Diffusing Capacity Of Lung Research Articles

Assessment of the value of 6-min walk test to predict the severity of interstitial lung disease among Indian patients

Introduction: The prevalence of interstitial lung disease (ILD) is increasing. High-resolution computerized tomography (HRCT), despite having limitations, remains the choice of method for diagnosis and assessment of severity of ILD. Objective: To determine the efficacy of 6-min walk test to assess the severity of the ILD compared to HRCT. Methodology: A cross-sectional study was done among 40 patients with ILD in a tertiary hospital in Hyderabad. The data included age, gender, smoking, HRCT, 6-min walk test, spirometry, diffusion lung capacity and medical history. Mann–Whitney U test, Kruskal–Wallis test, and ROC curve were used to determine the outcomes. Results: The mean age of participants was 57.18 + 13.01 years. 62.5% never smoked. Overall, 50% had severe ILD, and the rest had mild to moderate. The distance walked per 6-min, SpO2 before and SpO2 after, was significantly lower (p = 0.001; 0.002; <0.001, respectively) among patients with severe ILD than mild or moderate. The sensitivity and 1-specificity of the distance walked in 6-min to detect the severity of ILD was 0.90 and 0.31, respectively; sensitivity and 1-specificity of SpO2 before the test was 0.81 and 0.34, while that of SpO2 after the test was 0.90 and 0.17, respectively. Conclusion: This study found that the 6-min walk test is highly sensitive and specific for predicting the severity of ILD among patients. All three components of the 6-min walk test: distance, oxygen saturation before, and oxygen saturation after the test significantly lowered and were independent predictors of severe ILD.

Evaluation of the Relationship Between Pulmonary Perfusion Via Chest Digital Dynamic Radiography System and Diffusing Capacity Test.

Non-invasive, visual, and quantitative in vivo evaluation of pulmonary blood flow is helpful in assessing gas exchange at the alveolar level. A chest digital dynamic radiography system (CDDR) has the potential to visually and quantitatively express pulmonary haemodynamics using temporal changes in radiographic transparency synchronised with the heartbeat. The lung-diffusing capacity (DLCO) test involves membranous factors comprising the alveolar membrane, interstitium, and vascular walls. Additionally, DLCO includes pulmonary blood flow factors defined by pulmonary capillary blood flow and haemoglobin levels. In individuals lacking an alveolar septum, interstitial abnormalities or anaemia leading to changes in DLCO may reflect changes in the pulmonary blood flow. Here, we investigated the usefulness of CDDR in evaluating pulmonary blood flow by comparing it with DLCO.For pulmonary blood flow, we extracted and visualised signal changes in the lung field synchronised with heart rate during CDDR imaging and created a maximum intensity projection (MIP). The DLCO was measured using the single-breath method. Among the patients who underwent CDDR, 10 with FEV/FVC (FEV1.0%)>70% and 16 with COPD (FEV1.0%<70%) without noticeable interstitial changes were included, with a cutoff=70%/predicted value. MIP was compared as a pulmonary blood flow evaluation method in the DLCO≥70% group (control group: n=15) and the DLCO<70% group (decreased DLCO group: n=11). The mean and median values of MIP in the reduced group were lower than those in the control group (p<0.05).Pulmonary blood flow evaluated using CDDR may be able to assess pulmonary circulatory disturbances visually and quantitatively, as indicated by decreased pulmonary diffusion capacity in patients with negligible pulmonary interstitial changes and anaemia.

SPECT/CT to quantify early small airway disease and its relationship to clinical symptoms in smokers with normal lung function: a pilot study.

