Carbon Monoxide Transfer Coefficient Research Articles

Impaired diffusion at submaximal lung inflation in asthma and copd patients

IntroductionDissolved-phase 129Xe MRI metrics suggest that gas diffusion may be more compromised at submaximal lung inflation compared to maximal inflation. We hypothesized that this diffusion deficit could be detected by comparing the carbon monoxide transfer coefficient (Kco) at submaximal lung inflation to that measured routinely at total lung capacity (TLC). MethodsAsthma and COPD patients performed carbon monoxide diffusion tests, first at maximal lung inflation for routine Kco and alveolar volume VA and then, at a 30 % reduced inflation (redux; obtaining Kcoredux and VAredux). At both inflations mixing efficiency was determined as VA/TLC and VAredux/TLCredux to examine a potential effect on Kcoredux/Kco behavior. ResultsIn normal subjects (n=36), median Kcoredux/Kco amounted to 130 [IQR:122–136]% as expected for normal Kco recruitment response. However, 60 % of asthma patients (49/83) and 80 % of COPD patients (44/55) showed reduced Kco recruitment at submaximal inflation (Kcoredux/Kco<122 %). In the asthma group, with otherwise normal routine Kco, Kcoredux/Kco was significantly correlated with RV/TLC ratio (r=-0.53;P<0.001), but not with VA/TLC. In COPD patients, all with abnormal routine Kco, abnormal Kcoredux/Kco response occurred in those patients with lower FEV1, higher RV/TLC and lower VA/TLC (P<0.01 for all). ConclusionSizeable portions of COPD and asthma patients showed a lack of normal Kco recruitment at submaximal lung inflation, related to high RV/TLC. In asthma, this was the case despite normal Kco at full lung inflation, suggesting that hyperinflation at lung volumes less than TLC affects the carbon monoxide diffusion rate constant by distorting pulmonary capillaries and alveolar–capillary membranes.

Pulmonary function in patients with idiopathic scoliosis 40 years after diagnosis

BACKGROUND CONTEXTPulmonary function in patients with scoliosis has been a topic of concern, with some reports of markedly decreased ventilatory function leading to disability and increased mortality in patients with severe scoliosis. Only limited data is available concerning pulmonary function in adult patients with scoliosis. PURPOSETo report the long-term pulmonary function (PF) in patients diagnosed with idiopathic scoliosis (IS) compared with an age-matched population using extended pulmonary function testing (EPFT). STUDY DESIGN/SETTINGRetrospective clinical follow-up. PATIENT SAMPLEA total of 177 patients seen at our institution from 1972 to 1983 for a pediatric spinal deformity were assessed for inclusion in the study. About 77/129 eligible patients with IS (60%) partook in a clinical examination including radiographs, and EPFT. OUTCOME MEASURESThe EPFT values included forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, vital capacity (VC), total lung capacity (TLC), residual volume (RV), RV/TLC ratio, diffusion capacity of carbon monoxide (DLco), carbon monoxide transfer coefficient (KCO) and alveolar volume (VA). Results were expressed with z-scores derived from height and arm span normative data. Z-scores were calculated as z-score=Measured PF-Predicted PF /Relative standard deviation (RSD). The limits of normal, are defined as the 5th and 95th percentile limits (z-score between −1.645 and 1.645), respectively. METHODSPatients underwent a clinical examination with full spine standing radiographs and EFPT. The results were compared between patients with thoracic and thoracolumbar/lumbar (TL/L) main curves, and overall compared with a background population. Results were expressed with z-scores derived from height and arm span normative data. RESULTSOf 77 included patients, 76 (99%) were females with a mean age of 54.6±2.5 years. The mean follow-up time was 40.8±2.8 years. Forty-four patients had thoracic main curves, and 33 had TL/L main curves. We found no pulmonary impairment based on z-scores in the total cohort or between groups, with only patients who were current or previous smokers, having z-scores below the normal limits Patients with main thoracic curves displayed significantly lower PF on mean absolute values and mean z-scores on FEV1, FVC, FEV1/FVC ratio, VC, TLC, and DLco compared with main TL/L curves. Patients with thoracic curves had significantly larger Cobb angles at follow-up; 52±17° compared with 40±22° (p-value <.05) in the TL/L group. We found no linear association between thoracic Cobb angle and degree of pulmonary impairment assessed with DLco, TLC, and FVC. Comparison of pulmonary z-scores based on arm span data, differed significantly on FVC and TLC, with the arm span measurements showing lower mean z-scores (p-value <.05). CONCLUSIONSUsing EPFT, no pulmonary impairment could be demonstrated compared to the age-matched population 40 years after a diagnosis of IS. However, patients with thoracic curves had decreased PF compared to patients with TL/L curves although within the normal range. Thus, when treated as current guidelines suggest, patients with idiopathic scoliosis can expect the same long-term pulmonary function as the general population.

