Pulmonary Disease Research Articles

A novel Non-rodent animal model of hydrochloric acid-induced acute and chronic lung injury

Hydrochloric acid is one of the most prevalent and hazardous chemicals. Accidental spills occur in industrial plants or during transportation. Exposure to HCl can induce severe health impairment, including acute and chronic pulmonary diseases. We have previously described the molecular, structural, and functional aspects of the development of chronic lung injury and pulmonary fibrosis caused by intratracheal instillation of HCl in mice. Although mouse models of human disease have many advantages, rodents are evolutionary far from human and exhibit significant anatomical and physiological differences. Genetic and anatomic similarities between rabbits and humans are significantly higher. Rabbit models of HCl-induced lung injury have been used sparsely to evaluate acute lung injury. In this study, for the first time, we utilized rabbits as a model of HCl-induced pulmonary fibrosis and chronic lung injury. We present molecular, histological, and functional evidence that demonstrate the utility of using this model for studying new pharmaceutics against pulmonary fibrosis.

Sarcopenia's Impact Defined by Grip Strength and Muscle Mass on Post-hepatectomy Outcomes: A Multicenter Analysis.

Sarcopenia is diagnosed based on grip strength and skeletal muscle mass. Although decreased skeletal muscle mass has been reported to be associated with poor outcomes after hepatectomy, a few studies have included data on grip strength in hepatectomy candidates. This multicenter study investigated the clinical factors and postoperative complications associated with sarcopenia by assessing the grip strength and skeletal muscle mass in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). Data from patients who underwent hepatectomy for HCC between January 2020 and March 2022 were retrospectively collected from multi-institutional databases. Sarcopenia was defined as reduced grip strength and skeletal muscle mass. The patients were categorized into the sarcopenia and non-sarcopenia groups, and baseline characteristics and short term outcomes were compared between the two groups. Overall, 253 patients were included, among which 36 (14.2%) had sarcopenia. The sarcopenia group was significantly associated with older age, low body mass index, comorbid heart or chronic pulmonary disease, cerebrovascular accident history, and overall and major postoperative complications compared to the non-sarcopenia group. Among major postoperative complications [Clavien-Dindo classification (CDC) ≥III], the incidence of bile leakage and intra-abdominal abscess were higher in the sarcopenia group than in the non-sarcopenia group. Multivariate analysis revealed that sarcopenia was an independent risk factor for overall and major postoperative complications (CDC ≥III). Sarcopenia, defined by grip strength and skeletal muscle mass, is a predictor of overall and major complications after hepatectomy for HCC.

Best practice in COPD care: a health equity approach

There is a strong evidence base for the best care in chronic obstructive pulmonary disease (COPD) as outlined by the National Institute for Health and Care Excellence in its five fundamentals of COPD care: offer treatment and support to stop smoking; offer pneumococcal and influenza vaccinations; offer pulmonary rehabilitation if indicated; codevelop a personalised self-management plan; and optimise treatment for comorbidities. However, only a minority of those living with COPD receive or engage with all five interventions, with clear implications for outcomes. Further, barriers which prevent people who live with COPD accessing necessary care are unequally experienced. In order to overcome many of these barriers, clinicians caring for people with COPD must prioritise personalised treatment and continuity of care.

The Impact of Dietery Intervention on the Symptoms of Sleep Apneea and Stress Intake in Patients with Chronic Pulmonary Diseases

The Impact of Dietery Intervention on the Symptoms of Sleep Apneea and Stress Intake in Patients with Chronic Pulmonary Diseases

Exploring the association between magnesium deficiency and chronic obstructive pulmonary diseases in NHANES 2005–2018

Chronic Obstructive Pulmonary Disease (COPD) significantly impacts patients’ quality of life and burdens healthcare systems. Magnesium is crucial for lung function and reducing respiratory disease risk. This study investigates the association between Magnesium Depletion Score (MDS) and COPD and explores whether inflammatory markers mediate this relationship. A cross-sectional analysis was conducted using data from 30,490 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. MDS was calculated based on diuretic use, proton pump inhibitors, renal function, and alcohol consumption. Univariable and multivariable logistic regression analyses were performed to assess the association between MDS and COPD, adjusting for potential confounders. Mediation analysis was used to examine the roles of neutrophils, serum albumin, and the Systemic Immune-Inflammation Index (SII). In the univariable logistic model, higher MDS was significantly associated with increased COPD risk. Specifically, compared to MDS = 0, the odds ratios (OR) for COPD were 2.50, 4.12, 6.13, 8.53, and 7.81 for MDS = 1, 2, 3, 4, and 5, respectively (all P < 0.001). In the multivariable model, the ORs were 1.79, 2.25, 2.71, and 3.44 for MDS = 1, 2, 3, and 4, respectively (all P < 0.001). Higher neutrophil levels and SII were positively associated with increased COPD risk, while higher serum albumin levels were inversely associated. Mediation analysis indicated that neutrophils, serum albumin, and SII significantly mediated the MDS-COPD relationship. Higher MDS is significantly associated with increased COPD risk, mediated by systemic inflammation markers. Improving magnesium levels could potentially reduce COPD risk, warranting further research on magnesium supplementation in COPD prevention and management.