Smokers frequently display respiratory symptoms despite the fact that their pulmonary function tests (PFTs) can be normal. Quantitative lung ventilation single-photon emission computed tomography (SPECT/CT) can provide a quantification of lung ventilatory homogeneity and could prove useful as an early marker of airway disease in smokers. We measured the effects of smoking on regional ventilation distribution in subjects with normal lung function and evaluated whether ventilation distribution in these subjects is related to lung function tests results and clinical symptoms. Subjects without any history of respiratory disease were prospectively recruited and separated in two groups: active smokers (AS: ≥10 cigarettes/day and history of ≥15 pack-years) and never smokers (NS: lifetime exposure of <5 cigarettes). All subjects performed PFTs (which had to be normal, defined as z-score values of forced expiratory volume in 1s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, total lung capacity (TLC) residual volume and diffusion capacity (DLCO) all falling between -1.65 and +1.65) and underwent SPECT/CT with Technegas, which generated subject- specific ventilation heterogeneity maps. The area under the compensated coefficient of variation (CV) density curve for CV values > 40%, (AUC-CV40%) was used as the measure of ventilation heterogeneity. 30 subjects were recruited (15 per group). Subjects in the AS group displayed higher dyspnea levels (1 [1-2] vs. 0 [0-1] units on mMRC scale, p < 0.001). AUC- CV40% was significantly higher in the AS group (0.386 ± 0.106 vs. 0.293 ± 0.069, p = 0.004). AUC-CV40% was significantly correlated to FEV1 (rho = -0.47, p = 0.009), DLCO (rho = -0.49, p = 0.006), CAT score (rho = 0.55, p = 0.002) and mMRC score (rho = 0.54, p = 0.002). Subjects with mMRC >0 had higher AUC-CV40% values than those without dyspnea (0.289 ± 0.071 vs. 0.378 ± 0.102, p = 0.006), while FEV1 and DLCO were not different between those groups. ROC analyses showed that the AUC for AUC-CV40% in identifying subjects with mMRC score >0 was 0.78 (95%CI 0.61-0.95, p = 0.009), which was significantly higher than that of FEV1 and DLCO. In smokers with normal lung function, ventilatory inhomogeneities can be quantified using SPECT/CT. AUC-CV40% values are related to lung function decline and to respiratory symptomatology, suggesting a potential role for this marker in the evaluation of symptomatic smokers.

The Impact of Different Smoking Behavior on Pulmonary Function and Pulmonary Hypertension Among Chinese Male Patients with Chronic Obstructive Pulmonary Disease.

Cigarette smoking is the most recognized risk factor of chronic obstructive pulmonary disease (COPD) in China. However, there are no studies analyzing the impact of different smoking behaviors on pulmonary function and pulmonary hypertension (PH) among Chinese male patients with COPD. Chinese male smokers with COPD performed pulmonary function tests. Clinical characteristics, smoking behavior features, spirometry and echocardiographic results were compared between the two groups stratified by initial smoking age (18 years old) or complicated PH. The early-smoking group had more respiratory symptoms, more severe smoking behavior, worse pulmonary function with lower FEV1%pre (38.5% vs 70.2%) and FEV1/FVC% (47.5% vs 63.8%), and higher systolic pulmonary artery pressure (sPAP: 38.6 vs 33.9 mmHg) than the late-smoking group. Initiating smoking before adulthood was an independently contributing factor of ventilatory dysfunction and Global Initiative for Obstructive Lung Disease (GOLD) stage escalation. It also had a significant interaction with long smoking duration (≥30 years), characterized by markedly decreased lung volumes (VC%pre: 64.0% vs 84.5%), impaired diffusing capacity (DLCO%pre: 58.0% vs 76.8%) and severe emphysema (RV/TLC%pre: 145.2% vs 130.2%). COPD patients complicated with PH exhibited worse ventilatory function (FEV1%pre: 43.2% vs 56.2%), impaired diffusion capacity (DLCO%pre: 56.7% vs 77.1%) and decreased lung volume (VC%pre: 67.67% vs 75.38%). Both severe smoking behaviors and impaired pulmonary function had close correlations with sPAP. The early-smoking group exhibited predominantly ventilation dysfunction and had complex interactions with long smoking duration to further affect lung volume and diffusion capacity. Different smoking behaviors influenced variations of pulmonary dysfunction and comorbid PH in patients with COPD.

ЛЕГЕНЕВИЙ АЛЬВЕОЛЯРНИЙ ПРОТЕЇНОЗ: ВИПАДОК СУБТОТАЛЬНОГО УРАЖЕННЯ ПАРЕНХІМИ ЛЕГЕНЬ)

