Airway Inflammation and Cellular Stress in Noneosinophilic Atopic Asthma: Discussion

Nov-2-2014

Airway Inflammation and Cellular Stress in Noneosinophilic Atopic Asthma: DiscussionSimilarly, previous studies on NEA have evaluated steroid-treated asthmatic patients. Even if our patients were clinically stable and underinhaled the steroid treatment at the time of the assessment, we were still able to demonstrate two distinct groups according to sputum eosinophilia. Moreover, the existence of NEA has been confirmed in steroid-naive subjects and in subjects with current symptoms. Third, were we have used previously published data to set the normal sputum eosinophil count at < 2.2% of the total cell count. Although it is a commonly accepted approach to defining sputum eosinophilia based on eosinophil percentages, as can be seen from Table 2, there are NEA patients with higher absolute eosinophil counts than those for EA patients. This finding raises considerations as to whether absolute sputum eosinophil counts rather than percentages should be used to define sputum eosinophilia. more

Finally, dithiothreitol (DTT), a reducing agent that we used to homogenize sputum, might have affected the detection of inflammatory mediators in our sputum sol phase. However, spiking experiments showed good recovery for all mediators, and other investigators have shown no effect of DTT on their standard curves. Even if DTT has a small effect on any of these measurements, comparability between samples should be preserved. Airway inflammation in asthma patients is currently the subject of a number of studies investigating both the nature of inflammatory cells and of the cytokines present. The eosinophil is thought to be the most important cell involved in asthma pathogenesis, and for many years all asthma cases were assumed to be related to increased eosinophilic inflammation. However, the surprising finding that a subgroup of severe asthmatic patients shows normal airway eosinophil counts and high neutrophil counts led to the hypothesis that other inflammatory mechanisms, primarily neutrophilic, might be involved in the development of airway obstruction in these patients. There is now increasing evidence that NEA is much more frequent than previously thought, even among patients with mild asthma, and neutrophilia is presumed to be triggered by the activation of innate immunity. We have evaluated a cohort of atopic asthmatic subjects with a wide range of airflow limitation, from mild to severe, and found that only 54% of asthmatic patients belong to the eosinophilic phenotype. Similar percentages have been reported by other investigators. Patients with NEA showed no significant difference in the severity of airflow limitation or the response to short-acting (3-agonists compared to patients with EA.