Abstract Background and Aims Interstitial lung diseases (ILDs), encompassing both pediatric and adult cases, present a diverse spectrum of chronic conditions with variable prognosis. Despite limited therapeutic options beyond antifibrotic drugs and immunosuppressants, accurate diagnosis is challenging, often necessitating invasive procedures that may not be feasible for certain patients. Drawn against this background, experts across pediatric and adult ILD fields have joined forces in the RARE-ILD initiative to pioneer novel non-invasive diagnostic algorithms and biomarkers. Collaborating with the RARE-ILD consortium, the eurILDreg aims to comprehensively describe different ILDs, analyze genetically defined forms across age groups, create innovative diagnostic and therapeutic biomarkers, and employ artificial intelligence for data analysis. Methods The foundation of eurILDreg is built on a comprehensive parameter list developed and adopted by clinical experts, encompassing over 1,800 distinct parameters related to patient history, clinical examinations, diagnosis, lung function and biospecimen collection. This robust dataset is further enriched with daily assessments captured through the patientMpower app, including handheld spirometry and exercise tests, conducted on approximately 350 patients over the course of a year. This approach involves app-based daily assessments of quality of life, symptom tracking, handheld spirometry, saturation measurement, and the 1-min sit-to-stand test (1-STST). Additionally, pediatric data from the ChILD-EU registry will be integrated into the RARE-ILD Data Warehouse, with the ultimate goal of including a total of 4.000 ILD patients and over 100.000 biospecimen. Discussion The collaborative efforts within the consortium are poised to streamline research endeavors significantly, promising to advance patient-centered care, foster innovation, and shape the future landscape of interstitial lung disease research and healthcare practices. Trial Registration EurILDreg is registered in the German Clinical Trials Register (DRKS 00028968, 26.07.2022), and eurIPFreg is registered in ClinicalTrials.gov (NCT02951416).

The ability of bronchial amylase level for predicting ventilator associated pneumonia (VAP) has been extensively studied with conflicting results. This meta-analysis aimed to explore the value of bronchial amylase for predicting VAP in intubated adults. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched up to November 2023. The diagnostic odds ratio (DOR), sensitivity, and specificity were calculated. The summary receiver operating characteristic curve was estimated, and the area under the curve (AUROC) was calculated. Overall, six studies including 769 patients were included in this review, of whom 273 (36%) were developed VAP. The cutoff values of bronchial amylase level were ranged from 8.1 U/L to 4681.5U/L. Heterogeneity between studies was assessed with an overall Q = 1.99, I2 = 0, and P = 0.185, The pooled sensitivity and specificity for the overall population were 0.78 [95% confidence interval (CI) 0.67-0.86] and 0.75(95% CI 0.56-0.88) respectively. The DOR was 11(95% CI 3.0-40.0). The pooled AUROC was 0.83 (95%CI 0.80-0.86). The bronchial amylase is a helpful marker for predicting VAP in intubated adults. However, it cannot be recommended as the single definitive test for VAP, but rather it must be interpreted in context with information from careful medical history, physical examination, and when feasible, microbiological assessment.

Patients with alpha-1 antitrypsin deficiency (AATD) often experience substantial delays from the onset of symptoms to a diagnosis. We explored the impact of delayed diagnosis of AATD on healthcare costs and utilization by assessing costs/utilization before and after diagnosis. Retrospective claims data was used to conduct a longitudinal analysis of a cohort of patients with follow-up over four years in a commercial claims database was conducted. Patients with at least four years of claims experience between the years 2011 - 2017 were included in this study. Outcome measures were calculated for each year (Year 1 pre-index diagnosis, and Years 1, 2, and 3 post-index follow-up). Measures included healthcare costs (pharmacy and medical costs), medical costs, inpatient events, and emergency room visits. Unadjusted measures in the follow-up Year 1, Year 2, and Year 3 were compared to Year 1 pre-index. A separate multivariate analysis adjusting for age, sex, and comorbidities was conducted. Among 1258 patients, mean adjusted healthcare costs were significantly higher in Year 1 post-index compared to Year 1 pre-index ($51,785 vs $41,441, p = < 0.05). In Year 2 ($36,937 vs $41,441, p = < 0.05) and 3 ($28,558 vs $41,441, p = < 0.05) post-index, mean adjusted healthcare costs decreased compared to Year 1 pre-index. Adjusted medical costs were similar in Year 1 ($25,034) post-index compared to Year 1 ($22,952) pre-index but were significantly lower in Year 2 ($15,242 vs $25,034, p = < 0.05) and Year 3 ($8,779 vs $25,034, p = < 0.05) post-index. The frequency of inpatient and emergency room events was significantly lower in all three observation periods following diagnosis in the unadjusted analysis. The adjusted analysis showed similar findings, except for emergency room visits, which were similar across all observation periods. Patients with AATD had substantial healthcare costs/utilization in the year before diagnosis. Costs were significantly higher in the first year following diagnosis. However, subsequent years showed cost reductions to levels below pre-diagnosis. These data support the need for strategies to reduce the time from symptom onset to diagnosis.

