Chronic Lung Disease Research Articles

Continuous Positive Airway Pressure vs. High Velocity Nasal Cannula for weaning respiratory support of preterm infants

Abstract Objectives To compare the rates of Chronic Lung Disease (CLD) between premature infants weaned with either Continuous Positive Airway Pressure (CPAP) or High Velocity Nasal Cannula (HVNC). Methods This was a retrospective, observational cohort study at a level IV NICU including infants <34 weeks gestational age (GA) on NIV (noninvasive ventilation) for at least 5 days. Maternal and infant demographics and clinical data from the infant’s hospital course were collected. Infants were assigned to CPAP (n=175) and HVNC (n=48) cohorts based on which modality they were treated with for most of their time on NIV. Results Demographics and clinical characteristics were similar between the CPAP group and the HVNC group. The rates of CLD were significantly higher in the HVNC group as compared to the CPAP group (58.3 vs. 24.6 %, p<0.001). After logistic regression analysis was performed accounting for GA, invasive respiratory support requirement, sepsis and administration of antenatal corticosteroids, the HVNC group was found to be almost 4 times more likely to develop CLD. Further analysis using propensity score matching yielded similar results. Conclusions When used as the primary modality of noninvasive support, preterm infants on HVNC were more likely to develop CLD than those on CPAP.

Hypoxia-inducible factor 1α modulates acrolein-induced cellular damage in bronchial epithelial cells.

Hypoxia-inducible factor 1α modulates acrolein-induced cellular damage in bronchial epithelial cells.

Diagnostic Performance of Sarcopenia Screening Tests in Chronic Lung Disease Patients

Diagnostic Performance of Sarcopenia Screening Tests in Chronic Lung Disease Patients

Complete Blood Cell Count Parameters Predict Mortality in Patients with Hypersensitivity Pneumonitis

Background: Hypersensitivity pneumonitis (HP) represents a chronic lung disease with an unpredictable clinical course. There is a pressing need for clinically applicable prognostic biomarkers in patients with HP. Methods: This was an observational, retrospective study. We investigated the prognostic potential of complete blood count parameters in treatment-naïve patients diagnosed with HP between 15 December 2010 and 1 October 2023. Receiver operating characteristic (ROC) curve analysis identified the optimal cut-off thresholds for each parameter in terms of mortality prediction. Results: We included 129 patients diagnosed with HP [median age: 68.0 years (95% CI: 65.0 to 69.0), fibrotic HP: n = 85, 65.9%]. Patients with HP and an eosinophil count > 160 cells/μL [ROC curve, area under curve (AUC): 0.61] exhibited increased mortality risk compared to patients with HP and an eosinophil count ≤ 160 cells/μL [Kaplan–Meier, HR: 2.95 (95% CI: 1.36 to 6.42), p = 0.006]. Patients with HP and a monocyte count > 350 cells/μL (ROC curve, AUC: 0.52) had worse survival compared to patients with HP and a monocyte count lower than this threshold [Kaplan–Meier, HR: 2.48 (95% CI: 1.03 to 5.09), p = 0.04]. Patients with HP and an eosinophil–lymphocyte ratio (ELR) > 0.09 (ROC curve, AUC: 0.64) had a higher risk of mortality compared to patients with HP and ELR ≤ 0.09 [Kaplan–Meier, HR: 2.75 (95% CI: 1.3 to 5.78), p = 0.008]. Conclusions: This study demonstrated that eosinophil count, monocyte count, and ELR could be prognostic biomarkers in patients with HP. Further studies aiming to validate the prognostic potential of complete blood count parameters in patients with HP are greatly anticipated.

Understanding the childhood origins of asthma and COPD: insights from birth cohorts and studies across the lifespan.

Understanding the childhood origins of asthma and COPD: insights from birth cohorts and studies across the lifespan.

Effect of age, COPD severity and cigarette smoke exposure on bronchial epithelial barrier function.

