title: Non-invasive assessment of small airway remodelling in smokers.
abstract: Smoking associated COPD progression is likely to be directly linked to differential injury and repair dynamics in small airways (SA). Although IL8 is a well-accepted marker for injured airway epithelium, Clara cells [the predominant proliferating cells in SA] and SCGB1A1 protein [their major secretory product] have only recently emerged as potential SA repair markers. We therefore postulate that the SCGB1A1/IL8 ratio in the airways of smokers would be inversely associated with physiological, radiological and clinical measures of COPD. A cross-sectional cohort of 28 smokers undergoing surgery for peripheral nodule was recruited (24M/4F, age 61 +/- 11 y, FEV1s 76 +/- 20%, smoking 40 +/- 12 p.y). SCGB1A1 and IL8 were measured by ELISA in the induced sputum (IS) 3 to 5 days prior to surgery as well as by immunohistochemistry from lung tissue (also assessed morphometrically) obtained distant to the cancer surgery site. COPD was assessed using standard clinical, functional and radiological parameters. Log-transformed IS-SCGB1A1 was linearly correlated with SCGB1A1-positive epithelial cells detected via immunohistochemistry (r = .533, p = .001), while IS-IL8 was positively related to SA infiltrating neutrophils (Elastase-positive cells). There was a striking negative correlation between IS-SCGB1A1/IL8 levels and whole airway thickness [SA < 2 mm] at morphometry (r = -0.83, p < 0.0001). IS-SCGB1A1/IL8 levels were also inversely associated with nitrogen slope [r = -0.52, p < 0.001] and HRCT SA score [r = -0.51, p < 0.001]. In a multivariate analysis the IS-SCGB1A1/IL8 ratio was a stronger predictor than both the physiological and radiological measures of SA disease assessed. The SCGB1A1/IL8 ratio measured in sputum is a potentially valuable biomarker for non-invasive assessment of SA remodelling in smokers.
authors.affiliation: Dept of Respiratory Diseases, Chu Montpellier, France. a-bourdin@chu-montpellier.fr
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bourdin
authors.forename: Tom
authors.initials: T
authors.lastname: Kotsimbos
authors.forename: Khanh
authors.initials: K
authors.lastname: Nguyen
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vachier
authors.forename: Brigitte
authors.initials: B
authors.lastname: Mainprice
authors.forename: Martine
authors.initials: M
authors.lastname: Farce
authors.forename: Fabrice
authors.initials: F
authors.lastname: Paganin
authors.forename: Charles
authors.initials: C
authors.lastname: Marty-Ané
authors.forename: Hélène
authors.initials: H
authors.lastname: Vernhet
authors.forename: Phillippe
authors.initials: P
authors.lastname: Godard
authors.forename: Pascal
authors.initials: P
authors.lastname: Chanez
mesh_terms: D000368:Aged; D056151:Airway Remodeling; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D012129:Respiratory Function Tests; D012907:Smoking / Q000503:physiopathology*; D013183:Sputum / Q000378:metabolism*; D014598:Uteroglobin / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; C556389:SCGB1A1 protein, human; D014598:Uteroglobin