Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study

Michael W Sims,Angela Haczku,Michael F Beers,Sonja Kierstein,Ali I Musani,Reynold A Panettieri,Ruth M Tal-Singer

doi:10.1186/1465-9921-9-13

Michael W Sims, Angela Haczku + Show 5 more

Open Access

https://doi.org/10.1186/1465-9921-9-13

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Abstract

BackgroundSurfactant protein D (SP-D), an innate immune molecule, plays an important protective role during airway inflammation. Deficiency of this molecule induces emphysematous changes in murine lungs, but its significance in human COPD remains unclear.MethodsWe collected bronchoalveolar lavage fluid from 20 subjects with varying degrees of COPD (8 former smokers and 12 current smokers) and 15 asymptomatic healthy control subjects (5 never smokers, 3 remote former smokers, and 7 current smokers). All subjects underwent a complete medical history and pulmonary function testing. SP-D was measured by Enzyme-Linked ImmunoSorbent Assay. Statistical analysis was performed using nonparametric methods and multivariable linear regression for control of confounding. The effect of corticosteroid treatment on SP-D synthesis was studied in vitro using an established model of isolated type II alveolar epithelial cell culture.ResultsAmong former smokers, those with COPD had significantly lower SP-D levels than healthy subjects (median 502 and 1067 ng/mL, respectively, p = 0.01). In a multivariable linear regression model controlling for age, sex, race, and pack-years of tobacco, COPD was independently associated with lower SP-D levels (model coefficient -539, p = 0.04) and inhaled corticosteroid use was independently associated with higher SP-D levels (398, p = 0.046). To support the hypothesis that corticosteroids increase SP-D production we used type II alveolar epithelial cells isolated from adult rat lungs. These cells responded to dexamethasone treatment by a significant increase of SP-D mRNA (p = 0.041) and protein (p = 0.037) production after 4 days of culture.ConclusionAmong former smokers, COPD is associated with lower levels of SP-D and inhaled corticosteroid use is associated with higher levels of SP-D in the lung. Dexamethasone induced SP-D mRNA and protein expression in isolated epithelial cells in vitro. Given the importance of this molecule as a modulator of innate immunity and inflammation in the lung, low levels may play a role in the pathogenesis and/or progression of COPD. Further, we speculate that inhaled steroids may induce SP-D expression and that this mechanism may contribute to their beneficial effects in COPD. Larger, prospective studies are warranted to further elucidate the role of surfactant protein D in modulating pulmonary inflammation and COPD pathogenesis.

Highlights

Surfactant protein D (SP-D), an innate immune molecule, plays an important protective role during airway inflammation
SP-D levels in their bronchoalveolar lavage fluid (BALF) relative to healthy controls (p = 0.01), suggesting that Chronic obstructive pulmonary disease (COPD) is associated with lower levels of SP-D in the lung independent of smoking status (Figure 1)
Inhaled corticosteroid use was independently associated with SP-D levels Since previous studies from our laboratory suggested that corticosteroids may increase SP-D expression [13,24], we examined inhaled corticosteroid (ICS) use as a potential confounder in our study

Summary

Introduction

Surfactant protein D (SP-D), an innate immune molecule, plays an important protective role during airway inflammation. Deficiency of this molecule induces emphysematous changes in murine lungs, but its significance in human COPD remains unclear. Chronic obstructive pulmonary disease (COPD) is characterized, in part, by an abnormal inflammatory response of the lung to noxious particles or gases [1], cigarette smoke. Innate immunity is the vanguard of this multifactorial inflammatory response to cigarette smoke-induced lung injury and may play an important role in COPD pathogenesis. SP-D deficient mice display an abnormal pulmonary phenotype characterized by activated alveolar macrophages, increased levels of matrix metalloproteases and emphysematous changes in the lung parenchyma [15,16,17]. Because of the immunoprotective properties of SP-D, constitutive expression in the proximal and distal airspaces appears essential in order to maintain an immunologically hyporeactive tissue milieu under normal (non-infectious) conditions

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