Cartilage degradation can contribute to chronic airway obstruction and allow more powerful bron-choconstriction for a given degree of ASM contraction. Peribronchiolar fibrosis occurring in COPD small airways is believed to lead to centrilobular emphysema, resulting in loss of alveolar attachments and thereby contributing to a loss of elastic recoil and early closure of bronchioles during expiration. It has been proposed that small airway alterations might be the earlier stage of COPD, a theory supported by the clinical observation of isolated abnormalities of forced expiratory flow, midexpira-tory phase in the pulmonary function test of smok-ers. However, this has never been proven.
The number of infiltrating leukocytes, such as mast cells, eosinophils, and CD8+ and CD45 + T-cells, correlates with AHR in patients treated with inhaled corticosteroids (ICS). Sputum MMP-9 level is positively correlated with the FEV1 fall after allergen challenge and asthma severity. The BAL level of MMP-8 inversely correlates with FEVX in asthmatic patients. there
Other authors have also linked inflammation and structural alterations with the clinical stage of COPD. Sputum neutrophilia and CD8+ T-cells, macrophages, goblet-cell numbers, CD45+ cells, natural killer lymphocytes, and macrophage inflammatory protein-1a+ epithelial cells in bronchial biopsy specimens have all shown a negative relationship with FEV1. An increase in CD8+ T-cells in subepithelium of COPD-derived bronchial tissues is associated with the total pack-years of smoking. Sputum MMP-9 level is positively linked to neutrophil numbers and is negatively correlated with airflow obstruction in COPD. According to previous observations, structural alterations, combined with the inflammatory process, appear to be related to the magnitude of functional abnormalities in COPD and asthma (summarized in Table 2).
Table 2—Potential Influences of Airway Remodeling
|Reduction of maximal bronchoconstriction|
|Increase in the irreversible component of airway obstruction|
|Accelerated decline in pulmonary function|
|Persistence of AHR|
|Loss of smooth-muscle stretch relaxation from loss of airway distensibility|
|Increased contractile response|
|Loss of elastic recoil|