Search

Zewen Cheng,1 Jian Wu,1 Chun Xu,2 Xiaokun Yan1 1Department of Thoracic Surgery, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, 215000, People’s Republic of China; 2Department of Cardio-Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of ChinaCorrespondence: Xiaokun Yan, Department of Thoracic Surgery, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, 215000, People’s Republic of China, Email yanxk2008@126.comBackground: Observational studies have underscored a robust association between frailty and chronic obstructive pulmonary disease (COPD), yet the causality remains equivocal.Methods: This study employed bidirectional two-sample Mendelian randomization (MR) analysis. Univariable MR investigated the causal relationship between frailty and COPD. Genetic correlation was assessed using linkage disequilibrium score (LDSC) regression. Multivariable MR and mediation analysis explored the influence of various confounders and their mediating effects. The primary analytic approach was inverse variance weighted (IVW).Results: LDSC analysis revealed moderate genetic correlations between frailty and Global Biobank Meta-Analysis Initiative (GBMI) COPD (rg = 0.643, P = 6.66× 10− 62) as well as FinnGen COPD (rg = 0.457, P = 8.20× 10− 28). IVW analysis demonstrated that frailty was associated with increased risk of COPD in both the GBMI cohort (95% CI, 1.475 to 2.158; P = 2.40× 10− 9) and the FinnGen database (1.411 to 2.434; 9.02× 10− 6). Concurrently, COPD was identified as a susceptibility factor for frailty (P < 0.05). These consistent findings persisted after adjustment for potential confounders in MVMR. Additionally, mediation analysis revealed that walking pace mediated 19.11% and 15.40% of the impact of frailty on COPD risk, and 17.58% and 23.26% of the effect of COPD on frailty risk in the GBMI and FinnGen cohorts, respectively.Conclusion: This study has strengthened the current evidence affirming a reciprocal causal relationship between frailty and COPD, highlighting walking pace as a pivotal mediator.Keywords: frailty, COPD, Mendelian randomization, mediation analysis, causality

Abstract Objective Lung cancer (LC), the primary cause for cancer-related death globally is a diverse illness with various characteristics. Saliva is a readily available biofluid and a rich source of miRNA. It can be collected non-invasively as well as transported and stored easily. The process is also reproducible and cost-effective. The aim of this study was to evaluate the salivary expression of microRNAs let-7a-2, miR-221, and miR-20a in saliva and evaluate their efficacy, using multiple logistic regression (MLR) model, in diagnosis of lung cancer. Materials Samples of saliva were obtained from 40 lung cancer patients (20 lung adenocarcinoma and 20 lung squamous cell carcinoma) and 20 healthy controls. The levels of let-7a-2, miR-221, and miR-20a expression in saliva were assessed by RT-qPCR. Receiver operating characteristic (ROC) curve was utilized to assess the potential significance of miRNAs in saliva for lung cancer diagnosis with the use of multiple logistic regression (MLR), principal component analysis, and machine learning methods. Results Diagnostic odds ratio (DOR) of miR-20a in lung adenocarcinoma diagnosis versus healthy control was higher than miR-221, and DOR of miR-221 was higher than let-7a-2. miR-20a demonstrated a higher DOR for small cell lung carcinoma versus healthy control compared to let-7a-2, which in turn exhibited a higher DOR than miR-221. MLR of miR-221, let-7a-2, miR-20a, and smoking habit using main effects led to accuracy of 0.725 (sensitivity: 0.80, specificity: 0.65) and AUC = 0.795 for differentiation of small-cell lung carcinoma from lung adenocarcinoma. Our results showed that MLR based on salivary miRNAs could diagnose LUAD and SCLC from healthy control using main effects and two-way interactions with the accuracy of 0.90 (sensitivity = 0.95 and specificity = 0.85). Conclusion A salivary miRNA-based MLR model is a promising diagnostic tool for lung cancer, offering a non-invasive screening option for high-risk asymptomatic individuals.

Abstract Background Since 2021, COVID-19 has had a substantial impact on global health and continues to contribute to serious health outcomes. In Taiwan, most research has focused on hospitalized patients or mortality cases, leaving important gaps in understanding the broader effects of the disease and identifying individuals at high risk. This study aims to investigate the risk factors for disease progression through a nationwide population-based cohort study on COVID-19 in Taiwan. Methods This study included 15,056 patients diagnosed with COVID-19 between January 1, 2021, and December 31, 2021, using the Taiwan National Health Insurance Research Database. Baseline and clinical characteristics were collected to verify the association with progression to severity outcomes, including hospital admission, intensive care unit (ICU) admission, invasive ventilatory support, fatal outcome, and the composite outcome of these four events. Patients were observed for 30 days for disease progression. Multivariable logistic regression models were used to calculate odd ratios and 95% confidence intervals (CIs) for each outcome, adjusting for age, sex, region, risk factors, and vaccination status. Results Overall, 8,169 patients diagnosed during outpatient visits and 6,887 patients diagnosed during hospitalization were analyzed. Adjusting for age, sex, region, risk factors, and vaccination status, elderly patients had higher risks of hospital admission, ICU admission, invasive ventilatory support, fatal outcome, and composite outcome. Specifically, the risk of the fatal outcome was significantly higher for patients aged 75–84 (odds ratio: 6.11, 95% CI: 4.75–7.87) and those aged 85 years and older (12.70, 9.48–17.02). Patients with cardiovascular disease exhibited higher risks of hospital admission (1.60, 1.31–1.96), ICU admission (1.52, 1.31–1.78), invasive ventilatory support (1.57, 1.26–1.96), and fatal outcomes (1.26, 1.03–1.54) and the composite outcome (1.66, 1.20–1.54). Diabetes mellitus was identified as a significant risk factor for all clinical outcomes (hospital admission: 1.89, 1.53–2.35; ICU admission: 1.53, 1.30–1.79; invasive ventilatory support: 1.27, 1.01–1.60; the composite outcome: 1.45, 1.28–1.66), except for the fatal outcome. Conclusions This study indicated the impact of sex, age, and risk factors on the clinical outcomes of COVID-19 patients in Taiwan. Elderly patients and those with cardiovascular disease or diabetes mellitus had higher risks for severe outcomes, including hospitalization, ICU admission, invasive ventilatory support, and mortality. These findings can provide evidence for a better understanding of risk factors for disease progression and inform targeted intervention.

Abstract Background Initial antimicrobial therapy for pneumonia is frequently empirical and resistance to antimicrobial agents represents a great challenge to the treatment of patients hospitalized with pneumonia. We evaluated the frequency and antimicrobial susceptibility of Gram-negative bacteria causing pneumonia in US hospitals. Methods Bacterial isolates were consecutively collected (1/patient) from patients hospitalized with pneumonia and the susceptibility of Gram-negative bacilli (3,911 Enterobacterales and 2,753 non-fermenters) was evaluated by broth microdilution in a monitoring laboratory. Isolates were collected in 69 medical centers in 2020–2022. Aztreonam-avibactam was tested with avibactam at fixed 4 mg/L and a pharmacokinetic/pharmacodynamic susceptible (S) breakpoint of ≤ 8 mg/L was applied for comparison. Carbapenem-resistant Enterobacterales (CRE; isolates with MIC values of > 2 mg/L for imipenem and/or meropenem) isolates were screened for carbapenemases by whole genome sequencing. Results Gram-negative bacilli represented 71.1% of organisms. The most common Gram-negative species were Pseudomonas aeruginosa (22.4% of organisms), Klebsiella pneumoniae (8.8%), Escherichia coli (6.6%), Serratia marcescens (6.2%), Stenotrophomonas maltophilia (4.9%), and Enterobacter cloacae complex (4.8%). Aztreonam-avibactam inhibited 100.0% of Enterobacterales at ≤ 8 mg/L and 99.9% at ≤ 4 mg/L and showed potent activity against CRE (MIC50/90, 0.25/1 mg/L). Ceftazidime-avibactam and meropenem-vaborbactam were active against 89.4% and 88.5% of CREs, respectively. Aztreonam-avibactam retained activity against Enterobacterales non-susceptible to ceftazidime-avibactam and/or meropenem-vaborbactam (n = 19; MIC50/90, 0.25/4 mg/L). The most common carbapenemases were KPC (69.2% of CREs), NDM (9.6%), and SME (4.8%). A carbapenemase gene was not identified in 16.3% of CREs. Ceftazidime-avibactam and meropenem-vaborbactam were highly active against KPC and SME producers but showed limited activity against MBL producers. The most active comparators against CRE were tigecycline (95.2%S), amikacin (73.1%S), and gentamicin (60.6%S). Among Pseudomonas aeruginosa, 79.1% were inhibited at ≤ 8 mg/L of aztreonam-avibactam, 77.2% were meropenem susceptible, and 77.2% were piperacillin-tazobactam susceptible. Aztreonam-avibactam was highly active against S. maltophilia, inhibiting 99.5% of isolates at ≤ 8 mg/L. Conclusions Aztreonam-avibactam displayed potent in vitro activity against a large collection of contemporary Gram-negative organisms isolated from patients hospitalized with pneumonia, including CRE isolates resistant to ceftazidime-avibactam and/or meropenem-vaborbactam. Results of surveillance programs are valuable for planning empiric antimicrobial therapy guidelines and infection control measures.

