Dataset Information

Effect of aging on sputum inflammation and asthma control.

ABSTRACT:

Background

Aged asthmatic patients experience increased morbidity and mortality. Knowledge of the aging effect on airway inflammation and asthma control is limited.

Objective

We sought to compare airway inflammation and its relationship to asthma control in aged versus younger patients and determine whether differences are asthma specific or caused by "inflamm-aging."

Methods

We performed a prospective study of aged (>60 years) and younger (21-40 years) inner-city patients with asthma. After a run-in period to control for inhaled corticosteroid use, induced sputum was collected. Age-matched nonasthmatic control subjects were included to measure age-related inflammatory changes.

Results

Aged (mean age, 67.9 ± 5.1 years; n = 35) compared with younger (mean age, 30.8 ± 5.9 years; n = 37) asthmatic patients had significantly worse asthma control and lower FEV₁. Aged asthmatic patients had higher sputum neutrophil (30.5 × 10⁴/mL and 23.1%) and eosinophil (7.0 × 10⁴/mL and 3.8%) numbers and percentages compared with younger patients (neutrophils, 13.0 × 10⁴/mL [P < .01] and 6.9% [P < .01]; eosinophils, 2.0 × 10⁴/mL [P < .01] and 1.2% [P < .01]). Aged asthmatic patients had higher sputum IL-6 (P < .01) and IL-8 (P = .01) levels. No significant inflammatory differences between aged and younger control subjects were observed. In aged asthmatic patients increased sputum IL-6 and macrophage inflammatory protein 3α/CCL20 levels were significantly associated with decreased asthma control and increased sputum neutrophil numbers and IL-1β, IL-6, and macrophage inflammatory protein 3α/CCL20 levels were associated with hospitalization.

Conclusions

The inflammatory patterns of aged versus younger asthmatic patients are associated with increased sputum neutrophil and eosinophil values and cytokine levels related to neutrophil recruitment. Differences in airway inflammation can contribute to diminished asthma control in the aged. Further understanding of asthma pathophysiology in aged patients is needed to improve management of this vulnerable population.

SUBMITTER: Busse PJ

PROVIDER: S-EPMC5385166 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Effect of aging on sputum inflammation and asthma control.

Busse Paula J PJ Birmingham Janette M JM Calatroni Agustin A Manzi Joseph J Goryachokovsky Anna A Fontela Giselle G Federman Alex D AD Wisnivesky Juan P JP

The Journal of allergy and clinical immunology 20161008 6

<h4>Background</h4>Aged asthmatic patients experience increased morbidity and mortality. Knowledge of the aging effect on airway inflammation and asthma control is limited.<h4>Objective</h4>We sought to compare airway inflammation and its relationship to asthma control in aged versus younger patients and determine whether differences are asthma specific or caused by "inflamm-aging."<h4>Methods</h4>We performed a prospective study of aged (>60 years) and younger (21-40 years) inner-city patients ...[more]

PMID: 27725186

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Project description:Background: 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. Methods: We conducted a genome-wide analysis of microRNA and messenger RNA (mRNA) in the sputum from patients with asthma and correlated expression with clinical phenotypes. Weighted gene correlation network analysis (WGCNA) 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. 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 toll-like receptor (TLR) and 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

Effect of aging on sputum inflammation and asthma control.

Background

Objective

Methods

Results

Conclusions

Publications

Effect of aging on sputum inflammation and asthma control.

Similar Datasets

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