Diffusing Capacity Of Lung Research Articles

Predictive factors for interstitial lung disease progression in a Singapore systemic sclerosis cohort: a multicentre study.

Interstitial lung disease (ILD) in systemic sclerosis (SSc) is heterogeneous with varied progression rate. This study aimed to identify the baseline clinical characteristics associated with ILD progression within 1, 3 and 5 years of the diagnosis of ILD. This was a prospective, multicentre study - Systematic Sclerosis Cohort Singapore - conducted from January 2008 to February 2021, which included SSc patients with ILD diagnosed by high-resolution computed tomography. Progression of ILD was defined by forced vital capacity (FVC) decline ≥10% predicted or FVC decline 5%-9% predicted, with diffusing lung capacity of carbon monoxide decline ≥15% from the time of ILD diagnosis. Multivariable logistic and Cox regression analyses, adjusting for malignancy and treatment, were performed to determine independent risk factors of ILD progression. Of 124 SSc patients with ILD, 47.6% had limited cutaneous SSc, 33.9% had diffuse SSc and 18.5% had SSc-overlap. Progression of ILD was seen in 6%, 15% and 23% of patients within 1, 3 and 5 years, respectively. After adjusting for malignancy and treatment, anti-La was associated with ILD progression within 1 year (odds ratio [OR] 6.94, 95% confidence interval [CI]: 1.14-42.2; P = 0.04) and 3 years (OR 5.98, 95% CI: 1.31-27.4; P = 0.02), and anti-Scl-70 was associated with ILD progression within 5 years (OR 2.54, 95% CI: 1.05-6.12; P = 0.04). Analysing time to ILD progression as an outcome, anti-La was significantly associated with higher risk of ILD progression (hazard ratio 3.47, 95% CI: 1.18-10.2; P = 0.02). Time to ILD progression was 1.4 years in patients with anti-La versus 6.9 years in patients without anti-La (P = 0.02), and 4.7 years in patients with anti-Scl-70 versus 8.9 years in patients without anti-Scl-70 (P = 0.12). In this Asian cohort of SSc patients, autoantibodies may help to predict ILD progression rates.

A decision rule for identifying patients at high risk for impaired lung diffusion capacity after COVID-19

Aim. To elaborate a decision rule for identifying the main predictors of impaired lung diffusion capacity after COVID-19. Materials and methods. The retrospective study included 341 patients without underlying lung diseases (median age 48 years) who experienced COVID-19 with bilateral pneumonia. The median extent of parenchymal lesion in the acute phase of COVID-19 (CTmax) was 50%. Spirometry, body plethysmography, and lung diffusion capacity for carbon monoxide (DLCO) test were performed. The data were analyzed by descriptive statistics, correlation analysis, one-dimensional logistic regression analysis with an assessment of odds ratios (OR), and multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to assess the quality of the binary classifier model.Results. The initial model for predicting reduced DLCO (< 80% of predicted) included the following predictors: CTmax, time interval from the COVID-19 onset, gender, age, body mass index. Backward stepwise regression was applied, and a binary classifier model that includes CTmax was obtained. The sensitivity and specificity of the model for the training sample were 80 and 67%, respectively, for the test sample – 79 and 70%, respectively. The analysis of OR showed that OR > 1 was observed at СTmax > 40%.Conclusion. The decision rule was obtained for predicting impaired lung diffusion capacity after COVID-19 with virus-associated lung damage in patients without underlying bronchopulmonary diseases. Patients with CTmax > 40% require more thorough clinical follow-up with DLCO monitoring after the acute phase of COVID-19

Endothelial function in patients after severe or critical acute phase of COVID-19 one year after the disease onset