Abstract Background Veno-arterial (V-A) and veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) are crucial support modalities during lung transplantation, yet their comparative effectiveness remains unclear. Methods We conducted an 8-year retrospective analysis of 62 lung transplant recipients who received intraoperative ECMO (29 V-A, 33 V-V). Baseline characteristics, surgical parameters, and clinical outcomes were compared. To address potential selection bias, we employed entropy weighted inverse probability of treatment weighting (IPTW-EW). Results After IPTW-EW adjustment, V-A ECMO was associated with superior hemodynamic and respiratory parameters, including lower systolic pulmonary artery pressure (30 vs. 37 mmHg, p = 0.007), higher arterial oxygen partial pressure (119 vs. 78 mmHg, p = 0.002), and less severe pulmonary edema (Grade 1: 50% vs. 3%, Grade 2: 45% vs. 38%, Grade 3: 5% vs. 59%, p

Abstract Background Idiopathic pulmonary fibrosis (IPF) is the most common Interstitial Lung Disease (ILD). It is characterized by dyspnoea and a progressive decline in lung function, which negatively affects life. This study aimed to evaluate Health-Related Quality of Life (HRQoL) in IPF patients in Latin American countries. Methods Six countries (Argentina, Bolivia, Colombia, Chile, Mexico, and the Dominican Republic) enrolled patients with IPF. They answered the Saint George’s Respiratory Questionnaire for Idiopathic Pulmonary Fibrosis (SGRQ-I) and the Hospital Anxiety and Depression Scale (HADS). Demographic characteristics, the Torvan index, and a lung function test were also assessed. IPF was diagnosed according to the ATS/ERS/JRS/ALAT 2018 criteria. Results We enlisted 75 patients diagnosed with IPF; 81% were male, with an average age of 74 ± 7. The total SGRQ-I score was 49 ± 23, with a higher score in the activity domain of 70 ± 23. Torvan index average was 17 ± 6. We found that 28% presented anxiety and 35% depression. Besides, we observed that patients requiring oxygen had a worse quality of life (total SGRQ-I 62 ± 22 vs. 45 ± 22, p = 0.003) without finding differences in antifibrotic therapy. We did not find differences in HRQoL when dividing groups according to their altitude above sea level, except for a higher frequency of anxiety in patients living at sea level. Conclusions We found similar data compared to those reported in real-life European populations. We also found that anxiety and depression are prevalent. However, they are often underdiagnosed and, therefore, left untreated.

Abstract Background Diet plays a crucial role in intervening in the development of chronic obstructive pulmonary disease (COPD), yet previous studies have not investigated the impact of dietary intake of live microbes on COPD. This study aims to assess the relationship between the two. Methods Participants from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012 were selected. The exposure variable was the estimated intake of live microbes in the diet, categorized into low, medium, and high groups. The outcome variable was COPD. A multivariable logistic regression model was used to assess the relationship between estimated dietary intake of live microbes and the risk of COPD. Results In the fully adjusted multiple logistic regression model, participants with moderate and high dietary intake of live microbes showed a negative association with the prevalence of COPD compared to those with low estimated intake, with reductions of 38% (OR, 0.62; 95% CI: 0.39–0.99, P

Abstract Background High-intensity exercise is recommended for the pulmonary rehabilitation of patients with chronic obstructive pulmonary disease (COPD); however, it can cause an energy imbalance due to increased energy expenditure. Here, we aimed to explore the effect of reducing exercise intensity on energy balance in patients with COPD experiencing high-intensity training-induced weight loss. Methods All participants underwent high-intensity endurance and resistance training for a 2-week preliminary period. Those who lost more than 1% of their weight were then randomized to either continue high-intensity exercise (AA group) or switch to low-intensity exercise (AB group) for another 2 weeks (experimental period). Results The analysis included 30 participants (AA, n = 15; AB, n = 15). The AA group showed significant increases in body composition, dietary intake, nutritional status, muscle strength, and exercise capacity at week 4 than at week 2, with no significant changes in the AB group. After the experimental period, a greater proportion of the AA group had energy intake exceeding expenditure than did the AB group (80% vs. 40%). Conclusions In patients with COPD who lost body weight during pulmonary rehabilitation with high-intensity exercise, continuing this exercise had a more positive effect on body composition, nutritional status, physical function, and energy balance than did reducing exercise intensity. These results suggest the importance of continuing high-intensity exercise, while taking into consideration energy intake and nutritional therapy, even when body weight loss occurs during pulmonary rehabilitation in patients with COPD. Trial registration This study was retrospectively registered on the UMIN-CTR as UMIN000050976 on May 5, 2023.

Abstract Purpose The inflammatory response in animal models of chronic obstructive pulmonary disease (COPD) is activated by the NLR-family-pyrin-domain-containing-3 (NLRP3) inflammasome pathway, which is also known to play a role in obesity-related inflammation. The NLRP3/caspase-1/interleukin (IL)-1β pathway might be involved in the progression of COPD with increasing body mass index. To our knowledge, no previous studies have explored the role of NLRP3 inflammasome markers in linking COPD and obesity. Here, we aim to investigate this potential connection by examining levels of NLRP3, caspase-1, IL-1β, and IL-17A and to provide additional data on the expression of these molecules in relation to smoking status and COPD severity. Methods A case‒control study was conducted between July 2020 and March 2023. Peripheral blood mononuclear cells were isolated, and total RNA was extracted for real-time quantitative polymerase chain reaction (qPCR) analysis to measure the expression levels of inflammasome molecules. Results 29 subjects who were diagnosed with stable COPD and 32 controls were included in the data analysis. NLRP3 and IL-17A but not caspase-1 or IL-1β expression was significantly greater in the COPD group than in the control group. We detected a significant increase in NLRP3 levels in the smoker COPD group (p = 0.009) and nonsmoker COPD group (p = 0.045) compared with those in the nonsmoker control group. There was no significant correlation between BMI and the inflammasome markers. Conclusion As proinflammatory biomarkers, NLRP3 and IL-17A are prominent in stable COPD patients. Smoking may trigger NLRP3-mediated inflammation in stable COPD patients. The expression levels of NLRP3 inflammasome molecules did not differ in terms of disease severity or BMI. Graphical Abstract

Abstract Background Legionella pneumophila is an uncommon pathogen causing community-acquired atypical pneumonia. Acinetobacter baumannii is a major pathogen responsible for hospital-acquired pneumonia, but it rarely causes serious infections in a community setting. Without prompt and appropriate treatments, infection from either of these two pathogens can cause a high mortality rate. Concurrent infection from both L. pneumophila and A. baumannii can cause serious outcomes, but it has rarely been reported previously. Case presentation A 45-year-old male presented to our hospital with a productive cough and fever after staying in a local hotel. His chest computed tomography (CT) scan showed bilateral lower-lobe infiltration and left pleural effusion. Empirical antibiotics, including piperacillin-tazobactam, levofloxacin, meropenem, and doxycycline, were administered to him to treat community-acquired pneumonia. However, his condition deteriorated very rapidly, and he required endotracheal intubation and mechanical ventilation for respiratory support. Finally, metagenomic next-generation sequencing (mNGS) of his bronchoalveolar lavage fluid identified L. pneumophila and A. baumannii. The sputum culture demonstrated multidrug-resistant A. baumannii. He was diagnosed with pneumonia by concurrent infections from both L. pneumophila and A. baumannii. After careful consideration of the antibiotic susceptibility results and the antibacterial mechanism of each antibiotic, we switched the antibiotics to omadacycline and cefoperazone/sulbactam. His clinical symptoms gradually subsided. The repeat chest CT image showed no infiltration or pleural effusion. Conclusions Community-acquired pneumonia can be caused by concurrent infections of both L. pneumophila and A. baumannii. Close clinical monitoring, early pathogen detection and antibiotic susceptability tests, and appropriate antibiotic regimen adjustments should be applied to these patients who failed initial antibiotic treatments.

Abstract Introduction : Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is commonly used for diagnosing mediastinal lymphadenopathy. Despite a low complication rate, severe hemorrhage can occur which is reported in this literature, particularly in hypervascular conditions like Castleman disease. Methods A 54-year-old male with idiopathic multicentric Castleman disease underwent EBUS-TBNA for mediastinal lymph node sampling. During the procedure, vascular invasion led to significant bleeding, requiring immediate interventions including suctioning and therapeutic bronchoscopy. Results The patient experienced massive hemorrhage, resulting in airway obstruction, oxygen desaturation, and cardiac arrest. Aggressive resuscitation successfully restored cardiac rhythm after 15 min. The patient was then stabilized and transferred to the intensive care unit for monitoring. Conclusions This case underscores the risk of severe hemorrhage in hypervascular conditions during EBUS-TBNA. Pre-procedural imaging, careful planning, and immediate availability of hemostatic measures are crucial to reducing complications and improving outcomes in high-risk patients.

Abstract Background Cough variant asthma (CVA) is a specific type of asthma characterized by chronic cough as the sole or predominant symptom. Accurate diagnosis is crucial for effective treatment, yet bronchial provocation test is not always feasible in clinical settings. To identify independent predictors of CVA diagnosis, we developed a nomogram for predicting CVA. Univariate and multivariate logistic regression analyses were employed to construct the model, and the accuracy and consistency of the prediction model were subsequently validated. Methods We conducted a retrospective review of clinical data from 241 outpatients with chronic cough (≥ 8 weeks) who underwent bronchial provocation test at our hospital between January 2018 and December 2021. Patients were categorized into CVA group and Non-CVA group based on diagnostic criteria. Univariate analysis (chi-square and t-tests) was performed, followed by multivariate logistic regression to identify independent predictors. A nomogram was constructed using these predictors and validated using Bootstrap resampling (B = 200) to calculate the C-index. Additionally, receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were employed to assess the model's accuracy. Results Of the 241 outpatients, 156 (64.7%) were diagnosed with CVA. Multivariate analysis identified several independent predictors of CVA, including cough triggered by cold air (OR = 12.493, P = 0.019), exposure to pungent odors (OR = 3.969, P = 0.002), cough phasing (OR = 4.515, P

Abstract Background Pulmonary inflammatory myofibroblastic tumor (IMT) accounts for 0.04–0.7% of all lung tumors, and endobronchial IMT accounts for only 10% of all pulmonary IMTs. Little is known about the therapeutic outcomes of rigid bronchoscopy for endobronchial IMT. Here, we report a case series of eight patients with endobronchial IMT underwent rigid bronchoscopy. Methods We retrospectively analyzed eight patients with endobronchial IMT between January 2004 and December 2023. Results The median age of our patients was 36 years, and 62.5% were male. Dyspnea was the predominant symptom in cases where the tumor was centrally located (n = 6), whereas hemoptysis was the predominant symptom in peripherally located tumors (n = 2). Most cases had high contrast enhancement and a tumor stalk without bronchial wall invasion on computed tomography (CT) and bronchoscopy. Complete endoscopic resection and laser cauterization via rigid bronchoscopy were possible in five patients. There were only two cases in which tumors remained after the procedure, requiring additional treatment (chemotherapy and surgical resection, respectively). In one patient, surgical resection was performed three weeks after the procedure, and the surgical specimen was free of residual tumor. There was no mortality during the median follow-up duration of 18.8 months. Conclusions Endoscopic resection and laser cauterization using rigid bronchoscopy may serve as a safe and effective alternative treatment modality to surgery for patients with endobronchial IMT.

