Early Evidence of Chronic Obstructive Pulmonary Disease Obscured by Race-Specific Prediction Equations.

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES race-specific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD.

Causes of and Clinical Features Associated with Death in Tobacco Cigarette Users by Lung Function Impairment.

Rationale: Cigarette smoking contributes to the risk of death through different mechanisms. Objectives: To determine how causes of and clinical features associated with death vary in tobacco cigarette users by lung function impairment. Methods: We stratified current and former tobacco cigarette users enrolled in Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) into normal spirometry, PRISm (Preserved Ratio Impaired Spirometry), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-2 COPD, and GOLD 3-4 COPD. Deaths were identified via longitudinal follow-up and Social Security Death Index search. Causes of death were adjudicated after a review of death certificates, medical records, and next-of-kin interviews. We tested associations between baseline clinical variables and all-cause mortality using multivariable Cox proportional hazards models. Measurements and Main Results: Over a 10.1-year median follow-up, 2,200 deaths occurred among 10,132 participants (age 59.5 ± 9.0 yr; 46.6% women). Death from cardiovascular disease was most frequent in PRISm (31% of deaths). Lung cancer deaths were most frequent in GOLD 1-2 (18% of deaths vs. 9-11% in other groups). Respiratory deaths outpaced competing causes of death in GOLD 3-4, particularly when BODE index ⩾7. St. George's Respiratory Questionnaire score ⩾25 was associated with higher mortality in all groups: Hazard ratio (HR), 1.48 (1.20-1.84) normal spirometry; HR, 1.40 (1.05-1.87) PRISm; HR, 1.80 (1.49-2.17) GOLD 1-2; HR, 1.65 (1.26-2.17) GOLD 3-4. History of respiratory exacerbations was associated with higher mortality in GOLD 1-2 and GOLD 3-4, quantitative emphysema in GOLD 1-2, and airway wall thickness in PRISm and GOLD 3-4. Conclusions: Leading causes of death vary by lung function impairment in tobacco cigarette users. Worse respiratory-related quality of life is associated with all-cause mortality regardless of lung function.

Single-Inhaler Triple Therapy in Patients with Advanced COPD: Bayesian Modeling of the Healthcare Resource Utilization Data and Associated Costs from the IMPACT Trial.

Objectives: In the IMPACT trial (NCT02164513), triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) showed clinical benefit compared with dual therapy with either FF/VI or UMEC/VI in the treatment of chronic obstructive pulmonary disease (COPD). We used data from IMPACT to determine whether this translated into differences in COPD-related healthcare resource utilization (HRU) costs in a United Kingdom (UK) setting. Methods: In a within-trial analysis, individual patient data from the IMPACT intention-to-treat (ITT) population were analyzed to estimate rates of COPD-related HRU with FF/UMEC/VI, FF/VI, or UMEC/VI. A Bayesian approach was applied to address issues typically encountered with this kind of data, namely data missing due to early study withdrawal, subjects with zero reported HRU, and skewness. Rates of HRU were estimated under alternate assumptions of data being missing at random (MAR) or missing not at random (MNAR). UK-specific unit costs were then applied to estimated HRU rates to calculate treatment-specific costs. Results: Under each MNAR scenario, per patient per year (PPPY) rates of COPD-related HRU were lowest amongst those patients who received treatment with FF/UMEC/VI compared with those receiving either FF/VI or UMEC/VI. Although absolute HRU rates and costs were typically higher for all treatment groups under MNAR scenarios versus MAR, final economic conclusions were robust to patient withdrawals. Conclusions: PPPY rates were typically lower with FF/UMEC/VI versus FF/VI or UMEC/VI.

Race and Sex Differences in Mortality in Individuals with Chronic Obstructive Pulmonary Disease.

