Common Chronic Lung Disease Research Articles

Downstream Effects of Market Changes on Inhalers: Impacts on Individuals With Chronic Lung Disease.

COPD and asthma are two of the most common chronic lung diseases, affecting over 545 million people globally and 34 million in the United States. Annual health care costs related to chronic lung disease are estimated at €380 billion in the European Union, and $24-$50 billion in the United States averaging to $4,000 in out-of-pocket costs per person in the U.S. A full-text literature search was conducted for English publications between January 1, 2005-March 18, 2024. It returned over 5,000 publications that were further narrowed using key search words, resulting in 172 peer-reviewed articles. Using their experience and subject expertise, the authors further narrowed the peer-reviewed articles to 55 that were in their opinion relevant. Also, 38 recently published industry reports and news articles specific to downstream effects of inhaler market changes and the future impact were included. The literature suggests that individuals with chronic lung disease face increased challenges with access to inhaled medication due to rising medication costs, discontinuation of branded medications, introduction of generic medications not covered by insurance, exclusionary preferred drug list tactics that force health care providers into non-medical switching of medication or devices, and ongoing medication shortages. Providers experience ongoing hurdles in prescribing appropriate inhaled medications for individuals with chronic lung disease, including increased time and costs spent on administrative tasks due to inhaler denials, a loss of patient trust, and limits on their ability to prescribe appropriate inhaled medication for individuals with chronic lung disease.

Characterization of Pseudomonas aeruginosa from subjects with diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB), a chronic lung disease characterized by persistent P. aeruginosa infection, serves as an informative comparator to more common chronic lung diseases, such as cystic fibrosis (CF). This study aimed to better address the interplay between P. aeruginosa and chronically compromised airway environments through the examination of DPB P. aeruginosa strains, as existing literature regarding DPB is limited to case reports, case series, and clinical treatment guidelines. The evaluation of these features in the context of DPB, in tandem with prevailing knowledge of P. aeruginosa strains collected from more common chronic lung diseases (e.g., CF), can aid in the development of more effective strategies to combat respiratory P. aeruginosa infections in patients with chronic lung diseases.

Relationship between functional status and fatigue after COVID-19 infection: a multicenter study from Türkiye.

Symptoms of COVID-19 may persist for months. One of the persistent symptoms of COVID-19 is fatigue, which reduces functional status. The relationship between fatigue, functional status, and various other factors has received little attention, which this study aims to address.. Patients with COVID-19 infection were included in this multicenter cross-sectional study. Age, sex, body mass index (BMI), marital status, smoking status, presence and duration of chronic disease, comorbidity index, regular exercise habits, time since COVID-19 diagnosis, hospitalization status, length of hospital stay, intubation status, home oxygen therapy after discharge, participation in a pulmonary rehabilitation program, presence of dyspnea, presence of cough, presence of sputum, and modified Medical Research Council, Post-COVID Functional Status (PCFS), Fatigue Severity Scale (FSS), and EQ-5D-5L Questionnaire scores were recorded. We enrolled 1095 patients, including 603 (55%) men and 492 (45%) women with a mean age of 50 ± 14 years. The most common chronic lung disease was COPD (11%) and 266 (29%) patients had nonpulmonary disease. The median time elapsed since COVID-19 diagnosis was 5 months; the hospitalization rate was 47%. The median PCFS grade was 1 (0-4) and the median FSS score was 4.4 (1-7). The PCFS and FSS were positively correlated (r = 0.49, p < 0.01; OR: 1.88, 95% CI: 1.68-2.10). Both functional status and fatigue were associated with quality of life, which was lower in older patients, those with higher BMI, those with systemic disease, those not exercising regularly, and those with more severe COVID-19 infection (defined by dyspnea, pneumonia as indicated by computed tomography, hospitalization, length of stay, ICU admission, intubation, and the need for home oxygen after discharge). Fatigue may cause poorer functional status regardless of the time since COVID-19 diagnosis. In this study, patients with FSS scores of >4.78 showed moderate to severe functional limitations. It is important to address modifiable patient risk factors and reduce the severity of COVID-19 infection.

