Airway Collagen and Elastic Fiber Content Correlates with Lung Function in Equine Heaves.
AJP Lung Cellular and Molecular Physiology
Published online on May 30, 2014
Abstract
Background: The consequences on lung function and inflammation of alterations in the extracellular matrix affecting the peripheral airway wall in asthma are largely unknown. Hypothesis: Remodeling of collagen and elastic fibers in the peripheral airway wall leads to airway obstruction, and contributes to neutrophilic airway inflammation. Animals: 6 heaves-affected horses and 5 controls. Methods: Large peripheral lung biopsies were obtained from horses with heaves in clinical remission (Baseline) and during disease exacerbation and from age-matched controls. The area of collagen and elastic fiber content in the lamina propria was measured using histological staining techniques and corrected for airway size. Collagen type 1 and type 3 was further assessed from additional horses after postmortem lung samples using immunohistochemistry. The collagen breakdown products PGP and N-α-PGP, were also measured in bronchoalveolar lavage fluids (BALF) using mass spectrometry. Results: In comparison with controls, heaves-affected horses had an increase in collagen (p=0.05) and elastic fiber contents (p=0.04) at baseline. Collagen types 1 and 3 content was also significantly increased in diseased horses (p=0.015), when both collagen types were combined. No further change in collagen content was observed after a 30-day antigenic challenge. Airway collagen at baseline was positively correlated with pulmonary resistance in asthmatic horses (r²=0.78, p=0.03) and elastic fiber content was positively associated with pulmonary elastance in controls (r2=0.95, p= 0.02). No difference between groups was appreciated in PGP and N-α-PGP peptides in BALF. Clinical Importance: Increased airway wall collagen and elastic fiber content may contribute to residual obstruction in the asthmatic airways.