Increased Lung Function Research Articles

Longitudinal association between hemoglobin and lung function with insights into the incidence of airflow obstruction: an observational study

Background/AimsEvidence regarding the long-term association between hemoglobin (Hb) levels and lung function in individuals from the general population is scarce. This study aimed to determine the longitudinal association between Hb levels and lung function in a community-based population cohort in South Korea.MethodsWe used linear mixed regression analysis to evaluate the longitudinal associations between Hb levels and lung function parameters, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1/FVC. Additionally, we used a generalized estimating equation to calculate the odds ratio (OR) of airflow obstruction (AO) according to the Hb level.ResultsOver an 8-year biennial follow-up of 4,468 individuals (median age, 53.9 years; men, 49.0%), we observed that in men, Hb levels were positively associated with lung function (estimated values of FVC: 16.7 mL, FEV1: 15.5 mL, FEV1/FVC: 0.18%; all P < 0.001) and a decreased incidence of AO (OR = 0.83, P < 0.001). In women, Hb levels were positively associated with FVC but not with FEV1 or FEV1/FVC (estimated values of FVC: 4.7 mL, P = 0.045; FEV1: 3.1 mL, P = 0.142; FEV1/FVC: 0.01%, P = 0.838). The incidence of AO was not significantly different among women (OR = 0.93, P = 0.568). In postmenopausal women, higher Hb levels were associated with increased lung function (estimated values of FVC: 11.8 mL, P < 0.001; FEV1: 9.8 mL, P < 0.001; FEV1/FVC: 0.09%, P = 0.052), but the incidence of AO was not statistically significant (OR = 0.82, P = 0.129).ConclusionsA decreased Hb level was associated with reduced lung function and an increased incidence of AO in men.

A molecular toxicological study to explore potential health risks associated with ultrafine particle exposure in cold and humid indoor environments.

Environmental pollutants including ultrafine particulate matter (UFPs) and adverse meteorological conditions pose significant public health impacts, particularly affecting respiratory health. This study aims to elucidate the synergistic effects of cold-humid conditions and UFPs exposure on respiratory health, utilizing Carbon Black Nanoparticles (CB-NPs) as surrogates for UFPs. Through comprehensive lung function tests, histopathological examinations, and biomarker analyses, this research focuses on the modulation of oxidative stress signaling pathways and NF-κB activation. Male Balb/c mice were exposed to specific concentrations of CB-NPs (30-50 nm in diameter, 0.184 mg/(kg·day)) in a controlled environmental chamber mimicking cold (10°C/14°C) and humid (90 % RH) conditions over three weeks. The results indicate that exposure to CB-NPs alone increased lung function, oxidative stress (ROS, GSH, MDA), inflammation (IL-6, TNF-α, IL-1β), apoptosis (Caspase 3, Caspase 8, Caspase 9), and histopathological alterations in lung tissue. Furthermore, these effects were notably more severe under combined exposure with cold-humid conditions. These results suggest that the adverse effects of pollutants are not solely concentration-dependent but are exacerbated by specific environmental contexts. It is evident that Vitamin E (100 mg/kg/day) can attenuate these adverse effects, underscoring its potential as a protective agent against environmental stressor-induced air pollutants and cold humid conditions. Our findings suggest that the synergistic effects of environmental factors and pollutant exposure significantly impact respiratory health, providing valuable insights for the design of healthier indoor environments and the development of strategies to mitigate these risks.

Preoperative Inspiratory Muscle Training in Patients Undergoing Coronary Artery Bypass Graft Surgery: A Practical Guidance for Rehabilitation Physicians

Introduction: Coronary artery bypass graft (CABG) surgery increases the life expectancy of coronary artery disease patients, but the surgery itself causes postoperative pulmonary complications (PPC). PPC was associated with a decrease in respiratory muscle and lung function. Inspiratory muscle trainer (IMT) has been used in cardiac rehabilitation for post-CABG surgery patients. This review aimed at guiding clinical practitioners in preoperative IMT use. Methods: Articles written in English were searched using PubMed, EBSCOhost, and Google Scholar databases without limitation of year of publication used relevant keywords. The inclusion criteria were participants undergoing CABG surgery in the pre-operative period and were given threshold IMT. Result and Discussion: Preoperative IMT did not increase lung function, but it prevented a decrease in lung function postoperatively. The incidence of PPC was lower and the length of stay was shorter in patients who were given preoperative IMT compared to the control. Preoperative IMT also increased the strength and endurance of inspiratory muscles associated with decreased PPC. Conclusion: Preoperative IMT given to patients undergoing CABG surgery has been proven to prevent PPC and increase respiratory muscle function. This review provides practical guidance for preoperative IMT administration to improve outcomes of patients undergoing CABG surgery.

