The Effect of Chronic Altitude Exposure on COPD Outcomes in the SPIROMICS Cohort.

RATIONALE: Individuals with COPD have airflow obstruction and maldistribution of ventilation. For those living at high altitude, any gas exchange abnormality is compounded by reduced partial pressures of inspired oxygen. OBJECTIVES: Does residence at higher-altitude exposure affect COPD outcomes, including lung function, imaging characteristics, symptoms, health status, functional exercise capacity, exacerbations, or mortality? METHODS: From the SPIROMICS cohort, we identified individuals with COPD living below 1,000 ft (305 m) elevation (n= 1,367) versus above 4,000 ft (1,219 m) elevation (n= 288). Multivariable regression models were used to evaluate associations of exposure to high altitude with COPD-related outcomes. MEASUREMENTS AND MAIN RESULTS: Living at higher altitude was associated with reduced functional exercise capacity as defined by 6MWD (-32.3 m, (-55.7 to -28.6)). There were no differences in patient-reported outcomes as defined by symptoms (CAT, mMRC), or health status (SGRQ). Higher altitude was not associated with a different rate of FEV1 decline. Higher altitude was associated with lower odds of severe exacerbations (IRR 0.65, (0.46 to 0.90)). There were no differences in small airway disease, air trapping, or emphysema. In longitudinal analyses, higher altitude was associated with increased mortality (HR 1.25, (1.0 to 1.55)); however, this association was no longer significant when accounting for air pollution. CONCLUSIONS: Chronic altitude exposure is associated with reduced functional exercise capacity in individuals with COPD, but this did not translate into differences in symptoms or health status. Additionally, chronic high-altitude exposure did not affect progression of disease as defined by longitudinal changes in spirometry.

Health Professional vs Layperson Values and Preferences on Scarce Resource Allocation.

Importance: COVID-19 prompted rapid development of scarce resource allocation (SRA) policies to be implemented if demand eclipsed health systems' ability to provide critical care. While SRA policies follow general ethical frameworks, understanding priorities of those affected by policies and/or tasked with implementing them is critical. Objective: To evaluate whether community members and health care profesionals (HCP) agree with SRA protocols at the University of California (UC). Design, Setting, and Participants: This survey study used social media and community-partnered engagement to recruit participants to a web-based survey open to all participants aged older than 18 years who wished to enroll. This study was fielded between May and September 2020 and queried participants' values and preferences on draft SRA policy tenets. Participants were also encouraged to forward the survey to their networks for snowball sampling. Data were analyzed from July 2020 to January 2024. Main Outcomes and Measures: Survey items assessed values and preferences, graded on Likert scales. Agreement was tabulated as difference in Likert points between expressed opinion and policy tenets. Descriptive statistics were tested for significance by HCP status. Free text responses were analyzed using applied rapid qualitative analysis. Results: A total of 1545 participants aged older than 18 years (mean [SD] age 49 [16] years; 1149 female participants [74%], 478 health care practitioners [30%]) provided data on SRA values and preferences. Agreement with UC SRA policy as drafted was moderately high among respondents, ranging from 67% to 83% across domains. Higher agreement with the interim policy was observed for laypersons across all domains except health-related factors. HCPs agreed more strongly on average that resources should not be allocated to those less likely to survive (HCP mean, 3.70; 95% CI, 3.16-3.59; vs layperson mean, 3.38; 95% CI, 3.17-3.59; P = .002), and were more in favor of reallocating life support from patients less likely to those more likely to survive (HCP mean, 6.41; 95% CI, 6.15-6.67; vs layperson mean, 5.40; 95% CI, 5.23-5.58; P < .001). Transparency and trust building themes were common in free text responses and highly rated on scaled items. Conclusions and Relevance: This survey of SRA policy values found moderate agreement with fundamental principles of such policies. Engagement with communities affected by SRA policy should continue in iterative refinement in preparation for future crises.

Longitudinal Follow-Up of Participants With Tobacco Exposure and Preserved Spirometry.

