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1.
N Engl J Med ; 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31633896

RESUMO

BACKGROUND: Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials. METHODS: In this prospective, randomized trial, we assigned patients between the ages of 40 and 85 years who had COPD to receive either a beta-blocker (extended-release metoprolol) or placebo. All the patients had a clinical history of COPD, along with moderate airflow limitation and an increased risk of exacerbations, as evidenced by a history of exacerbations during the previous year or the prescribed use of supplemental oxygen. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. The primary end point was the time until the first exacerbation of COPD during the treatment period, which ranged from 336 to 350 days, depending on the adjusted dose of metoprolol. RESULTS: A total of 532 patients underwent randomization. The mean (±SD) age of the patients was 65.0±7.8 years; the mean forced expiratory volume in 1 second (FEV1) was 41.1±16.3% of the predicted value. The trial was stopped early because of futility with respect to the primary end point and safety concerns. There was no significant between-group difference in the median time until the first exacerbation, which was 202 days in the metoprolol group and 222 days in the placebo group (hazard ratio for metoprolol vs. placebo, 1.05; 95% confidence interval [CI], 0.84 to 1.32; P = 0.66). Metoprolol was associated with a higher risk of exacerbation leading to hospitalization (hazard ratio, 1.91; 95% CI, 1.29 to 2.83). The frequency of side effects that were possibly related to metoprolol was similar in the two groups, as was the overall rate of nonrespiratory serious adverse events. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group. CONCLUSIONS: Among patients with moderate or severe COPD who did not have an established indication for beta-blocker use, the time until the first COPD exacerbation was similar in the metoprolol group and the placebo group. Hospitalization for exacerbation was more common among the patients treated with metoprolol. (Funded by the Department of Defense; BLOCK COPD ClinicalTrials.gov number, NCT02587351.).

2.
J Palliat Med ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31657654

RESUMO

Background: Guidelines recommend that pulmonary clinicians involve palliative care in chronic obstructive pulmonary disease (COPD); however, integration before advanced stage, that is, early palliative care, is rare. Objective: To explore and compare pulmonary and palliative care clinician perspectives on barriers, facilitators, and potential referral criteria for early palliative care in COPD. Design: Qualitative descriptive formative evaluation study. Setting/Subjects: Pulmonary and palliative care clinicians at a tertiary academic medical center. Measurements: Transcribed interviews were thematically analyzed by specialty to identify within- and across-specialty perspectives on barriers, facilitators, and referral criteria. Results: Twelve clinicians (n = 6 pulmonary, n = 6 palliative care) participated. Clinicians from both specialties agreed that early palliative care could add value to disease-focused COPD care. Perspectives on many barriers and facilitators were shared between specialties along broad educational, clinical, and operational categories. Pulmonary and palliative care clinicians shared concerns about the misconception that palliative care was synonymous to end-of-life care. Pulmonologists were particularly concerned about the potential risks of opioids and benzodiazepines in COPD. Both specialties stressed the need for clearly defined roles, consensus referral criteria, and novel delivery models. Although no single referral criterion was discussed by all, frequent hospitalizations and emotional symptoms were raised by most across disciplines. Multimorbidity and poor prognosis were discussed only by palliative care clinicians, whereas medication adherence was discussed only by pulmonary clinicians. Conclusions: Pulmonary and palliative care clinicians supported early palliative care in COPD. Continued needs include addressing pulmonologists' misconceptions of palliative care, establishing consensus referral criteria, and implementing novel early palliative care models.

3.
Int J Chron Obstruct Pulmon Dis ; 14: 1779-1787, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496677

RESUMO

Despite maximal medical therapy, a subset of patients with chronic obstructive pulmonary disease continue to suffer acute exacerbations. It is also clear that a subset of this population has elevated blood eosinophils. In addition to clearly responding better to inhaled corticosteroids, it is also possible that this subgroup may benefit from biologic treatments targeting eosinophilic inflammation. Mepolizumab, a humanized monoclonal antibody against interleukin-5 (IL-5), may have a therapeutic effect in a subgroup of patients with COPD and eosinophilic airway inflammation. In this review, we discuss the biologic rationale for mepolizumab targeting IL-5 in eosinophilic COPD as well as the results of recently published clinical trials.