Long-Term Clinical Efficacy of Elexacaftor-Tezacaftor-Ivacaftor in People With Cystic Fibrosis and Preexisting Advanced Lung Disease at Treatment Initiation

BackgroundElexacaftor-tezacaftor-ivacaftor (ETI) is associated with increased forced expiratory volume in the first second (FEV1), decreased exacerbation frequency, and increased body mass index (BMI) in people with Cystic Fibrosis (pwCF) [1, 2]. Landmark clinical trials excluded patients with advanced lung disease (ALD) as defined by FEV1<40%. We have previously reported an improvement in ppFEV1 of 7.9% after 3 months of ETI in people with CF and ALD (ACFLD)[3]. The long-term effects of ETI on this cohort are unknown. This study reports the efficacy of ETI following 24 months of treatment in people with ACFLD. Study DesignWe conducted a retrospective cohort study of adult patients with FEV1<40% and/or other high-risk features defined by the 2019 CFF lung transplant guidelines who were started on ETI between September 2019 and February 2020. Response to therapy was assessed with repeat spirometry measured at 12 and 24 months. All measurements were taken outside of an acute exacerbation. Demographics and clinical data including BMI and pulmonary exacerbation frequency were extracted from the medical record. Results57 of 64 people with ACFLD showed improved lung function with a mean change in ppFEV1 of 6.74% (p = <0.001, 95% CI 4.25 – 9.23%) between baseline and 24 months of treatment. BMI increased by a mean change of 1.55 kg/m2 (p = <0.001, 95% CI 0.93 – 2.18 kg/m2) during this interval. The annual exacerbation rate between the year before ETI and 24 months on ETI declined with a median of 1 fewer per year (p = 0.0007). InterpretationPeople with ACFLD experienced a significant increase in lung function at 24 months on ETI, although less than those with higher baseline lung function compared to prior studies [1, 2]. They also had an increase in BMI and a decline in the rate of annual pulmonary exacerbations.

Efficacy and safety of moxibustion as a complementary and alternative therapy for asthma: A systematic review and meta-analysis

ObjectiveThis systematic review of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of moxibustion as a complementary or alternative treatment for asthma. MethodsSeven databases were searched up to June 23, 2024, to identify RCTs assessing moxibustion for bronchial asthma. The outcomes of interest included response to treatment, asthma control, quality of life, lung function, immunological indicators, and incidence of adverse events (AEs). The treatment effects were measured by proportional odds ratios or mean differences with 95% confidence intervals. ResultsThirty-seven RCTs (n = 2,879) were included. Moderate- to very low-quality evidence showed that compared with anti-asthmatic drugs alone, moxibustion plus anti-asthmatic drugs led to a significantly better response and greater increases in lung function, asthma control, and IgE levels. However, the combination therapy had no effect on children’s quality of life. In the active comparisons, moxibustion resulted in a superior response to treatment and a greater improvement in asthma control and had comparable effects on lung function, quality of life, and IgE levels compared with anti-asthmatic drugs. The effects of moxibustion on the proportions of CD4 + and CD8 + T cells and the eosinophil count were inconsistent between the add-on and active comparisons. All reported AEs related to moxibustion were mild. ConclusionsMoxibustion, as an adjunctive treatment or used alone, may improve the response to treatment, lung function, asthma control, and IgE levels in patients with asthma with good safety. Its effects on children’s quality of life and immune cell levels remain uncertain.

The relevance of eosinophils in chronic obstructive pulmonary disease: inflammation, microbiome, and clinical outcomes.

