ABSTRACT
P4 Table 1Characteristics of the subjectsCharacteristics Subjects with ILAs on LDCT (n = 39) Age, yr, mean (± SD) 68.8 (± 4.3) Gender, n (%) Female 15 (38.5) Male 24 (61.5) Smoking status, n (%) Current 7 (17.9) Ex 32 (82.1) Respiratory symptoms, n (%) None 19 (48.7) Cough 3 (7.7) Dyspnoea 9 (23.1) Cough & dyspnoea 6 (15.4) N/A 2 (5.1) Physical examination findings, n (%) None 5 (12.8) Crackles 17 (43.6) N/A 17 (43.6) Baseline lung function,%pred, median (range) FEV1,% pred 91 (58 – 130) FVC,% pred 94.8 (65 – 143) TLco,% pred 57.6 (28.4 – 98.8) Kco,% pred 79.5 (36.4 – 94) MDT Diagnosis ILAs, n (%) 8 (20.5) ILD, n (%) IPF 14 (35.9) Smoking-related ILD 6 (15.4) Hypersensitivity pneumonitis 4 (10.3) PPFE 3 (7.7) Sarcoidosis 1 (2.6) Post-COVID ILD 1 (2.6) Vasculitis 1 (2.6) Unclassifiable 1 (2.6) Treatment, n (%) Smoking cessation advice 6 (15.4) Antifibrotic 7 (17.9) Immunomodulatory treatment 2 (5.1) None 23 (59) ResultsILAs of >5% extent on LDCT were identified in 39/1853 (2.1%) subjects screened between August 2018 and April 2021 (table 1). Respiratory symptoms were present in 18/39 (46.1%) and crackles were auscultated in 17 of 22 subjects (77.3%) undergoing physical examination. Past exposure to potential environmental triggers was noted in 21/39 (53.8%). Diagnostic bronchoalveolar lavage was performed in 7/39 (17.9%) and one patient underwent transbronchial lung cryobiopsy. After MDT discussion, ILD was concluded in 31/39 (79.5%) cases, of which 14/31 (45.2%) were diagnosed with IPF. In the IPF subgroup, antifibrotics were initiated in 7/14 (50%) of cases. In those diagnosed with other ILDs, immunomodulatory treatment was initiated in 2/25 (8%) subjects.ConclusionA large proportion of individuals with newly identified ILAs have an abnormal clinical examination and respiratory symptoms, consistent with the widely held suspicion that ILD is underdiagnosed in the community. Lung cancer screening in this demographic provides a unique opportunity to address this unmet health metric. Earlier identification of ILD, specifically IPF, allows institution of antifibrotic therapies proven to modify the natural history of the disease by preserving lung function and extending life. The cost-effectiveness of this approach for ILD screening warrants detailed evaluation.
ABSTRACT
Rationale: In this study we aimed to determine whether a gene signature predictive of idiopathic pulmonary fibrosis mortality could be repurposed to predict COVID-19 severity. Methods: We analyzed expression level of 50 genes of the 52-gene signature in publically available datasets from COVID-19-Discovery (N=11), COVID-19-Validation (N=100), IPF-University of Chicago (N=45), and IPF-Imperial College London (N=55) cohorts. A COVID-19-Single cell cohort (N=7 subjects, N=145 single cells) was used to identify the cellular sources of the signature. The Scoring Algorithm of Molecular Subphenotypes (SAMS) was used to calculate Up and Down scores. Results: Up and Down Scores derived from the COVID-19-Discovery cohort were used to identify 50-gene risk profiles in the COVID-19-Validation cohort. A High-risk profile significantly predicted ICU admission (AUC: 0.78, 95%CI:0.68-0.85,P<0.0001) and mechanical ventilation (0.77, 95%CI:0.675-0.84,P<0.0001). High-risk subjects were significantly older, had higher Apache II, SOFA, Charlson Disease Severity Index, CRP, and d-dimer levels. They also had shorter ventilator-free and hospital-free days. Same COVID-19, Up and Down score cutoffs were predictive of transplant-free survival and mortality in IPF-University of Chicago (HR:4.16, 95%CI 1.3-13.28,P=0.0012) and IPF-Imperial College London (HR:4.0,95%CI 1.61-9.92,P=0.001) cohort. 50-gene expression analysis in single cells demonstrated higher proportion of CD14+ and CD16+ monocytes, red blood cells, neutrophils, and dendritic cells in high-risk subjects. Higher proportions of CD4 and CD8 T cells, natural killer, B cells, and immunoglobulin-producing plasmablasts were seen in low-risk subjects. Conclusion: 50-gene risk profiles predict ICU admission and need for mechanical ventilation in COVID-19. Single-cell analysis revealed potentially related immune responses associated with COVID-19 and IPF severity.
ABSTRACT
Rationale: The natural history of recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unknown. Because fibrosis with persistent physiological deficit is a previously described feature of patients recovering from similar coronaviruses, treatment represents an early opportunity to modify the disease course, potentially preventing irreversible impairment. Objectives: Determine the incidence of and describe the progression of persistent inflammatory interstitial lung disease (ILD) following SARS-CoV-2 when treated with prednisolone.