Comorbidity Patterns in Chronic Obstructive Pulmonary Disease and Their Associations with Service Utilization

Background The prevalence of combinations of comorbidities and their associations with inpatient service utilization and readmission among patients with chronic obstructive pulmonary disease (COPD) have not been extensively examined. To address this gap in knowledge, an observational prospective study was conducted using retrospective data. Aims To identify patterns of comorbidities linked to length of hospital stay, daily expenses, and one-year readmission. Methods The 30 most common comorbidities were identified in patients with secondary diagnoses using the association rule mining (ARM) method. Regression models were used to examine the relationships between combinations of comorbidities and service utilization, with adjustments for covariates. Results The five most prevalent comorbidities were pulmonary heart disease (40.99%), ischemic heart disease (38.97%), heart failure (36.77%), hypertension (34.11%), and respiratory disorders (19.12%). Most combinations of comorbidities identified by ARM showed significant associations with an extended length of stay (>13 days), increased daily expenses (>930 CNY), and reduced readmission rates. Among these combinations, glycoprotein metabolism disorder had the strongest association with prolonged length of stay (adjusted odds ratio [aOR]): 1.89, 95% confidence interval [CI]: 1.82–1.95). Conversely, the combination of other brain diseases and respiratory failure was linked to higher daily expenses (aOR: 11.34, 95% CI: 10.58–12.15), and the presence of pulmonary heart disease was associated with elevated one-year readmission rates (aOR: 1.41, 95% CI: 1.37–1.46). Conclusion Common combinations of comorbidities among inpatients with COPD were identified from an extensive collection of discharge medical records. Furthermore, the associations between comorbidities, inpatient service usage, and readmission rates were determined.

5-year valve academic research consortium-3 outcomes and predictors of mortality in a 10-year Asian transcatheter aortic valve implantation registry

Abstract Background Transaortic valvular implantation (TAVI) has revolutionised the management of aortic stenosis (AS). Uptake in Asia has caught up in recent years, after an initial lag due to expensive cost, limited subsidies, and scarce accessibility. Hence, longitudinal outcomes of TAVI remain largely unknown in Asian patients. Purpose This study aims to present the 5-year mortality endpoints in an Asian cohort followed up over a decade. Methods 253 patients with symptomatic severe aortic stenosis status post TAVI were retrospectively enrolled at a tertiary academic hospital from 2010-2021. The main outcomes were defined as short-term (30-day), mid-term (1-year) and long-term (5-year) all-cause mortality. Baseline demographics, procedural findings and clinical outcomes were analysed. Kaplan-Meier curves and multiple Cox regression analyses were constructed. Results The mean age was 75.2 + 10.2 years. 120 (47.4%) patients were female and 167 (66%) were Chinese. 168 patients (66.7%) received balloon-expandable valves, 80 patients (31.7%) underwent self-expandable valves, and 4 patients (1.6%) had mechanical-expandable valves. Malignancy was associated with worse short-term mortality at 30-days (HR 3.65, p = 0.054), while pulmonary disease and previous stroke were associated with worse long-term mortality at 5-years (HR 2.27, p = 0.012 and HR 2.02, p = 0.064). Worse all-cause mortality at 30-days, 1-year and 5-years were associated with high NT-Pro BNP levels (HR 1.04, p = 0.046; HR 1.05, p = 0.002 and HR 1.04, p &amp;lt; 0.001), the presence of peripheral arterial disease (PAD) (HR 4.32, p = 0.056; HR 4.48, p = 0.006 and HR 2.43, p = 0.023) and chronic kidney disease (CKD) (HR 6.19, p = 0.006; HR 6.77, p &amp;lt; 0.001 and HR 2.09, p = 0.008). Society of Thoracic Surgery (STS) score (HR 1.11, p = 0.001; HR 1.13, p &amp;lt; 0.001 and HR 1.12, p &amp;lt; 0.001) and Valve Academic Research Consortium (VARC) III endpoints of acute kidney injury (AKI) (HR 6.68, p = 0.047, HR 10.8, p &amp;lt; 0.001 and HR 6.99, p &amp;lt; 0.001), cardiogenic shock (HR 26.3, p &amp;lt; 0.001, HR 12.0, p &amp;lt; 0.001 and HR 4.29, p = 0.011) and structural complications (HR 40.3, p &amp;lt; 0.001, HR 18.1, p &amp;lt; 0.001 and HR 5.18, p = 0.008) were associated with worse all –cause mortality at time-points of 30-days, 1-year and 5-years respectively. On multivariate analyses adjusted for comorbidities and outcomes, STS score and structural complications were independent predictors of 30-day, 1-year, and 5-year all-cause mortality (HR 1.16; p = 0.003, HR 1.09, p = 0.003 and HR 1.10, p &amp;lt; 0.001) and (HR 62.7, p &amp;lt; 0.007; HR 18.9, p &amp;lt; 0.001 and HR 10.6, p = 0.001) respectively. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) use was protective of survival within 1-year (HR 0.37, p = 0.022). Conclusions STS score and VARC III endpoints of structural complications were reliable predictors of all-cause mortality in Asian patients with TAVI. ACE inhibitor and ARB use was protective against mortality at 1-year.Cox regression analysesKaplan-Meier curves