Abstract Background Mesenchymal to epithelial transition factor (MET) dysregulation in non-small-cell-lung-cancer (NSCLC) is understudied, with scant data on treatment outcomes. Methods We retrospectively examined 160 NSCLC patients: 125 with primary MET mutations (further classified into MET exon 14 (METex14) skipping mutations and primary MET amplifications) and 35 with secondary MET amplifications. Patients underwent varied treatments: Chemotherapy, Immune monotherapy, Crizotinib, or Savolitinib. Secondary MET amplification patients were grouped by treatment: Group A (Class Ib MET-TKI with third-generation EGFR-TKI), Group B (Crizotinib with first-generation EGFR-TKI), and Group C (Crizotinib alone). One hundred and thirty patients have completed the whole treatment process. Their data were included in the study's survival analysis (included 95 patients with primary MET mutations and 35 patients with secondary MET amplifications). Results Among METex14 skipping mutations patients (n = 57), median progression free survival (PFS) was: Chemotherapy 7.64 m, Crizotinib 8.5 m, Savolitinib 9.3 m, and Immunotherapy 3.87 m. Targeted therapies and chemotherapy significantly outperformed Immunotherapy. Sub-group analysis indicated splice donor region mutations benefited more than those at the polypyrimidine tract (9.23 m vs. 4.03 m, P = 0.038). For primary MET amplifications (n = 38), PFS was: Chemotherapy 2.84 m, Crizotinib 3.80 m, Savolitinib 5.23 m, and Immunotherapy 3.30 m. Patients with copy number (CN) > 5 had longer PFS than CN ≤ 5 (5.17 m vs. 3.44 m, P = 0.039). In secondary MET amplifications (n = 35), Group A and B had similar PFS (6.77 m and 6.57 m) versus Group C (3.13 m). Dual-target therapy PFS showed no difference between CN ≤ 5 and CN > 5 (8.63 m vs. 6.27 m, P = 0.29). Conclusion NSCLC patients with METex14 skipping mutations benefit more from targeted therapies, especially those with splice donor mutations. MET amplification patients benefit universally from targeted therapies; primary MET amplifications show higher benefits with increased copy numbers. For secondary MET amplifications post-EGFR-TKI resistance, dual-target therapy surpasses Crizotinib monotherapy, independent of MET copy number.

Abstract Background Glomus tumors (GTs) are rare, comprising only 2% of all soft tissue tumors. Pulmonary GTs are exceptionally rare, with fewer than 80 cases reported to date. Little is known about the therapeutic outcomes of rigid bronchoscopy for endobronchial GT. Methods This is a case series of four patients with endobronchial GT who underwent therapeutic rigid bronchoscopy between February 2021 and June 2024. Results The ages of the patients in our series ranged from 32 to 75 years, and all patients were male. Cough and blood-tinged sputum were present in all patients with endobronchial GT. The tumor sizes ranged from 1 to 3 cm. Complete endoscopic resection and laser cauterization via rigid bronchoscopy were achieved in two patients. One patient had incomplete resection of a 3-cm tumor in the segmental bronchus that showed radiological evidence of bronchial wall invasion. This patient subsequently underwent lobectomy seven months after bronchoscopic resection. The fourth patient was lost to follow-up. There was no mortality throughout the follow-up periods that ranged from 2.8 to 42.5 months. Factors favoring successful rigid bronchoscopy resection for endobronchial GT include a benign tumor in the central airways without bronchial wall invasion. Conclusion Endoscopic resection and laser cauterization using rigid bronchoscopy may be a viable option for patients with endobronchial GT when surgery is not practical. Clinical trial number Not applicable.

Abstract Background In this study, we aimed to explore the association between baseline and early changes in the neutrophil-to-lymphocyte ratio (NLR) and the 30-day mortality rate in patients having anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis with interstitial lung disease (DM-ILD). Methods Overall, 263 patients with anti-MDA5 DM-ILD from four centers in China were analyzed. Multivariate logistic regression analysis was used to evaluate the impact of baseline NLR on the 30-day mortality rate in patients with anti-MDA5-positive DM-ILD. Furthermore, a generalized additive mixed model (GAMM) was applied to compare the NLR variations over time between 30-day survival group and non-survival group. Results Two hundred sixty-three patients with anti-MDA5-positive DM-ILD were divided into different groups based on their NLR and whether they survived or not within 30 days. The multivariate logistic regression analysis, accounting for confounding factors, identified an elevated baseline NLR as a prognostic indicator for 30-day mortality in patients with anti-MDA5-positive DM-ILD (hazard ratio 2.68, 95% confidence interval [CI] 1.18,6.00, P = 0.019). Furthermore, the GAMM results indicated that the NLR gradually increased more in the non-survival group compared with the survival group within 14 days of admission, with a daily average increase of 1.03 (β = 1.03; 95% CI, 0.75–1.31; P

Abstract Background Reports of autoimmune diseases coexisting with autoimmune pulmonary alveolar proteinosis (autoimmune PAP; APAP) are extremely rare. APAP coexisting with autoimmune diseases may often be misdiagnosed as connective tissue disease–associated interstitial lung disease (ILD). Here, we describe a rare case of a patient with systemic sclerosis who was diagnosed with APAP after the exacerbation of lung opacities during treatment with immunosuppressive agents. Case presentation A 72-year-old woman was diagnosed with systemic sclerosis (SSc) at the age of 68, and initiated treatment with prednisolone (PSL). At the age of 70, she was diagnosed with ILD associated with SSc. Despite intravenous cyclophosphamide (IVCY), no improvement was observed. A significant elevation of Krebs von den Lungen-6 (KL-6) and a crazy-paving pattern on chest computed tomography (CT) are observed. Bronchoscopy showed milky white bronchoalveolar lavage fluid (BALF) and histology of periodic acid-Schiff (PAS) stain-positive eosinophilic granular material. Serum anti granulocyte–macrophage colony-stimulating factor (GM-CSF) antibodies were measured, and the result was positive, leading to the diagnosis of APAP. Conclusion In patients with interstitial lung shadows who do not improve with immunosuppressive treatment, PAP is one of the differential diagnoses that should be considered. All physicians should be aware that the appropriate diagnosis of PAP and the measurement of serum anti-GM-CSF antibodies will critically affect patient outcomes.

Abstract Chronic breathlessness is a debilitating symptom with detrimental impact on individuals and carers. However, little is known about the experiences of community-dwelling, frail, older adults living with chronic breathlessness. To explore, (i) the psychological impact of living with chronic breathlessness, (older frail adult patients, carers) and (ii) how patients, carers, and clinicians experience identification and assessment of chronic breathlessness in the primary care setting. In-depth semi-structured interviews with eligible older adults (≥65 years; moderate to severe frailty [electronic Frailty Index >0.36]), and carers recruited from a community-based Integrated Care Centre in England. Clinicians were recruited from the Centre and affiliated GP practices. Recorded in-person interviews were transcribed and subjected to reflexive thematic analysis using Total Dyspnoea and Breathing Space conceptual frameworks. 20 patients (9 females), carers (4 spouses, 1 daughter), and clinicians (5 GPs, 3 advanced clinical practitioners, 2 nurses) were interviewed. Four themes were identified: (1) Widespread negative impact of chronic breathlessness. Breathlessness adversely impacts physical and psychological wellbeing. (2) Barriers to optimal health-seeking and identification of chronic breathlessness. Breathlessness is ‘one of many’ symptoms, and not prioritised in ‘one appointment, one problem’ consultations. Clinicians do not routinely ask about breathlessness. Patients are unaware of breathlessness-specific therapies. (3) Variations in chronic breathlessness management. Management is limited; few are offered evidence-based treatments (e.g., handheld fan) and patients find their own strategies. (4) Need for education and information. Clinicians felt helpless about breathlessness management, and patients lacked understanding and had low expectations of receiving help for this symptom. Breathlessness adversely impacts the psychological wellbeing of older frail adults. Chronic breathlessness in older, frail adults is invisible, unidentified and unmanaged in primary care. Evidence-based breathlessness interventions are available, but not routinely implemented with few patients accessing them. Proactive identification, assessment and management of breathlessness in primary care is needed to support adults living with chronic breathlessness.