Bicaudal D2 autoantibodies are highly specific for systemic sclerosis

Objective Autoantibodies directed against the intracellular protein bicaudal D2 (BICD2) have been identified as a specific marker of systemic sclerosis (SSc). Since autoantibodies are of value in predicting disease onset and identifying meaningful clinical subsets, as well as having prognostic value, this study aimed to establish the prevalence of BICD2 autoantibodies (anti-BICD2) in a cohort of patients with connective tissue disease and healthy controls. Method In this cross-sectional study, 363 patients with connective tissue disease (121 SSc, 141 systemic lupus erythematosus, 101 myositis, and 100 blood donors) were tested for the presence of anti-BICD2. All SSc patients were tested for specific anti-nuclear antibodies (ANAs), and clinical and laboratory associations were evaluated in the SSc patients, stratified by anti-BICD2 status. Results In the SSc cohort, 35 patients had autoantibodies directed against BICD2. The specificity of anti-BICD2 in SSc patients was 96.5%; however, the sensitivity was only 28.9%. Anti-BICD2 and centromere autoantibodies were present together in 91% of the anti-BICD2-positive SSc patients, and in none of the cases was anti-BICD2 the only antibody present. Anti-BICD2-positive patients had lower forced expiratory volume in 1 s (FEV1) (p = 0.01) and lower carbon monoxide transfer coefficient (KCO) (p = 0.01) than anti-BICD2-negative SSc patients, but they had higher forced vital capacity (p = 0.03). Conclusion Autoantibodies against BICD2 were highly specific for SSc patients. Reduced FEV1 and KCO in anti-BICD2-positive patients may indicate that the presence of anti-BICD2 is associated with altered lung function in an unknown pathophysiological manner, which awaits further elucidation.

Optimizing cardiopulmonary rehabilitation duration for long COVID patients: an exercise physiology monitoring approach

The presence of prolonged symptoms after COVID infection worsens the workability and quality of life. 200 adults with long COVID syndrome were enrolled after medical, physical, and mental screening, and were divided into two groups based on their performance. The intervention group (n = 100) received supervised rehabilitation at Department of Pulmonology, Semmelweis University with the registration number 160/2021 between 01/APR/2021–31/DEC/2022, while an age-matched control group (n = 100) received a single check-up. To evaluate the long-term effects of the rehabilitation, the intervention group was involved in a 2- and 3-month follow-up, carrying out cardiopulmonary exercise test. Our study contributes understanding long COVID rehabilitation, emphasizing the potential benefits of structured cardiopulmonary rehabilitation in enhancing patient outcomes and well-being. Significant difference was found between intervention group and control group at baseline visit in pulmonary parameters, as forced vital capacity, forced expiratory volume, forced expiratory volume, transfer factor for carbon monoxide, transfer coefficient for carbon monoxide, and oxygen saturation (all p < 0.05). Our follow-up study proved that a 2-week long, patient-centered pulmonary rehabilitation program has a positive long-term effect on people with symptomatic long COVID syndrome. Our data showed significant improvement between two and three months in maximal oxygen consumption (p < 0.05). Multidisciplinary, individualized approach may be a key element of a successful cardiopulmonary rehabilitation in long COVID conditions, which improves workload, quality of life, respiratory function, and status of patients with long COVID syndrome.

Des taux élevés d’auto-anticorps anti-topo-isomérase-1 sont associés à l’extension de la fibrose cutanée et à la progression vasculaire chez les patients atteints de sclérodermie systémique

