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 MRI in patients with severe asthma? STUDY DESIGN AND METHODS: Eighty-five patients with severe asthma and 15 healthy control participants underwent 129Xe ventilation MRI. Sputum cytometry was performed to evaluate airway inflammation and to stratify patients with asthma into four cellular phenotypes (paucigranulocytic, eosinophilic, neutrophilic, and mixed-granulocytic). Abnormal ventilation, quantified as the postbronchodilator MRI ventilation defect percent (VDP), was compared between asthma sputum cellular phenotypes and with healthy control participants. Demographics, clinical characteristics, and sputum cytokine levels of patients with paucigranulocytic asthma and 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 14 of 32 patients with asthma with paucigranulocytic sputum (44%), 14 of 22 with eosinophilic bronchitis (64%), 9 of 12 with neutrophilic bronchitis (75%), and 17 of 19 with mixed-granulocytic bronchitis (89%). Compared with healthy control participants, MRI VDP was higher in participants with asthma with an eosinophilic phenotype (adjusted P = .0002), neutrophilic phenotype (adjusted P = .0001), and mixed-granulocytic phenotype (adjusted P < .0001) but not paucigranulocytic phenotype (adjusted P = .051). Among patients with paucigranulocytic asthma, those with an MRI VDP above the upper limit of normal were older (P = .006), had higher fractional exhaled nitric oxide (P = .02), and higher CT mucus scores (P < .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.