Pneumothorax is a potential complication following computed tomography-guided lung biopsy (CT-LB). However, the relationship between the lung needle path CT attenuation values and risk of post-procedural immediate pneumothorax remains unclear. The study aims to investigate this relationship. The present single-center retrospective cohort study analyzed the data obtained from 453 patients who underwent CT-LB from 2019 to 2022. The relationship between the lung needle path CT attenuation values and post-procedural immediate pneumothorax was assessed using restricted cubic splines, which were adjusted for potential confounders, and validated using linear and nonlinear binomial logistic models. A total of 453 patients (mean age: 60.2 ± 12.0 years old, 217 male patients) were evaluated. The incidence of post-procedural immediate pneumothorax was 41.06% (186/453). The median needle path CT attenuation was - 831 Hounsfield units (Hu). The linear models indicated an unstable association between lung needle path CT attenuation and post-procedural immediate pneumothorax (odds ratio: 0.99, 95% confidence interval: 0.99-1.00). The nonlinear analysis identified an inflection point at a CT attenuation value of -805 Hu. A stronger negative link was identified for needle path CT attenuation values below - 805 Hu (odds ratio: 0.99, 95% confidence interval: 0.98-0.99) between the needle path CT attenuation value and pneumothorax, while no statistically significant association was identified between these when the CT attenuation value was above - 805 Hu. There is a nonlinear association between the lung needle path CT attenuation values and risk of post-procedural immediate pneumothorax. For CT attenuation values below - 805 Hu, increasing the needle path CT attenuation values might reduce the risk of pneumothorax.

Acetaminophen is a commonly used analgesic after surgery, and its impact on prognosis in patients with acute respiratory distress syndrome (ARDS) has not been studied. This study explores the association between the use of acetaminophen and the risk of mortality in patients with ARDS. In this retrospective cohort study, 3,227 patients with ARDS who had or had not received acetaminophen were obtained from the Medical Information Mart for Intensive Care IV, patients were divided into acetaminophen and non- acetaminophen groups. In-hospital mortality of ARDS patients was considered as primary end point. We used univariate and multivariate Cox regression analyses to assess the relationship of acetaminophen use and in-hospital mortality in patients with ARDS. Subgroup analysis was performed according to age, gender, and severity of ARDS. Of the total patients, 2,438 individuals were identified as acetaminophen users. The median duration of follow-up was 10.54 (5.57, 18.82) days. The results showed that the acetaminophen use was associated with a decreased risk of in-hospital mortality [hazard ratio (HR) = 0.67, 95% confidence interval (CI): 0.57-0.78]. Across various subgroups of patients with ARDS based on age, gender, and severity, acetaminophen use exhibited an association with reduced risk of in-hospital mortality. Acetaminophen use was associated with in-hospital mortality of patients with ARDS. Acetaminophen therapy may represent a promising therapeutic option for ARDS patients and warrants further investigation.

Congenital lung malformations (CLMs) are among the rare anomalies that can be diagnosed by bronchoscopy and imaging. They can cause various respiratory symptoms and complications, especially in children with congenital heart disease. This is an interesting case report of a child with a rare combination of congenital anomalies affecting the airway. We report a case of a 3.5-year-old boy with multiple congenital anomalies and respiratory problems since birth. He had a history of mild autism, developmental delay, and sensitivity to smell and smoke. He presented with hoarseness, shortness of breath, severe coughing, and severe wheezing, which worsened with the flu. He underwent bronchoscopy and other diagnostic tests, which revealed a posterior laryngeal cleft, a tracheal bronchus, and a very narrow distal trachea. He was treated with nebulizers, antibiotics, and serum therapy and showed improvement. This case illustrates a rare combination of airway malformations that require a multidisciplinary approach. We presented a case of rare pulmonary malformations and chronic respiratory symptoms that improved with conventional pharmacotherapy. Increased awareness and understanding of these anomalies among healthcare providers can lead to earlier diagnosis and improved patient outcomes.

