Association Between Eosinophil Apoptosis in Induced Sputum and Asthma Severity in Children

Background: There is increasing evidence that the disorder of eosinophil apoptosis contributes to the mechanism of prominent airway inflammation in asthma. However the relationship between dysregulation of eosinophil apoptosis and severity of childhood asthma is still unclear

The aim: investigate the relationship between eosinophil apoptosis in induced sputum and severity of asthma in children.

Methods: Eighty six children aged 6-12 years with asthma and 32 age-matched healthy controls were observed. Diagnosis of asthma was made using a clinical questionnaire, physical examination and skin prick tests (SPTs). Lung function, and induced sputum analysis were measured in all patients. Total and antigen specific IgE levels were assessesed by ELISA. Eosonophils apoptosis was determined by staining nuclei with propidium iodide, and analyzed with a FACScan. Expression Apo-1/Fas antigen (CD95) in sputum eosinophils was assessed by immunohistochemical staining techniques.

Results: Diagnosis of asthma was confirmed by positive SPT and increased total and specific IgE levels. Asthma severity (assessed by FEV1, peak expiratory flow (PEF) variability and daily symptom scores) complied with mild and moderate asthma.

The percentage sputum eosinophils was expressively increased (threshold of < 3%) in all asthmatic children (compared to control group) and directly correlated with peripheral blood eosinophilia, skin sensitization, increased level of total and specific IgE and clinical symptoms of asthma and all of these markers were more significant in children with moderate asthma (p<0.05).

Asthma children showed decreased eosinophils apoptosis (“apoptotic ratio”-AR) in induced sputum as compared to controls (p<0,001), which directly correlated with predicted value of FEV1, PEF variability and inversely with symptoms score (p=0,005), and was significantly lower in patients with moderate asthma than those in patients with mild (p=0,001).

More of that, these parameters also correlated with decreased expression of Apo-1/Fas antigen (CD95), especially in moderate asthmatic children (p<0.05).

Conclusions: Our investigation:

1. confirms that reduced eosinophil apoptosis in induced sputum associated with increased clinical severity of asthma in children
2. provides additional evidence that eosinophil apoptosis may be important in the resolution of eosinophilic airway inflammation in asthma, because of their prolonged survival that maintains inflammation.