BackgroundAnti-centromere antibodies, anti-topoisomerase-1 antibodies (ATA), and anti-RNA-polymerase III antibodies are three Systemic Sclerosis (SSc)-specific autoantibodies. Their detection is helpful in determining the prognosis. We aimed to evaluate whether ATA levels were associated with disease severity at diagnosis or disease progression during follow-up in ATA positive patients. MethodsWe conducted a single-centre French retrospective observational study, between 2014 and 2021. ATA positive patients fulfilling the ACR/EULAR 2013 classification criteria for SSc with a minimal follow-up of 1 year and 2 ATA dosages were included. SSc patients with high IgG ATA levels at baseline (>240IU/mL) were compared with SSc patients with low levels (≤240IU/mL), at inclusion and at 1 and 3 years. A variation of at least 30 % of ATA levels was considered significant. ResultsFifty-nine SSc patients were included and analysed. There was a predominance of women and of patients with diffuse interstitial lung disease. Patients with high ATA levels exhibited a higher skin sclerosis assessed by the modified Rodnan skin score (P=0.0480). They had a lower carbon monoxide transfer coefficient (P=0.0457), a lower forced vital capacity (FVC) (P=0.0427) and more frequently had a FVC under 80 %, when compared to patients with low ATA levels (P=0.0423). Initial high ATA levels were associated with vascular progression at one year (21.95 % vs. 0 %; P=0.0495). ConclusionATA levels are associated with skin sclerosis and vascular progression in SSc. Beyond the detection of ATA, quantifying this autoantibody might be of interest in predicting disease severity and prognosis in SSc.

Anxiety in Patients with Post-COVID Syndrome: Associated Factors.

The term "post-COVID-19 syndrome" describes a range of symptoms persisting beyond the acute phase of the disease. These symptoms predominantly include fatigue, muscle pain, shortness of breath, and psychological issues. Research additionally suggests the possibility of long-term neurological and psychiatric impairment associated with COVID-19. The study included patients who visited the post-COVID outpatient clinic between April 2020 and June 2022. The examination included the detailed history taking, including the COVID-19 course, posteroanterior chest X-ray and pulmonary function tests. Anxiety level was assessed using the Beck Anxiety Inventory (BAI). The relationship between anxiety, demographic data, and course of the disease, need for hospital admission during the acute phase, oxygen therapy, post-inflammatory changes on the chest X-ray and lung function parameters was investigated. This study included 1756 patients who experienced COVID-19 and visited a post-COVID outpatient clinic. The majority of individuals experienced a mild form of the infection. The results showed that younger age and female gender were associated with significantly higher anxiety scores. Inpatients had lower BAI values than those who were not hospitalized during acute phase. Patients with post-inflammatory changes on chest X-ray had surprisingly lower BAI values. Lower values of FEV1 (forced expiratory volume in 1 second), DLCO (diffusing capacity of the lungs for carbon monoxide), and KCO (carbon monoxide transfer coefficient) were associated with significantly higher BAI values. Female gender was associated with higher levels of anxiety. In contrast, higher FEV1 values reduced the risk of a pathological level of anxiety. In our study, the influence of age, gender, inpatient care during the acute phase of infection, the presence of post-inflammatory changes on the chest diagram and selected parameters of lung function (FEV1, DLCO, and KCO) were shown to be important factors in the assessment of anxiety symptoms in post-COVID patients.

Post-COVID changes in lung function 6 months after veno-venous extracorporeal membrane oxygenation: a prospective observational clinical trial.

Severe coronavirus disease 2019 (COVID-19) may require veno-venous extracorporeal membrane oxygenation (V-V ECMO). While V-V ECMO is offered in severe lung injury to COVID-19, long-term respiratory follow-up in these patients is missing. Therefore, we aimed at providing comprehensive data on the long-term respiratory effects of COVID-19 requiring V-V ECMO support during the acute phase of infection. In prospective observational cohort study design, patients with severe COVID-19 receiving invasive mechanical ventilation and V-V ECMO (COVID group, n = 9) and healthy matched controls (n = 9) were evaluated 6 months after hospital discharge. Respiratory system resistance at 5 and 19 Hz (R5, R19), and the area under the reactance curve (AX5) was evaluated using oscillometry characterizing total and central airway resistances, and tissue elasticity, respectively. R5 and R19 difference (R5-R19) reflecting small airway function was also calculated. Forced expired volume in seconds (FEV1), forced expiratory vital capacity (FVC), functional residual capacity (FRC), carbon monoxide diffusion capacity (DLCO) and transfer coefficient (KCO) were measured. The COVID group had a higher AX5 and R5-R19 than the healthy matched control group. However, there was no significant difference in terms of R5 or R19. The COVID group had a lower FEV1 and FVC on spirometry than the healthy matched control group. Further, the COVID group had a lower FRC on plethysmography than the healthy matched control group. Meanwhile, the COVID group had a lower DLCO than healthy matched control group. Nevertheless, its KCO was within the normal range. Severe acute COVID-19 requiring V-V ECMO persistently impairs small airway function and reduces respiratory tissue elasticity, primarily attributed to lung restriction. These findings also suggest that even severe pulmonary pathologies of acute COVID-19 can manifest in a moderate but still persistent lung function impairment 6 months after hospital discharge. NCT05812196.

