Severe Chronic Lung Disease Research Articles

Utility of serum uric acid levels in excluding pulmonary hypertension in severe chronic lung disease: insights from a tertiary care center

Hyperuricemia is a known predictor of World Health Organization (WHO) Group 1 pulmonary hypertension (PH) (pulmonary arterial hypertension), but its role in excluding PH secondary to chronic lung diseases (WHO Group 3) remains unclear. We retrospectively analyzed data from 323 patients with severe chronic pulmonary diseases who underwent evaluation for lung transplantation at a tertiary medical center between June 2017 and February 2023. We examined the association between hyperuricemia (serum uric acid > 6 mg/dL or > 0.357 mmol/L) and PH [mean pulmonary arterial pressure (MPAP) > 20 mmHg]. Compared to the normouricemia group (n = 211), hyperuricemic patients (n = 112) were more likely to be younger (P = 0.02), male (P < 0.001), and present with PH (P = 0.001) and severe PH (MPAP > 35 mmHg; P < 0.001). These patients also had a higher body mass index (P = 0.004), plasma N-terminal pro-B-type natriuretic peptide (P < 0.001), serum creatinine (P < 0.001), and C-reactive protein levels (P = 0.03). Significant associations with PH included higher body mass index (P = 0.005), uric acid levels (P < 0.001), total lung capacity (P = 0.02), and residual volume (P = 0.01); shorter 6-min walk test distance (P = 0.005); and lower forced expiratory volume in one second (P = 0.006) and diffusing capacity for carbon monoxide (P < 0.001). Multivariate analysis showed elevated uric acid levels remained significantly associated with PH (OR 1.29, 95% CI 1.05–1.58, P = 0.01). In conclusion, normal serum uric acid levels serve as a significant predictor for excluding pulmonary hypertension in patients with severe chronic lung diseases.

Exploring research trends and hotspots on oxidative stress and bronchopulmonary dysplasia: Insights from bibliometric and visualized study.

Bronchopulmonary dysplasia (BPD) is a severe chronic lung disease primarily affecting premature infants, often resulting from prolonged mechanical ventilation and oxygen therapy. Oxidative stress plays a critical role in the pathogenesis of BPD, contributing to lung injury, inflammation, and impaired lung development. Despite extensive research, there is a need to systematically map out the research trends and hotspots in this field to inform future studies and therapeutic strategies. This study utilized bibliometric and visualized analysis to explore global research trends and hotspots on oxidative stress and BPD from 2004 to 2024. A comprehensive literature search was conducted in the Web of Science Core Collection, focusing on publications related to oxidative stress and BPD. Tools such as VOSviewer, Citespace, and the R package Bibliometrix were employed to analyze Coauthorship, co-citation, and keyword co-occurrence networks, as well as to identify emerging research fronts and influential studies. The analysis identified 597 relevant publications, showing a steady increase in research output over the 20-year period, with a significant surge in the last decade. The United States led in research contributions, followed by China and Germany, with notable collaborations among these countries. Coauthorship analysis highlighted key research institutions, such as Harvard University and the University of California, as central nodes in the research network. Thematic clustering revealed five major research areas: antioxidant mechanisms, inflammation, molecular pathways, lung development, and therapeutic interventions. The keyword co-occurrence analysis showed a shift in research focus over time. Early studies concentrated on basic pathophysiological mechanisms, while recent research has increasingly focused on advanced molecular techniques, such as gene expression and targeted therapies. Notably, the study identified emerging research hotspots, including the role of extracellular vesicles and cellular senescence in BPD, as well as the potential therapeutic applications of antioxidants like superoxide dismutase mimetics. This bibliometric study provides a comprehensive overview of the research landscape on oxidative stress and BPD, identifying key trends, influential authors, and emerging research topics. The findings underscore the importance of continued research in this field, particularly in translating basic scientific insights into clinical applications to improve outcomes for infants affected by BPD. The study also highlights potential areas for future investigation, including the development of novel therapeutic strategies targeting oxidative stress in BPD.

