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Alveolar macrophage phagocytosis is impaired in children with poorly controlled asthma

https://doi.org/10.1016/j.jaci.2008.03.008Get rights and content

Background

Lower respiratory tract infection is a differentiating feature of children with poorly controlled asthma.

Objective

Given the role of alveolar macrophages (AMs) in innate immunity, we hypothesized that AM phagocytosis might be impaired in poorly controlled asthma.

Methods

Bronchoalveolar lavage fluid AMs were isolated from 28 asthmatic children (moderate asthma, n = 12; severe asthma, n = 16), 10 nonasthmatic children with chronic cough treated with inhaled corticosteroids, and 10 healthy adult control subjects. AMs were stimulated with LPS and exposed to fluorescein isothiocyanate–conjugated Staphylococcus aureus for 2 hours. Phagocytosis was quantified by using a phagocytic index (PI) calculated from the percentage of phagocytic cells multiplied by the relative fluorescence (RFU) units of S aureus per cell. Apoptosis was determined from the percentage of cells positive for poly (adenosine diphosphate–ribose) polymerase.

Results

Phagocytosis as measured by using the unstimulated PI was decreased in subjects with poorly controlled asthma (healthy control subjects, 9330 ± 3992 RFU; chronic cough, 9042 ± 5976 RFU; moderate asthma, 4361 ± 2536 RFU; severe asthma, 3153 ± 1886 RFU; P < .001) and remained unchanged with LPS stimulation. Children with severe asthma also had increased AM apoptosis, both the unstimulated and LPS-simulated states (P < .001), which correlated with the PI.

Conclusions

AM function is compromised in children with poorly controlled asthma and is characterized by decreased phagocytosis and increased apoptosis.

Section snippets

Sample

Children 5 to 17 years of age undergoing flexible bronchoscopy with bronchoalveolar lavage (BAL) for clinical indications were recruited from the outpatient pulmonary clinic at Emory University. Indications for bronchoscopy included (1) poor asthma control despite maximum ICS doses, (2) suspected aspiration, (3) suspected atypical infection, or (4) confirmation of habitual cough or vocal cord dysfunction. This study was approved by the Emory University Institutional Review Board. Informed

Results

Thirty-four children with poorly controlled asthma (severe asthma, n = 18) were recruited for the study. Four children (severe asthma, n = 2) had BAL fluid colonization with Streptococcus pneumoniae, Moraxella catarrhalis, or both and were excluded from data analyses. Ten children with chronic cough treated with ICSs served as control subjects. All children in this group had been receiving ICSs for at least 16 weeks before bronchoscopy (median, 30 weeks; range, 16-52 weeks). Postbronchoscopy

Discussion

This is the first study to demonstrate impairment of AM phagocytosis in children with poorly controlled asthma. In subjects with moderate and severe asthma, phagocytosis was decreased by more than 50% compared with that seen in adult and pediatric control subjects. AM apoptosis was also greater in asthmatic subjects and increased further with LPS stimulation. These data suggest that the airway innate immune response might be impaired in children with poorly controlled asthma, a finding that

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    Supported with funds from National Institutes of Health (NIH)/National Institute of Nursing Research KO1 NR010548, NIH/National Center for Research Resources K12 RR017643 and KL2 RR025009, and NIH/National Heart, Lung, and Blood Institute SARP RO1 HL69170.

    Disclosure of potential conflict of interest: W. G. Teague is on the speakers' bureau for Merck. The rest of the authors have declared that they have no conflict of interest.

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