Use of Antibiotics in Infancy and Asthma in Childhood: Confounded or Causal Relationship? A Critical Review of the Literature

Childhood asthma is among the most common chronic lung diseases in the pediatric population, having substantial consequences on the everyday life of children and their caregivers. There remains a lack of a singular, efficacious strategy for averting the inception of childhood asthma. The rate of pediatric antibiotic usage continues to be high, which makes it crucial to understand whether there exists a causal link between the use of antibiotics in infancy and the development of asthma in childhood. In this rostrum, we conduct a critical review of the literature concerning the association of infant antibiotic use and the onset of childhood asthma. Drawing upon the results of 5 meta-analyses addressing this topic and of a recent randomized controlled trial, a notable association emerges between antibiotic exposure in the first year of life and the occurrence of childhood asthma that appears to be beyond potential study limitations (such as reverse causation, confounding by indication, and recall bias). Furthermore, we highlight the need for additional research in this field that could improve our understanding of important aspects of this association and lead to the design of an intervention aimed to deliver antibiotics safely during early life and reduce the burden of childhood asthma.

Incidence and Predictors of Bronchopulmonary Dysplasia Development and Severity Among Preterm Infants Born at 32 Weeks of Gestation or Less.

Background As the most common chronic lung disease (CLD) related to premature birth, bronchopulmonary dysplasia (BPD) is associated with long-term lung disease along with cardiovascular and neurodevelopmental disorders. However, data on the incidence and predictors of BPD in Qatar are lacking. Objectives In this study, we aimed to determine the incidence of BPD among infants born at ≤ 32 weeks gestational age (GA) at our neonatal unit, and identify risk factors for the development of BPD and moderate-severe BPD. Methods This was a retrospective observational cohort study conducted at a single site: a level-III neonatal intensive care unit (NICU) in Qatar. We included 1539 neonates born at ≤ 32 weeks of gestation with birth weights of ≤ 1500 grams who were admitted to the NICU between 2017 and 2020. Univariate and multivariate logistic regression analyses were performed to identify potential factors and predictors and their possible associations with the development of BPD and moderate-severe BPD. We also applied BPD classifications to determine the variability in the incidence of BPD in our cohort according to various definitions (2001 National Institute of Child Health and Human Development (NICHD) Diagnostic Criteria, 2016 Revisions of NICHD Criteria, and 2019 Neonatal Research Network Jensen Grading). Results A total of 451 infants (29.3%) had BPD (BPD group) while 1088 (70.7%) did not (non-BPD group), and the overall incidence of BPD was 29.3%. The most relevant risk factors associated with a higher risk of developing BPD identified in the multivariate logistic regression analysis were appropriate weight for gestational age (adjusted OR (aOR) 3.67, 95%CI 2.02-6.67, P < 0.001), presence of patent ductus arteriosus (PDA) (aOR 2.61, 95%CI 1.86-3.66, P < 0.001), late-onset sepsis (aOR 2.16; 95%CI 1.29-3.62; P = 0.003), and use of invasive ventilation (aOR 1.90; 95%CI 1.35-2.69; P < 0.001). The most relevant independent risk factors associated with a higher risk for developing moderate-severe BDP were postnatal steroids (aOR 7.12, 95%CI 3.77-13.44, P < 0.001), use of inhaled nitric oxide (aOR 3.65, 95%CI 1.48-9.01, P = 0.005), use of invasive ventilation (aOR 2.13, 95%CI 1.13-4.00, P = 0.019), late-onset sepsis (aOR 2.07, 95%CI 1.10-3.91, P = 0.025), and male sex (aOR 2.04, 95%CI 1.24-3.36, P = 0.005). The difference in the distribution of BPD severity across the three different definitions of NICHD was significant (P < 0.001). Conclusion The results of this study showed that the incidence of BPD remained high in infants born at ≤ 32 weeks of gestational age and birth weight <1500 g with appropriate weight for gestational age. The presence of PDA at birth or first echocardiography, late-onset sepsis, and use of invasive ventilation were significant risk factors for the incidence of BPD. The identification of risk factors will contribute to the implementation of lung-protective strategies for at-risk infants who may benefit from potential preventive therapy.