Sternum-sparing multivessel coronary surgery as a routine procedure: Midterm results of total coronary revascularization via left anterior thoracotomy

ObjectiveA sternum-sparing approach of minimally invasive total coronary revascularization via left anterior thoracotomy demonstrated promising early outcomes in unselected patients with coronary artery multivessel disease. Follow-up data are still missing. MethodsFrom November 2019 to September 2023, coronary artery bypass grafting via left anterior minithoracotomy on cardiopulmonary bypass and cardioplegic cardiac arrest was performed as a routine procedure in 392 consecutive, nonemergency patients (345 men; 67.0 ± 9.9 years; range, 32-88 years). All patients had multivessel coronary artery disease (77.6% 3-vessel-disease, 22.4% 2-vessel-disease, and 32.9% left main stenosis). Patients at old age (older than a 80 years, 12.5%), with severe left ventricular dysfunction (ejection fraction <30%, 7.9%), diabetes mellitus (34.9%), massive obesity (body mass index > 35, 8.9%), and chronic lung disease (17.1%) were included. Mean European System for Cardiac Operative Risk Evaluation II score was 2.9 ± 2.8. Mean midterm follow-up (100%) was 15.2 ± 10.7 months (range, 0.1-39.5 months). ResultsLeft internal thoracic artery (99.0%), radial artery (70.4%), and saphenous vein grafts (57.4%) were used, and 70.4% of patients received at least 2 arterial grafts. A total of 3.0 ± 0.8 anastomoses (range, 2-5 anastomoses) per patient were performed to revascularize the territories of left anterior descending (98.7%), circumflex (91.6%), and right coronary (70.9%) artery. Complete anatomical revascularization was achieved in 95.1%. At follow-up, all-cause-mortality, myocardial infarction, repeat revascularization, and stroke was 3.1%, 1.5%, 5.4%, and 0.7%, respectively. Overall major adverse cardiac and cerebrovascular events rate was 8.7%. ConclusionsThis is the first report of midterm follow-up after routine sternum-sparing total coronary revascularization via left anterior thoracotomy for multivessel coronary artery disease with a high rate of multiple arterial grafting and complete anatomical revascularization. Outcome was favorable and similar to that of contemporary conventional coronary artery bypass grafting.

Risk factors associated with pulmonary hypertension in patients with active tuberculosis and tuberculous destroyed lung: a retrospective study

Pulmonary tuberculosis (TB) can result in irreversible damage and lead to tuberculous destructive lung (TDL), a severe chronic lung disease that is associated with a high mortality rate. Additionally, pulmonary hypertension (PH) is a hemodynamic disorder that can be caused by lung diseases. The objective of this study is to investigate the risk factors associated with PH in active TB patients diagnosed with TDL. We conducted a retrospective review of the medical records of 237 patients who were diagnosed with TDL, active pulmonary tuberculosis, and underwent echocardiography at the Third People’ Hospital of Shenzhen from January 1, 2016, to June 30, 2023. Univariate and multivariate logistic regression analyses were performed to identify factors that correlated with the development of pulmonary hypertension. Univariate and multivariate logistic regression analyses revealed that several factors were associated with an increased risk of pulmonary hypertension (PH) in individuals with tuberculosis destroyed lung (TDL). These factors included age (OR = 1.055), dyspnea (OR = 10.728), D-dimer (OR = 1.27), PaCO2 (OR = 1.040), number of destroyed lung lobes (OR = 5.584), bronchiectasis (OR = 3.205), and chronic pleuritis (OR = 2.841). When age, D-dimer, PaCO2, and number of destroyed lung lobes were combined, the predictive value for PH in patients with TDL was found to be 80.6% (95% CI 0.739–0.873),with a sensitivity of 76.6% and specificity of 73.2%. Advanced age, elevated D-dimer levels, hypercapnia, and severe lung damage were strongly correlated with the onset of PH in individuals with active pulmonary tuberculosis (PTB) and TDL. Furthermore, a model incorporating age, D-dimer, PaCO2, and the number of destroyed lung lobes might be valuable in predicting the occurrence of PH in patients with active PTB and TDL.

Tolerability of Daratumumab Amongst Asian Patients with Plasma Cell Dyscrasias - A Single Centre Experience.