The role of cardiopulmonary rehabilitation in the recovery of right ventricular function and right ventricular-pulmonary artery coupling in convalescent COVID-19 patients

Abstract Introduction Coronavirus disease-19 (COVID-19) is predominantly a respiratory disease, but simultaneous cardiovascular impairment has been documented, even in the post-acute phase. Subclinical right ventricular (RV) dysfunction is often described and mainly attributed to parenchymal lung damage (ARDS) or pulmonary vascular complications such as pulmonary embolism. Cardiopulmonary rehabilitation programs play an integral part in the long-term management of chronic cardiovascular and pulmonary diseases and lately have been proven useful in managing post-COVID-19 sequelae. Purpose The aim of this study is to assess the impact of a post-COVID-19 rehabilitation program in the recovery of right ventricular function and right ventricular-pulmonary artery coupling in convalescent COVID-19 patients. Methods 40 convalescent COVID-19 patients were evaluated one and three months after the acute phase of the disease. 30 subjects participated in a 3-month cardiopulmonary rehabilitation program (study group) and 10 did not (control group). Right ventricular function echocardiographic parameters (right ventricular global longitudinal strain (RVGLS) and pulmonary artery systolic pressure (PASP)) were evaluated and right ventricular-arterial coupling (RVAC) was estimated via the RVGLS/PASP ratio. Results A total of 40 patients were included in this study, of whom 30 underwent cardiopulmonary rehabilitation. There were no major differences in the prevalence of cardiovascular risk factors between the two groups. When examining right ventricular parameters at baseline, RVGLS (Rehabilitation: -23.1 (4.1) % vs. No rehabilitation: -23.0 (4.7) %, p=0.94) and PASP (Rehabilitation: 28 (6) mmHg vs. No rehabilitation: 25 (4) mmHg, p=0.08) did not differ statistically between the two groups. RVAC was also similar at baseline (Rehabilitation: -0.96 (0.28) %/mmHg vs. No rehabilitation: -0.86 (0.27) %/mmHg, p=0.30). At follow-up, patients who underwent cardiopulmonary rehabilitation exhibited a significant improvement in RVGLS (from Τ0: -23.1 (4.2) % to T1: -24.3 (4) %, p&amp;lt;0.001), PASP (from T0: 28 (6) mmHg to T1: 27 (5) mmHg, p=0.016), and RVAC (from T0: -0.86 (0.27) %/mmHg to T1: -0.93 (0.26) %/mmHg, p&amp;lt;0.001). In the no rehabilitation group, RVGLS (from T0: -23.0 (4.7) % to T1: -23.2 (4.4) %, p=0.19), PASP (from T0: 25 (4) mmHg to T1: 25 (4) mmHg, p=0.17), and RVAC (from T0: -0.96 (0.28) %/mmHg to T1: -0.96 (0.27) %/mmHg, p=0.60) were not significantly altered at follow-up. We detected a statistically significant interaction of intervention with RVGLS (p=0.024) and RVAC (p=0.012) (Figure 1). Conclusion Subclinical right ventricular dysfunction is present in convalescent COVID-19 patients. Cardiopulmonary rehabilitation can accelerate the improvement of RVAC by mediating both the RV afterload reduction (PASP) and improving RV function.Figure 1

Association between echocardiographic parameters and abnormal spirometry among chronic heart failure patients

Abstract Background A significant proportion (10-40%) of heart failure (HF) patients have concomitant pulmonary disease which have negative effects on cardiovascular outcome of patients. Because of the similarities in symptoms between HF and pulmonary disease, the prevalence of concomitant pulmonary disease may be underestimated. Early detection manage accordingly may improve outcomes of HF patients. We aimed to study clinical and echocardiographic parameters identifying HF patients with concomitant pulmonary disease. Methods This cross-sectional study included adults (age≥18 years) who were diagnosed with HF. The echocardiogram, arterial blood gas and pulmonary function test (PFT) were performed. The patients were classified into normal and abnormal (obstructive and restrictive) PFT patterns. The primary outcome was the association between echocardiographic parameters and abnormal PFT. The receiver operating characteristic (ROC) curve was performed to evaluate diagnostic performance of echocardiographic parameter in detecting abnormal PFT. Results A total of 57 patients was enrolled, of which 32 patients (56.14%) had normal PFT, 14 patients (24.56%) had obstructive PFT, and 11 patients (19.30%) had restrictive PFT. The clinical characteristics were not different between groups. ROC curve demonstrated that only left atrial volume index (LAVI) and main pulmonary artery (MPA) diameter had significant diagnostic accuracy to predict abnormal PFT with AUC of 0.72 (95%CI 0.57-0.87) and 0.66 (95%CI 0.51-0.80) respectively. Using combination of LAVI (cutoff 40mm2/m2) and MPA diameter (cutoff 22.0 mm) had a sensitivity of 95.7% (95%CI 78.05-99.89%) and specificity of 41.94% (95%CI 24.55-60.92%) in detection patients with abnormal PFT. Conclusion Almost half of HF had concomitant abnormal PFT. The combination of LAVI and MPA diameter can identify patients with abnormal PFT with high negative predictive value and should be considered as screening parameters in HF patients.

