Alveolar membrane and capillary function in COVID-19 convalescents: insights from chest MRI.

OBJECTIVES: To investigate potential presence and resolution of longer-term pulmonary diffusion limitation and microvascular perfusion impairment in COVID-19 convalescents. MATERIALS AND METHODS: This prospective, longitudinal study was carried out between May 2020 and April 2023. COVID-19 convalescents repeatedly and age/sex-matched healthy controls once underwent MRI including hyperpolarized 129Xe MRI. Blood samples were obtained in COVID-19 convalescents for immunophenotyping. Ratios of 129Xe in red blood cells (RBC), tissue/plasma (TP), and gas phase (GP) as well as lung surface-volume ratio were quantified and correlations with CD4+/CD8+ T cell frequencies were assessed using Pearson's correlation coefficient. Signed-rank tests were used for longitudinal and U tests for group comparisons. RESULTS: Thirty-five participants were recruited. Twenty-three COVID-19 convalescents (age 52.1 ± 19.4 years, 13 men) underwent baseline MRI 12.6 ± 4.2 weeks after symptom onset. Fourteen COVID-19 convalescents underwent follow-up MRI and 12 were included for longitudinal comparison (baseline MRI at 11.5 ± 2.7 weeks and follow-up 38.0 ± 5.5 weeks). Twelve matched controls were included for comparison. In COVID-19 convalescents, RBC-TP was increased at follow-up (p = 0.04). Baseline RBC-TP was lower in patients treated on intensive care unit (p = 0.03) and in patients with severe/critical disease (p = 0.006). RBC-TP correlated with CD4+/CD8+ T cell frequencies (R = 0.61/ - 0.60) at baseline. RBC-TP was not significantly different compared to matched controls at follow-up (p = 0.25). CONCLUSION: Impaired microvascular pulmonary perfusion and alveolar membrane function persisted 12 weeks after symptom onset and resolved within 38 weeks after COVID-19 symptom onset. CLINICAL RELEVANCE STATEMENT: 129Xe MRI shows improvement of microvascular pulmonary perfusion and alveolar membrane function between 11.5 ± 2.7 weeks and 38.0 ± 5.5 weeks after symptom onset in patients after COVID-19, returning to normal in subjects without significant prior disease. KEY POINTS: • The study aims to investigate long-term effects of COVID-19 on lung function, in particular gas uptake efficiency, and on the cardiovascular system. • In COVID-19 convalescents, the ratio of 129Xe in red blood cells/tissue plasma increased longitudinally (p = 0.04), but was not different from matched controls at follow-up (p = 0.25). • Microvascular pulmonary perfusion and alveolar membrane function are impaired 11.5 weeks after symptom onset in patients after COVID-19, returning to normal in subjects without significant prior disease at 38.0 weeks.

Effect of CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor on pulmonary ventilation derived by 3D phase-resolved functional lung MRI in cystic fibrosis patients.