Management of lung diseases under ultrasound monitoring: potential to make bronchopulmonary dysplasia in preterm infants as an avoidable disease

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants. Despite significant progress in the understanding of its etiology, mechanisms, prevention, and treatment, the prognosis remains poor. BPD not only has a high mortality rate but also causes persistent respiratory, neurological, and cardiovascular impairments in survivors. The author's team has successfully prevented the occurrence of BPD by managing neonatal lung diseases under lung ultrasound monitoring for nearly 7 years, opening up a new approach in BPD prevention. This article provides a brief overview of the approach, aiming to facilitate further research and provide more scientifically sound management strategies to prevent or minimize the occurrence of BPD.

IRF4 affects the protective effect of regulatory T cells on the pulmonary vasculature of a bronchopulmonary dysplasia mouse model by regulating FOXP3

BackgroundBronchopulmonary dysplasia (BPD) is a common chronic lung disease in preterm infants, characterised by compromised alveolar development and pulmonary vascular abnormalities. Emerging evidence suggests that regulatory T cells (Tregs) may confer protective effects on the vasculature. Knockdown of their transcription factor, interferon regulatory factor 4 (IRF4), has been shown to promote vascular endothelial hyperplasia. However, the involvement of Tregs and IRF4 in the BPD pathogenesis remains unclear. This study aimed to investigate the regulation of Tregs by IRF4 and elucidate its potential role in pulmonary vasculature development in a BPD mouse model.MethodsThe BPD model was established using 85% hyperoxia exposure, with air exposure as the normal control. Lung tissues were collected after 7 or 14 days of air or hyperoxia exposure, respectively. Haematoxylin–eosin staining was performed to assess lung tissue pathology. Immunohistochemistry was used to measure platelet endothelial cell adhesion molecule-1 (PECAM-1) level, flow cytometry to quantify Treg numbers, and Western blot to assess vascular endothelial growth factor (VEGFA), angiopoietin-1 (Ang-1), forkhead box protein P3 (FOXP3), and IRF4 protein levels. We also examined the co-expression of IRF4 and FOXP3 proteins using immunoprecipitation and immunofluorescence double staining. Furthermore, we employed CRISPR/Cas9 technology to knock down the IRF4 gene and observed changes in the aforementioned indicators to validate its effect on pulmonary vasculature development in mice.ResultsElevated IRF4 levels in BPD model mice led to FOXP3 downregulation, reduced Treg numbers, and impaired pulmonary vascular development. Knockdown of IRF4 resulted in improved pulmonary vascular development and upregulated FOXP3 level.ConclusionIRF4 may affect the protective role of Tregs in the proliferation of pulmonary vascular endothelial cells and pulmonary vascular development in BPD model mice by inhibiting the FOXP3 level.

Differential lung gene expression identified Zscan2 and Bag6 as novel tissue repair players in an experimental COPD model.

Chronic obstructive pulmonary disease is a common chronic lung disease with an ever-increasing incidence. Despite years of drug research and approvals, we are still not able to halt progress or restore normal lung function. Our previous studies have demonstrated that liver growth factor-LGF has an effect on the repair of the affected tissue in a mouse model of cigarette smoke exposure, but by what pathways it achieves this is unknown. The present study aimed to identify differentially expressed genes between emphysematous mice treated with LGF to identify potential therapeutic targets for the treatment of pulmonary emphysema. The emphysema mouse model was induced by prolonged exposure to cigarette smoke. To determine the gene expression profile of the lung in smokers treated or not with LGF, lung messenger RNA gene expression was assessed with the Agilent Array platform. We carried out differentially expressed gene analysis, functional enrichment and validated in treated mouse lung samples. The treated group significantly improved lung function (~35%) and emphysema level (~20%), consistent with our previous published studies. Microarray analysis demonstrated 290 differentially expressed genes in total (2.0-fold over or lower expressed). Injury repair-associated genes and pathways were further enhanced in the lung of LGF treated mice. The expression trends of two genes (Zscan2 and Bag6) were different in emphysematous lungs treated with LGF compared to untreated lungs. Therefore, Zscan2 and Bag6 genes could play a role in regulating inflammation and the immune response in the lung that undergoes partial lung regeneration. However, further studies are necessary to demonstrate this causal relationship.