Chronic obstructive pulmonary disease is caused by the inhalation of noxious particles such as cigarette smoke. The pathophysiological features include airway inflammation, alveolar destruction, and poorly reversible airflow obstruction. A subgroup of patients with chronic obstructive pulmonary disease has higher blood eosinophil counts, associated with an increased response to inhaled corticosteroids and increased biomarkers of pulmonary type 2 inflammation. Emerging evidence shows that patients with chronic obstructive pulmonary disease with increased pulmonary eosinophil counts have an altered airway microbiome. Higher blood eosinophil counts are also associated with increased lung function decline, implicating type 2 inflammation in progressive pathophysiology in chronic obstructive pulmonary disease. We provide a narrative review of the role of eosinophils and type 2 inflammation in the pathophysiology of chronic obstructive pulmonary disease, encompassing the lung microbiome, pharmacological targeting of type 2 pathways in chronic obstructive pulmonary disease, and the clinical use of blood eosinophil count as a chronic obstructive pulmonary disease biomarker.

Clinical, economic, and societal burden of cystic fibrosis and the impact of the CFTR modulator, lumacaftor/ivacaftor: an assessment using linked registry data in Sweden

Aims We aimed to describe the clinical, economic, and societal burdens of cystic fibrosis (CF) and impact of CF transmembrane conductance regulator modulator (CFTRm) treatment on people with CF, caregivers, and healthcare systems. Material and methods This retrospective study used linked real-world data from Swedish national population-based registries and the Swedish CF Quality Registry to assess clinical, economic, and societal burden and CFTR impact in CF. Records from people with CF and a ten-fold control population without CF matched by sex, birth year, and location were compared during 2019. Outcomes for a subset aged >6 years initiating lumacaftor/ivacaftor (LUM/IVA) in 2018 were compared 12 months pre- and post-treatment initiation. Results People with CF (n = 743) had >10 times more inpatient and outpatient specialist visits annually vs controls (n = 7406). Those aged >18 had an additional 77·7 (95% CI: 70·3, 85·1) days of work absence, at a societal cost of €11,563 (95% CI: 10,463, 12,662), while caregivers of those aged <18 missed an additional 6.1 (5.0, 7.2) workdays. With LUM/IVA treatment, people with CF (n = 100) had significantly increased lung function (mean change in ppFEV1 [3·8 points; 95% CI: 1·1, 6·6]), on average 0·5 (95% CI: −0·8, −0·2) fewer pulmonary exacerbations and 45·2 (95% CI: 13·3, 77·2) fewer days of antibiotics. Days of work lost by caregivers of people with CF aged <18 decreased by 5·4 days (95% CI: 2·9, 7·9). Conclusion CF is associated with a high clinical economic and societal burden in Sweden. Improvements in clinical status observed in people with CF treated with LUM/IVA were reflected in reduced caregiver and societal burden.

The Possible Roles of IL-4/IL-13 in the Development of Eosinophil-Predominant Severe Asthma.

Bronchial asthma is characterized by airway inflammation, airway hyperresponsiveness, and reversible airway obstruction. Eosinophils contribute to the pathogenesis of airway disease mainly by releasing eosinophil-specific granules, lipid mediators, superoxide anions, and their DNA. Type-2 cytokines such as interleukin (IL)-4 and IL-13 also play roles in the development of bronchial asthma. Among these cytokines, IL-4 is involved in T-cell differentiation, B-cell activation, B-cell differentiation into plasma cells, and the production of immunoglobulin E. Although IL-13 has similar effects to IL-4, IL-13 mainly affects structural cells, such as epithelial cells, smooth muscle cells, and fibroblasts. IL-13 induces the differentiation of goblet cells that produce mucus and induces the airway remodeling, including smooth muscle hypertrophy. IL-4 and IL-13 do not directly activate the effector functions of eosinophils; however, they can induce eosinophilic airway inflammation by upregulating the expression of vascular cell adhesion molecule-1 (for adhesion) and CC chemokine receptor 3 ligands (for migration). Dupilumab, a human anti-IL-4 receptor α monoclonal antibody that inhibits IL-4 and IL-13 signaling, decreases asthma exacerbations and mucus plugs and increases lung function in moderate to severe asthma. In addition, dupilumab is effective for chronic rhinosinusitis with nasal polyps and for atopic dermatitis, and IL-4/IL-13 blocking is expected to suppress allergen sensitization, including transcutaneous sensitization and atopic march.