BACKGROUND. The SARS-CoV-2 virus not only causes respiratory diseases but also significantly impacts endothelial function, which may be one of the mechanisms for developing long-term consequences of coronavirus disease (COVID-19). OBJECTIVE. To determine the levels of endothelial function markers (endothelin-1, thrombomodulin) in the peripheral blood of individuals who experienced non-hospital pneumonia on the background of COVID-19, in the early post-acute phase and one year after the onset of the disease, and to analyze the changes in individual levels of these markers. MATERIALS AND METHODS. The main group consisted of 16 individuals (age – 57.5 (43.8; 64.5) years, 8 (50.0 %) men, 7 (50.0 %) women), who were examined twice: at visit 1 – on day 60.0 (56.3; 62.5) from the onset of the disease; at visit 2 – on day 312.5 (300.0; 365.0) from the onset of the disease. The control group consisted of 10 individuals (age – 58.5 (39.5; 67.8) years, 4 (40.0 %) men, 6 (60.0 %) women). General clinical and laboratory methods were used, as well as an assessment of lung diffusion capacity (DLсо). RESULTS. At visit 1, the clinical status of 16 (100.0 %) individuals in the main group was impaired. At visit 2, the clinical status of 12 (75.0 %) individuals normalized, while 4 (25.0 %) individuals showed improvement; the severity of dyspnea according to the mMRC scale and heart rate decreased, and SpO2 and DLсо levels increased (p<0.01, p<0.01, p<0.01, and p=0.03, respectively). The level of endothelin-1 in the control group was 14.6 (11.7; 17.0) pg/ml, and the thrombomodulin level was 451.7 (403.9; 652.4) pg/ml. The level of endothelin-1 at visit 1 in the main group was 11.1 (6.8; 15.9) pg/ml, and at visit 2 – 14.4 (11.2; 20.0) pg/ml (p=0.02), not differing from the control group (p=0.48 and p=0.61, respectively). The level of thrombomodulin at visit 1 in the main group was 723.1 (689.1; 1012.2) pg/ml, and at visit 2 – 811.5 (713.3; 911.7) pg/ml (p=0.40), which was higher than in the control group (p=0.01 and p=0.01, respectively). CONCLUSIONS. One year after COVID-19, most individuals show normalization of clinical status and improvement in lung diffusion capacity; however, elevated thrombomodulin levels persist, which requires further investigation. In some patients, the level of endothelin-1 also increases, which is why they should be monitored not only by a family doctor or a pulmonologist but also by a cardiologist.

Association between Left Atrial Function and Survival in Systemic Sclerosis.

Systemic sclerosis (SSc) is a multisystemic autoimmune disorder in which cardiac involvement is frequent and portends negative prognosis. Left ventricular (LV) diastolic dysfunction is one of the most common cardiac alterations in these patients, and left atrial (LA) reservoir strain (ƐR) measurement using speckle tracking echocardiography has been proposed as a novel parameter for a better assessment of LV diastolic function. Therefore, the aim of this study was to test the prognostic value of ƐR in a large multicenter cohort of SSc patients. In total, 311 SSc patients (54 ± 14 years, 85% female) were included from two different centers. Echocardiography was performed at the time of first visit, including ƐR measurement. Over a median follow-up of 132 (interquartile range: 110 to 157) months, 67 (21.5%) patients experienced the outcome of all-cause mortality. Spline curve analysis identified an optimal cut-off value of 30% for ƐR, and patients with ƐR ≤ 30% showed a 10-year cumulative survival rate of 71% as compared to 88% for patients with ƐR > 30% (log-rank p < 0.001). At the multivariable Cox regression analysis, ƐR was independently associated with the endpoint (HR 1.830; 95% confidence interval (CI) 1.031-3.246; p = 0.039) together with age (HR 1.071, 95% CI 1.043 to 1.099; p < 0.001), sex (female) (HR 0.444, 95% CI 0.229 to 0.861; p = 0.016), and diffusing lung capacity for carbon monoxide (HR 0.969 95% CI 0.956 to 0.982; p < 0.001). ƐR is of independent prognostic value in SSc and might help optimizing risk stratification in these patients.

CXCL10 predicts autoimmune features and a favorable clinical course in patients with IIP: post hoc analysis of a prospective and multicenter cohort study

BackgroundInterstitial pneumonia with autoimmune features (IPAF), which does not meet any of the criteria for connective tissue diseases (CTD), has been attracting an attention in patients with idiopathic interstitial pneumonia (IIP). However, the biomarkers that reflect the clinical course of these patients have not been fully elucidated.ObjectiveTo identify useful serum biomarkers reflecting CTD-related features and favorable prognoses in patients with IIP.MethodsThis was a post hoc analysis of a prospective and multicenter cohort study between 2015 and 2020. Newly diagnosed patients with IIP were consecutively enrolled, and 74 autoimmune features and autoantibodies were comprehensively checked during IIP diagnosis. Serum levels of CXCL10, CXCL1, CCL2, BAFF, angiopoietin-2, and leptin were evaluated at the time of IIP diagnosis.ResultsTwo hundred twenty-two patients (159 men and 63 women) with IIP were enrolled. The median observation duration was 36 months. The median age was 71 years old, and median %forced vital capacity (FVC) was 84.1% at the time of IIP diagnosis. The proportion of patients who met the classification criteria for IPAF was 11.7%. In patients with high serum CXCL10, changes in both %FVC and %diffusion lung capacity for carbon monoxide at one year were significantly higher than those in patients with low CXCL10 (p = 0.014 and p = 0.009, respectively), whereas these changes were not significant for other chemokines and cytokines. High CXCL10 levels were associated with acute/subacute onset (p < 0.001) and the diagnosis of nonspecific interstitial pneumonia with organizing pneumonia overlap (p = 0.003). High CXCL10 levels were related to a higher classification of IPAF (relative risk for IPAF was 3.320, 95%CI: 1.571–7.019, p = 0.003) and lower classification of progressive pulmonary fibrosis (PPF; relative risk for PPF was 0.309, 95%CI: 0.100-0.953, p = 0.027) compared to those with low CXCL10. Finally, survival was higher in patients with IPF and high CXCL10 (p = 0.044), and high CXCL10 was a significant prognostic factor in multivariate Cox proportional hazards models (hazard ratio 0.368, p = 0.005).ConclusionsHigh serum levels of CXCL10 are associated with CTD-related features, the favorable clinical course, and survival in patients with IIP, especially IPF.Clinical trial numberNot applicable.

Correlation of serum Krebs von den Lungen-6 levels with fibrosis score on high resolution chest tomography and pulmonary function parameters in treatment naïve Idiopathic Pulmonary Fibrosis.

While serum Krebs von den Lungen-6 (KL-6) has been found to be a helpful biomarker in interstitial lung diseases for evaluating disease severity and progression, especially in connective tissue disease-associated interstitial lung disease (CTD ILD) and idiopathic non-specific interstitial pneumonia (NSIP), data on correlation of serum KL-6 levels with radiological fibrosis and pulmonary function parameters is lacking in treatment naïve Idiopathic Pulmonary Fibrosis (IPF) patients. Serum KL-6 levels were measured in thirty-nine treatment naïve newly detected IPF patients using automated immunofluorescence enzyme assay (AIA) by Tosoh Corporation, bioscience division, Tokyo, Japan. Fibrosis score was calculated by independent visual assessment of the pattern and severity of abnormalities on high resolution computed tomography (HRCT) thorax. HRCT fibrosis scores were correlated with serum KL-6 levels and pulmonary function parameters like forced vital capacity (FVC), diffusion capacity of lung for carbon monoxide (DLco). Median value of serum KL-6 levels was 1519 U/ml (range 199.41-6055 U/ml). There was positive correlation of serum KL-6 with HRCT fibrosis score (r=0.692, p<0.001) and negative correlation with FVC (r=-0.511, p=0.001) and DLco (r=-0.354, p=0.043). In the HRCT fibrosis score pattern subset analysis, the presence of reticulation revealed weak negative and statistically insignificant correlation (r=-0.116, p=0.481) while traction bronchiectasis and honeycombing exhibited statistically significant positive correlation (r=0.425, p=0.007; r=0.584, p<0.001 respectively) with serum KL-6 levels. Serum KL-6 levels showed a positive correlation with the degree of fibrotic abnormalities on HRCT thorax and pulmonary function parameters, indicating a potential use of serum KL-6 in monitoring of parenchymal fibrosis in Idiopathic Pulmonary fibrosis.

SARS-CoV-2 infection induces hyaluronan production in vitro and hyaluronan levels in COVID-19 patients relate to morbidity and long-term lung impairment: a prospective cohort study.

We previously demonstrated that the lungs of deceased COVID-19 patients were filled with a clear hydrogel consisting of hyaluronan (HA). In this translational study, we investigated the role of HA at all stages of COVID-19 disease to map the consequences of elevated HA on morbidity and identify the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced HA production. A reduced alveolar surface area was observed in the lungs of deceased COVID-19 patients compared to healthy controls, as visualized by a 3D rendering of lung morphology using light-sheet fluorescence microscopy. We confirmed the presence of HA in lung biopsies and found large quantities of proinflammatory fragmented HA. The association of systemic HA in blood plasma and disease severity was assessed in patients with mild (WHO Clinical Progression Scale, WHO-CPS, 1-5) and severe COVID-19 (WHO-CPS, 6-9) during the acute and convalescent phases and related to lung function. We found that systemic levels of HA were high during acute COVID-19 disease, remained elevated during convalescence, and were associated with a reduced diffusion capacity. In vitro 3D-lung models, differentiated from primary human bronchial epithelial cells, were used to study the effects of SARS-CoV-2 infection on HA metabolism, and transcriptomic analyses revealed a dysregulation of HA synthases and hyaluronidases, both contributing to increased HA in apical secretions. Furthermore, corticosteroid treatment reduced the inflammation and downregulated HA synthases. Our findings demonstrate that HA plays a role in COVID-19 morbidity and that sustained elevated HA concentrations may contribute to long-term respiratory impairment.IMPORTANCEThis study provides insights into the role of hyaluronan (HA) in the severity and long-term impact of COVID-19 on lung function. Through extensive morphological examination of lung tissues and a multicenter study, we identified that HA levels are significantly elevated in COVID-19 patients, correlating with a reduced lung diffusion capacity during convalescence. Using a 3D-lung model, we further uncovered how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 infection causes a dysregulated HA metabolism, leading to increased HA production. Our findings provide valuable insights into the pathogenesis of SARS-CoV-2 and suggest that targeting HA metabolism could offer new therapeutic avenues for managing COVID-19, particularly to prevent long-term lung impairment. Additionally, HA holds potential as a biomarker for predicting disease severity, which could guide personalized treatment strategies.

Lung function in patients with asthma in the post-COVID period

Aim. To assess the lung function in patients with bronchial asthma (BA) after new-onset coronavirus infection.Materials and methods. Fifty-five patients who underwent COVID-19 participated in the study under conditions of voluntary informed consent. The main group consisted of 30 patients with mild BA, the comparison group – 25 patients without chronic respiratory diseases (CRD). According to chest computed tomography (CT) findings, the degree of lung parenchyma involvement was classified as follows: mild COVID-19 (CT 0 stage) in 14 patients; moderate COVID-19 (CT 1-2 stages) in 27 patients; and severe COVID-19 (CT 3-4 stages) in 14 patients. Lung function tests were conducted once, adhering to both Russian and international standards.Results. In patients with BA, obstructive pulmonary function impairment was predominant at CT 1-2 stages (79%), CT 0 stage (67%), and CT 3-4 stages (43%). Lung diffusion capacity (LDC) was impaired predominantly in CT 3-4 stages in both BA patients and those without CRD, occurring in 57% of cases. Analysis of lung function showed that LDC reduction was detected in 17% of BA cases and 24% of non-CRD cases. There were no statistically significant changes in pulmonary ventilation among BA patients with impaired LDC compared to patients without CRD.Conclusion. All patients with respiratory symptoms after COVID-19 should undergo comprehensive lung function assessment to identify bronchial obstruction, impaired lung diffusion capacity, and ensure timely intervention.

Long-term consequences of the functional state of the respiratory system after SARS-CoV-2-associated lung damage

Aim. To study the dynamics of respiratory system function in patients without a history of bronchopulmonary pathology after SARS-CoV-2 infection with virus-associated lung damage.Materials and methods. A retrospective study was conducted on 29 patients (median age 46 [43-51] years) at two stages: visit 1 (1-4 months) and visit 2 (8-13 months) from the onset of COVID-19. Data from spirometry, bodyplethysmography, diffusion capacity test, impulse oscillometry (IOS), and chest computed tomography (CT) obtained during the acute phase of the disease (CTmax), as well as dyspnea assessed by the mMRC scale, were analyzed.Results. The median CTmax was 75%, and 66% of patients received treatment in the intensive care unit. At visit 1, dyspnea was of mild or moderate severity. Medians of vital capacity (VC), total lung capacity (TLC), residual volume (RV), and diffusion capacity of the lungs (DLco) were reduced (&lt;80% predicted). The median forced expiratory volume in the first second (FEV1) and IOS parameters were within normal ranges. However, increased reactance area (AX) and absolute frequency dependence of resistance (R5–R20) were found in 59% and 24% of cases, respectively. At visit 2, mild dyspnea persisted. Lung volumes were within normal limits, with statistically significant differences between visits. The median DLco was reduced at visit 1 but increased to normal at visit 2, with statistically significant differences between visits. The median IOS parameters remained within normal limits, with no statistically significant differences between visits. However, in visit 1 increased AX and (R5–R20) were observed in 59% and 24%, in visit 2 – 45% and 17% of cases, respectively, with no statistically significant differences between visits.Conclusions. Among the long-term functional consequences of SARS-CoV-2 infection with virus-associated lung damage, decreased lung diffusion capacity (reduced DLco) and small airway dysfunction (increased AX and/or R5-R20) were noted in some patients. Impulse oscillometry should be included in the comprehensive functional assessment plan for patients after SARS-CoV-2 infection to diagnose small airway dysfunction.

The role of breathing biomechanics and diffusing lung capacity in post-COVID dyspnoea formation

The role of breathing biomechanics and diffusing lung capacity in post-COVID dyspnoea formation

Predictors of Discharge With Supplemental Oxygen After Lobectomy for Lung Cancer

BackgroundBefore lung cancer resection, patients inquire about dyspnea and the potential need for supplemental oxygen. The objective of this study was to identify predictors of discharge with supplemental oxygen for patients undergoing lobectomy for lung cancer. MethodsUsing The Society of Thoracic Surgeons General Thoracic Surgery Database, study investigators conducted a retrospective cohort study of patients who underwent lobectomy for lung cancer from July 2018 to December 2021. Multivariable logistic regression was used to determine the adjusted association of pulmonary function with discharge on supplemental oxygen and identify independent predictors of discharge with supplemental oxygen. Pulmonary function was modeled as the minimum of either predicted postoperative forced expiratory volume in 1 second or predicted postoperative diffusing capacity of lung for carbon monoxide. ResultsOverall, 2100 (8.4%) patients who underwent lobectomy were discharged with supplemental oxygen. Those patients with a minimum of either predicted postoperative forced expiratory volume in 1 second or predicted postoperative diffusing capacity of lung for carbon monoxide ≤60% had a progressively increased risk of discharge with supplemental oxygen than patients with minimum function >60%. The 2 strongest predictors of discharge with supplemental oxygen were increasing body mass index (25-29 kg/m2: adjusted odds ratio [aOR], 1.38; 95% CI, 1.21-1.57; 30-39 kg/m2: aOR, 2.14; 95% CI, 1.88-2.45; ≥40 kg/m2: aOR, 3.51; 95% CI, 2.79-4.39; reference, 18.5-24 kg/m2) and former (aOR, 2.04; 95% CI, 1.67-2.52) or current (aOR, 2.61; 95% CI, 2.10-3.26) smoking status (reference, never smoker). ConclusionsOf those patients who underwent lobectomy for lung cancer, 8.4% were discharged with supplemental oxygen. The study identified preoperative independent predictors of discharge with supplemental oxygen that may be useful during shared decision-making discussions of treatment options for lung cancer and setting expectations with patients.

Management and outcomes of interstitial lung disease associated with anti-synthetase syndrome: A systematic literature review.

Anti-synthetase syndrome (ASS) is a chronic autoimmune condition, with interstitial lung disease (ILD) being a key feature. This systematic literature review (SLR; CRD42023416414) aimed to summarise treatments and outcomes of ILD associated with ASS (ASS-ILD). Databases were searched for articles discussing ASS-ILD management and outcomes, published 1946-September 2023.Screening and data-extraction were performed by two reviewers. Meta-analysis, using a random effects model, and paired t-tests, were undertaken where appropriate to evaluate post-treatment-change in Pulmonary Function Tests (PFT). Ten articles were included, comprising 514 patients: 67.8% female, mean age 52.4years (SD4.6). Baseline high-resolution computed tomography was documented in 447 patients (86.9%); the most common pattern was non-specific interstitial pneumonia (n = 220; 49.2%). The most common myositis-associated autoantibody was anti-Jo1 (48%) with 27.8% having associated anti-Ro52 antibodies.Pooled estimates, after meta-analysis, for baseline Forced Vital Capacity (FVC) was 60.8% predicted (SE 2.1), and Diffusion Capacity of Lungs for Carbon Monoxide (DLco) was 49.8% (SE 3.5). After one-year, pooled improvement in FVC was 14.1% from baseline (SE 3.1) and in DLco was 15.1% (SE 2.8). Paired t-test demonstrated significant overall improvement in FVC (p = 0.007) and DLco (p = 0.002).Patients receiving RTX had 12.2% improvement in FVC and 2.9% increase in DLco at one-year; for patients receiving CYC, there was 17% improvement and 6.3% increase, respectively. 28 deaths were reported. Our SLR, the first to summarise management and outcomes of ASS-ILD, found no conclusive difference between effectiveness of treatments. More robust trials are required to reduce morbidity and mortality resulting from ASS-ILD.

High antinuclear antibody titer is associated with increased mortality risk in patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a diagnosis of exclusion, requiring that potential etiologies of interstitial lung disease be ruled out. Antinuclear antibody (ANA) testing is commonly performed in individuals with IPF, but the clinical significance of ANA positivity remains uncertain. A retrospective search identified 161 patients diagnosed with IPF between May 2010 and January 2021. Data on ANA titers at the time of diagnosis were available in all cases. Mean age of the patients was 66.4 ± 9.6 years; 70.8% were male. ANA titers were high (≥ 1:160) in 25.4% of the cohort. Baseline characteristics were comparable between those with high and low ANA titers. During follow-up (median 28 months), 93 patients (57%) died. On Cox proportional-hazards analysis with lung transplantation entered as a competing risk and adjusting for potential confounders (age, sex, and baseline forced vital capacity and diffusing lung capacity for carbon monoxide), ANA ≥ 1:160, as a dichotomized variable, was significantly associated with case-specific mortality (HR 2.25, 95% CI 1.14−4.42, P = 0.02) and older age (for each 10-year increment, HR 1.55, 95% CI 1.07−2.25, P = 0.02). High ANA titers appear to be associated with increased mortality in IPF. This finding emphasizes the potential prognostic value of ANA testing. Further studies are needed to validate these findings and explore their implications for patient management.