Rationale: Despite differences in chronic obstructive pulmonary disease (COPD) comorbidities, race- and sex-based differences in all-cause mortality and cause-specific mortality are not well described. Objectives: To examine mortality differences in COPD by race-sex and underlying mechanisms. Methods: Medicare claims were used to identify COPD among REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort participants. Mortality rates were calculated using adjudicated causes of death. Hazard ratios (HRs) for mortality comparing race-sex groups were modeled with Cox proportional hazards regression. Results: In the 2,148-member COPD subcohort, 49% were women, and 34% were Black individuals; 1,326 deaths occurred over a median 7.5 years (interquartile range, 3.9-10.5 yr) follow-up. All-cause mortality per 1,000 person-years comparing Black versus White men was 101.1 (95% confidence interval [CI], 88.3-115.8) versus 93.9 (95% CI, 86.3-102.3; P = 0.99); comparing Black versus White women, all-cause mortality per 1,000 person-years was 74.2 (95% CI, 65.0-84.8) versus 70.6 (95% CI, 63.5-78.5; P = 0.99). Cardiovascular disease (CVD) was the leading cause-specific mortality among all race-sex groups. HR for CVD and chronic lung disease mortality were nonsignificant comparing Black versus White men. HR for CVD death was higher in Black compared with White women (HR, 1.44; 95% CI, 1.06-1.95), whereas chronic lung disease death was lower (HR, 0.44; 95% CI, 0.25-0.77). These differences were attributable to higher CVD risk factor burden among Black women. Conclusions: In the REGARDS COPD cohort, there were no race-sex differences in all-cause mortality. CVD was the most common cause of death for all race-sex groups with COPD. Black women with COPD had a higher risk of CVD-related mortality than White women. CVD comorbidity management, especially among Black individuals, may improve mortality outcomes.

Chronic obstructive pulmonary disease risk assessment tools: is one better than the others?

PURPOSE OF REVIEW: Risk assessment tools are essential in COPD care to help clinicians identify patients at higher risk of accelerated lung function decline, respiratory exacerbations, hospitalizations, and death. RECENT FINDINGS: Conventional methods of assessing risk have focused on spirometry, patient-reported symptoms, functional status, and a combination of these tools in composite indices. More recently, qualitatively and quantitatively assessed chest imaging findings, such as emphysema, large and small airways disease, and pulmonary vascular abnormalities have been associated with poor long-term outcomes in COPD patients. Although several blood and sputum biomarkers have been investigated for risk assessment in COPD, most still warrant further validation. Finally, novel remote digital monitoring technologies may be valuable to predict exacerbations but their large-scale performance, ease of implementation, and cost effectiveness remain to be determined. SUMMARY: Given the complex heterogeneity of COPD, any single metric is unlikely to fully capture the risk of poor long-term outcomes. Therefore, clinicians should review all available clinical data, including spirometry, symptom severity, functional status, chest imaging, and bloodwork, to guide personalized preventive care of COPD patients. The potential of machine learning tools and remote monitoring technologies to refine COPD risk assessment is promising but remains largely untapped pending further investigation.

Higher COPD Assessment Test Score Associated With Greater Exacerbations Risk: A Post Hoc Analysis of the IMPACT Trial.

