寡细胞型哮喘:气道阻塞与炎症的解偶联

2018/07/09

   摘要
   在哮喘患者中,气道炎症和治疗反应存在异质性,这促使人们意识到识别特定表型的必要性。基于诱导痰炎症细胞计数的分析,哮喘患者可分为四种表型:嗜酸性粒细胞型哮喘,嗜中性粒细胞型哮喘,混合粒细胞型哮喘和寡细胞型哮喘(PGA)。PGA是一种哮喘表型,表现为无痰液或血液中嗜酸性粒细胞或嗜中性粒细胞数量增加,并且抗炎治疗无法有效控制症状。尽管尚无充分的调查研究,PGA是稳定期哮喘患者最常见的哮喘表型。然而,PGA有时被低估是由于其仅依赖于诱导痰细胞计数,而在队列研究中诱导痰细胞计数是可变的,这促进了改进生物标志物的必要性。重要的是,研究报导吸入糖皮质激素对PGA患者的气道炎症标志物的作用有限,因此PGA可能是一种潜在的“类固醇不敏感”表型,需要探索其他治疗方法。PGA表现为由气道内结构改变如气道平滑肌(ASM)组织肥大等因素造成的呼吸道阻塞与气道内炎症的解偶联。动物模型提供的证据表明,引起气道高反应性和ASM增厚的过程独立于炎症发生,可能是负稳态过程消失的结果。总的来说,进一步了解PGA,重点关注疾病特征,患病率,临床意义和动物研究中的病理生物学,可能会提供精准的治疗方法,从而改善PGA临床结局。



(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2018 Jun 18. pii: S0091-6749(18)30861-3. )
 
 
Paucigranulocytic asthma: The uncoupling of airway obstruction from inflammation.

Tliba O, Panettieri RA.

Abstract
Among patients with asthma, heterogeneity exists regarding the pattern of airway inflammation and response to treatment, prompting the necessity of recognizing specific phenotypes. Based on the analysis of inflammatory cell count in induced sputum, patients with asthma can be classified in four unique phenotypes; eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma (PGA). PGA is an asthma phenotype with no evidence of elevated numbers of eosinophils or neutrophils in sputum or blood, and in which anti-inflammatory therapies are ineffective in controlling symptoms. While under-investigated, PGA is the most common asthma phenotype in patients with stable asthma. However, PGA is sometimes underestimated due to the exclusive reliance on induced sputum cell count which is variable among cohorts of studies prompting the necessity of developing improved biomarkers. Importantly, investigators have reported that inhaled corticosteroids had limited effect on airway inflammatory markers in patients with PGA defining, therefore, PGA as a potentially "steroid-insensitive" phenotype that requires exploration of alternative therapies. PGA manifests as an uncoupling of airway obstruction from airway inflammation that can be driven by structural changes within the airways such as airway smooth muscle (ASM) tissue hypertrophy. Animal models provide evidence that processes evoking airway hyperresponsiveness and ASM thickening occur independent from inflammation and may be a consequence of a loss of negative homeostatic processes. Collectively, further understanding of PGA with focus on the characterization, prevalence, clinical significance and pathobiology derived from animal studies will likely provide precision therapies that will improve PGA clinical outcomes.


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