Importance: People who smoked cigarettes may experience respiratory symptoms without spirometric airflow obstruction. These individuals are typically excluded from chronic obstructive pulmonary disease (COPD) trials and lack evidence-based therapies. Objective: To define the natural history of persons with tobacco exposure and preserved spirometry (TEPS) and symptoms (symptomatic TEPS). Design, Setting, and Participants: SPIROMICS II was an extension of SPIROMICS I, a multicenter study of persons aged 40 to 80 years who smoked cigarettes (>20 pack-years) with or without COPD and controls without tobacco exposure or airflow obstruction. Participants were enrolled in SPIROMICS I and II from November 10, 2010, through July 31, 2015, and followed up through July 31, 2021. Exposures: Participants in SPIROMICS I underwent spirometry, 6-minute walk distance testing, assessment of respiratory symptoms, and computed tomography of the chest at yearly visits for 3 to 4 years. Participants in SPIROMICS II had 1 additional in-person visit 5 to 7 years after enrollment in SPIROMICS I. Respiratory symptoms were assessed with the COPD Assessment Test (range, 0 to 40; higher scores indicate more severe symptoms). Participants with symptomatic TEPS had normal spirometry (postbronchodilator ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity >0.70) and COPD Assessment Test scores of 10 or greater. Participants with asymptomatic TEPS had normal spirometry and COPD Assessment Test scores of less than 10. Patient-reported respiratory symptoms and exacerbations were assessed every 4 months via phone calls. Main Outcomes and Measures: The primary outcome was assessment for accelerated decline in lung function (FEV1) in participants with symptomatic TEPS vs asymptomatic TEPS. Secondary outcomes included development of COPD defined by spirometry, respiratory symptoms, rates of respiratory exacerbations, and progression of computed tomographic-defined airway wall thickening or emphysema. Results: Of 1397 study participants, 226 had symptomatic TEPS (mean age, 60.1 [SD, 9.8] years; 134 were women [59%]) and 269 had asymptomatic TEPS (mean age, 63.1 [SD, 9.1] years; 134 were women [50%]). At a median follow-up of 5.76 years, the decline in FEV1 was -31.3 mL/y for participants with symptomatic TEPS vs -38.8 mL/y for those with asymptomatic TEPS (between-group difference, -7.5 mL/y [95% CI, -16.6 to 1.6 mL/y]). The cumulative incidence of COPD was 33.0% among participants with symptomatic TEPS vs 31.6% among those with asymptomatic TEPS (hazard ratio, 1.05 [95% CI, 0.76 to 1.46]). Participants with symptomatic TEPS had significantly more respiratory exacerbations than those with asymptomatic TEPS (0.23 vs 0.08 exacerbations per person-year, respectively; rate ratio, 2.38 [95% CI, 1.71 to 3.31], P < .001). Conclusions and Relevance: Participants with symptomatic TEPS did not have accelerated rates of decline in FEV1 or increased incidence of COPD vs those with asymptomatic TEPS, but participants with symptomatic TEPS did experience significantly more respiratory exacerbations over a median follow-up of 5.8 years.

Eosinophil recovery in hospitalized COVID-19 patients is associated with lower rates of ICU admission and in-hospital mortality: An observational cohort analysis.

BACKGROUND: Admission eosinopenia (<100 cells/µL) is associated with poor clinical outcomes in hospitalized COVID-19 patients. However, the effects of eosinophil recovery (defined as reaching ≥50 eosinophils/µL) during hospitalization on COVID-19 outcomes have been inconsistent. METHODS: The study included 1,831 patients admitted to UCLA hospitals between February 2020 and February 2021 with PCR-confirmed COVID-19. Using competing risk regression and modeling eosinophil recovery as a time-dependent covariate, we evaluated the longitudinal relationship between eosinophil recovery and in-hospital outcomes including ICU admission, need for mechanical ventilation, and in-hospital mortality. All analyses were adjusted for covariates including age, BMI, tobacco smoke exposure, comorbidities known to be risk factors for COVID-19 mortality, and treatments including dexamethasone and remdesivir. RESULTS: Eosinophil recovery was evaluated in patients with <50 eosinophils/µL on admission (n = 1282). These patients cumulatively amassed 11,633 hospital patient-days; 3,985 of those days qualified as eosinophil recovery events, which were represented by 781 patients achieving at least one instance of eosinophil recovery during hospitalization. Despite no significant difference in the rate of mechanical ventilation, eosinophil recoverers had significantly lower rates of in-hospital mortality (aHR: 0.44 [0.29, 0.65], P = 0.001) and ICU admission (aHR: 0.25 [0.11, 0.61], P = 0.002). CONCLUSION: Trending eosinophil counts during hospitalization is simple and can be performed in resource-limited healthcare settings to track the inflammatory status of a patient. Lack of eosinophil recovery events can identify those at risk for future progression to severe COVID.