Transcatheter versus surgical aortic valve replacement in patients younger than 65 years: analysis from the national inpatient sample database

Abstract Background Data on the relative utilization and outcomes of transcatheter aortic valve replacement (TAVR) versus surgical AVR (SAVR) in patients &amp;lt;65 years are limited. Purpose To compare the relative utilization and outcomes of TAVR versus SAVR in patients &amp;lt;65 years in the United States. Methods We queried the National Inpatient Sample (2016-2020) to identify patients &amp;lt;65 years hospitalized for isolated AVR. In-hospital outcomes of TAVR versus SAVR were compared using multivariable regression and propensity-matching analyses. Results Of 74,155 patients aged &amp;lt;65 years hospitalized for isolated AVR, 17,300 (23.3%) underwent isolated TAVR, and 56,855 (76.7%) underwent isolated SAVR. From 2016-2020, the use of TAVR increased, while the use of SAVR decreased in patients &amp;lt;65 years (both ptrend&amp;lt;0.01). Factors independently associated with TAVR selection in patients &amp;lt;65 years included female sex, congestive heart failure, pulmonary disease, renal failure, liver disease, cancer, and prior revascularization. Factors independently associated with SAVR selection included bicuspid aortic valve. After adjustment for baseline characteristics, TAVR was associated with lower odds of in-hospital mortality (adjusted odds ratio [aOR] 0.61, 95% confidence interval [CI] 0.38-0.97), stroke (aOR 0.58, 95% CI 0.38-0.90), acute kidney injury (aOR 0.41, 95% CI 0.34-0.49), and major bleeding (aOR 0.62, 95% CI 0.38-0.96), and higher vascular complications compared with SAVR (aOR 2.39, 95% CI 1.75-3.24). Length of stay was shorter and nonhome discharges were lower with TAVR (all p&amp;lt;0.01). Similar findings were observed in the propensity-matched cohort. Conclusions This nationwide observational analysis showed that TAVR is a feasible treatment option for patients &amp;lt;65 years with lower in-hospital mortality and resource utilization compared with SAVR.Central Illustration

Does the presence of severe pulmonary hypertension affect survival at 5 years follow-up in patients who underwent TAVI for severe aortic stenosis?

Abstract Background Pulmonary hypertension (PH) is common in patients with severe aortic stenosis (AS) and is associated with increased mortality after transcatheter aortic valve implantation (TAVI) as well as surgical aortic valve replacement (SAVR). Preprocedural systolic pulmonary artery pressure (sPAP) often improves after TAVI because the most common type of PH is postcapillary PH secondary to left-sided heart disease, which potentially improves after treatment for AS. However, there are limited data regarding the prognostic impact on outcomes after TAVI and their predictors. Purpose The aim of this study is to compare survival at 5 years between patients with severe PH against those who did not have severe PH who underwent TAVI. Methods Between January 2012 until December 2022, we carried out a retrospective study of all patients who underwent TAVI at our hospital. Severe PH was defined as the presence of sPAP &amp;gt;40mmHg on echocardiography. Patients with aortic regurgitation and mixed aortic valve disease were excluded. Co-morbid pulmonary disease was defined as the presence of any significant pulmonary disease including COPD and Asthma. Co-morbid neurological disease was defined as the presence of any significant neurological disease including CVA/ TIA. Diabetes mellitus was defined as per WHO and included patients who were diet, medication and insulin controlled. Survival status and date of death were ascertained from our electronic health records. Counts and incidence rates of clinical outcomes at 5-year follow-up were computed from Kaplan-Meier analysis (See Figure 1). A Cox proportional hazards model was used to compute HRs and 95% CIs for the study outcomes. Results Of the 274 patients available for analysis, 115 (14%) patients had severe PH. The mean age was 84 years in both cohorts whilst patients in the severe PH cohort were frailer by Katz Index Score. Death occurred in 67 patients out of 115 patients who had severe PH and in 87 out of 158 patients who did not have severe PH after a median follow-up time of 4.1 years (58% vs 55%; adjusted HR: 1.04; 95% CI: 0.71-1.51; P = 0.86). Conclusion Our data shows that presence of severe pulmonary hypertension in severe aortic disease patients who had undergone TAVI did not affect survival at 5 years follow up compared to patients without severe pulmonary hypertension undergoing TAVI. Determining predictors of mortality in this high-risk cohort is likely to be complex and multifactorial, owing to the severe multi-comorbidity precluding them from SAVR.

Rising From the Rubble: Air Quality Concerns in Post-Earthquake Afghanistan.

This position paper highlights the dire impacts of environmental and household air pollution, which were responsible for 6.7 million deaths globally in 2019. These deaths occurred predominantly in low- and middle-income countries, with Afghanistan reporting the highest age-adjusted mortality rate. The situation worsens during large-scale disasters like earthquakes, which release more pollutants into the air, exacerbating health risks and leading to severe conditions such as pulmonary diseases. Because political factors may hinder foreign NGOs and similar organizations from providing direct support, the frequent occurrence of earthquakes in Afghanistan underscores the critical need for emergency response training for local residents. Consequently, it is essential to provide ERT training, including the proper use of protective equipment, to local populations as well as disseminating risk communication through online technologies and other appropriate means.