The role and mechanism of macrophage autophagy in the experimental model of chronic obstructive pulmonary disease.

Macrophages play an important role in chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) impairs autophagy in alveolar macrophages from COPD patients, and autophagic impairment leads to reduced clearance of protein aggregates, dysfunctional mitochondria, and defective bacterial delivery to lysosomes. However, the exact function of lung macrophage autophagy in the pathogenesis of CS-induced COPD remains largely unknown. Western blot detected the expression of autophagy-related proteins induced by CSE. The model of COPD mice was established by CS exposure combined with CSE intraperitoneal injection. Double immunofluorescence was used to measure the CD206+LC3B+ cells. The morphological changes and effects on lung function were observed. Masson staining detected the changes in collagen fibers in lung tissue. The expression levels of E-cadherinb and N-cadherinb were detected by immunohistochemistry. Western blot detected the expression of ATP6V1E1 in lung tissue. At 24 hours of exposure to CSE, the expression levels of LC3B (microtubule-associated protein 1A/1B-light chain 3B) and P62 (nucleoporin 62) were highest at 1% CSE and AGT5 (nucleoporin 62) at 2.5% CSE; at 48 hours, the expression levels of LC3B, P62 and AGT5 were highest at 2.5% CSE, and as the intervention time increased.CD206+LC3B+ cells were significantly higher in the COPD group. Enhanced macrophage autophagy may promote emphysema formation and aggravate lung function damage. The expression of E-cadherinb in lung tissue of the COPD group was decreased, and N-cadherinb expression was increased; the expression of E-cadherinb was increased, and N-cadherinb expression was decreased in ATG5myeΔ COPD mice. The expression of ATP6V1E1 in the lung tissue was increased in the COPD group; ATP6V1E1 expression was decreased in the lung tissues of ATG5myeΔ COPD mice. CSE enhanced macrophage autophagy, leads to increased lung function impairment and collagenous fiber in lung tissue, as well as promotes epithelial-mesenchymal transition, and eventually leads to small airway remodeling, which may be achieved through the ATG5/ATP6V1E1 pathway.

The effect of craniocervical flexion and neck endurance exercises plus pulmonary rehabilitation on pulmonary function in spinal cord injury: a pilot single-blinded randomised controlled trial.

Randomised controlled trial with computerised allocation, assessor blinding and intention-to-treat analysis. This study wanted to prove that cervicocranial flexion exercise (CCFE) and superficial neck flexor endurance training combined with common pulmonary rehabilitation is feasible for improving spinal cord injury people's pulmonary function. Taoyuan General Hospital, Ministry of Health and Welfare: Department of Physiotherapy, Taiwan. Thirteen individuals who had sustained spinal cord injury for less than a year were recruited and randomised assigned into two groups. The experimental group was assigned CCFEs and neck flexor endurance training plus normal cardiopulmonary rehabilitation. The control group was assigned general neck stretching exercises plus cardiopulmonary rehabilitation. Lung function parameters such as forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, peak expiratory flow rate (PEFR), inspiratory capacity (IC), dyspnoea, pain, and neck stiffness were recorded once a week as short-term outcome measure. The experimental group showed significant time effects for FVC (pre-therapy: 80.4 ± 21.4, post-therapy: 86.9 ± 16.9, p = 0.021, 95% CI: 0.00-0.26) and PEFR (pre-therapy: 67.0 ± 33.4; post-therapy: 78.4 ± 26.9, p = 0.042, 95% CI: 0.00-0.22) after the therapy course. Furthermore, the experimental group showed significant time effects for BDI (experimental group: 6.3 ± 3.0; control group: 10.8 ± 1.6, p = 0.012, 95% CI: 0.00-0.21). The exercise regime for the experimental group could efficiently increase lung function due to the following three reasons: first, respiratory accessory muscle endurance increases through training. Second, posture becomes less kyphosis resulting increasing lung volume. Third, the ratio between superficial and deep neck flexor is more synchronised. TYGH108045. NCT04500223.

