Annals of the American Thoracic Society最新文献

Rationale: Oral appliance therapy (OAT) is an effective treatment for many people with obstructive sleep apnea (OSA). However, OSA pathogenesis is heterogeneous, and, in ∼50% of cases, OAT does not fully control OSA. Objectives: This study aimed to control OSA in individuals with an incomplete response to OAT alone by using additional targeted therapies informed by OSA endotype characterization. Methods: Twenty-three people with OSA (apnea-hypopnea index [AHI], 41 ± 19 events/h) not fully resolved (AHI, >10 events/h) with OAT alone were prospectively recruited. OSA endotypes were characterized pretherapy during a detailed physiology study night. Initially, an expiratory positive airway pressure (EPAP) valve and supine avoidance device therapy were added to target the impaired anatomical endotype. Those with residual OSA (AHI, >10 events/h) then received one or more nonanatomical interventions based on endotype characterization. This included O₂ (4 L/min) to reduce high loop gain (unstable respiratory control) and 80/5 mg atomoxetine-oxybutynin to increase pharyngeal muscle activity. Finally, if required, OAT was combined with EPAP and continuous positive airway pressure (CPAP) therapy. Results: Twenty participants completed the study. OSA was successfully controlled (AHI, <10 events/h) with combination therapy in all but one participant (17 of 20 without CPAP). OAT plus EPAP and supine avoidance therapy treated OSA in 10 (50%) participants. OSA was controlled in five (25%) participants with the addition of O₂ therapy, one with atomoxetine-oxybutynin, and one required O₂ plus atomoxetine-oxybutynin. Two participants required CPAP for their OSA, and another was CPAP intolerant. Conclusions: These novel prospective findings highlight the potential of precision medicine to inform targeted combination therapy to treat OSA. Clinical trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN12618001995268).

Rationale: Obstructive sleep apnea (OSA) is a heterogeneous syndrome with various endotypic traits and symptoms. A link among symptoms, endotypes, and disease prognosis has been proposed but remains unsupported by empirical data. Objectives: To link symptom profiles and endotypes by clustering endotypic traits estimated using polysomnographic signals. Methods: We recruited 509 patients with moderate to severe OSA from a single sleep center. Polysomnographic data were collected between May 2020 and January 2022. Endotypic traits, namely arousal threshold, upper airway collapsibility, loop gain, and upper airway muscle compensation, were retrieved using polysomnographic signals during non-rapid eye movement periods. We used latent class analysis to group participants into endotype clusters. Demographic and polysomnographic parameter differences were compared between clusters, and associations between endotype clusters and symptom profiles were examined using logistic regression analyses. Results: Three endotype clusters were identified, characterized by high collapsibility/loop gain, low arousal threshold, and low compensation, respectively. Patients in each cluster exhibited similar demographic characteristics, but those in the high collapsibility/loop gain cluster had the highest proportion of obesity and severe oxygen desaturation observed in polysomnographic studies. The low compensation cluster was characterized by fewer sleepy symptoms and exhibited a lower rate of diabetes mellitus. Compared with the excessively sleepy group, disturbed sleep symptoms were associated with the low arousal threshold cluster (odds ratio, 1.89; 95% confidence interval, 1.16-3.10). Excessively sleepy symptoms were associated with the high collapsibility/loop gain cluster (odds ratio, 2.16; 95% confidence interval, 1.39-3.37) compared with the minimally symptomatic group. Conclusions: Three pathological endotype clusters were identified among patients with moderate to severe OSA, each exhibiting distinct polysomnographic characteristics and clinical symptom profiles.