BACKGROUND: In the InforMing the PAthway of COPD Treatment (IMPACT) trial, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduced moderate/severe exacerbation rates versus FF/VI and UMEC/VI in patients with chronic obstructive pulmonary disease (COPD). This post hoc analysis tested the relationship between baseline health status, risk of future exacerbations, and efficacy outcomes. METHODS: IMPACT was a Phase 3, double-blind, 52-week trial in patients with symptomatic COPD (COPD Assessment Test [CAT] score ≥10) and ≥1 moderate/severe exacerbation in the prior year randomized 2:2:1 to FF/UMEC/VI 100/62.5/25mcg, FF/VI 100/25mcg, or UMEC/VI 62.5/25mcg. Annual rate of on-treatment moderate/severe exacerbations, lung function, and safety were analyzed by continuous baseline CAT score. RESULTS: Moderate/severe exacerbation rates increased with increasing baseline CAT scores in FF/UMEC/VI and UMEC/VI arms. There was a very small increase in on-treatment pneumonia rates at higher baseline CAT scores across all treatment arms. FF/UMEC/VI reduced moderate/severe exacerbation rates versus UMEC/VI (i.e., the inhaled corticosteroid effect) consistently across the range of CAT scores. The reduction with FF/UMEC/VI versus FF/VI (i.e., the long-acting muscarinic antagonist effect) was greatest at lower CAT scores and appeared lesser at higher CAT scores. Improvements in lung function were observed with FF/UMEC/VI versus FF/VI and UMEC/VI, regardless of baseline CAT score. CONCLUSIONS: The CAT score was predictive of exacerbation risk. Worse baseline health status was associated with higher moderate/severe exacerbation and pneumonia rates. Irrespective of baseline CAT score, FF/UMEC/VI improved lung function, and reduced the annual moderate/severe exacerbation rates versus dual therapy. Results indicate an overall favorable benefit-risk profile of triple versus dual therapy, irrespective of CAT score. Clinical Trial Registration:GSK (CTT116855/NCT02164513).

Racial Segregation and Respiratory Outcomes among Urban Black Residents with and at Risk of Chronic Obstructive Pulmonary Disease.

Rationale: Racial residential segregation has been associated with worse health outcomes, but the link with chronic obstructive pulmonary disease (COPD) morbidity has not been established.Objectives: To investigate whether racial residential segregation is associated with COPD morbidity among urban Black adults with or at risk of COPD.Methods: Racial residential segregation was assessed using isolation index, based on 2010 decennial census and baseline address, for Black former and current smokers in the multicenter SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), a study of adults with or at risk for COPD. We tested the association between isolation index and respiratory symptoms, physiologic outcomes, imaging parameters, and exacerbation risk among urban Black residents, adjusting for established COPD risk factors, including smoking. Additional mediation analyses were conducted for factors that could lie on the pathway between segregation and COPD outcomes, including individual and neighborhood socioeconomic status, comorbidity burden, depression/anxiety, and ambient pollution.Measurements and Main Results: Among 515 Black participants, those residing in segregated neighborhoods (i.e., isolation index ⩾0.6) had worse COPD Assessment Test score (ß = 2.4; 95% confidence interval [CI], 0.7 to 4.0), dyspnea (modified Medical Research Council scale; ß = 0.29; 95% CI, 0.10 to 0.47), quality of life (St. George's Respiratory Questionnaire; ß = 6.1; 95% CI, 2.3 to 9.9), and cough and sputum (ß = 0.8; 95% CI, 0.1 to 1.5); lower FEV1% predicted (ß = -7.3; 95% CI, -10.9 to -3.6); higher rate of any and severe exacerbations; and higher percentage emphysema (ß = 2.3; 95% CI, 0.7 to 3.9) and air trapping (ß = 3.8; 95% CI, 0.6 to 7.1). Adverse associations attenuated with adjustment for potential mediators but remained robust for several outcomes, including dyspnea, FEV1% predicted, percentage emphysema, and air trapping.Conclusions: Racial residential segregation was adversely associated with COPD morbidity among urban Black participants and supports the hypothesis that racial segregation plays a role in explaining health inequities affecting Black communities.

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.

Contribution of Individual and Neighborhood Factors to Racial Disparities in Respiratory Outcomes.