We investigated the effect of age, cigarette smoke and COPD severity on epithelial barrier function. Primary bronchial epithelial cells (PBECs) were obtained from bronchial brushings in 8 younger and 8 older never-smokers; 7 older ex-smokers without COPD 8 COPD GOLD (Global Initiative for Chronic Obstructive Lung Disease) I-III and 6 COPD GOLD IV patients, and cultured in the absence/presence of cigarette smoke extract (CSE). Epithelial barrier function was assessed by electric resistance sensing and expression of junctional and antioxidant genes/proteins quantified by qPCR/immunodetection. Epithelial barrier function was comparable between PBECs from younger and older never-smokers. PBECs from ex-smokers had significantly lower barrier function compared to never-smokers, with a further decrease in COPD GOLD IV. CSE decreased epithelial barrier function from which PBECs from never-smokers, but not ex-smokers with and without COPD, recovered. Restoration of barrier function was accompanied by increased expression of barrier and antioxidant genes. At baseline, PBECs from ex-smokers with and without COPD had higher expression of junctional and antioxidant genes compared to never smokers. However, exposure to CSE increased antioxidant (SOD1-3, CAT) gene expression only in PBECs from never-smokers and ex-smokers without COPD. In conclusion, our data indicate that cigarette smoking and COPD severity are associated with reduced epithelial barrier function, which is potentially driven by an imbalance in the antioxidant response.

Frailty in Pulmonary Hypertension: A Multidimensional Comorbidity.

Pulmonary hypertension (PH) is a complex and irreversible pulmonary vascular disease with a significant impact on patients' lives. PH is categorized into 5 groups based on its etiology. Frailty is a multifaceted disorder that leads to physical, social, cognitive, and psychological decline. Several studies have linked a high occurrence of frailty to heart failure and chronic lung diseases, however the prevalence and impact of frailty in pulmonary arterial hypertension (PAH) remains largely unexplored. At the molecular level, inflammation, oxidative stress, cellular senescence, and mitochondrial dysfunction play a pivotal role in the pathophysiology of frailty in PH. Dysfunction of cardiac, respiratory, and skeletal muscles results in exercise intolerance, which promotes deconditioning and frailty. Exercise training in PAH, heart failure and chronic lung disease has shown promise in improving quality of life and exertion tolerance, while improving frailty scores, and quality of life. Properly designed studies are needed to elucidate the predictive value of frailty, and to identify assessment and treatment tools in PH particularly PAH, to aid clinicians in individualizing care plans and improving patient outcomes. In this narrative review we describe the pathobiology of frailty in PH, assessment tools, the impact of frailty on different PH groups and suggestions of potential interventions.

Development of a Polidocanol-based Human In Vitro Model to Explore Airway Epithelial Repair.

The human airway epithelium is a primary site of toxicant exposure and crucial in the pathogenesis of acute and chronic lung disease (CLD). In CLD, the airway epithelium is frequently altered and distorted, and its restoration is desirable. The mechanisms underlying human aberrant epithelial regeneration, however, are poorly understood. Importantly, our knowledge about airway epithelial injury and regeneration largely stems from mouse models, yet airways differ considerably between mice and humans. We hypothesized that treatment of differentiated primary human bronchial epithelial cells (phBECs, or HBEC) with polidocanol or naphthalene would allow for studying mechanisms of human airway epithelial injury and regeneration. Injury of differentiated phBECs with 0.04%, but not 0.1% PDOC, resulted in full restoration of a functional epithelium and epithelial barrier integrity as monitored by qRT-PCR analysis, immunofluorescence stainings, and transepithelial electrical resistance measurements. Regeneration was associated with a transient but not parallel increase of p21+ and KRT17+ cells. Providing proof-of-concept, DAPT, an inhibitor of Notch signaling, blunted the restoration of secretory cell types post 0.04% PDOC injury. Differentiation of phBECs in presence of cigarette smoke extract (CSE) or ethanol as first hit significantly impaired the regeneration capacity of phBECs. While naphthalene is known to specifically induce club cell depletion in mouse airways, it failed to do so in phBECs. In conclusion, using fully differentiated phBECs treated with PDOC, we successfully established and thoroughly characterized a human in vitro system that will facilitate studies of mechanisms involved in susceptibility to injury as well as human airway repair and regeneration.

Clinical Impact and Cost-Effectiveness of Updated 2023/24 COVID-19 mRNA Vaccination in High-Risk Populations in the United States.

