Airway Inflammation and Cellular Stress in Noneosinophilic Atopic Asthma: Comment
We have gone further in evaluating NEA and measured sputum immunopositivity for stress-related proteins such as HO-1, iNOS, and nitroty-rosine. Inflammatory and oxidant stimuli induce the cellular expression of iNOS and HO-1.> Nitric oxide under aerobic conditions reacts with oxygen and superoxide anion radicals to yield peroxynitrite. Peroxynitrite leads to tyrosine nitration, making nitrotyrosine an indicator of the involvement of nitric oxide in irreversible oxidative reactions. We have used these molecules to assess the inflammatory and oxidative load imposed on the cells present in the airways of EA and NEA patients, and have found no difference between the two groups. Previous inves-tigators have demonstrated increased numbers of HO-1-positive, iNOS-positive, and nitrotyrosine-positive cells in sputum and bronchial or lung biopsy specimens from asthmatic patients compared to those from healthy subjects. To the best of our knowledge, until today no study had evaluated the differences in these parameters between NEA and EA patients. Our results showing no difference in stress-induced enzyme and nitrotyrosine levels indicate a similar intensity of inflammatory and oxidant stimuli in the airways of NEA and EA patients. This finding is in accordance with the similar severity of airflow limitation that we found in NEA and EA patients, and does not favor the hypothesis that NEA is predictive of increased asthma severity. Source
In the second part of our study, we compared NEA to COPD patients. Considering previous re-ports of neutrophilia and steroid resistance in NEA patients, we looked for similarities in airway inflammation and cellular stress between these two groups. Our study showed decreased neutrophil counts, lower MPO levels, and a tendency toward decreased IL-8 levels in NEA patients compared to those in COPD patients (p = 0.17). These results suggest that neutrophilic inflammation is less prominent in the airways of NEA patients compared to those of COPD patients. The lack of a statistically significant difference in IL-8 levels despite the strong difference in neutrophil numbers could be due to the fact that other mediators, such as leuko-triene B4, might be more powerful neutrophil che-moattractants than IL-8. Total cell counts were also decreased in NEA patients, which probably reflects a less intense inflammatory process in the airways of these patients. An interesting finding, but one that was not surprising, was that of decreased ECP levels in NEA patients compared to those in COPD patients. This is very much associated with the decreased neutrophil numbers found in NEA patients and with the reported release of ECP from these cells.