7.
Eur Respir J ; 54(4)2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31439683

RESUMO

The characteristics that predict progression to overt chronic obstructive pulmonary disease (COPD) in smokers without spirometric airflow obstruction are not clearly defined.We conducted a post hoc analysis of 849 current and former smokers (≥20 pack-years) with preserved spirometry from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort who had baseline computed tomography (CT) scans of lungs and serial spirometry. We examined whether CT-derived lung volumes representing air trapping could predict adverse respiratory outcomes and more rapid decline in spirometry to overt COPD using mixed-effect linear modelling.Among these subjects with normal forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio, CT-measured residual volume (RVCT) to total lung capacity (TLCCT) ratio varied widely, from 21% to 59%. Over 2.5±0.7 years of follow-up, subjects with higher RVCT/TLCCT had a greater differential rate of decline in FEV1/FVC; those in the upper RVCT/TLCCT tertile had a 0.66% (95% CI 0.06%-1.27%) faster rate of decline per year compared with those in the lower tertile (p=0.015) regardless of demographics, baseline spirometry, respiratory symptoms score, smoking status (former versus current) or smoking burden (pack-years). Accordingly, subjects with higher RVCT/TLCCT were more likely to develop spirometric COPD (OR 5.7 (95% CI 2.4-13.2) in upper versus lower RVCT/TLCCT tertile; p<0.001). Other CT indices of air trapping showed similar patterns of association with lung function decline; however, when all CT indices of air trapping, emphysema, and airway disease were included in the same model, only RVCT/TLCCT retained its significance.Increased air trapping based on radiographic lung volumes predicts accelerated spirometry decline and progression to COPD in smokers without obstruction.

9.
J Cardiopulm Rehabil Prev ; 39(5): 344-349, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31348127

RESUMO

PURPOSE: Adherence to pulmonary rehabilitation (PR) is low. This qualitative study used the PRECEDE model to identify predisposing (intrapersonal), reinforcing (interpersonal), and enabling (structural) factors acting as barriers or facilitators of adherence to PR, and elicit recommendations for solutions from patients with chronic obstructive pulmonary disease (COPD). METHODS: Focus groups with COPD patients who had attended PR in the past year were conducted. Sessions were recorded, transcribed verbatim, and coded independently by 2 coders, who then jointly decided on the final coding scheme. Data were summarized across groups, and analysis was used a thematic approach with constant comparative method to generate categories. RESULTS: Five focus groups with 24 participants each were conducted. Participants (mean age 62 yr) were 54% male, and 67% black. More than half had annual income less than $20 000, 17% were current smokers, and 54% had low adherence (less than 35% of prescribed PR sessions). The most prominent barriers included physical ailments and lack of motivation (intrapersonal), no support system (interpersonal), transportation difficulties, and financial burden (structural). The most prominent facilitators included health improvement, personal determination (intrapersonal), support from peers, family, and friends (interpersonal), and program features such as friendly staff and educational component of sessions (structural). Proposed solutions included incentives to maintain motivation, tobacco cessation support (intrapersonal), educating the entire family (interpersonal), transportation assistance, flexible program scheduling, and financial assistance (structural). CONCLUSION: Health limitations, social support, transportation and financial difficulties, and program features impact ability of patients to attend PR. Interventions addressing these interpersonal, intrapersonal, and structural barriers are needed to facilitate adherence to PR.