Montelukast Sodium to Prevent and Treat Bronchopulmonary Dysplasia in Very Preterm Infants: A Quasi-Randomized Controlled Trial.

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants and lacks effective methods for prevention and treatment. The aim of this study is to explore the efficacy and safety of montelukast in preventing or treating BPD in preterm infants. The preterm infants with BPD risk factors were divided randomly into a montelukast group and a control group. In the montelukast group, preterm infants were given 1 mg/kg of montelukast sodium daily. There was no placebo in the control group. There was no significant difference in the incidence of moderate or severe BPD between the two groups (31.8% vs. 35%). The duration of respiratory support in the montelukast group was shorter than that in the control group (36.4 ± 12.8 d vs. 43.1 ± 15.9 d, p = 0.037). The pulmonary severity score (PSS) at 21 days of life in the montelukast group was significantly lower than that in the control group (0.56 ± 0.13 vs. 0.62 ± 0.14, p = 0.048). There were no significant differences in the duration of mechanical ventilation, length of stay, hospitalization expenses, or incidence of adverse events. Although montelukast cannot alleviate the severity of BPD, it may shorten the duration of respiratory support and decrease the PSS in very preterm infants. There were no significant adverse drug events associated with montelukast treatment.

Gm15886-Hipk1 Signaling Pathway Plays Important Roles in the Pathogenesis of Bronchopulmonary Dysplasia Mice

Background: Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in the respiratory system of premature infants. Gm15886, as a lncRNA, is highly expressed in lung tissue of BPD newborn mice. Aims: This study aimed to clarify the roles of the Gm15886 gene in the pathogenesis of BPD mice by determining the expression of Gm15886 and Hipk1 in lung tissues. Methods: Sequence and localization of the Gm15886 gene and the related information of its adjacent genes were obtained using the UCSC browsing tool. The targeting gene of the Gm15886 was predicted using the Ensemble database and double luciferase assay. Neonatal C57BL/6J mice were exposed to 95% hyperoxia for 7 days to generate the hyperoxia-induced BPD mouse model. RT-PCR assay was used to detect Gm15886, Hipk1, and VEGF gene transcriptions in lung tissues in the development process of BPD (0, 3, 5, and 7 days). The pathological changes in lung tissues and Hipk1/VEGF gene transcription in lung tissues were detected in the Gm15886 gene silenced BPD mice. Results: Gm15886 gene transcription in lung tissues was significantly increased in mice of the hyperoxia model group compared to that in the air control group (p&lt;0.05). Gm15886 gene could completely bind and interact with the base sequence within the second exon of the Hipk1 gene. Hipk1 was a targeting gene for Gm15886. Gene transcription and expression of Hipk1 were remarkably enhanced in mice of the hyperoxia model group compared to that in the air control group (p&lt;0.05). The silencing of the Gm15886 gene improved alveolar morphology and markedly downregulated Hipk1 and upregulated VEGF gene transcription compared to those in the Blank vector BPD group (p&lt;0.05). Conclusions: Gm15886-Hipk1 signaling pathway plays a critical role in the pathogenesis of BPD through modulating Hipk1 and VEGF gene transcription. This study might provide a theoretical basis for the treatment of BPD.

Assessment of Work Ability of Patients with COPD in Relation to the Workplace.

