Increased Levels of Elastase and α₁-Antitrypsin in Sputum of Asthmatic Patients

Abstract

Asthma and chronic bronchitis are inflammatory diseases associated with remodeling of the extracellular matrix (ECM). Elastin, a major component of the ECM in the airways, has been previously found to be disrupted in asthma and chronic bronchitis. This study was aimed at evaluating whether elastin disruption might be associated with an imbalance between elastase (active and total) and alpha1-proteinase inhibitor (alpha1-PI), the main inhibitor of elastase. We measured elastase and alpha1-PI in induced sputum obtained from 16 control subjects, 10 healthy smokers, 19 asthmatic patients, and 10 chronic bronchitis patients. We also assessed the possible origin of elastase, evaluating its levels in sputum with reference to differential cell counts. We found that in induced sputum obtained from asthmatic and chronic bronchitis patients, the levels of both total and active elastase were significantly increased as compared with those of control subjects and healthy smokers and were significantly correlated with the percentage of neutrophils. In addition, in asthma and chronic bronchitis patients, the levels of active and total elastase were inversely correlated with the degree of airway obstruction as assessed from FEV1 values. This study shows that airway inflammation in asthma and chronic bronchitis is associated with high levels of active elastase, which may play a role in the pathogenesis of airway remodeling.

Neutrophilic airway inflammation and IL‐17

“…The concentration of neutrophil elastase within the airway lumen is also increased in severe asthma, even when there is no detectable airway infection present (2)(3)(4). An increase in neutrophil elastase is also detected in the airways in chronic bronchitis and in COPD (3,39). The same is the case for cystic fibrosis and ARDS (17,19,40).…”

“…There is evidence from clinical studies that an exaggerated recruitment and activation of neutrophilic granulocytes in the airways is linked to the clinical course of several inflammatory diseases in the airways and lungs, such as asthma (1)(2)(3)(4)(5)(6)82), nonspecific bronchial hyperreactivity (BHR) (7), chronic bronchitis (3,(8)(9)(10), chronic obstructive pulmonary disease (COPD) (3,(11)(12)(13), cystic fibrosis (14)(15)(16)(17), and acute respiratory distress syndrome (18)(19)(20). The referred evidence has been gathered analysing cellular contents in bronchial tissue, in bronchoalveolar lavage (BAL) fluid, in bronchial biopsies, in induced sputum and in peripheral blood.…”

“…In severe asthma, for example, it can be detected in the submucosa of bronchi, even when no eosinophils are present, underlining the possibility that the neutrophil itself is more pivotal for developing severe asthma than is the eosinophil (6). The concentration of neutrophil elastase within the airway lumen is also increased in severe asthma, even when there is no detectable airway infection present (2)(3)(4). An increase in neutrophil elastase is also detected in the airways in chronic bronchitis and in COPD (3,39).…”

The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma

“…BOUSQUET et al [60] reported that biopsy samples from asthmatics showed altered elastin staining. In addition, VIGNOLA et al [61] showed that the enzyme responsible for elastin degradation, elastase, was increased in sputum samples from asthmatics compared with healthy controls. Apart from elastin degradation, it is proposed that neutrophil elastase can also act as a smooth muscle mitogen [62] and promotes mucin gene expression by cleavage of EGF receptor ligands [63].…”

Superoxide release and cellular gluthatione peroxidase activity in leukocytes from children with persistent asthma

“…They release enzymes, including extracellular matrix-degrading proteases, elastase, cytokines, and reactive oxygen species, which have been implicated in lung injury (3). The reported effects of reactive oxygen species in asthma include a decrease of betaadrenergic function in lungs, airway smooth muscle contraction, increased vascular permeability, bronchial hyperresponsiveness, increased mucus secretion, impaired ciliary activity, generation of chemotactic factors, lipid peroxidation, and secondary production of mediators with a bronchoconstrictor effect (4,5).…”