Rationale: Black adults have worse health outcomes compared with white adults in certain chronic diseases, including chronic obstructive pulmonary disease (COPD).Objectives: To determine to what degree disadvantage by individual and neighborhood socioeconomic status (SES) may contribute to racial disparities in COPD outcomes.Methods: Individual and neighborhood-scale sociodemographic characteristics were determined in 2,649 current or former adult smokers with and without COPD at recruitment into SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). We assessed whether racial differences in symptom, functional, and imaging outcomes (St. George's Respiratory Questionnaire, COPD Assessment Test score, modified Medical Research Council dyspnea scale, 6-minute-walk test distance, and computed tomography [CT] scan metrics) and severe exacerbation risk were explained by individual or neighborhood SES. Using generalized linear mixed model regression, we compared respiratory outcomes by race, adjusting for confounders and individual-level and neighborhood-level descriptors of SES both separately and sequentially.Measurements and Main Results: After adjusting for COPD risk factors, Black participants had significantly worse respiratory symptoms and quality of life (modified Medical Research Council scale, COPD Assessment Test, and St. George's Respiratory Questionnaire), higher risk of severe exacerbations and higher percentage of emphysema, thicker airways (internal perimeter of 10 mm), and more air trapping on CT metrics compared with white participants. In addition, the association between Black race and respiratory outcomes was attenuated but remained statistically significant after adjusting for individual-level SES, which explained up to 12-35% of racial disparities. Further adjustment showed that neighborhood-level SES explained another 26-54% of the racial disparities in respiratory outcomes. Even after accounting for both individual and neighborhood SES factors, Black individuals continued to have increased severe exacerbation risk and persistently worse CT outcomes (emphysema, air trapping, and airway wall thickness).Conclusions: Disadvantages by individual- and neighborhood-level SES each partly explain disparities in respiratory outcomes between Black individuals and white individuals. Strategies to narrow the gap in SES disadvantages may help to reduce race-related health disparities in COPD; however, further work is needed to identify additional risk factors contributing to persistent disparities.

Effect of Age on the Efficacy and Safety of Once-Daily Single-Inhaler Triple-Therapy Fluticasone Furoate/Umeclidinium/Vilanterol in Patients With COPD: A Post Hoc Analysis of the Informing the Pathway of COPD Treatment Trial.

BACKGROUND: In the Informing the Pathway of COPD Treatment (IMPACT) trial, single-inhaler triple-therapy fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) reduced moderate/severe exacerbation rates vs FF/VI and UMEC/VI in patients with symptomatic COPD and a history of exacerbations, with a similar safety profile. RESEARCH QUESTION: Are trial outcomes with single-inhaler triple-therapy FF/UMEC/VI vs FF/VI and UMEC/VI affected by age in patients with symptomatic COPD and a history of exacerbations? STUDY DESIGN AND METHODS: IMPACT was a phase III, double-blind, 52-week trial. Patients ≥ 40 years of age with symptomatic COPD and ≥ 1 moderate/severe exacerbation in the previous year were randomly assigned 2:2:1 to FF/UMEC/VI 100/62.5/25 µg, FF/VI 100/25 µg, or UMEC/VI 62.5/25 µg. End points assessed by age included annual rate of moderate/severe exacerbations, change from baseline (CFB) in trough FEV1, proportion of St. George's Respiratory Questionnaire (SGRQ) responders (≥ 4 units decrease from baseline in SGRQ total score), and safety. RESULTS: The intention-to-treat population comprised 10,355 patients; 4,724 (46%), 4,225 (41%), and 1,406 (14%) were ≤ 64, 65 to 74, and ≥ 75 years of age, respectively. FF/UMEC/VI reduced on-treatment moderate/severe exacerbation rates vs FF/VI (% reduction [95% CI]: ≤ 64 years, 8% [-1 to 16]; P = .070; 65-74 years, 22% [14-29]; P < .001; ≥ 75 years, 18% [3-31]; P = .021) and vs UMEC/VI (≤ 64 years, 16% [7-25]; P = .002; 65-74 years, 33% [25-41]; P < .001; ≥ 75 years, 24% [6-38]; P = .012), with greatest rate reduction seen in the 65 to 74 and ≥ 75 years subgroups. Post hoc analyses of CFB in trough FEV1 and proportion of SGRQ responders at week 52 were significantly greater with FF/UMEC/VI than with FF/VI or UMEC/VI in all subgroups. No new safety signals were identified. INTERPRETATION: FF/UMEC/VI reduced the rate of moderate/severe exacerbations and improved lung function and health status vs FF/VI and UMEC/VI irrespective of age for most end points, with a similar safety profile. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02164513; URL: www.clinicaltrials.govCTT116855.