Hypercapnia and lung function parameters in chronic obstructive pulmonary disease

BackgroundIn advanced chronic obstructive pulmonary disease (COPD), hypercapnia may occur due to severe bronchial obstruction with lung hyperinflation. Non-invasive ventilation (NIV) provides the standard of care intended to achieve physiological PCO2 levels, thereby reducing overall mortality. The present study aimed to evaluate pulmonary function parameters derived from spirometry (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1]), body plethysmography (residual volume [RV], total lung capacity [TLC]), and lung diffusion capacity for carbon monoxide (single-breath method [DCO-SB], alveolar-volume corrected values [DCO-VA]) as predictors of chronic hypercapnia in patients with advanced COPD.MethodsThis monocentric, retrospective observational study included 423 COPD patients. Receiver operating characteristic (ROC) curve analysis and cross-validation were used to assess lung function parameters’ diagnostic accuracy for predicting chronic hypercapnia, with the resulting performance expressed as area under the ROC curve (AUROC). We performed univariable and multivariable binary logistic regression analysis to determine if these parameters were independently associated with chronic hypercapnia, with probabilities reported as odds ratios [OR] with 95% confidence intervals [95%CI].ResultsFVC% (AUROC 0.77 [95%CI 0.72–0.81], P < 0.01) and FEV1% (AURIC 0.75 [95%CI 0.70–0.79], P < 0.01) exhibited reasonable accuracy in the prediction of chronic hypercapnia, whereas lung diffusion capacity performed poorly (AUROC 0.64 [95%CI 0.58–0.71] for DCO-SB%, P < 0.01). FVC% (OR 0.95 [95%CI 0.93–0.97], P < 0.01) and FEV1% (OR 0.97 [95%CI 0.94–0.99], P = 0.029) were the only parameters associated independently with chronic hypercapnia in logistic regression analysis. FVC and FEV1 thresholds that best separated hypercapnic from normocapnic subjects reached 56% and 33% of predicted values.ConclusionsRoutinely collected pulmonary function parameters, particularly FVC% and FEV1%, may predict chronic hypercapnia during COPD progression.

Inflammatory profiles are associated with long COVID up to 6 months after COVID-19 onset: A prospective cohort study of individuals with mild to critical COVID-19.

After initial COVID-19, immune dysregulation may persist and drive post-acute sequelae of COVID-19 (PASC). We described longitudinal trajectories of cytokines in adults up to 6 months following SARS-CoV-2 infection and explored early predictors of PASC. RECoVERED is a prospective cohort of individuals with laboratory-confirmed SARS-CoV-2 infection between May 2020 and June 2021 in Amsterdam, the Netherlands. Serum was collected at weeks 4, 12 and 24 of follow-up. Monthly symptom questionnaires were completed from month 2 after COVID-19 onset onwards; lung diffusion capacity (DLCO) was tested at 6 months. Cytokine concentrations were analysed by human magnetic Luminex screening assay. We used a linear mixed-effects model to study log-concentrations of cytokines over time, assessing their association with socio-demographic and clinical characteristics that were included in the model as fixed effects. 186/349 (53%) participants had ≥2 serum samples and were included in current analyses. Of these, 101/186 (54%: 45/101[45%] female, median age 55 years [IQR = 45-64]) reported PASC at 12 and 24 weeks after COVID-19 onset. We included 37 reference samples (17/37[46%] female, median age 49 years [IQR = 40-56]). In a multivariate model, PASC was associated with raised CRP and abnormal diffusion capacity with raised IL10, IL17, IL6, IP10 and TNFα at 24 weeks. Early (0-4 week) IL-1β and BMI at COVID-19 onset were predictive of PASC at 24 weeks. Our findings indicate that immune dysregulation plays an important role in PASC pathogenesis, especially among individuals with reduced pulmonary function. Early IL-1β shows promise as a predictor of PASC.

Pirfenidone in Idiopathic Pulmonary Fibrosis: Real-World Observation on Efficacy and Safety, Focus on Patients Undergoing Antithrombotic and Anticoagulant.

