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Race is associated with differences in airway inflammation in patients with asthma.

ABSTRACT: BACKGROUND:African American subjects have a greater burden from asthma compared with white subjects. Whether the pattern of airway inflammation differs between African American and white subjects is unclear. OBJECTIVE:We sought to compare sputum airway inflammatory phenotypes of African American and white subjects treated or not with inhaled corticosteroids (ICSs; ICS+ and ICS-, respectively). METHODS:We performed a secondary analysis of self-identified African American and white subjects with asthma enrolled in clinical trials conducted by the National Heart, Lung, and Blood Institute-sponsored Asthma Clinical Research Network and AsthmaNet. Demographics, clinical characteristics, and sputum cytology after sputum induction were examined. We used a sputum eosinophil 2% cut point to define subjects with either an eosinophilic (?2%) or noneosinophilic (<2%) inflammatory phenotype. RESULTS:Among 1018 participants, African American subjects (n = 264) had a lower FEV1 percent predicted (80% vs 85%, P < .01), greater total IgE levels (197 vs 120 IU/mL, P < .01), and a greater proportion with uncontrolled asthma (43% vs 28%, P < .01) compared with white subjects (n = 754). There were 922 subjects in the ICS+ group (248 African American and 674 white subjects) and 298 subjects in the ICS- group (49 African American and 249 white subjects). Eosinophilic airway inflammation was not significantly different between African American and white subjects in either group (percentage with eosinophilic phenotype: ICS+ group: 19% vs 16%, P = .28; ICS- group: 39% vs 35%, P = .65; respectively). However, when adjusted for confounding factors, African American subjects were more likely to exhibit eosinophilic airway inflammation than white subjects in the ICS+ group (odds ratio, 1.58; 95% CI, 1.01-2.48; P = .046) but not in the ICS- group (P = .984). CONCLUSION:African American subjects exhibit greater eosinophilic airway inflammation, which might explain the greater asthma burden in this population.

SUBMITTER: Nyenhuis SM

PROVIDER: S-EPMC5494010 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Race is associated with differences in airway inflammation in patients with asthma.

Nyenhuis Sharmilee M SM Krishnan Jerry A JA Berry Alalia A Calhoun William J WJ Chinchilli Vernon M VM Engle Linda L Grossman Nicole N Holguin Fernando F Israel Elliot E Kittles Rick A RA Kraft Monica M Lazarus Stephen C SC Lehman Erik B EB Mauger David T DT Moy James N JN Peters Stephen P SP Phipatanakul Wanda W Smith Lewis J LJ Sumino Kaharu K Szefler Stanley J SJ Wechsler Michael E ME Wenzel Sally S White Steven R SR Ackerman Steven J SJ

The Journal of allergy and clinical immunology 20170106 1

<h4>Background</h4>African American subjects have a greater burden from asthma compared with white subjects. Whether the pattern of airway inflammation differs between African American and white subjects is unclear.<h4>Objective</h4>We sought to compare sputum airway inflammatory phenotypes of African American and white subjects treated or not with inhaled corticosteroids (ICSs; ICS+ and ICS-, respectively).<h4>Methods</h4>We performed a secondary analysis of self-identified African American and ...[more]

PMID: 28069248

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Project description:Rationale: MicroRNAs are potent regulators of biologic systems that are critical to tissue homeostasis. Individual microRNAs have been identified in airway samples. However, a systems analysis of the microRNA-mRNA networks present in the sputum that contribute to airway inflammation in asthma has not been published.Objectives: Identify microRNA and mRNA networks in the sputum of patients with asthma.Methods: We conducted a genome-wide analysis of microRNA and mRNA in the sputum from patients with asthma and correlated expression with clinical phenotypes. Weighted gene correlation network analysis was implemented to identify microRNA networks (modules) that significantly correlate with clinical features of asthma and mRNA expression networks. MicroRNA expression in peripheral blood neutrophils and lymphocytes and in situ hybridization of the sputum were used to identify the cellular sources of microRNAs. MicroRNA expression obtained before and after ozone exposure was also used to identify changes associated with neutrophil counts in the airway.Measurements and Main Results: Six microRNA modules were associated with clinical features of asthma. A single module (nely) was associated with a history of hospitalizations, lung function impairment, and numbers of neutrophils and lymphocytes in the sputum. Of the 12 microRNAs in the nely module, hsa-miR-223-3p was the highest expressed microRNA in neutrophils and was associated with increased neutrophil counts in the sputum in response to ozone exposure. Multiple microRNAs in the nely module correlated with two mRNA modules enriched for TLR (Toll-like receptor) and T-helper cell type 17 (Th17) signaling and endoplasmic reticulum stress. hsa-miR-223-3p was a key regulator of the TLR and Th17 pathways in the sputum of subjects with asthma.Conclusions: This study of sputum microRNA and mRNA expression from patients with asthma demonstrates the existence of microRNA networks and genes that are associated with features of asthma severity. Among these, hsa-miR-223-3p, a neutrophil-derived microRNA, regulates TLR/Th17 signaling and endoplasmic reticulum stress.

Dataset Information

Race is associated with differences in airway inflammation in patients with asthma.

Publications

Race is associated with differences in airway inflammation in patients with asthma.

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