OBJECTIVES: To investigate whether 3D phase-resolved functional lung (PREFUL)-MRI parameters are suitable to measure response to elexacaftor/tezacaftor/ivacaftor (ETI) therapy and their association with clinical outcomes in cystic fibrosis (CF) patients. METHODS: Twenty-three patients with CF (mean age: 21; age range: 14-46) underwent MRI examination at baseline and 8-16 weeks after initiation of ETI. Morphological and 3D PREFUL scans assessed pulmonary ventilation. Morphological images were evaluated using a semi-quantitative scoring system, and 3D PREFUL scans were evaluated by ventilation defect percentage (VDP) values derived from regional ventilation (RVent) and cross-correlation maps. Improved ventilation volume (IVV) normalized to body surface area (BSA) between baseline and post-treatment visit was computed. Forced expiratory volume in 1 second (FEV1) and mid-expiratory flow at 25% of forced vital capacity (MEF25), as well as lung clearance index (LCI), were assessed. Treatment effects were analyzed using paired Wilcoxon signed-rank tests. Treatment changes and post-treatment agreement between 3D PREFUL and clinical parameters were evaluated by Spearman's correlation. RESULTS: After ETI therapy, all 3D PREFUL ventilation markers (all p < 0.0056) improved significantly, except for the mean RVent parameter. The BSA normalized IVVRVent was significantly correlated to relative treatment changes of MEF25 and mucus plugging score (all |r| > 0.48, all p < 0.0219). In post-treatment analyses, 3D PREFUL VDP values significantly correlated with spirometry, LCI, MRI global, morphology, and perfusion scores (all |r| > 0.44, all p < 0.0348). CONCLUSIONS: 3D PREFUL MRI is a very promising tool to monitor CFTR modulator-induced regional dynamic ventilation changes in CF patients. CLINICAL RELEVANCE STATEMENT: 3D PREFUL MRI is sensitive to monitor CFTR modulator-induced regional ventilation changes in CF patients. Improved ventilation volume correlates with the relative change of mucus plugging, suggesting that reduced endobronchial mucus is predominantly responsible for regional ventilation improvement. KEY POINTS: • 3D PREFUL MRI-derived ventilation maps show significantly reduced ventilation defects in CF patients after ETI therapy. • Significant post-treatment correlations of 3D PREFUL ventilation measures especially with LCI, FEV1 %pred, and global MRI score suggest that 3D PREFUL MRI is sensitive to measure improved regional ventilation of the lung parenchyma due to reduced inflammation induced by ETI therapy in CF patients. • 3D PREFUL MRI-derived improved ventilation volume (IVV) correlated with MRI mucus plugging score changes suggesting that reduced endobronchial mucus is predominantly responsible for regional ventilation improvement 8-16 weeks after ETI therapy.

Phase-resolved Functional Lung (PREFUL) MRI-derived Ventilation and Perfusion Parameters Predict Future Lung Transplant Loss.

Background Chronic lung allograft dysfunction (CLAD), the physiologic correlate of chronic rejection, remains a major barrier to long-term survival following lung transplant. Biomarkers for early prediction of future transplant loss or death due to CLAD might open a window of opportunity for early diagnosis and treatment of CLAD. Purpose To evaluate the prognostic use of phase-resolved functional lung (PREFUL) MRI in predicting CLAD-related transplant loss or death. Materials and Methods In this prospective, longitudinal, single-center study, PREFUL MRI-derived ventilation and parenchymal lung perfusion parameters of bilateral lung transplant recipients without clinically suspected CLAD were assessed 6-12 months (baseline) and 2.5 years (follow-up) after transplant. MRI scans were acquired between August 2013 and December 2018. Regional flow volume loop (RFVL)-based ventilated volume (VV) and perfused volume were calculated using thresholds and spatially combined as ventilation-perfusion (V/Q) matching. Spirometry data were obtained on the same day. Exploratory models were calculated using receiver operating characteristic analysis, and subsequent survival analyses (Kaplan-Meier, hazard ratios [HRs]) of CLAD-related graft loss were performed to compare clinical and MRI parameters as clinical end points. Results At baseline MRI examination, 132 clinically stable patients of 141 patients (median age, 53 years [IQR, 43-59 years]; 78 men) were included (nine were excluded for deaths not associated with CLAD), 24 of which had CLAD-related graft loss (death or retransplant) within the observational period of 5.6 years. PREFUL MRI-derived RFVL VV was a predictor of poorer survival (cutoff, 92.3%; log-rank P = .02; HR for graft loss, 2.5 [95% CI: 1.1, 5.7]; P = .02), while perfused volume (P = .12) and spirometry (P = .33) were not predictive of differences in survival. In the evaluation of percentage change at follow-up MRI (92 stable patients vs 11 with CLAD-related graft loss), mean RFVL (cutoff, 97.1%; log-rank P < .001; HR, 7.7 [95% CI: 2.3, 25.3]), V/Q defect (cutoff, 498%; log-rank P = .003; HR, 6.6 [95% CI: 1.7, 25.0]), and forced expiratory volume in the first second of expiration (cutoff, 60.8%; log-rank P < .001; HR, 7.9 [95% CI: 2.3, 27.4]; P = .001) were predictive of poorer survival within 2.7 years (IQR, 2.2-3.5 years) after follow-up MRI. Conclusion Phase-resolved functional lung MRI ventilation-perfusion matching parameters were predictive of future chronic lung allograft dysfunction-related death or transplant loss in a large prospective cohort who had undergone lung transplant. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Fain and Schiebler in this issue.

