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2.
Sci Rep ; 9(1): 11367, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31388056

RESUMO

Metabolomics is an emerging science that can inform pathogenic mechanisms behind clinical phenotypes in COPD. We aimed to understand disturbances in the serum metabolome associated with respiratory outcomes in ever-smokers from the SPIROMICS cohort. We measured 27 serum metabolites, mostly amino acids, by 1H-nuclear magnetic resonance spectroscopy in 157 white ever-smokers with and without COPD. We tested the association between log-transformed metabolite concentrations and one-year incidence of respiratory exacerbations after adjusting for age, sex, current smoking, body mass index, diabetes, inhaled or oral corticosteroid use, study site and clinical predictors of exacerbations, including FEV1% predicted and history of exacerbations. The mean age of participants was 53.7 years and 58% had COPD. Lower concentrations of serum amino acids were independently associated with 1-year incidence of respiratory exacerbations, including tryptophan (ß = -4.1, 95% CI [-7.0; -1.1], p = 0.007) and the branched-chain amino acids (leucine: ß = -6.0, 95% CI [-9.5; -2.4], p = 0.001; isoleucine: ß = -5.2, 95% CI [-8.6; -1.8], p = 0.003; valine: ß = -4.1, 95% CI [-6.9; -1.4], p = 0.003). Tryptophan concentration was inversely associated with the blood neutrophil-to-lymphocyte ratio (p = 0.03) and the BODE index (p = 0.03). Reduced serum amino acid concentrations in ever-smokers with and without COPD are associated with an increased incidence of respiratory exacerbations.

4.
J Asthma ; : 1-8, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31418600

RESUMO

Rationale: Prior evidence suggests that there may be an association between asthma and food insecurity. We sought to describe the prevalence of food insecurity access, defined as having sufficient resources for appropriate foods in Lima, Peru, and evaluate its association with asthma status and control. Methods: We analyzed data from 553 children with asthma and 268 healthy controls aged nine to 19 years living in two peri-urban communities in Lima, Peru, in 2013. We used the Household Food Insecurity Access Scale to assess food insecurity. We defined uncontrolled asthma as an asthma control test score ≤19. We used multivariable logistic regressions to determine the relationship between asthma outcomes and food insecurity adjusting for age, sex, socioeconomic status, body mass index, and setting. Results: Average age was 14.2 years (SD 2.7). There was a high prevalence of household food insecurity in our study: 330 participants (40.2%) were food insecure, and average food insecurity access score was 2.7 points (SD 4.2). While being food insecure was not associated with asthma status (OR = 1.23, 95% CI 0.85 to 1.79; p = 0.28), it was associated with a higher odds of having uncontrolled asthma (OR = 2.01, 95% CI 1.13 to 3.59; p = 0.02). Each one-unit increase in food insecurity score (higher scores indicating more insecurity) was associated with 8% higher odds of having uncontrolled asthma (OR = 1.08, 95% CI 1.02 to 1.14; p < 0.01). Conclusions: Worse asthma control was associated with food insecurity. Future studies are needed to better understand the role of food security in determining the success of treatment strategies.

5.
Eur Respir J ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31439683

RESUMO

The characteristics that predict progression to overt 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 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 to forced vital capacity ratio (FEV1/FVC), CT-measured residual volume to total lung capacity ratio (RVCT/TLCCT) 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 to 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 (odds ratio=5.7 [95%CI=2.4-13.2] in upper versus lower RVCT/TLCCTtertile; 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.

6.
Respir Res ; 20(1): 153, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307479

RESUMO

BACKGROUND: Quantitative computed tomographic (QCT) imaging-based metrics enable to quantify smoking induced disease alterations and to identify imaging-based clusters for current smokers. We aimed to derive clinically meaningful sub-groups of former smokers using dimensional reduction and clustering methods to develop a new way of COPD phenotyping. METHODS: An imaging-based cluster analysis was performed for 406 former smokers with a comprehensive set of imaging metrics including 75 imaging-based metrics. They consisted of structural and functional variables at 10 segmental and 5 lobar locations. The structural variables included lung shape, branching angle, airway-circularity, airway-wall-thickness, airway diameter; the functional variables included regional ventilation, emphysema percentage, functional small airway disease percentage, Jacobian (volume change), anisotropic deformation index (directional preference in volume change), and tissue fractions at inspiration and expiration. RESULTS: We derived four distinct imaging-based clusters as possible phenotypes with the sizes of 100, 80, 141, and 85, respectively. Cluster 1 subjects were asymptomatic and showed relatively normal airway structure and lung function except airway wall thickening and moderate emphysema. Cluster 2 subjects populated with obese females showed an increase of tissue fraction at inspiration, minimal emphysema, and the lowest progression rate of emphysema. Cluster 3 subjects populated with older males showed small airway narrowing and a decreased tissue fraction at expiration, both indicating air-trapping. Cluster 4 subjects populated with lean males were likely to be severe COPD subjects showing the highest progression rate of emphysema. CONCLUSIONS: QCT imaging-based metrics for former smokers allow for the derivation of statistically stable clusters associated with unique clinical characteristics. This approach helps better categorization of COPD sub-populations; suggesting possible quantitative structural and functional phenotypes.

