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Quantity of IgG response to SARS-CoV-2 spike glycoprotein predicts pulmonary recovery from COVID-19.
Nairz, M, Sahanic, S, Pizzini, A, Böhm, A, Tymoszuk, P, Mitterstiller, AM, von Raffay, L, Grubwieser, P, Bellmann-Weiler, R, Koppelstätter, S, et al
Scientific reports. 2022;(1):3677
Abstract
The CovILD study is a prospective, multicenter, observational cohort study to systematically follow up patients after coronavirus disease-2019 (COVID-19). We extensively evaluated 145 COVID-19 patients at 3 follow-up visits scheduled for 60, 100, and 180 days after initial confirmed diagnosis based on typical symptoms and a positive reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We employed comprehensive pulmonary function and laboratory tests, including serum concentrations of IgG against the viral spike (S) glycoprotein, and compared the results to clinical data and chest computed tomography (CT). We found that at the 60 day follow-up, 131 of 145 (90.3%) participants displayed S-specific serum IgG levels above the cut-off threshold. Notably, the highly elevated IgG levels against S glycoprotein positively correlated with biomarkers of immune activation and negatively correlated with pulmonary function and the extent of pulmonary CT abnormalities. Based on the association between serum S glycoprotein-specific IgG and clinical outcome, we generated an S-specific IgG-based recovery score that, when applied in the early convalescent phase, accurately predicted delayed pulmonary recovery after COVID-19. Therefore, we propose that S-specific IgG levels serve as a useful immunological surrogate marker for identifying at-risk individuals with persistent pulmonary injury who may require intensive follow-up care after COVID-19.
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Lung Ultrasound Findings in the Postanesthesia Care Unit Are Associated With Outcome After Major Surgery: A Prospective Observational Study in a High-Risk Cohort.
Zieleskiewicz, L, Papinko, M, Lopez, A, Baldovini, A, Fiocchi, D, Meresse, Z, Boussuges, A, Thomas, PA, Berdah, S, Creagh-Brown, B, et al
Anesthesia and analgesia. 2021;(1):172-181
Abstract
BACKGROUND Postoperative pulmonary complications are associated with increased morbidity. Identifying patients at higher risk for such complications may allow preemptive treatment. METHODS Patients with an American Society of Anesthesiologists (ASA) score >1 and who were scheduled for major surgery of >2 hours were enrolled in a single-center prospective study. After extubation, lung ultrasound was performed after a median time of 60 minutes by 2 certified anesthesiologists in the postanesthesia care unit after a standardized tracheal extubation. Postoperative pulmonary complications occurring within 8 postoperative days were recorded. The association between lung ultrasound findings and postoperative pulmonary complications was analyzed using logistic regression models. RESULTS Among the 327 patients included, 69 (19%) developed postoperative pulmonary complications. The lung ultrasound score was higher in the patients who developed postoperative pulmonary complications (12 [7-18] vs 8 [4-12]; P < .001). The odds ratio for pulmonary complications in patients who had a pleural effusion detected by lung ultrasound was 3.7 (95% confidence interval, 1.2-11.7). The hospital death rate was also higher in patients with pleural effusions (22% vs 1.3%; P < .001). Patients with pulmonary consolidations on lung ultrasound had a higher risk of postoperative mechanical ventilation (17% vs 5.1%; P = .001). In all patients, the area under the curve for predicting postoperative pulmonary complications was 0.64 (95% confidence interval, 0.57-0.71). CONCLUSIONS When lung ultrasound is performed precociously <2 hours after extubation, detection of immediate postoperative alveolar consolidation and pleural effusion by lung ultrasound is associated with postoperative pulmonary complications and morbi-mortality. Further study is needed to determine the effect of ultrasound-guided intervention for patients at high risk of postoperative pulmonary complications.
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Circulating white blood cells and lung function impairment: the observational studies and Mendelian randomization analysis.
