Sputum Cellularity and MRI Ventilation Defects in Severe Asthma.
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BACKGROUND: 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. RESEARCH QUESTION: What is the effect of different sputum cellular phenotypes on abnormal ventilation evaluated by 129Xe magnetic resonance imaging (MRI) in patients with severe asthma? STUDY DESIGN AND METHODS: Eighty-five patients with severe asthma and 15 healthy controls underwent 129Xe 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. RESULTS: 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). INTERPRETATION: 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.