7.
Eur Respir J ; 54(2)2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31164433

RESUMO

Perturbations in airway mucus properties contribute to lung function decline in patients with chronic obstructive pulmonary disease (COPD). While alterations in bulk mucus rheology have been widely explored, microscopic mucus properties that directly impact on the dynamics of microorganisms and immune cells in the COPD lungs are yet to be investigated.We hypothesised that a tightened mesh structure of spontaneously expectorated mucus (i.e. sputum) would contribute to increased COPD disease severity. Here, we investigated whether the mesh size of COPD sputum, quantified by muco-inert nanoparticle (MIP) diffusion, correlated with sputum composition and lung function measurements.The microstructure of COPD sputum was assessed based on the mean squared displacement (MSD) of variously sized MIPs measured by multiple particle tracking. MSD values were correlated with sputum composition and spirometry. In total, 33 samples collected from COPD or non-COPD individuals were analysed.We found that 100 nm MIPs differentiated microstructural features of COPD sputum. The mobility of MIPs was more hindered in sputum samples from patients with severe COPD, suggesting a tighter mucus mesh size. Specifically, MSD values inversely correlated with lung function.These findings suggest that sputum microstructure may serve as a novel risk factor for COPD progression and severity.

8.
Respir Res ; 20(1): 86, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068182

RESUMO

BACKGROUND: Platelet count is a prognostic indicator in the general population and elderly. Thrombocytosis during acute exacerbation of COPD (AECOPD) has been associated with mortality; however, the relationship between platelet count and mortality in stable COPD is unknown. METHODS: We performed post hoc secondary analysis on a subsample of 1797 patients in the Study to Understand Mortality and Morbidity in COPD (SUMMIT) who had blood samples drawn at baseline. Participants were current or former smokers, 40-80 years old with moderate COPD and history or increased risk of cardiovascular (CV) disease. The primary outcome was on and post-treatment all-cause mortality. Secondary outcomes included first-on-treatment moderate/severe AECOPD and on-treatment CV composite event (CV death, myocardial infarction, stroke, unstable angina and transient ischemic attack). Multivariable Cox proportional hazards models were used to investigate study endpoint associations with platelet count quintile grouping, continuous platelet count utilizing two-term fractional polynomials, and categories of low, normal and high platelet count (< 150, ≥150 to < 300, ≥300 × 109/L). RESULTS: Patients were followed for 2.3 ± 0.9 years for vital status and 1.6 ± 1.1 years for morbidity endpoints during which 105 (5.8%) died, 651 (36.2%) experienced AECOPD (159 with severe AECOPD) and 86 (4.8%) experienced a CV event. A U-shaped association between platelet count and all-cause mortality was observed. Compared to the third quintile group (Q3) of platelet count, risk of death was increased in the lowest quintile group (Q1; hazard ratio [HR]: 1.73; 95% confidence interval [CI]: 0.93-3.23) and highest quintile group (Q5; HR: 1.66; 95%CI: 0.89-3.10), though point estimates were imprecise. Using clinical cutoffs, compared with normal platelet counts (≥150 to < 300 × 109/L), risk of all-cause mortality was nominally increased among patients with thrombocytopenia (HR: 1.46; 95%CI: 0.81-2.64) and high platelet count (HR: 1.66; 95%CI: 0.96-2.86). Compared with Q3, CV events were nominally increased for Q5 (HR: 1.71; 95%CI: 0.83-3.49) and Q1 (HR: 1.41; 95%CI: 0.70, 2.85). There was no association between platelet count and AECOPD. CONCLUSIONS: In stable COPD platelet count demonstrated a U-shaped association with increased risk of 3-year all-cause mortality, though a platelet count level above or below which risk of mortality was increased could not be definitively identified. TRIAL REGISTRATION: ClinicalTrials.gov NCT01313676 .