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.

The added value of haemoglobin to height, age, and sex to predict DLCO in subjects with preserved exercise capacity.

The single breath diffusion capacity for carbon monoxide (DLCO) captures several aspects of the role of the lung in meeting the metabolic demands of the body. The magnitude of the independent contributors to the DLCO is unknown. The aim of this study was to investigate the factors that independently contribute to the DLCO. The objective was to investigate the impact of height, age, sex and haemoglobin on DLCO, alveolar volume (VA) and carbon monoxide transfer coefficient (KCO). Study participants were pre-screened based on normal exercise capacity achieved during an incremental cardio-pulmonary exercise testing (CPET) using cycle ergometry at McMaster University Medical Center between 1988-2012. Participants who had an FEV1>80% predicted, with an FEV1/FVC ≥0.7 and who achieved a maximum power output ≥80% were selected for analysis. In total, 16,298 subjects [61% male, mean height 1.70m (range 1.26-2.07), age 49 yrs (10-94), weight 79 kg (23-190) had DLCO measured while demonstrating normal spirometry and exercise capacity. The DLCO increased exponentially with height, was 15% greater in males, increased with age yearly until 20, then decreased yearly after the age of 35, and was 6% higher per gram of haemoglobin (5.58*Height(m)1.69*1.15 in Males*(1-0.006*Age>35)*(1+0.01*Age<20) *(1+0.06*Hb gm/dl), (r = 0.76). Height, age, sex, and haemoglobin all have independent influence on the DLCO in subjects with normal spirometry and preserved exercise capacity.

Differential impacts between fat mass index and fat-free mass index on patients with COPD

BackgroundDifferences in the clinical impacts of fat mass index (FMI) and fat-free mass index (FFMI) remain unclear in patients with chronic obstructive pulmonary disease (COPD). We hypothesized that FMI and FFMI have different impacts on 1) emphysema and 2) pulmonary function and health-related quality of life of COPD patients. MethodsPatients with COPD (n = 228), enrolled in a multicenter prospective 3-year cohort were classified into four groups based on baseline median FMI and FFMI values. Emphysema assessed as the ratio of low attenuation area to total lung volume (LAA%) on computed tomography, pulmonary function, and health-related quality of life assessed using the St. George's Respiratory Questionnaire (SGRQ) were compared. ResultsThe four groups had statistically significant differences in LAA%, pulmonary function, and SGRQ scores. The Low FMI Low FFMI group exhibited the highest LAA%, lowest pulmonary function, and worst SGRQ scores among the four groups. In addition, these differences were consistent over 3 years. Multivariate analysis showed that low FMI was associated with high LAA%, low inspiratory capacity/total lung capacity (IC/TLC), and carbon monoxide transfer coefficient (KCO). In contrast, low FFMI was associated with these factors as well as worse SGRQ scores. ConclusionFMI and FFMI have different effects on the clinical manifestations of COPD. Both low fat and muscle mass contributed to severe emphysema, whereas only low muscle mass contributed to worse health-related quality of life in patients with COPD.

Dynamic Prediction of Pulmonary Hypertension in Systemic Sclerosis Using Landmark Analysis.

Pulmonary hypertension (PH) is a serious complication of systemic sclerosis (SSc). In this study, we explored the prediction of short-term risk for PH using serial pulmonary function tests (PFTs) and other disease features. SSc patients in whom disease onset occurred ≥10 years prior to data retrieval and for whom autoantibody specificity and PFT data were available were included in this study. Mixed-effects modeling was used to describe changes in PFTs over time. Landmarking was utilized to include serial assessments and stratified Cox proportional hazards regression analysis with landmarks as strata was used to develop the PH prediction models. We analyzed data from 1,247 SSc patients, 16.3% of whom were male and 35.8% of whom had diffuse cutaneous SSc. Anticentromere, antitopoisomerase, and anti-RNA polymerase antibodies were observed in 29.8%, 22.0%, and 11.4% of patients, respectively, and PH developed in 13.6% of patients. Over time, diffusing capacity for carbon monoxide (DLco) and carbon monoxide transfer coefficient (Kco) declined in all SSc patients (up to 1.5% per year) but demonstrated much greater annual decline (up to 4.5% and 4.8%, respectively) in the 5-7 years preceding PH diagnosis. Comparisons between multivariable models including either DLco, Kco, or forced vital capacity (FVC)/DLco ratio, demonstrated that both absolute values and change over the preceding year in those measurements were strongly associated with the risk of PH (hazard ratio [HR] 0.93 and 0.76 for Kco and its change; HR 0.90 and 0.96 for DLco and its change; and HR 1.08 and 2.01 for FVC/DLco ratio and its change; P < 0.001 for all). The Kco-based model had the greatest discriminating ability (Harrell's C-statistic 0.903). Our findings strongly support the importance of PFT trends over time in identifying patients at risk of developing PH.