Protocol Summary of the COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE) Validation in Primary Care Study.

Chronic obstructive pulmonary disease (COPD) often remains undiagnosed and untreated. To date, COPD screening/case finding has not been designed to identify clinically significant COPD, disease ready for therapies beyond smoking cessation. Herein, we describe the ongoing prospective, pragmatic cluster-randomized controlled trial to assess specificity and sensitivity of the COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE) tool consisting of 5 questions and peak expiratory flow. The tool is designed to identify clinically significant COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ratio <.70 plus FEV1% predicted <60% or increased risk for exacerbation) and the trial will explore the impact of CAPTURE-based screening on COPD diagnosis and treatment rates in primary care patients. Of a total planned enrollment of 5000 English- or Spanish-speaking patients 45 to 80 years of age without a prior COPD diagnosis from 100 primary care practices, a total of 68 practices and 3064 patients have been enrolled in the study. Practices are centrally randomized to either usual care or clinician receipt of patient-level CAPTURE results. All clinicians receive basic COPD education with those in intervention practices also receiving CAPTURE interpretation education. In a single visit, patient participants complete a CAPTURE screening, pre- and post-bronchodilator spirometry and baseline demographic and health questionnaires to validate CAPTURE sensitivity, specificity, and predictive value of identifying undiagnosed, clinically significant COPD. One-year follow-up chart reviews and participant surveys assess the impact of sharing versus not sharing CAPTURE results with clinicians on clinical outcomes including level of respiratory symptoms and events and clinicians' initiation of recommendation-concordant COPD care. This is one of the first U.S. studies to validate and assess impact of a simple COPD screening tool in primary care.

Comprehensive stereological assessment of the human lung using multiresolution computed tomography.

The application of stereology to lung casts and two-dimensional microscopy images is the gold standard for quantification of the human lung anatomy. However, these techniques are labor intensive, involving fixation, embedding, and histological sectioning of samples and thus have prevented comprehensive studies. Our objective was to demonstrate the application of stereology to volumetric multiresolution computed tomography (CT) to efficiently and extensively quantify the human lung anatomy. Nontransplantable donor lungs from individuals with no evidence of respiratory disease (n = 13) were air inflated, frozen at 10 cmH2O, and scanned using CT. Systematic uniform random samples were taken, scanned using micro-CT, and assessed using stereology. The application of stereology to volumetric CT imaging enabled comprehensive quantification of total lung volume, volume fractions of alveolar, alveolar duct, and tissue, mean linear intercept, alveolar surface area, alveolar surface area density, septal wall thickness, alveolar number, number-weighted mean alveolar volume, and the number and morphometry of terminal and transitional bronchioles. With the use of this data set, we found that women and men have the same number of terminal bronchioles (last generation of conducting airways), but men have longer terminal bronchioles, a smaller wall area percentage, and larger lungs due to a greater number of alveoli per acinus. The application of stereology to multiresolution CT imaging enables comprehensive analysis of the human lung parenchyma that identifies differences between men and women. The reported data set of normal donor lungs aged 25-77 yr provides reference data for future studies of chronic lung disease to determine exact changes in tissue pathology.NEW & NOTEWORTHY Stereology has been the gold standard to quantify the three-dimensional lung anatomy using two-dimensional microscopy images. However, such techniques are labor intensive. This study provides a method that applies stereology to volumetric computed tomography images of frozen whole human lungs and systematic uniform random samples. The method yielded a comprehensive data set on the small airways and parenchymal lung structures, highlighting morphometric sex differences and providing a reference data set for future pathological studies.

Cost-Effectiveness Of Once-Daily Single-Inhaler Triple Therapy In COPD: The IMPACT Trial.