Abstract This survey aimed to investigate the availability of drugs for stable chronic obstructive pulmonary disease (COPD) treatment in Chinese hospitals and to determine whether drug availability significantly varied among hospitals with different characteristics. A well-constructed questionnaire was designed according to the Chinese Guidelines for the Diagnosis and Management of COPD (revised version 2021). Both inhaled drugs (monotherapy, double therapy and triple therapy) and oral drugs (expectorants, theophylline, antibiotics, and bacterial lysates) were included in this survey. Doctors from different hospitals completed the survey via WeChat. The availability of each category and kind of drug was analyzed based on final valid responses. Subgroup analyses were also conducted to reveal drug availability in hospitals with different characteristics. A total of 1018 hospitals with different characteristics were enrolled in this survey, with 53.73% of which establishing independent respiratory departments. Insufficient supply of COPD-related drugs was observed, with only short-acting β2 agonists (80.6%), expectorants (88.2%) and antibiotics (84.3%) reaching 80%. Results of subgroup analyses suggested that primary hospitals were associated with poorer availability of all kinds of drugs than secondary and tertiary hospitals (all p

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal disease of the lungs. It is characterized by pulmonary and extrapulmonary comorbidities. So far, little is known as regards the prevalence of cardiovascular comorbidities in IPF patients. This study aims to investigate the prevalence of cardiovascular comorbidities in patients with IPF and correlate it with different radiological and laboratory indices of disease severity. Methods This prospective case–control study was performed on 134 IPF patients above 18 years. Diagnosis of IPF was based on diagnostic radiologic criteria addressed by ATS guidelines. Patients were recruited from the Pulmonology Department, Assiut University Hospitals, from June 2023 to June 2024. Cardiac comorbidities were assessed by ECG and echocardiography. All patients had C-reactive protein (CRP), Krebs von den Lungen-6 (KL-6), and lipid profile including cholesterol level, triglyceride level, HDL-cholesterol level, and LDL-cholesterol level measured. Patients were divided into two groups: IPF patients with cardiovascular comorbidities and IPF patients without cardiovascular comorbidities. Comparison between both groups as regards clinical, radiological, and laboratory criteria was carried out. Results The studied group consists predominantly of females (65%). Sixty out of the 134 documented IPF patients had cardiovascular comorbidities (44.7%), cardiomyopathy (mean ± SD: 43.63 ± 10.56), pulmonary hypertension (mean ± SD: 41.67 ± 15.32), ECG-ischemic changes (40.0%), and atrial fibrillation (13.3%). IPF patients with cardiovascular comorbidities vs. patients without had higher radiological HRCT total fibrosis score TFS (P value

Abstract Background A growing body of evidence suggests that prolonged use of inhaled corticosteroids (ICS) and proton pump inhibitors (PPIs) is associated with increased risks of pneumonia. A substantial proportion of people with idiopathic pulmonary fibrosis (IPF) are prescribed PPIs or ICS to treat common comorbidities, giving rise to concerns that use of these medications may be associated with potential harms in this patient population. Methods We used UK Clinical Practice Research Datalink (CPRD) Aurum primary care data linked to national mortality and hospital admissions data to create a cohort of people diagnosed with IPF on or after 1 January 2010. Patients were assigned to one of three exposure categories according to their prescribing history in the 12 months prior to IPF diagnosis as follows: “regular” users (≥ 4 prescriptions), “irregular” users (1–3 prescriptions) and “non-users” (no prescriptions). We explored the association between PPI/ICS prescription and pneumonia hospitalisation and all-cause mortality using multinomial Cox regression models. Results A total of 17,105 people met our study inclusion criteria; 62.6% were male and 15.9% were current smokers. Median age at IPF diagnosis was 76.7 years (IQR: 69.6–82.7). 19.9% were regularly prescribed PPIs, and 16.0% ICS, prior to IPF diagnosis. Regular prescribing of PPIs and ICS was positively associated with hospitalisation for pneumonia; the adjusted HR for pneumonia hospitalisation comparing regular PPI users with non-users was 1.14 (95%CI: 1.04–1.24); for regular ICS users the corresponding HR was 1.40 (95%CI: 1.25–1.55). We also observed a small increased risk for all-cause mortality in the “regular ICS user” group compared with the “non-user” control group (HRadj = 1.19, 1.06–1.33). We found no evidence of an association between PPI prescribing and all-cause mortality. Conclusion Prolonged prescription of medications used to treat common comorbidities in IPF may be associated with increased risks for severe respiratory infections. These findings point to a need to adopt an adequate risk–benefit balance approach to the prescribing of ICS-containing inhalers and PPIs in people with IPF without evidence of comorbidities, especially older patients and/or those with more advanced disease in whom respiratory infections are more likely to result in poorer outcomes.

Abstract Background The effect of immunosuppression on clinical manifestations and outcomes was unclear in elderly patients with CAP. Methods Elderly hospitalised patients with CAP were consecutively enrolled and were divided into immunocompromised hosts (ICHs) or non-ICHs groups. Clinical manifestations, severity, and outcomes were compared. The logistic regression model was used to determine the association between immunosuppression and outcomes. The primary outcome was 30-day mortality. Results A total of 822 patients were enrolled, of whom 133 (16.2%) were immunocompromised. There were no differences between the two groups in vital signs, oxygenation, admission laboratory tests, need for mechanical ventilation and intensive care unit admission, except for a lower lymphocyte count in the ICH group (0.9*10^9/L, IQR 0.6–1.3*10^9/L [ICH group] vs. 1.2*10^9/L, IQR 0.8–1.7*10^9/L [non-ICH group]; p 0.05). After adjusting for age, sex, and comorbidities, immunosuppression was significantly associated with a higher risk of 30-day mortality (odds ratio 5.004, 95% CI [2.618–9.530]). Conclusions Immunosuppression was independently associated with an increased risk of 30-day mortality. CURB-65 may underestimate the mortality risk of ICHs.

Abstract Background Neutrophil extracellular trap (NET) formation has been implicated as a pathogenic mechanism in both rheumatoid arthritis (RA) and interstitial lung disease (ILD). However, the role of NETs in RA-associated ILD (RA-ILD) and the mechanisms driving NET formation remain unclear. This study aimed to assess the involvement of NETs in RA-ILD and elucidate the underlying mechanisms. Methods Single-cell sequencing was used to identify changes in the quantity and function of neutrophils in the lung tissue of a zymosan A (ZYM)-induced interstitial pneumonia arthritis model. Additionally, nuclear receptor 4A3 (NR4A3) interference was performed in HL-60 cells to assess its impact on NET formation and the transformation of MRC-5 cells into myofibroblasts. The clinical relevance of plasma myeloperoxidase-DNA (MPO-DNA), citrullinated histone 3 (Cit-H3), and cell-free DNA was evaluated in RA-ILD patients with different imaging types via a commercial enzyme-linked immunosorbent assay (ELISA). Results In the ZYM-treated SKG mouse model, which recapitulates key features of RA-ILD, an increased population of neutrophils in the lung tissue was primarily responsible for NET formation. Mechanistically, we found that interference with NR4A3 expression enhanced NET formation in HL-60 cells, which in turn promoted the differentiation of MRC-5 cells into myofibroblasts. Clinically, plasma MPO-DNA levels are elevated in patients with RA-nonspecific interstitial pneumonia (RA-NSIP), whereas Cit-H3 levels are elevated in RA-usual interstitial pneumonia (RA-UIP) patients compared with healthy subjects. ROC curve analysis further revealed that the combination of plasma MPO-DNA, rheumatoid factor (RF), and anti-citrullinated protein (anti-CCP) and the combination of Cit-H3, RF, and anti-CCP were superior diagnostic panels for NSIP and UIP in RA-ILD patients, respectively. Moreover, compared with those from healthy controls, neutrophils from patients with RA-UIP and RA-NSIP demonstrated a significantly increased ability to form NETs and induce the differentiation of MRC-5 cells into myofibroblasts. Specifically, RA-UIP patients exhibited a greater capacity for NET formation and the differentiation of MRC-5 cells into myofibroblasts than did RA-NSIP patients. Conclusions These findings suggest that targeting NETs may be a novel therapeutic approach for treating ILD in RA patients.

Abstract Background Bronchopulmonary dysplasia (BPD) is a chronic lung condition of premature neonates, yet without an established pharmacological treatment. The BPD rabbit model exposed to 95% oxygen has been used in recent years for drug testing. However, the toxicity of the strong hyperoxic hit precludes a longer-term follow-up due to high mortality after the first week of life. This study aimed to extend the preterm rabbit model to postnatal day (PND) 14 to mimic the evolving phase of BPD and enable the investigation of therapeutic interventions at later and more relevant time points. Methods Preterm rabbit pups delivered on the 28th day of gestation were either exposed to room air or different degrees of hyperoxia (50% and 70% O2) for 14 days. Single (immediately after birth) or double (at birth and at PND5) intratracheal lipopolysaccharide (LPS) administrations were also tested in combination with 50% O2. Age-matched rabbits delivered vaginally at term were used as controls. Survival, weight gain, lung function, pulmonary artery micro-ultrasound Doppler analysis, lung histology (alveolarization, lung injury score, and design-based stereology), and longitudinal micro-CT imaging were used to compare the outcomes at PND14. Results Premature birth itself, without any other BPD hit, was associated with lung function deficits, delayed lung development, and cardiovascular abnormalities. The BPD-like lung phenotype was enhanced by 70% O2 but not by 50% O2 hyperoxia. Intratracheal LPS delivered immediately after birth was associated with significantly higher lung injury scores at PND14 and increased tissue damping, a marker of parenchymal air resistance. Conclusion Several strategies are feasible to extend the preterm rabbit model of BPD to PND14. Preterm birth at the saccular phase itself, even in the absence of other postnatal BPD hits, was associated with lung function deficits, delayed lung development, and cardiovascular abnormalities compared with age-matched term rabbit pups. Enhanced BPD-like phenotypes can be further achieved by continued exposure to moderate hyperoxia (70% O2) and the intratracheal administration of LPS.