Medium-long term prognosis prediction for idiopathic pulmonary fibrosis patients based on quantitative analysis of fibrotic lung volume

PurposeTo investigate the prognostic value of quantitative analysis of CT among patients with idiopathic pulmonary fibrosis (IPF) by quantifying the fibrosis extent and to attempt to provide precise medium-long term prognostic predictions for individual patients.MethodsThis was a retrospective cohort study that included 95 IPF patients in Zhongshan Hospital, Fudan University. 64 patients firstly diagnosed with IPF from 2009 to 2015 was included as the derivation cohort. Information regarding sex, age, the Gender-Age-Physiology (GAP) index, high-resolution computed tomography (HRCT) images, survival status, and pulmonary function parameters including forced vital capacity (FVC), FVC percent predicted (FVC%pred), diffusing capacity of carbon monoxide (DLCO), DLCO percent predicted (DLCO%pred), carbon monoxide transfer coefficient (KCO), KCO percent predicted (KCO%pred) were collected. 31 patients were included in the validation cohort. The Synapse 3D software was used to quantify the fibrotic lung volume (FLV) and total lung volume (TLV). The ratio of FLV to TLV was calculated and labeled CTFLV/TLV%, reflecting the extent of fibrosis. All the physiological variants and CTFLV/TLV% were analyzed for the dimension of survival through both univariate analysis and multivariate analysis. Formulas for predicting the probability of death based on the baseline CTFLV/TLV% were calculated by logistic regression, and validated by the validation cohort.ResultsThe univariate analysis indicated that CTFLV/TLV% along with DLCO%pred, KCO%pred and GAP index were significantly correlated with survival. However, only CTFLV/TLV% was meaningful in the multivariate analysis for prognostic prediction (HR 1.114, 95% CI 1.047–1.184, P = 0.0006), and the best cutoff was 11%, based on receiver operating characteristic (ROC) curve analysis. The survival times for the CTFLV/TLV% ≤ 11% and CTFLV/TLV% > 11% groups were significantly different. Given the CTFLV/TLV% data, the death probability of a patient at 1 year, 3 years and 5 years could be calculated by using a particular formula. The formulas were tested by the validation cohort, showed high sensitivity (88.2%), specificity (92.8%) and accuracy (90.3%).ConclusionQuantitative volume analysis of CT might be useful for evaluating the extent of fibrosis in the lung. The CTFLV/TLV% could be a valuable biomarker for precisely predicting the medium-long term prognosis of individual patients with IPF.

Prognostic Relevance of Cardiopulmonary Exercise Testing for Patients with Chronic Thromboembolic Pulmonary Hypertension.

Background: Following acute pulmonary embolism (PE), a relevant number of patients experience decreased exercise capacity which can be associated with disturbed pulmonary perfusion. Cardiopulmonary exercise testing (CPET) shows several patterns typical for disturbed pulmonary perfusion. Research question: We aimed to examine whether CPET can also provide prognostic information in chronic thromboembolic pulmonary hypertension (CTEPH). Study Design and Methods: We performed a multicenter retrospective chart review in Germany between 2002 and 2020. Patients with CTEPH were included if they had ≥6 months of follow-up and complete CPET and hemodynamic data. Symptom-limited CPET was performed using a cycle ergometer (ramp or Jones protocol). The association of anthropometric data, comorbidities, symptoms, lung function, and echocardiographic, hemodynamic, and CPET parameters with survival was examined. Mortality prediction models were calculated by Cox regression with backward selection. Results: 345 patients (1532 person-years) were included; 138 underwent surgical treatment (pulmonary endarterectomy or balloon pulmonary angioplasty) and 207 received only non-surgical treatment. During follow-up (median 3.5 years), 78 patients died. The death rate per 1000 person-years was 24.9 and 74.2 in the surgical and non-surgical groups, respectively (p < 0.001). In age- and sex-adjusted Cox regression analyses, CPET parameters including peak oxygen uptake (VO2peak, reflecting cardiopulmonary exercise capacity) were prognostic in the non-surgical group but not in the surgical group. In mortality prediction models, age, sex, VO2peak (% predicted), and carbon monoxide transfer coefficient (% predicted) showed significant prognostic relevance in both the overall cohort and the non-surgical group. In the non-surgical group, Kaplan–Meier analysis showed that patients with VO2peak below 53.4% predicted (threshold identified by receiver operating characteristic analysis) had increased mortality (p = 0.007). Interpretation: The additional measurement of cardiopulmonary exercise capacity by CPET allows a more precise prognostic evaluation in patients with CTEPH. CPET might therefore be helpful for risk-adapted treatment of CTEPH.