Chronic obstructive pulmonary disease (COPD) is one of the most common chronic lung diseases and is an important cause of mortality and morbidity in the world. Chronic obstructive pulmonary disease is a heterogeneous and multisystemic disease. Aims of the study was to assess workability of patients with COPD in relation to the workplace. Prospective study. The study was conducted on 150 patients with COPD. Each patient was examined by an occupational medicine specialist and a standardized COPD Questionnaire was completed. A physical examination was performed with special emphasis on auscultatory findings on the lungs. Spirometric testing was performed. Using the statistical methods, the results of the parameters of temporary (number of lost working days) and permanent incapacity (exercised right to some kind of disability) of the examined group were analyzed. Descriptive statistics. SPSS 10.0. Results of the study showed that out of 150 patients, 48.67% had preserved working capacity for jobs. There are mostly jobs without special working conditions. Out of 150 patients, 51.33% had reduced working capacity for jobs. These are mostly workplaces with special working conditions, where respondents are exposed to the harmfulness of the workplace. Reduced working capacity was found in 51.33% of examined simple.

Nutrition-based implications and therapeutics in the development and recovery of bronchopulmonary dysplasia

Premature births account for over 10% of live births worldwide. Bronchopulmonary dysplasia (BPD) represents a severe sequela in neonates born very prematurely and remains the most common chronic neonatal lung disease, often leading to serious adverse consequences in adulthood. Nutrition plays a crucial role in lung development and repair. Ongoing research has primarily focused on the pathogenesis and prevention of BPD in preterm birth. However, infants with established BPD need specialist medical care that persists throughout their hospitalization and continues after discharge. This manuscript aims to highlight the impact of growth and nutrition on BPD and highlight research gaps to provide direction for future studies. Protective practices include ensuring adequate early energy delivery through parenteral nutrition and enteral feedings while carefully monitoring total fluid intake and the use of breast milk over formula. These nutritional strategies remain the same for infants with established BPD with the addition of limiting the use of diuretics and steroids; but if employed, monitoring carefully without compromising total energy delivery. Functional nutrient supplements with a potential protective role against BPD are revisited, despite the limited evidence of their efficacy, including vitamins, trace elements, zinc, lipids, and sphingolipids. Planning post-intensive care and outpatient longitudinal nutrition support is critical in caring for an infant with established BPD.

A digital health application for managing pediatric asthma: Use and benefits

ABSTRACTChildhood asthma is a common and serious chronic lung disease. Mobile health (mHealth) technologies may assist clinical providers, caregivers, and children in managing pediatric asthma. This study evaluated the Nemours app, an mHealth application. We examined: a) frequency of data access by providers and feature use by caregivers (parents/legal guardians) of 5–11-year-old children diagnosed with asthma and b) whether utilization was related to benefits. Nine providers (allergists/pulmonologists) and 80 patient-families (caregiver/child dyads) participated. Two-years of retrospective data were obtained for asthma control, in-person urgent healthcare utilization, and app utilization. Six-months of prospective data included asthma control, in-person urgent healthcare utilization, app utilization, surveys, and health literacy screeners. Providers (56%) accessed app data and caregivers (61%) utilized the app. Caregiver use of messaging feature predicted gains in health literacy scores (b = .44, p = .041), suggesting app use may offer some educational benefits. Implementation of strategies that support app engagement and utilization may help to maximize intended benefits.