Daratumumab is increasingly incorporated into the standard treatment regimens for patients with plasma cell dyscrasias in Asia, especially with cost-containment measures implemented by various regional health authorities. This analysis aimed to study daratumumab's tolerability amongst Asian patients. This is a retrospective medical records review of patients who received daratumumab between November 2016 and August 2021 as part of routine clinical care. Sixty-two patients were included in the study: 62.9% had renal impairment, and 27.4% had creatinine clearance (CrCl) \<30ml/min. Forty-five patients (72.6%) received daratumumab combination therapy, with a median 1 line of prior therapy. The median duration of follow-up was 12.4 months, and the median duration patients were on treatment with daratumumab was 12.3 months. Twenty-one of 62 (33.9%) patients experienced infusion-related reactions (IRRs) after the first dose of intravenous daratumumab. Seven developed mostly grades 1 and 2 respiratory events, and 14 showed grades 1 and 2 non-respiratory IRRs. Only one patient experienced a grade 1 IRR with the second infusion, with none developing any IRRs in the third or subsequent infusions. Eight (12.9%) patients were affected by hematological adverse events (AEs), mostly grades 2 and 3, with one experiencing grade-4 neutropenia without sepsis. Six (9.7%) patients experienced non-hematological AEs, the commonest being pneumonia and other infections, with one developing Nocardia pneumonia (grade 4) 14 months after the initiation of daratumumab. In conclusion, daratumumab is tolerable amongst Asian patients, including the elderly, and patients with severe renal impairment and chronic lung diseases.

Myeloid Zfhx3 deficiency protects against hypercapnia-induced suppression of host defense against influenza A virus.

Hypercapnia, elevation of the partial pressure of CO2 in blood and tissues, is a risk factor for mortality in patients with severe acute and chronic lung diseases. We previously showed that hypercapnia inhibits multiple macrophage and neutrophil antimicrobial functions and that elevated CO2 increases the mortality of bacterial and viral pneumonia in mice. Here, we show that normoxic hypercapnia downregulates innate immune and antiviral gene programs in alveolar macrophages (AMØs). We also show that zinc finger homeobox 3 (Zfhx3) - a mammalian ortholog of zfh2, which mediates hypercapnic immune suppression in Drosophila - is expressed in mouse and human macrophages. Deletion of Zfhx3 in the myeloid lineage blocked the suppressive effect of hypercapnia on immune gene expression in AMØs and decreased viral replication, inflammatory lung injury, and mortality in hypercapnic mice infected with influenza A virus. To our knowledge, our results establish Zfhx3 as the first known mammalian mediator of CO2 effects on immune gene expression and lay the basis for future studies to identify therapeutic targets to interrupt hypercapnic immunosuppression in patients with advanced lung disease.

Patient Characteristics and Outcomes Associated with Sentinel Protection Device Use in Patients with Aortic Valve Disease Undergoing TAVR in a "Real-World" Setting.

Transcatheter aortic valve replacement (TAVR) has become the dominant treatment for aortic valve disease. While TAVR safety has improved over time, concern remains over the occurrence of cerebrovascular accidents (CVA) secondary to device placement, which is associated with increased morbidity and mortality. The Sentinel Cerebral Protection System (CPS) was developed to reduce the risk of embolic strokes associated with debris produced during TAVR. Studies evaluating Sentinel CPS efficacy have produced conflicting results, and there is little understanding of which patients are selected for device placement in "real-world" settings. With no existing guidelines on device use, the purpose of this study was to describe and compare the characteristics of patients who receive CPS with those who do not in a "real-world" setting of consecutive TAVR patients and evaluate its impact on postoperative complications, namely stroke. This was a single-center, retrospective study of all patients undergoing TAVR between July 1, 2019, and December 31, 2020. Patient demographics, baseline, and perioperative characteristics were collected prospectively using the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry and our institution's TAVR database for analysis. Postoperative outcomes were assessed using primary endpoints of in-hospital/30-day stroke and the composite of death, stroke, and bleeding/vascular events at one-year. To adjust for baseline differences, a propensity score was developed including all factors that were different between groups, and Multivariate Cox Regression analysis was used to control for these differences. Patient follow-up was 97% complete at 12 months with 100% echocardiographic follow-up. A total of 242 consecutive patients (57.9% male) were analyzed, with a mean age of 79.9 9 years. Of these patients, 134 (55.4%) received the Sentinel CPS and 108 (44.6%) did not. Sentinel CPS patients were more likely to be male, not on dialysis, without prior CVA or pacemaker, had less severe chronic lung disease, and were lower operative risk compared to concurrent non-CPS patients. CPS patients were also found to have higher hemoglobin and albumin levels, lower creatinine, and were less likely to be on immunosuppressant therapy. The incidence of in-hospital/30-day stroke after TAVR did not differ between CPS and non-CPS patients (0.0% vs. 1.9%; p = 0.198). Unadjusted analyses at one-year showed a lower occurrence of the composite endpoint in CPS patients compared non-CPS patients (8.3% vs. 17.0%; p = 0.034). After adjustment, the hazard ratio (Adj HR) for the CPS group was no longer significantly associated with a lower composite endpoint (Adj HR = 0.609, 95% CI 0.244-1.523; p = 0.289). Both unadjusted (p = 0.233) and adjusted (p = 0.132) analyses showed no difference in the incidence of stroke at one-year. Our study demonstrates that in a "real-world" setting, the Sentinel CPS device is more likely to be used in healthier and less complex patients. In analyses adjusted for illness severity and patient complexity, CPS use did not have a significant effect on the incidence of in-hospital/30-day stroke or the composite endpoint of death, stroke, and bleeding/vascular events at one-year.