Association between DLCO index and the severity of heart failure: a cross-sectional study

Background The prognostic role of diffusing capacity of the lung for carbon monoxide (DLCO) in heart failure has not been thoroughly investigated. Therefore, this study aimed to evaluate DLCO variation in different systolic and diastolic heart failure stages. Methods This was a prospective cross-sectional study on 51 patients with systolic (reduced LVEF) or diastolic (preserved LVEF) chronic heart failure (CHF). All patients underwent a standard DLCO test. The associations between the severity of heart failure and reduced carbon monoxide transfer factor (TLCO), carbon monoxide transfer coefficient (KCO), and alveolar volume (VA) were investigated. Data were analysed using SPSS software version 16. p-Values below 0.05 were considered statistically significant. Results The mean age of participants was 59.29 ± 14.91 years, with 72% of the study population being male. Systolic heart failure was observed in 47% of patients, diastolic heart failure in 18%, and a mixed systolic and diastolic pattern in 35%. There were significant differences between TLCO percentage in patients with CHF types and the New York Heart Association (NYHA) functional classes (p = 0.042). Overall, an ejection fraction (EF) of less than 25% correlated with 3%, 53%, and 0.78 declines in TLCO, KCO%, and KCO index, respectively. Conclusion Despite the lack of statistically significant differences between DLCO indices and CHF severity, decreased DLCO parameters correlated with reduced EF. Therefore, DLCO testing might be helpful to predict HF severity.

Do Childhood Cancer Survivors Have Reduced Lung Function Compared To Healthy Individuals?

PURPOSE: to evaluate lung function in childhood cancer survivors (CCS) compared to age and sex-matched controls in Norway and Switzerland. METHODS: In this multicenter European cross-sectional study (Oslo, Bergen, Basel), 157 CCS and 113 controls (age range 9-18 years) performed spirometry and whole-body plethysmography, and measured lung diffusion capacity and blood haemoglobin levels, according to guidelines. Forced expiratory volume in one sec (FEV1), forced vital capacity (FVC), total lung capacity (TLC), transfer coefficient (KCO) and total lung diffusion capacity for carbon monoxide (DLCO) were recorded. Predicted values were according to Global Lung Initiative. RESULTS: Mean age (standard deviation) of all participants was 13.4 (2.6) years. The most common cancer diagnoses were leukemia (50%), brain tumors (11%) and lymphoma (10%). The majority (77%) of CCS had received chemotherapy with anthracyclines. Tabulated preliminary data showing differences between CCS and controls: CONCLUSIONS: Lung function was well preserved in CCS despite significant differences between CCS and controls. There was no evidence of diffusion limitation induced by treatment toxicity.

Phenotyping exercise limitation of patients with Interstitial Fibrosing Lung Disease: the importance of exercise hemodynamics