Therapeutic Effect of Atorvastatin on Interleukin-13- Induced Lung Pathology

PPurpose: Asthma is a common chronic lung disease, in which interleukin (IL)-13 is implicated as a central regulator of IgE synthesis, mucus hypersecretion, airway hyperresponsiveness (AHR), and fibrosis. This study was designed to determine the anti-inflammatory effect of atorvastatin, a widely used lipid-lowering agent, on IL-13-induced lung pathology through the modulation of macrophages. Methods: Atorvastatin (40 mg/ kg) was given to transgenic mice overexpressing IL-13 (IL-13 TG mice) and their wild type littermates by oral gavage for 2 weeks. AHR, the number of inflammatory cells in the airway, and cytokine levels in IL-13 TG mice were measured. Using the alveolar macrophage (AM) cell line CRL-2456, the direct effect of atorvastatin on macrophages activated by recombinant IL-13 was assessed. Results: Significant reduction in total leukocytes and alleviation of AHR were observed with the administration of atorvastatin in IL-13 TG mice compared to those without atorvastatin treatment (P &lt; 0.05). Atorvastatin administration resulted in the upregulation of IL-10 in the lungs of IL-13 TG mice (P &lt; 0.05). In addition, mRNA expression of connective tissue growth factor, fibronectin, and type III collagen as well as chord length enhanced by IL-13 overexpression were reduced by atorvastatin administration (P &lt; 0.05). M2 macrophage markers were decreased, while the M1 macrophage marker was increased upon atorvastatin treatment (P &lt; 0.05). Administration of atorvastatin resulted in improved removal of apoptotic cells (P &lt; 0.05). Conclusion: The results of this study reveal the potential of atorvastatin as an effective anti-asthmatic agent by reducing IL-13-induced lung inflammation via the modulation of macrophage polarization.

Human pulmonary microvascular endothelial cell DDAH1-mediated nitric oxide production promotes pulmonary smooth muscle cell apoptosis in co-culture.

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants, and pulmonary hypertension (PH) develops in 25%-40% of patients with BPD, increasing morbidity and mortality. BPD-PH is characterized by vasoconstriction and vascular remodeling. Nitric oxide (NO) is a pulmonary vasodilator and apoptotic mediator made in the pulmonary endothelium by NO synthase (eNOS). Asymmetric dimethylarginine (ADMA) is an endogenous eNOS inhibitor, primarily metabolized by dimethylarginine dimethylaminohydrolase-1 (DDAH1). Our hypothesis is that DDAH1 knockdown in human pulmonary microvascular endothelial cells (hPMVEC) will result in lower NO production, decreased apoptosis, and greater proliferation of human pulmonary arterial smooth muscle cells (hPASMC), whereas DDAH1 overexpression will have the opposite effect. hPMVECs were transfected with small interfering RNA targeting DDAH1 (siDDAH1)/scramble or adenoviral vector containing DDAH1 (AdDDAH1)/AdGFP for 24 h and co-cultured for 24 h with hPASMC. Analyses included Western blot for cleaved and total caspase-3, caspase-8, caspase-9, β-actin; trypan blue exclusion for viable cell numbers; terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL); and BrdU incorporation. Small interfering RNA targeting DDAH1 (siDDAH1) transfected into hPMVEC resulted in lower media nitrites, cleaved caspase-3 and caspase-8 protein expression, and TUNEL staining; and greater viable cell numbers and BrdU incorporation in co-cultured hPASMC. Adenoviral-mediated transfection of the DDAH1 gene (AdDDAH1) into hPMVEC resulted in greater cleaved caspase-3 and caspase-8 protein expression and lower viable cell numbers in co-cultured hPASMC. Partial recovery of hPASMC viable cell numbers after AdDDAH1-hPMVEC transfection was observed when media were treated with hemoglobin to sequester NO. In conclusion, hPMVEC-DDAH1-mediated NO production positively regulates hPASMC apoptosis, which may prevent/attenuate aberrant pulmonary vascular proliferation/remodeling in BPD-PH.NEW & NOTEWORTHY BPD-PH is characterized by vascular remodeling. NO is an apoptotic mediator made in the pulmonary endothelium by eNOS. ADMA is an endogenous eNOS inhibitor metabolized by DDAH1. EC-DDAH1 overexpression resulted in greater cleaved caspase-3 and caspase-8 protein expression and lower viable cell numbers in co-cultured SMC. After NO sequestration, SMC viable cell numbers partially recovered despite EC-DDAH1 overexpression. EC-DDAH1-mediated NO production positively regulates SMC apoptosis, which may prevent/attenuate aberrant pulmonary vascular proliferation/remodeling in BPD-PH.