Wu, X, Wang, C, Li, H, Meng, H, Jie, J, Fu, M, Bai, Y, Li, G, Wei, W, Feng, Y, et al
Annals of medicine. 2021;(1):1118-1128
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Abstract
BACKGROUND Circulating white blood cell (WBC) counts have been related to lung function impairment, but causal relationship was not established. We aimed to evaluate independent effects and causal relationships of WBC subtypes with lung function. METHODS The 19,159 participants from NHANES 2011-2012 (n = 3570), coke-oven workers (COW, n = 1762) and Dongfeng-Tongji (DFTJ, n = 13,827) cohorts were included in the observational studies. The associations between circulating counts of WBC subtypes and prebronchodilator lung function were evaluated by linear regression models and LASSO regression was used to select effective WBC subtypes. Summary statistics for WBC-associated SNPs were extracted from literature, and Mendelian randomization (MR) analysis with inverse-variance weighted (IVW) method was applied to estimate the causal effects of total WBC and subtypes on lung function among 4012 subjects from COW (n = 1126) and DFTJ cohorts (n = 2886). RESULTS Total WBC counts were negatively associated with lung function among three populations and their pooled analysis indicated that per 1 × 109 cells/L increase in total WBC was associated with 36.13 (95% CI: 30.35, 41.91) mL and 25.23 (95% CI: 19.97, 30.50) mL decrease in FVC and FEV1, respectively. Independent associations with lung function were found for neutrophils, monocytes, eosinophils and basophils (all p < .05), except lymphocytes. Besides, IVW MR analysis showed that genetically predicted total WBC and neutrophil counts were associated with reduced FVC (p = .017 and .021, respectively) and FEV1 (p = .048 and .043, respectively). CONCLUSIONS WBC subtypes were independently associated with lower lung function except lymphocytes. Our findings suggest that circulating neutrophils may be causal factors in lung function impairment.KEY MESSAGESWhite blood cell (WBC) subtypes were negatively associated with lung function level except lymphocytes in the observational studies.Associations of WBC subtypes with lung function may be modified by sex and smoking.Mendelian randomization analysis shows that neutrophils may be causal factors in lung function impairment.
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Characteristics and treatable traits of patients with chronic obstructive pulmonary disease (COPD) with and without paid employment.
Jacobsen, PA, van 't Hul, AJ, Djamin, RS, Antons, JC, de Man, M, Weinreich, UM, Spruit, MA, Janssen, DJA
Respiratory research. 2021;(1):147
Abstract
INTRODUCTION Patients with COPD are vulnerable to workforce detachment. Better knowledge of features associated with paid work loss might be of help to design and select appropriate interventions. METHOD This cross-sectional study aimed to explore the presence of treatable traits in COPD patients without paid work. Patients with COPD below 65 years at first referral to a hospital-based patient clinic were included. Using binary logistic regression analysis, the relationship between paid work and the following characteristics was explored: low daily physical activity, exercise, active smoking, Medical Research Council dyspnea scale (MRC), poor nutritional status, exacerbations, and fatigue (checklist individual strength (CIS)). Variables were adjusted for age, sex, forced expiratory volume in 1 s (FEV 1), and education level. RESULTS In total, 191 patients (47.3%) were without paid work. The following treatable traits were related to not being in paid work: < 5000 steps/day (OR 2.36, 95% CI (1.52-3.68)), MRC ≥ 3 (OR 1.78, 95%CI (1.14-2.77)), CIS ≥ 36 points (OR 1.78, 95% CI (1.10-2.87)), six-minute walk distance (6MWD) < 70% of predicted (OR 2.62, 95% CI (1.69-4.06)), and ≥ 2 exacerbations per year (OR 1.80, 95% CI (1.12-2.92)). Significant differences were also seen in age (OR 1.06, 95% CI (1.02-1.10) per year), FEV 1% predicted (OR 0.98, 95% CI (0.97-1.00) per % predicted increase), and medium/high education level (OR 0.62, 95% CI (0.41-0.93)). When adjusting for all variables the only treatable trait that remained significant was 6MWD. CONCLUSION Patients without paid work are more likely to have treatable traits with 6MWD revealing the most significant association.
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Lung macrophages drive mucus production and steroid-resistant inflammation in chronic bronchitis.
Andelid, K, Öst, K, Andersson, A, Mohamed, E, Jevnikar, Z, Vanfleteren, LEGW, Göransson, M
Respiratory research. 2021;(1):172
Abstract
BACKGROUND Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from chronic bronchitis (CB) and display steroid-resistant inflammation with increased sputum neutrophils and macrophages. Recently, a causal link between mucus hyper-concentration and disease progression of CB has been suggested. METHODS In this study, we have evaluated the steroid sensitivity of purified, patient-derived sputum and alveolar macrophages and used a novel mechanistic cross-talk assay to examine how macrophages and bronchial epithelial cells cross-talk to regulate MUC5B production. RESULTS We demonstrate that sputum plug macrophages isolated from COPD patients with chronic bronchitis (COPD/CB) are chronically activated and only partially respond to ex vivo corticosteroid treatment compared to alveolar macrophages isolated from lung resections. Further, we show that pseudo-stratified bronchial epithelial cells grown in air-liquid-interface are inert to direct bacterial lipopolysaccharide stimulation and that macrophages are able to relay this signal and activate the CREB/AP-1 transcription factor complex and subsequent MUC5B expression in epithelial cells through a soluble mediator. Using recombinant protein and neutralizing antibodies, we identified a key role for TNFα in this cross-talk. CONCLUSIONS For the first time, we describe ex vivo pharmacology in purified human sputum macrophages isolated from chronic bronchitis COPD patients and identify a possible basis for the steroid resistance frequently seen in this population. Our data pinpoint a critical role for chronically activated sputum macrophages in perpetuating TNFα-dependent signals driving mucus hyper-production. Targeting the chronically activated mucus plug macrophage phenotype and interfering with aberrant macrophage-epithelial cross-talk may provide a novel strategy to resolve chronic inflammatory lung disease.