Peak oxygen pulse response during maximal cardiopulmonary exercise testing on a treadmill: applicability analysis of the FRIEND registry prediction equation in a Brazilian healthy sample

Abstract Background Peak oxygen uptake (VO2peak), measured by cardiopulmonary exercise test (CPET), is an established variable for prognostic assessment. Other VO2peak-derived variables, such as the peak oxygen pulse (peakO2pulse), also provide valuable information for risk stratification in patients with cardiac diseases. For individualized assessment, the measured peakO2pulse can be compared to reference standards using predictive equations, such as the FRIEND Registry [peakO2pulse = 23.2 – (0.09 × Age) – (6.6 × Sex (female:1; male: 0)]. However, the applicabilty of this equation in a Brazilian population sample has never been evaluated. Purpose To conduct an external validation of the FRIEND registry prediction equation for treadmill peakO2pulse in a sample of healthy Brazilian individuals. Methods Cross-sectional study involving subjects assessed by treadmill CPET in the Brazilian Midwest region from January 2011 to March 2020. Inclusion criteria: healthy individuals aged ≥ 20 years with a peak respiratory exchange ratio ≥ 1.00. Exclusion criteria: history of cardiovascular or pulmonary disease, presence of cardiovascular risk factors (hypertension, diabetes mellitus, current smoking, and obesity), and abnormalities on CPET. Variables were described as median and interquartile range (IQR). Statistical comparisons between measured and predicted values were conducted using the Wilcoxon signed rank test, including the calculation of the median differences and the 95% confidence interval (CI). Furthermore, Bland-Altman agreement analysis was utilized to assess the concordance between measured and estimated values. Results A total of 7,843 CPETs were performed. After applying inclusion and exclusion criteria, 3,544 assessments were included (1,574 females and 1,970 males) aged between 20 to 80 years. In the females, the median and IQR of measured peakO2pulse and predicted values were 10.4 (9.0; 12.1) and 13.1 (12.3; 13.7) ml/beat, respectively. This difference was statistically significant (p &amp;lt; 0.001), with a median difference of 2.54 mL/beat (95% CI: 2.40; 2.69). For males, the measured and predicted values were 17.3 (15.1; 19.7) and 19.7 (19.0; 20.2) ml/beat, respectively. The median difference was statistically significant at 2.26 mL/beat (95% CI: 2.11; 2.46) (p &amp;lt; 0.001) (Figure 1). Bland-Altman agreement analysis indicated a bias of 2.33 mL/beat (95% limits of agreement: -2.17 to 6.83) in females and 2.15 mL/beat (95% limits of agreement: -4.34 to 8.65) in males (Figure 2). Conclusions The study reveals that measured median peakO2pulse values are consistently lower than predicted across both sexes, highlighting a significant bias, which limits the applicability of the FRIEND registry prediction equation in the Brazilian population and underscores the international heterogeneity of the variable. The findings advocate for the development of region-specific reference standards to enhance accuracy in predicting peakO2pulse values.

Exploring the Role of Narrative Medicine in the Cultivation of Humanistic Spirit among Respiratory Medicine Interns

Objective: To explore the role of narrative medicine in cultivating the humanistic spirit of respiratory medicine interns. Methods: Thirty interns were selected, all of whom were received by the respiratory department of our hospital from September 2023 to June 2024 and underwent narrative medicine teaching. Scores on narrative medicine knowledge, empathy ability, humanistic care ability, and teaching recognition were compared before and after the internship. Results: Compared to before the internship, the interns’ scores on narrative medicine knowledge were significantly higher after the internship, as were their empathy and humanistic care scores (P &lt; 0.05). Among the 30 interns, 25 expressed interest in narrative medicine, and 29 were willing to continue with the narrative medicine teaching model. Conclusion: The application of narrative medicine in respiratory medicine internship teaching is highly effective. It cultivates the humanistic spirit of interns, improves their empathy and humanistic care abilities, and is worthy of wider implementation.

Determinants of tuberculosis site among 1035 cases in Frankfurt, 2008-2023: does lineage matter?