9.
BMC Pulm Med ; 19(1): 97, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31122230

RESUMO

BACKGROUND: Omega-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and derivatives, play a key role in the resolution of inflammation. Higher intake has been linked to decreased morbidity in several diseases, though effects on respiratory diseases like COPD are understudied. METHODS: The National Health and Nutrition Examination Survey (NHANES), with a focus on dietary assessment, provides a unique opportunity to explore relationships between omega-3 intake and morbidity in respiratory diseases marked by inflammation in the United States (US) population. We investigated relationships between ALA or EPA + DHA intake and respiratory symptoms among US adults with COPD, as well as variation in relationships based on personal characteristics or exposures. RESULTS: Of 878 participants, mean age was 60.6 years, 48% were current smokers, and 68% completed high school. Omega-3 intake was, 1.71 ± 0.89 g (ALA), and 0.11 ± 0.21 g (EPA + DHA). Logistic regression models, adjusting for age, gender, race, body mass index, FEV1, education, smoking status, pack-years, total caloric intake, and omega-6 (linoleic acid, LA) intake demonstrated no primary associations between omega-3 intake and respiratory symptoms. Interaction terms were used to determine potential modification of relationships by personal characteristics (race, gender, education) or exposures (LA intake, smoking status), demonstrating that at lower levels of LA intake, increasing ALA intake was associated with reduced odds of chronic cough (pint = 0.015) and wheeze (pint = 0.037). EPA + DHA, but not ALA, was associated with reduced symptoms only among current smokers who did not complete high school. CONCLUSIONS: Individual factors should be taken into consideration when studying the association of fatty acid intake on respiratory diseases, as differential responses may reveal susceptible subgroups.

10.
J Aerosol Med Pulm Drug Deliv ; 32(4): 189-199, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30964381

RESUMO

Background: Little is known of the repeatability and reliability of mucociliary clearance (MCC) in former tobacco smokers who have both chronic obstructive pulmonary disease (COPD) and chronic bronchitis (CB). Less is known of the effect of roflumilast, a selective inhibitor of PDE4, on MCC in these patients. Methods: Former tobacco smokers with COPD and CB were treated for 4 weeks with either roflumilast, or placebo, in a randomized, crossover trial. The following were measured on two baseline and two posttreatment visits: MCC values through 90 minutes, following inhalation of 99mtechnetium sulfur colloid and gamma camera imaging; outer:inner (O:I) deposition ratio; forced expiratory volume in 1 second (FEV1); and symptom scores. Comparisons included: MCC measures through 30 minutes (MCC30), 60 minutes (MCC60), and 90 minutes (MCC90) on the two baseline visits (n = 9) and mean change [(roflumilast - baseline)-(placebo - baseline)] for MCC30, MCC60, MCC90, and FEV1 (n = 8). Associations between MCC measurements, FEV1 and O:I ratio with symptom scores were also examined. Results: Pearson correlation tests indicated good repeatability for baseline measures of MCC30, MCC60, and MCC90 and intraclass correlation coefficients indicated good reliability. Only FEV1 (percent predicted) improved significantly following roflumilast treatment. There were no statistically significant correlations between MCC measures and symptom scores. Lower FEV1 values were significantly associated with increased shortness of breath (dyspnea), and lower O:I ratios (more inner region deposition) were significantly associated with increased cough and sputum. Conclusions: Measurements of MCC30, MCC60, and MCC90 are repeatable and reliable in former tobacco smokers with both COPD and CB. One month of treatment with roflumilast did not improve MCC in this limited study. Airway narrowing in the larger, central airways of these subjects could lead to decreased FEV1, increased inner region deposition of the radiolabeled particles, and the associated increase in symptoms of dyspnea, cough, and sputum.

11.
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 the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, a US general population-based cohort, and SPIROMICS, a study of COPD. A weighted GRS was calculated from 83 single nucleotide polymorphisms 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 airways measures, attenuated associations between the GRS and FEV1/FVC by 100% and 60% in MESA and SPIROMICS, respectively. Lung structure (P<.0001), but not the GRS (P>.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.