Rad1 attenuates DNA double-strand breaks and cell cycle arrest in type II alveolar epithelial cells of rats with bronchopulmonary dysplasia

BackgroundBronchopulmonary dysplasia (BPD) is the most common and serious chronic lung disease in preterm infants with pathological characteristics of arrested lung development. DNA double-strand breaks (DSBs) are a serious manifestation of oxidative stress damage, but little is known about the role of DSBs in BPD. The current study set out to detect DSB accumulation and cell cycle arrest in BPD and study the expression of genes related to DNA damage and repair in BPD through DNA damage signaling pathway-based PCR array to determine a suitable target to improve arrested lung development associated with BPD.MethodsDSB accumulation and cell cycle arrest were detected in a BPD animal model and primary cells, then a DNA damage signaling pathway-based PCR array was used to identify the target of DSB repair in BPD.ResultsDSB accumulation and cell cycle arrest were shown in BPD animal model, primary type II alveolar epithelial cells (AECII) and cultured cells after exposure to hyperoxia. Of the 84 genes in the DNA damage-signaling pathway PCR array, eight genes were overexpressed and 11 genes were repressed. Rad1, an important protein for DSB repair, was repressed in the model group. Real-time PCR and western blots were used to verify the microarray results. Next, we confirmed that silencing Rad1 expression aggravated the accumulation of DSBs and cell cycle arrest in AECII cells, whereas its overexpression alleviated DSB accumulation and cell cycle arrest.ConclusionsThe accumulation of DSBs in AECII might be an important cause of alveolar growth arrest associated with BPD. Rad1 could be an effective target for intervention to improve this arrest in lung development associated with BPD.

Treatment with oral or inhaled bronchodilator without inhaled corticosteroids in bronchial asthma: A dangerous weapon!

Abstract Bronchial asthma is the most common chronic lung disease in the obstructive airway disease category with the characteristic feature of “reversible” airflow obstruction. Despite an increase in awareness of risk factors, diagnosis, and treatment options available to treat bronchial asthma, more than half of cases received irrational treatment. Inadequate treatment is reasoning more morbidity and mortality of this easily treatable disease. Inhaled short- and long-acting bronchodilators, antimuscarinic agents, and inhaled corticosteroids (ICSs) are the cornerstone of the treatment of asthma and are categorized as “rescue and controller” role in disease management. Bronchodilators without ICSs are not recommended because of more harm than benefit in bronchial asthma. ICSs are the gold standard and the recommended treatment for asthma due to their anti-inflammatory and disease-modifying property labeled as “game changer role.” Bronchodilators with ICSs will have added benefit of symptom control, improvement in quality of life, and decrease in exacerbation. Combo of bronchodilators with ICSs will decrease the overall cost of care in asthma by improving disease control and decrease in emergency room visits and hospitalizations in intensive care units due to exacerbations.

Changes in targeted metabolomics in lung tissue of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common chronic lung disease and its incidence is steadily increasing. COPD patients and mouse models of COPD share some similarities in lung pathology and physiology. We performed this study to explore the potential metabolic pathways involved in the pathogenesis of COPD and to discover the COPD-associated biomarkers. Furthermore, we aimed to examine how much the mouse model of COPD was similar and different to human COPD in terms of the altered metabolites and pathways. Twenty human lung tissue samples (ten COPD and ten controls) and twelve mice lung tissue samples (six COPD and six controls) were analyzed by targeted HM350 metabolomics, and multivariate and pathway analysis were performed by Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The counts of many metabolites such as amino acids, carbohydrates and carnitines were changed in both COPD patients and mice compared to controls, respectively. While lipid metabolism was changed only in COPD mice. After KEGG analysis, we found these altered metabolites involved in COPD through aging, apoptosis, oxidative stress and inflammation pathways. The expressions of metabolites changed in both COPD patients and cigarette smoke exposed (CS-exposed) mice. And there were also some differences between COPD patients and mouse models due to the differences between species. Our study suggested the dysregulation in amino acid metabolism, energy production pathway and perhaps lipid metabolism may be significantly related to the pathogenesis of COPD.