Background: We assessed the cost-effectiveness of single-inhaler fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) versus FF/VI or UMEC/VI from a Canadian public healthcare perspective, incorporating data from the IMPACT trial in chronic obstructive pulmonary disease (COPD) (NCT02164513). Methods: Baseline inputs and treatment effects from IMPACT were populated into the validated GALAXY-COPD disease progression model. Canadian unit costs and drug costs (Canadian dollars [C$], 2017) were applied to healthcare resource utilization and treatments. Future costs and health outcomes were discounted at 1.5% annually. Analyses were probabilistic, and outputs included exacerbation rates, costs, and life years (LYs) and quality-adjusted life years (QALYs) gained. Results: Compared with FF/VI and UMEC/VI over a lifetime horizon, the analyses predicted that treatment with FF/UMEC/VI resulted in fewer moderate and severe exacerbations, more LYs and more QALYs gained, with a small incremental cost. The base-case incremental cost-effectiveness ratio (ICER) per QALY gained was C$18,989 (95% confidence interval [CI]: C$14,665, C$25,753) versus FF/VI and C$13,776 (95% CI: C$9787, C$19,448) versus UMEC/VI. FF/UMEC/VI remained cost-effective versus both FF/VI and UMEC/VI in all sensitivity analyses, including in scenario analyses that considered different intervention and comparator discontinuation rates, and treatment effects for subsequent therapy. Conclusion: Treatment with FF/UMEC/VI was predicted to improve outcomes and be a cost-effective treatment option for patients with symptomatic COPD and a history of exacerbations compared with FF/VI or UMEC/VI, in Canada.

Diffusing Capacity of Carbon Monoxide in Assessment of COPD.

BACKGROUND: Diffusing capacity of the lung for carbon monoxide (Dlco) is inconsistently obtained in patients with COPD, and the added benefit of Dlco testing beyond that of more common tools is unknown. OBJECTIVE: The goal of this study was to determine whether lower Dlco is associated with increased COPD morbidity independent of emphysema assessed via spirometry and CT imaging. METHODS: Data for 1,806 participants with COPD from the Genetic Epidemiology of COPD (COPDGene) study 5-year visit were analyzed, including pulmonary function testing, quality of life, symptoms, exercise performance, and exacerbation rates. Dlco percent predicted was primarily analyzed as a continuous variable and additionally categorized into four groups: (1) Dlco and FEV1 > 50% (reference); (2) only Dlco ≤ 50%; (3) only FEV1 ≤ 50%; and (4) both ≤ 50% predicted. Outcomes were modeled by using multivariable linear and negative binomial regression, including emphysema and FEV1 percent predicted among other confounders. RESULTS: In multivariable analyses, every 10% predicted decrease in Dlco was associated with symptoms and quality of life (COPD Assessment Test, 0.53 [P < .001]; St. George's Respiratory Questionnaire, 1.67 [P < .001]; Medical Outcomes Study Short Form 36 Physical Function, -0.89 [P < .001]), exercise performance (6-min walk distance, -45.35 feet; P < .001), and severe exacerbation rate (rate ratio, 1.14; P < .001). When categorized, severe impairment in Dlco alone, FEV1 alone, or both Dlco and FEV1 were associated with significantly worse morbidity compared with the reference group (P < .05 for all outcomes). CONCLUSIONS: Impairment in Dlco was associated with increased COPD symptoms, reduced exercise performance, and severe exacerbation risk even after accounting for spirometry and CT evidence of emphysema. These findings suggest that Dlco should be considered for inclusion in future multidimensional tools assessing COPD.

Heterogeneous burden of lung disease in smokers with borderline airflow obstruction.

