Airway Inflammation and Cellular Stress in Noneosinophilic Atopic Asthma: Summary
Previous investigators have shown that an important factor that might influence the number of sputum neutrophils is age and that neutrophil numbers increase with increasing age (specifically, numbers in persons > 50 years of age). Therefore, one might attribute the increased number of neutrophils that we found in COPD patients compared to those in NEA patients to the significant age difference between the two groups. We did not succeed in recruiting patients in similar age groups because, in general, the first diagnosis of COPD is established in subjects who are > 40 to 50 years of age. However, we think that the difference found between NEA and COPD patients is disease specific rather than age specific because the neutrophil numbers in our COPD group were higher than the number that should be expected from healthy subjects in similar age group (mean, 68.5%; SD, 20.6%), based on data from the study by Thomas et al. more
Previous studies have shown the increased expression of HO-1 and iNOS, and the increased formation of nitrotyrosine in asthmatic patients and COPD patients. Ichinose et al have demonstrated a relative increase in nitrotyrosine levels in COPD patients compared to those in asthma patients, but no difference in iNOS levels, suggesting that NO is mainly consumed via oxidative reactions in COPD patients compared to asthma patients. Our results confirm and extend these findings to patients with NEA, and indicate that NEA, like EA, is associated with lower degrees of airway oxidative stress compared to COPD.
Although COPD patients showed increased oxidative stress, a similar increase in the expression of HO-1, which is induced by oxidant stimuli, was not detected. Maestrelli et al have reported deficient HO-1 expression in patients with severe COPD compared to control smokers. Moreover, it has been shown that microsatellite polymorphism in the HO-1 gene promoter is associated with the susceptibility to emphysema. These findings and ours suggest that an impairment of the HO-1 pathway in COPD patients may be involved in the pathogenesis of the disease.
In conclusion, despite previous evidence for airway neutrophilia and steroid resistance in NEA patients, as in COPD patients, this study reported significantly decreased neutrophilic inflammation and oxidative stress in NEA patients compared to COPD patients. This evidence clearly suggests that NEA is distinct from COPD. Contrary to previous observations, in which similar numbers of neutrophils, and neutrophilic and eosinophilic markers were seen, a similar expression of stress-related proteins was found to exist in atopic patients with NEA and EA, which suggests that there might be similarities in airway inflammation between NEA and EA patients. However, larger studies are needed to investigate further the clinical and inflammatory characteristics of NEA before we are able to categorize asthma patients into those with or without eosinophilic inflammation. Moreover, to be able to interpret whether NEA is a distinct phenotype it is necessary to show whether the phenotype is reproducible.