In the post-pandemic era, people with underlying medical conditions continue to be at increased risk for severe COVID-19 disease, yet COVID-19 vaccination uptake remains low. This study estimated the clinical and economic impact of updated 2023/24 Moderna COVID-19 vaccination among high-risk adults versus no 2023/24 vaccination and versus updated Pfizer/BioNTech vaccination. A static Markov model was adapted for high-risk adults, including immunocompromised (IC), chronic lung disease (CLD), chronic kidney disease (CKD), cardiovascular disease (CVD), and diabetes mellitus (DM) populations in the United States (US). Vaccination with the updated Moderna vaccine at current coverage rates was estimated to prevent considerable COVID-19 hospitalizations in CLD (101,309), DM (97,358), CVD (47,830), IC (14,834), and CKD (13,558) populations versus no 2023/24 vaccination. Vaccination also provided net medical cost-savings of US$399 million (M)-2129M (healthcare payer) and $457M-2531M (societal perspective), depending on population. The return-on-investment was positive across all conditions ($1.10-$2.60 gain for every $1 invested). Healthcare savings increased with a relative 10% increase in current vaccination coverage ($439M-$2342M), and from meeting US 2030 targets of 70% coverage ($1096M-$5707M). Based on higher vaccine effectiveness observed in real-world evidence studies, updated Moderna vaccination was estimated to prevent additional COVID-19 hospitalizations in DM (13,105), CLD (10,359), CVD (6241), IC (1979), and CKD (942) versus Pfizer/BioNTech's updated vaccine, with healthcare payer and societal cost-savings, making it the dominant strategy. Healthcare savings per patient vaccinated with Moderna versus Pfizer/BioNTech's updated vaccine were $31.00-$59.00, depending on population. Results were robust across sensitivity/scenario analyses. Updated 2023/24 Moderna COVID-19 vaccination was estimated to provide significant health benefits through prevention of COVID-19 in high-risk populations, and cost-savings to healthcare payers and society, versus no 2023/24 vaccination and updated Pfizer/BioNTech vaccination. Increasing current low COVID-19 vaccination coverage rates was estimated to be cost-saving while preventing many more severe infections and hospitalizations in these high-risk populations. A graphical abstract is available with this article.

Shared roles of immune and stromal cells in the pathogenesis of human bronchiolitis obliterans syndrome.

Bronchiolitis obliterans syndrome (BOS) is a progressive, fatal obstructive lung that occurs following lung transplant, where it is termed chronic lung allograft dysfunction BOS (CLAD-BOS), or as the primary manifestation of pulmonary chronic graft versus host disease (cGVHD-BOS) following allogeneic hematopoietic stem cell transplant. Disease pathogenesis is poorly understood, however chronic alloreactivity is common to both conditions, suggesting a shared pathophysiology. We performed single-cell RNA-Seq (scRNA-Seq) on explanted human lungs from 4 CLAD-BOS patients, 3 cGVHD-BOS patients, and 3 deceased controls to identify cell types, genes, and pathways enriched in BOS to better understand disease mechanisms. In both forms of BOS, we found an expanded population of CD8+ tissue resident memory T-cells (TRM), which was distinct to BOS compared to other chronic lung diseases. In addition, BOS samples expressed genes and pathways associated with macrophage chemotaxis and proliferation, including in non-immune cell populations. We also identify dysfunctional stromal cells in BOS, characterized by pro and anti-fibrotic gene programs. These data suggest substantial cellular and molecular overlap between CLAD- and cGVHD-BOS and therefore, common pathways for possible therapeutic intervention.

Interplay of health-related quality of life and comorbidities in people with type 2 diabetes mellitus treated in primary care settings in Austria: a countrywide cross-sectional study

ObjectivesThis study assessed the health-related quality of life (HRQoL) and its relationship with clinical factors and comorbidities in people with type 2 diabetes mellitus (T2DM) treated in primary care settings.DesignCross-sectional...

Comparative Outcomes of Left Main and Nonleft Main Percutaneous Coronary Intervention from the Excellence in Coronary Artery Disease (XLCAD) Registry.

Comparative Outcomes of Left Main and Nonleft Main Percutaneous Coronary Intervention from the Excellence in Coronary Artery Disease (XLCAD) Registry.

Relationships between soil health and dynamics of soil potential pathogenic microbiota in functional domains of Xi'an urban greenspaces, China.

Relationships between soil health and dynamics of soil potential pathogenic microbiota in functional domains of Xi'an urban greenspaces, China.