Introduction and objectiveLeft-heart dysfunction and pulmonary vasculopathy are increasingly recognized as contributing factors of exercise capacity limitation in interstitial fibrosing lung disease (IFLD). Moreover, the clinical significance of exercise pulmonary hypertension (ePH) in pulmonary and cardiac diseases has been documented, representing a risk factor for decreased exercise capacity and survival, progression to resting pulmonary hypertension (PH) and overall clinical worsening.We conducted a prospective study aiming at: (a) assessing the prevalence of PH and ePH in a cohort of 40 functionally limited patients with IFLD, (b) determining the post-capillary (postC) or pre-capillary (preC) etiology of either PH or ePH in this cohort, and (c) examining the correlations between invasively and non-invasively measured exercise variables among hemodynamic groups. Patients and methods40 IFLD patients underwent cardiopulmonary evaluation, including: clinical examination, lung function tests, 6-minute walking test, heart ultrasonography, cardiopulmonary exercise test and, finally, right heart catheterization (RHC). Resting hemodynamic evaluation was followed by the exercise protocol proposed by Herve et al, using a bedside cycle ergometer in the supine position. Abnormal elevation of mean pulmonary artery pressure (mPAP) above 30mmHg during exercise, with respect to abnormal elevation of cardiac output (CO) below 10 L/min (mPAP–CO ratio ⩾3 mmHg·min·L−1) was used to define ePH (Herve et al, 2015). Secondary hemodynamic evaluation involved detection of abnormal pulmonary arterial wedge pressure (PAWP) increase at peak exercise in relation to CO. Specifically, ΔPAWP/ΔCO >2 mmHg/L per minute determined an abnormal PAWP elevation (Bentley et al, 2020). ResultsAmong the 40-patient cohort, 25% presented postC PH, 37.5% preC PH, 27.5% ePH, with the remaining 10% recording normal hemodynamics. PAWP evaluation during exercise revealed a postC etiology in 4 out of the 11 patients presenting ePH, and a postC etiology in 6 out of the 15 patients presenting resting preC PH. Mean values of non-invasive variables did not display statistically significant differences among hemodynamic groups, except for: diffusing capacity for carbon monoxide (DLCO), carbon monoxide transfer coefficient (KCO) and the ratio of functional vital capacity to DLCO (FVC%/DLCO%), which were lower in both ePH and PH groups (p < 0.05). Resting values of CO, cardiac index (CI), stroke volume (SV) and pulmonary vascular compliance (PVC) were significantly impaired in ePH, preC-PH and postC-PH groups when compared to the normal group. ConclusionsBoth PH and ePH were highly prevalent within the IFLD patient group, suggesting that RHC should be offered more frequently in functionally limited patients. Diffusion capacity markers must thus guide decision making, in parallel to clinical evaluation. ePH was associated to lower resting CO and PVC, in a similar way to resting PH, indicating the relevance of cardiopulmonary function to exercise limitation. Finally, the use of the ΔPAWP/ΔCO>2 criterion further uncovered PH of postcapillary etiology, highlighting the complexity of hemodynamics in IFLD.ClinicalTrials.gov ID: NCT03706820

Lung Diffusing Capacity in Dutch Special Operations Forces Divers Exposed to Oxygen Rebreathers over 18 Years

Exposure to hyperoxic conditions can induce pulmonary oxygen toxicity (POT). Divers of the Special Operations Forces (SOF) use oxygen rebreather systems during dives, and therefore are frequently exposed to hyperoxic conditions. Few studies have reported on POT in this population. This study reports on long-term pulmonary function tests (PFTs) and diffusing capacity in SOF divers to test the hypothesis that these measures of pulmonary function do not change clinically significantly during their career. The Royal Netherlands Navy performs yearly medical assessments of its military divers. All PFT and diffusing capacity data of SOF divers between the years 2000 and 2020 were analyzed using generalized estimating equations. The study included 257 SOF divers (median age, 27; interquartile range, 24–32), with 1612 dive medical assessments and a maximum follow-up time of 18.8 years. Alveolar volume (VA) and the diffusing capacity of carbon monoxide (TLCO) were significantly lower at baseline in smokers. Although these parameters were within the normal range, they declined over time and were significantly associated with age and years of diving. Smoking additionally affected TLCO and the transfer coefficient for carbon monoxide (KCO). TLCO and KCO were reduced by years of diving with oxygen rebreathers, albeit over clinically insignificant ranges, but smoking increased these changes by factors of 10 and 15, respectively.

Different Smoking Statuses on Survival and Emphysema in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

ObjectiveTo investigate the association between different smoking statuses and survival and emphysema in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).MethodsThis retrospective study included patients admitted from October 2014 to September 2017. Demographic, clinical, laboratory, imaging, impulse oscillometry, and traditional pulmonary function data were collected. The relationship between smoking and EI was analyzed via binary logistic regression after adjusting for other factors. Survival was analyzed using the Kaplan–Meier method and the log rank test.ResultsThe patients with AECOPD (357 cases) were identified (and stratified into three groups: never smoked (NS; n=83), former smokers (FS, n=118), and current smokers (CS; n=156). Compared with CS, NS were older and predominantly female. No differences were observed in respiratory symptoms and acute exacerbation between CS and NS. NS had higher resistance and reaction in the central and peripheral airways, while CS exhibited more severe diffuse dysfunction. CS demonstrated more severe and extensive emphysema. Smoking was an independent risk factor for emphysema after adjusting for age, forced expiratory volume in the first second over predicted value, BMI, leukocyte count, and carbon monoxide transfer coefficient. No difference in 5-year survival rates between NS and CS was established.ConclusionCS has the worst pulmonary function, suggesting a more important destruction of the lung parenchyma, while AECOPD without smoking risk factors mostly affects the airways. Impulse oscillometry can be used for imaging airway-dominant AECOPD. There was no difference in the 5-year survival rate.