12.
Am J Respir Crit Care Med ; 199(12): 1478-1486, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30922077

RESUMO

Rationale: Higher indoor particulate matter (PM) concentrations are linked with increased asthma morbidity. Dietary intake of fatty acids, also linked with asthma outcomes, may influence this relationship. Objectives: To determine the relationship between omega-3 and omega-6 fatty acid intake and pediatric asthma morbidity, and the association between fatty acid intake and strength of indoor, PM-related asthma symptoms, albuterol use, and systemic inflammation. Methods: Analyses included 135 children with asthma enrolled in the AsthmaDIET Study. At baseline, 3 months, and 6 months, data included: week-long average home indoor concentration of PM ≤2.5 µm in aerodynamic diameter and PM ≤10 µm in aerodynamic diameter, dietary intake of omega-3 and omega-6 fatty acids, daily symptoms, and peripheral blood leukocytes. Asthma severity and lung function were assessed at baseline. Multivariable regression models, adjusted for known confounders, were used to determine associations between each fatty acid and outcomes of interest, with interaction terms (fatty acids × PM) in longitudinal analyses. Measurements and Main Results: Higher omega-6 intake associated with increased odds of increased asthma severity (P = 0.02), and lower FEV1/FVC ratio (P = 0.01). Higher omega-3 intake associated with reduced effect of indoor PM ≤2.5 µm in aerodynamic diameter on symptoms (P < 0.01), whereas higher omega-6 intake associated with amplified effect of indoor PM ≤2.5 µm in aerodynamic diameter on symptoms and circulating neutrophil percentage (P < 0.01). Conclusions: Omega-3 and omega-6 intake are associated with pediatric asthma morbidity and may modify the asthmatic response to indoor PM.

13.
J Allergy Clin Immunol Pract ; 7(6): 1868-1873.e5, 2019 Jul - Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30857941

RESUMO

BACKGROUND: Metabolic dysfunction may contribute to worsened asthma in obesity. The relationship between prediabetes and diabetes, metabolic conditions more common in obesity, and asthma outcomes is not well characterized. OBJECTIVE: We sought to determine the association between prediabetes/diabetes and asthma exacerbations in an obese asthma cohort. METHODS: A retrospective cohort of US obese adults with asthma, aged 18-64, was created from a claims-based health services database spanning 2010 to 2015. Individuals with a hemoglobin A1c (HbA1c) measurement were identified, categorized as within normal (<5.6%), prediabetes (5.7% to 6.4%), and diabetes (≥6.5%) ranges. Exacerbations, defined as asthma-related hospitalization, emergency department visit, or corticosteroid prescription ±14 days of an asthma-related outpatient visit, were ascertained. Associations were fit with zero-inflated negative binomial models, adjusted for age, sex, region, smoking, medication use, and comorbidities. RESULTS: A total of 5722 individuals were identified. Higher HgbA1c was associated with higher asthma exacerbation rates. In the fully adjusted model, compared with individuals with normal HbA1c, those in the prediabetes range had a 27% higher rate (95% confidence interval [CI], 5% to 52%), and those in the diabetes range had a 33% higher rate (95% CI, 2% to 73%). CONCLUSIONS: Prediabetes and diabetes were associated with higher rates of asthma exacerbation among obese adults with asthma. Results support evidence that insulin resistance and metabolic syndrome, metabolic features common in prediabetes/diabetes, can influence asthma morbidity.

14.
Nat Commun ; 10(1): 880, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30787307

RESUMO

Asthma is a complex disease with striking disparities across racial and ethnic groups. Despite its relatively high burden, representation of individuals of African ancestry in asthma genome-wide association studies (GWAS) has been inadequate, and true associations in these underrepresented minority groups have been inconclusive. We report the results of a genome-wide meta-analysis from the Consortium on Asthma among African Ancestry Populations (CAAPA; 7009 asthma cases, 7645 controls). We find strong evidence for association at four previously reported asthma loci whose discovery was driven largely by non-African populations, including the chromosome 17q12-q21 locus and the chr12q13 region, a novel (and not previously replicated) asthma locus recently identified by the Trans-National Asthma Genetic Consortium (TAGC). An additional seven loci reported by TAGC show marginal evidence for association in CAAPA. We also identify two novel loci (8p23 and 8q24) that may be specific to asthma risk in African ancestry populations.


Assuntos
Afro-Americanos/genética , Asma/genética , Predisposição Genética para Doença/genética , Asma/epidemiologia , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 8/genética , Loci Gênicos , Estudo de Associação Genômica Ampla , Hispano-Americanos/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Estados Unidos/epidemiologia
15.
J Allergy Clin Immunol Pract ; 7(6): 1815-1822.e2, 2019 Jul - Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30763731

