Serajeddini Hana, Thakar Ashutosh, Kjarsgaard Melanie, Huang Chynna, Ragunayakam Nandhitha, Sandhu Ekamdeep, Garrido Carmen Venegas, Friedlander Yonni, Konyer Norm, Zhang Kayla, Tan Nadia Suray, Radford Katherine, Mukherjee Manali, Nair Parameswaran, Svenningsen Sarah
Firestone Institute for Respiratory Health; Department of Medicine, Division of Respirology, McMaster University, Hamilton, Ontario, Canada.
Firestone Institute for Respiratory Health; Imaging Research Centre, St Joseph's Healthcare Hamilton.
Chest. 2025 May 20. doi: 10.1016/j.chest.2025.05.013.
Airway inflammation is a hallmark feature of asthma characterized by elevated eosinophils and/or neutrophils. Eosinophils in sputum can contribute to ventilation defects. The functional consequence of other types of cellularity on ventilation is unknown.
What is the effect of different sputum cellular phenotypes on abnormal ventilation evaluated by Xe magnetic resonance imaging (MRI) in patients with severe asthma?
Eighty-five patients with severe asthma and 15 healthy controls underwent Xe ventilation MRI. Sputum cytometry was performed to evaluate airway inflammation and stratify patients with asthma into four cellular phenotypes (paucigranulocytic, eosinophilic, neutrophilic, and mixed-granulocytic). Abnormal ventilation, quantified as the post-bronchodilator MRI ventilation defect percent (VDP), was compared between asthma sputum cellular phenotypes and to healthy controls. Demographics, clinical characteristics, and sputum cytokine levels of paucigranulocytic asthmatics with MRI VDP above and below the upper limit of normal were also compared.
Ventilation was abnormal (MRI VDP above the upper limit of normal) for 44% (14 of 32) of asthmatics with paucigranulocytic sputum, 64% (14 of 22) of those with eosinophilic bronchitis, 75% (9 of 12) with neutrophilic bronchitis, and 89% (17 of 19) with mixed-granulocytic bronchitis. Compared to healthy controls, MRI VDP was higher in asthma participants with a eosinophilic (adjusted p=0.0002), neutrophilic (adjusted p=0.0001), and mixed-granulocytic phenotype (adjusted p<0.0001) but not paucigranulocytic (adjusted p=0.051). Among paucigranulocytic asthmatics, those with an MRI VDP above the upper limit of normal were older (p=0.006), had higher fractional exhaled nitric oxide (p=0.02), and higher computed tomography mucus scores (p<0.0001).
In severe asthma, ventilation is abnormal in the presence of intraluminal cellular inflammation, irrespective of phenotype. Abnormal ventilation in paucigranulocytic asthma may be due to airway mucus and is often associated with elevated fractional exhaled nitric oxide.
气道炎症是哮喘的一个标志性特征，其特点是嗜酸性粒细胞和/或中性粒细胞增多。痰液中的嗜酸性粒细胞可导致通气功能障碍。其他类型细胞成分对通气的功能影响尚不清楚。
在重度哮喘患者中，不同痰液细胞表型对通过氙磁共振成像（MRI）评估的异常通气有何影响？
85例重度哮喘患者和15名健康对照者接受了氙通气MRI检查。进行痰液细胞计数以评估气道炎症，并将哮喘患者分为四种细胞表型（少粒细胞型、嗜酸性粒细胞型、中性粒细胞型和混合粒细胞型）。比较哮喘痰液细胞表型与健康对照者之间的异常通气情况，异常通气以支气管扩张剂后MRI通气缺陷百分比（VDP）进行量化。还比较了MRI VDP高于和低于正常上限的少粒细胞型哮喘患者的人口统计学、临床特征和痰液细胞因子水平。
少粒细胞型痰液的哮喘患者中有44%（32例中的14例）通气异常（MRI VDP高于正常上限），嗜酸性粒细胞性支气管炎患者中有64%（22例中的14例），中性粒细胞性支气管炎患者中有75%（12例中的9例），混合粒细胞性支气管炎患者中有89%（19例中的17例）。与健康对照者相比，嗜酸性粒细胞型（校正p=0.0002）、中性粒细胞型（校正p=0.0001）和混合粒细胞型表型（校正p<0.0001）的哮喘参与者的MRI VDP较高，但少粒细胞型（校正p=0.051）则不然。在少粒细胞型哮喘患者中, MRI VDP高于正常上限的患者年龄较大（p=0.006），呼出一氧化氮分数较高（p=0.02），计算机断层扫描黏液评分较高（p<0.0001）。
在重度哮喘中，无论表型如何，管腔内细胞炎症存在时通气均异常。少粒细胞型哮喘的异常通气可能归因于气道黏液，且常与呼出一氧化氮分数升高有关。