10.
Lancet Respir Med ; 7(9): 745-756, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31281061

RESUMO

BACKGROUND: Previous studies have highlighted a relationship between reduction in rate of exacerbations with therapies containing inhaled corticosteroids (ICS) and baseline blood eosinophil count in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial showed that once-daily single-inhaler triple therapy significantly reduced exacerbations versus dual therapies. Blood eosinophil counts and smoking status could be important modifiers of treatment response to ICS. We aimed to model these relationships and their interactions, including outcomes other than exacerbations. METHODS: IMPACT was a phase 3, randomised, double-blind, parallel-group, 52-week global study comparing once-daily single-inhaler triple therapy (fluticasone furoate-umeclidinium-vilanterol) with dual inhaled therapy (fluticasone furoate-vilanterol or umeclidinium-vilanterol). Eligible patients had moderate-to-very-severe COPD and at least one moderate or severe exacerbation in the previous year. We used fractional polynomials to model continuous blood eosinophil counts. We used negative binomial regression for numbers of moderate and severe exacerbations, severe exacerbations, and pneumonia. We modelled differences at week 52 in trough FEV1, St George's Respiratory Questionnaire (SGRQ) total score, and Transition Dyspnoea Index using repeated measurements mixed effect models. IMPACT was registered with ClinicalTrials.gov, number NCT02164513. FINDINGS: The magnitude of benefit of regimens containing ICS (fluticasone furoate-umeclidinium-vilanterol n=4151 and fluticasone furoate-vilanterol n=4134) in reducing rates of moderate and severe exacerbations increased in proportion with blood eosinophil count, compared with a non-ICS dual long-acting bronchodilator (umeclidinium-vilanterol n=2070). The moderate and severe exacerbation rate ratio for triple therapy versus umeclidinium-vilanterol was 0·88 (95% CI 0·74 to 1·04) at blood eosinophil count less than 90 cells per µL and 0·56 (0·47 to 0·66) at counts of 310 cells per µL or more; the corresponding rate ratio for fluticasone furoate-vilanterol versus umeclidinium-vilanterol was 1·09 (0·91 to 1·29) and 0·56 (0·47 to 0·66), respectively. Similar results were observed for FEV1, Transition Dyspnoea Index, and SGRQ total score; however, the relationship with FEV1 was less marked. At blood eosinophil counts less than 90 cells per µL and at counts of 310 cells per µL or more, the triple therapy versus umeclidinium-vilanterol treatment difference was 40 mL (95% CI 10 to 70) and 60 mL (20 to 100) for trough FEV1, -0·01 (-0·68 to 0·66) and 0·30 (-0·37 to 0·97) for Transition Dyspnoea Index score, and -0·01 (-1·81 to 1·78) and -2·78 (-4·64 to -0·92) for SGRQ total score, respectively. Smoking status modified the relationship between observed efficacy and blood eosinophil count for moderate or severe exacerbations, Transition Dyspnoea Index, and FEV1, with former smokers being more corticosteroid responsive at any eosinophil count than current smokers. INTERPRETATION: This analysis of the IMPACT trial shows that assessment of blood eosinophil count and smoking status has the potential to optimise ICS use in clinical practice in patients with COPD and a history of exacerbations. FUNDING: GlaxoSmithKline.

11.
Chest ; 156(2): 228-238, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154041

RESUMO

The Genetic Epidemiology of COPD (COPDGene) study is a noninterventional, multicenter, longitudinal analysis of > 10,000 subjects, including smokers with a ≥ 10 pack-year history with and without COPD and healthy never smokers. The goal was to characterize disease-related phenotypes and explore associations with susceptibility genes. The subjects were extensively phenotyped with the use of comprehensive symptom and comorbidity questionnaires, spirometry, CT scans of the chest, and genetic and biomarker profiling. The objective of this review was to summarize the major advances in the clinical epidemiology of COPD from the first 10 years of the COPDGene study. We highlight the influence of age, sex, and race on the natural history of COPD, and the impact of comorbid conditions, chronic bronchitis, exacerbations, and asthma/COPD overlap.

12.
JAMA ; 321(24): 2438-2447, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31237643

RESUMO

Importance: According to numerous current guidelines, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV1:FVC) of less than 0.70, yet this fixed threshold is based on expert opinion and remains controversial. Objective: To determine the discriminative accuracy of various FEV1:FVC fixed thresholds for predicting COPD-related hospitalization and mortality. Design, Setting, and Participants: The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 4 US general population-based cohorts (Atherosclerosis Risk in Communities Study; Cardiovascular Health Study; Health, Aging, and Body Composition Study; and Multi-Ethnic Study of Atherosclerosis). Participants aged 45 to 102 years were enrolled from 1987 to 2000 and received follow-up longitudinally through 2016. Exposures: Presence of airflow obstruction, which was defined by a baseline FEV1:FVC less than a range of fixed thresholds (0.75 to 0.65) or less than the lower limit of normal as defined by Global Lung Initiative reference equations (LLN). Main Outcomes and Measures: The primary outcome was a composite of COPD hospitalization and COPD-related mortality, defined by adjudication or administrative criteria. The optimal fixed FEV1:FVC threshold was defined by the best discrimination for these COPD-related events as indexed using the Harrell C statistic from unadjusted Cox proportional hazards models. Differences in C statistics were compared with respect to less than 0.70 and less than LLN thresholds using a nonparametric approach. Results: Among 24 207 adults in the pooled cohort (mean [SD] age at enrollment, 63 [10.5] years; 12 990 [54%] women; 16 794 [69%] non-Hispanic white; 15 181 [63%] ever smokers), complete follow-up was available for 11 077 (77%) at 15 years. During a median follow-up of 15 years, 3925 participants experienced COPD-related events over 340 757 person-years of follow-up (incidence density rate, 11.5 per 1000 person-years), including 3563 COPD-related hospitalizations and 447 COPD-related deaths. With respect to discrimination of COPD-related events, the optimal fixed threshold (0.71; C statistic for optimal fixed threshold, 0.696) was not significantly different from the 0.70 threshold (difference, 0.001 [95% CI, -0.002 to 0.004]) but was more accurate than the LLN threshold (difference, 0.034 [95% CI, 0.028 to 0.041]). The 0.70 threshold provided optimal discrimination in the subgroup analysis of ever smokers and in adjusted models. Conclusions and Relevance: Defining airflow obstruction as FEV1:FVC less than 0.70 provided discrimination of COPD-related hospitalization and mortality that was not significantly different or was more accurate than other fixed thresholds and the LLN. These results support the use of FEV1:FVC less than 0.70 to identify individuals at risk of clinically significant COPD.