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease, characterized by the intraalveolar accumulation of surfactant-like lipoprotein substance. There are three forms of the disease: autoimmune (formerly known as idiopathic), secondary and congenital PAP. The disturbances of surfactant metabolism (protein-lipoid complex secreted by type II pneumocytes) play the crucial role in the development of the disease. Surfactant decreases a surface tension of alveoli and prevents its collapse at the end of the expiration and takes part in protection against infections as well. Surfactant is inactivated through the transformation into the surface-inactive aggregates, which are mainly absorbed by type II pneumocytes. The rest of surfactant are catabolized by alveolar macrophages (AM). This process is regulated by cytokines, especially granulocyte-macrophage colony-stimulating factor (GM-CSF) being the most important of them. Disturbances of interrelation between GM-CSF and cellular receptors blocks the signals to effector cells for surfactant deactivation. This is resulted in excessive accumulation of surfactant in alveoli. General lavage of the lung is a standard method of symptomatic management of PAP. Contemporary pathogenesis treatment uses two approaches — increasing the clearance of surfactant by means of exogenous GM-CSF administration and decreasing the level of GM-CSF antibodies using the rituximab and plasmapheresis. Due to the use of broncho-alveolar lavage (BAL) 5-year survival rate of th patients reaches 95 %. The mortality depends on the area of lung lesion and reversely correlated with the timely diagnosis and treatment. We report the case of subtotal lung parenchyma lesion associated with severe respiratory failure in 46 years old patient. Three series of BAL (5 procedures in each with 1-2 months interval) were performed using the limited volume of lavage fluid due to the severity of the patient’s condition. The results was an improvement of clinical condition, resolution of respiratory failure, significant reduction of the size of the lesions, improved lung transparency on CT scan, restoration of lung diffusion and total lung capacity. Conclusion. Therapeutic BAL is an effective method of PAP management. The outcome of clinical case presented and our many years experience confirm not only the effectiveness of conventional BAL with reduced lavage volume application but also a safety of fiberoptic bronchoscopy, especially in patients with subtotal involvement of lung parenchyma. Key words: pulmonary alveolar proteinosis, subtotal pulmonary parenchyma involvement, pulmonary bronchoalveolar lavage, efficiency.

Low pre-immunotherapy forced vital capacity is associated with poor outcomes in non-small cell lung cancer patients receiving immunotherapy regardless of prior treatment history.

Many patients with lung cancer have underlying chronic lung diseases. We assume that baseline lung functions might also affect the prognosis of non-small cell lung cancer (NSCLC) patients receiving immunotherapy. We aimed to assess the impact of pretreatment clinical parameters, including lung function measures such as forced vital capacity (FVC), on the prognosis of patients with NSCLC following immune checkpoint inhibitors (ICIs) therapy. Retrospective multicenter study. Study subjects were consecutively selected from a multicenter cohort of patients with NSCLC who were undergoing immunotherapy. Patients were selected regardless of their initial cancer stage and prior treatment. The primary outcome was immunotherapy-related overall survival (iOS), defined as the duration from the initiation of immunotherapy to the time patients were censored. Spirometry values were acquired before bronchodilator application and were performed within the year before the first ICI treatment. We selected 289 patients for evaluation. The median iOS was 10.9 months (95% confidence interval (CI), 7.5-14.3). Programmed death-ligand 1 (PD-L1) expression, tested by SP263, was <1% in 20.9%, 1%-49% in 44.3%, and ⩾50% in 32.6% of the patients. ICI was used most often as second-line treatment (70.2%), followed by first line (13.1%), and third line (11.4%). In the Kaplan-Meier analysis, the median iOS of the low FVC group was significantly shorter than that in the preserved FVC group (6.10 (95% CI, 4.45-7.76) months vs 14.40 (95% CI, 10.61-18.34) months, p < 0.001)). A Cox regression analysis for iOS showed that age, poor performance status, PD-L1 expression measured by SP263, stage at diagnosis, and FVC (% predicted) were independent predictive factors. When we replaced FVC (%) in the multivariable analysis with forced expiratory volume in 1 s (%), diffusing lung capacity for carbon monoxide (DLco; %), or DLco (absolute), each of the pulmonary function factors showed a significant association with iOS. Pre-immunotherapy FVC (%) predicted immunotherapy-related outcomes in NSCLC patients, regardless of initial stage at diagnosis and prior treatment modalities.