Three-Month Variability of Commonly Evaluated Biomarkers in Clinically Stable COPD.

Introduction: Clinical decisions in chronic obstructive pulmonary disease (COPD) treatment often utilize serially assessed physiologic parameters and biomarkers. To better understand the reliability of these tests, we evaluated changes in commonly assessed biomarkers over 3 months in patients with clinically stable COPD. Methods: We performed an observational prospective cohort study of 89 individuals with clinically stable COPD, defined as no exacerbation history within 3 months of enrollment. Biomarkers included lung function and functional performance status, patient-reported outcomes of symptoms and health status, and blood markers of inflammation. The correlation between testing at baseline and at 3-month follow-up was reported as the intraclass correlation coefficient (ICC). "Outliers" had significant variability between tests, defined as >1.645 standard deviations between the two measurements. Differences in clinical features between outliers and others were compared. Results: Participants with COPD (n = 89) were 70.5 ± 6.7 years old, 54 (61%) male, had a 40 pack-year smoking history with 24.7% being current smokers, and postbronchodilator forced expiratory volume in one second (FEV1) 62.3 ± 22.7% predicted. The biomarkers with excellent agreement between the initial and the follow-up measurements were FEV1 (ICC = 0.96), Saint George's Respiratory Questionnaire (SGRQ) (ICC = 0.98), COPD Assessment Test (CAT) (ICC = 0.93) and C-reactive protein (CRP) (ICC = 0.90). By contrast, parameters showing less robust agreement were 6-minute walking distance (ICC = 0.75), eosinophil count (ICC = 0.77), erythrocyte sedimentation rate (ICC = 0.75) and white blood cell count (ICC = 0.48). Individuals with greater variability in biomarkers reported chronic bronchitis more often and had higher baseline SGRQ and CAT scores. Conclusion: Our study evaluated the stability of commonly assessed biomarkers in clinically stable COPD and showed excellent agreement between baseline and three-month follow-up values for FEV1, SGRQ, CAT and CRP. Individuals with chronic bronchitis and more symptomatic disease at baseline demonstrated greater variability in 3-month interval biomarkers.

Tobacco consumption behavior change during the COVID-19 pandemic is associated with perceived COVID threat.

Rationale: Tobacco use is a risk factor for COVID-19 adverse outcomes. Despite health implications, data conflict regarding COVID-19 and tobacco consumption. We present results from a survey of health behaviors during the pandemic to identify how COVID-19 influenced tobacco use. Methods: A national internet-based survey was deployed between May-September 2020. We analyzed participants who reported current or former smoking. We tabulated change in tobacco use, whether changes related to COVID-19, and measures of anxiety, depression, and novel perceived COVID-19 threat scale. We employed multinomial logistic regression to determine associations between these items and tobacco consumption. Results: We identified 500 respondents who reported ever smoking previously, 150 of which were currently smoking. Of 220 participants who reported any use of vapes, 110 were currently vaping. Increased perceived threat of COVID-19 was associated with both increased (aRRincrease 1.75, 95% CI [1.07-2.86], P = 0.03) and decreased (aRRdecrease 1.72 [1.04-2.85], P = 0.03) tobacco consumption relative to no change. There were no significant relationships found between perceived threat of COVID-19 and vaping behavior. Conclusions: As perceived COVID-19 threat increased, people were more likely to increase or decrease their smoking than stay the same, even after controlling for anxiety and depression, both of which can affect smoking in either direction. Further study into motivators of increasing or decreasing affected tobacco consumption, and how barriers to care from safer-at-home policies and changes in care delivery moderate change in tobacco use will aid planning tobacco reduction interventions during the ongoing and future respiratory viral pandemics.

Changes in Lung Volumes with Spirometric Disease Progression in COPD.