Abstract Extrapulmonary tuberculosis (EPTB) presents with nonspecific symptoms which can pose a diagnostic challenge. Currently, there are no clear predictors for EPTB. We aimed to identify these factors for better diagnosis and disease control. We included tuberculosis cases reported in Frankfurt from 2008-2023, with available clinical and whole genome sequencing data. According to WHO criteria, cases with pulmonary or combined pulmonary and extrapulmonary symptoms were categorised as pulmonary tuberculosis, while exclusively extrapulmonary symptoms were categorised as extrapulmonary tuberculosis. We assessed the association between EPTB and M. tuberculosis lineage, comorbidities and demographic characteristics using logistic regression, calculating crude and adjusted odds ratios (aOR). Of the 1035 reported tuberculosis cases, 272 had exclusively extrapulmonary disease and 136 had both pulmonary and extrapulmonary disease. In the univariable analysis, lineages 1 and 3 were significantly associated with extrapulmonary disease compared to lineage 4. However, this association was not observed in the multivariable analysis. In the final regression model, females were more likely to develop EPTB than men (aOR: 1.65, CI: 1.19-2.27). The odds of developing extrapulmonary disease were higher among patients born in the South-East Asian (aOR: 6.48, CI: 3.72-11.43) and Eastern Mediterranean (aOR: 5.54, CI: 3.41-9.11) than in other regions. Among the comorbidities, diabetes was found to be negatively associated with extrapulmonary disease (aOR: 0.50, CI: 0.26-0.91). Our results indicate that host factors such as geographic origin and sex are stronger predictors for extrapulmonary presentation of tuberculosis than a specific lineage. We recommend increasing physicians’ awareness of the nonspecific presentation of EPTB and adapting screening programmes, particularly for patients from South-East Asian and Eastern Mediterranean regions to foster more effective tuberculosis control measures. Key messages • Our study highlights the importance of considering host factors in predicting extrapulmonary tuberculosis, indicating their stronger influence compared to specific M. tuberculosis lineages. • Increased physicians’ awareness of the nonspecific symptoms of EPTB and targeted screening programs for high-risk populations are crucial for enhancing tuberculosis control measures.

Transpulmonary proteome gradients identify inflammatory pathways involved in the development of pulmonary vasculopathy in heart failure

Abstract Background Some, but not all, patients with heart failure (HF) develop pulmonary vascular disease (PVD), which contributes to poor prognosis. Mechanisms leading to PVD in HF are poorly understood. Unbiased analysis of transpulmonary gradients may identify not only markers but also mediators of PVD by identifying proteins that may be consumed or elaborated across the lungs. Purpose Examine hemodynamics and transpulmonary proteome gradients in HFrEF and controls. Methods 21 non-HF controls and 160 patients with advanced HFrEF underwent pulmonary artery (PA) catheterization with blood sampling from the PA catheter in the wedged position (02sat &amp;gt; 90%, indicating pulmonary venous blood) and the un-wedged position to obtain transpulmonary proteome gradients. Samples from controls and HF from the highest quartile (Q4, n=40) and lowest quartile (Q1, n=40) of pulmonary vascular resistance (PVR) were analyzed using proteomic PEA assay of 275 proteins (Olink Target 96, panels CVII, CVIII, Inflammation). Pulmonary artery concentrations ("markers") or transpulmonary fold-change gradients (i.e. putative "mediators") of normalized protein expression (NPX) were plotted against significance; Benjamini–Hochberg FDR&amp;lt;0.05 considered as significant. Results Patients displayed typical characteristics of HFrEF (age 56±8y, NYHA 3.0 ±0.6, 87% males, LVEF 24±9.6%), Controls had similar anthropometrics, gender and age. Comparing all HF to Con, 38 markers of HF were identified (NPX fold-change&amp;gt;2), including 33 up (top 5: NTproBNP, BNP, GDF15, FGF23, IL8) and 5 down. HF patients in Q1 had median PVR 1.5 (IQR: 0.3-1.7) WU and those in Q4 had PVR 5.4 (4.3-6.6) WU. Comparison of Q1 and Q4 identified 3 protein markers of high PVR in PA blood from HF: chemokine CCL3, TNFRSF13B and surfactant protein-D (PSP-D). Examination of protein gradients from HF lungs (Figure) showed significant uptake of 14 protein mediators, most of which were associated with inflammatory responses (top 5: OSM, MMP9, CCL19, BNP, TR), and release of 8 mediators (top 4: IL-6, IL33, CCL4, CXCL10). In contrast, protein gradients were negligible in controls. Patients in Q4 PVR group were characterized by the highest pulmonary uptake of OSM (Oncostatin-M), lymphatic chemokine CCL19, BNP, MMP9, and had more significant transpulmonary release of IL6 and IL33. Across all patients, OSM lung uptake was the strongest correlate of transpulmonary pressure gradient (r=-0.3, p&amp;lt;0.001). Conclusions Lungs of patients with HF, and particularly those with high PVR, display abnormal uptake and release of proinflammatory CC and CXC chemokines and cytokines from IL1 and IL6 family, along with increased pulmonary uptake of IL6-type cytokine Oncostatin-M, a known mediator of lung inflammation and fibrosis, that acts via gp130/JAK/STAT, suggesting a novel role in PVD due to HF.Transpulmonary proteome in HF patients

