Morphologic determinants of airway responsiveness in chronic smokers.

Abstract

Nonspecific bronchial hyperresponsiveness (NSBH) occurs in asthmatics and in smokers who have airway obstruction. NSBH may be caused by different mechanisms in these conditions. We hypothesized that NSBH in smokers was a consequence of the structural changes that occur in chronic obstructive pulmonary disease (COPD) and lead to airway obstruction. We measured nonspecific bronchial responsiveness, assessed by PC20, in 77 smokers who had mild to moderate airflow obstruction prior to lung resection for a pulmonary nodule. We related airway responsiveness to baseline airway function (FEV1 % predicted), to functional (PLmax, PL90, and P-V curve shape) and morphometric (alveolar attachments) markers of lung elasticity as well as to thickening in small airways. Airway wall thickness, internal and external to the outer border of smooth muscle was quantified by plotting the square root of airway wall area versus a marker of airway size, airway internal perimeter (Pi). PC20 was significantly related to FEV1% predicted and PLmax. and when these functional parameters were controlled for, PC20 was also inversely related to airway wall thickness. There was also a trend for the most responsive patients to have fewer alveolar attachments per millimeter on the external perimeter of the airway walls. These data suggest that exaggerated nonspecific airway narrowing in COPD is secondary to structural changes caused by the disease.

Clinical relevance of airway remodelling in airway diseases

“…Therefore, it is likely that the AHR seen in COPD simply reflects normal smooth muscle shortening around an airway that is already narrowed due to airway wall remodelling. This is supported by the study of RIESS et al [180] who showed that airway responsiveness in 77 smokers who underwent lung resection was negatively related not only to baseline lung function, but also to lung recoil, and was positively related to airway wall thickness. These findings support theoretical models based on measured airway dimensions [140].…”

Long Term Cigarette Smoke Exposure Does Not Increase Airway Responsiveness in Rats

“…However, an increase in airway responsiveness is an important finding in long term smokers [2,6] where it may be an important indicator of increased decline in pulmonary function [12,21,24,28]. We have also shown previously [23] that the airway walls in human cigarette smokers with increased airway responsiveness were thicker, and Nagai et al [16] found correlations between airway responsiveness and bronchiolar fibrosis grades in their analysis of the patients in the National Institute of Health Intermittent Positive Pressure Breathing Trial.…”

Noninflammatory mechanisms of airway hyper-responsiveness in bronchial asthma: an overview

“…Patients with COPD do not have very marked airway wall thickening, but they do breathe at lower lung elastic recoil despite an increased end-expiratory lung volume. The decreased elastic recoil, which is caused by proteolytic lung destruction, will be accompanied by a decrease in parenchymal shear modulus [Riess et al 1996]. Decreased lung volumes, due for example to abdominal obesity, are also critical in this respect and may favor airway narrowing, as they are associated with reduced tethering forces of lung parenchyma to keep the airways open [Bates et al 1997;Ding et al 1987].…”