Heterogeneity of non-cystic-fibrosis bronchiectasis in multiethnic Singapore: A prospective cohort study at a tertiary pulmonology centre.

INTRODUCTION: Non-cystic fibrosis bronchiectasis (NCFB) is a highly heterogenous disease. We describe the clinical characteristics of NCFB patients and evaluate the performance of Bronchiectasis Severity Index (BSI) in predicting mortality. METHODS: Patients attending the bronchiectasis clinic between August 2015 and April 2020 with radiologically proven bronchiectasis on computed tomography were recruited. Clinical characteristics, spirometry, radiology, microbiology and clinical course over a median period of 2.4 years is presented. RESULTS: A total of 168 patients were enrolled in this prospective cohort study. They were predominantly women (67.8%), Chinese (87.5%) and never-smokers (76.9%). Median age of diagnosis was 64 years (interquartile range 56-71) and the most common aetiology was "idiopathic" bronchiectasis (44.6%). Thirty-nine percent had normal spirometries. Compared to female patients, there were more smokers among the male patients (53.8% versus 8.5%, P<0.001) and a significantly larger proportion with post-tuberculous bronchiectasis (37.0% vs 15.8%, P=0.002). Fifty-five percent of our cohort had a history of haemoptysis. Lower body mass index, presence of chronic obstructive pulmonary disease, ever-smoker status, modified Reiff score, radiological severity and history of exacerbations were risk factors for mortality. Survival was significantly shorter in patients with severe bronchiectasis (BSI>9) compared to those with mild or moderate disease (BSI<9). The hazard ratio for severe disease (BSI>9) compared to mild disease (BSI 0-4) was 14.8 (confidence interval 1.929-114.235, P=0.01). CONCLUSION: The NCFB cohort in Singapore has unique characteristics with sex differences. Over half the patients had a history of haemoptysis. The BSI score is a useful predictor of mortality in our population.

Chronic Cough With Non-Resolving Mass-like Consolidation.

CASE PRESENTATION: A 72-year-old Chinese man presented with a 5-month history of chronic dry cough, weight loss, and progressive dyspnea. There was no associated hemoptysis, hoarseness, epistaxis, or fever on systemic review. He was a nonsmoker and had no family history of malignancy. He was treated for pulmonary TB 40 years ago. A chest radiograph (Fig 1) showed mass-like consolidation in the right midzone with loss of the right hilar border, a small right pleural effusion, and bi-apical scarring. On physical examination, he was afebrile and normotensive, and he had pulse oxygen saturation of 97%. Examination of the chest was remarkable only for reduced breath sounds over the right chest. He did not have digital clubbing, distended neck veins, or cervical lymphadenopathy.

High-risk chest radiographic features associated with COVID-19 disease severity.

OBJECTIVES: High-risk CXR features in COVID-19 are not clearly defined. We aimed to identify CXR features that correlate with severe COVID-19. METHODS: All confirmed COVID-19 patients admitted within the study period were screened. Those with suboptimal baseline CXR were excluded. CXRs were reviewed by three independent radiologists and opacities recorded according to zones and laterality. The primary endpoint was defined as hypoxia requiring supplemental oxygen, and CXR features were assessed for association with this endpoint to identify high-risk features. These features were then used to define criteria for a high-risk CXR, and clinical features and outcomes of patients with and without baseline high-risk CXR were compared using logistic regression analysis. RESULTS: 109 patients were included. In the initial analysis of 40 patients (36.7%) with abnormal baseline CXR, presence of bilateral opacities, multifocal opacities, or any upper or middle zone opacity were associated with supplemental oxygen requirement. Of the entire cohort, 29 patients (26.6%) had a baseline CXR with at least one of these features. Having a high-risk baseline CXR was significantly associated with requiring supplemental oxygen in univariate (odds ratio 14.0, 95% confidence interval 3.90-55.60) and multivariate (adjusted odds ratio 8.38, 95% CI 2.43-28.97, P = 0.001) analyses. CONCLUSION: We identified several high-risk CXR features that are significantly associated with severe illness. The association of upper or middle zone opacities with severe illness has not been previously emphasized. Recognition of these specific high-risk CXR features is important to prioritize limited healthcare resources for sicker patients.

Clinical utility of chest radiography for severe COVID-19.

BACKGROUND: Chest radiography (CXR) is performed more widely and readily than CT for the management of coronavirus disease (COVID-19), but there remains little data on its clinical utility. This study aims to assess the diagnostic performance of CXR, with emphasis on its predictive value, for severe COVID-19 disease. METHODS: A retrospective cohort study was conducted, 358 chest radiographs were performed on 109 COVID-19 patients (median age 44.4 years, 58 males and 30 with comorbidities) admitted between 22 January 2020 and 15 March 2020. Each CXR was reviewed and scored by three radiologists in consensus using a 72-point COVID-19 Radiographic Score (CRS). Disease severity was determined by the need for supplemental oxygen and mechanical ventilation. RESULTS: Patients who needed supplemental oxygen (n=19, 17.4%) were significantly older (P<0.001) and significantly more of them had co-morbidities (P=0.011). They also had higher C-reactive protein (CRP) (P<0.001), higher lactate dehydrogenase (LDH) (P<0.001), lower lymphocyte count (P<0.001) and lower hemoglobin (Hb) (P=0.001). Their initial (CRSinitial) and maximal CRS (CRSmax) were higher (P<0.001). Adjusting for age and baseline hemoglobin, the AUROC of CRSmax (0.983) was as high as CRPmax (0.987) and higher than the AUROC for lymphocyte countmin (0.897), and LDHmax (0.900). The AUROC for CRSinitial was slightly lower (0.930). CRSinitial ≥5 had a sensitivity of 63% and specificity of 92% in predicting the need for oxygen, and 73% sensitivity and 88% specificity in predicting the need for mechanical ventilation. CRS between the 6th and 10th day from the onset of symptoms (CRSD6-10) ≥5 had a sensitivity of 89% and specificity of 95% in predicting the need for oxygen, and 100% sensitivity and 86% specificity in predicting the need for mechanical ventilation. CONCLUSIONS: Adjusting for key confounders of age and baseline Hb, CRSmax performed comparable to or better than laboratory markers in the diagnosis of severe disease. CXR performed between the 6th and 10th days from symptom onset was a better predictor of severe disease than CXR performed earlier at presentation. A benign clinical course was seen in CXR that were normal or had very mild abnormalities.

A Dynamic Immune Response Shapes COVID-19 Progression.

The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis. We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for 3 to 4 weeks in all three patients. Cytokine analyses of whole blood revealed increased cytokine expression in the single most severe case. However, most inflammatory gene expression peaked after respiratory function nadir, except expression in the IL1 pathway. Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T cell activation that could exacerbate disease or prolong the infection. Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19. This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies.