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Introduction: Since COVID-19 first surfaced in 2019, it has seriously threatened public health. The most prevalent symptoms are respiratory ones. This study aimed to present the correlation between the severity of the clinical presentation of the disease and the results of respiratory function tests conducted within 6 months after hospital discharge. Methodology: This retrospective study included 99 patients with confirmed SARS-CoV-2 virus infection. Of all patients 24.2% had accentuated bronchovascular pattern, 9.1% had unilateral, and 29.3% had bilateral pneumonia. In comparison, 35.4% patients had diffuse changes, which were described as acute respiratory distress syndrome (ARDS) on computed tomography (CT). Results: Patients with unilateral, bilateral pneumonia or diffuse lung damage had significantly lower forced vital capacity (FVC) values. They were treated with non-invasive mechanical ventilation (NIV) or invasive mechanical ventilation (MV) and had lower FVC values (0.039). A negative, weak correlation existed between CT findings during the infection and Diffusing capacity for carbon monoxide (DLCO) measured after the infection (0.003). A negative, weak correlation was found between oxygen therapy, the use of NIV, and MV findings during the infection with DLCO. A negative correlation was noted between leukocyte values during the infection and forced expiratory volume in the first second (FEV1) and FVC after the infection. Conclusions: Patients with COVID-19 infection who need oxygen support and MV continue to suffer from loss of respiratory function after the resolution of COVID-19 infection. These findings highlight the negative predictive value of pulmonary tests in the long-term follow-up for the development of PC-ILD as well as decreased pulmonary capacity. [ABSTRACT FROM AUTHOR]

Long coronavirus disease (COVID) is estimated to occur in up to 20% of patients with coronavirus disease 2019 (COVID-19) infections, with many having persistent pulmonary symptoms. Mesenchymal stromal cells (MSCs) have been shown to have powerful immunomodulatory and anti-fibrotic properties. Autologous adipose-derived (AD) stromal vascular fraction (SVF) contains MSC and other healing cell components and can be obtained by small-volume lipoaspiration and administered on the same day. This study was designed to study the safety of AD SVF infused intravenously to treat the pulmonary symptoms of long COVID. Five subjects with persistent cough and dyspnea after hospitalization and subsequent discharge for COVID-19 pneumonia were treated with 40 million intravenous autologous AD SVF cells and followed for 12 months, to include with pulmonary function tests and computed tomography scans of the lung. SVF infusion was safe, with no significant adverse events related to the infusion out to 12 months. Four subjects had improvements in pulmonary symptoms, pulmonary function tests, and computed tomography scans, with some improvement noted as soon as 1 month after SVF treatment. It is not possible to distinguish between naturally occurring improvement or improvement caused by SVF treatment in this small, uncontrolled study. However, the results support further study of autologous AD SVF as a treatment for long COVID. [ABSTRACT FROM AUTHOR]

Background: Connective tissue diseases (CTDs) are one of the most common causes among the known etiologies of interstitial lung disorders (ILDs). Parenchymal involvement in CTDs confers a significant risk of mortality as well as morbidity with serious consequences. The present study aims to correlate dyspnoea scores with high-resolution computed tomography (HRCT) changes, spirometry, diffusing capacity for carbon monoxide (DLCO), and 6-Minute Walk Test (6MWT) among different types of CTD-ILDs. Methodology: The hospital-based observational, cross-sectional study was performed over 1 year among 60 patients with CTD-ILDs. The dyspnoea score (modified Medical Research Centre grade), HRCT thorax pattern with a percentage of involvement, and functional parameters (forced vital capacity (FVC), DLCO, 6-Minute Walking Distance (6MWD)) were compared among different CTD-ILD groups. Results were computed using Microsoft Excel. Results: Systemic sclerosis (SSc) was the most common cause of CTD-ILDs (43%) with a predominant nonspecific interstitial pneumonia pattern (71% of all SSc-ILDs), followed by rheumatoid arthritis (RA) (30%) with a predominance of usual interstitial pneumonia (55% of all RA-ILDs). Other cases included dermatomyositis (6%), mixed connective tissue disease (6%), and Sjögren disease (3%). Three percent of the patients remained unclassified. The difference in the HRCT pattern was seen between RA- and SSc-ILDs, which was statistically significant (p = 0.00035). The mean FVC was 1.68L and the mean 6MWD was 316 m. 6MWD showed a positive correlation with FVC and DLCO (r = 0.67 and 0.78). The percentage of the HRCT thorax involvement showed a negative correlation with FVC and 6MWD but not in linear regression (p = 0.000281 and 4.27e–08, r = –0.45 and −0.67, confidence interval (CI) 95%). DLCO had a negative linear regression with HRCT thorax involvement (r = –0.93, CI 95%) showing superiority over other functional parameters. Conclusion: The integration of clinical data, the extent of involvement in HRCT thorax, and physiological parameters, especially DLCO, provide a holistic approach to better understand CTD-ILDs.

Background: Respiratory symptoms may persist for several weeks following the initial coronavirus disease 2019 (COVID-19) infection. The aims and objectives were to assess the clinical symptoms, pulmonary functions, and radiological changes and to assess the cardio-vascular complications in post-COVID-19 patients. Methods: This observational study was conducted in the Department of Pulmonary Medicine in collaboration with the Department of Cardiology, SCBMCH, Cuttack, from March 2021 to August 2022 on 75 post-COVID-19 patients with respiratory symptoms from 4 weeks to 2 years after treatment for COVID-19 infection. Post-COVID patients having previous respiratory diseases were excluded from the study. Results: Among 75 patients, the most common age group was 18–30 years with a male-to-female ratio of 2.5:1. Based on O2 requirement, patients were divided into the mild symptomatic group and moderate to severe pneumonia group. The most common respiratory symptom was dyspnea, followed by cough with expectoration. Bilateral crepitations were found in 17% of cases. C-reactive protein (CRP) and D-dimer were increased in 38.6% and 32% of patients, respectively. 42.6% had abnormal chest X-ray, and the most common abnormal finding was reticular thickening. In spirometry, the restrictive pattern and mixed pattern were the predominant types documented in 49.3% and 13.3% of cases, respectively, which were significant in the moderate–severe group. Diffusion capacity of the lungs for carbon monoxide (DLCO) was performed in only 19 patients (mild group 13 and moderate–severe group 6). Twelve (63.2%) patients had abnormal DLCO. P- values were significant for RV (0.0482) and RV/TLC (0.0394). High-resolution computed tomography (HRCT) of the thorax was abnormal in 55.7% with the most common abnormalities as inter- and intra-lobular septal thickening. The left ventricular ejection fraction was preserved in all patients, with right atrium and right ventricle enlargement in 2.6% and pulmonary hypertension in 4.0% of participants. Conclusion: All post-COVID-19 patients having respiratory symptoms after recovery from acute COVID-19 may be referred by family care physicians to a dedicated post-COVID center for further evaluation, management, and early rehabilitation to decrease the morbidity in recovered patients. Persistent increased blood parameters like TLC, N/L ratio, RBS, CRP, and D-dimer seen in recovered post-COVID-19 patients. The long-term impact of CT findings on respiratory symptoms, pulmonary functions, and quality of life is unknown. Cardiovascular abnormalities in post-COVID-19 patients are infrequent.

Background: Recovery from acute COVID-19 may be slow and incomplete: cases of Post-Acute Sequelae of COVID (PASC) are counted in millions, worldwide. We aimed to explore if and how the pre-existing Socio-economic-status (SES) influences such recovery. Methods: We analyzed a database of 1536 consecutive patients from the first wave of COVID-19 in Italy (February-September 2020), previously admitted to our referral hospital, and followed-up in a dedicated multidisciplinary intervention. We excluded those seen earlier than 12 weeks (the conventional limit for a possible PASC syndrome), and those reporting a serious complication from the acute phase (possibly accounting for symptoms persistence). We studied whether the exposition to disadvantaged SES (estimated through the Italian Institute of Statistics's model – ISTAT 2017) was affecting recovery outcomes, that is: symptoms (composite endpoint, i.e. at least one among: dyspnea, fatigue, myalgia, chest pain or palpitations); Health-Related-Quality-of-Life (HRQoL, as by SF-36 scale); post-traumatic-stress-disorder (as by IES-R scale); and lung structural damage (as by impaired CO diffusion, DLCO). Results: Eight-hundred and twenty-five patients were included in the analysis (median age 59 years; IQR: 50–69 years, 60.2% men), of which 499 (60.5%) were previously admitted to hospital and 27 (3.3%) to Intensive-Care Unit (ICU). Those still complaining of symptoms at follow-up were 337 (40.9%; 95%CI 37.5–42.2%), and 256 had a possible Post-Traumatic Stress Disorder (PTSD) (31%, 95%CI 28.7–35.1%). DLCO was reduced in 147 (19.6%, 95%CI 17.0–22.7%). In a multivariable model, disadvantaged SES was associated with a lower HRQoL, especially for items exploring physical health (Limitations in physical activities: OR = 0.65; 95%CI = 0.47 to 0.89; p = 0.008; AUC = 0.74) and Bodily pain (OR = 0.57; 95%CI = 0.40 to 0.82; p = 0.002; AUC = 0.74). We did not observe any association between SES and the other outcomes. Conclusions: Recovery after COVID-19 appears to be independently affected by a pre-existent socio-economic disadvantage, and clinical assessment should incorporate SES and HRQoL measurements, along with symptoms. The socioeconomic determinants of SARS-CoV-2 disease are not exclusive of the acute infection: this finding deserves further research and specific interventions. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) play a pivotal role in a variety of physiologically relevant processes, including lung inflammation. Recent attention has been directed toward EV-derived microRNAs (miRNAs), such as miR-191-5p, particularly in the context of inflammation. Here, we investigated the impact of miR-191-5p-enriched EVs on the activation of NF-κB and the expression of molecules associated with inflammation such as interleukin-8 (IL-8). To this aim, cells of bronchial epithelial origin, 16HBE, were transfected with miR-191-5p mimic and inhibitor and subsequently subjected to stimulations to generate EVs. Then, bronchial epithelial cells were exposed to the obtained EVs to evaluate the activation of NF-κB and IL-8 levels. Additionally, we conducted a preliminary investigation to analyze the expression profiles of miR-191-5p in EVs isolated from the plasma of patients diagnosed with chronic obstructive pulmonary disease (COPD). Our initial findings revealed two significant observations. First, the exposure of bronchial epithelial cells to miR-191-5p-enriched EVs activated the NF-kB signaling and increased the synthesis of IL-8. Second, we discovered the presence of miR-191-5p in peripheral blood-derived EVs from COPD patients and noted a correlation between miR-191-5p levels and inflammatory and functional parameters. Collectively, these data corroborate and further expand the proinflammatory role of EVs, with a specific emphasis on miR-191-5p as a key cargo involved in this process. Consequently, we propose a model in which miR-191-5p, carried by EVs, plays a role in airway inflammation and may contribute to the pathogenesis of COPD. [ABSTRACT FROM AUTHOR]

Background: Pulmonary tuberculosis (TB) remains a major public health issue in India, with high incidence and mortality. The current literature on post-TB sequelae functional defects focuses heavily on spirometry, with conflicting obstruction vs. restriction data, lacks advanced statistical analysis, and has insufficient data on diffusion limitation and functional impairment. Objective: This study aimed to thoroughly evaluate post-tubercular sequelae after treatment, assessing chest radiology, spirometry, diffusing capacity, and exercise capacity. Methods: A total of 85 patients were studied at a university teaching hospital in Mysuru. The data collected included characteristics, comorbidities, smoking history, and respiratory symptoms. The investigations included spirometry, DLCO, chest X-rays with scoring, and 6MWT. Results: Of the patients, 70% had abnormal X-rays post-treatment, correlating with reduced lung function. Additionally, 70% had impaired spirometry with obstructive/restrictive patterns, and 62.2% had reduced DLCO, with females at higher risk. Smoking increased the risk of sequelae. Conclusions: Most patients had residual radiological/lung function abnormalities post-treatment. Advanced analyses provide insights into obstructive vs. restrictive defects. Ongoing research should explore pathogenetic mechanisms and therapeutic modalities to minimize long-term post-TB disability. [ABSTRACT FROM AUTHOR]

Exercise training is recommended for pulmonary hypertension (PH). Post hoc analysis of the PH and Home‐Based (PHAHB) trial stratified patients into two groups based on median diffusing capacity of the lungs for carbon monoxide (DLCO). Patients with higher DLCO had a greater improvement in physical activity performance in response to exercise training, compared to those with lower DLCO. DLCO may be an important consideration in prescribing exercise in PH. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients suffering from melanoma or metastatic cutaneous squamous cell carcinoma profit from immune checkpoint blockade as a therapy. Pneumonitis is a rare but potentially fatal immune-related adverse event, and even more subclinical damage is most likely to occur. The sensitive marker lung clearance index, integrated into pulmonary function testing, was used to detect possible early pulmonary impairment. As slightly impaired lung function could be observed, we recommend the sensitive marker lung clearance index as a diagnostic method that should be implemented into the clinical routine follow-ups during immune checkpoint therapy in order to enable possible further recommendations. Background: Immune checkpoint blockade (ICB) has presented a breakthrough in the treatment of malignant tumors and increased the overall survival of patients with various tumor entities. ICB may also cause immune-related adverse events, such as pneumonitis or interstitial lung disease. The lung clearance index (LCI) is a multiple-breath washout technique offering information on lung pathology in addition to conventional spirometry. It measures the degree of pulmonary ventilation inhomogeneity and allows early detection of pulmonary damage, especially that to peripheral airways. Methods: This cross-sectional study compared the lung function of patients with melanoma or metastatic cutaneous squamous cell carcinoma who received programmed cell death 1 (PD-1) and cytotoxic T-Lymphocyte-associated Protein 4 (CTLA-4) antibodies, alone or in combination, to age- and sex-matched controls. Lung function was assessed using spirometry, according to American Thoracic Society and European Respiratory Society standards, the LCI, and a diffusion capacity of carbon monoxide (DLCO) measurement. Results: Sixty-one screened patients and thirty-eight screened controls led to nineteen successfully included pairs. The LCI in the ICB-treated patients was 8.41 ± 1.15 (mean ± SD), which was 0.32 higher compared to 8.07 ± 1.17 in the control group, but the difference was not significant (p = 0.452). The patients receiving their ICB therapy for under five months showed a significantly lower LCI (7.98 ± 0.77) compared to the ICB patients undergoing therapy for over five months (9.63 ± 1.22) at the point of testing (p = 0.014). Spirometric analysis revealed that the forced expiratory volume between 25 and 75% of the forced vital capacity (FEF25–75%) in the ICB-treated patients was significantly reduced (p = 0.047) compared to the control group. DLCO (%predicted and adjusted for hemoglobin) was 94.4 ± 19.7 in the ICB patients and 93.4 ± 21.7 in the control group (p = 0.734). Conclusions: The patients undergoing ICB therapy showed slightly impaired lung function compared to the controls. Longer periods of ICB treatment led to deterioration of the LCI, which may be a sign of a subclinical inflammatory process. The LCI is feasible and may be easily integrated into the clinical daily routine and could contribute to early detection of pulmonary (auto-)inflammation. [ABSTRACT FROM AUTHOR]

Abstract Limited information is available regarding the association between preoperative lung function and postoperative pulmonary complications (PPCs) in patients with esophageal cancer who undergo esophagectomy. This is a retrospective cohort study. Patients were classified into low and high lung function groups by the cutoff of the lowest fifth quintile of forced expiratory volume in 1 s (FEV1) %predicted (%pred) and diffusing capacity of the carbon monoxide (DLco) %pred. The PPCs compromised of atelectasis requiring bronchoscopic intervention, pneumonia, and acute lung injury/acute respiratory distress syndrome. Modified multivariable-adjusted Poisson regression model using robust error variances and inverse probability treatment weighting (IPTW) were used to assess the relative risk (RR) for the PPCs. A joint effect model considered FEV1%pred and DLco %pred together for the estimation of RR for the PPCs. Of 810 patients with esophageal cancer who underwent esophagectomy, 159 (19.6%) developed PPCs. The adjusted RR for PPCs in the low FEV1 group relative to high FEV1 group was 1.48 (95% confidence interval [CI] = 1.09–2.00) and 1.98 (95% CI = 1.46–2.68) in the low DLco group relative to the high DLco group. A joint effect model showed adjusted RR of PPCs was highest in patients with low DLco and low FEV1 followed by low DLco and high FEV1, high DLco and low FEV1, and high DLco and high FEV1 (Reference). Results were consistent with the IPTW. Reduced preoperative lung function (FEV1 and DLco) is associated with post-esophagectomy PPCs. The risk was further strengthened when both values decreased together.

Abstract Background Postoperative respiratory failure is the most frequent complication in postsurgical patients. The purpose of this study is to assess whether pulmonary function testing in high-risk patients during preoperative assessment detects previously unknown respiratory impairments which may influence patient outcomes. Methods A targeted patient screening by spirometry and the measurement of the diffusing capacity of the lung for carbon monoxide (DLCO) was implemented in the anesthesia department of a tertiary university hospital. Patients of all surgical disciplines who were at least 75 years old or exhibited reduced exercise tolerance with the metabolic equivalent of task less than four (MET

Background: Postoperative respiratory failure is the most frequent complication in postsurgical patients. The purpose of this study is to assess whether pulmonary function testing in high-risk patients during preoperative assessment detects previously unknown respiratory impairments which may influence patient outcomes. Methods: A targeted patient screening by spirometry and the measurement of the diffusing capacity of the lung for carbon monoxide (DLCO) was implemented in the anesthesia department of a tertiary university hospital. Patients of all surgical disciplines who were at least 75 years old or exhibited reduced exercise tolerance with the metabolic equivalent of task less than four (MET < 4) were examined. Clinical characteristics, history of lung diseases, and smoking status were also recorded. The statistical analysis entailed t-tests, one-way ANOVA, and multiple linear regression with backward elimination for group comparisons. Results: Among 256 included patients, 230 fulfilled the test quality criteria. Eighty-one (35.2%) patients presented obstructive ventilatory disorders, out of which 65 were previously unknown. 38 of the newly diagnosed obstructive disorders were mild, 18 moderate, and 9 severe. One hundred forty-five DLCO measurements revealed 40 (27.6%) previously unknown gas exchange impairments; 21 were mild, 17 moderate, and 2 severe. The pulmonary function parameters of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and DLCO were significantly lower than the international reference values of a healthy population. Patients with a lower ASA class and no history of smoking exhibited higher FVC, FEV1, and DLCO values. Reduced exercise tolerance with MET < 4 was strongly associated with lower spirometry values. Conclusions: Our screening program detected a relevant number of patients with previously unknown obstructive ventilatory disorders and impaired pulmonary gas exchange. This newly discovered sickness is associated with low metabolic equivalents and may influence perioperative outcomes. Whether optimized management of patients with previously unknown impaired lung function leads to a better outcome should be evaluated in multicenter studies. Trial registration: German Registry of Clinical Studies (DRKS00029337), registered on: June 22nd, 2022. [ABSTRACT FROM AUTHOR]

Abstract Exercise training is recommended for pulmonary hypertension (PH). Post hoc analysis of the PH and Home‐Based (PHAHB) trial stratified patients into two groups based on median diffusing capacity of the lungs for carbon monoxide (DLCO). Patients with higher DLCO had a greater improvement in physical activity performance in response to exercise training, compared to those with lower DLCO. DLCO may be an important consideration in prescribing exercise in PH.

Reduced lung diffusing capacity for carbon monoxide (DLCO) at rest and increased ventilation (⩒E)-carbon dioxide output (⩒CO2) during exercise are frequent findings in dyspneic smokers with largely preserved FEV1. It remains unclear whether low DLCO and high ⩒E-⩒CO2 are mere reflections of alveolar destruction (i.e. emphysema) or impaired pulmonary perfusion in non-emphysematous tissue contributes to these functional abnormalities. Sixty-four smokers (41 males, FEV1= 84 ± 13%predicted) underwent pulmonary function tests, an incremental exercise test, and quantitative chest computed tomography. Total pulmonary vascular volume (TPVV) was calculated for the entire segmented vascular tree (VIDA Vision™). Using the median % low attenuation area (-950 HU), participants were dichotomized into “Trace” or “Mild” emphysema (E), each group classified into preserved versus reduced DLCO. Within each emphysema subgroup, participants with abnormally low DLCO showed lower TPVV, higher ⩒E-⩒CO2, and exertional dyspnea than those with preserved DLCO (p

BackgroundFew studies have assessed lung function in Hispanic subjects recovering from mild COVID-19. Therefore, we examined the prevalence of impaired pulmonary diffusing capacity for carbon monoxide (DLCO) as defined by values below the lower limit of normal (

Background and Objectives: Assessment of the prothrombotic, proinflammatory, and functional status of a cohort of COVID-19 patients at least two years after the acute infection to identify parameters with potential therapeutic and prognostic value. Materials and Methods: We conducted a retrospective, descriptive study that included 117 consecutive patients admitted to Iasi Pulmonary Rehabilitation Clinic for reassessment and a rehabilitation program at least two years after a COVID-19 infection. The cohort was divided into two groups based on the presence (n = 49) or absence (n = 68) of pulmonary fibrosis, documented through high-resolution computer tomography. Results: The cohort comprises 117 patients, 69.23% females, with a mean age of 65.74 ± 10.19 years and abnormal body mass index (31.42 ± 5.71 kg/m2). Patients with pulmonary fibrosis have significantly higher levels of C-reactive protein (CRP) (p < 0.05), WBC (7.45 ± 7.86/mm3 vs. 9.18 ± 17.24/mm3, p = 0.053), neutrophils (4.68 ± 7.88/mm3 vs. 9.07 ± 17.44/mm3, p < 0.05), mean platelet volume (MPV) (7.22 ± 0.93 vs. 10.25 ± 0.86 fL, p < 0.05), lactate dehydrogenase (p < 0.05), and D-dimers (p < 0.05), but not ferritin (p = 0.470), reflecting the chronic proinflammatory and prothrombotic status. Additionally, patients with associated pulmonary fibrosis had a higher mean heart rate (p < 0.05) and corrected QT interval (p < 0.05). D-dimers were strongly and negatively correlated with diffusion capacity corrected for hemoglobin (DLCO corr), and ROC analysis showed that the persistence of high D-dimers values is a predictor for low DLCO values (ROC analysis: area under the curve of 0.772, p < 0.001). The results of pulmonary function tests (spirometry, body plethysmography) and the 6-minute walk test demonstrated no significant difference between groups, without notable impairment within either group. Conclusions: Patients with COVID-19-related pulmonary fibrosis have a persistent long-term proinflammatory, prothrombotic status, despite the functional recovery. The persistence of elevated D-dimer levels could emerge as a predictive factor associated with impaired DLCO. [ABSTRACT FROM AUTHOR]

Background: Few studies have looked at how SARS-CoV-2 affects pulmonary function, exercise capacity, and health-related quality of life over time. The purpose of this study was to evaluate these characteristics in post COVID-19 subjects 1 year after recovery. Methods: The study included two groups. The case group included post COVID-19 subjects who had recovered after a year, and the control group included healthy participants who had never tested positive for COVID-19. Results: The study screened 90 participants, 42 of whom met the eligibility criteria. The findings revealed that the majority of post COVID-19 subjects had relatively normal lung function 1-year post-recovery. A significant reduction in DLCO (B/P%) was observed in the case group vs. control. The exercise capacity test revealed a clinically significant difference in distance walked and a significant difference in the dyspnea post-walk test in the case group compared to the control group. The case group's health-related quality of life domain scores were significantly affected in terms of energy/fatigue, general health, and physical function. Conclusions: The post COVID-19 subjects were shown to have well-preserved lung function after 1 year. However, some degree of impairment in diffusion capacity, exercise capacity, and health-related quality of life remained. [ABSTRACT FROM AUTHOR]

The relationship between carbon monoxide diffusing capacity (DLCO) measurement in patients being evaluated for heart transplantation is poorly understood. We collected pretransplant pulmonary function testing (PFT) data on 157 transplant recipients over a 10-year span. Due to a few common reasons such as intensive care unit hospitalization, only 47% of candidates underwent DLCO measurement. However, there were no differences in outcomes regardless of whether or not the test was available to guide candidate selection. No PFT value correlated with pulmonary complications and only forced expiratory volume in 1 second correlated with survival. We conclude that in subjects otherwise eligible for heart transplantation, DLCO measurement carries no significant discriminatory power. Furthermore, due to extensive variability in utilization, arguments on the grounds of equity could be made to eliminate such testing.

Abstract Background The SARS-CoV2 pandemic impacted many critically ill patients, causing sequelae, affecting lung function, and involving the musculoskeletal system. We evaluated the association between lung function and muscle quality index in severely ill post-COVID-19 patients. Methods A cross-sectional study was conducted on a post-COVID-19 cohort at a third-level center. The study included patients who had experienced severe-to-critical COVID-19. Anthropometric measurements, such as body mass index (BMI) and handgrip strength, were obtained to calculate the muscle quality index (MQI). Additionally, spirometry, measurements of expiratory and inspiratory pressure, and an assessment of DLCO in the lungs were performed. The MQI was categorized into two groups: low-MQI (below the 50th percentile) and high-MQI (above the 50th percentile), based on sex. Group differences were analyzed, and a multivariate linear regression analysis was performed to assess the association between respiratory function and MQI. Results Among the 748 patients analyzed, 61.96% required mechanical ventilation, and the median hospital stay was 17 days. In patients with a low MQI, it was observed that both mechanical respiratory function and DLCO were lower. The multivariate analysis revealed significantly lower findings in mechanical respiratory function among patients with a low MQI. Conclusion The Low-MQI is an independent predictor associated with pulmonary function parameters in subjects with Post-COVID-19 syndrome.

Background. The diffusing capacity of the lungs for carbon monoxide (DLCO) represents the most sensitive independent factor for highlighting the interstitial lung disease associated with rheumatoid arthritis (RA-ILD). Many studies have analyzed this association between RA and lung modifications because it correlates with a decrease in the patients’ quality of life and a higher mortality. Objective. This study aimed to highlight the importance of DLCO as a predictor of ILD progression in RA, beside the pattern on high-resolution chest CT (HRCT) and the double seropositivity of the disease. Patients and method. This prospective cohort study, carried out between august 2022 and may 2023, included 48 RA patients with ILD, fulfilling the 1987 ACR or 2010 ACR/EULAR classification criteria. Important attention was paid to respiratory functional tests, immunological changes, and specific lung pattern on HRCT. Patients with current malignancies, active infections or Overlap syndrome were excluded from the study. Results. 48 RA patients, mostly women (81%) with a mean age of 65.54±10.58 years old and a median age of RA onset of 52.58±11.36 years, were included. The proportion of patients with a decreased DLCO was 64.6%. Using statistical tests, we found significant correlations between DLCO and age, double seropositivity and a specific pulmonary pattern on HRCT. Conclusion. ILD, an underrecognized disease, may be considered one of the most serious of all extra-articular manifestations in RA, the risk for mortality being triple in these cases. Our results are in correlation with the published data and support the key role of DLCO in the diagnosis and follow-up of these patients.

Objective:In our study, we aimed to investigate the long-term effects of the acute phase parameters of C-reactive protein, procalcitonin, D-dimer, lymphocyte, thrombocyte and ferritin on the respiratory function parameters in patients hospitalized due to Coronavirus disease-2019 (COVID-19) pneumonia.Method:The present study was carried out with the retrospective evaluation of patients with COVID-19 pneumonia, who were hospitalized in Medipol University Hospital between March 2020 and June 2021, and who were 6 months to 1 year after discharge. The relationship between pulmonary function test results and acute period laboratory findings of 52 patients who applied for control purposes 6 months after discharge was examined.Results:Diffusing capacity for carbon monoxide (DLCO) (pred) value in 26 patients (50%), total lung capacity (TLC) value in 9 patients (17.3%), and residual volume (RV) (pred) value in 10 patients (19.2%) were below 80%. As a result of multiple linear regression analysis in our study, the maximum D-dimer level and maximum procalcitonin level were determined by DLCO (% pred) (adjusted R2 =0.645; p

Background Few studies have looked at how SARS-CoV-2 affects pulmonary function, exercise capacity, and health-related quality of life over time. The purpose of this study was to evaluate these characteristics in post COVID-19 subjects 1 year after recovery. Methods The study included two groups. The case group included post COVID-19 subjects who had recovered after a year, and the control group included healthy participants who had never tested positive for COVID-19. Results The study screened 90 participants, 42 of whom met the eligibility criteria. The findings revealed that the majority of post COVID-19 subjects had relatively normal lung function 1-year post-recovery. A significant reduction in DLCO (B/P%) was observed in the case group vs. control. The exercise capacity test revealed a clinically significant difference in distance walked and a significant difference in the dyspnea post-walk test in the case group compared to the control group. The case group’s health-related quality of life domain scores were significantly affected in terms of energy/fatigue, general health, and physical function. Conclusions The post COVID-19 subjects were shown to have well-preserved lung function after 1 year. However, some degree of impairment in diffusion capacity, exercise capacity, and health-related quality of life remained.

Background: The SARS-CoV2 pandemic impacted many critically ill patients, causing sequelae, affecting lung function, and involving the musculoskeletal system. We evaluated the association between lung function and muscle quality index in severely ill post-COVID-19 patients. Methods: A cross-sectional study was conducted on a post-COVID-19 cohort at a third-level center. The study included patients who had experienced severe-to-critical COVID-19. Anthropometric measurements, such as body mass index (BMI) and handgrip strength, were obtained to calculate the muscle quality index (MQI). Additionally, spirometry, measurements of expiratory and inspiratory pressure, and an assessment of DLCO in the lungs were performed. The MQI was categorized into two groups: low-MQI (below the 50th percentile) and high-MQI (above the 50th percentile), based on sex. Group differences were analyzed, and a multivariate linear regression analysis was performed to assess the association between respiratory function and MQI. Results: Among the 748 patients analyzed, 61.96% required mechanical ventilation, and the median hospital stay was 17 days. In patients with a low MQI, it was observed that both mechanical respiratory function and DLCO were lower. The multivariate analysis revealed significantly lower findings in mechanical respiratory function among patients with a low MQI. Conclusion: The Low-MQI is an independent predictor associated with pulmonary function parameters in subjects with Post-COVID-19 syndrome. [ABSTRACT FROM AUTHOR]

Since the beginning of the pandemic, both COVID-19-associated coagulopathy biomarkers and a plethora of endothelial biomarkers have been proposed and tested as prognostic tools of severity and mortality prediction. As the pandemic is gradually being controlled, attention is now focusing on the long-term sequelae of COVID-19. In the present study, we investigated the role of endothelial activation/dysfunction in long COVID syndrome. This observational study included 68 consecutive long COVID patients and a healthy age and sex-matched control group. In both groups, we measured 13 endothelial biomarkers. Moreover, in the long COVID patients, we evaluated fatigue and dyspnea severity, lung diffusion capacity (DLCO), and the 6-min walk (6MWT) test as measures of functional capacity. Our results showed that markers of endothelial activation/dysfunction were higher in long COVID patients, and that soluble intracellular adhesion molecule 1 (sICAM-1) and soluble vascular adhesion molecule 1 (sVCAM-1) negatively correlated with lung diffusion and functional capacity (sICAM-1 vs. DLCO, r = −0.306, p = 0.018; vs. 6MWT, r = −0.263, p = 0.044; and sVCAM-1 vs. DLCO, r= −0.346, p = 0.008; vs. 6MWT, r = −0.504, p < 0.0001). In conclusion, evaluating endothelial biomarkers alongside clinical tests might yield more specific insights into the pathophysiological mechanisms of long COVID manifestations. [ABSTRACT FROM AUTHOR]

BACKGROUND: The 2017 American Thoracic Society/European Respiratory Society (ATS/ERS) diffusing capacity of the lung for carbon monoxide (DLCO) standards specify a control rule for assessing biologic quality control (BioQC) but have limited guidance on how to establish expected values for control rule variables. This study aimed to determine expected values for DLCO BioQC using coefficient of variation (CV) and compare that the mean ± 2 SD control rule yields the same precision as mean ± 12% of the mean. METHODS: DLCO BioQC data were col-lected from a multi-center inhaled medication study. This descriptive study spanned 42 months ending in 2018. The annual DLCO CV was based upon 10 DLCO values separated by at least 5 d. The root mean square CV (RMSCV) was computed for each year and Friedman test evaluated within subject annual CV changes. Ninetieth percentile values were computed for annual control rule limits/mean DLCO. RESULTS: Of 217 BioQCs, the study's first year had 168 subjects with fewer in subsequent years. Annual CV values from RMSCV were 5.3, 4.5, and 4.6% in years 1, 2, and 3, respectively. No change was seen in the CV for those subjects with data for all 3 years, n = 24, P = .07. The 90th percentile of measurements 2 SD/mean DLCO were 15, 12.4, and 11% in years 1, 2, and 3, respectively. CONCLUSIONS: A DLCO BioQC CV ≤ 6% is achievable across multiple sites, technologists, and brands of equipment. This CV value assures that measurements for control rule variables emerge from an expected range. A control rule of mean ± 2 SD appeared to yield similar results as the mean ± 12% of the mean rule reported in the 2017 ATS/ERS DLCO standards. [ABSTRACT FROM AUTHOR]

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A 48-year-old woman who had been receiving long-term interferon-β for 8 years for multiple sclerosis developed drug-induced World Health Organization group I pulmonary arterial hypertension. Triple therapy for pulmonary arterial hypertension and suspension of interferon-β led to improvement from a high-risk to low-risk state and improvement in exercise hemodynamics, including vascular distensibility, and right ventricle-pulmonary artery coupling. (Level of Difficulty: Advanced.).

Aim. Assess the functional state of trespiratory system and effectiveness of therapeutic tactics for broncho-obstructive syndrome (BOS) in patients in the post-COVID period. Materials and methods. A two-center cohort prospective study included 10 456 and 89 patients, respectively. A comprehensive assessment of the respiratory system included clinical, laboratory and functional data, spirometry, body plethysmography, and a study of diffusive capacity of the lungs (DLCO). Therapy consisted of budesonide suspension or fixed combination beclomethasone dipropionate/formoterol (EMD BDP/FORM). Results. The frequency of BOS in the cohort was 72% (7497 patients). In 13% (n=974) of cases, bronchial asthma was diagnosed for the first time, in 4.4% (n=328) chronic obstructive pulmonary disease. Risk factors for the development and decrease in DLCO in the post-COVID period were identified. In the group of complex instrumental examination of lung function, the absence of violations of spirometric data and indicators determined by body plethysmography was determined. Conclusion. Risk factors for BOS in post-COVID period are atopy, a history of frequent acute respiratory infections, smoking, blood eosinophilia, moderate and severe forms of COVID-19. The advantage of a fixed combination of EMD BDP/FORM in MART mode compared with nebulized suspension budesonide + solution of salbutamol in treatment of BOS was shown. Risk factors for DLCO disorders were established: severe COVID-19, hospitalization in the intensive care unit, the need for additional oxygen therapy.

Abstract Aims Diffusing capacity of the lung for carbon monoxide (DLCO) reduction is common in heart failure (HF) and is associated with a worse prognosis. Correlations between DLCO and pulmonary hypertension (PH) are unclear, and published data are conflicting; it has been shown that DLCO impairment may persist or even worsen after normalization of pulmonary pressures following left ventricle assist device (LVAD) implantation, maybe reflecting persistent pulmonary damage. We aimed to investigate the impact of pre‐implant DLCO and central haemodynamics on outcome in patients with advanced HF implanted with a LVAD. Methods and results We retrospectively analysed pre‐implant and post‐implant data from 42 patients implanted with a LVAD at our institution. Out of 42 patients, 35 had post‐capillary PH before implantation, including 17 with combined post‐ and pre‐capillary PH (Cpc‐PH). Median DLCO was 59% (IQR 47–68%), and it inversely correlated with pulmonary vascular resistance (PVR) (P 0.037) and diastolic pulmonary gradient (DPG) (P 0.042). Compared with baseline, LVAD resulted in improvement in LV diameter (LVDd, P

Background. The diffusing capacity of the lungs for carbon monoxide (DLCO) represents the most sensitive independent factor for highlighting the interstitial lung disease associated with rheumatoid arthritis (RA-ILD). Many studies have analyzed this association between RA and lung modifications because it correlates with a decrease in the patients’ quality of life and a higher mortality. Objective. This study aimed to highlight the importance of DLCO as a predictor of ILD progression in RA, beside the pattern on high-resolution chest CT (HRCT) and the double seropositivity of the disease. Patients and method. This prospective cohort study, carried out between august 2022 and may 2023, included 48 RA patients with ILD, fulfilling the 1987 ACR or 2010 ACR/EULAR classification criteria. Important attention was paid to respiratory functional tests, immunological changes, and specific lung pattern on HRCT. Patients with current malignancies, active infections or Overlap syndrome were excluded from the study. Results. 48 RA patients, mostly women (81%) with a mean age of 65.54±10.58 years old and a median age of RA onset of 52.58±11.36 years, were included. The proportion of patients with a decreased DLCO was 64.6%. Using statistical tests, we found significant corelations between DLCO and age, double seropositivity and a specific pulmonary pattern on HRCT. Conclusion. ILD, an underrecognized disease, may be considered one of the most serious of all extra-articular manifestations in RA, the risk for mortality being triple in these cases. Our results are in correlation with the published data and support the key role of DLCO in the diagnosis and follow-up of these patients. [ABSTRACT FROM AUTHOR]

Abstract Introduction There are no published studies assessing the evolution of combined determination of the lung diffusing capacity for both nitric oxide and carbon monoxide (DLNO and DLCO) 12 months after the discharge of patients with COVID-19 pneumonia. Methods Prospective cohort study which included patients who were assessed both 3 and 12 months after an episode of SARS-CoV-2 pneumonia. Their clinical status, health condition, lung function testings (LFTs) results (spirometry, DLNO-DLCO analysis, and six-minute walk test), and chest X-ray/computed tomography scan images were compared. Results 194 patients, age 62 years (P25–75, 51.5–71), 59% men, completed the study. 17% required admission to the intensive care unit. An improvement in the patients’ exercise tolerance, the extent of the areas of ground-glass opacity, and the LFTs between 3 and 12 months following their hospital discharge were found, but without a decrease in their degree of dyspnea or their self-perceived health condition. DLNO was the most significantly altered parameter at 12 months (19.3%). The improvement in DLNO-DLCO mainly occurred at the expense of the recovery of alveolar units and their vascular component, with the membrane factor only improving in patients with more severe infections. Conclusions The combined measurement of DLNO-DLCO is the most sensitive LFT for the detection of the long-term sequelae of COVID-19 pneumonia and it explain better their pathophysiology.

Simple Summary: Since the approval of durvalumab for the treatment of unresectable non-small-cell lung cancer UICC stage III, the 5-year overall survival rates have risen from below 20% to 50%. Although the validity of lung function testing has been questioned, for long-term survivors, residual pulmonary capacity after treatment is very important in terms of quality of life. The clinically most widely used lung function parameters are forced expiratory volume in one second (FEV1) and carbon monoxide diffusing capacity (DLCO). As the latter represents the alveolar compartment, it seems more suitable in the radiotherapy context. In the current analysis, we can show that DLCO correlates with radiation dosimetry and the incidence of pneumonitis. Hence, from a clinical point of view, peri-treatment lung function testing is indispensable as it helps to optimize radiation treatment planning and predicts pulmonary toxicity. Introduction: Durvalumab following chemoradiotherapy (CRT) for non-small cell lung cancer stage III has become the standard of care (SoC) in the past few years. With this regimen, 5-year overall survival (OS) has risen to 43%. Therefore, adequate pulmonary function (PF) after treatment is paramount in long-term survivors. In this respect, carbon monoxide diffusing capacity (DLCO), which represents the alveolar compartment, seems to be a suitable measure for residual lung capacity. The aim of the current analysis was to correlate DLCO with pneumonitis and radiation dose. Patients and methods: One hundred and twelve patients with histologically confirmed NSCLC III treated between 2015/10 and 2022/03 were eligible for this study. Patients received two cycles of platinum-based induction chemotherapy followed by high-dose radiotherapy (RT). As of 2017/09, durvalumab maintenance therapy was administered for one year. The clinical endpoints were based on the thresholds jointly published by the European Respiratory Society (ERS) and the American Thoracic Society (ATS). Pre-treatment DLCO of 60% was correlated to the incidence of pneumonitis, whereas the post-treatment DLCO decline of 10% was related to radiation dose. Results: Patients with a pre-treatment DLCO < 60% had a higher probability of pneumonitis (n = 98; r = 0.175; p-value 0.042), which could be reproduced in the subgroup of patients who did not receive durvalumab (n = 40; r = 0.288; p-value 0.036). In these individuals, the decline in DLCO ≥ 10% depended significantly on the size of the lung volume receiving between 45% and 65% (V65–45%) of the total radiation dose (r = 0.354; p-value = 0.020) and V20 Total Lung (r = 0.466; corrected p-value = 0.042). Conclusions: The current analysis revealed that DLCO is a predictor for clinically relevant pneumonitis and a monitoring tool for post-treatment lung function as it correlates with radiation dose. This underlines the importance of peri-treatment lung function testing. [ABSTRACT FROM AUTHOR]

Aims: Diffusing capacity of the lung for carbon monoxide (DLCO) reduction is common in heart failure (HF) and is associated with a worse prognosis. Correlations between DLCO and pulmonary hypertension (PH) are unclear, and published data are conflicting; it has been shown that DLCO impairment may persist or even worsen after normalization of pulmonary pressures following left ventricle assist device (LVAD) implantation, maybe reflecting persistent pulmonary damage. We aimed to investigate the impact of pre‐implant DLCO and central haemodynamics on outcome in patients with advanced HF implanted with a LVAD. Methods and results: We retrospectively analysed pre‐implant and post‐implant data from 42 patients implanted with a LVAD at our institution. Out of 42 patients, 35 had post‐capillary PH before implantation, including 17 with combined post‐ and pre‐capillary PH (Cpc‐PH). Median DLCO was 59% (IQR 47–68%), and it inversely correlated with pulmonary vascular resistance (PVR) (P 0.037) and diastolic pulmonary gradient (DPG) (P 0.042). Compared with baseline, LVAD resulted in improvement in LV diameter (LVDd, P < 0.001), mitral regurgitation (P 0.022), and PH (mPAP 24 vs. 36 mmHg, P < 0.001; PAWP 12 vs. 23 mmHg, P 0.001; pulmonary artery compliance, CPA 3.1 vs. 1.9 mL/mmHg, P 0.021). Lower DLCO and Cpc‐PH at baseline were associated with a better LV reverse remodelling post‐implantation (P 0.027 for LVDd) but also with a smaller gain in CPA (P 0.049). Conclusions: Before LVAD implantation, DLCO impairment is associated with higher PVR and DPG, suggesting that it might be an expression of persistent pulmonary damage occurring in Cpc‐PH. After LVAD implantation, both LV dimension and haemodynamics improve. Lower pre‐implant DLCO is associated with better LV reverse remodelling. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with significant mortality. Prognostic biomarkers to identify rapid progressors are urgently needed to improve patient management. Since the lysophosphatidic acid (LPA) pathway has been implicated in lung fibrosis in preclinical models and identified as a potential therapeutic target, we aimed to investigate if bioactive lipid LPA species could be prognostic biomarkers that predict IPF disease progression. LPAs and lipidomics were measured in baseline placebo plasma of a randomized IPF-controlled trial. The association of lipids with disease progression indices were assessed using statistical models. Compared to healthy, IPF patients had significantly higher levels of five LPAs (LPA16:0, 16:1, 18:1, 18:2, 20:4) and reduced levels of two triglycerides species (TAG48:4-FA12:0, -FA18:2) (false discovery rate < 0.05, fold change > 2). Patients with higher levels of LPAs had greater declines in diffusion capacity of carbon monoxide over 52 weeks (P < 0.01); additionally, LPA20:4-high (≥median) patients had earlier time to exacerbation compared to LPA20:4-low (

Abstract Background The mid-term respiratory sequelae in survivors of severe COVID-19 appear highly heterogeneous. In addition, factors associated with respiratory sequelae are not known. In this monocentric prospective study, we performed a multidisciplinary assessment for respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. We analysed factors associated with severe persistent respiratory impairment, amongst demographic, COVID-19 severity, and 3-month assessment. Methods Patients with severe SARS-CoV-2 pneumonia requiring ≥ 4L/min were included for a systematic 3-month visit, including respiratory assessment (symptoms, lung function, CT scan), muscular evaluation (body composition, physical function and activity, disability), psychopathological evaluation (anxiety, depression, post-traumatic stress disorder-PTSD) and quality of life. A cluster analysis was performed to identify subgroups of patients based on objective functional measurements: DLCO, total lung capacity and 6-min walking distance (6MWD). Results Sixty-two patients were analysed, 39% had dyspnea on exercise (mMRC ≥ 2), 72% had DLCO

Abstract Background Few studies have assessed lung function in Hispanic subjects recovering from mild COVID-19. Therefore, we examined the prevalence of impaired pulmonary diffusing capacity for carbon monoxide (DLCO) as defined by values below the lower limit of normal (

Introduction: There are no published studies assessing the evolution of combined determination of the lung diffusing capacity for both nitric oxide and carbon monoxide (DLNO and DLCO) 12 months after the discharge of patients with COVID-19 pneumonia. Methods: Prospective cohort study which included patients who were assessed both 3 and 12 months after an episode of SARS-CoV-2 pneumonia. Their clinical status, health condition, lung function testings (LFTs) results (spirometry, DLNO-DLCO analysis, and six-minute walk test), and chest X-ray/computed tomography scan images were compared. Results: 194 patients, age 62 years (P25–75, 51.5–71), 59% men, completed the study. 17% required admission to the intensive care unit. An improvement in the patients' exercise tolerance, the extent of the areas of ground-glass opacity, and the LFTs between 3 and 12 months following their hospital discharge were found, but without a decrease in their degree of dyspnea or their self-perceived health condition. DLNO was the most significantly altered parameter at 12 months (19.3%). The improvement in DLNO-DLCO mainly occurred at the expense of the recovery of alveolar units and their vascular component, with the membrane factor only improving in patients with more severe infections. Conclusions: The combined measurement of DLNO-DLCO is the most sensitive LFT for the detection of the long-term sequelae of COVID-19 pneumonia and it explain better their pathophysiology. [ABSTRACT FROM AUTHOR]

Reduced lung diffusing capacity for carbon monoxide (DLCO) at rest and increased ventilation (⩒E)-carbon dioxide output (⩒CO2) during exercise are frequent findings in dyspneic smokers with largely preserved FEV1. It remains unclear whether low DLCO and high ⩒E-⩒CO2 are mere reflections of alveolar destruction (i.e. emphysema) or impaired pulmonary perfusion in non-emphysematous tissue contributes to these functional abnormalities. Sixty-four smokers (41 males, FEV1= 84 ± 13%predicted) underwent pulmonary function tests, an incremental exercise test, and quantitative chest computed tomography. Total pulmonary vascular volume (TPVV) was calculated for the entire segmented vascular tree (VIDA Vision™). Using the median % low attenuation area (-950 HU), participants were dichotomized into “Trace” or “Mild” emphysema (E), each group classified into preserved versus reduced DLCO. Within each emphysema subgroup, participants with abnormally low DLCO showed lower TPVV, higher ⩒E-⩒CO2, and exertional dyspnea than those with preserved DLCO (p < 0.05). TPVV (r = 0.34; p = 0.01), but not emphysema (r = −0.05; p = 0.67), correlated with lower DLCO after adjusting for age and height. Despite lower emphysema burden, Trace-E participants with reduced DLCO had lower TPVV, higher dyspnea, and lower peak work rate than the Mild-E with preserved DLCO (p < 0.05). Interestingly, TPVV (but not emphysema) correlated inversely with both dyspnea-work rate (r = −0.36, p = 0.004) and dyspnea-⩒E slopes (r = −0.40, p = 0.001). Reduced pulmonary vascular volume adjusted by emphysema extent is associated with low DLCO and heightened exertional ventilation in dyspneic smokers with minor emphysema. Impaired perfusion of non-emphysematous regions of the lungs has greater functional and clinical consequences than hitherto assumed in these subjects. [ABSTRACT FROM AUTHOR]