Genetic testing in pulmonary hypertension in adults and children

Abstract Pathogenic genetic variants have been found in patients with different forms of pulmonary arterial hypertension (PAH). Our aim was to define the genetic background of patients with idiopathic PAH (IPAH), heritable PAH (HPAH), pulmonary veno-occlusive disease (PVOD) and PAH associated with congenital heart disease (PAH-CHD); both in adult and pediatric age. REHAP and REHIPED are Spanish, voluntary, multicenter registries that include patients with PAH. REHAP started in 2007 and includes patients over 18 years of age. REHIPED started in 2009 and collects patients between 2 months and 18 years of age. Patients with IPAH, HPAH, PVOD and PAH-CHD who have undergone a genetic testing were included. 413 adults and 122 children were analyzed. From 2011, Sanger sequencing and multiplex ligation-dependent probe amplification were used to detect genetic variants in the BMPR2, TBX4, and KCNK3 genes. Since 2014, a next generation sequencing (NGS) panel of 21 genes was applied. In 2017 this panel was expanded to cover 35 genes, and in 2019, it was expanded to 37 genes. Since 2020, whole-exome sequencing has been applied for the previously followed-up patients without known pathogenic/likely pathogenic (P/LP) genetic variants, and for each incident case. There was a statistically significant difference (p 0.031) in the etiologies among adults and children. The etiologies in adults were 242 (59%) IPAH, 25 (6%) HPAH, 83 (20%) PAH-CHD, 63 (15%) PVOD. The etiologies in children were 66 (54%) IPAH, 8 (7%) HPAH, 38 (31%) PAH-CHD, and 10 (8%) PVOD. The genetic testing had a variant in 121 (29%) adults (56% pathogenic, 9% likely pathogenic, 32% VUS) and 63 (52%) children (65% pathogenic, 16% LP, 19% VUS) (adults vs children p &amp;lt; 0.001). BMPR2 was the most frequent variant in both populations, followed by EIF2AK4. Patients with HAPH and PVOD are more likely to have a genetic variant, while PAH-CHD are the less likely to have one; both in adults and children (p&amp;lt;0.001). The etiology was reclassified after the genetic testing in 13% adults and 19% children (p 0.08); including 6 adults and 4 children initially classified as IPAH and then diagnosed of PVOD when a P/LP variant was found in EIF2AK4. Also, 5 children were initially diagnosed as IPAH and then reclassified as multisystemic disorders (4 NFU1 and 1 MECP2) In conclusion, a significant number of patients with PAH have a variant in genetic testing, especially if they are diagnosed in pediatric age. BMPR2 is the most frequent variant in our cohort, followed by EIF2AK4. Knowing the genetic background of our patients enables a better classification and understanding of the disease. This is especially important in patients initially diagnosed of PAHI who are then classified as PVOD. Also, knowing the genetic background may help develop new treatments in the future.

Direct annual healthcare costs in survivors of acute pulmonary embolism: estimates based on a prospective multicentre cohort study

Abstract Background Patients surviving acute pulmonary embolism (PE) necessitate long-term care and follow-up. However, the economic impact of PE on healthcare systems after the acute event remains largely unknown. Purpose To estimate the direct cost of PE during the first year after discharge from hospital for the index event, focusing on rehospitalizations, anticoagulant medication, and outpatient follow-up. Methods We analyzed the data from a multicentre cohort study of 1017 unselected patients with confirmed acute symptomatic PE in Germany. After the index episode, the costs of which were not considered, patients prospectively followed an outpatient visit plan at 3, 12 and 24 months. All rehospitalisations were documented with the main and accompanying diagnoses; hospital costs were calculated based on current reimbursement in the German Diagnosis Research Groups (G-DRG) system. The duration and type (central unique drug identifier) of anticoagulant treatment was documented at each visit. Per-patient costs of ambulatory follow-up visits and tests were calculated by multiplying (i) the costs of each visit/test (German ambulatory healthcare services reimbursement catalogue) by (ii) the probability π (0.0≤π≤1.0) of needing that specific service, based on the PE follow-up algorithm of the ESC Guidelines which we populated with the actual results per step in the present study (Figure). The primary analysis was conducted in all patients with ≥3-month follow-up. An additional sensitivity analysis included only the patients completing ≥12-month follow-up. We additionally identified the baseline predictors for the number of rehospitalizations and costs using multivariable zero-inflated Poisson and hurdle regression and accounting for censored data. Results Of 1017 enrolled patients, 958 (94%) were included in the primary analysis. Of them, 24% were rehospitalized, for a marginal mean of 0.34 (bootstrapped 95% CI: 0.30-0.39) readmissions per PE survivor. Age, coronary artery, pulmonary and kidney disease, diabetes, and (in the sensitivity analysis) cancer, emerged as independent cost predictors by multivariable hurdle gamma regression (Table). Estimated overall rehospitalisation costs were €1138 (95% CI 896-1420) per patient (€1171 [908-1479] in the sensitivity analysis). Mean anticoagulation duration was 330 days, with estimated per-patient costs of €1050 (€1190 in the sensitivity analysis). Per-patient costs of ambulatory follow-up visits and tests were estimated at €182, yielding a total cost of illness per PE survivor of €2370-2543. For the entire country, the annual direct costs after acute PE would thus amount to €202-217 million. Conclusions By estimating per-patient costs and identifying major cost drivers of post-PE care, the present study may inform decisions concerning implementation and reimbursement of follow-up programmes aiming at improved overall cardiovascular prevention.TableFigure

Elevated cancer biomarkers in patients with severe heart failure could be a potential predictor of mortality during LVAD support