A WNT mimetic with broad spectrum FZD-specificity decreases fibrosis and improves function in a pulmonary damage model

BackgroundWnt/β-catenin signaling is critical for lung development and AT2 stem cell maintenance in adults, but excessive pathway activation has been associated with pulmonary fibrosis, both in animal models and human diseases such as idiopathic pulmonary fibrosis (IPF). IPF is a detrimental interstitial lung disease, and although two approved drugs limit functional decline, transplantation is the only treatment that extends survival, highlighting the need for regenerative therapies.MethodsUsing our antibody-based platform of Wnt/β-catenin modulators, we investigated the ability of a pathway antagonist and pathway activators to reduce pulmonary fibrosis in the acute bleomycin model, and we tested the ability of a WNT mimetic to affect alveolar organoid cultures.ResultsA WNT mimetic agonist with broad FZD-binding specificity (FZD1,2,5,7,8) potently expanded alveolar organoids. Upon therapeutic dosing, a broad FZD-binding specific Wnt mimetic decreased pulmonary inflammation and fibrosis and increased lung function in the bleomycin model, and it impacted multiple lung cell types in vivo.ConclusionsOur results highlight the unexpected capacity of a WNT mimetic to effect tissue repair after lung damage and support the continued development of Wnt/β-catenin pathway modulation for the treatment of pulmonary fibrosis.

Evaluation the Effect of Supplements Containing Vitamin D and Trace Elements in Patients with Moderate to Severe Asthma.

Asthma is a common and major allergic disease in the world. We aimed to investigate the impact of supplements with vitamin D, folic acid, selenium, zinc, and copper in patients with moderate to severe asthma. In this clinical trial study 70 patients above six years old with moderate to severe asthma, were divided into two groups, randomly; one group received daily Asmavit syrup, 10 ml (Asmavit, Vitabiotics Ltd, London, UK), and the other group received daily 1000 IU vitamin D3 drops (Asmavit, Vitabiotics Ltd, London, UK) for two months along with ordinary treatment for asthma. Clinical and physical examinations, immunological and biochemical tests were carried out for each patient before and after the treatment. The mean age of patients was 39.9± 14.7 years old, and the mean disease duration was 8.8 ± 9.8 years. A significant increase in lung function, asthma control, and quality of life score tests was observed in both groups after the treatment (P< 0.05). There was no significant difference in cytokines expression levels before and after the treatment with vitamin D3 or Asmavit (P> 0.05). Serum levels of selenium and folic acid before treatment were correlated with disease severity, while post-treatment vitamin D levels significantly increased FEV1 (P> 0.05). Oxidative stress levels reduced in both groups, with greater reduction in the vitamin D group (P< 0.05). Supplements, particularly vitamin D, when combined with standard asthma treatment, may effectively improve clinical symptoms and enhance the quality of life for asthmatic patients.

P. aeruginosa tRNA-fMet halves secreted in outer membrane vesicles suppress lung inflammation in cystic fibrosis.

Although tobramycin increases lung function in people with cystic fibrosis (pwCF), the density of Pseudomonas aeruginosa (P. aeruginosa) in the lungs is only modestly reduced by tobramycin; hence, the mechanism whereby tobramycin improves lung function is not completely understood. Here, we demonstrate that tobramycin increases 5' tRNA-fMet halves in outer membrane vesicles (OMVs) secreted by laboratory and CF clinical isolates of P. aeruginosa. The 5' tRNA-fMet halves are transferred from OMVs into primary CF human bronchial epithelial cells (CF-HBEC), decreasing OMV-induced IL-8 and IP-10 secretion. In mouse lungs, increased expression of the 5' tRNA-fMet halves in OMVs attenuated KC (murine homolog of IL-8) secretion and neutrophil recruitment. Furthermore, there was less IL-8 and neutrophils in bronchoalveolar lavage fluid isolated from pwCF during the period of exposure to tobramycin versus the period off tobramycin. In conclusion, we have shown in mice and in vitro studies on CF-HBEC that tobramycin reduces inflammation by increasing 5' tRNA-fMet halves in OMVs that are delivered to CF-HBEC and reduce IL-8 and neutrophilic airway inflammation. This effect is predicted to improve lung function in pwCF receiving tobramycin for P. aeruginosa infection.NEW & NOTEWORTHY The experiments in this report identify a novel mechanism, whereby tobramycin reduces inflammation in two models of CF. Tobramycin increased the secretion of tRNA-fMet halves in OMVs secreted by P. aeruginosa, which reduced the OMV-LPS-induced inflammatory response in primary cultures of CF-HBEC and in mouse lung, an effect predicted to reduce lung damage in pwCF.