BACKGROUND: The identification of smoking-related lung disease in current and former smokers with normal FEV1 is complex, leading to debate regarding using a ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) of less than 0.70 versus the predicted lower limit of normal (LLN) for diagnosis of airflow obstruction. We hypothesized that the discordant group of ever-smokers with FEV1/FVC between the LLN and 0.70 is heterogeneous, and aimed to characterize the burden of smoking-related lung disease in this group. METHODS: We compared spirometry, chest CT characteristics, and symptoms between 161 ever-smokers in the discordant group and 940 ever-smokers and 190 never-smokers with normal FEV1 and FEV1/FVC > 0.70 in the SPIROMICS cohort. We also estimated sensitivity and specificity for diagnosing objective radiographic evidence of chronic obstructive pulmonary disease (COPD) using different FEV1/FVC criteria thresholds. RESULTS: The discordant group had more CT defined emphysema and non-emphysematous gas trapping, lower post-bronchodilator FEV1 and FEF25-75, and higher respiratory medication use compared with the other two groups. Within the discordant group, 44% had radiographic CT evidence of either emphysema or non-emphysematous gas trapping; an FEV1/FVC threshold of 0.70 has greater sensitivity but lower specificity compared with LLN for identifying individuals with CT abnormality. CONCLUSIONS: Ever-smokers with normal FEV1 and FEV1/FVC <  0.70 but > LLN are a heterogeneous group that includes significant numbers of individuals with and without radiographic evidence of smoking-related lung disease. These findings emphasize the limitations of diagnosing COPD based on spirometric criteria alone.

COPD Care in the 21st Century: A Public Health Priority.

COPD is an underdiagnosed, undertreated, and yet largely preventable disease. COPD affects millions of Americans on a daily basis, accounts for tens of thousands of deaths per year, and costs billions to the United States health-care system annually. Further, it impacts the quality of life for patients living with the disease. COPD care is fragmented in the United States, with a high level of responsibility placed on patients and their primary care physicians. Pulmonary specialists care for a minority of patients with COPD in the United States. Unfortunately, tobacco dependence, which is the leading cause of COPD, remains prevalent. Further, women and those with low socioeconomic status continue to share a relatively greater burden of disease. Exacerbations are experienced frequently by patients and contribute to high rates of emergency department visits and in-patient admissions and readmissions as well as high medical costs to the United States economy. Numerous strategies have been proposed to combat these high rates, including the use of discharge bundles, hospital at-home programs, telemedicine, and tele-rehabilitation, but no single best strategy has emerged. The COPD National Action Plan was introduced in 2017 as part of a multi-stakeholder endeavor to encourage collaboration among various patients, caregivers, physicians, researchers, and policymakers to optimize awareness, diagnosis, and treatment of this disease. It is time to make COPD care a public health priority.

Improving the Affordability of Prescription Medications for People with Chronic Respiratory Disease. An Official American Thoracic Society Policy Statement.

BACKGROUND: Mounting evidence indicates that out-of-pocket costs for prescription medications, particularly among low- and middle-income patients with chronic diseases, are imposing financial burden, reducing medication adherence, and worsening health outcomes. This problem is exacerbated by a paucity of generic alternatives for prevalent lung diseases, such as asthma and chronic obstructive pulmonary disease, as well as high-cost medicines for rare diseases, such as cystic fibrosis. Affordability and access challenges are especially salient in the United States, as citizens of many other countries pay lower prices for and have greater access to prescription medications. METHODS: The American Thoracic Society convened a multidisciplinary committee comprising experts in health policy pharmacoeconomics, behavioral sciences, and clinical care, along with individuals providing industry and patient perspectives. The report and its recommendation were iteratively developed over a year of in-person, telephonic, and electronic deliberation. RESULTS: The committee unanimously recommended the establishment of a publicly funded, politically independent, impartial entity to systematically draft evidence-based pharmaceutical policy recommendations. The goal of this entity would be to generate evidence and action steps to ensure people have equitable and affordable access to prescription medications, to maximize the value of public and private pharmaceutical expenditures on health, to support novel drug development within a market-based economy, and to preserve clinician and patient choice regarding personalized treatment. An immediate priority is to examine the evidence and make recommendations regarding the need to have essential medicines with established clinical benefit from each drug class in all Tier 1 formularies and propose recommendations to reduce barriers to timely generic drug availability. CONCLUSIONS: By making explicit, evidence-based recommendations, the entity can support the establishment of coherent national policies that expand access to affordable medications, improve the health of patients with chronic disease, and optimize the use of public and private resources.