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a disease that primarily occurs in elderly individuals. However, it is difficult to diagnose and has a complex disease course. High-resolution computed tomography (HRCT) and lung function testing are crucial for its diagnosis and follow-up. However, the correlation of HRCT findings with lung function test results has not been extensively investigated. Methods This study retrospectively analysed the medical records and images of patients with IPF. Patients with evident emphysema and lung cancer were excluded. The diagnosis of all the included cases was confirmed following a discussion among specialists from multiple disciplines. The correlation of HRCT findings, including fibrotic score, HRCT lung volume, pulmonary artery trunk (PA) diameter and pulmonary vascular volume (PVV), with lung function test parameters, such as forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), was analysed. Results A total of 32 patients were included. Higher fibrotic and PVV scores were significantly correlated with lower DLCO (r = − 0.59, p = 0.01; r = − 0.43, p = 0.03, respectively) but not with FVC. Higher PVV score significantly correlated with higher fibrotic score (r = 0.59, p

Abstract Background Some COVID-19 survivors present lung function abnormalities during follow-up, particularly reduced carbon monoxide lung diffusing capacity (DLCO). To investigate risk factors and underlying pathophysiology, we compared the clinical characteristics and levels of circulating pulmonary epithelial and endothelial markers in COVID-19 survivors with normal or reduced DLCO 6 months after discharge. Methods Prospective, observational study. Clinical characteristics during hospitalization, and spirometry, DLCO and plasma levels of epithelial (surfactant protein (SP) A (SP-A), SP-D, Club cell secretory protein-16 (CC16) and secretory leukocyte protease inhibitor (SLPI)), and endothelial (soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and Angiopoietin-2) 6 months after hospital discharge were determined in 215 COVID-19 survivors. Results DLCO was

RationaleFactors associated with long-term sequelae emerging after the acute phase of COVID-19 (so called “long COVID”) are unclear. Here, we aimed to identify risk factors for the development of COVID-19 sequelae in a prospective cohort of subjects hospitalized for SARS-CoV-2 infection and followed up one year after discharge.MethodsA total of 324 subjects underwent a comprehensive and multidisciplinary evaluation one year after hospital discharge for COVID-19. A subgroup of 247/324 who consented to donate a blood sample were tested for a panel of circulating cytokines.ResultsIn 122 patients (37.8%) there was evidence of at least one persisting physical symptom. After correcting for comorbidities and COVID-19 severity, the risk of developing long COVID was lower in the 109 subjects admitted to the hospital in the third wave of the pandemic than in the 215 admitted during the first wave, (OR 0.69, 95%CI 0.51-0.93, p=0.01). Univariable analysis revealed female sex, diffusing capacity of the lungs for carbon monoxide (DLCO) value, body mass index, anxiety and depressive symptoms to be positively associated with COVID-19 sequelae at 1 year. Following logistic regression analysis, DLCO was the only independent predictor of residual symptoms (OR 0.98 CI 95% (0.96-0.99), p=0.01). In the subgroup of subjects with normal DLCO (> 80%), for whom residual lung damage was an unlikely explanation for long COVID, the presence of anxiety and depressive symptoms was significantly associated to persistent symptoms, together with increased levels of a set of pro-inflammatory cytokines: interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-12, IL-1β, IL-17. In logistic regression analysis, depressive symptoms (p=0.02, OR 4.57 [1.21-17.21]) and IL-12 levels (p=0.03, OR 1.06 [1.00-1.11]) 1-year after hospital discharge were independently associated with persistence of symptoms.ConclusionsLong COVID appears mainly related to respiratory sequelae, prevalently observed during the first pandemic wave. Among patients with little or no residual lung damage, a cytokine pattern consistent with systemic inflammation is in place.

IntroductionSarcoidosis is a chronic multisystem inflammatory disease which may affect any organ. Also bone can be involved both directly and indirectly. Data on BMD values and fragility fractures in sarcoidosis patients are few and heterogeneous. This study aimed to characterized the presence of fracture and the relative risk factors in patients with sarcoidosis.Materials and methodsIn this single center cross-sectional study we evaluated 252 sarcoidosis patients (54.7 ± 12.1 years) compared to sex-and age matched healthy controls. We measured BMD at lumbar spine, at femoral neck and at total hip. Moreover, the presence of fragility fractures was collected during osteoporosis visit and all radiological images were examined for the presence of any vertebral fracture according to Genant’s method’s. Lung function measurements, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, and diffusion capacity for carbon monoxide (DLCO) were assessed.ResultsBone Mineral Density T-scores were lower in patients affected by sarcoidosis with respect to those obtained in healthy controls, but the difference was statistically significant only for BMD-LS (p < 0.01) and BMD-TH (p < 0.05). Moreover, BMD values at all skeletal sites were significantly associated with DLCO (%) (p < 0.05). The prevalence of fragility fracture was higher in patients with sarcoidosis than in healthy controls (30.6 vs. 12.3%). The patients with ≥3 vertebral fracture had lower values of FVC (%), FEV1 (%), and DLCO (%). Multiple regression analyses showed that BMI was positively associated with fragility fracture, while BMD-TH, DLCO(%) and therapy use was negatively associated.ConclusionsVertebral fractures represent a frequent complication in patients with sarcoidosis. Furthermore, the number of vertebral fractures was linked with a worsening in pulmonary functional tests. Therefore, the degree of severity of the sarcoidosis disease appears to be the main determinant of bone fragility.

Background: The mid-term respiratory sequelae in survivors of severe COVID-19 appear highly heterogeneous. In addition, factors associated with respiratory sequelae are not known. In this monocentric prospective study, we performed a multidisciplinary assessment for respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. We analysed factors associated with severe persistent respiratory impairment, amongst demographic, COVID-19 severity, and 3-month assessment.Methods: Patients with severe SARS-CoV-2 pneumonia requiring ≥ 4L/min were included for a systematic 3-month visit, including respiratory assessment (symptoms, lung function, CT scan), muscular evaluation (body composition, physical function and activity, disability), psychopathological evaluation (anxiety, depression, post-traumatic stress disorder-PTSD) and quality of life. A cluster analysis was performed to identify subgroups of patients based on objective functional measurements: DLCO, total lung capacity and 6-min walking distance (6MWD).Results: Sixty-two patients were analysed, 39% had dyspnea on exercise (mMRC ≥ 2), 72% had DLCO < 80%, 90% had CT-scan abnormalities; 40% had sarcopenia/pre-sarcopenia and 31% had symptoms of PTSD. Cluster analysis identified a group of patients (n = 18, 30.5%) with a severe persistent (SP) respiratory impairment (DLCO 48 ± 12%, 6MWD 299 ± 141 m). This SP cluster was characterized by older age, severe respiratory symptoms, but also sarcopenia/pre-sarcopenia, symptoms of PTSD and markedly impaired quality of life. It was not associated with initial COVID-19 severity or management.Conclusions and Clinical Implication: We identified a phenotype of patients with severe persistent respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. Our results highlight the need for multidisciplinary assessment and management after severe SARS-CoV-2 pneumonia. Trial registration The study was registered on ClinicalTrials.gov (May 6, 2020): NCT04376840. [ABSTRACT FROM AUTHOR]

Background: Up to 53% of individuals who had mild COVID-19 experience symptoms for >3-month following infection (Long-CoV). Dyspnea is reported in 60% of Long-CoV cases and may be secondary to impaired exercise capacity (VO2peak) as a result of pulmonary, pulmonary vascular, or cardiac insult. This study examined whether cardiopulmonary mechanisms could explain exertional dyspnea in Long-CoV. Methods: A cross-sectional study of participants with Long-CoV (n = 28, age 40 ± 11 years, 214 ± 85 days post-infection) and age- sex- and body mass index-matched COVID-19 naïve controls (Con, n = 24, age 41 ± 12 years) and participants fully recovered from COVID-19 (ns-CoV, n = 14, age 37 ± 9 years, 198 ± 89 days post-infection) was conducted. Participants self-reported symptoms and baseline dyspnea (modified Medical Research Council, mMRC, dyspnea grade), then underwent a comprehensive pulmonary function test, cardiopulmonary exercise test, exercise pulmonary diffusing capacity measurement, and rest and exercise echocardiography. Results: VO2peak, pulmonary function and cardiac/pulmonary vascular parameters were not impaired in Long- or ns-CoV compared to normative values (VO2peak: 106 ± 25 and 107 ± 25%predicted, respectively) and cardiopulmonary responses to exercise were otherwise normal. When Long-CoV were stratified by clinical dyspnea severity (mMRC = 0 vs mMRC≥1), there were no between-group differences in VO2peak. During submaximal exercise, dyspnea and ventilation were increased in the mMRC≥1 group, despite normal operating lung volumes, arterial saturation, diffusing capacity and indicators of pulmonary vascular pressures. Interpretation: Persistent dyspnea after COVID-19 was not associated with overt cardiopulmonary impairment or exercise intolerance. Interventions focusing on dyspnea management may be appropriate for Long-CoV patients who report dyspnea without cardiopulmonary impairment. [ABSTRACT FROM AUTHOR]