Abstract Background Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapidly evolving interstitial lung disease (ILD), driving its mortality. Specific imaging-based biomarkers associated with the evolution of lung disease are needed to help predict and quantify ILD. Methods We evaluated the potential of an automated ILD quantification system (icolung®) from chest CT scans, to help in quantification and prediction of ILD progression in SSc-ILD. We used a retrospective cohort of 75 SSc-ILD patients to evaluate the potential of the AI-based quantification tool and to correlate image-based quantification with pulmonary function tests and their evolution over time. Results We evaluated a group of 75 patients suffering from SSc-ILD, either limited or diffuse, of whom 30 presented progressive pulmonary fibrosis (PPF). The patients presenting PPF exhibited more extensive lesions (in % of total lung volume (TLV)) based on image analysis than those without PPF: 3.93 (0.36–8.12)* vs. 0.59 (0.09–3.53) respectively, whereas pulmonary functional test showed a reduction in Force Vital Capacity (FVC)(pred%) in patients with PPF compared to the others : 77 ± 20% vs. 87 ± 19% (p

Abstract The Alertapnée study followed 555 adults with obstructive sleep apnea treated with CPAP and found that the occurrence of Cheyne-Stokes respiration (CSR) was linked to a 14-fold increase in the risk of significant cardiac events (SCE) after one year. However, the progression and clinical significance of CSR episodes over time remain unclear. This ancillary study aimed to assess CSR progression and clinical outcomes during a second year of follow-up in 66 patients who had experienced at least one CSR episode in the first year. The study focused on the number of nights with CSR, percentage of CSR, SCEs. Results showed that 62 of 66 patients with CSR in the first year also experienced CSR in the second year, with a significant increase in the median number of CSR nights, particularly when CSR was related to cardiovascular conditions (37 vs. 19 nights, p = 0.006). Patients who experienced a SCE in year 2 had significantly more nights with CSR (median 48/90nights; IQR = 35) and a significantly greater mean percentage of CSR (median 13.8%; interquartile range (IQR) = 13.7) as compared with patients free of SCE (median 9.5/90 nights IQR = 27.8 (p = 0.012); 6.1% IQR = 4.5 (p = 0.008), respectively). In conclusion, CSR occurrence and severity depend on the underlying condition. CSR related to cardiovascular aetiology increases over time and is associated with SCEs, whereas CSR linked to non-cardiovascular conditions does not indicate a poor prognosis. Identifying CSR patterns related to cardiovascular aetiologies could enable early detection of SCEs through telemonitoring in CPAP-treated patients.

Abstract Background Severe and critical COVID-19 is characterized by pulmonary viral infection with SARS-CoV-2 resulting in local and systemic inflammation. Dexamethasone (DEX) has been shown to improve outcomes in critically ill patients; however, its effect on tissue remodeling, particularly collagen turnover, remains unclear. This study investigated the association between circulating extracellular matrix (ECM) remodeling neo-epitopes and COVID-19 severity, their relationship with mortality, and the effect of DEX on these markers. Methods We conducted a multi-center prospective cohort study involving 226 COVID-19 patients: 157 with severe disease admitted to the ward and 69 with critical disease admitted to the ICU. Plasma samples were collected at ICU admission and at discharge or death. Circulating collagen degradation (C3M, C4Ma3, and C6M) and synthesis (PRO-C3, PRO-C4, and PRO-C6) neo-epitopes were measured. Longitudinal analysis of ECM neo-epitope changes during ICU stay and their association with mortality was performed, along with an evaluation of the impact of DEX treatment on these markers. Results Critically ill patients exhibited higher levels of collagen degradation (reflecting inflammatory driven ECM destruction) (C3M, C6M) and collagen synthesis (strongly related to fibroblast activity) (PRO-C3, PRO-C6) neo-epitopes than severe patients. Increased collagen turnover, measured during ICU stay, was associated with mortality. Non-survivors displayed rising levels of collagen degradation and synthesis markers over time, whereas survivors had stable or declining levels. In non-survivors without DEX treatment, C6M and PRO-C6 levels were significantly increased, whereas these elevations were less pronounced in patients treated with DEX. Conclusion Our findings suggest that elevated collagen turnover is associated with poor outcomes in critically ill COVID-19 patients. DEX treatment appeared to attenuate ECM remodeling, although this effect was not linked to improved survival. Further studies are needed to confirm these observations and better understand the role of ECM remodeling in COVID-19 and the potential therapeutic impact of corticosteroids.

Abstract Background MicroRNAs (miRNAs) are crucial post-transcriptional regulators involved in inflammatory diseases, such as asthma. Poor lung function and airflow issues in childhood are linked to the development of chronic obstructive pulmonary disease (COPD) in adulthood. Methods We analyzed small RNA-Seq data from 365 peripheral whole blood samples from the Genetics of Asthma in Costa Rica Study (GACRS) for association with airflow levels measured by FEV1/FVC. Differentially expressed (DE) miRNAs were identified using DESeq2 in R, adjusting for covariates and applying a 10% false discovery rate (FDR). The analysis included 361 samples and 649 miRNAs. The two DE miRNAs were further tested for association with airflow obstruction in a study of adult former smokers with and without COPD. Results We found 1 upregulated and 1 downregulated miRNA in participants with airflow below the threshold compared to those above it. In the adult study, the same miRNAs were upregulated and downregulated in individuals with FEV1/FVC 0.7, showing suggestive statistical evidence. The target genes of these miRNAs were enriched for PI3K-Akt, Hippo, WNT, MAPK, and focal adhesion pathways. Conclusions Two differentially expressed miRNAs were associated with airflow levels in children with asthma and airflow obstruction in adults with COPD. This suggests that shared genetic regulatory systems may influence childhood airflow and contribute to adulthood airflow obstruction.

Abstract Background Pulmonary arterial hypertension (PAH) is a progressive disorder that can lead to right ventricular failure and severe consequences. Despite extensive efforts, limited progress has been made in preventing the progression of PAH. Mitochondrial dysfunction is implicated in the development of PAH, but the key mitochondrial functional alterations in the pathogenesis have yet to be elucidated. Methods We integrated three microarray datasets from the Gene Expression Omnibus (GEO), including 222 lung samples (164 PAH, 58 controls), for differential expression and functional enrichment analyses. Machine learning identified key mitochondria-related signaling pathways. PAH and control lung tissue samples were collected, and transcriptomic and metabolomic profiling were performed. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis investigated shared pathways, and canonical correlation analysis assessed gene-metabolite relationships. Results In the GEO datasets, mitochondria-related signaling pathways were significantly enriched in PAH samples, in particular the electron transport chain (ETC) in mitochondrial oxidative phosphorylation system. Notably, the electron transport from cytochrome c to oxygen in ETC was identified as the most crucial mitochondria-related pathway, which was down-regulated in PAH samples. Transcriptomic profiling of the clinical lung tissue analysis identified 14 differentially expressed genes (DEGs) related to mitochondrial function. Metabolomic analysis revealed three differential metabolites in PAH samples: increased 3-phenyllactic acid and ADP, and decreased citric acid. Mitochondria-related genes highly correlated with these metabolites included KIT, OTC, CAMK2A, and CHRNA1. Conclusions Down-regulation of electron transport from cytochrome c to oxygen in mitochondrial ETC and disruption of the citric acid cycle homeostasis may contribute to PAH pathogenesis. 3-phenyllactic acid emerges as a potential novel diagnostic biomarker for PAH. These findings offer insights for developing novel PAH therapies and diagnostics.

Abstract Progressive forms of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), are deadly disorders lacking non-invasive biomarkers for assessment of early disease activity, which presents a major obstacle in disease management. Excessive extracellular matrix (ECM) deposition is a hallmark of these disorders, with fibronectin being an abundant ECM glycoprotein that is highly upregulated in early fibrosis and serves as a scaffold for the deposition of other matrix proteins. Due to its role in active fibrosis, we are targeting fibronectin as a biomarker of early lung fibrosis disease activity via the PEGylated fibronectin-binding polypeptide (PEG-FUD). In this work, we demonstrate the binding of PEG-FUD to the fibrotic lung throughout the course of bleomycin-induced murine model of pulmonary fibrosis. We first analyzed the binding of radiolabeled PEG-FUD following direct incubation to precision cut lung slices from mice at different stages of experimental lung fibrosis. Then, we administered fluorescently labeled PEG-FUD subcutaneously to mice over the course of bleomycin-induced pulmonary fibrosis and assessed peptide uptake 24 h later through ex vivo tissue imaging. Using both methods, we found that peptide targeting to the fibrotic lung is increased during the fibrogenic phase of the single dose bleomycin lung fibrosis model (days 7 and 14 post-bleomycin). At these timepoints we found a correlative relationship between peptide uptake and fibrotic burden. These data suggest that PEG-FUD targets fibronectin associated with active fibrogenesis in this model, making it a promising candidate for a clinically translatable molecular imaging probe to non-invasively determine pulmonary fibrosis disease activity, enabling accelerated therapeutic decision-making.

BACKGROUND: The 2022 invasion of Ukraine by the Russian Federation triggered a refugee crisis, affecting the multidrug-/rifampicin-resistant TB (MDR/RR-TB) prevalence in neighbouring countries. This study examines the epidemiological trends and characteristics of MDR/RR-TB patients in Poland, focusing on the relative contribution of Ukrainian refugees. METHODS: Data from the Polish National Tuberculosis Registry and EPIC Project database, covering MDR/RR-TB cases reported between 2010 and Q1 2024, were analysed. RESULTS: The study included 794 MDR/RR-TB cases, showing a demographic shift post-2022. During the 10-year period up to 2021, a median of 48 MDR/RR-TB cases were reported annually in Poland. After 2022, these numbers doubled: 104 cases were reported in 2022 and 101 cases in 2023. Simultaneously, the number of Ukrainian MDR/RR-TB patients increased from 77 (13%) during 2010–2021 to 127 (58%) from 2022 to Q1 2024. CONCLUSION: Poland is observing an increased number of cases of MDR/RR-TB associated with the large number of displaced Ukrainian citizens who are now residing in Poland. There is a need to monitor the epidemiology of MDR/RR-TB and seek optimal screening and management strategies for TB among refugees from countries with high MDR/RR-TB incidence in Poland and Europe.