P63.10 Safety of Simultaneously Performed Radiotherapy in Patients With Small-Cell Lung Cancer Undergoing Atezolizumab Treatment

In September 2019 Atezolizumab was approved for extended disease small cell lung cancer (ED-SCLC) in combination with cytotoxic chemotherapy by the European Medicines Agency (EMA). In the clinical trial IMpower133 only 22 out of 201 patients received prophylactic cranial radiotherapy (PCI) during their treatment with Atezolizumab (either during induction chemo-/immunotherapy or during maintenance immunotherapy). To our knowledge, no other clinical studies have reported efficacy or safety regarding the combination of radiotherapy (PCI, whole brain radiotherapy (WBRT) or consolidating thoracic radiotherapy) with Atezolizumab as single agent or in combination with chemotherapy. In the clinical routine these safety data are urgently needed for treatment decisions of (radio)-oncologists. We performed a retrospective data analysis of all patients with SCLC who were treated at the Department of Medical Oncology, Evang. Kliniken Essen-Mitte from January 2019 until March 2021. Patients with combined chemo-/immunotherapy as induction treatment or with immunotherapy as maintenance were compared to those without any immunotherapy receiving similar radiotherapies. In case of thoracic radiotherapy, pulmonary function before and after irradiation was measured. Odds-Ratio for any documented adverse events were calculated. PFS for the different groups will be calculated. 33 SCLC patients underwent cranial and/or thoracal irradiation (a group of 16 patients received both treatments yet) and were investigated. Atezolizumab was administered to 11 patients. There were no severe adverse events in patients with cranial radiotherapy regardless of simultaneously administered immunotherapy. In patients with thoracic radiotherapy, there was no significant difference in grade I to III adverse events. However, grade IV adverse events did only appear in patients without immunotherapy. Less than half of the patients had progression of their disease until March 2021.Therefore, PFS will be calculated in the next months and compared for the different subgroups. In five patients, who have already finished thoracic radiotherapy with immunotherapy maintenance and performed pulmonary function tests until March 2021, there is preliminary evidence for no deterioration of pulmonary function (forced one-second capacity (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, diffusing capacity for carbon monoxide (DLCO) and Carbon monoxide transfer coefficient (KCO)) compared to patients with thoracic radiotherapy without any immunotherapy. The addition of radiotherapy to immunotherapy seems not to be associated with increased toxicity in SCLC patients.

Serum IGFBP-2 in systemic sclerosis as a prognostic factor of lung dysfunction

Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (ILD), driving its mortality. Specific biomarkers associated with the progression of this lung disease are highly needed. We aimed to identify specific biomarkers of SSc-ILD to predict the evolution of the disease. For this, we compared prospectively serum levels of several biomarkers associated with lung fibrosis in SSc patients (n = 102), among which SSc-no ILD (n = 63) and SSc-ILD (n = 39), compared to healthy subjects (HS) (n = 39). We also performed a longitudinal study in a subgroup of 28 patients analyzing biomarkers variations and pulmonary function tests over a period of 2 years. Serum level of IGFBP-2 was significantly increased in SSc patients compared to HS, and negatively correlated with pulmonary function (assessed by carbon monoxide transfer coefficient (KCO)) (r = − 0.29, p < 0.01). Two-year longitudinal analysis in a subgroup of 28 SSc patients determined that IGFBP-2 variation was positively correlated with KCO at 2-year follow-up (r = 0.6, p < 0.001). SSc patients with a lower variation of IGFBP-2 (less than 22%) presented significant deterioration of pulmonary function at 2-year follow-up (p < 0.01). ROC curve analysis enabled us to identify that baseline IGFBP-2 > 105 ng/ml was associated with a poor outcome (KCO < 70% predicted) at 2-year follow-up (AUC = 0.75, p < 0.05). We showed for the first time that serum levels of IGFBP-2 might be a prognostic factor of the development of SSc-ILD.