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Characteristics of chronic obstructive pulmonary disease patients with robust progression of emphysematous change.
Tsutsumi, A, Chubachi, S, Irie, H, Sasaki, M, Yamada, Y, Sugiura, H, Jinzaki, M, Nakamura, H, Asano, K, Betsuyaku, T, et al
Scientific reports. 2021;(1):9548
Abstract
Emphysema is a major pathological change in chronic obstructive pulmonary disease (COPD). However, the annual changes in the progression of emphysematous have not been investigated. We aimed to determine possible baseline predicting factors of the change in emphysematous progression in a subgroup of COPD patients who demonstrated rapid progression. In this observational study, we analyzed patients with COPD who were followed up by computed tomography (CT) at least two times over a 3-year period (n = 217). We divided the annual change in the low attenuation area percentage (LAA%) into quartiles and defined a rapid progression group (n = 54) and a non-progression group (n = 163). Predictors of future changes in emphysematous progression differed from predictors of high LAA% at baseline. On multivariate logistic regression analysis, low blood eosinophilic count (odds ratio [OR], 3.22; P = 0.04) and having osteoporosis (OR, 2.13; P = 0.03) were related to rapid changes in emphysematous progression. There was no difference in baseline nutritional parameters, but nutritional parameters deteriorated in parallel with changes in emphysematous progression. Herein, we clarified the predictors of changes in emphysematous progression and concomitant deterioration of nutritional status in COPD patients.
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Frequency and functional translation of low muscle mass in overweight and obese patients with COPD.
Machado, FVC, Spruit, MA, Groenen, MTJ, Houben-Wilke, S, van Melick, PP, Hernandes, NA, Schols, AMWJ, Pitta, F, Wouters, EFM, Franssen, FME
Respiratory research. 2021;(1):93
Abstract
BACKGROUND Cut offs for fat-free mass index (FFMI) and appendicular skeletal muscle mass index (ASMI) are available for diagnosing low muscle mass in patients with COPD. This study aimed to investigate: (1) the frequency of low muscle mass (FFMI and ASMI) applying different cut-offs and (2) the functional translation (clinical impact) of low muscle mass, in patients with COPD stratified into BMI categories. METHODS Patients with COPD were assessed regarding body composition, exercise capacity, quadriceps muscle strength, symptoms of anxiety and depression, dyspnea and quality of life upon referral to pulmonary rehabilitation. The proportion of patients with low muscle mass was compared among BMI categories. Clinical outcomes between patients with normal and low muscle mass within each BMI category were compared. RESULTS 469 patients with COPD were included for analyses. The frequency of patients classified as low FFMI varied significantly according to the choice of cut-off (32 to 54%; P < 0.05), whereas the frequency of patients with low ASMI was 62%. When applying age-gender-BMI-specific cut-offs, 254 patients (54%) were classified as low FFMI. The choice of the cut-off affected the frequency of patients with low muscle mass in all BMI categories. Overweight and obese patients with low muscle mass were more frequently males and presented worse pulmonary function, exercise capacity and muscle strength compared with overweight and obese patients with normal muscle mass. CONCLUSIONS Approximately half of the overweight and obese patients with COPD have low muscle mass when applying age-gender-BMI-specific cut-offs. Low muscle mass is associated with worse functional outcomes in overweight and obese COPD patients.
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Vitamin D deficiency is associated with respiratory symptoms and airway wall thickening in smokers with and without COPD: a prospective cohort study.
Ghosh, AJ, Moll, M, Hayden, LP, Bon, J, Regan, E, Hersh, CP, ,
BMC pulmonary medicine. 2020;(1):123
Abstract
BACKGROUND Previous studies have established a higher prevalence of vitamin D deficiency in patients with COPD, but the relationship between vitamin D levels and COPD exacerbations remains controversial. In addition, the effect of vitamin D levels on imaging characteristics remains mostly unexplored. Using cross-sectional and longitudinal follow up data from the COPDGene Study, we assessed the association between vitamin D levels on respiratory symptoms, exacerbations, and imaging characteristics. We hypothesized that vitamin D deficiency will be associated with worse respiratory-related outcomes. METHODS Current and former smokers between ages 45-80 were enrolled the COPDGene Study. Subjects completed questionnaires, spirometry, six-minute walk test, and chest computed tomography scans. A subset of subjects had measurement of serum concentration of 25-hydroxyvitamin D (25(OH)D). Vitamin D deficiency was defined as serum concentration less than 20 ng/mL. Longitudinal follow up was conducted via a web-based or telephone questionnaire. RESULTS Vitamin D levels were measured on 1544 current and former smokers, of which 981 subjects had sufficient vitamin D levels and 563 subjects had vitamin D deficiency. Subjects with vitamin D deficiency were younger with increased likelihood of being African American, being current smokers, having a lower percent predicted FEV1, and having COPD. Vitamin D deficiency was associated with worse quality of life, increased dyspnea, decreased exercise tolerance, and increased frequency of severe exacerbations. Vitamin D deficiency was also associated with increased segmental airway wall thickness on chest CT scans. CONCLUSION Vitamin D deficiency was associated with increased respiratory symptoms, decreased functional status, increased frequency of severe exacerbations, as well as airway wall thickening on chest CT scans. Further research is needed to determine the potential impact of vitamin D supplementation to improve disease outcomes.