Dose-response relationship between lung function and chest imaging response to silica exposures in artificial stone manufacturing workers

BackgroundOccupational exposure to artificial stone, a popular material used for countertops, can cause accelerated silicosis, but the precise relationship between silica dose and disease development is unclear.ObjectivesThis study evaluated the impact of silica exposure on lung function and chest imaging in artificial stone manufacturing workers.MethodsQuestionnaire and spirometry assessments were administered to workers in two plants. A high-exposure subset underwent further evaluation, including chest CT and DLco. Weighting factors, assigned as proxies for silica exposure, were based on work tasks. Individual cumulative exposures were estimated using area concentration measurements and time spent in specific areas. Exposure-response associations were analyzed using linear and logistic regression models.ResultsAmong 65 participants, the mean cumulative silica exposure was 3.61 mg/m3-year (range 0.0001 to 44.4). Each 1 mg/m3-year increase was associated with a 0.46% reduction in FVC, a 0.45% reduction in FEV1, and increased lung function abnormality risk (aOR = 1.27, 95% CI = 1.03–1.56). Weighting factors correlated with cumulative exposures (Spearman correlation = 0.59, p < 0.0001), and weighted tenure was associated with lung function abnormalities (aOR = 1.04, 95% CI = 1.01–1.09). Of 37 high-exposure workers, 19 underwent chest CT, with 12 (63%) showing abnormal opacities. Combining respiratory symptoms, lung function, and chest X-ray achieved 91.7% sensitivity and 75% specificity for predicting chest CT abnormalities.ConclusionLung function and chest CT abnormalities occur commonly in artificial stone workers. For high-exposure individuals, abnormalities on health screening could prompt further chest CT examination to facilitate early silicosis detection.

Long-term efficacy of house dust mite sublingual immunotherapy on clinical and pulmonary function in patients with asthma and allergic rhinitis

BackgroundA previous study reported that house dust mite (HDM) sublingual immunotherapy (SLIT) for 48 weeks was effective as add on treatment for allergic asthma; however, data regarding its long-term efficacy is scarce. ObjectiveThis open-label extension study aimed to evaluate the effect of HDM SLIT on asthma control, pulmonary function, airway inflammation and remodeling throughout the 5-year treatment period. MethodsA total of 140 patients with asthma and allergic rhinitis sensitized to HDM were randomized to receive either drugs alone or drugs plus SLIT for 5 years. Asthma Control Questionnaire (ACQ)-5, Asthma Quality of Life Questionnaire (AQLQ), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), spirometry, quantitative computed tomography, and type 2 biomarkers were assessed. ResultsAn improvement in the ACQ-5, AQLQ, and RQLQ scores was observed in the SLIT group compared with the control group. HDM SLIT increased lung function and reduced the percentage of airway wall area (WA/Ao). The levels of fractional exhaled nitric oxide (FeNO), blood eosinophil, serum specific IgE (s-IgE) for HDM, and total IgE decreased and were sustained during the 5 years. The change in type 2 biomarkers correlated with change in AQLQ score. Based on receiver operating characteristic (ROC) analysis for predicting responders, the area under the ROC curve in FEV1% predicted, WA/Ao, FeNO, and s-IgE was high. Multivariate regression analysis showed that the strongest predictor of responders was FeNO. ConclusionsHDM SLIT continued to provide sustained efficacy, improve lung function, and prevent progression of airway inflammation and remodeling in asthma through to year 5.

Arrestin beta 1 Regulates Alveolar Progenitor Renewal and Lung Fibrosis.