Analysis of Respiratory System Functional Parameters at Different Time Points after COVID-19

The objective: to define the type and evaluate the severity of respiratory functional disorders after COVID-19. \Subjects and Methods. A retrospective observational study was conducted. The following parameters were analyzed: demographic data, data from chest computed tomography during the acute period of the disease (CTmax), parameters of pulmonary function tests (PFT) – spirometry, body plethysmography and diffusion test. Those data were collected in 341 patients, 262 (76.8%) of them were men (median age – 48 (41.5–57) years, median durtaion of Period A (onset of COVID-19 before PFT) made 53 (28.5–111) days). Depending on duration of Period A, patients were divided into three groups: Group 1 – up to 90 days (n=221), Group 2 – 90-180 days (n=80), and Group 3 – more than 180 days (n=40). In patients of Groups 1, 2 and 3, in 68.3%, 47.5% and 32,5% of cases, respectively, disorders of diffusing lung capacity were recorded, which were associated to a greater extent with CTmax, and to a lesser extent with duration of Period A. The restrictive type of ventilation disorders was observed in 33.5% and 11% of cases in Groups 1 and 2, no restriction was detected in Group 3, airway obstruction was detected in 8%, 5%, 7.5% of cases in Groups 1, 2 and 3 respectively.Conclusion. Disorder of diffusing lung capacity was the most common functional disorder of the respiratory system after COVID-19, and therefore it is advisable to include a diffusion test along with spirometry to the examination plan of such patients.

FOXP3+ regulatory T cells are associated with the severity and prognosis of sarcoidosis.

Sarcoidosis is an inflammatory granulomatous disease of unknown etiology with predominant lung involvement. Organ involvement and disease severity, as well as the nature of immune alterations, vary among patients leading to a range of clinical phenotypes and outcomes. Our objective was to evaluate the association of disease course and immune responses in pulmonary sarcoidosis. In this prospective cohort study of 30 subjects, most of whom were followed for one year, we evaluated 14 inflammatory markers in plasma, 13 Treg/T cell flow cytometry markers and 8 parameters of FOXP3+ Treg biology, including suppressive function, epigenetic features and stability. We identified a set of 13 immunological parameters that differ in sarcoidosis subjects in comparison with healthy donors. Five of those were inversely correlated with suppressive function of Tregs in sarcoidosis, and six (TNFα, TNFR I and II, sCD25, Ki-67 and number of Tregs) were particularly upregulated or increased in subjects with thoracic lymphadenopathy. Treg suppressive function was significantly lower in patients with thoracic lymphadenopathy, and in patients with higher burdens of pulmonary and systemic symptoms. A combination of five inflammatory markers, Ki-67 expression, Treg function, and lung diffusion capacity evaluated at study entry predicted need for therapy at one year follow-up in 90% of cases. Tregs may suppress ongoing inflammation at local and systemic levels, and TNFα, TNFR I and II, sCD25 and Ki-67 emerge as attractive biomarkers for in vivo sarcoid inflammatory activity.

Post-COVID syndrome and capillary bed abnormalities detected by videocapillaroscopy

Post-COVID syndrome (PCS) is a pressing problem in clinical practice. Dyspnea, along with neurologic and cardiovascular symptoms, is the most common symptom indicating low exercise capacity (EC) that reduces quality of life. The aim of this study was to investigate shortness of breath and the capillary bed abnormalities detected video capillaroscopy (VCS) in patients with PCS.Methods. The study included patients with PCS (n = 60) suffering from shortness of breath. Dyspnea was assessed using the 6-minute walk test (6-MWT). The capillary bed abnormality was diagnosed using VCS.Results. Patients with ACL walked an average of 79.5% of the predicted distance in the 6-MWT. They also had a decrease in pulse oximetry readings. The patients were divided into 2 groups: 1st – patients with desaturation, 2nd – patients without desaturation. Significant differences were observed between patients with and without desaturation, especially in the 6-MWT distance, pulse oximetry, and dyspnea before and after the 6-MWT. Patients with desaturation had a higher desaturation-to-distance ratio, a higher O2-GAP index, and higher cardiac effort levels, as well as a significant decrease in the proportion of perfused capillaries (PPC), mean capillary density, and a marked increase in the proportion of tortuous and branched capillaries. There was a direct correlation between PPC and diffusing lung capacity for carbon monoxide (DLCO), and carbon monoxide transfer coefficient (DLCO/Va), distance traveled during the 6-MWT and percentage (%) of predicted distance, inverse correlation between PPC and cardiac effort. There was a direct correlation between the percentage (%) of capillary recovery and 6-MWT distance and the percentage (%) of predicted distance, as well as an inverse correlation with the ratio of desaturation indicators and walking distance. Similarly, there was a direct correlation between mean capillary density and DLCO/Va, while the proportion (%) of tortuous capillaries was inversely correlated with DLCO, and the proportion (%) of branched capillaries was inversely correlated with DLCO/Va.Conclusion. The multifactorial nature of the mechanisms of dyspnea in patients with PCS was demonstrated, with the important role of vasculopathy. Continuous monitoring of pulse oximetry, heart rate and VCS are effective methods to screen and assess the condition of patients with PCS and dyspnea.