The ventilatory physiopathology of patients with interstitial lung disease (ILD) remains poorly understood. We aimed to personalize a mechanical simulator to model healthy and ILD profiles ventilation, and to evaluate the effect of spontaneous breathing on respiratory mechanics at rest and during exercise. In a 2-compartment lung simulator (ASL 5000®), we modeled 1 healthy and 3 ILD profiles, at rest and during exercise, based on physiological data from literature and patients. Measurements were: tidal volume, end-expiratory lung volume, driving pressure, transpulmonary driving pressure, dynamic alveolar strain, mechanical power, and time lag of inspiratory flow between compartments 1 and 2. Healthy and ILD models were validated: maximum differences between real and simulated tidal volume were 5% (96ml) and 6% (54ml) at rest and during exercise respectively, considered clinically negligible. When we simulated lung inhomogeneity (compliance in compartment 1 > compartment 2), tidal volume, end-expiratory lung volume, driving pressure and mechanical power increased in compartment 1 and decreased in compartment 2. Driving transpulmonary pressure and dynamic alveolar strain increased in compartment 2 and decreased in compartment 1. Time lag of inspiratory flow between compartments 1 and 2 was positively correlated with a difference of compliance between compartments (r = 0.98, CI95% (0.9106; 0.9962), p < 0.0001). In this bench study, we personalized a mechanical simulator thatmodels the lung inhomogeneity and spontaneous breathing of healthy subjects and ILD patients at rest and during exercise. Our results suggest that lung inhomogeneity could increase lung vulnerability to volo-atelec-trauma mechanisms in ILD. Further physiological studies are needed to evaluate the impact of this vulnerability on acute or chronic ILD worsening.

The association of lipoprotein-associated phospholipase A2 (Lp-PLA2) with various cardiovascular events has been well-established. However, the exploration of its potential involvement in Chronic obstructive pulmonary disease (COPD) is currently limited. Therefore, our study aims to examine the relationship between Lp-PLA2 and pulmonary conditions, including emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction, to provide further evidence of a possible association with COPD development. Using data from the Southwest Hospital Health Management Center, spanning January 2013 to July 2024, we analyze relationship of serum Lp-PLA2 levels with diffuse pulmonary emphysema and pulmonary functions. In univariate analysis, group differences were assessed with t-tests for numerical variables and Chi-square tests for categorical data. Variables found to be statistically significant (two-sided P < 0.05) in univariate analysis were subsequently included as covariates in multivariate analysis, performed using a binary logistic regression model. Odds ratios and 95% confidence intervals were calculated to assess the differences. We established 2 case-control populations: the Imaging population (1056 subjects, mean age 57.666 ± 8.700 years old, 89.9% male) selected from 24,670 initial records, and the Pulmonary Function population (279 subjects, mean age 52.082 ± 11.473 years old, 71.4% male) selected from 1868 initial records. Univariate analysis revealed that serum Lp-PLA2 levels were significantly higher in patients with diffuse pulmonary emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction compared to those without (454.682 ± 141.382U/L vs. 423.330 ± 140.658U/L, P < 0.001; 475.059 ± 157.181U/L vs. 420.824 ± 142.119U/L, P = 0.006; 475.31 ± 148.980U/L vs. 439.036 ± 157.977U/L, P = 0.049, respectively). Multivariate analysis further showed higher Lp-PLA2 levels were associated with increased risks of diffuse pulmonary emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction. Using Lp-PLA2 ≤ 300 U/L as reference, odds ratios for the aforementioned conditions showed a gradually increasing trend with every 100U/L increase in Lp-PLA2 levels. Our preliminary study suggests that Lp-PLA2 is independently associated with diffuse pulmonary emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction, which are commonly seen in COPD development. These findings indicated a possible association between Lp-PLA2 and COPD, though further validation is needed in a large cohort of COPD patients.

Chronic obstructive pulmonary disease (COPD) is a significant respiratory disorder in humans characterized by persistent airway constriction or obstruction due to chronic bronchitis and pulmonary emphysema. Various methods of inducing COPD in mouse models are frequently used in COPD research; however, these cannot completely reproduce histopathologic lesions. This study aimed to establish a new COPD mouse model that reproduces histopathological lesions closely resembling clinical COPD within a shorter induction time. The new strategy involved the co-administration of porcine pancreatic elastase (PPE) and lipopolysaccharide (LPS), with PPE intended to induce pulmonary emphysema and LPS intended to induce chronic bronchitis. Male C57BL/6J mice were administered PPE (8 U/kg) on days 0 and 3 and LPS (400µg/kg) on days 6, 9, 12, and 15. Each administration was performed using a noninvasive intubation-mediated intratracheal instillation method with a laryngoscope. Postmortem examination on day 22 revealed that pulmonary emphysema and chronic bronchitis were simultaneously induced in 90.91% of the lung lobes. Molecular studies revealed higher messenger ribonucleic acid (mRNA) expression levels of interleukin-6(IL-6) and matrix metalloproteinase-12(MMP-12) associated with the pathogenesis of COPD. A new method was developed to establish a COPD mouse model that displays a more severe representation of the histopathological findings of clinical COPD than previous COPD models. It also reduces the time required for model induction. This newly developed COPD mouse model is expected to be a valuable tool for the pathogenesis and therapeutic research on human COPD.