The molecular mechanisms that regulate progressive pulmonary fibrosis remain poorly understood. Type 2 alveolar epithelial cells (AEC2s) function as adult stem cells in the lung. We previously showed that there is a loss of AEC2s and a failure of AEC2 renewal in the lungs of idiopathic pulmonary fibrosis (IPF) patients. We also reported that beta-arrestins are the key regulators of fibroblast invasion, and beta-arrestin 1 and 2 deficient mice exhibit decreased mortality, decreased matrix deposition, and increased lung function in bleomycin-induced lung fibrosis. However, the role of beta-arrestins in AEC2 regeneration is unclear. In this study, we investigated the role and mechanism of Arrestin beta 1 (ARRB1) in AEC2 renewal and in lung fibrosis. We used conventional deletion as well as cell type-specific deletion of ARRB1 in mice and found that Arrb1 deficiency in fibroblasts protects mice from lung fibrosis, and the knockout mice exhibit enhanced AEC2 regeneration in vivo, suggesting a role of fibroblast-derived ARRB1 in AEC2 renewal. We further found that Arrb1-deficient fibroblasts promotes AEC2 renewal in 3D organoid assays. Mechanistically, we found that CCL7 is among the top downregulated cytokines in Arrb1 deficient fibroblasts and CCL7 inhibits AEC2 regeneration in 3D organoid experiments. Therefore, fibroblast ARRB1 mediates AEC2 renewal, possibly by releasing chemokine CCL7, leading to fibrosis in the lung.

Effects of Everolimus in Modulating the Host Immune Responses against Mycobacterium tuberculosis Infection.

The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (P13K/AKT/mTOR) pathway plays a key role in tuberculosis (TB) pathogenesis and infection. While the activity levels of this pathway during active infection are still debated, manipulating this pathway shows potential benefit for host-directed therapies. Some studies indicate that pathway inhibitors may have potential for TB treatment through upregulation of autophagy, while other studies do not encourage the use of these inhibitors due to possible host tissue destruction by Mycobacterium tuberculosis (M. tb) and increased infection risk. Investigating further clinical trials and their use of pathway inhibitors is necessary in order to ascertain their potential for TB treatment. This paper is particularly focused on the drug everolimus, an mTOR inhibitor. One of the first clinical trials sponsored by the Aurum Institute showed potential benefit in using everolimus as an adjunctive therapy for tuberculosis. Infection with tuberculosis is associated with a metabolic shift from oxidative phosphorylation towards glycolysis. The everolimus arm in the clinical trial showed further reduction than the control for both maximal and peak glycolytic activity. Compared with control, those receiving everolimus demonstrated increased lung function through forced expiratory volume in 1 s (FEV1) measurements, suggesting that everolimus may mitigate inflammation contributing to lung damage.

Predictors of Transition Outcomes in Cystic Fibrosis: Analysis of National Patient Registry and CF RISE (Responsibility. Independence. Self-care. Education) Data

ObjectiveTo identify predictors of change in lung function and body weight during healthcare transition in cystic fibrosis (CF). MethodsWe conducted a retrospective cohort study using data from the CF Foundation Patient Registry (CFFPR) and the web-based transition program CF RISE (Responsibility. Independence. Self-care. Education) for patients ages 16 to 25 who transitioned to adult care from 2013 through 2019. We modeled change in FEV1 % predicted and weight using linear regression fit with generalized estimating equations. Predictors included gap in care (time between last pediatric and first adult outpatient visit), transition program engagement, and sociodemographic and medical factors. ResultsAmong 12,420 adolescents and young adults (AYAs), 3,876 transitioned to adult care with a median gap in care of 7.6 months. Patients from CF centers with higher rates of CF RISE engagement had improved lung function and weight at their first adult outpatient visit. Coverage on a parent’s insurance plan and absence of CF complications predicted increased lung function. History of a non-lung transplant and sinus disease predicted increased weight. Comorbid diabetes mellitus and gaps in care >3 months predicted decreased lung function with longer gaps in care associated with greater decrease. A gap in care of 6-9 months predicted decreased weight. Control variables including baseline FEV1 and weight, and exacerbation status were also statistically significant. ConclusionsFindings suggest two promising targets to improve transition of AYAs with CF: increasing AYA engagement in CF RISE and reducing gaps in care during the transition period.