English

Introduction: Lung diffusion capacity of carbon monoxide (DLCO) provides a measure of gas transfer in the lungs, which increase in relation to exercise and decrease in the presence of lung interstitial disease. The aim of this study is to evaluate the changes in lung diffusion after anaerobic and aerobic exercise in a cycle ergometer. Material and method: The participants were 9 healthy active subjects, including six females and three males (age: 24.3 ± 3.1 years). Lung diffusion capacity for carbon monoxide (DLCO) was studied under two different protocols: In the first day, DLCO was measured at SL at rest (SL-R), after 30-s maximal exercise (SL-ANA), and after 15-min moderate continuous exercise (SL-AER). In the second day, DLCO was evaluated at rest at SL, and then at HA (4,000 m) at rest (HA-R) and after 30-min of moderate interval exercise (HA-AER). Results: There was an increase in DLCO from rest to after SL-ANA (32.5 ± 6.4 to 40.3 ± 11.6 mL·min-1·mmHg-1, P = 0.027). In the second day, DLCO was evaluated at rest at SL, and then at HA (4,000 m) at rest (HA-R) and after 30-min of moderate interval exercise (HA-AER). During HA exposure, there was no changes in DLCO, either at HA-R, or after HA-AER. Conclusions: Lung diffusion capacity largely increased after 30-s maximal exercise in a cycle ergometer, although the O2 -dependence is small during this type of anaerobic exercise. Thus, exercise intensity may be a key modulator of the changes in lung diffusing capacity in relation to exercise.

Individuals with psychosis present a reduced lung diffusion capacity and early spirometry alterations: Results from a cross-sectional study

ObjectiveIndividuals with psychosis present a greater prevalence of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). These chronic respiratory diseases are preceded by early lung function alterations; such as preserved ratio impaired spirometry (PRISm) or normal spirometry but low diffusion capacity of the lung for carbon monoxide (DLCO). However, there is no previous evidence on these lung function alterations in psychosis. The aim of this study is to evaluate the risk of having spirometry and DLCO alterations in subjects with psychosis compared with a control group. MethodsCross-sectional study on a cohort of 170 individuals including 96 subjects with psychosis and 74 sex-age-and smoking habit matched healthy controls. All subjects were under 60 years-old, and without COPD or asthma. Respiratory function was evaluated through spirometry. Clinical characteristics and DLCO values were recorded. ResultsPatients with psychosis showed lower spirometry results, both in terms of absolute and percentage of Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1). Absolute and percentage levels of diffusion were also lower in patients with psychosis. The percentage of individuals with DLCO<80% was higher among patients with psychosis (75% vs. 40%, p < 0.001). And the prevalence of PRISm was higher among patients with psychosis (10.4% vs. 1.4%, p < 0.001). Multivariate logistic regression analysis indicated that psychosis was an independent predictor of DLCO<80% (OR 5.67, CI95% 1.86–17.27). ConclusionPatients with psychosis and females had early alterations in lung function. These results suggest that early screening for lung disease should be encouraged in psychosis.

Kidney Transplant Recipients Show Limited Lung Diffusion Capacity but Similar Hydrogen Peroxide Exhalation as Healthy Matched Volunteers: A Pilot Study.