2659. Substantially Elevated Influenza Risk in Vaccinated Immunocompromised Adults and High-Risk Patients Relative to All Vaccinated

Abstract Background Annual influenza vaccine is universally recommended for high-risk adults, but effectiveness varies between 19-60% in the general population by season and is markedly lower for specific high-risk groups, underscoring the need for novel prophylactic interventions. Though abundant in vaccine effectiveness studies, direct evidence quantifying influenza risk in vaccinated high-risk adults is limited. We aimed to estimate incidence of post-vaccination medically attended influenza-like Illness (ILI) and subsequent hospitalization among adults with chronic diseases and immunosuppression. Methods U.S. adults who received an influenza vaccine in influenza seasons 2015-2019 were identified using Optum commercial claims database (inpatient and outpatient). Known risk factors for influenza were assessed prior to vaccination, while medically attended ILI and subsequent hospitalization (within 30 days) were ascertained post-vaccination. Incidence rates and 95% confidence intervals (CI) were estimated for individual patient risk subgroup during the study period while maintaining sample independence across years. Relative risks were calculated using all vaccinated with or without risk as control. Results Among 5,195,160 vaccinated adults (median age 65; 73% with ≥1 comorbid condition), annual incidence of medically attended ILI was 2.04 [95% CI 2.03-2.06] per 100 person-years and 0.25 [0.25-0.26] per 100 person-years for ILI-related hospitalization. ILI-related hospitalization risk was the highest for immunocompromised transplant patients (5.6-13.9 relative risk ratio [RR] versus all vaccinated), late-stage kidney disease (RR: 5.4-7.4), and severe chronic lung disease (RR: 4.6-5.4), with likelihood of hospitalization after ILI up to 51.3%. More than half of ILI-related hospitalizations were in individuals with chronic obstructive pulmonary disorder, heart failure, or late-stage kidney disease. Conclusion Immunocompromised and individuals with severe chronic cardiopulmonary or renal disease retained the highest residual risk of ILI-related hospitalization despite vaccination. Additional prophylactic intervention complementing vaccination could potentially offer enhanced protection for these patients. Disclosures Natalia Zemlianskaia, PhD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Amanda Zheutlin, PhD, Janssen Pharmaceuticals: Employee Yoshihiko Murata, MD, PhD, Gilead Sciences: Current employee of Gilead Sciences|Gilead Sciences: Stocks/Bonds|Merck Research Laboratories: Listed as co inventor in a patent|Merck Research Laboratories: Former employee of Merck Research Laboratories|ViiV Healthcare: Former employee of ViiV Healthcare Jyotsna Bhattacharya, MD, FAAP, Janssen Pharmaceuticals: Current Employee|Janssen Pharmaceuticals: Stocks/Bonds Geoffroy Coteur, PhD, Janssen Pharmaceutica: Honoraria|Janssen Pharmaceutica: Stocks/Bonds Gabriela Ispas, PhD, Janssen Pharmaceuticals: Current Employee|Janssen Pharmaceuticals: Stocks/Bonds Jorge Villacian, MD, Janssen Pharmaceuticals: Current Employee|Janssen Pharmaceuticals: Stocks/Bonds Jason Chien, MD, MS, Janssen Biopharma: Stocks/Bonds David Hong, MD, Janssen: Former employee|Janssen: Stocks/Bonds|Spero Therapeutics: Employee Jennings Xu, BA, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Breno Neri, PhD, Janssen R&amp;D: Full time employment|Janssen R&amp;D: Stocks/Bonds Khaled Sarsour, PhD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Tripthi Kamath, PhD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Xinggang lIU, MD, PhD, Janssen Pharmaceuticals: Current employee|Janssen Pharmaceuticals: Stocks/Bonds