Infection-Related Preterm Birth

Abstract Preterm birth (PTB), predominantly induced by intraamniotic inflammation, stands as the foremost contributor to neonatal morbidity and mortality globally. Fetal inflammatory response syndrome, stemming from the activation of the innate immune system, signifies the occurrence of funisitis or chorionic vasculitis. Maternal-fetal complications associated with infection-related PTB encompass maternal sepsis, fetal demise, neonatal sepsis, neonatal neurological impairment, and chronic lung disease. The inflammatory cascade is initiated when Toll-like receptors present on immune cells within the fetal membranes and the female reproductive tract encounter pathogen-associated molecular patterns derived from infectious agents. Subsequently, the nuclear factor kappa-light-chain-enhancer of activated B cells facilitates the transcription of cytokines. The accumulation of neutrophils compromises the tissue integrity of the fetal membranes, leading to membrane rupture via the secretion of matrix metalloproteinases. Elevated prostaglandin levels prompt uterine contractions and cervical remodeling, resulting in progressive cervical effacement and dilation, ultimately culminating in fetal delivery. The diagnosis of PTB should encompass three pivotal criteria: gestational age, uterine activity, and the consequences of that uterine activity. The diagnosis of chorioamnionitis is established through a combination of clinical manifestations, laboratory findings, identification of infectious microorganisms, and placental pathology. Fetal monitoring involves antenatal ultrasonography and non-stress testing. The management of infection-related PTB involves controlling and treating the infection, timing delivery to coincide with optimal fetal lung maturity, and optimizing outcomes for both the mother and neonate. Current preventive strategies for PTB primarily focus on inhibiting myometrial contractions that arise from the inflammatory cascade initiating PTB. An understanding of these pathways serves as the cornerstone for the development of therapeutic interventions aimed at preventing PTB.

Advances in predictive models for idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrotic lung disease of unknown etiology, primarily affecting middle-aged and elderly individuals. Chest imaging and histopathology are characterized by usual interstitial pneumonia (UIP). Without treatment, the median survival of patients is 3-5 years. Disease progression or acute exacerbation in IPF patients indicates a poor survival prognosis. Therefore, identification and establishment of predictive models for assessing IPF disease behavior may allow early prediction of disease progression, facilitating timely intervention or adjustment of therapeutic strategies to improve outcomes. This review aimed to summarized recent advances in IPF predictive models and to highlight key issues that need to be addressed.

Tissue-resident Klebsiella quasipneumoniae contributes to progression of idiopathic pulmonary fibrosis by triggering macrophages mitophagy in mice

Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic interstitial lung disease with unclear underlying pathogenic mechanisms. Dysbiosis of the lung microbiota is believed to be associated with the development of fibrosis; however, the roles of the microbiome in the respiratory functions of hosts with IPF remain poorly understood. To investigate the relationship between the lung microbiome and the pathological processes of idiopathic pulmonary fibrosis under laboratory conditions, C57BL/6 J mice were exposed to bleomycin and observed at 7, 14, 21, and 28 days post-exposure. 16S rDNA analysis revealed that the lung microbial community exhibited dysbiosis in the bleomycin-induced pulmonary fibrosis model, characterized by an abnormally high proportion of Klebsiella quasipneumoniae (K. quasipneumoniae), as confirmed by RNA fluorescence in situ hybridization. Throughout the progression of experimental pulmonary fibrosis, Tax4Fun analysis indicated that the abundance of K. quasipneumoniae differed significantly between model mice and control mice, correlating with the sustained activation of reactive oxygen species (ROS) pathways. Importantly, the dysbiosis of K. quasipneumoniae may serve as a critical factor triggering increased ROS levels, accompanied by macrophage mitophagy, ultimately leading to the overexpression of TGF-β1, a key player in the pathogenesis of pulmonary fibrosis. These findings suggest that lung microbiota dysbiosis exacerbates the progression of bleomycin-induced pulmonary fibrosis related to macrophage mitophagy.

Dehydrocorydaline attenuates bleomycin-induced pulmonary fibrosis by inhibiting fibroblast activation

BackgroundPulmonary fibrosis (PF) is an irreversible, progressive, chronic and fatal interstitial lung disease with limited therapeutic options. Dehydrocorydaline (DHC), derived from the traditional Chinese medicinal plant Corydalis yanhusuo, has exhibited a variety of pharmacological properties. Nevertheless, the potential function and mechanism of DHC in the management of PF have yet to be elucidated.PurposeTo evaluate the therapeutical efficacy of DHC in different PF models and elucidate its underlying mechanism.MethodsA well-established Bleomycin-induced PF mouse model and human precision-cut lung slices (hPCLS) following fibrosis-inducing cocktail stimulation were employed. The antifibrotic effects of DHC on PF were measured by histopathological manifestation, immunofluorescent staining and expression levels of fibrosis related markers. Human primary pulmonary fibroblasts (HPFs) were used to explore the impact of DHC on fibroblast function and the underlying mechanism.ResultsHere, we demonstrated that DHC exhibited a therapeutic efficacy in Bleomycin-induced PF mouse model with a dose dependent, as well as in hPCLS after fibrosis-inducing cocktail stimulation, as evidenced by histopathological staining, decrease of Fibronectin, Collagen 1 and α-SMA expression. Additionally, in vitro experiments indicated that DHC effectively suppressed fibroblast to myofibroblast transition, but had no significant effect on the proliferation and migration of fibroblast. Mechanistic studies revealed that the inhibitory effect of DHC on fibroblast activation was dependent on the endoplasmic reticulum stress, thereby inhibiting TGF-β/SMAD signal pathway.ConclusionsOur study implied that DHC hold a promise therapeutic approach against PF by suppressing fibroblast activation. The safety and efficacy of DHC have been preliminary demonstrated in a mouse model.Graphical