Assuntos
Volume Expiratório Forçado , Hospitalização/estatística & dados numéricos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Capacidade Vital , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/mortalidade , Medição de Risco/métodos
13.
BMC Pulm Med ; 19(1): 116, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242944

RESUMO

BACKGROUND: With rising medical costs, stakeholders and healthcare professionals are exploring community-based solutions to relieve the burden of chronic diseases and reduce health care spending. The community health worker (CHW) model is one example that has proven effective in improving patient outcomes globally. We sought to systematically describe the effectiveness of community health worker interventions in improving patient reported outcomes and reducing healthcare utilization in the adult asthma and chronic obstructive pulmonary disease (COPD) populations in the U.S. METHODS: Studies were included if they were a randomized control trial or involved a pre-post intervention comparison with clearly stated disease specific outcomes, targeted adult patients with asthma or COPD, and were performed in the United States. Risk of bias was assessed using the Cochrane Risk of Bias tool. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria and was registered with PROSPERO. RESULT: The search yielded 4013 potential articles, of which 47 were chosen for full-text review and 4 were chosen for inclusion; all focused on asthma and three had a comparison group. CHW interventions demonstrated improvement in asthma-related quality of life, asthma control, home trigger scores, and asthma symptom free days. There were no studies that reported COPD specific outcomes as a result of CHW interventions. CONCLUSION: Emerging evidence suggests CHW interventions may improve some aspects of asthma related disease burden in adults, however additional studies with consistent outcome measures are needed to confirm their effectiveness. Further research is also warranted to evaluate the use of community health workers in the COPD population.

14.
Ann Am Thorac Soc ; 16(8): 1024-1033, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31039003

RESUMO

Rationale: Little direction exists on how to integrate early palliative care in chronic obstructive pulmonary disease (COPD).Objectives: We sought to identify patient and family caregiver early palliative care needs across stages of COPD severity.Methods: As part of the Medical Research Council Framework developmental phase for intervention development, we conducted a formative evaluation of patients with moderate to very severe COPD (forced expiratory volume in 1 s [FEV1]/FVC < 70% and FEV1 < 80%-predicted) and their family caregivers. Validated surveys on quality of life, anxiety and depressive symptoms, and social isolation quantified symptom severity. Semi-structured interviews were analyzed for major themes on early palliative care and needs in patients and family caregivers and across COPD severity stages.Results: Patients (n = 10) were a mean (±SD) age of 60.4 (±7.5) years, 50% African American, and 70% male, with 30% having moderate COPD, 30% severe COPD, and 40% very severe COPD. Family caregivers (n = 10) were a mean age of 58.3 (±8.7) years, 40% African American, and 10% male. Overall, 30% (n = 6) of participants had poor quality of life, 45% (n = 9) had moderate-severe anxiety symptoms, 25% (n = 5) had moderate-severe depressive symptoms, and 40% (n = 8) reported social isolation. Only 30% had heard of palliative care, and most participants had misconceptions that palliative care was end-of-life care. All participants responded positively to a standardized description of early palliative care and were receptive to its integration as early as moderate stage. Five broad themes of early palliative care needs emerged: 1) coping with COPD; 2) emotional symptoms; 3) respiratory symptoms; 4) illness understanding; and 5) prognostic awareness. Coping with COPD and emotional symptoms were commonly shared early palliative care needs. Patients with very severe COPD and their family caregivers prioritized illness understanding and prognostic awareness compared with those with moderate-severe COPD.Conclusions: Patients with moderate to very severe COPD and their family caregivers found early palliative care acceptable and felt it should be integrated before end-stage. Of the five broad themes of early palliative care needs, coping with COPD and emotional symptoms were the highest priority, followed by respiratory symptoms, illness understanding, and prognostic awareness.