Rationale: Cough is a commonly reported symptom in idiopathic pulmonary fibrosis (IPF) that negatively impacts patient-reported quality of life (QoL). However, both the burden of cough at diagnosis and the behavior of cough over time have not been systematically described in patients with IPF. Objectives: By utilizing data prospectively collected as part of the PROFILE study, we sought to assess cough burden and the impact that this has on QoL within a cohort of patients with newly diagnosed IPF. We also reexamined the previously described relationship between cough and mortality and the association of cough with the MUC5B promoter polymorphism. Methods: The PROFILE study is a multicenter, prospective, observational, longitudinal cohort study of incident IPF. Scores on the Leicester Cough Questionnaire (LCQ) were recorded at baseline in 632 subjects and then repeated 6 monthly in a subset (n = 216) of the cohort. Results: The median LCQ score at diagnosis was 16.1 (interquartile range, 6.5). LCQ scores remained stable over the subsequent year in the majority of patients. There was a weak association between LCQ score and baseline lung function, with worse cough-related QoL associated with more severe physiological impairment. Cough scores were not associated with subsequent mortality after correcting for baseline lung function. Furthermore, there was no relationship between LCQ score and MUC5B promoter polymorphism status. Conclusions: The burden of cough in IPF is high. Although cough is weakly associated with disease severity at baseline, cough-specific QoL, as measured by the LCQ, confers no prognostic value. Cough-specific QoL burden remains relatively stable over time and does not associate with MUC5B promoter polymorphism.

Rationale: The healthcare industry sometimes makes payments to physicians for nonresearch and research purposes in the United States. Objectives: We aimed to evaluate the trends in nonresearch and research industry payments to pulmonologists since the inception of the Open Payments database in 2013. Methods: Using the Open Payments database between August 2013 and December 2021, this population-based observational cohort study examined nonresearch and research payments made by the healthcare industry to pulmonologists registered in the National Plan and Provider Enumeration System in the United States. We performed descriptive analyses on payment data and generalized estimating equations for payment trends. Results: Of 12,488 active pulmonologists, 11,074 (88.7%) accepted a total of 2,246,412 payments totaling $1,053,344,669. Total payments were $253,405,965 (24.1%) in nonresearch, $17,382,904 (1.7%) in direct research, and $782,555,800 (74.3%) in associated research payments between 2013 and 2021. Median per-physician payments (interquartile range) were $2,342 ($496 to $8,299) for nonresearch, $4,688 ($1,435 to $21,803) for direct research, and $95,927 ($20,300 to $344,995) for associated research payments. The top 1%, 5%, and 10% of pulmonologists accepted 37.3%, 71.9%, and 83.7% of the total nonresearch payments. The per-physician nonresearch payments increased by 2.9% (95% confidence interval [CI], 1.2 to 4.7; P = 0.001) annually between 2014 and 2019 and decreased by 50.2% (95% CI, -55.3 to -44.6; P < 0.001) in 2020, whereas there was no yearly change in research payments. Conclusions: Nearly 90% of pulmonologists received nonresearch and research payments from the healthcare industry in the United States. Nonresearch payments have been increasing since the inception of the Open Payments database.

Rationale/Objectives: Antibiotic selection for in-hospital treatment of pulmonary exacerbations (PEx) in people with cystic fibrosis (CF) is typically guided by previous respiratory culture results or past PEx antibiotic treatment. In the absence of clinical improvement during PEx treatment, antibiotics are frequently changed in search of a regimen that better alleviates symptoms and restores lung function. The clinical benefits of changing antibiotics during PEx treatment are largely uncharacterized. Methods: This was a retrospective cohort study using the Cystic Fibrosis Foundation Patient Registry Pediatric Health Information System. PEx were included if they occurred in children with CF from 6 to 21 years old who had been treated with intravenous antibiotics between January 1, 2006, and December 31, 2018. PEx with lengths of stay <5 or >21 days or for which treatment was delivered in an intensive care unit were excluded. An antibiotic change was defined as the addition or subtraction of any intravenous antibiotic between Hospital Day 6 and the day before hospital discharge. Inverse probability of treatment weighting was used to adjust for disease severity and indication bias, which might influence a decision to change antibiotics. Results: In all, 4,099 children with CF contributed 18,745 PEx for analysis, of which 8,169 PEx (43.6%) included a change in intravenous antibiotics on or after Hospital Day 6. The mean change in pre- to post-treatment percent predicted forced expiratory volume in 1 second (ppFEV₁) was 11.3 (standard error, 0.21) among events in which an intravenous antibiotic change occurred versus 12.2 (0.18) among PEx without an intravenous antibiotic change (P = 0.001). Similarly, the odds of return to ⩾90% of baseline ppFEV₁ were less for PEx with antibiotic changes than for those without changes (odds ratio [OR], 0.89 [95% confidence interval (CI), 0.80-0.98]). The odds of returning to ⩾100% of baseline ppFEV₁ did not differ between PEx with versus without antibiotic changes (OR, 0.94 [95% CI, 0.86-1.03]). In addition, PEx treated with intravenous antibiotic changes were associated with higher odds of future PEx (OR, 1.17 [95% CI, 1.12-1.22]). Conclusions: In this retrospective study, changing intravenous antibiotics during PEx treatment in children with CF was common and not associated with improved clinical outcomes.

