Functional significance of increased airway smooth muscle in asthma and COPD

It is not clear how airway pathology relates to the severity of airflow obstruction and increased bronchial responsiveness in cystic fibrosis (CF) patients. The aim of this study was to measure the airway dimensions of CF patients and to estimate the importance of these dimensions to airway resistance using a computational model.Airway dimensions were measured in lungs obtained from CF patients who had undergone lung transplantation (n=12), lobectomy (n=1), or autopsy (n=4). These dimensions were compared to those of airways from lobectomy specimens from 72 patients with various degrees of chronic obstructive pulmonary disease (COPD). The airway dimensions of the CF and COPD patients were introduced into a computational model to study their effect on airway resistance.The inner wall and smooth muscle areas of peripheral CF airways were increased 3.3-and 4.3-fold respectively compared to those of COPD airways. The epithelium was 53% greater in height in peripheral CF airways. The sensitivity and maximal plateau resistance of the computed dose/response curves were substantially increased in the CF patients compared to COPD patients.The changes in airway dimensions of cystic fibrosis patients probably contribute to the severe airflow obstruction, and to increased bronchial responsiveness, in these patients. Eur Respir J 2000; 15: 735±742.

Section: Airway Dimensions Airflow Obstruction and Bronchial Responssupporting

confidence: 67%

“…To predict the effect of airway dimensions on airway resistance, a computational model, as described by WIGGS et al [22] and modified by LAMBERT et al [23], was used. Briefly, the geometry of the bronchial tree in the model is a dichotomously branching network with 16 generations.…”

Section: Airway Dimensions and Computational Model For Airway Resistancementioning

confidence: 99%

Cartilaginous airway wall dimensions and airway resistance in cystic fibrosis lungs

Tiddens¹,

Koopman²,

Lambert³

et al. 2000

“…Since the smooth muscle contributes relatively more to the thickness of the airway wall in the peripheral airways, the effects of smooth muscle hypertrophy and hyperplasia may be expected to be greater in the smaller airways. One analysis suggests that an increase in the amount of muscle will have the greatest effects on maximal narrowing in asthma, especially in small airways [60].…”

Section: The Relationship Between Airway Structure and Functionmentioning

confidence: 99%

Airway smooth muscle in health and disease; methods of measurement and relation to function

James¹,

Carroll²

2000

Smooth muscle is present and probably functional in the airways in utero and increases in absolute area during growth with little further change during adulthood. It encircles the entire airway below the level of the main bronchus, in a roughly circular orientation, except at high lung volumes. It occupies relatively more of the airway wall in the peripheral airways, reaching a maximum in the membranous bronchioles. Measurement of smooth muscle area in the airway wall is confounded by clinical classification of cases, methods of tissue retrieval and preparation, staining and orientation of sections, magnification, image analysis and statistical methods of comparison between groups. Airway smooth muscle area is pathologically increased in inflammatory conditions of the airways such as chronic obstructive pulmonary disease, in relation to airways obstruction, and asthma, in relation to severity and airway size (between 25 and 250% compared with control cases). It is increased in sudden infant death syndrome, but there are few studies in other conditions such as bronchiectasis. In asthma, smooth muscle must shorten (not necessarily to an abnormal degree) for the structural abnormalities of the airway to manifest as excessive airway narrowing. Not surprisingly there is renewed interest in the relationships between the mechanical and contractile properties of smooth muscle, parenchymal properties and lung volume and how these interact to determine smooth muscle length. The relative importance of smooth muscle area and mechanical properties, altered airway structure and airway inflammation in disease are yet to be determined.

“…Morphometric studies of airway smooth muscle in asthma have demonstrated that there is an increase in airway smooth muscle mass which is accounted for by hyperplasia and also by hypertrophy [4,5]. Such an increase in airway smooth muscle mass could contribute to the exaggerated airway narrowing observed in asthma [6,8] and may result from the action of growth factors released during the chronic inflammatory process. It has yet to be demonstrated that airway smooth muscle in asthma has a proliferative phenotype.…”

mentioning

confidence: 99%

Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

Chung

2000

131

In addition to its contractile properties, airway smooth muscle may contribute to the pathogenesis of asthma by increased proliferation, and by the expression and secretion of pro‐inflammatory cytokines and mediators. Studies of airway smooth muscle cells in culture have shown that many mitogenic mediators can induce proliferation, and that these may therefore, contribute to the increase in airway smooth muscle mass observed in asthma. Other mechanisms for airway smooth muscle proliferation include the interaction with inflammatory cells such as T‐cells and eosinophils. Airway smooth muscle cells may also be a source of inflammatory mediators and cytokines, in particular chemokines, thus implicating airway smooth muscle cells as contributors to the inflammatory mechanisms of asthma. The pro‐activating signals for converting airway smooth muscle cells into a proliferative and secretory cell in asthma are unknown, but may include viruses and immunoglobulin E. Airway smooth muscle contractility may also be altered in response to inflammation. Airway smooth muscle cells may play an important interactive role with inflammatory and other structural cells, contributing to inflammation, injury and repair of the airways. Such a recognition makes it imperative to consider the airway smooth muscle as a target of therapeutic drugs for suppressing not only the contractile but also the proliferative and secretory effects of asthma.