute pancreatitis. Further analyses were done to determine the clinical impact of elevated triglyceride levels (i.e., sedation changes) and risk factors for pancreatitis development. Results: Of 11,828 patients included, 33.2% (n = 3,922) had triglyceride levels measured, of whom 21.7% (n = 851) had hypertriglyceridemia at 4.5 days (SD = 6.8) after propofol initiation. Of those still requiring sedation, 70.4% (n = 576/818) received alternative sedatives after developing hypertriglyceridemia. Pancreatitis occurred in 1.2% of patients (n = 47/3,922) and was more frequent in those with hypertriglyceridemia (3.2%, 27/851; vs. 0.7%, 20/3,071; P < 0.001). After adjustment for potential confounding variables, each 100 mg/dl increase in triglyceride levels was associated with an 11% increase in risk of pancreatitis. Propofol dose was not associated with pancreatitis development. Conclusions: Acute pancreatitis is uncommon in patients receiving propofol infusion, and it occurs over a wide range of triglyceride levels, indicating a multifactorial pathophysiology. Hypertriglyceridemia frequently prompts the use of alternative sedatives. Further study is needed to determine how to best monitor and treat hypertriglyceridemia in critically ill patients receiving propofol infusion.