Abstract Introduction Owing to increasing numbers of heart failure patients a search for new biomarkers predicting prognosis is desirable. Background The purpose of this study was to analyze levels of cancer biomarkers in patients with severe heart failure before or after left ventricular assist device (LVAD) implantation and estimate its impact on survival during LVAD support. Methods We retrospectively analyzed data of all consecutive 168 LVAD recipients (92.8%- male, mean age 53.3 years ( median - 56.6, SD 12.0 ), median INTERMACS profile- 3.0, ischemic etiology of heart failure- 52.4%, 41.0% post CRT-D and 54.8% post ICD implantation, 36.9 post IABP, 5.4% post ECMO%, 11.9% post CABG and 8.9% post other cardiac surgery before LVAD implantation) implanted with continuous-flow LVAD (59.5%-HeartMate3, 35.1%- HeartWare, 5.4%-Heart Mate II) in our institution within years 2009-2023. Among comorbidities 63% of patients had atrial fibrillation or flutter, 41.6%- diabetes, 37.5%- arterial hypertension, 48.8%-renal failure, 7.1% pulmonary obstructive disease, 56.5% had pulmonary hypertension with mean pulmonary artery pressure above 25 mm Hg in right heart catheterization and 47% of patients had a history of cardiac arrest or sustained ventricular arrythmia before LVAD implantation. The overall mortality was 44.0 %. 31% patients were transplanted during LVAD support and in 4 patients (2.3%) LVAD was explanted or deactivated. Patient were followed to death, heart transplantation, LVAD explantation or the end of observation in our institution. Mean time of LVAD support was 885 days (1-2570). 23% of patients had right ventricular failure (RVF) early post LVAD implantation while 7.7% had late form of RVF. Results Serum concentrations of cancer biomarkers: carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, carbohydrate antigen(CA)-125 and alpha fetoprotein (AFP) taken before (56 patients -33.3%) or after (24 patients-14.3%) LVAD implantation were analyzed. Mean values, rate of abnormal results and correlation of abnormal results of CEA, CA19-9, CA-125, AFP with mortality during LVAD support were depicted in Table 1. No statistically significant correlations were found between levels of abovementioned cancer biomarkers and mortality though a trend towards increased mortality could be observed for abnormal results of CEA and Ca 19-9 taken before LVAD implantation. No malignant neoplasms were found in all analyzed patients except of one in whom a recurrence of lymphoma was found 2 months after LVAD implantation. Conclusions Patients with severe heart failure before and after LVAD implantation may present abnormal values of cancer biomarkers despite no found neoplasms. Our observation suggests that elevated cancer biomarker levels could predict mortality in heart failure patients after LVAD implantation. Further research is needed to confirm this thesis and investigate mechanisms of this phenomenon.

8.G. Scientific session: The German National Cohort (NAKO): Current state, follow up data collection and selected results

Abstract This workshop aims to give an overview on current state and selected results of the German National Cohort (NAKO). NAKO is the largest, multidisciplinary population-based cohort study in Germany. The overall aims of NAKO are: 1) to elucidate pathways to major chronic diseases such as diabetes, cancer, cardiovascular, pulmonary, neuro-psychiatric, and infectious diseases, focusing on determinants and exposures (e.g., socioeconomic, psychosocial, behavioural, occupational, and environmental factors); 2) to assess regional differences; and to improve prevention and early detection of disease. Between 2014 and 2019 more than 205,000 men and women aged 20-74 years at baseline were recruited in 18 study centres across Germany. During their examination participants underwent an extensive programme including a face-to-face interview, self-administered, computer-based questionnaires, in-depth biomedical examinations, and the collection of various bio-samples. In addition, at 5 study centres a subgroup of almost 31,000, received whole-body magnet resonance imaging (MRI). In 4-5 year intervals, all study participants are re-invited for examination at the study centres. The first re-examination started in October 2018 and will be finished in July 2024. In parallel the pilot phase for the second re-examination will start in May 2024. The programme for both re-examinations is similar to the baseline programme. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. During the COVID-19 pandemic two supplemental questionnaires focusing on pandemic-related aspects were provided to all NAKO participants at two different time points. The first COVID-19 questionnaire collected data on more than 160,000 participants during the first COVID-19-related lockdown in Spring 2020. The questionnaire included questions on general state of health, Sars-CoV-2 symptoms, changes in psychosocial, socioeconomic, and behavioural factors (e.g., physical activity). The workshop session consists of four presentations. The first presentation will provide insights into the extensive examination programme of NAKO, will give a short overview on the current state and plans for follow-up of data collection. In addition, it will briefly inform about possibilities to get access to NAKO data. Furthermore, the workshop will include three presentations on selected results of NAKO to demonstrate its broad research scope. The presentations will focus on the following topics: 1) cardiovascular disease and sex differences according to socioeconomic position, 2) cognitive functioning according to income, employment and living alone, 3) physical activity and changes during the COVID-19 pandemic. Key messages • Due to the large sample size, and the broad research scope, NAKO provides an excellent resource to scientists form different research disciplines and enforces interdisciplinary collaborations. • The workshop will be informative to researchers who are planning to work with NAKO data as data access within the European Union/the European Economic Area is open since spring 2024.