Patients with end-stage chronic kidney disease show higher systemic oxidative stress and exhale more hydrogen peroxide (H2O2) than healthy controls. Kidney transplantation reduces oxidative stress and H2O2 production by blood polymorphonuclear leukocytes (PMNs). Kidney transplant recipients (KTRs) may be predisposed to an impairment of lung diffusing capacity due to chronic inflammation. Lung function and H2O2 concentration in the exhaled breath condensate (EBC) were compared in 20 KTRs with stable allograft function to 20 healthy matched controls. Serum interleukin eight (IL-8) and C-reactive protein (CRP), blood cell counts, and spirometry parameters did not differ between groups. However, KTRs showed lower total lung diffusing capacity for carbon monoxide, corrected for hemoglobin concentration (TLCOc), in comparison to healthy controls (92.1 ± 11.5% vs. 102.3 ± 11.9% of predicted, p = 0.009), but similar EBC H2O2 concentration (1.63 ± 0.52 vs. 1.77 ± 0.50 µmol/L, p = 0.30). The modality of pre-transplant renal replacement therapy had no effect on TLCOc and EBC H2O2. TLCOc did not correlate with time after transplantation. In this study, TLCOc was less reduced in KTRs in comparison to previous reports. We suggest this fact and the non-elevated H2O2 exhalation exhibited by KTRs, may result perhaps from the evolution of the immunosuppressive therapy.

Early lung diffusion abnormalities and airways' inflammation in children with type 1 diabetes.

Type 1 diabetes (T1D) impacts lung function and exercise capacity in adults, but limited information is available in children. We hypothesize that T1D causes alterations in pulmonary function and cardiorespiratory fitness, i.e., exercise capacity, at early stages of the disease, due to the presence of inflammation and vascular damage. Therefore, we aim to investigate pulmonary function before and after exercise in children with T1D as compared to age matched healthy controls. Twenty-four children with T1D and twenty healthy controls underwent body plethysmography, diffusion lung capacity for carbon monoxide and fractional exhaled nitric oxide at rest and after cardio-pulmonary exercise test. In children with T1D, baseline total lung capacity and diffusion lung capacity for carbon monoxide were reduced as compared to healthy controls. Children with T1D also showed a reduced exercise capacity associated with poor aerobic fitness. Accordingly, diffusion lung capacity for carbon monoxide tended to increase with exercise in healthy controls, while no change was observed in children with T1D. Fractional exhaled nitric oxide was significantly higher at baseline and tended to increase with exercise in children with T1D, while no changes were observed in healthy controls. Altered diffusion lung capacity for carbon monoxide, increased fractional exhaled nitric oxide and a poor aerobic fitness to exercise suggests the presence of early pulmonary abnormalities in children with T1D.

The alveolar-capillary unit in the physiopathological conditions of heart failure: identification of a potential marker.

In this review, we describe the structure and function of the alveolar-capillary membrane and the identification of a novel potential marker of its integrity in the context of heart failure (HF). The alveolar-capillary membrane is indeed a crucial structure for the maintenance of the lung parenchyma gas exchange capacity, and the occurrence of pathological conditions determining lung fluids accumulation, such as HF, might significantly impair lung diffusion capacity altering the alveolar-capillary membrane protective functions. In the years, we found that the presence of immature forms of the surfactant protein-type B (proSP-B) in the circulation reflects alterations in the alveolar-capillary membrane integrity. We discussed our main achievements showing that proSP-B, due to its chemical properties, specifically binds to high-density lipoprotein, impairing their antioxidant activity, and likely contributing to the progression of the disease. Further, we found that immature proSP-B, not the mature protein, is related to lung abnormalities, more precisely than the lung function parameters. Thus, to the list of the potential proposed markers of HF, we add proSP-B, which represents a precise marker of alveolar-capillary membrane dysfunction in HF, correlates with prognosis, and represents a precocious marker of drug therapy.

Increased minute ventilation-to-carbon dioxide slope during cardiopulmonary exercise test is associated with poor postoperative outcome following lung cancer resection.

Ventilatory efficiency [minute ventilation-to-carbon dioxide output slope (VE/VCO2 slope)] can be measured at sub-maximal workload during cardiopulmonary exercise test. The aim of this study is to assess the association between VE/VCO2 slope and outcome after lung cancer resections. Retrospective, single-centre analysis on all patients undergoing lung resection for cancer (April 2014-August 2022) and with a preoperative cardiopulmonary exercise test. VE/VCO2 slope >40 was chosen as high-risk threshold. Logistic regression analysis was used to test the association of VE/VCO2 slope and several patient- and surgery-related factors with 90-day mortality. A total of 552 patients were included (374 lobectomies, 81 segmentectomies, 55 pneumonectomies and 42 wedge resections). Seventy-four percent were minimally invasive procedures. Cardiopulmonary morbidity was 32%, in-hospital/30-day mortality 6.9% and 90-day mortality 8.9%. A total of 137 patients (25%) had a slope of >40. These patients were older (72 vs 70 years, P = 0.012), had more frequently coronary artery disease (17% vs 10%, P = 0.028), lower carbon monoxide lung diffusion capacity (57% vs 68%, P < 0.001), lower body mass index (25.4 vs 27.0 kg/m2, P = 0.001) and lower peak VO2 (14.9 vs 17.0 ml/kg/min, P < 0.001) than those with a lower slope. The cardiopulmonary morbidity among patients with a slope of >40 was 40% vs 29% in those with lower slope (P = 0.019). Ninety-day mortality was 15% vs 6.7% (P = 0.002). The 90-day mortality of elderly patients with slope >40 was 21% vs 7.8% (P = 0.001). After adjusting for peak VO2 value, extent of operation and other patient-related variables in a logistic regression analysis, VE/VCO2 slope retained a significant association with 90-day mortality. VE/VCO2 slope was strongly associated with morbidity and mortality following lung resection and should be included in the functional algorithm to assess fitness for surgery.