Exploring the mechanism of Gentiana rigescens Franch. in the treatment of pulmonary fibrosis based on network pharmacology

Pulmonary fibrosis (PF) is a severe chronic interstitial lung disease with high mortality, and there is currently a lack of definite and effective treatment methods. Studies have found that gentiopicroside, a secoiridoid glycoside compound derived from plants of the Gentiana genus, can significantly improve pulmonary inflammation and fibrosis lesions in mice with pulmonary fibrosis. However, the mechanism of its anti-fibrotic effect is unclear. Therefore, in this study, we employed network pharmacology's virtual computer technology to investigate the potential mechanism underlying the anti-pulmonary fibrosis effect of Gentianae Radix et Rhizome (Longdan in Chinese, GRR). Our findings offer valuable theoretical insights and serve as a guiding reference for future experimental investigations. A total of 10 active compounds and 920 drug-target proteins were identified from the TCMSP database. The compound-target-pathway-disease network showed that GRR could potentially treat PF by regulating the MDM2, ERBB2 and VEGFA, signaling pathways through its key targets, including AKT1, TNF, and MAPK1. The protein‒protein interaction network revealed that these targets had strong interactions with each other, indicating a potential synergistic effect of GRR in treating PF. The GO and KEGG enrichment analyses further supported the potential anti-pulmonary fibrosis mechanisms of GRR, including regulating the inflammatory response, ECM-receptor interaction, and TGF-beta signaling pathways. Our study provides a systematic analysis of the potential anti-pulmonary fibrosis mechanisms of GRR based on network pharmacology. These findings could contribute to the development of novel treatments for PF and provide a basis for further experimental studies.

Unraveling the Mysteries of Cystic Fibrosis: Causes, Symptoms, and Treatment Strategies

In this work we present the most relevant and important data, so that the reader will be able to identify the disease "Cystic Fibrosis", regardless of the fact that in Mexico this disease is not common, thanks to the fact that in Mexico and in the world newborns are screened. In this way the rate of this disease in Mexico and the world was reduced. In Mexico, there are 350 new cases every year, said the General Director of the National Center for Gender Equity and Reproductive Health, Dr. Ricardo García Cavazos. Thanks to this data, the purpose of this work is to guide readers in the identification of this disease and in this way generate a positive and active influence in the identification of this disease. This disease is a disease that has its historical antecedents since the year 1595, when with the thought of a spell on a girl during her autopsy, the first clinical data that are characteristic of this disease were given. Being in the 70's where with the passage of time and as new knowledge came to what we know today. Cystic fibrosis is an inherited multisystem disorder of children and adults, it is the leading cause of severe chronic lung disease in children. Cystic fibrosis occurs most often in white populations in Northern Europe, North America and Australia/New Zealand and is inherited in an autosomal recessive manner.

Hypercapnia increases ACE2 expression and pseudo-SARS-CoV-2 entry in bronchial epithelial cells by augmenting cellular cholesterol.

Patients with chronic lung disease, obesity, and other co-morbid conditions are at increased risk of severe illness and death when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hypercapnia, the elevation of CO2 in blood and tissue, commonly occurs in patients with severe acute and chronic lung disease, including those with pulmonary infections, and is also associated with high mortality risk. We previously reported that hypercapnia increases viral replication and mortality of influenza A virus infection in mice. We have also shown that culture in elevated CO2 upregulates expression of cholesterol synthesis genes in primary human bronchial epithelial cells. Interestingly, factors that increase the cholesterol content of lipid rafts and lipid droplets, platforms for viral entry and assembly, enhance SARS-CoV-2 infection. In the current study, we investigated the effects of hypercapnia on ACE2 expression and entry of SARS-CoV-2 pseudovirus (p-SARS-CoV-2) into airway epithelial cells. We found that hypercapnia increased ACE2 expression and p-SARS-CoV-2 uptake by airway epithelium in mice, and in cultured VERO and human bronchial epithelial cells. Hypercapnia also increased total cellular and lipid raft-associated cholesterol in epithelial cells. Moreover, reducing cholesterol synthesis with inhibitors of sterol regulatory element binding protein 2 (SREBP2) or statins, and depletion of cellular cholesterol, each blocked the hypercapnia-induced increases in ACE2 expression and p-SARS-CoV-2 entry into epithelial cells. Cigarette smoke extract (CSE) also increased ACE2 expression, p-SARS-CoV-2 entry and cholesterol accumulation in epithelial cells, an effect not additive to that of hypercapnia, but also inhibited by statins. These findings reveal a mechanism that may account, in part, for poor clinical outcomes of SARS-CoV-2 infection in patients with advanced lung disease and hypercapnia, and in those who smoke cigarettes. Further, our results suggest the possibility that cholesterol-lowering therapies may be of particular benefit in patients with hypercapnia when exposed to or infected with SARS-CoV-2.

