title: Black-pigmented material in airway macrophages from healthy children: association with lung function and modeled PM10.
abstract: Epidemiologic studies in children suggest that chronic inhalation of carbonaceous particulate matter < or = 10 pm in aerodynamic diameter (PM10) attenuates the normal growth of lung function. However, the relation between markers of PM10 exposure and the quantity of particles entering the pediatric airway is unclear. Experimental studies have shown that particles entering the lower airway remain visible in the cytoplasm of airway macrophages (AMs) for several months. We hypothesized that particle loading of AMs, detected as black-pigmented material, reflects individual exposure of healthy children to PM10. In this study, we aimed to establish the relation between the median area of black material in AMs (measured as the two-dimensional area of black material ["black area"] per AM per child) and (1) lung function, and (2) level of primary PM10 at the child's home address as estimated by dispersion modeling (referred to as "modeled primary PM10"). We also performed a series of exploratory analyses assessing the association between the median black area in AMs and (1) variables that could modify individual exposure, and (2) airway inflammation. To achieve these aims, AMs were sampled using induced sputum from children in Leicestershire, United Kingdom, and lung function was determined by spirometry. Data from 64 of 116 children who provided adequate induced sputum samples were analyzed. The area of the black material in AMs was determined by an analysis of digitized light-microscopic images of 100 randomly chosen AMs per child. There was a significant inverse association between size of black area in AMs and lung function: each 1.0-microm2 increase in the area of the black material in AMs was associated with a 17.0% (95% confidence interval [CI], 5.6 to 28.4) reduction in forced expiratory volume in one second (FEV1), a 12.9% (95% CI, 0.9 to 24.8) reduction in forced vital capacity (FVC), and a 34.7% (95% CI, 11.3 to 58.1) reduction in forced expiratory flow between 25% and 75% of forced vital capacity (FEF25%-75%). These associations were not affected by bronchodilator treatment. There was also an association between modeled exposure to primary PM10 and area of black material in AMs: each 1.0-microg/m3 increase in primary PM10 was associated with an increase of 0.10 microm2 (95% CI, 0.01 to 0.18) in black area in AMs. There was no significant association between the median black area in AMs and age, height, weight, sex, activity level, and levels of neutrophilic airway inflammation in the induced sputum. We conclude that the median area of black material in AMs in children is a promising marker of individual exposure to carbonaceous PM10 and that our data strengthen the epidemiologic data suggesting that PM10 impairs the growth of lung function in children.
authors.affiliation: Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, London, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Grigg
authors.forename: Neeta
authors.initials: N
authors.lastname: Kulkarni
authors.forename: Nevil
authors.initials: N
authors.lastname: Pierse
authors.forename: Lesley
authors.initials: L
authors.lastname: Rushton
authors.forename: Christopher
authors.initials: C
authors.lastname: O'Callaghan
authors.forename: Andrew
authors.initials: A
authors.lastname: Rutman