Background: Abnormal lung volumes representing air trapping identify the subset of smokers with preserved spirometry who develop spirometric chronic obstructive pulmonary disease (COPD) and adverse outcomes. However, how lung volumes evolve in early COPD as airflow obstruction develops remains unclear. Methods: To establish how lung volumes change with the development of spirometric COPD, we examined lung volumes from the pulmonary function data (seated posture) available in the U.S. Department of Veterans Affairs electronic health records (n=71,356) and lung volumes measured by computed tomography (supine posture) available from the COPD Genetic Epidemiology (COPDGene®) study (n=7969) and the SubPopulations and InterMediate Outcome Measures In COPD Study (SPIROMICS) (n=2552) cohorts, and studied their cross-sectional distributions and longitudinal changes across the airflow obstruction spectrum. Patients with preserved ratio-impaired spirometry (PRISm) were excluded from this analysis. Results: Lung volumes from all 3 cohorts showed similar patterns of distributions and longitudinal changes with worsening airflow obstruction. The distributions for total lung capacity (TLC), vital capacity (VC), and inspiratory capacity (IC) and their patterns of change were nonlinear and included different phases. When stratified by airflow obstruction using Global initiative for chronic Obstructive Lung Disease (GOLD) stages, patients with GOLD 1 (mild) COPD had larger lung volumes (TLC, VC, IC) compared to patients with GOLD 0 (smokers with preserved spirometry) or GOLD 2 (moderate) disease. In longitudinal follow-up of baseline GOLD 0 patients who progressed to spirometric COPD, those with an initially higher TLC and VC developed mild obstruction (GOLD 1) while those with an initially lower TLC and VC developed moderate obstruction (GOLD 2). Conclusions: In COPD, TLC, and VC have biphasic distributions, change in nonlinear fashions as obstruction worsens, and could differentiate those GOLD 0 patients at risk for more rapid spirometric disease progression.

Impact of Marijuana Smoking on COPD Progression in a Cohort of Middle-Aged and Older Persons.

Background: Limited data are available regarding marijuana smoking's impact on the development or progression of chronic obstructive pulmonary disease (COPD) in middle-aged or older adults with a variable history of tobacco cigarette smoking. Methods: We divided ever-tobacco smoking participants in the SubPopulations and InteRmediate Outcomes In COPD Study (SPIROMICS) into 3 groups based on self-reported marijuana use: current, former, or never marijuana smokers (CMSs, FMSs or NMSs, respectively). Longitudinal data were analyzed in participants with ≥2 visits over a period of ≥52 weeks. Measurements: We compared CMSs, FMSs, and NMSs, and those with varying amounts of lifetime marijuana use. Mixed effects linear regression models were used to analyze changes in spirometry, symptoms, health status, and radiographic metrics; zero-inflated negative binomial models were used for exacerbation rates. All models were adjusted for age, sex, race, baseline tobacco smoking amount, and forced expiratory volume in 1 second (FEV1) %predicted. Results: Most participants were followed for ≥4 years. Annual rates of change in FEV1, incident COPD, respiratory symptoms, health status, radiographic extent of emphysema or air trapping, and total or severe exacerbations were not different between CMSs or FMSs versus NMSs or between those with any lifetime amount of marijuana use versus NMSs. Conclusions: Among SPIROMICS participants with or without COPD, neither former nor current marijuana smoking of any lifetime amount was associated with evidence of COPD progression or its development. Because of our study's limitations, these findings underscore the need for further studies to better understand longer-term effects of marijuana smoking in COPD.

Integration and evaluation of chest X-ray artificial intelligence in clinical practice.

Purpose: To integrate and evaluate an artificial intelligence (AI) system that assists in checking endotracheal tube (ETT) placement on chest x-rays (CXRs) in clinical practice. Approach: In clinical use over 17 months, 214 CXR images were ordered to check ETT placement with AI assistance by intensive care unit (ICU) physicians. The system was built on the SimpleMind Cognitive AI platform and integrated into a clinical workflow. It automatically identified the ETT and checked its placement relative to the trachea and carina. The ETT overlay and misplacement alert messages generated by the AI system were compared with radiology reports as the reference. A survey study was also conducted to evaluate usefulness of the AI system in clinical practice. Results: The alert messages indicating that either the ETT was misplaced or not detected had a positive predictive value of 42% (21/50) and negative predictive value of 98% (161/164) based on the radiology reports. In the survey, radiologist and ICU physician users indicated that they agreed with the AI outputs and that they were useful. Conclusions: The AI system performance in real-world clinical use was comparable to that seen in previous experiments. Based on this and physician survey results, the system can be deployed more widely at our institution, using insights gained from this evaluation to make further algorithm improvements and quality assurance of the AI system.