Treatment with interleukin (IL)-5/IL-5 receptor antibodies in patients with severe eosinophilic asthma and COPD.

Background: Anti-eosinophilic therapy with interleukin-5/interleukin-5-receptor antibodies represents an established treatment for patients with severe eosinophilic asthma (SEA) but did not show clinical efficacy in patients with COPD. The objective of the present study was to evaluate treatment response to anti-eosinophilic antibody therapy in patients with asthma and COPD. Methods: A retrospective comparison of pulmonary function testing, oral corticosteroid intake, quality of life and pulmonary symptom control in patients with SEA and COPD and 1:1 propensity score matched patients suffering from SEA alone was performed. All patients received treatment with either mepolizumab or benralizumab. Data were assessed prior to antibody treatment start and after 6 months of therapy. Results: Data from 84 patients (42 patients with SEA and COPD and 42 patients with SEA) were analysed. After 6 months of treatment, patients in both groups showed improved forced expiratory volume in 1 s (improvement by 11% (IQR 5-18) in the SEA and COPD group versus 15% (IQR -3-23); p=0.637) and decreased oral corticosteroid dosages (median reduction by 3 mg in the SEA and COPD group versus 5 mg; p=0.070), without significant differences between groups. Pulmonary symptom control and quality of life improved in both groups. A significant decrease in eosinophils could be measured in both groups with similar cell numbers prior to treatment initiation (600 cells·µL-1 in the SEA and COPD group versus 500 cells·µL-1). Conclusion: Anti-eosinophilic therapy with interleukin-5/interleukin-5-receptor antibodies shows clinical efficacy in patients with SEA and COPD comparable to treatment response in patients with SEA alone.

Association of radiological lung pattern and respiratory mechanics with potential for lung recruitment in patients with COVID-ARDS: a retrospective cohort study.

BACKGROUND: The ventilatory management of COVID-ARDS is controversial, especially with regard to the different subtypes and associated PEEP titration. A higher PEEP may be beneficial only in patients with potential for lung recruitment. The assessment of lung recruitment may be guided by lung imaging, such as electric impedance tomography or recruitment computed tomography, but is complex and not established in routine clinical practice. Therefore, bedside identification of recruitable ARDS phenotypes can aid in PEEP titration in clinical settings. METHODS: In this retrospective consecutive cohort study in 40 patients with moderate-to-severe COVID-ARDS, we assessed lung recruitment using the recruitment-to-inflation ratio (R/I) in moderate-to-severe COVID-ARDS. Evidence of recruitment (R/I ≥ 0.5) was compared between clinical and computed tomography data. RESULTS: Of the included patients, 28 (70%) were classified as recruiters by the R/I. Lung recruitment was associated with higher compliance and was not associated with a consolidated lung pattern assessed using CT. Even in the tertile of patients with the highest compliance (37-70 ml/mbar), eight (73%) patients were classified as recruitable. Patients classified as recruitable presented a lower reticular lung pattern (2% vs. 6%, p = 0.032). CONCLUSIONS: Prediction of lung recruitment is difficult based on routine clinical data but may be improved by assessment of radiographic lung patterns. A bedside assessment of recruitment is necessary to guide clinical care. Even a high compliance may not rule out the potential for lung recruitment.