A novel corpus of molecular to higher-order events that facilitates the understanding of the pathogenic mechanisms of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a severe and progressive chronic fibrosing interstitial lung disease with causes that have remained unclear to date. Development of effective treatments will require elucidation of the detailed pathogenetic mechanisms of IPF at both the molecular and cellular levels. With a biomedical corpus that includes IPF-related entities and events, text-mining systems can efficiently extract such mechanism-related information from huge amounts of literature on the disease. A novel corpus consisting of 150 abstracts with 9297 entities intended for training a text-mining system was constructed to clarify IPF-related pathogenetic mechanisms. For this corpus, entity information was annotated, as were relation and event information. To construct IPF-related networks, we also conducted entity normalization with IDs assigned to entities. Thereby, we extracted the same entities, which are expressed differently. Moreover, IPF-related events have been defined in this corpus, in contrast to existing corpora. This corpus will be useful to extract IPF-related information from scientific texts. Because many entities and events are related to lung diseases, this freely available corpus can also be used to extract information related to other lung diseases such as lung cancer and interstitial pneumonia caused by COVID-19.

High levels of antibodies 6 months after COVID-19 vaccination in children with severe chronic diseases: A prospective longitudinal case series.

High levels of antibodies 6 months after COVID-19 vaccination in children with severe chronic diseases: A prospective longitudinal case series.

Sildenafil in Pulmonary Hypertension Associated with Bronchopulmonary Dysplasia: Friend or Foe?

Sildenafil is a phosphodiesterase-5 inhibitor used to treat pulmonary hypertension, although its efficiency remains disputed in the neonatal population. We aimed to assess the clinical use of this drug in extremely premature infants diagnosed with pulmonary hypertension associated to bronchopulmonary dysplasia. This is a retrospective study of 18 patients born at ≤ 32 weeks gestational age with pulmonary hypertension complicating moderate to severe bronchopulmonary dysplasia, which was diagnosed on echocardiography at 36 weeks corrected gestational age. Median corrected gestational age at starting sildenafil was 48 weeks (range 32-60). In 4 cases there was a period of > 2 weeks between the evidence of moderate-severe pulmonary hypertension and starting sildenafil. In all other cases it was started as soon as the diagnosis was suspected or confirmed. All infants tolerated the use of sildenafil. However, 5 babies (26.31%) died despite ongoing intensive care, and 5 babies (26.31%) died after having care redirected due to severe chronic lung disease (1 due to co-existing neurological abnormality), with on overall mortality of this study of 52.62%. Eight babies (42.1%) survived: 5 continued on sildenafil until hospital discharge, 1 continued on transfer to the paediatric intensive care unit and 2 stopped while inpatients. Upon follow up to 2 years of age, out of the 5 patients who continued upon hospital discharge, 4 stopped at 6, 7, 12 and 18 months respectively, with 1 child being lost to follow up. Two patients (10.52%) restarted sildenafil use later in childhood. Echocardiographic evidence of improvement was noted in 58% (11 cases), with no improvement in 6 cases (32%) and incorrect original diagnosis in 1 case (5%). One infant died less than a week from the initiation of treatment. sildenafil use showed no clinical improvement of pulmonary hypertension complicating moderate to severe bronchopulmonary dysplasia in extremely premature infants.