Effects of chronic neonatal hyperoxia-induced bronchopulmonary dysplasia on breathing, energy expenditure, and growth in young, adolescent, and adult mice

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease associated with preterm birth. Growth failure is common in infants with BPD and is associated with increased resting metabolic rate (RMR). Whether increased RMR and growth failure are a consequence of BPD lung pathology per se, or a consequence of clinical interventions remains unknown. Herein, we sought to determine the effects of BPD-like lung injury on breathing, growth, and energy expenditure in C57BL/6J male mice exposed to chronic hyperoxia (Hx; 70% O2; n=5) or normoxia (Nx; n=6) in the neonatal period (postnatal day (P) 0-14). Consistent with prior reports and human BPD, Hx lungs at P21 had reduced alveoli and alveolar density indicated via H&amp;E lung sections. Also, Hx mice had altered respiratory responses to acute hypoxia (10 min; 12% O2) including a reduced hypoxic ventilatory response (108±6 Nx vs 89±4 % Hx; p&lt;0.05) and drive to breathe (tidal volume/inspiratory time; 0.98±0.06 vs 0.76±0.04; p&lt;0.05). The pattern of breathing during the acute challenge favors longer inspiratory time (132±6 vs 170±9 ms, p&lt;0.05) which may reflect a compensatory response to reduced alveoli. Despite these differences, no differences in body composition (body, fat and fat-free masses, and total body water) were observed at P21, 6wks, or 8wks of life. Furthermore, there were no differences in ingestive behaviors, or total or resting aerobic heat production (kcal/h) at 8 wks of age, yet Hx mice had reduced locomotor activity (199±10 vs 154±11 m/d; p&lt;0.05) which may indicate reduced exercise capacity. In a subset of mice (n=2/group), a 20% increase in right ventricular mass was noted, consistent with some degree of pulmonary hypertension, along with a 3% decrease in hematocrit, which may reflect a programmed change in hematopoiesis after early-life Hx. Together, these data document the impact of BPD-like lung injury on key physiological parameters and support the iconoclastic concept that BPD pathology per se does not drive increased RMR or growth failure. By extension, other factors – possibly including side-effects of well-intentioned clinical interventions – may underly growth failure in children with BPD. We speculate that sodium depletion resulting from diuretic therapy, which is common for this condition and known to impact infant growth, may be an important contributor to growth failure in infants with BPD. GCM: AHA 20CDA35310121; JLG: DK133121, HL134850, and HL084207; JLS: DK133121 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Anti-Inflammatory Peptide TnP Is a Candidate Molecule for Asthma Treatment.

Asthma is the most common chronic lung disease, with increasing morbidity and mortality worldwide. Accumulation of peribronchial leukocytes is the hallmark of asthma, in particular, eosinophils, which have been reported as the primary cell associated with the induction of airway hyperresponsiveness. Continued exacerbation and accumulation of other leukocytes, such as neutrophils, Th1, and Th17 cells correlate with many of the long-term effects of asthma, such as airway remodeling. We have patented the TnP family of synthetic cyclic peptides, which is in the preclinical phase of developmental studies for chronic inflammatory diseases. The aim of this work was to investigate whether TnP could show anti-inflammatory activity in a murine model of asthma that includes a mixed phenotype of eosinophilic and neutrophilic inflammation. For this, Balb/c mice, sensitized with OVA and exposed to 1% challenge with OVA aerosol, were submitted to prophylactic treatment, receiving TnP at 0.3 mg/kg orally, 1 h before each challenge. We found that sensitized mice challenged with OVA and treated with TnP showed no airway hyperreactivity or lung remodeling. TnP acts systemically in secondary lymphoid organs and locally in the lung, inhibiting the production of Th2/Th17 cytokines. Furthermore, TnP prevented the infiltration of eosinophils and neutrophils in the BAL and lung tissue, inhibited the production of IgE/IgG1, prevented hyperplasia of mucus-producing cells, and decreased the thickening and deposition of sub-epithelial collagen. Our results showed TnP as a candidate molecule for the treatment of airway remodeling associated with inflammatory diseases, such as asthma.