15.
BMJ Open ; 9(5): e027175, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31079085

RESUMO

OBJECTIVES: While awareness of cigarette smoking's harmful effects has increased, determinants associated with smoking status remain understudied, including potential racial differences. We aim to examine factors associated with former versus current smoking status and assess whether these associations differed by race. SETTING: We performed a cross-sectional analysis using the population-based Reasons for Geographic and Racial Differences in Stroke(REGARDS)study. OUTCOME MEASURES: Logistic regression was used to calculate the OR of former smoking status compared with current smoking status with risk factors of interest. Race interactions were tested using multiplicative interaction terms. RESULTS: 16 463 participants reported smoking at least 100 cigarettes in their lifetime. Seventy-three per cent (n=12 067) self-reported former-smoker status. Physical activity (reference (REF) <3×/week; >3×/week: OR=1.26, 95% CI 1.11 to 1.43), adherence to Mediterranean diet (REF: low; medium: OR=1.46, 95% CI 1.27 to 1.67; high: OR=2.20, 95% CI 1.84 to 2.64), daily television viewing time (REF: >4 hours; <1 hour: OR=1.32, 95% CI 1.10 to 1.60) and abstinence from alcohol use (REF: heavy; none: OR=1.50, 95% CI 1.18 to 1.91) were associated with former-smoker status. Male sex, higher education and income $35 000-$74 000 (REF: <$20 000) were also associated with former-smoker status. Factors associated with lower odds of reporting former-smoker status were younger age (REF: ≥65 years; 45-64 years: OR=0.34, 95% CI 0.29 to 0.39), black race (OR=0.62, 95% CI 0.53 to 0.72) and single marital status (REF: married status; OR=0.66, 95% CI 0.51 to 0.87), being divorced (OR=0.60, 95% CI 0.50 to 0.72) or widowed (OR=0.70, 95% CI 0.57 to 0.85). Significant interactions were observed between race and alcohol use and dyslipidaemia, such that black participants had higher odds of reporting former-smoker status if they were abstinent from alcohol (OR=2.32, 95% CI 1.47 to 3.68) or had a history of dyslipidaemia (OR=1.31, 95% CI 1.06 to 1.62), whereas these relationships were not statistically significant in white participants. CONCLUSION: Efforts to promote tobacco cessation should consist of targeted behavioural interventions that incorporate racial differences.

17.
Ann Am Thorac Soc ; 16(7): 826-835, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30908927

RESUMO

Rationale: The American Thoracic Society (ATS)/European Respiratory Society defines a positive bronchodilator response (BDR) by a composite of BDR in either forced expiratory volume in 1 second (FEV1) and/or forced vital capacity (FVC) greater than or equal to 12% and 200 ml (ATS-BDR). We hypothesized that ATS-BDR components would be differentially associated with important chronic obstructive pulmonary disease (COPD) outcomes. Objectives: To examine whether ATS-BDR components are differentially associated with clinical, functional, and radiographic features in COPD. Methods: We included subjects with COPD enrolled in the COPDGene study. In the main analysis, we excluded subjects with self-reported asthma. We categorized BDR into the following: 1) No-BDR, no BDR in either FEV1 or FVC; 2) FEV1-BDR, BDR in FEV1 but no BDR in FVC; 3) FVC-BDR, BDR in FVC but no BDR in FEV1; and 4) Combined-BDR, BDR in both FEV1 and FVC. We constructed multivariable logistic, linear, zero-inflated negative binomial, and Cox hazards models to examine the association of BDR categories with symptoms, computed tomography findings, change in FEV1 over time, respiratory exacerbations, and mortality. We also created models using the ATS BDR definition (ATS-BDR) as the main independent variable. Results: Of 3,340 COPD subjects included in the analysis, 1,083 (32.43%) had ATS-BDR, 182 (5.45%) had FEV1-BDR, 522 (15.63%) had FVC-BDR, and 379 (11.34%) had Combined-BDR. All BDR categories were associated with FEV1 decline compared with No-BDR. Compared with No-BDR, both ATS-BDR and Combined-BDR were associated with higher functional residual capacity %predicted, greater internal perimeter of 10 mm, and greater 6-minute-walk distance. In contrast to ATS-BDR, Combined-BDR was independently associated with less emphysema (adjusted beta regression coefficient, -1.67; 95% confidence interval [CI], -2.68 to -0.65; P = 0.001), more frequent respiratory exacerbations (incidence rate ratio, 1.25; 95% CI, 1.03-1.50; P = 0.02) and severe exacerbations (incidence rate ratio, 1.34; 95% CI, 1.05-1.71; P = 0.02), and lower mortality (adjusted hazards ratio, 0.76; 95% CI, 0.58-0.99; P = 0.046). Sensitivity analysis that included subjects with self-reported history of asthma showed similar findings. Conclusions: BDR in both FEV1 and FVC indicates a COPD phenotype with asthma-like characteristics, and provides clinically more meaningful information than current definitions of BDR.

