Airway Inflammation and Cellular Stress in Noneosinophilic Atopic Asthma
Airway inflammation is considered to be the hallmark in asthma pathogenesis. However, the known hypothesis that T-cells produce T-helper type 2 cytokines, which trigger an eosinophilic inflammatory response in atopic asthmatic patients, has been questioned. There is now significant evidence that noneosinophilic asthma (NEA) exists. Link
Although NEA has been associated with increased numbers of pulmonary neutrophils,2 other studies- have failed to verify this finding. Furthermore, it is unclear whether asthma patients with noneosino-philic airway inflammation show a clinical phenotype that is clearly different from that seen in “classic” eosinophilic asthma (EA). NEA might be more frequent in patients with severe persistent asthma, and it might predict a poor response to steroid treatment.’ However, a substantial number of patients with mild and moderate asthma also have demonstrated noneosinophilic airway inflammation. Interestingly, both airway neutrophilia and steroid resistance are major features of COPD. Although this suggests that there may be similarities in airway inflammation between NEA and COPD patients, there is no evidence so far to support such an hypothesis.
Sputum induction is a safe and reproducible technique, and sputum analysis offers insight into many biological processes of the airways. Characteristic inflammatory changes in patients with asthma have been identified in sputum and include, besides airway eosinophilia, increased numbers of cytokines and chemokines, and increased expression of stress-related proteins, like heme-oxygenase (HO) and inducible nitric oxide synthase (iNOS). Only a few studies have investigated changes in those parameters in patients with NEA.
In the present study, indexes of neutrophilic and eosinophilic airway inflammation (ie, sputum cell counts, sputum supernatant eosinophilic cationic protein [ECP], myeloperoxidase [MPO], interleukin [IL]-8, and granulocyte macrophage colony-stimulating factor [GM-CSF] levels) and cellular stress (ie, HO-1, iNOS, and nitrotyrosine expression) were evaluated in sputum samples from patients with NEA, and were compared to those from EA and COPD patients.