129Xe MRI Ventilation Defects in Asthma: What is the Upper Limit of Normal and Minimal Clinically Important Difference?

RATIONALE AND OBJECTIVES: The minimal clinically important difference (MCID) and upper limit of normal (ULN) for MRI ventilation defect percent (VDP) were previously reported for hyperpolarized 3He gas MRI. Hyperpolarized 129Xe VDP is more sensitive to airway dysfunction than 3He, therefore the objective of this study was to determine the ULN and MCID for 129Xe MRI VDP in healthy and asthma participants. MATERIALS AND METHODS: We retrospectively evaluated healthy and asthma participants who underwent spirometry and 129XeMRI on a single visit; participants with asthma completed the asthma control questionnaire (ACQ-7). The MCID was estimated using distribution- (smallest detectable difference [SDD]) and anchor-based (ACQ-7) methods. Two observers measured VDP (semiautomated k-means-cluster segmentation algorithm) in 10 participants with asthma, five-times each in random order, to determine SDD. The ULN was estimated based on the 95% confidence interval of the relationships between VDP and age. RESULTS: Mean VDP was 1.6 ± 1.2% for healthy (n = 27) and 13.7 ± 12.9% for asthma participants (n = 55). ACQ-7 and VDP were correlated (r = .37, p = .006; VDP = 3.5·ACQ + 4.9). The anchor-based MCID was 1.75% while the mean SDD and distribution-based MCID was 2.25%. VDP was correlated with age for healthy participants (p = .56, p =.003; VDP = .04·Age-.01). The ULN for all healthy participants was 2.0%. By age tertiles, the ULN was 1.3% ages 18-39 years, 2.5% for 40-59 years and 3.8% for 60-79 years. CONCLUSION: The 129Xe MRI VDP MCID was estimated in participants with asthma; the ULN was estimated in healthy participants across a range of ages, both of which provide a way to interpret VDP measurements in clinical investigations.

CT Mucus Score and 129Xe MRI Ventilation Defects After 2.5 Years' Anti-IL-5Rα in Eosinophilic Asthma.

BACKGROUND: We previously showed in patients with poorly controlled eosinophilic asthma that a single dose of benralizumab resulted in significantly improved Asthma Control Questionnaire (ACQ-6) score and 129Xe MRI ventilation defect percent (VDP) 28 days postinjection, and 129Xe MRI VDP and CT airway mucus occlusions were shown to independently predict this early ACQ-6 response to benralizumab. RESEARCH QUESTION: Do early VDP responses at 28 days persist, and do FEV1, fractional exhaled nitric oxide, and mucus plug score improve during a 2.5 year treatment period? STUDY DESIGN AND METHODS: Participants with poorly controlled eosinophilic asthma completed spirometry, ACQ-6, and MRI, 28 days, 1 year, and 2.5 years after initiation of treatment with benralizumab; chest CT was acquired at enrollment and 2.5 years later. RESULTS: Of 29 participants evaluated at 28 days post-benralizumab, 16 participants returned for follow-up while on therapy at 1 year, and 13 participants were evaluable while on therapy at 2.5 years post-benralizumab initiation. As compared with 28 days post-benralizumab, ACQ-6 score (2.0 ± 1.4) significantly improved after 1 year (0.5 ± 0.6, P = .02; 95% CI, 0.1-1.1) and 2.5 years (0.5 ± 0.5, P = .03; 95% CI, 0.1-1.1). The mean VDP change at 2.5 years (-4% ± 3%) was greater than the minimal clinically important difference, but not significantly different from VDP measured 28 days post-benralizumab. Mucus score (3 ± 4) was significantly improved at 2.5 years (1 ± 1, P = .03; 95% CI, 0.3-5.5). In six of eight participants with previous occlusions, mucus plugs vanished or substantially diminished 2.5 years later. VDP (P < .001) and mucus score (P < .001) measured at baseline, but not fractional exhaled nitric oxide or FEV1, independently predicted ACQ-6 score after 2.5 years. INTERPRETATION: In poorly controlled eosinophilic asthma, early MRI VDP responses at 28 days post-benralizumab persisted 2.5 years later, alongside significantly improved mucus scores and asthma control.

A 68-Year-Old Woman With Refractory Cough and Insidious Tracheal Thickening.

CASE PRESENTATION: A 68-year-old woman presented to a subspecialty complex-airways-disease clinic with chronic cough. She had a 10-pack-year history of smoking, quit over 35 years ago, and had mild atopy (dust mite) and mild rhinitis. She did not have any relevant occupational exposure or comorbidities. Her cough was relentless day and night, associated with incontinence, vomiting, and social and functional impairment. It had been present for years, though it changed in nature over time. She also reported one to two episodes of streaky hemoptysis. She had not noticed significant benefit with nasal or inhaled corticosteroids, but short bursts of prednisone had temporarily modestly improved her cough.

Pulmonary Functional MRI and CT in a Survivor of Bronchiolitis and Respiratory Failure Caused by e-Cigarette Use.

Although nearly 3,000 e-cigarette-related hospitalizations have been reported in North America, the long-term outcomes in these patients have not been described. We followed an 18-year-old boy who survived acute critical illness and respiratory failure related to 5 months of e-cigarette use. Chronic irreversible airflow obstruction and markedly abnormal 129Xe MRI ventilation heterogeneity was observed and persisted 8 months after hospital discharge, despite improvement in quality-of-life and chest CT findings. Lung clearance index and oscillometry measures were also highly abnormal at 8 months postdischarge. Although 129Xe MRI ventilation abnormalities were dominant in the lung apices and central lung regions, the pattern of ventilation defects was dissimilar to ventilation heterogeneity observed in patients with obstructive lung disease, such as asthma and COPD. Our findings underscore the long-term functional impacts of e-cigarette-related lung injury in survivors of critical illness; longitudinal evaluations may shed light on the pathophysiologic mechanisms that drive e-cigarette-related lung disease.

Multi-dimensional Assessment of IPF Across a Wide Range of Disease Severity.

PURPOSE: The pathophysiology of idiopathic pulmonary fibrosis (IPF) is complex, and its clinical course is difficult to predict. Perceived dyspnea, exercise capacity, and lung physiology have all been associated with mortality outcomes in IPF, but the significance of these relationships is unclear. We sought to investigate the correlation among these variables and their independent predictive capability in determining mortality outcomes. METHODS: Four-hundred-thirty-seven patients diagnosed with IPF from three independent centers were included in the study. Medical Research Council Dyspnea Score (MRCDS), 6-min walk distance (6MWD), and pulmonary function tests were determined at baseline. The end-point was 18-month transplant-free survival. RESULTS: Correlations between MRCDS, 6MWD, forced vital capacity (FVC), and diffusing lung capacity for carbon monoxide were either very weak or weak. Calculation of variance inflation factors demonstrated absence of collinearity among these variables. Univariate regression analysis and c-statistics identified MRCDS, 6MWD, and FVC as significant predictors of 18-month transplant-free survival. Multivariate regression analysis retained MRCDS, 6MWD, and FVC as independent predictors of mortality. To ensure generalizability, we confirmed the results in subgroups of patients stratified according to baseline FVC, and further by considering lung transplant as a competing event to death. CONCLUSIONS: In a cohort of patients with IPF encompassing a wide range of disease severity, baseline perceived exertional dyspnea, exercise capacity, and lung function are weakly correlated to each other, translating in the absence of collinearity. MRCDS, 6MWD, and FVC are significant and independent predictors of outcome, suggesting that a multi-dimensional assessment of IPF is prognostically appropriate and advantageous.