BACKGROUND: The loop-mediated isothermal amplification for TB (TB-LAMP) assay is more cost-effective and accessible than the Xpert ® MTB/RIF assay. This study aimed to evaluate the diagnostic performance of the TB-LAMP assay in individuals with and without HIV infection. METHODS: Patients aged ≥15 years presenting with symptoms of TB were included in the study. The TB-LAMP assay was performed alongside routine TB diagnostic methods, including the Xpert assay and smear microscopy, to evaluate discrepancies in test results and associated factors. RESULTS: A total of 903 patients were enrolled in the study. The positive percentage agreement for smear microscopy and TB-LAMP compared with the Xpert assay was respectively 54.3% (95% CI 46.6–61.8) and 76.6% (95% CI 69.9–82.6). Among HIV-positive individuals, the positive percentage agreement was 42.5% (95% CI 32.9–52.4) for smear microscopy and 68.9% (95% CI 59.1–77.5) for TB-LAMP. Factors such as age >60 years (adjusted OR 3.29, 95% CI 0.32–33.83), loss of appetite (aOR 0.30, 95% CI 0.13–0.70), and HIV-positive status (aOR 3.29, 95% CI 1.12–9.63) were associated with discrepancies between TB-LAMP and Xpert results. CONCLUSIONS: TB-LAMP demonstrated better agreement with the Xpert assay compared with smear microscopy in detecting TB among HIV-positive patients, suggesting that TB-LAMP could effectively replace smear microscopy.

BACKGROUND: Drug-resistant TB (DR-TB) remains a public health concern in Kenya, with an estimated 2,500 individuals acquiring DR-TB annually. Despite significant progress in DR-TB management, the treatment success rate (TSR) in 2021 stood at 77%, falling short of the 85% target. This low TSR occurs amidst a complex range of treatment challenges, including psychosocial factors. The aim of this study was to assess the impact of integrating psychosocial and economic empowerment interventions into standard DR-TB care. METHODS: A convergent mixed-method approach was employed, involving interviews with 217 participants, including persons with DR-TB and key stakeholders, using a structured questionnaire. The study was conducted in Kenya’s two highest DR-TB burden counties between October and November 2023. RESULTS: The study found that 55% of respondents experienced psychological depression during treatment, with financial constraints identified as the primary trigger (70.6%). Only 49% of persons with DR-TB joined psychosocial support groups, and of these, 90% demonstrated improved treatment adherence. Additionally, individuals with DR-TB who participated in income-generating activities had a treatment adherence rate of 95%, compared to 88% among those not engaged in such activities. CONCLUSION: Patient-centred approaches involving socio-economic support systems are crucial in addressing treatment adherence barriers, thereby leading to improved treatment outcomes.

BACKGROUND: Cancer increases the risk of developing TB disease; however, there are limited data on the magnitude of risk by cancer type and timing after diagnosis of cancer in low TB incidence settings. METHODS: We conducted a nested case-control study of persons in Quebec between 1993 and 2017, including people with TB disease and matched controls. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) of developing TB among people with cancer overall, by sub-type, and by time from cancer to TB diagnosis. RESULTS: There were 4,283 people with TB disease and 268,420 matched controls. The median age for people with TB disease and controls was respectively 46 years (IQR 30–67) and 36 years (24–47). Prior exposure to cancer was associated with TB disease (aOR 6.3, 95% CI 5.3–7.6). The risk of TB diagnosis was highest within 3 months of cancer diagnosis (aOR 26.6, 95% CI 19.6–36.2), with 60% of diagnoses of TB disease occurring within 6 months of cancer diagnosis. CONCLUSION: Risk of TB varies over time and by cancer type. Screening and treatment should be considered for potentially preventable TB (diagnosed more than 6 months post-cancer), particularly in those with respiratory, haematologic, and head and neck cancers.

OBJECTIVE: To compare the persistent clinical symptoms, chest X-ray (CXR), spirometry and echocardiography results in adolescent survivors of drug-susceptible (DS) and drug-resistant (DR) pulmonary TB (PTB). METHODS: This retrospective cohort study was conducted in 52 adolescent PTB survivors. We compared persistent clinical symptoms, CXR, spirometry and echocardiography in DS-TB and DR-TB survivors. χ 2 test was used to compare groups (P < 0.05 significant), logistic regression analysis was used to identify risk factors, and Many-Factor Rasch Measurement Version Facets 3.86.0 was used to assess the multi-rater agreement of CXR. RESULTS: Significant differences were found in persistent clinical symptoms (higher in DS-TB survivors), CXR, and spirometry abnormalities (higher in DR-TB survivors). The echocardiography revealed a low pulmonary hypertension probability in both groups. Adolescent PTB survivors with comorbidity have 1.5 times the risk of developing pulmonary sequelae compared to non-sequelae. CONCLUSION: Pulmonary sequelae in adolescent PTB survivors were documented in both DS and DR-TB. Monitoring after treatment completion was necessary for PTB survivors, especially in adolescents.

BACKGROUND: TB preventive treatment (TPT) prevents the development of TB disease in individuals at risk of progression from infection to disease. However, implementation of TPT for children is poor in most high-burden settings. The long duration and pill burden of the 6-month once-daily isoniazid regimen (6H) pose significant barriers to completion. We aimed to understand children’s, caregivers’, and healthcare providers’ experiences of the 12-week once-weekly rifapentine and isoniazid (3HP) regimen using a dispersible tablet formulation in South Africa. METHODS: Serial, in-depth qualitative interviews with 20 child-caregiver dyads, including 5 children living with HIV (CLWH) and 9 healthcare providers across two study sites implementing a pharmacokinetic and safety trial of 3HP, were analysed deductively. RESULTS: Of those with experience using both 3HP and 6H, caregivers and healthcare providers preferred 3HP, and study participants reported that the 3HP formulation was more palatable and easier to prepare and administer. Caregivers and healthcare providers were concerned about optimally integrating 3HP into routine care, primarily due to its once-weekly administration. Children with HIV preferred the once-daily 6H regimen for its ease of use with their daily antiretroviral therapy. CONCLUSIONS: 3HP reduced the administration burden for children and their caregivers. Once weekly, 3HP dosing will require education and adherence support to ensure completion.

BACKGROUND: Pulmonary TB (PTB) predominantly affects individuals of working age. We sought to characterise the occupations of people newly diagnosed with PTB in Karachi, Pakistan, by type and physical intensity. DESIGN/METHODS: We did a secondary analysis of data from a study evaluating the diagnostic accuracy of artificial intelligence-based chest X-ray (CXR) analysis software, where individuals had been evaluated for active PTB using sputum cultures and had provided information on occupation. We used an accelerometer-validated US National Health and Nutrition Examination Survey-based job categorisation to assign physical activity levels to participant-reported occupations as High, Intermediate, or Low. RESULTS: Among 272 participants with microbiologically confirmed PTB (women: 130/272, 48%; median age: 29 years, IQR 22–45), 78% (211/272) had smear-positive disease, and 96% (260/272) had data on occupation. Unemployment was common (women: 70/122, 57%; men: 23/138, 17%). Most women reporting an occupation were homemakers (21/52, 40%), and 54% (28/52) had an intermediate- or a high physical activity occupation. Among men reporting an occupation, 35% (40/115) were labourers, and 79% (91/115) had an intermediate- or high-physical activity occupation. CONCLUSION: The majority of individuals with PTB were in their working age, had extensive disease, and had intermediate or high physical activity occupations, suggesting economic vulnerability due to physical impairment.

Chunchun Yu,1 Mengying Xu,1 Xinyue Pang,2 Yuting Zhang,3 Xinmei Cao,2 Yixin Xu,1 Shuai Huang,1 Hongjun Zhao,4 Chengshui Chen1,3,4 1Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 3Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, Zhejiang, 315302, People’s Republic of China; 4Zhejiang Province Engineering Research Center for Endoscope Instruments and Technology Development, Department of Pulmonary and Critical Care Medicine, Quzhou People’s Hospital, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, 324000, People’s Republic of ChinaCorrespondence: Hongjun Zhao; Chengshui Chen, Zhejiang Province Engineering Research Center for Endoscope Instruments and Technology Development, Department of Pulmonary and Critical Care Medicine, Quzhou People’s Hospital, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, 324000, People’s Republic of China, Email zhaohongjun@wmu.edu.cn; chenchengshui@wmu.edu.cnPurpose: This study aims to construct a contemporaneous symptom network of inpatients with Exacerbation of Chronic Obstructive Pulmonary Disease (ECOPD) based on the symptom cluster, identify core and bridge symptoms, and patient subgroups with different symptom clusters based on individual differences in the intensity of patient symptom experiences.Patients and Methods: This study used convenience sampling to collect demographic, symptom, auxiliary examination, and prognosis information of 208 inpatients with ECOPD from April 2022 to October 2023. The data underwent exploratory factor analysis (EFA), symptom network analysis, latent class analysis (LCA), Spearman correlation analysis, Wilcoxon signed-rank test, single-factor regression and multiple-factor stepwise regression.Results: In hospitalized patients with ECOPD, symptom network analysis revealed that loss of appetite was the core symptom, while chest distress was the bridge symptom. Through LCA analysis, two symptom subgroups were identified: a high-symptom group (53.8%) and a low-symptom group (46.2%). This suggests that there is significant heterogeneity in symptom experience among ECOPD individuals. Patients in the high-symptom group had a higher probability of experiencing symptom clusters related to nutrition-sleep.Conclusion: The combination of symptom network analysis and LCA comprehensively captures the symptom/symptom cluster characteristics and accounts for the heterogeneity of ECOPD patients from both individual and group perspectives. This study identifies core symptoms, bridge symptoms, and symptom subgroups, offering valuable insights for precision symptom management in ECOPD.Keywords: chronic obstructive pulmonary disease, COPD, exacerbation, precision care, network analysis, latent class analysis

