Sputum Cellularity and MRI Ventilation Defects in Severe Asthma

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 4 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 to healthy control participants. Demographics, clinical characteristics, and sputum cytokine levels of patients with paucigranulocytic asthma with MRI VDP above and below the upper limit of normal were also compared. RESULTS: In patients with asthma, ventilation was abnormal (MRI VDP above the upper limit of normal) for 44% (14 of 32) of those with paucigranulocytic sputum, 64% (14 of 22) with eosinophilic bronchitis, 75% (9 of 12) with neutrophilic bronchitis, and 89% (17 of 19) with mixed-granulocytic bronchitis. Compared to healthy control participants, MRI VDP was higher in participants with asthma with eosinophilic (adjusted P = .0002), neutrophilic (adjusted P = .0001), and mixed-granulocytic phenotypes (adjusted P < .0001) but not a paucigranulocytic phenotype (adjusted P = .051). Among participants 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: Our results indicate that 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 was shown to often be associated with elevated fractional exhaled nitric oxide.