Paucigranulocytic asthma: Uncoupling of airway obstruction from inflammation.
Paucigranulocytic asthma: Uncoupling of airway obstruction from inflammation.
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DOI：
10.1016/j.jaci.2018.06.008
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发表时间：
2019-04
期刊：
影响因子：
--
通讯作者：
Panettieri RA Jr
中科院分区：
文献类型：
--
作者：
Tliba O;Panettieri RA Jr
在哮喘患者中，气道炎症模式和对治疗的反应存在异质性，这就凸显了识别特定表型的必要性。基于对诱导痰中炎症细胞计数的分析，哮喘患者可分为四种独特表型：嗜酸性粒细胞性哮喘、中性粒细胞性哮喘、混合粒细胞性哮喘和少粒细胞性哮喘（PGA）。PGA是一种哮喘表型，其痰液或血液中嗜酸性粒细胞或中性粒细胞数量并无增多迹象，而且抗炎治疗对控制症状无效。尽管研究尚不充分，但PGA却是稳定期哮喘患者中最常见的哮喘表型。然而，由于仅依赖诱导痰细胞计数（而该计数在不同研究队列中存在差异），PGA有时会被低估，因此有必要开发更完善的生物标志物。重要的是，研究人员报告称，吸入性糖皮质激素对PGA患者气道炎症标志物的作用有限，因此将PGA定义为一种潜在的 “激素不敏感” 表型，这就需要探索替代疗法。PGA表现为气道阻塞与气道炎症脱钩，这可能是由气道内结构变化（如气道平滑肌（ASM）组织肥大）所导致。动物模型表明，引发气道高反应性和ASM增厚的过程独立于炎症发生，可能是体内负向稳态调节过程缺失的结果。总体而言，进一步聚焦于动物研究中PGA的特征描述、患病率、临床意义和病理生物学，有望带来精准治疗，改善PGA的临床结局。
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 “steroidinsensitive” 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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DOI：
10.1164/ajrccm/141.5_pt_1.1327
发表时间：
1990-05-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
EBINA, M;YAEGASHI, H;TANEMURA, M
通讯作者：
TANEMURA, M
影响因子：
2.8
作者：
Braun, A;Quarcoo, D;Renz, H
通讯作者：
Renz, H
DOI：
10.1164/ajrccm/147.3.540
发表时间：
1993-03-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
CORRIGAN, CJ;HACZKU, A;KAY, AB
通讯作者：
KAY, AB
影响因子：
158.5
作者：
Cox, Gerard;Thomson, Neil C.;Olsen, M.
通讯作者：
Olsen, M.
影响因子：
3.7
作者：
Cooper PR;Mesaros AC;Zhang J;Christmas P;Stark CM;Douaidy K;Mittelman MA;Soberman RJ;Blair IA;Panettieri RA
通讯作者：
Panettieri RA