Idiopathic pulmonary fibrosis (IPF) is a rare and progressive interstitial lung disease characterized by irreversible distortion of lung architecture and subsequent loss of pulmonary function. Pirfenidone is an antifibrotic agent associated with increased progression-free survival and overall survival rates, but it carries multiple side effects. The aim of the study was to examine the efficacy and safety profile of pirfenidone in a real-life context, with a focus on the concomitant use of antithrombotic and/or anticoagulant treatments. The clinical and functional data (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], diffusing lung capacity for carbon monoxide [DLCO], and 6 min walking test distance [6MWD]) of all IPF patients treated with pirfenidone and referred to our two centers between 2019 and 2022 were retrospectively analyzed at baseline, 6 and 12 months after the start of treatment. A total of 55 IPF subjects undergoing pirfenidone treatment were included in the analysis (45.5% females, median [IQR] age at disease onset 68.0 [10.0] years, median [IQR] age at baseline 69.0 [10.8] years). Compared to baseline, at 12 months, FVC (86.0% vs. 80.0%; p = 0.023) and DLCO (44.0% vs. 40.0%; p = 0.002) were significantly reduced, while FEV1 (p = 0.304) and 6MWD (p = 0.276) remained stable; no significant change was recorded at 6 months. Most of the reported adverse events were mild or moderate. Gastrointestinal intolerance (9.1%) was the main cause of treatment discontinuation. A total of 5% of patients reported at least one minor bleeding event, although all episodes occurred in those receiving concomitant antithrombotic or anticoagulant. Overall, this real-life experience confirms the efficacy and safety profile of pirfenidone in the case of the concomitant use of antithrombotic and/or anticoagulant drugs.

Pretransplant NT-proBNP levels are associated with mortality among lung transplant recipients.

The prognostic significance of pretransplant N-terminal pro-brain (B)-type natriuretic peptide (NT-proBNP) level has not been investigated in lung transplant recipients. The electronic files of 173 patients with chronic lung disease who underwent lung transplantation in 2018-2022 at a tertiary medical center were retrospectively reviewed. Right heart catheterization (RHC) and NT-proBNP determination were performed preoperatively in all cases. Pretransplant demographic, clinical, and laboratory data were compared between posttransplant survivors and nonsurvivors. Correlations of NT-proBNP values with lung function and RHC parameters and all-cause mortality were analyzed. NT-proBNP level correlated positively with mean pulmonary artery pressure (R = 0.51, p < 0.001) and pulmonary vascular resistance (PVR) (R = 0.45, p = 0.0013), and negatively with diffusing lung capacity for carbon monoxide (R = -0.25, p = 0.0017), cardiac index (R = -0.26, p = 0.001), and cardiac output (R = -0.23, p = 0.004). Over a median follow-up time of 23.22 months, 74 patients died. On univariate analysis, mortality was significantly associated with higher log-NT-proBNP (hazard ratio [HR] = 0.54, 95% confidence interval [CI] 1.15-2.05, p = 0.016), older age at transplant registration (HR = 1.033, 95% CI 1.009-1.058, p = 0.0068), higher PVR (HR 1.15, 95% CI 1.07-1.23, p = 0.015), and lower cardiac output (HR = 0.62, 95% CI 0.42-0.92, p = 0.045). On multivariate analysis adjusted for age, sex, and body mass index, mortality significance was maintained only for higher log-NT-proBNP (HR = 1.54, 95% CI 1.12-2.11, p = 0.007). Among lung transplant recipients, pretransplant NT-proBNP levels correlated well with RHC parameters and were strongly associated with posttransplantation mortality. Assessment of NT-proBNP may improve risk stratification of lung transplant candidates.

The correlation between serum levels of laminin, type IV collagen, type III procollagen N-terminal peptide and hyaluronic acid with the progression of post-COVID-19 pulmonary fibrosis.

COVID-19 patients often suffer from post-COVID-19 acute sequelae (PASC). Pulmonary fibrosis has the most significant long-term impact on the respiratory health of patients, known as post-COVID-19 pulmonary fibrosis (PC19-PF). PC19-PF can be caused by acute respiratory distress syndrome (ARDS) or COVID-19-induced pneumonia. Individuals who experience COVID-19 pneumonia symptoms (including cough, shortness of breath, dyspnea on exertion, and desaturation) for at least 12 weeks after diagnosis, almost all develop PC19-PF. Extracellular matrix molecules: laminin (LN), type IV collagen (IV Col), procollagen III N-terminal peptide (PIIINP), and hyaluronic acid (HA) are involved in the development and progression of PC19-PF. This study aimed to investigate the relationship between the progression of PC19-PF and serum levels of laminin, IV COL, PIIINP, and hyaluronic acid. This retrospective study included 162 PC19-PF patients treated and 160 healthy controls who received treatment at Shenzhen Longgang District Third People's Hospital, Hebei PetroChina Central Hospital and Changzhi People's Hospital from January 2021 to December 2023. Serum levels of LN, IV COL, PIIINP, and HA were detected by chemiluminescence immunoassay using commercial kits. Predicted forced vital capacity percentage (FVC% pred), predicted carbon monoxide lung diffusion capacity percentage (DLCO% pred), high-resolution computed tomography (HRCT) scores were assessed, and patient mortality was compared with healthy controls. Serum levels of LN, IV Col, PIIINP, and HA were significantly higher in PC19-PF or CTD-ILD patients than in healthy controls (all p < 0.05), and they were further elevated in acute exacerbation cases (all p < 0.01). In patients, HA was positively associated with HRCT scores and negatively associated with FVC% pred and DLCO% pred (all p < 0.05). Serum levels of LN, IV COL, PIIINP, and HA were significantly lower in surviving patients than in those who deceased (all p > 0.05). Serum levels of LN, IV C, PIIINP, and HA may affect the progression of PC19-PF and may serve as indicators of PC19-PF severity.