Efficacy of non-conventional synthetic DMARDs for patients with rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis

ObjectivesWe conducted a systematic review and meta-analysis to determine the efficacy of non-conventional synthetic disease-modifying antirheumatic drug (ncs-DMARD) strategies on patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD).MethodsPubMed, EMBASE,...

Cardiopulmonary exercise testing in people with minimally impaired multiple sclerosis

BackgroundMultiple sclerosis (MS) is a chronic demyelinating inflammatory disorder of the central nervous system that may affect respiratory system at the later stages of the disease. The aim of our study was to evaluate respiratory function and cardiopulmonary exercise testing in ambulatory without aid people with MS (pwMS), and to investigate quality of life parameters and fatigue in this population. Methods25 pwMS and 16 healthy controls were included in this study. Pulmonary function tests were performed and were followed by proper cardiopulmonary exercise testing with the use of treadmill. Quality of life assessment was done with SF-36 questionnaire. ResultsThe mean age of the patient group was 38.4 ± 8.2 years. Spirometric values were within normal limits, and so did lung diffusion capacity, while maximal voluntary ventilation was reduced. In cardiopulmonary exercise testing the patient group showed impairment compared to control group. The statistically significant lower parameters were V'O2 peak, V'CO2 peak, RER, V'O2/kg peak, V'CO2/kg peak, oxygen pulse peak and V'E/V'CO2 slope. Moreover, there was a negative and statistically significant correlation between CPET values and BMI and MFIS, while there was a positive and statistically significant correlation with quality of life, evaluated by SF-36. ConclusionOur study showed that the main cardiopulmonary exercise testing parameters were affected in ambulatory pwMS, even without evidence of respiratory symptoms. Therefore, these people should be evaluated for pulmonary function compromise.

Structural and functional impairments of skeletal muscle in patients with postacute sequelae of SARS-CoV-2 infection.

Following acute coronavirus disease 2019 (COVID-19), a substantial proportion of patients showed symptoms and sequelae for several months, namely the postacute sequelae of COVID-19 (PASC) syndrome. Major phenomena are exercise intolerance, muscle weakness, and fatigue. We aimed to investigate the physiopathology of exercise intolerance in patients with PASC syndrome by structural and functional analyses of skeletal muscle. At least 3 mo after infection, nonhospitalized patients with PASC (n = 11, age: 54 ± 11 yr; PASC) and patients without long-term symptoms (n = 12, age: 49 ± 9 yr; CTRL) visited the laboratory on four nonconsecutive days. Spirometry, lung diffusion capacity, and quality of life were assessed at rest. A cardiopulmonary incremental exercise test was performed. Oxygen consumption (V̇o2) kinetics were determined by moderate-intensity exercises. Muscle oxidative capacity (k) was assessed by near-infrared spectroscopy. Histochemical analysis, O2 flux (JO2) by high-resolution respirometry, and quantification of key molecular markers of mitochondrial biogenesis and dynamics were performed in vastus lateralis biopsies. Pulmonary and cardiac functions were within normal range in all patients. V̇o2peak was lower in PASC than CTRL (24.7 ± 5.0 vs. 32.9 ± 7.4 mL·min-1·kg-1, respectively, P < 0.05). V̇o2 kinetics was slower in PASC than CTRL (41 ± 12 vs. 30 ± 9 s-1, P < 0.05). k was lower in PASC than CTRL (1.54 ± 0.49 vs. 2.07 ± 0.51 min-1, P < 0.05). Citrate synthase, peroxisome proliferator-activated receptor-γ coactivator (PGC)1α, and JO2 for mitochondrial complex II were significantly lower in PASC vs. CTRL (all P values <0.05). In our cohort of patients with PASC, we showed limited exercise tolerance mainly due to "peripheral" determinants. Substantial reductions were observed for biomarkers of mitochondrial function, content, and biogenesis. PASC syndrome, therefore, appears to negatively impact skeletal muscle function, although the disease is a heterogeneous condition.NEW & NOTEWORTHY Several months after mild acute SARS-CoV-2 infection, a substantial proportion of patients present persisting, and often debilitating, symptoms and sequelae. These patients show reduced quality of life due to exercise intolerance, muscle weakness, and fatigue. The present study supports the hypothesis that "peripheral" impairments at skeletal muscle level, namely, reduced mitochondrial function and markers of mitochondrial biogenesis, are major determinants of exercise intolerance and fatigue, "central" phenomena at respiratory, and cardiac level being less relevant.