Chronic Obstructive Pulmonary Disease is Not Associated with In-Hospital Mortality in COVID-19: An Observational Cohort Analysis.

Background: Chronic obstructive pulmonary disease (COPD) is associated with worsened outcomes in COVID-19 (coronavirus disease 2019). However, data remain fraught with heterogeneity and bias from comorbid conditions. Additionally, data on the impact of COPD-specific factors, such as pre-hospital medications and pulmonologist involvement, remain sparse. Objective: We report a single-center analysis of COPD patients hospitalized with COVID-19 compared to those without COPD. Primary outcomes include ICU admission, mechanical ventilation, and in-hospital mortality. Methods: We evaluated all patients ≥40 years admitted with PCR-confirmed COVID-19 between February 2020 and February 2021. COPD was defined by documented ICD-10 diagnosis of COPD, confirmed smoking history, and active bronchodilator use. We compared outcomes between COPD patients and the remainder of the COVID-19 cohort. Multivariable analyses were adjusted for age, sex, smoking status, and comorbid conditions. Results: Of 1537 hospitalized COVID-19 patients, 122 (7.9%) carried a diagnosis of COPD. The COPD cohort was older (74 ± 13 vs 66 ± 15 years, P < 0.001) and more often former smokers (P < 0.001). Comorbid conditions including diabetes, cardiovascular disease, and kidney disease were more prevalent in the COPD group (P < 0.001). After adjusting for comorbid conditions, the COPD cohort had higher severity scores and trended towards fewer hospital-free days. Among patients with COPD, pre-hospital use of aspirin was associated with decreased ICU admissions (aHR 0.56, P = 0.049) and mechanical ventilation (aHR 0.25, P = 0.008), while LAMAs (long-acting muscarinic antagonists) were associated with decreased in-hospital mortality (aHR 0.34, P = 0.047). Involvement of pulmonology in pre-hospital management of COPD was not found to significantly affect outcomes. Conclusion: When corrected for comorbid illnesses, COPD was associated with more severe disease but not with increased ICU admission, mechanical ventilation, or in-hospital mortality rates. Among COPD patients, prehospital treatment with aspirin and COPD-directed therapies were associated with improved outcomes.

Bronchodilators in Tobacco-Exposed Persons with Symptoms and Preserved Lung Function.

BACKGROUND: Many persons with a history of smoking tobacco have clinically significant respiratory symptoms despite an absence of airflow obstruction as assessed by spirometry. They are often treated with medications for chronic obstructive pulmonary disease (COPD), but supporting evidence for this treatment is lacking. METHODS: We randomly assigned persons who had a tobacco-smoking history of at least 10 pack-years, respiratory symptoms as defined by a COPD Assessment Test score of at least 10 (scores range from 0 to 40, with higher scores indicating worse symptoms), and preserved lung function on spirometry (ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ≥0.70 and FVC ≥70% of the predicted value after bronchodilator use) to receive either indacaterol (27.5 µg) plus glycopyrrolate (15.6 µg) or placebo twice daily for 12 weeks. The primary outcome was at least a 4-point decrease (i.e., improvement) in the St. George's Respiratory Questionnaire (SGRQ) score (scores range from 0 to 100, with higher scores indicating worse health status) after 12 weeks without treatment failure (defined as an increase in lower respiratory symptoms treated with a long-acting inhaled bronchodilator, glucocorticoid, or antibiotic agent). RESULTS: A total of 535 participants underwent randomization. In the modified intention-to-treat population (471 participants), 128 of 227 participants (56.4%) in the treatment group and 144 of 244 (59.0%) in the placebo group had at least a 4-point decrease in the SGRQ score (difference, -2.6 percentage points; 95% confidence interval [CI], -11.6 to 6.3; adjusted odds ratio, 0.91; 95% CI, 0.60 to 1.37; P = 0.65). The mean change in the percent of predicted FEV1 was 2.48 percentage points (95% CI, 1.49 to 3.47) in the treatment group and -0.09 percentage points (95% CI, -1.06 to 0.89) in the placebo group, and the mean change in the inspiratory capacity was 0.12 liters (95% CI, 0.07 to 0.18) in the treatment group and 0.02 liters (95% CI, -0.03 to 0.08) in the placebo group. Four serious adverse events occurred in the treatment group, and 11 occurred in the placebo group; none were deemed potentially related to the treatment or placebo. CONCLUSIONS: Inhaled dual bronchodilator therapy did not decrease respiratory symptoms in symptomatic, tobacco-exposed persons with preserved lung function as assessed by spirometry. (Funded by the National Heart, Lung, and Blood Institute and others; RETHINC ClinicalTrials.gov number, NCT02867761.).