Epigenetic profiles integrated with transcriptomic reveal the difference between COPD and PRISm in KOCOSS-NIH

In 2023, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) introduced a provision regarding preserved ratio-impaired spirometry (PRISm), a presumed pre-stage of Chronic Obstructive Pulmonary Disease (COPD), into the COPD guidelines. However, further research in this area is needed. Our study aimed to investigate the epigenetic differences between PRISm and COPD. EWAS (n = 572) and RNA-sequencing (n = 60) were performed on blood samples from the COPD registry, and EWAS was replicated in the KoGES cohort data (n = 98). Our findings revealed significant epigenetic differences between patients with PRISm and COPD. 39,980 CpG-sites displayed differential methylation between PRISm and COPD. Seven gene regions—EEF1A2, EMP2, EPCAM, MTSS1L, ARHGEF10, HYDIN, and FADS2 were not only differentially methylated but also exhibited differential expression. The consistency of differential methylation of CpG sites in five genes, excluding ARHGEF10 and MTSS1L, was replicated in the KoGES study, affirming the distinction between COPD and PRISm. Our research identified seven gene regions as critical contributors related to the modulation of gene expression, including CpG sites that differentiate COPD from PRISm. These results highlight the significance of DNA methylation changes in distinguishing PRISm from COPD and shed light on potential mechanisms by which methylation alterations impact lung function.

Early nintedanib deployment in COVID-19 interstitial lung disease (ENDCOV-I): study protocol of a randomised, double-blind, placebo-controlled trial

IntroductionIn December 2019, the novel SARS-CoV-2 triggered a global pneumonia outbreak, leading to millions of deaths worldwide. A subset of survivors faces increased morbidity and mortality, particularly due to subacute...

Docosahexaenoic Acid and Its Metabolites Protects Against Ozone-induced Pulmonary Inflammation.

Ozone (O3) is an air pollutant that induces pulmonary inflammation and injury, leading to increased susceptibility and exacerbation of chronic lung diseases. Furthermore, ambient O3 levels are expected to rise with increasing global temperatures. Docosahexaenoic acid (DHA) is an omega-3 (n-3) polyunsaturated fatty acid (PUFA) primarily found in oily fish that reduces inflammation and enhances the resolution of inflammation. This is partially attributed to DHA-derived oxylipins termed specialized pro-resolving mediators (SPMs) that have anti-inflammatory/pro-resolving properties. However, whether dietary DHA protects the lungs from O3-induced inflammation and injury is unclear. We hypothesized that dietary DHA supplementation increases pulmonary SPMs and thereby decreases O3-induced pulmonary inflammation. To test this, C57BL/6J mice were fed control diet or DHA-enriched diet (2% kcal from DHA) for 6 weeks, exposed to filtered air (FA) or 1 ppm O3 for 3h (comparable to an O3 Action Day for humans), and necropsied 24h or 48h following exposure. DHA supplementation reduced airspace neutrophilia, decreased cytokine production, and promoted transcriptomic signatures for leukocyte chemotaxis and fatty acid oxidation. Furthermore, dietary DHA increased pulmonary DHA and its oxylipins while decreasing pro-inflammatory n-6 PUFAs and their oxylipins. Oropharyngeal aspiration of DHA-oxylipins 14-HDHA or maresin 1 (MaR1) decreased O3-induced airspace neutrophilia and reduced bone marrow-derived macrophage production of neutrophil chemokines Cxcl1 and Cxcl2. These findings reveal that dietary DHA protects the lungs from O3 exposure by driving 14-HDHA and MaR1 production, which reduces neutrophil recruiting chemokine production by macrophages. This pathway highlights a potential therapeutic dietary approach for mitigating air pollution-induced pulmonary inflammation.