Increased airway iron parameters and risk for exacerbation in COPD: an analysis from SPIROMICS.

TitleIncreased airway iron parameters and risk for exacerbation in COPD: an analysis from SPIROMICS.
Publication TypePublication
Year2020
AuthorsZhang WZ, Oromendia C, Kikkers SAnn, Butler JJ, O'Beirne S, Kim K, O'Neal WK, Freeman CM, Christenson SA, Peters SP, J Wells M, Doerschuk C, Putcha N, Barjaktarevic I, Woodruff PG, Cooper CB, Bowler RP, Comellas AP, Criner GJ, Paine R, Hansel NN, Han MK, Crystal RG, Kaner RJ, Ballman KV, Curtis JL, Martinez FJ, Cloonan SM
JournalSci Rep
Volume10
Issue1
Pagination10562
Date Published2020 06 29
ISSN2045-2322
KeywordsAdult, Aged, Aged, 80 and over, biomarkers, Bronchoalveolar Lavage Fluid, Disease Progression, Female, Ferritins, Forced Expiratory Volume, Humans, Iron, Iron-Binding Proteins, Lung, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, Risk Factors, Severity of Illness Index
Abstract

Levels of iron and iron-related proteins including ferritin are higher in the lung tissue and lavage fluid of individuals with chronic obstructive pulmonary disease (COPD), when compared to healthy controls. Whether more iron in the extracellular milieu of the lung associates with distinct clinical phenotypes of COPD, including increased exacerbation susceptibility, is unknown. We measured iron and ferritin levels in the bronchoalveolar lavage fluid (BALF) of participants enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD (SPIROMICS) bronchoscopy sub-study (n = 195). BALF Iron parameters were compared to systemic markers of iron availability and tested for association with FEV % predicted and exacerbation frequency. Exacerbations were modelled using a zero-inflated negative binomial model using age, sex, smoking, and FEV % predicted as clinical covariates. BALF iron and ferritin were higher in participants with COPD and in smokers without COPD when compared to non-smoker control participants but did not correlate with systemic iron markers. BALF ferritin and iron were elevated in participants who had COPD exacerbations, with a 2-fold increase in BALF ferritin and iron conveying a 24% and 2-fold increase in exacerbation risk, respectively. Similar associations were not observed with plasma ferritin. Increased airway iron levels may be representative of a distinct pathobiological phenomenon that results in more frequent COPD exacerbation events, contributing to disease progression in these individuals.

DOI10.1038/s41598-020-67047-w
Alternate JournalSci Rep
PubMed ID32601308
PubMed Central IDPMC7324559
Grant ListHHSN268200900019C / HL / NHLBI NIH HHS / United States
U24 HL141762 / HL / NHLBI NIH HHS / United States
P30 ES005605 / ES / NIEHS NIH HHS / United States
HHSN268200900015C / HL / NHLBI NIH HHS / United States
R01 HL122438 / HL / NHLBI NIH HHS / United States
HHSN268200900014C / HL / NHLBI NIH HHS / United States
HHSN268200900018C / HL / NHLBI NIH HHS / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
P01 HL114501 / HL / NHLBI NIH HHS / United States
U01 HL128964 / HL / NHLBI NIH HHS / United States
R00 HL125899 / HL / NHLBI NIH HHS / United States
HHSN268200900016C / HL / NHLBI NIH HHS / United States
K23 HL123778 / HL / NHLBI NIH HHS / United States
K24 HL137013 / HL / NHLBI NIH HHS / United States
HHSN268200900020C / HL / NHLBI NIH HHS / United States
HHSN268200900017C / HL / NHLBI NIH HHS / United States
T32 HL134629 / HL / NHLBI NIH HHS / United States
HHSN268200900013C / HL / NHLBI NIH HHS / United States
R01 HL136682 / HL / NHLBI NIH HHS / United States
MS#: 
MS170
Manuscript Full Title: 
Increased airway iron parameters and risk for exacerbation in COPD: an analysis from SPIROMICS.
Manuscript Lead/Corresponding Author Affiliation: 
Weill Cornell Medical Center
ECI: 
Manuscript Status: 
Published and Public