CORTICOSTEROID THERAPY FOR ACUTE ASTHMA : A SYSTEMATIC REVIEW

Background: Asthma is a chronic inflammatory disorder of the airways which affects 300 million people worldwide. Asthma places a huge burden in multiple nations. The main care components for asthma include assessment and monitoring, patient education, addressing environmental controls and comorbid conditions, and pharmaceutical therapy. Corticosteroids therapy is used for maintenance of asthma. While Systemic corticosteroids are often regarded as the first-line treatment for acute asthma since they are unmistakably linked to a quicker recovery to baseline function. The aim: This study aims to show effectiveness of corticosteroid therapy for acute asthma. Methods: By comparing itself to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. So, the experts were able to make sure that the study was as up-to-date as it was possible to be. For this search approach, publications that came out between 2013 and 2023 were taken into account. Several different online reference sources, like Pubmed and ScienceDirect, were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Results: In the PubMed database, the results of our search brought up 60 articles, whereas the results of our search on ScienceDirect brought up 117 articles. The results of the search conducted by title screening yielded a total 15 articles for PubMed and 7 articles for ScienceDirect. We compiled a total of 9 papers, 6 of which came from PubMed and 3 of which came from ScienceDirect. We excluded 1 duplicate article and 1 review article. In the end, we included seven research (RCT) that met the criteria. Conclusion: Corticosteroids therapy, whether oral, intravenous and inhaled, is effective to increase lung function (PEF), improve symptoms, and has fewer side effects. Corticosteroids therapy is also effective to reduce admission or hospitalization rate in severe acute asthma.

The Impact of Metabolic Syndrome Risk Factors on Lung Function Impairment: Cross-Sectional Study.

Metabolic syndrome (MetS) is a constellation of risk factors increasingly present in the world's population. People with this syndrome are at an increased risk of cardiovascular disease and type 2 diabetes mellitus. Moreover, evidence has shown that it affects different organs. MetS and its risk factors are independently associated with impaired lung function, which can be quantified through spirometric variables. This study aims to determine whether a high number of MetS criteria is associated with increased lung function decline. We conducted a descriptive cross-sectional study with a random sample of 1980 workers. Workers with acute respiratory pathology (eg, influenza), chronic respiratory pathology (eg, chronic bronchitis), or exposure to substances harmful to the lungs (eg, organic and inorganic dust) were not included. MetS was established based on harmonized criteria, and lung function was assessed according to spirometric variables. On the basis of these, classification into restrictive lung disease (RLD), obstructive lung disease, and mixed lung disease (MLD) was performed. In addition, the association between MetS and lung function was established based on analysis of covariance, linear trend analysis, and multiple linear regression. MetS was associated with worse lung function according to all the spirometric parameters analyzed (percentage of predicted forced expiratory volume in 1 second: mean 83, SD 13.8 vs mean 89.2, SD 12.8; P<.001 and percentage of predicted forced vital capacity: mean 85.9, SD 11.6 vs mean 92, SD 11.3; P<.001). Moreover, those diagnosed with MetS had a higher prevalence of lung dysfunction (41% vs 21.9%; P<.001), RLD (23.4% vs 11.2%; P<.001), and MLD (7.3% vs 2.2%; P<.001). Furthermore, an increasing number of MetS criteria was associated with a greater impairment of pulmonary mechanics (P<.001). Similarly, with an increasing number of MetS criteria, there was a significant linear trend (P<.001) in the growth of the prevalence ratio of RLD (0 criteria: 1, 1: 1.46, 2: 1.52, 3: 2.53, 4: 2.97, and 5: 5.34) and MLD (0 criteria: 1, 1: 2.68, 2: 6.18, 3: 9.69, and 4: 11.37). Regression analysis showed that the alteration of all MetS risk factors, adjusted for various explanatory variables, was significantly associated with a worsening of spirometric parameters, except for forced expiratory volume in 1 second/forced vital capacity. The findings have shown that an increase in cardiometabolic risk factors is associated with a more significant worsening of spirometric variables and a higher prevalence of RLD and MLD. As spirometry could be a crucial tool for monitoring patients at risk of developing chronic pathologies, we conclude that this inexpensive and easily accessible test could help detect changes in lung function in patients with cardiometabolic disorders. This highlights the need to consider the importance of cardiometabolic health in lung function when formulating public health policies.