Cannabis consumption is associated with lower COVID-19 severity among hospitalized patients: a retrospective cohort analysis.

BACKGROUND: While cannabis is known to have immunomodulatory properties, the clinical consequences of its use on outcomes in COVID-19 have not been extensively evaluated. We aimed to assess whether cannabis users hospitalized for COVID-19 had improved outcomes compared to non-users. METHODS: We conducted a retrospective analysis of 1831 patients admitted to two medical centers in Southern California with a diagnosis of COVID-19. We evaluated outcomes including NIH COVID-19 Severity Score, need for supplemental oxygen, ICU (intensive care unit) admission, mechanical ventilation, length of hospitalization, and in-hospital death for cannabis users and non-users. Cannabis use was reported in the patient's social history. Propensity matching was used to account for differences in age, body-mass index, sex, race, tobacco smoking history, and comorbidities known to be risk factors for COVID-19 mortality between cannabis users and non-users. RESULTS: Of 1831 patients admitted with COVID-19, 69 patients reported active cannabis use (4% of the cohort). Active users were younger (44 years vs. 62 years, p < 0.001), less often diabetic (23.2% vs 37.2%, p < 0.021), and more frequently active tobacco smokers (20.3% vs. 4.1%, p < 0.001) compared to non-users. Notably, active users had lower levels of inflammatory markers upon admission than non-users-CRP (C-reactive protein) (3.7 mg/L vs 7.6 mg/L, p < 0.001), ferritin (282 µg/L vs 622 µg/L, p < 0.001), D-dimer (468 ng/mL vs 1140 ng/mL, p = 0.017), and procalcitonin (0.10 ng/mL vs 0.15 ng/mL, p = 0.001). Based on univariate analysis, cannabis users had significantly better outcomes compared to non-users as reflected in lower NIH scores (5.1 vs 6.0, p < 0.001), shorter hospitalization (4 days vs 6 days, p < 0.001), lower ICU admission rates (12% vs 31%, p < 0.001), and less need for mechanical ventilation (6% vs 17%, p = 0.027). Using propensity matching, differences in overall survival were not statistically significant between cannabis users and non-users, nevertheless ICU admission was 12 percentage points lower (p = 0.018) and intubation rates were 6 percentage points lower (p = 0.017) in cannabis users. CONCLUSIONS: This retrospective cohort study suggests that active cannabis users hospitalized with COVID-19 had better clinical outcomes compared with non-users, including decreased need for ICU admission or mechanical ventilation. However, our results need to be interpreted with caution given the limitations of a retrospective analysis. Prospective and observational studies will better elucidate the effects cannabis use in COVID-19 patients.

Risk of COPD exacerbation is increased by poor sleep quality and modified by social adversity.