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Overweight, obesity and significant weight gain in adult patients with cystic fibrosis association with lung function and cardiometabolic risk factors.
Bonhoure, A, Boudreau, V, Litvin, M, Colomba, J, Bergeron, C, Mailhot, M, Tremblay, F, Lavoie, A, Rabasa-Lhoret, R
Clinical nutrition (Edinburgh, Scotland). 2020;(9):2910-2916
Abstract
BACKGROUND For patients with cystic fibrosis (CF), maintaining a normal BMI is associated with better pulmonary function (FEV1) and survival. Given therapy improvements, some patients are now overweight, obese or present rapid weight gain. However, the impact of being overweight on clinical outcomes (e.g. FEV1 & metabolic complications) remains unknown. METHODS Baseline data from 290 adult CF patients and observational follow-up (3.5 years; n = 158) were collected. BMI categories: underweight (UW < 18.5 kg/m2), normal (NW 18.5-26.9 kg/m2), and overweight/obese (OW ≥ 27 kg/m2). Follow-up data (weight change over time): weight loss (WL>10%), stable (WS), and weight gain (WG>10%). BMI categories and follow-up data were compared to FEV1 and cardiometabolic parameters: glucose tolerance, estimated insulin resistance (IR), blood pressure (BP), and lipid profile. RESULTS For BMI categories, 35 patients (12.1%) were UW, 235 (81.0%) NW, and 20 (6.9%) OW. Compared to UW and NW patients, OW patients are older (p < 0.001), had less pancreatic insufficiency (p = 0.009), a higher systolic BP (p = 0.004), higher LDL (p < 0.001), and higher IR (p < 0.001). Compared to UW patients, OW patients had a better FEV1 (p < 0.001). For weight change, WL was observed in 7 patients (4.4%), WS in 134 (84.8%) and WG in 17 patients (10.8%). Compared to WL and WS patients, WG patients had a 5% increase in FEV1 accompanied by higher IR (p = 0.017) and triglycerides (p < 0.001). No differences were observed for glucose tolerance for neither BMI nor weight change. CONCLUSION A higher weight or weight gain over time are associated with a better FEV1 but also some unfavorable cardiometabolic trends.
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Comparative study of lung ultrasound and chest computed tomography scan in the assessment of severity of confirmed COVID-19 pneumonia.
Zieleskiewicz, L, Markarian, T, Lopez, A, Taguet, C, Mohammedi, N, Boucekine, M, Baumstarck, K, Besch, G, Mathon, G, Duclos, G, et al
Intensive care medicine. 2020;(9):1707-1713
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PURPOSE The relationship between lung ultrasound (LUS) and chest computed tomography (CT) scans in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia is not clearly defined. The primary objective of our study was to assess the performance of LUS in determining severity of SARS-CoV-2 pneumonia compared with chest CT scan. Secondary objectives were to test the association between LUS score and location of the patient, use of mechanical ventilation, and the pulse oximetry (SpO2)/fractional inspired oxygen (FiO2) ratio. METHODS A multicentre observational study was performed between 15 March and 20 April 2020. Patients in the Emergency Department (ED) or Intensive Care Unit (ICU) with acute dyspnoea who were PCR positive for SARS-CoV-2, and who had LUS and chest CT performed within a 24-h period, were included. RESULTS One hundred patients were included. LUS score was significantly associated with pneumonia severity assessed by chest CT and clinical features. The AUC of the ROC curve of the relationship of LUS versus chest CT for the assessment of severe SARS-CoV-2 pneumonia was 0.78 (CI 95% 0.68-0.87; p < 0.0001). A high LUS score was associated with the use of mechanical ventilation, and with a SpO2/FiO2 ratio below 357. CONCLUSION In known SARS-CoV-2 pneumonia patients, the LUS score was predictive of pneumonia severity as assessed by a chest CT scan and clinical features. Within the limitations inherent to our study design, LUS can be used to assess SARS-CoV-2 pneumonia severity.