Endothelial dysfunction in autoimmune, pulmonary, and kidney systems, and exercise tolerance following SARS-CoV-2 infection.

Long COVID is characterized by persistent symptoms beyond 3-months of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection that last for at least 2 months and cannot be explained by an alternative diagnosis. Autonomic, immunologic, endothelial, and hypercoagulation are implicated as possible mechanisms of long COVID symptoms. Despite recognition of the public health challenges posed by long COVID, the current understanding of the pathophysiological underpinnings is still evolving. In this narrative review, we explore the long-term effects of SARS-CoV-2 infection on T cell activation such as autoimmune disorders and endothelial cell dysfunction involving vascular impairments within pulmonary and renal architecture. We have described how endothelial dysfunction and vascular abnormalities may underscore findings of exercise intolerance by way of impaired peripheral oxygen extraction in individuals with long COVID.

Low diffusion capacity predicts poor prognosis in extensive stage small cell lung cancer: a single-center analysis of 10 years.

BACKGROUND: Poor pulmonary function and chronic obstructive pulmonary disease (COPD) are associated with poorer overall survival (OS) in non-small-cell lung cancer (NSCLC) patients. Few studies have investigated the association between pulmonary function and OS in small-cell lung cancer (SCLC) patients. We compared the clinical characteristics of extensive disease SCLC (ED-SCLC) with or without moderately impaired diffusion capacity for carbon monoxide (DLco) and investigated the factors associated with survival in ED-SCLC patients. METHODS: This retrospective single-center study was performed between January 2011 and December 2020. Of the 307 SCLC patients who received cancer therapy during the study, 142 with ED-SCLC were analyzed. The patients were divided into DLco < 60% group and DLco ≥ 60% groups. OS and predictors of poor OS were analyzed. RESULTS: The median OS of the 142 ED-SCLC patients was 9.3 months and the median age was 68 years. In total, 129 (90.8%) patients had a history of smoking, and 60 (42.3%) had COPD. Thirty-five (24.6%) patients were assigned to the DLco < 60% group. Multivariate analysis revealed that DLco < 60% (odds ratio [OR], 1.609; 95% confidence interval [CI], 1.062-2.437; P = 0.025), number of metastases (OR, 1.488; 95% CI, 1.262-1.756; P < 0.001), and < 4 cycles of first-line chemotherapy (OR, 3.793; 95% CI, 2.530-5.686; P < 0.001) were associated with poor OS. Forty (28.2%) patients received < 4 cycles of first-line chemotherapy; the most common reason for this was death (n = 22, 55%) from grade 4 febrile neutropenia (n = 15), infection (n = 5), or massive hemoptysis (n = 2). The DLco < 60% group had a shorter median OS than the DLco ≥ 60% group (10.6 ± 0.8 vs. 4.9 ± 0.9 months, P = 0.003). CONCLUSIONS: In this study, approximately one quarter of the ED-SCLC patients had DLco < 60%. Low DLco (but not forced expiratory volume in 1 s or forced vital capacity), a large number of metastases, and < 4 cycles of first-line chemotherapy were independent risk factors for poor survival outcomes in patients with ED-SCLC.

The evaluation of DLCO changes in patients with relatively higher lung shunt fractions receiving TARE.

OBJECTIVE: Transarterial radioembolization (TARE) with Yttrium-90 (90Y) labeled microspheres is an effective locoregional treatment option for patients with primary and metastatic liver cancer. However, TARE is also associated with radiation-induced lung injury due to hepatopulmonary shunting. If a large proportion of the injected radionuclide microspheres (more than 15%) is shunted, a rare but lethal complication may develop: radiation-induced pneumonitis (RP). Diffusion capacity of the lungs for carbon monoxide (DLCO) is a valuable test to assess lung function and a decrease in DLCO may indicate an impairment in gas exchange caused by the lung injury. Some previous researches have been reported the most consistent changes in pulmonary function tests after external beam radiotherapy are recorded with DLCO. This study aimed to examine the changes in DLCO after TARE with glass microspheres in newly treated and retreated patients with relatively higher lung shunt fractions. METHODS: We prospectively analyzed forty consecutive patients with liver malignancies who underwent lobar or superselective TARE with 90Y glass microspheres. DLCO tests were performed at baseline and on days 15, 30, and 60 after the treatment. All patients were followed up clinically and radiologically for the development of RP. RESULTS: A statistically significant decrease was found in the DLCO after the first treatment (81.4 ± 13.66 vs. 75.25 ± 13.22, p = 0.003). The frequency of the patients with impaired DLCO at baseline was significantly increased after the first treatment (37.5 vs 57.5% p < 0.05). In the retreated group (n = 8), neither the DLCO (71.5 ± 10.82 vs. 67.50 ± 11.24, p = 0.115) nor the frequency of patients with impaired DLCO (25 vs 25%, p = 1) did not significantly change. Also, the change in DLCO values did not significantly correlate with lung shunt fraction, administered radiation dose, and absorbed lung dose after the first and second treatments (p > 0.05 for all). None of the patients developed RP. CONCLUSION: Our study showed that a significant reduction in DLCO after TARE may occur in patients with relatively higher lung shunt fractions. Further studies with larger sample sizes are needed to better investigate the changes in DLCO in patients with high lung shunt fractions.

The effect of selective internal radiation therapy with yttrium-90 resin microspheres on lung carbon monoxide diffusion capacity.

BACKGROUND: Selective internal radiation therapy (SIRT) with embolization of branches of the hepatic artery is a valuable therapeutic tool for patients with hepatic malignancies; however, it is also associated with lung injury risk due to shunting. Diffusion capacity of the lungs for carbon monoxide (DLCO) is a clinically significant lung function test, and worsening in DLCO is suggested to reflect a limited gas exchange reserve caused by the potential toxicity of chemoradiotherapy or it may be a marker of related lung injury. This study aimed to examine the changes in DLCO during SIRT with resin microspheres in newly treated and retreated patients. Forty consecutive patients who received SIRT for a variety of malignant conditions were included. All subjects were treated with Yttrium-90 labelled resin microspheres. DLCO tests were performed after the procedures. In addition, patients were specifically followed for radiation pneumonitis. RESULTS: The mean DLCO did not significantly change after the first (82.8 ± 19.4 vs. 83.1 ± 20.9, p = 0.921) and the second treatments (87.4 ± 19.7 vs. 88.6 ± 23.2, p = 0.256). Proportion of patients with impaired DLCO at baseline was not altered significantly after the first (37.5 vs. 45.0%, p = 0.581) and the second treatments (27.3 vs. 27.3%, p = 1.000). Also, percent change in DLCO values did not correlate with radiation dose, lung shunt fraction, or lung exposure dose (p > 0.05 for all comparisons). None of the patients developed radiation pneumonitis. CONCLUSIONS: Our results suggest that no significant change in DLCO in association with SIRT occurs, both after the first or the second treatment sessions. Further larger studies possibly with different protocols are warranted to better delineate DLCO changes after SIRT in a larger spectrum of patients.