Phagocytosis of fossil fuel particulates by macrophages in children with asthma

Abstract

BackgroundAirway macrophages clear inhaled soot (black carbon) from traffic fumes. Macrophages from children with asthma have impaired phagocytosis of bacteria, and prostaglandin E2 (PGE2) is associated with impaired phagocytosis by macrophages. We sought to assess whether macrophage phagocytosis of soot was impaired, and to measure prostanoid metabolites, in children with asthma. MethodsIn this cross-sectional study, airway macrophages were obtained from 72 children aged 7–14 years by sputum induction with nebulised 4·5% saline. Children were classified as: healthy controls (n=39); mild asthma, defined as British Thoracic Society (BTS) step 1–2 (n=13); or moderate-to-severe asthma (BTS step 3–5) (n=20), and recruited from a UK paediatric outpatient clinic. Healthy controls were recruited as part of the London Low Emission Zone study. Macrophage black carbon was assessed with image analysis by an assessor masked to asthma severity. Exposure to air pollution was calculated by means of the London Air Quality Toolkit. Urinary PGE2 metabolites were measured with high performance liquid chromatography-tandem mass spectrometry. The effect of PGE2 on phagocytosis of black carbon by rat airway macrophages was assessed with an in-vitro phagocytosis assay using urban particulate matter collected from air filters placed at city centre sites in Leicester, UK. Written informed consent was obtained from children and parents (Research Ethics Committee reference 11-LO-1732 and 08/H0704/139). FindingsChildren with moderate-to-severe asthma had lower airway macrophage black carbon than did controls (median 0·19 mm2 [IQR 0·11–0·26] vs 0·35 [0·16–0·49], p<0·0366, Mann-Whitney U test). Airway macrophage black carbon in children with mild asthma was much the same as in controls. Air pollution exposure at the home address did not differ between groups. Moderate to severe asthma was associated with an increase in the urinary PGE2 metabolite, 13,14-dihydro-15-keto-tetranor-PGE2 (median 668 pg/mg creatinine [IQR 293–937] vs 471 [315–623], p<0·05, Mann-Whitney U test). In the 33 children with asthma, this urinary PGE2 metabolite was inversely associated with macrophage carbon (Spearman r =−0·47, p<0·0062). PGE2 suppressed phagocytosis by rat airway macrophages of urban particulate matter to 57% (IQR 41–95) of controls (p<0·0215, Wilcoxon signed rank test). InterpretationMacrophage phagocytosis of black carbon derived from fossil fuel is impaired in moderate-to-severe childhood asthma. This process is associated with raised urinary concentrations of 13,14-dihydro-15-keto-tetranor-PGE2. PGE2 also impairs phagocytosis of black carbon and urban particulate matter by rat airway macrophages in vitro, and is therefore a plausible mediator underlying the impaired phagocytosis seen in macrophages from children with asthma. We now aim to replicate these findings in differentiated human macrophages and to establish airway concentrations of PGE2 from exhaled breath condensate samples taken from these children. Our results suggest a possible mechanism underlying the observation that traffic-derived air pollution adversely affects children with asthma, because they may be less able to clear inhaled particles effectively. FundingBarts and The London Charity.