Yu Ding,1 Yuxia Liu,2 Jianjian Yu,2 Chengsen Cai,2 Lina Fu,2 Jie Zhu,3 Shengzhen Yang,4 Yu Jiang,1 Jun Wang2 1The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 4Department of Pulmonary, Rizhao Hospital of Traditional Chinese Medicine, Rizhao, People’s Republic of ChinaCorrespondence: Jun Wang, Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China, Email jnwj660606@163.comPurpose: The C-reactive protein (CRP)–albumin–lymphocyte (CALLY) index is a newly developed biomarker that combines measurements of CRP, serum albumin, and lymphocyte count. This index provides a thorough assessment of a patient’s inflammation level, nutritional condition, and immunological function. The objective of this study is to examine the correlation between the CALLY index and all-cause mortality in COPD patients.Methods: We calculated the CALLY index using data from the National Health and Nutrition Examination Survey (NHANES) for the 2007– 2008 and 2009– 2010 cycles, extracted from the participants’ peripheral blood samples. The study utilized Kaplan-Meier curves, restricted cubic spline (RCS) curves, and Cox regression analysis to evaluate the relationship between the CALLY index and the risk of all-cause mortality in COPD patients. To assess the predictive accuracy of the CALLY index, we calculated the area under the receiver operating characteristic (ROC) curve (AUC).Results: The study included 1,048 participants and found a significant negative correlation between the CALLY index and all-cause mortality in patients with COPD. The CALLY index was a major predictor of survival in COPD patients [fully adjusted model: in the 3rd quartile, HR = 1.61, 95% CI: 1.02– 2.52, p = 0.039; in the 2nd quartile, HR = 2.11, 95% CI: 1.22– 3.65, p = 0.008; in the 1st quartile, HR = 3.12, 95% CI: 2.00– 4.85, p < 0.001]. The RCS curves demonstrated a non-linear association between the CALLY index and all-cause mortality in COPD patients. The areas under the curve (AUC) in predicting 5- and 10-year all-cause mortality were 0.693 and 0.656.Conclusion: The CALLY index has a strong relationship with all-cause mortality in patients with COPD in the US and could serve as a prognostic biomarker for these patients.Keywords: chronic obstructive pulmonary disease, the C-reactive protein–albumin–lymphocyte index, national health and nutrition examination survey, biomarker

Li Zhou,1– 4 Cunqiao Han,5 Yue Zhou1– 4 1Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2West China School of Nursing, Sichuan University, Chengdu, People’s Republic of China; 3Disaster Medical Center, Sichuan University, Chengdu, People’s Republic of China; 4Nursing Key Laboratory of Sichuan Province, Chengdu, People’s Republic of China; 5Department of Emergency Medicine, Shangjinnanfu Hospital, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Yue Zhou, Department of Emergency Medicine, West China Hospital, Sichuan University, No. 37 Guoxue Road, Chengdu, 610041, Sichuan, People’s Republic of China, Tel +86-028-62539203, Email zhouyuesccd@163.comBackground: This study aims to investigate the association between vitamin D levels and the risk of severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD).Methods: We conducted a prospective observational study with 636 COPD patients admitted for exacerbations between January 2021 and December 2022. Patients were categorized based on serum 25-hydroxyvitamin D levels: severe deficiency (< 10 ng/mL), deficiency (10– 20 ng/mL), insufficiency (20– 30 ng/mL), or sufficiency (> 30 ng/mL). Severe exacerbation was defined when the patient visits an emergency room or is hospitalized due to COPD exacerbation. Multivariate Cox regression was used to evaluate the risk associated with vitamin D deficiency.Results: Over an 18-month follow-up, 178 (28.0%) patients experienced at least one severe exacerbation. The severe deficiency group had the highest exacerbation rate (40.6%), followed by deficiency (27.8%), insufficiency (22.5%), and sufficiency (18.1%) groups (P< 0.01). Multivariate Cox regression analysis showed that severe vitamin D deficiency was significantly associated with an increased risk of severe exacerbations (HR=2.74, 95% CI: 1.55– 4.84; P< 0.01) compared to vitamin D sufficiency.Conclusion: Severe vitamin D deficiency is a significant predictor of severe COPD exacerbations, highlighting the importance of routine vitamin D assessment and supplementation in COPD management.Keywords: acute exacerbations, COPD, risk factors, vitamin D deficiency

Wolfgang Mayr,1,&ast; Andreas Triantafyllopoulos,2,3,&ast; Anton Batliner,2,3 Björn W Schuller,2– 5 Thomas M Berghaus1,6 1Department of Cardiology, Respiratory Medicine and Intensive Care, University Hospital Augsburg, Augsburg, Germany; 2Chair of Health Informatics (CHI), Department of Clinical Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany; 3Munich Center for Machine Learning (MCML), Munich, Germany; 4Group on Language Audio, & Music (GLAM), Imperial College, London, UK; 5Munich Data Science Institute (MDSI), Munich, Germany; 6Medical Faculty, Ludwig Maximilians University of Munich, Munich, Germany&ast;These authors contributed equally to this workCorrespondence: Wolfgang Mayr, Department of Cardiology, Respiratory Medicine and Intensive Care, University Hospital Augsburg, Stenglinstrasse 2, Augsburg, D-86156, Germany, Email wolfgang.mayr@uk-augsburg.de Andreas Triantafyllopoulos, Chair of Health Informatics, Department of Clinical Medicine, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Straße 22, Munich, 81675, Germany, Email andreas.triantafyllopoulos@tum.deBackground: Chronic obstructive pulmonary disease (COPD) affects breathing, speech production, and coughing. We evaluated a machine learning analysis of speech for classifying the disease severity of COPD.Methods: In this single centre study, non-consecutive COPD patients were prospectively recruited for comparing their speech characteristics during and after an acute COPD exacerbation. We extracted a set of spectral, prosodic, and temporal variability features, which were used as input to a support vector machine (SVM). Our baseline for predicting patient state was an SVM model using self-reported BORG and COPD Assessment Test (CAT) scores.Results: In 50 COPD patients (52% males, 22% GOLD II, 44% GOLD III, 32% GOLD IV, all patients group E), speech analysis was superior in distinguishing during and after exacerbation status compared to BORG and CAT scores alone by achieving 84% accuracy in prediction. CAT scores correlated with reading rhythm, and BORG scales with stability in articulation. Pulmonary function testing (PFT) correlated with speech pause rate and speech rhythm variability.Conclusion: Speech analysis may be a viable technology for classifying COPD status, opening up new opportunities for remote disease monitoring.Keywords: COPD, pathological speech, feature interpretation, personalization, digital health

Angela T Burge,1,2 Narelle S Cox,1,3 Simone Dal Corso,1 Arwel W Jones,1 Fahrayhansyah Muhammad Faqih,1 Anne E Holland1– 4 1School of Translational Medicine, Monash University, Melbourne, VIC, Australia; 2Department of Physiotherapy, Alfred Health, Melbourne, VIC, Australia; 3Institute for Breathing and Sleep, Melbourne, VIC, Australia; 4Department of Respiratory Medicine, Alfred Health, Melbourne, VIC, AustraliaCorrespondence: Angela T Burge, Respiratory Research@Alfred, Monash University, Level 6 The Alfred Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia, Email angela.burge@monash.eduPurpose: Oral corticosteroids (OCS) are recommended for the treatment of exacerbations in people with COPD; however, high cumulative lifetime doses (≥ 1000mg prednisolone-equivalent) are associated with adverse health effects. This issue is well defined in asthma but is less well understood in COPD. The aim of this study was to examine cumulative OCS dispensed to people with COPD over 12 months.Patients and Methods: This was a secondary analysis of data from two randomised controlled trials involving people with COPD followed up for 12 months following pulmonary rehabilitation. Clinical and administrative (respiratory-related hospital admissions and emergency presentations, dispensed OCS and COPD maintenance medications) data were examined to determine cumulative OCS dose relative to the 1000mg threshold and the relationship with clinical features.Results: Of 232 participants (126 females, age mean 68 ± SD 9 years, FEV1 53 ± 22% predicted), 48% (n = 112) were dispensed OCS at least once over 12 months. Sixty-two participants (26%) were dispensed ≥ 1000mg. Participants with a high cumulative dose were more likely to have had a respiratory admission (OR 4.1, 95% CI 2.3 to 8.7) and greater breathlessness (modified Medical Research Council scale ≥ 2, OR 2.5, 95% CI 1.3 to 5.0); no relationship with disease severity or maintenance medications was demonstrated.Conclusion: One in four people with COPD were dispensed unsafe lifetime cumulative OCS doses over a period of only 12 months. Further work is needed to determine the magnitude of this issue in COPD and strategies to address exposure to high doses of OCS.Keywords: exacerbations, systemic corticosteroids, prescriptions, side effects

Abstract Background Cavernous hemangiomas can occur in various internal organs like the liver, kidney, bladder, and skin, or even in subcutaneous tissues. However, they rarely occur in the lungs, making pulmonary cavernous hemangiomas (PCH) an uncommon finding. Herein, we report a rare case of pulmonary cavernous hemangioma that was surgically resected. Case presentation A 16-year-old adolescent patient was diagnosed with a pulmonary cavernous hemangioma during a physical examination. During the entry physical examination, a chest X-ray showed shadows in the upper lobe of the right lung. The patient was admitted to the Thoracic Surgery Department for further assessment. The patient had a one-year history of smoking; however, he did not experience any clinical symptoms related to respiratory diseases. Among tumor markers assessed, only the cytokeratin-19 fragment (CYFRA21-1) was elevated. Chest computed tomography (CT) showed irregular soft tissue lesions in the upper lobe of the right lung. The lesion presented as a shallow lobe with clear boundaries, accompanied by the presence of spicules around it. The lesion showed mild to moderate uniform enhancement in the arterial phase and slightly reduced in the venous phase on imaging. The lesion was anatomically close to adjacent bronchus and blood vessels. In addition, the patient had multiple enlarged lymph nodes in the mediastinum. In summary, the thoracic surgeon could not rule out the possibility of lung malignant tumors and chose to proceed with surgical excision to secure a conclusive diagnosis. Post-operative histological examination showed that the lesion consisted of dilated nodular hyperplasia rich in red blood cells, leading to a diagnosis of PCH. No recurrence has been observed since postoperative follow-up. Case presentation We reported a rare PCH case, reviewed the clinical features, imaging findings, histopathological features, and treatment options of PCH based on relevant literature, and gained a further understanding of PCH.