STUDY OBJECTIVES: Sleep is an important dimension in the care of chronic obstructive pulmonary disease (COPD), but its relevance to exacerbations is unclear. We wanted to assess whether sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI) is associated with an increased risk of COPD exacerbations and does this differ by socio-environmental exposures. METHODS: We included 1647 current and former smokers with spirometrically confirmed COPD from the SPIROMICS cohort. We assessed incidence rate ratios for exacerbation using zero-inflated negative binomial regression adjusting for demographics, medical comorbidities, and multiple metrics of disease severity, including respiratory medications, airflow obstruction, and symptom burden. Our final model adjusted for socio-environmental exposures using the Area Deprivation Index, a composite measure of contemporary neighborhood quality, and Adversity-Opportunity Index, a composite measure of individual-level historic and current socioeconomic indicators. We used a pre-determined threshold of 20% missingness to undertake multiple imputation by chained equations. As sensitivity analyses, we repeated models in those with complete data and after controlling for prior exacerbations. As an exploratory analysis, we considered an interaction between socio-environmental condition and sleep quality. RESULTS: After adjustment for all co-variates, increasing PSQI scores (range 0-21) were associated with a 5% increased risk for exacerbation per point (p = .001) in the imputed dataset. Sensitivity analyses using complete cases and after controlling for prior exacerbation history were similar. Exploratory analysis suggested less effect among those who lived in poor-quality neighborhoods (p-for-interaction = .035). CONCLUSIONS: Poor sleep quality may contribute to future exacerbations among patients with COPD. This represents one target for improving disease control. CLINICAL TRIAL REGISTRATION: Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). ClinicalTrials.gov Identifier# NCT01969344. Registry URL: https://clinicaltrials.gov/ct2/show/.

Reversible Airflow Obstruction Predicts Future Chronic Obstructive Pulmonary Disease Development in the SPIROMICS Cohort: An Observational Cohort Study.

Rationale: Chronic obstructive pulmonary disease (COPD) is defined by fixed spirometric ratio, FEV1/FVC < 0.70 after inhaled bronchodilators. However, the implications of variable obstruction (VO), in which the prebronchodilator FEV1/FVC ratio is less than 0.70 but increases to 0.70 or more after inhaled bronchodilators, have not been determined. Objectives: We explored differences in physiology, exacerbations, and health status in participants with VO compared with reference participants without obstruction. Methods: Data from the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort were obtained. Participants with VO were compared with reference participants without obstruction. Measurements and Main Results: We assessed differences in baseline radiographic emphysema and small airway disease at study entry, baseline, and change in lung function by spirometry, functional capacity by 6-minute walk, health status using standard questionnaires, exacerbation rates, and progression to COPD between the two groups. All models were adjusted for participant characteristics, asthma history, and tobacco exposure. We assessed 175 participants with VO and 603 reference participants without obstruction. Participants with VO had 6.2 times the hazard of future development of COPD controlling for other factors (95% confidence interval, 4.6-8.3; P < 0.001). Compared with reference participants, the VO group had significantly lower baseline pre- and post-bronchodilator (BD) FEV1, and greater decline over time in post-BD FEV1, and pre- and post-BD FVC. There were no significant differences in exacerbations between groups. Conclusions: Significant risk for future COPD development exists for those with pre- but not post-BD airflow obstruction. These findings support consideration of expanding spirometric criteria defining COPD to include pre-BD obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT01969344).

Forced Expiratory Flow at 25%-75% Links COPD Physiology to Emphysema and Disease Severity in the SPIROMICS Cohort.

BACKGROUND: Forced expiratory volume in 1 second (FEV1) is central to the diagnosis of chronic obstructive pulmonary disease (COPD) but is imprecise in classifying disease burden. We examined the potential of the maximal mid-expiratory flow rate (forced expiratory flow rate between 25% and 75% [FEF25%-75%]) as an additional tool for characterizing pathophysiology in COPD. OBJECTIVE: To determine whether FEF25%-75% helps predict clinical and radiographic abnormalities in COPD. STUDY DESIGN AND METHODS: The SubPopulations and InteRediate Outcome Measures In COPD Study (SPIROMICS) enrolled a prospective cohort of 2978 nonsmokers and ever-smokers, with and without COPD, to identify phenotypes and intermediate markers of disease progression. We used baseline data from 2771 ever-smokers from the SPIROMICS cohort to identify associations between percent predicted FEF25%-75% (%predFEF25%-75%) and both clinical markers and computed tomography (CT) findings of smoking-related lung disease. RESULTS: Lower %predFEF25-75% was associated with more severe disease, manifested radiographically by increased functional small airways disease, emphysema (most notably with homogeneous distribution), CT-measured residual volume, total lung capacity (TLC), and airway wall thickness, and clinically by increased symptoms, decreased 6-minute walk distance, and increased bronchodilator responsiveness (BDR). A lower %predFEF25-75% remained significantly associated with increased emphysema, functional small airways disease, TLC, and BDR after adjustment for FEV1 or forced vital capacity (FVC). INTERPRETATION: The %predFEF25-75% provides additional information about disease manifestation beyond FEV1. These associations may reflect loss of elastic recoil and air trapping from emphysema and intrinsic small airways disease. Thus, %predFEF25-75% helps link the anatomic pathology and deranged physiology of COPD.

