Inflammation‐dependent and independent airway remodelling in asthma

• Published in: Respirology (Carlton, Vic.) Vol. 23; no. 12; pp. 1138 - 1145
• Main Authors: Elliot, John G., Noble, Peter B., Mauad, Thais, Bai, Tony R., Abramson, Michael J., McKay, Karen O., Green, Francis H.Y., James, Alan L.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.12.2018; Wiley Subscription Services, Inc
• Subjects: Adult; airway morphology; Airway Remodeling - immunology; Asthma; Asthma - immunology; Asthma - pathology; Autopsy; Basement Membrane - pathology; Extracellular matrix; Female; Humans; Inflammation; Inflammation - pathology; Male; Phenotypes; Respiratory System - immunology; Respiratory System - pathology; Respiratory tract; Respiratory tract diseases; Smooth muscle; stereology; stereology; asthma; inflammation; airway morphology
• ISSN: 1323-7799; 1440-1843; 1440-1843
• DOI: 10.1111/resp.13360

ABSTRACT Background and objective The pathology of asthma is characterized by airway inflammation (granulocytic (GA) or paucigranulocytic (PGA)) and remodelling of airway structures. However, the relationship between inflammatory phenotypes and remodelling is unclear. We hypothesized that some features of airway remodelling are dependent on granulocytic airway inflammation while others are not. Methods Post‐mortem airway sections from control subjects (n = 48) and cases of asthma with (n = 51) or without (n = 29) granulocytic inflammation in the inner airway wall were studied. The thickness of the airway smooth muscle (ASM) layer, basement membrane and inner and outer airway walls, the size and number of ASM cells, the volume fraction of extracellular matrix within the ASM layer, ASM shortening and luminal mucus were estimated. Airway dimensions were compared between the three subject groups. Results In cases of PGA, only the thickness of the ASM layer and basement membrane was increased compared with control subjects. In cases of GA, not only the ASM and basement membrane were increased in thickness, but there was also increased inner and outer airway wall thickness and increased narrowing of the airway lumen due to ASM shortening and mucus obstruction, compared with control subjects. Granulocytic inflammation was observed more often in cases of fatal asthma. Conclusion These findings suggest that inner and outer wall thickening coexists with inflammation, whereas thickening of the ASM layer and basement membrane may be present even in the absence of inflammation. Remodelling of the ASM layer and basement membrane may therefore be less susceptible to anti‐inflammatory therapy. Findings suggest that inner and outer wall thickening coexists with airway inflammation, whereas airway smooth muscle and basement membrane remodelling may be partly independent of airway inflammation and therefore not reversible by anti‐inflammatory treatment. See related Editorial