18.
Am J Respir Crit Care Med ; 200(6): 721-731, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30925230

RESUMO

Rationale: Chronic obstructive pulmonary disease (COPD) has been associated with numerous genetic variants, yet the extent to which its genetic risk is mediated by variation in lung structure remains unknown.Objectives: To characterize associations between a genetic risk score (GRS) associated with COPD susceptibility and lung structure on computed tomography (CT).Methods: We analyzed data from MESA Lung (Multi-Ethnic Study of Atherosclerosis Lung Study), a U.S. general population-based cohort, and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). A weighted GRS was calculated from 83 SNPs that were previously associated with lung function. Lung density, spatially matched airway dimensions, and airway counts were assessed on full-lung CT. Generalized linear models were adjusted for age, age squared, sex, height, principal components of genetic ancestry, smoking status, pack-years, CT model, milliamperes, and total lung volume.Measurements and Main Results: MESA Lung and SPIROMICS contributed 2,517 and 2,339 participants, respectively. Higher GRS was associated with lower lung function and increased COPD risk, as well as lower lung density, smaller airway lumens, and fewer small airways, without effect modification by smoking. Adjustment for CT lung structure, particularly small airway measures, attenuated associations between the GRS and FEV1/FVC by 100% and 60% in MESA and SPIROMICS, respectively. Lung structure (P < 0.0001), but not the GRS (P > 0.10), improved discrimination of moderate-to-severe COPD cases relative to clinical factors alone.Conclusions: A GRS associated with COPD susceptibility was associated with CT lung structure. Lung structure may be an important mediator of heritability and determinant of personalized COPD risk.

19.
Ann Am Thorac Soc ; 16(8): 982-989, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30865842

RESUMO

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation. Spirometry loops are not smooth curves and have undulations and peaks that likely reflect heterogeneity of airflow.Objectives: To assess whether the Peak Index, the number of peaks adjusted for lung size, is associated with clinical outcomes.Methods: We analyzed spirometry data of 9,584 participants enrolled in the COPDGene study and counted the number of peaks in the descending part of the expiratory flow-volume curve from the peak expiratory flow to end-expiration. We adjusted the peaks count for the volume of the lungs from peak expiratory flow to end-expiration to derive the Peak Index. Multivariable regression analyses were performed to test associations between the Peak Index and lung function, respiratory morbidity, structural lung disease on computed tomography (CT), forced expiratory volume in 1 second (FEV1) decline, and mortality.Results: The Peak Index progressively increased from Global Initiative for Chronic Obstructive Lung Disease stage 0 through 4 (P < 0.001). On multivariable analysis, the Peak Index was significantly associated with CT emphysema (adjusted ß = 0.906; 95% confidence interval [CI], 0.789 to 1.023; P < 0.001) and small airways disease (adjusted ß = 1.367; 95% CI, 1.188 to 1.545; P < 0.001), St. George's Respiratory Questionnaire score (adjusted ß = 1.075; 95% CI, 0.807 to 1.342; P < 0.001), 6-minute-walk distance (adjusted ß = -1.993; 95% CI, -3.481 to -0.506; P < 0.001), and FEV1 change over time (adjusted ß = -1.604; 95% CI, -2.691 to -0.516; P = 0.004), after adjustment for age, sex, race, body mass index, current smoking status, pack-years of smoking, and FEV1. The Peak Index was also associated with the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index and mortality (P < 0.001).Conclusions: The Peak Index is a spirometry metric that is associated with CT measures of lung disease, respiratory morbidity, lung function decline, and mortality.Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

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