Lung ultrasound in the assessment of interstitial lung disease in patients with connective tissue disease: Performance in comparison with high-resolution computed tomography.

To investigate clinical relevance of performing lung ultrasound (LUS) in patients with connective tissue disease (CTD)-associated interstitial lung disease (ILD) in comparison with high-resolution computed tomography (HRCT). This single-centre study enrolled eligible patients with CTD-ILD from the prospective LUS registry. Total B-lines were detected by assessment at 14 sites via LUS. Forced vital capacity, diffusing lung capacity for carbon monoxide (DLCO), DLCO/alveolar volume, 6-minute walking distance, and the ILD-GAP index were used as ILD prognostic parameters. Correlations were examined using single and multiple regression analyses. Sixty-seven patients were enrolled, including 29 with idiopathic inflammatory myopathy or anti-synthetase syndrome, 25 with systemic sclerosis (SSc), 10 with rheumatoid arthritis, and 3 with mixed connective tissue disease. The total number of B-lines correlated with ILD extent on HRCT in patients with CTD-ILD (r = 0.66; P < 0.001), particularly in patients with SSc-ILD (r = 0.78; P < 0.001). Total B-lines and ILD extent on HRCT showed comparable correlations with prognostic parameters, while multiple regression analysis revealed the limited benefit of performing LUS in addition to HRCT in predicting correlations with prognostic factors. LUS serves as an alternative tool for assessing the severity and prognosis of patients with CTD-ILD.

Medium-Term Disability and Long-Term Functional Impairment Persistence in Survivors of Severe COVID-19 ARDS: Clinical and Physiological Insights

BackgroundAlthough the medium- and long-term sequelae of survivor of acute respiratory distress syndrome (ARDS) of any cause have been documented, little is known about the way in which COVID-19-induced ARDS affects functional disability and exercise components. Our aims were to examine the medium-term disability in severe COVID-19-associated ARDS survivors, delineate pathophysiological changes contributing to their exercise intolerance, and explore its utility in predicting long-term functional impairment persistence. MethodsWe studied 108 consecutive subjects with severe COVID-19 ARDS who remained alive 6 months after intensive care unit (ICU) discharge. Lung morphology was assessed with chest non-contrast CT scans and CT angiography. Functional evaluation included spirometry, plethysmography, muscle strength, and diffusion capacity, with assessment of gas exchange components through diffusing capacity of nitric oxide. Disability was assessed through an incremental exercise test, and measurements were repeated 12 and 24 months later in patients with functional impairments. ResultsAt 6 months after ICU discharge, a notable dissociation between morphological and clinical-functional sequelae was identified. Moderate-severe disability was present in 47% of patients and these subjects had greater limitation of ventilatory mechanics and gas exchange, as well as greater symptomatic perception during exercise and a probable associated cardiac limitation. Female sex, hypothyroidism, reduced membrane diffusion component, lower functional residual capacity, and high-attenuation lung volume were independently associated with the presence of moderate-severe functional disability, which in turn was related to higher frequency and greater intensity of dyspnea and worse quality of life. Out of the 71 patients with reduced lung volumes or diffusion capacity at 6 months post-ICU discharge, only 19 maintained a restrictive disorder associated with gas exchange impairment at 24 months post-discharge. In these patients, 6-month values for diffusion membrane component, maximal oxygen uptake, ventilatory equivalent for CO2, and dead space to tidal volume ratio were identified as independent risk factors for persistence of long-term functional sequelae. ConclusionsLess than half of survivors of COVID-19 ARDS have moderate-severe disability in the medium term, identifying several risk factors. In turn, diffusion membrane component and exercise tolerance at 6-month ICU discharge are independently associated with the persistence of long-term functional sequelae.