Role of Collagen in Airway Mechanics

Collagen is the most abundant airway extracellular matrix component and is the primary determinant of mechanical airway properties. Abnormal airway collagen deposition is associated with the pathogenesis and progression of airway disease. Thus, understanding how collagen affects healthy airway tissue mechanics is essential. The impact of abnormal collagen deposition and tissue stiffness has been an area of interest in pulmonary diseases such as cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In this review, we discuss (1) the role of collagen in airway mechanics, (2) macro- and micro-scale approaches to quantify airway mechanics, and (3) pathologic changes associated with collagen deposition in airway diseases. These studies provide important insights into the role of collagen in airway mechanics. We summarize their achievements and seek to provide biomechanical clues for targeted therapies and regenerative medicine to treat airway pathology and address airway defects.

Altered Airway Mechanics in the Context of Obesity and Asthma

The obesity epidemic is causing a rise in asthma incidence due to the appearance of an obesity-specific late-onset non-allergic (LONA) phenotype. We investigated why only a subset of obese participants develop LONA asthma by determining how obesity, both alone and in combination with LONA asthma, affects the volume dependence of respiratory system impedance. We also determined how obesity and asthma affect impedance during and following challenge with the PC20 dose of methacholine. We found during passive exhalation that all obese participants, in contrast to lean controls and lean asthmatics, experienced similarly profound elevations in lung elastance as they approached functional residual capacity. We also found, however, that the LONA asthmatics had a greater negative dependence of airway resistance on lung volume over the middle of the volume range compared to the other groups. Methacholine challenge with the PC20 dose led to comparable changes in respiratory system impedance in the 4 study groups, but the doses themselves were substantially lower in both obese and lean asthmatic participants compared to obese and lean controls. Also, the obese LONA asthmatics had higher breathing frequencies and lower tidal volumes post challenge compared to the other participants. Taken together, these results suggest that all obese individuals experience substantial lung collapse as they approach FRC, presumably due to the weight of the chest wall. It remains unclear why obese LONA asthmatics are hyperresponsive to methacholine while obese non-asthmatic individuals are not.