Ayad Mohammed Salem,1 Noor Al Khathlan,2 Abdulelah Fawzi Alharbi,3 Turki Alghamdi,3 Saleh AlDuilej,3 Mohammed Alghamdi,3 Majed Alfudhaili,3 Ahmed Alsunni,1 Talay Yar,1 Rabia Latif,1 Nazish Rafique,1 Lubna Al Asoom,1 Hussein Sabit4 1Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2Department of respiratory care, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 3College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 4Department of Genetics, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaCorrespondence: Ayad Mohammed SalemDepartment of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, PO Box 2114, Dammam, 31451, Saudi ArabiaEmail ayadsalem@iau.edu.saBackground: The sequelae of COVID-19 pneumonia on pulmonary function and airways inflammation are still an area of active research.Objective: This research aimed to explore the long-term impact of COVID-19 pneumonia on the lung function after three months from recovery.Methods: Fifty subjects (age 18– 60 years) were recruited and classified into two groups: the control group (30 subjects) and the post-COVID-19 pneumonia group (20 patients). Pulmonary function tests, spirometry, body plethysmography [lung volumes and airway resistance (Raw)], diffusion capacity for carbon monoxide (DLCO), and fractional exhaled nitric oxide (FeNO), were measured after at least 3 months post-recovery.Results: Significant reduction in total lung capacity (TLC), forced vital capacity (FVC), forced expiratory volume (FEV1), FEV1/FEV, and diffusing capacity for carbon monoxide (DLCO) was observed in post-COVID-19 subjects compared to controls. Restrictive lung impairment was observed in 50% of post-COVID-19 cases (n = 10) compared to 20% in the control group (n = 6, P = 0.026). In addition, mild diffusion defect was detected in 35% (n = 7) of the post-COVID-19 group compared to 23.3% (n = 7) in the controls (P = 0.012).Conclusion: COVID-19 pneumonia has an impact on the lung functions in terms of restrictive lung impairment and mild diffusion defect after three months from recovery. Therefore, a long-term follow-up of the lung function in post-COVID-19 survivors is recommended.Keywords: COVID-19, pneumonia, PFT, DLCO, FeNO

Abstract Background Secondary polycythemia is associated with cigarette smoking and chronic obstructive pulmonary disease (COPD). However, the prevalence of polycythemia in COPD and the contributing risk factors for polycythemia in COPD have not been extensively studied. Methods We analyzed the presence of secondary polycythemia in current and former smokers with moderate to very severe COPD at the five-year follow-up visit in the observational COPDGene study. We used logistic regression to evaluate the association of polycythemia with age, sex, race, altitude, current smoking status, spirometry, diffusing capacity for carbon monoxide (DLCO), quantitative chest CT measurements (including emphysema, airway wall thickness, and pulmonary artery to aorta diameter ratio), resting hypoxemia, exercise-induced hypoxemia, and long-term oxygen therapy. Results In a total of 1928 COPDGene participants with moderate to very severe COPD, secondary polycythemia was found in 97 (9.2%) male and 31 (3.5%) female participants. In a multivariable logistic model, severe resting hypoxemia (OR 3.50, 95% CI 1.41–8.66), impaired DLCO (OR 1.28 for each 10-percent decrease in DLCO % predicted, CI 1.09–1.49), male sex (OR 3.60, CI 2.20–5.90), non-Hispanic white race (OR 3.33, CI 1.71–6.50), current smoking (OR 2.55, CI 1.49–4.38), and enrollment in the Denver clinical center (OR 4.42, CI 2.38–8.21) were associated with higher risk for polycythemia. In addition, continuous (OR 0.13, CI 0.05–0.35) and nocturnal (OR 0.46, CI 0.21–0.97) supplemental oxygen were associated with lower risk for polycythemia. Results were similar after excluding participants with anemia and participants enrolled at the Denver clinical center. Conclusions In a large cohort of individuals with moderate to very severe COPD, male sex, current smoking, enrollment at the Denver clinical center, impaired DLCO, and severe hypoxemia were associated with increased risk for secondary polycythemia. Continuous or nocturnal supplemental oxygen use were associated with decreased risk for polycythemia.

Summary: Background: The long-term prognosis of COVID-19 survivors remains poorly understood. It is evidenced that the lung is the main damaged organ in COVID-19 survivors, most notably in impairment of pulmonary diffusion function. Hence, we conducted a meta-analysis of the potential risk factors for impaired diffusing capacity for carbon monoxide (DLCO) in convalescent COVID-19 patients. Methods: We performed a systematic search of PubMed, Web of Science, Embase, and Ovid databases for relevant studies from inception until January 7, 2022, limited to papers involving human subjects. Studies were reviewed for methodological quality. Fix-effects and random-effects models were used to pool results. Heterogeneity was assessed using I2. The publication bias was assessed using the Egger's test. PROSPERO registration: CRD42021265377. Findings: A total of eighteen qualified articles were identified and included in the systematic review, and twelve studies were included in the meta-analysis. Our results showed that female (OR: 4.011; 95% CI: 2.928–5.495), altered chest computerized tomography (CT) (OR: 3.002; 95% CI: 1.319–6.835), age (OR: 1.018; 95% CI: 1.007–1.030), higher D-dimer levels (OR: 1.012; 95% CI: 1.001–1.023) and urea nitrogen (OR: 1.004;95% CI: 1.002–1.007) were identified as risk factors for impaired DLCO. Interpretation: Pulmonary diffusion capacity was the most common impaired lung function in recovered patients with COVID-19. Several risk factors, such as female, altered chest CT, older age, higher D-dimer levels and urea nitrogen are associated with impairment of DLCO. Raising awareness and implementing interventions for possible modifiable risk factors may be valuable for pulmonary rehabilitation. Funding: This work was financially supported by Emergency Key Program of Guangzhou Laboratory (EKPG21-29, EKPG21-31), Incubation Program of National Science Foundation for Distinguished Young Scholars by Guangzhou Medical University (GMU2020-207).

Background: Up to 53% of individuals who had mild COVID-19 experience symptoms for >3-month following infection (Long-CoV). Dyspnea is reported in 60% of Long-CoV cases and may be secondary to impaired exercise capacity (VO2peak) as a result of pulmonary, pulmonary vascular, or cardiac insult. This study examined whether cardiopulmonary mechanisms could explain exertional dyspnea in Long-CoV.Methods: A cross-sectional study of participants with Long-CoV (n = 28, age 40 ± 11 years, 214 ± 85 days post-infection) and age- sex- and body mass index-matched COVID-19 naïve controls (Con, n = 24, age 41 ± 12 years) and participants fully recovered from COVID-19 (ns-CoV, n = 14, age 37 ± 9 years, 198 ± 89 days post-infection) was conducted. Participants self-reported symptoms and baseline dyspnea (modified Medical Research Council, mMRC, dyspnea grade), then underwent a comprehensive pulmonary function test, cardiopulmonary exercise test, exercise pulmonary diffusing capacity measurement, and rest and exercise echocardiography.Results: VO2peak, pulmonary function and cardiac/pulmonary vascular parameters were not impaired in Long- or ns-CoV compared to normative values (VO2peak: 106 ± 25 and 107 ± 25%predicted, respectively) and cardiopulmonary responses to exercise were otherwise normal. When Long-CoV were stratified by clinical dyspnea severity (mMRC = 0 vs mMRC≥1), there were no between-group differences in VO2peak. During submaximal exercise, dyspnea and ventilation were increased in the mMRC≥1 group, despite normal operating lung volumes, arterial saturation, diffusing capacity and indicators of pulmonary vascular pressures.Interpretation: Persistent dyspnea after COVID-19 was not associated with overt cardiopulmonary impairment or exercise intolerance. Interventions focusing on dyspnea management may be appropriate for Long-CoV patients who report dyspnea without cardiopulmonary impairment.