Chronic lung disease in Saudi preterm infants

Background: Despite advances in neonatal medicine, chronic lung disease (CLD) remains a major cause of pulmonary morbidity in preterm infants. Objective: To determine the prevalence of CLD and to identify the possible risk factors that may predict the development of CLD. Patients and Methods: A retrospective study of preterm infants admitted to the NICU between July 2011 and June 2022 with gestational age (GA) < 32 weeks and birth weight (BW) < 1500 g was performed. Results: A total of 706 preterm infants were included in the study, of whom 202 (28.6%) infants developed CLD. Of the 202 preterm infants who developed CLD, 194 survivors; 93 (47.9%) had mild, 58 (29.9%) had moderate and 43 (22.2%) had severe CLD. Multivariate analysis showed that low GA (odds ratio [OR]: 0.62; 95% confidence interval [CI]: 0.43-0.98), low BW (OR: 20.6; 95% CI: 17.1-29.3), use of mechanical ventilation (OR: 1.07; 95% CI: 0.87-1.54), higher peak inspiratory pressure (PIP) (OR: 1.48; 95% CI: 1.44-1.91), higher fraction of inspired oxygen (FiO2) use (OR: 0.11; 95% CI: 0.05-0.19), duration of mechanical ventilation (OR: 3.56; 95% CI: 4.28-3.75) and frequent blood transfusion (OR: 0.65; 95% CI: 0.53-0.87) were identified as the main risk factors for the development of CLD. Conclusions: The prevalence of CLD among preterm infants was 28.6%. The most relevant predictors of CLD were GA, BW, mechanical ventilation, higher PIP, higher FiO2 use, duration of mechanical ventilation and frequent blood transfusion.

Pulmonary vascular disease and exercise hemodynamics in chronic liver disease

Background & aimsPortopulmonary hypertension (POPH) and hepatopulmonary syndrome (HPS) are severe pulmonary vascular complications of chronic liver disease and strongly associated with morbidity and mortality. The prevalence of these complications is relatively high in patients evaluated for liver transplantation, however it is virtually unknown in patients with stable chronic liver disease. MethodsWe assessed the pulmonary hypertension (PH) and HPS prevalence in a prospective registry study of our liver out-patient clinic in a tertiary center. Between 2011 and 2016, consecutive patients with cirrhosis or non-cirrhotic portal hypertension were prospectively enrolled after written informed consent. We excluded patients with acute decompensation of liver disease and other causes of PH like severe chronic heart or lung diseases and chronic thromboembolic PH. HPS was diagnosed using contrast enhanced echocardiography and blood gas analysis. Patients were screened for PH using an algorithm implementing severity of dyspnea, echocardiography, cardiopulmonary exercise testing and exercise echocardiography employing a threshold of systolic pulmonary arterial pressure (SPAP) = 50 mmHg at peak exercise. If the algorithm indicated an increased PH risk, patients were invited for invasive investigations by means of right heart and hepatic vein catheter. We defined POPH as resting mPAP≥21 mmHg and PVR>3WU and PAWP<15 mmHg, mild PH as resting mPAP = 21–24 mmHg, and exercise PH as mPAP>30 mmHg and TPR >3 WU at peak exercise. ResultsTwo-hundred-five patients were enrolled (male 75%; cirrhosis 96%; median age 57 yrs). Sixty-seven patients (33%) fulfilled HPS criteria but only two (1.0%) for severe (PaO2:50–60 mmHg) or very severe HPS (PaO2<50 mmHg). In 18/77 patients (23%) undergoing exercise echocardiography, SPAP at peak exercise exceeded 50 mmHg. Finally, n = 3 (1.5%) patients were invasively diagnosed with POPH, n = 4 (2.9%) with mild PH and n = 2 with exercise PH. ConclusionIn chronic liver disease, excluding acute decompensation and other causes of PH, POPH and severe HPS are rare findings while mild to moderate HPS and mild PH or exercise PH are more frequent.

The hemodynamic characteristics of severe chronic lung disease referred for lung transplantation.