Trends in Endotracheal Intubation During In-Hospital Cardiac Arrests: 2001-2018.

OBJECTIVES: Airway management during in-hospital cardiac arrest represents a fundamental component of resuscitative efforts, yet little is known about temporal trends in intubation during in-hospital cardiac arrest. Our objective was to investigate changes in in-hospital cardiac arrest airway management over time and in response to national guideline updates. DESIGN: Observational cohort study of a prospectively collected database. SETTING: Multicenter study of hospitals participating in the "Get With The Guidelines-Resuscitation" registry from January 1, 2001, to December 31, 2018. SUBJECTS: Adult patients who experienced an in-hospital cardiac arrest and did not have an invasive airway in place prior to the arrest. INTERVENTIONS: The primary outcome was the rate of intra-arrest intubation from 2001 to 2018. We constructed multivariable regression models with generalized estimating equations to determine the annual adjusted odds of intubation. We also assessed the timing of intubation relative to the onset of pulselessness and other arrest measures. We used an interrupted time-series analysis to assess the association between the 2010 Advanced Cardiac Life Support guideline update and intubation rates. MEASUREMENTS AND MAIN RESULTS: One thousand sixty-six eight hundred patients from 797 hospitals were included. From 2001 to 2018, the percentage of patients intubated during an arrest decreased from 69% to 55% for all rhythms, 73% to 60% for nonshockable rhythms, and 58% to 36% for shockable rhythms (p < 0.001 for trend for all 3 groups). The median time from onset of pulselessness to intubation increased from 5 minutes in 2001 (interquartile range, 2-8 min) to 6 minutes in 2018 (interquartile range, 4-10 min) (p < 0.001 for trend). Following the 2010 guideline update, there was a downward step change and a steeper decrease over time in the rate of intubation as compared to the preintervention period (p < 0.001). CONCLUSIONS: Endotracheal intubation rates during in-hospital cardiac arrest have decreased significantly over time, with a more substantial decline following the updated 2010 guideline that prioritized chest compressions over airway management.

Effects of Obstructive Sleep Apnea and Obesity on 30-Day Readmissions in Patients with Chronic Obstructive Pulmonary Disease: A Cross-Sectional Mediation Analysis.

Rationale: Comorbidity is a significant driver of health status and healthcare utilization in chronic obstructive pulmonary disease (COPD). Obstructive sleep apnea (OSA) portends poorer outcomes, whereas obesity is protective. Objectives: We describe the prevalence and influence of these comorbidities on COPD readmissions. Methods: We collated discharge records for COPD exacerbations spanning 2010-2016 from the Nationwide Readmissions Database using Medicare's Hospital Readmissions Reduction Program criteria, with OSA-COPD overlap identified by concomitant diagnosis code for OSA. We used mixed-effects logistic regression to predict readmission odds. A cross-sectional mediation analysis was performed to evaluate the extent that OSA attenuated obesity's impact on readmission. Results: Of 1,662,983 qualifying COPD discharges, 19.1% carried a diagnosis of obesity and 12.9% had OSA, with both diagnoses present in 7.8%. In unadjusted analyses, obesity (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.03-1.05; P < 0.001) and OSA (OR, 1.11; 95% CI, 1.10-1.13; P < 0.001) had increased readmission odds. In models adjusted for patient and hospital characteristics, 71% of readmission risk from obesity was attributable to OSA. When additionally adjusted for Charlson Comorbidity Index, we found that OSA remained a significant risk factor (OR, 1.05; 95% CI, 1.03-1.06; P < 0.001), whereas obesity remained protective (OR, 0.96; 95% CI, 0.94-0.97; P < 0.001) even after accounting for OSA. Conclusions: A significant proportion of patients with COPD suffer comorbid OSA and obesity with resultant readmission risk. Interestingly, obesity's protective effect attenuates readmission odds from OSA. Taken together, OSA and aggregate comorbidity influence readmissions in patients with COPD. Testing for and treating OSA-COPD overlap may provide a mechanism to reduce avoidable readmissions.