RESUMO

BACKGROUND: Indoor fine particulate air pollution (PM2.5) is linked to asthma morbidity; however, whether vitamin D status influences individual susceptibility to airborne exposures is unclear. OBJECTIVE: We aimed to determine if vitamin D modifies the effects of indoor PM2.5 on asthma symptoms in urban children. METHODS: A total of 120 children aged 5 to 12 years with physician-diagnosed asthma were evaluated at baseline and every 3 months for 9 months. Indoor PM2.5, serum 25-hydroxy vitamin D (25-OH D) levels, and asthma symptoms were simultaneously assessed at each time point. Adjusting for confounders, generalized estimating equations assessed the 3-way interaction effects of 25-OH D, obesity, and PM on asthma symptoms. RESULTS: Children were of mean (standard deviation [SD]) age 9.7 (2.2) years, 36% were obese, and 95% self-reported black race. Mean (SD) PM2.5 indoor exposure was 38.2 (42.9) µg/m3 and 25-OH D was 19.1 (7.5) ng/mL. Three-way interaction models demonstrated significantly greater PM2.5-associated effects on daytime asthma symptoms only among obese children with low 25-OH D levels (odds ratio [OR]PM2.5 = 1.26, P = .049 at vitamin D = 15.5 ng/mL, increasingly stronger PM effects at levels <15.5 ng/mL). In homes with increased PM2.5, higher 25-OH D was associated with decreased symptom odds (eg, ORVitamin D = 0.87; P = .049 at PM2.5 = 52.5 µg/m3, increasingly protective effects >52.5 µg/m3) among obese children. CONCLUSIONS: Among obese urban children with asthma, low individual 25-OH D enhanced adverse respiratory effects associated with indoor PM2.5. In high PM2.5 environments, 25-OH D was protective against asthma symptoms. Optimizing vitamin D status in children may help reduce asthma morbidity driven by indoor air pollution.

18.
Sci Rep ; 9(1): 279, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30670753

RESUMO

We have previously shown that high fat diet (HFD) for 2 weeks increases airway hyperresponsiveness (AHR) to methacholine challenge in C57BL/6J mice in association with an increase in IL-1ß levels in lung tissue. We hypothesize that obesity increases AHR via the IL-1ß mechanism, which can be prevented by caloric restriction and IL-1ß blockade. In this study, we fed C57BL/6J mice for 8 weeks with several hypercaloric diets, including HFD, HFD supplemented with fructose, high trans-fat diet (HTFD) supplemented with fructose, either ad libitum or restricting their food intake to match body weight to the mice on a chow diet (CD). We also assessed the effect of the IL-1ß receptor blocker anakinra. All mice showed the same total respiratory resistance at baseline. All obese mice showed higher AHR at 30 mg/ml of methacholine compared to CD and food restricted groups, regardless of the diet. Obese mice showed significant increases in lung IL-1 ß mRNA expression, but not the protein, compared to CD and food restricted mice. Anakinra abolished an increase in AHR. We conclude that obesity leads to the airway hyperresponsiveness preventable by caloric restriction and IL-1ß blockade.

19.
Chest ; 155(5): 908-917, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30684474

RESUMO

BACKGROUND: Chronic respiratory symptoms and exacerbation-like events are common among ever-smokers without airflow limitation on spirometry. The pathobiology of respiratory disease in this subgroup remains poorly defined, but may be due to underlying inflammation that overlaps with COPD or asthma. We hypothesized that symptoms, exacerbations, and functional measures of disease severity among smokers with preserved spirometry would be associated with markers of systemic inflammation, similar to what is reported in bone fide COPD, rather than elevated type 2 inflammation, which is often present in asthma. METHODS: We measured inflammatory markers associated with COPD (C-reactive protein [CRP], fibrinogen, soluble tumor necrosis factor receptors [sTNFRSF1A and sTNFRSF1B], and blood/sputum neutrophils) and type 2 inflammation (IgE and blood/sputum eosinophils) in smokers with preserved spirometry (postbronchodilator FEV1/FVC ≥ 0.70) from the Subpopulations and Intermediate Outcome Measures In COPD Study (SPIROMICS). We evaluated the relationship of these markers with respiratory symptom burden (dichotomized by a COPD assessment test score cutoff of 10, diagnosis of chronic bronchitis), exacerbations, 6-minute walk distance, and lung function on the basis of FEV1. RESULTS: CRP was associated with increased symptom burden (on the basis of COPD assessment test score and diagnosis of chronic bronchitis) and a greater number of exacerbations in the year before study enrollment. sTNFRSF1A was associated with symptom burden on the basis of COPD assessment test score. CRP and sTNFRSF1A levels negatively correlated with 6-minute walk distance. IgE and eosinophils were not associated with these outcomes. CONCLUSIONS: Markers of inflammation including CRP and sTNFRSF1A are enriched among symptomatic smokers with preserved spirometry, suggesting an overlap with the underlying pathophysiology of COPD.

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