Dynamics of functional changes in the respiratory system after COVID-19-associated lung injury at one year after hospital discharge

Morphological examination reveals microcirculation disorders in combination with small areas of lung damage in the long term after COVID-19. Therefore, the function of the respiratory system should be assessed after COVID-19. Aim of this study was to evaluate the dynamics of respiratory dysfunction in patients with COVID-19-associated lung injury using a complex examination of lung function (spirometry, body plethysmography, and lung diffusion testing) one year after hospital discharge. Methods. 60 patients (38 men/22 women, aged 39 to 80 years) with a diagnosis of “COVID-19-associated interstitial process in the lungs” were examined. Lung function (spirometry, body plethysmography, and lung diffusion capacity testing) was examined in all patients twice, at 1 – 6 months (visit 1) and at 12 – 24 months (visit 2) after hospital discharge. Results. At visit 1, 60% of patients had restrictive pulmonary ventilation disorders. Obstructive ventilation disorders were detected in only 1 patient. Decreased lung diffusion capacity (D CO corr.) was found in 78% of patients. At visit 2, obstructive disorders were detected in 1 patient, and the frequency of restrictive ventilation disorders was 29%. Decreased DLCO corr. was noted in 57% of cases. The parameters of pulmonary ventilation and pulmonary gas exchange function differed significantly between visits. Significant correlations were found between changes in the functional parameters of the respiratory system and disorders identified at visit 1 after hospital discharge. Conclusion. Thus, there is a decrease in the lung diffusion capacity and the rate of restrictive ventilation disorders even one year after severe COVID-19-associated lung injury. However, our results suggest a marked improvement in respiratory system function over time.

Assessment of Pulmonary Functions in COVID-19 Survivors and their Clinical Correlation at 6-month Follow-up

Background: Long term impact of COVID-19 on pulmonary functions is still an area of active research. Objective: To assess pulmonary functions and their relationship with clinical severity of disease among COVID-19 survivors at six-month follow-up after being discharged from the hospital. Methods: It was a hospital based prospective observational six-month follow-up study. After fulfillment of all inclusion and exclusion criteria, subjects underwent spirometry and diffusion capacity of lung for carbon monoxide (DLco). Ninety-six subjects had completed the tests and were enrolled for the study. Categorization of subjects was made based on their clinical disease severity profile according to Government of India guidelines. Test results were correlated with clinical severity of disease. Results: Of 96 subjects, 46 were mild, 28 were moderate, 18 were severe and 4 were critical cases. Majority of subjects had normal spirometry (65.6 %) and DLco (66.6 %). Among abnormal lung functions, the commonest was reduced DLco (33.3%) followed by restrictive (18.7%), small airway disease (10.4 %), obstructive (3.1 %) and mixed (2%) spirometry patterns. With the advancement of clinical disease severity, the frequency of restrictive pattern (P&lt;0.01) and reduced DLco increases significantly (P&lt;0.05). Conclusion: After six months, few COVID-19 survivors had residual lung function impairment in terms of reduced DLco and restrictive spirometry pattern. Hence, we recommend regular lung function assessment with various methods such as spirometry and DLco in COVID-19 survivors and advocate more large scale - long term follow-up studies to investigate the further progression or resolution in these abnormalities over the time.