Rationale: Sepsis and septic shock are associated with microcirculatory dysfunction, which is believed to contribute to sepsis-induced organ failure. Vasodilators have been proposed to improve tissue perfusion in sepsis, but the overall survival impact of this strategy is unclear. Objectives: To evaluate the impact of systemic vasodilator administration in patients with sepsis and septic shock on mortality. Methods: We conducted a meta-analysis using a random effects model. Published and unpublished randomized trials in adult patients with sepsis and septic shock were included when comparing the use of systemic vasodilators against no vasodilators. The primary outcome was 28-30-day mortality, and secondary outcomes were organ function and resource use measures. Results: We included eight randomized trials (1,076 patients). In patients randomized to vasodilator arms compared with those randomized to treatment without vasodilators, the 28-30-day mortality risk ratio was 0.74 (95% confidence interval, 0.54-1.01). In a chronological cumulative meta-analysis, the association between vasodilators and survival improved over time. In a prespecified subgroup analysis in 104 patients in two randomized trials, prostacyclin analogues were associated with a decreased rate of 28-30-day mortality among patients with sepsis and septic shock (risk ratio, 0.46; 95% confidence interval, 0.25-0.85). Conclusions: In patients with sepsis and septic shock, administration of vasodilators is not associated with decreased 28-30-day mortality, but the confidence interval suggests potential benefit, and the meta-analysis might lack power. Prostacyclin appears the most promising. The results of this meta-analysis should encourage randomized trials evaluating the impact of vasodilators on mortality in sepsis.

Rationale: Despite the importance of sepsis surveillance, no optimal approach for identifying sepsis hospitalizations exists. The Centers for Disease Control and Prevention Adult Sepsis Event Definition (CDC-ASE) is an electronic medical record-based algorithm that yields more stable estimates over time than diagnostic coding-based approaches but may still result in misclassification. Objectives: We sought to assess three approaches to identifying sepsis hospitalizations, including a modified CDC-ASE. Methods: This cross-sectional study included patients in the Veterans Affairs Ann Arbor Healthcare System admitted via the emergency department (February 2021 to February 2022) with at least one episode of acute organ dysfunction within 48 hours of emergency department presentation. Patients were assessed for community-onset sepsis using three methods: 1) explicit diagnosis codes, 2) the CDC-ASE, and 3) a modified CDC-ASE. The modified CDC-ASE required at least two systemic inflammatory response syndrome criteria instead of blood culture collection and had a more sensitive definition of respiratory dysfunction. Each method was compared with a reference standard of physician adjudication via medical record review. Patients were considered to have sepsis if they had at least one episode of acute organ dysfunction graded as "definitely" or "probably" infection related on physician review. Results: Of 821 eligible hospitalizations, 449 were selected for physician review. Of these, 98 (21.8%) were classified as sepsis by medical record review, 103 (22.9%) by the CDC-ASE, 132 (29.4%) by the modified CDC-ASE, and 37 (8.2%) by diagnostic codes. Accuracy was similar across the three methods of interest (80.6% for the CDC-ASE, 79.6% for the modified CDC-ADE, and 84.2% for diagnostic codes), but sensitivity and specificity varied. The CDC-ASE algorithm had sensitivity of 58.2% (95% confidence interval [CI], 47.2-68.1%) and specificity of 86.9% (95% CI, 82.9-90.2%). The modified CDC-ASE algorithm had greater sensitivity (69.4% [95% CI, 59.3-78.3%]) but lower specificity (81.8% [95% CI, 77.3-85.7%]). Diagnostic codes had lower sensitivity (32.7% [95% CI, 23.5-42.9%]) but greater specificity (98.6% [95% CI, 96.7-99.55%]). Conclusions: There are several approaches to identifying sepsis hospitalizations for surveillance that have acceptable accuracy. These approaches yield varying sensitivity and specificity, so investigators should carefully consider the test characteristics of each method before determining an appropriate method for their intended use.