Systemic Markers of Inflammation in Smokers With Symptoms Despite Preserved Spirometry in SPIROMICS.

TitleSystemic Markers of Inflammation in Smokers With Symptoms Despite Preserved Spirometry in SPIROMICS.
Publication TypePublication
Year2019
AuthorsGarudadri S, Woodruff PG, Han MK, Curtis JL, R Barr G, Bleecker ER, Bowler RP, Comellas A, Cooper CB, Criner G, Dransfield MT, Hansel NN, Paine R, Krishnan JA, Peters SP, Hastie AT, Martinez FJ, O'Neal WK, Couper DJ, Alexis NE, Christenson SA
JournalChest
Volume155
Issue5
Pagination908-917
Date Published2019 05
ISSN1931-3543
Keywordsasthma, biomarkers, C-Reactive Protein, Female, Fibrinogen, Humans, Immunoglobulin E, Inflammation, Longitudinal Studies, Male, Middle Aged, Outcome Assessment, Health Care, Pulmonary Disease, Chronic Obstructive, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II, Severity of Illness Index, smoking, Spirometry, Symptom Assessment, United States
Abstract

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 FEV/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 FEV.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.

DOI10.1016/j.chest.2018.12.022
Alternate JournalChest
PubMed ID30684474
PubMed Central IDPMC6533449
Grant ListHHSN268200900019C / HL / NHLBI NIH HHS / United States
U24 HL141762 / HL / NHLBI NIH HHS / United States
P30 ES005605 / ES / NIEHS NIH HHS / United States
P30 ES006694 / ES / NIEHS NIH HHS / United States
HHSN268200900015C / HL / NHLBI NIH HHS / United States
HHSN268200900016C / HL / NHLBI NIH HHS / United States
I01 CX000911 / CX / CSRD VA / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
HHSN268200900018C / HL / NHLBI NIH HHS / United States
HHSN268200900013C / HL / NHLBI NIH HHS / United States
HHSN268200900014C / HL / NHLBI NIH HHS / United States
K23 HL123778 / HL / NHLBI NIH HHS / United States
K24 HL137013 / HL / NHLBI NIH HHS / United States
HHSN268200900017C / HL / NHLBI NIH HHS / United States
HHSN268200900020C / HL / NHLBI NIH HHS / United States
MS#: 
MS146
Manuscript Full Title: 
Systemic Markers of Inflammation in Smokers With Symptoms Despite Preserved Spirometry in SPIROMICS.
Manuscript Lead/Corresponding Author Affiliation: 
Clinical Center: San Francisco (University of California at San Francisco)
ECI: 
Manuscript Status: 
Published and Public