Autoimmune Responses in Severe Asthma

Asthma and autoimmune diseases both result from a dysregulated immune system, and have been conventionally considered to have mutually exclusive pathogenesis. Autoimmunity is believed to be an exaggerated Th1 response, while asthma with a Th2 underpinning is congruent with the well-accepted Th1/Th2 paradigm. The hypothesis of autoimmune involvement in asthma has received much recent interest, particularly in the adult late-onset non-atopic patients (the “intrinsic asthma”). Over the past decades, circulating autoantibodies against diverse self-targets (beta-2-adrenergic receptors, epithelial antigens, nuclear antigens, etc.) have been reported and subsequently dismissed to be epiphenomena resulting from a chronic inflammatory condition, primarily due to lack of evidence of causality/pathomechanism. Recent evidence of ‘granulomas’ in the lung biopsies of severe asthmatics, detection of pathogenic sputum autoantibodies against autologous eosinophil proteins (e.g., eosinophil peroxidase) and inadequate response to monoclonal antibody therapies (e.g., subcutaneous mepolizumab) in patients with evidence of airway autoantibodies suggest that the role of autoimmune mechanisms be revisited. In this review, we have gathered available reports of autoimmune responses in the lungs, reviewed the evidence in the context of immunogenic tissue-response and danger-associated molecular patterns, and constructed the possibility of an autoimmune-associated pathomechanism that may contribute to the severity of asthma.

Value of small airway function and sputum eosinophils number monitoring in children with cough variant asthma at remission period / 中华实用儿科临床杂志

Objective To investigate the value of small airway function and sputum eosinophils number monitoring in children with cough variant asthma at remission period.Methods Pulmonary function parameters and induced sputum samples from 52 children with cough variant asthma at remission period were collected.The indicators of small airway function included forced expiratory flow after 25％,50％ and 75％ (MEF25,MEF50 and MEF75) were recorded.Sputum eosinophils number was measured.Sixteen healthy children were taken as control group.Results Small airway function was impaired in different degrees in the children with cough variant asthma at remission period.The MEF50 of the cough variant asthma patients were much lower than that of control group (P ＜ 0.01).Compared with control group,the sputum eosinophils numbers in children with cough variant asthma at remission period were much higher (P ＜0.01).The damages of small airway function were significant in recurrent frequency ≥3 times/year than that of those ＜ 3 times/year.Children associated both with MEF50 less than 80％ and sputum eosinophils numbers ≥4％ were more easy to relapse.Conclusion Monitoring both of small airway function and sputum eosinophils number is important in children with cough variant asthma at remission period.

Cholinergics, airway eosinophils and asthma exacerbation in the elderly.

Cholinomimetic agents have a number of potential indications in an ageing population. This case series emphasises the need to exercise caution while prescribing cholinergic drugs in elderly patients with asthma, particularly in patients with a history of virus-induced exacerbations and airway eosinophilia.

A study on the relevance of eosinophil counts in induced sputum and fractional concentration of exhaled NO and lung functions in asthmatics / 中华全科医师杂志

Objective To investigate the correlations between eosinophil counts in induced sputum and lung function (FENO) and evaluate these parameters in medication adjustment in patients with asthma.Methods Sixty-five outpatients with mild to moderate persistent asthma ( mild,32 ; moderate,33 ) from January to August 2008 were enrolled in the study.All were treated with combined medications comprising inhaled corticosteroids plus long-acting β2 agonists for 1 year.Lung function (FEV1％ and PEF％ ),eosinophil counts in induced sputum,FENO,and Asthma Control Test (ACT) scores were obtained at regular follow-up intervals.Twenty-one healthy volunteers served as controls,and lung function,eosinophil counts in induced sputum,and FENO were also obtained.Results Sixty-three subjects completed 1-year or longer follow-up.Lung function of 63 subjects recovered quickly in the early days and improved slowly during the following 6 months.FENO decreased from (61 ± 25 ) nmol/L at baseline to ( 32 ± 19 ) nmol/L by the third month (q =7.32,P＜0.05) and to (22 ± 12) nmol/L by the sixth month,which showed significant difference from normal controls [ ( 13 ± 8) nmol/L; q =6.63,P ＜ 0.05 ].Eosinophil counts in induced sputum of the asthma group at baseline were (0.093 ±0.023) × 109/L and decreased to (0.032 ±0.011)× 109/L by the third month,which was significantly different from baseline and normal controls [ (0.005 ±0.003) × 106/ml; q =5.49,P ＜0.05 and q =5.87,P ＜0.05,respectively].FENO showed a significantly positive correlation with eosinophil counts in induced sputum in the first 6 months (r1 =0.612,r2 =0.558,r3 =0.675; all P＜0.05) and a negative correlation with FEV1 (r1 =-0.537,r3 =-0.658,r6 ＝ -0.623,r9 =-0.537,r12 =-0.597 ; all P ＜0.05 ) at any time point of the study.The ACT score of 63 subjects at baseline was 14 ±3,and the scores after treatment for 1,3,6,9,and 12 months were 18 ±5,19 ±7,23 ±2,24 ± 1,and 24 ± 1,respectively; at the same time,significant difference was found ( F =5.72,P ＜ 0.05).Effectiveness was found according to the ACT score only 1 month after treatment.Conclusion The parameters of FENO and eosinophil counts in induced sputum were sensitive in the detection of airway inflammation and may be useful in evaluation of the efficacy of treatment and adjustment of medication regimens.