Severe pulmonary hypertension (PH) is not common even in patients with severe chronic lung disease (CLD) but data on hemodynamic characteristics among patients with severe CLD is scarce. All adult patients who had right heart catheterization for lung transplant assessment for severe CLD in the only lung transplant service and for PAH management in the only tertiary pulmonary hypertension service in Hong Kong from 2010 to 2020 were included and classified into CLD group and PAH group. Patient characteristics and hemodynamic parameters were analyzed. There were 153 patients included with 106 patients in the CLD group and 47 in the PAH group. There were only 19.8% of the patients in the CLD group had severe pulmonary hypertension. Patients in the CLD group had significantly lower systolic pulmonary arterial pressure (PAPs), lower mean pulmonary arterial pressure (PAPm), higher cardiac index, and lower PVR when compared with the PAH group (p < 0.001). The area under curve (AUC) of PAPs, PAPm, and PVR were excellent, 0.973, 0.970, and 0.938, respectively for discrimination between CLD and PAH on receiver operator characteristics curve analysis. Optimal cutoff values were 55.5 mmHg, 35.5 mmHg, and 6.1 Wood Units for PAPs, PAPm, and PVR with Youden Index 0.85, 0.80, and 0.82, respectively. There were distinct hemodynamic characteristics between the CLD group and the PAH group. Systolic pulmonary arterial pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance are useful to discriminate between the phenotype of severe CLD and PAH.

Impact of Time Point of Extracorporeal Membrane Oxygenation on Mortality and Morbidity in Congenital Diaphragmatic Hernia: A Single-Center Case Series.

Since there are no data available on the influence of the time point of ECMO initiation on morbidity and mortality in patients with congenital diaphragmatic hernia (CDH), we investigated whether early initiation of ECMO after birth is associated with a beneficial outcome in severe forms of CDH. All neonates with CDH admitted to our institution between 2010 until 2020 and undergoing ECMO treatment were included in this study and divided into four different groups: (1) ECMO initiation < 12 h after birth (n = 143), (2) ECMO initiation between 12–24 h after birth (n = 31), (3) ECMO initiation between 24–120 h after birth (n = 48) and (4) ECMO initiation > 120 h after birth (n = 14). The mortality rate in the first (34%) and fourth group (43%) was high and in the second group (23%) and third group (12%) rather low. The morbidity, characterized by chronic lung disease (CLD), did not differ significantly in the three groups; only patients in which ECMO was initiated >120 h after birth had an increased rate of severe CLD. Our data, although not randomized and limited due to small study groups, suggest that very early need for ECMO and ECMO initiation > 120 h after birth is associated with increased mortality.

The Additional Medical Expenditure Caused by Depressive Symptoms among Middle-Aged and Elderly Patients with Chronic Lung Diseases in China.

Depression is one of the most common comorbidities in patients with chronic lung diseases (CLDs). Depressive symptoms have an obvious influence on the health function, treatment, and management of CLD patients. In order to investigate the additional medical expenditure caused by depressive symptoms among middle-aged and elderly patients with CLDs in China, and to estimate urban–rural differences in additional medical expenditure, our study used data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) investigation. A total of 1834 middle-aged and elderly CLD patients were included in this study. A generalized linear regression model was used to analyze the additional medical expenditure on depressive symptoms in CLD patients. The results show that depressive symptoms were associated with an increase in medical costs in patients with CLDs. Nevertheless, the incremental medical costs differed between urban and rural patients. In urban and rural patients with more severe comorbid CLD and depressive symptoms (co-MCDs), the total additional medical costs reached 4704.00 Chinese Yuan (CNY) (USD 711.60) and CNY 2140.20 (USD 323.80), respectively. Likewise, for patients with lower severity co-MCDs, the total additional medical costs of urban patients were higher than those of rural patients (CNY 4908.10 vs. CNY 1169.90) (USD 742.50 vs. USD 176.90). Depressive symptoms were associated with increased medical utilization and expenditure among CLD patients, which varies between urban and rural areas. This study highlights the importance of mental health care for patients with CLDs.

Caspase-1 and interleukin-18 in children with post infectious bronchiolitis obliterans: a case-control study.

Caspase-1 level was increased in patients with PIBO which suggests that inflammasome activation may have a role in fibrosis; however, IL-18 level was found to be low. Mediators other than IL-18 may be involved in the inflammatory pathway in PIBO. Further immunological studies investigating inflammasome pathway are needed for PIBO with chronic inflammation. • Post infectious bronchiolitis obliterans (PIBO) is a rare, severe chronic lung disease during childhood which is associated with inflammation and fibrosis which lead to partial or complete luminal obstruction especially in small airways. • The exact immunological mechanisms of PIBO in childhood are not fully known. • Inflammasome activation persists even years after acute infection and may play a role in fibrosis in PIBO. • Mediators other than IL-18 may be involved in these inflammatory pathway.