Abstract Background Systemic sclerosis (SSc) is a rare connective tissue disease, frequently affecting the skin, lungs, and pulmonary vasculature. Approximately 30–50% of SSc patients develop interstitial lung disease (SSc-ILD), with 30–35% of related deaths attributed to it. Even though men are less likely to develop systemic sclerosis, they have a higher incidence of SSc-ILD than women, and they tend to develop it at a younger age with a higher mortality rate. Sex differences in protein expression in the blood of patients with SSc-ILD have not been reported to date. We aimed to identify sex differences in serum protein expression between men and women with SSc-ILD. Methods Serum specimens of patients with SSc-ILD underwent dual mass spectrometry (LC-MS/MS) analysis. The association between protein biomarkers and sex was assessed through logistic regression. Time to event analysis was performed to determine any differences in the time to FVC decline of > 5% and the proportion of subjects who experienced FVC decline of > 5% by sex over the total period of observation. The association between biomarkers and sex was assessed through logistic regression. For proteins that were dichotomized, chi-squared testing was used. Multivariable regression models adjusting for meaningful clinical variables were also performed. Results The cohort consisted of 211 subjects, 162 women and 47 men with a median follow-up of 3.52 years. No significant sex differences were found in the time to FVC decline of > 5% or > 10%. Among the 704 proteins identified, forty differed significantly between sexes. After adjusting for multiple testing, Autotaxin remained significantly higher in women. Autotaxin, known to activate lysophosphatidic acid and promote fibrosis, suggests a potential role in modulating fibrotic processes in SSc-ILD. Conclusions This study is the first to report sex-specific serum protein differences in patients with SSc-ILD, with Autotaxin remaining significantly different after adjusting for multiple testing. These proteins could influence disease progression and treatment response and underscore the importance of personalized therapeutic strategies and further research into sex-related molecular pathways in SSc-ILD. Clinical trial number Not applicable.

Abstract Objectives Complete removal of the tumor and surrounding tissue is the most important prognostic factor such as survival after surgery. When the tumor invades the phrenic nerve, the impact of intraoperative phrenic nerve sacrifice on the short- and long-term prognosis of patients is not clear. This study aims to explore the differences in prognosis between patients with malignant thymoma with and without phrenic nerve sacrifice during surgery, as well as analyze related factors. Methods A total of 209 patients who underwent thymoma resection in the Department of Thoracic Surgery at our hospital from February 2006 to November 2022 were collected for retrospective analysis. The groups were divided into two according to the presence or absence of intraoperative phrenic nerve sacrifice. A comparative analysis was conducted on postoperative complications, long-term survival recurrence between the two groups. Cox regression was used to analyze the factors related to the differences in short- and long-term prognosis between two groups. Results 29.6% of patients developed phrenic nerve sacrifice during thymoma surgery. Compared to patients without phrenic nerve sacrifice, the long-term survival rate was lower (P = 0.031). The independent risk factors for reduced long-term survival were intraoperative phrenic nerve sacrifice, secondary postoperative complications, and modified Masaoka staging III/IV. Conclusion Our data show that nearly one-third of patients develop phrenic nerve sacrifice during complete resection of thymoma. Phrenic nerve sacrifice has significant impact on short-term complications and long-term survival. Secondary postoperative complications and modified Masaoka staging III/IV are also risk factors for reduced long-term survival.

Abstract Genome-wide association studies (GWAS) have identified genetic variants robustly associated with asthma. A potential near-term clinical application is to calculate polygenic risk score (PRS) to improve disease risk prediction. The value of PRS, as part of numerous multi-source variables used to define asthma, remains unclear. This study aims to evaluate PRS and define most informative thresholds in relation to conventional clinical and physiological criteria of asthma using a multivariate statistical method. Clinical and genome-wide genotyping data were obtained from the Quebec City Case-Control Asthma Cohort (QCCCAC), which is an independent cohort from previous GWAS. PRS was derived using LDpred2 and integrated with other asthma phenotypes by means of Principal Component Analysis with Optimal Scaling (PCAOS). PRS was considered using ‘ordinal level of scaling’ to account for non-linear information. In two dimensional PCAOS space, the first component delineated individuals with and without asthma, whereas the severity of asthma was discerned on the second component. The positioning of high vs. low PRS in this space matched the presence and absence of airway hyperresponsiveness, showing that PRS delineated cases and controls at the same extent as a positive bronchial challenge test. The top 10% and the bottom 5% of the PRS were the most informative thresholds to define individuals at high and low genetic risk of asthma in this cohort. PRS used in a multivariate method offers a decision-making space similar to hyperresponsiveness in this cohort and highlights the most informative and asymmetrical thresholds to define high and low genetic risk of asthma.

Abstract Background Paraquat (PQ) is a widely used pesticide, can cause severe intoxication and respiratory failure. Myrtenol (Mrl), an essential oil derived in various plants, exhibits several biological properties, including anti-inflammatory and antioxidant activities. This study aims to investigate the protective potential of Mrl against oxidative stress and inflammation caused by PQ exposure. Methods Twenty-five Wistar albino rats were divided into the following groups (n = 5 in each group): a control group (treated by dimethyl sulfoxide (DMSO)), a PQ group (exposed to 54 mg/m³ aerosol PQ), and two treatment groups that were exposed to PQ aerosol and administered oral Mrl at doses of 25 mg/kg/day and 50 mg/kg/day, respectively. The final group was exposed to PQ aerosol and treated with oral dexamethasone at a dose of 0.03 mg/kg/day. Various hematological, oxidative, inflammatory, and pathological indices were measured at the conclusion of the treatment period. Results PQ decreases the levels or activities of superoxide dismutase (SOD), catalase (CAT), and Thiol, while increasing the levels or activities of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA). Mrl restored activites of SOD, and CAT, as well as thiol levels to near-control values while reducing TNF-α, IL-6, and MDA levels. Pathological studies further confirmed the therapeutic effects of Mrl. Conclusion The results of this study demonstrate the promising therapeutic effects of Mrl against inhaled PQ in rats.

Abstract Background Prevalence of potential drug-drug interactions (pDDIs) in adult patients with severe asthma on biological therapy and their clinical significance have not been fully addressed, thus the aim of this study was to investigate them. Methods In this retrospective observational study, patients who were diagnosed with severe asthma and to whom biological therapy was prescribed between September 2015 and December 2020, were enrolled. The study was conducted at the Department of Allergic and Obstructive Pulmonary Diseases, Clinic for Lung Diseases Jordanovac, Clinical Hospital Center Zagreb. Data on demographic characteristics as well as concomitant medication were collected. The analysis of pDDIs was conducted via Lexicomp® online software. Interactions of significance levels A and B were only recorded, while those of levels C, D and X were further analysed. The collected data was processed via Microsoft Excel 365 software. Results 60 adult patients, 60% female and 40% male, with median age of 56.2 years, were enrolled. The incidence of pDDIs was 86.67%. Total number of pDDIs detected was 518, out of which 43.24%, 45%, 4.44% and 7.3% of clinical significance B, C, D and X. Interactions of level C, D and X were recorded in, as follows: 83.33%, 25% and 33.33% patients with an average of 4.66, 1.53 and 1.9 interactions per patient. Only 13.33% of the patients had none of the potential clinically significant DDI. Most drug pairs contained at least one antiasthmatic drug. Muscarinic receptor antagonists, oral corticosteroids, β2 agonists and methylxanthines showed potential of entering into clinically significant DDIs, while leukotriene antagonists and biologicals showed no potential for the above. Conclusion Prevalence of potential drug-drug interactions in patients with severe asthma on biological therapy is high. The majority of identified interactions have moderate to high level of clinical significance. Their identification, prevention and resolution could contribute to optimizing therapy, maximizing its therapeutic effect and avoiding undesirable adverse events.

Abstract Background Chronic obstructive pulmonary disease (COPD) and asthma are the two most prevalent chronic respiratory diseases, significantly impacting public health. Utilizing clinical questionnaires to identify and differentiate patients with COPD and asthma for further diagnostic procedures has emerged as an effective strategy to address this issue. We developed a new diagnostic tool, the COPD-Asthma Differentiation Questionnaire (CAD-Q), to differentiate between COPD and asthma in adults. Methods A cross-sectional study with diagnostic test analysis was done. Relevant clinical variables for diagnosing COPD and asthma were identified through crude Odds Ratios (OR) and a logistic regression model provided adjusted ORs. The CAD-Q, including sensitivity, specificity, predictive values, likelihood ratios, and ROC-curve, was compared to the LFQ, CDQ, PUMA, “Could it be COPD,” and COPD-PS questionnaires. Results 235 (52.9%) patients had COPD and 209 (47.1%) had asthma. A score ≥ 20 on the CAD-Q questionnaire showed a ROC-curve of 70% (95% CI: 65–75; p

Abstract Background Behçet’s disease (BD) is a multisystem inflammatory disorder that can affect various organs, including the lungs. Pulmonary manifestations are rare and typically present as pulmonary artery aneurysms. Case presentation We report the case of a 56-year-old East Asian male with a 27-year history of BD, who had no respiratory symptoms, such as hemoptysis, cough, or fever. Chest imaging revealed lymph node enlargement and a lung mass, initially raising concerns of malignancy. Despite the suspicious radiological findings, three biopsies, including a surgical biopsy, were all negative for malignancy. Remarkably, over the course of 2 years, these pulmonary manifestations spontaneously regressed without any specific treatment for lung involvement, and the patient remained in a stable BD state. Conclusions BD patients are at an increased risk for malignancy compared to healthy controls, making it crucial to differentiate between malignancy and BD-related pulmonary abnormalities. This case highlights that, in the absence of active BD symptoms, lymphadenopathy and lung masses can occur and may resolve spontaneously. Accurate diagnosis and vigilant monitoring are essential in BD patients but BD-related lung involvement should be considered in similar cases.