Search Results (154)

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease predominantly of the small airways and parenchyma. COPD lungs exhibit an influx of circulating innate immune cells, which, when isolated, display impaired functions, including imbalanced protease secretion. In addition to immune cells, the extracellular matrix (ECM) plays a crucial role in COPD pathology. Remodeling of the ECM can generate ECM fragments, which can be released into circulation and subsequently induce pro-inflammatory responses. COPD is a heterogeneous disease, and serological biomarkers can be used to sub-categorize COPD patients for targeted treatments and optimal recruitment in clinical trials. This study evaluated fragments of calprotectin, collagen type VI, and versican, generated by neutrophil elastase and matrix metalloproteinases (MMP-) 2 and 12, respectively, as potential biomarkers of COPD disease, severity, and endotypes. Lower plasma levels of a neoepitope marker of calprotectin, indicative of activated neutrophils (nordicCPa9-HNETM), were detected in COPD donors compared to controls. CPa9-HNE was associated with milder disease, higher degree of air-trapping, and higher serum levels of MMP-2. Deposition of CPa9-HNE levels in lung tissue revealed no differences between groups. Taken together, CPa9-HNE was found to be a potential marker of mild COPD, but further studies are warranted to validate our findings. Full article

Asthma, the most common chronic respiratory condition in children, involves airway inflammation, hyper-responsiveness, and frequent exacerbation that worsen the airflow and inflammation. Exosomes, extracellular vesicles carrying microRNAs (miRNAs), play a key role in cell communication alongside other types of communication and are promising markers of asthma severity. This study compares exosomal miRNA and long non-coding RNA (lncRNA) profiles in boys with asthma, focusing on differences between those with normal lung functions and those with severe airflow obstruction. This study enrolled 20 boys aged 9–18 years with asthma, split into two groups based on their lung function. Ten had normal lung function (NLF; FEV1/FVC > 0.84, FEF75% > 69% predicted), while ten had severe airflow obstruction (SAO; FEV1/FVC < 0.70, FEF75 < 50% predicted). Saliva and blood samples were collected. Exosomes were isolated, quantified, and analyzed via small RNA sequencing to identify differentially expressed (DE) miRNA and lncRNA profiles. Bioinformatic tools were then used to explore potential miRNA biomarkers linked to asthma severity. SAO subjects were more likely to exhibit allergen sensitization, higher IgE levels, and more eosinophils. We identified 27 DE miRNAs in plasma and 40 DE miRNAs in saliva. Additionally, five key miRNAs were identified in both saliva and plasma which underline important pathways such as neurotrophins, T-cell receptor, and B-cell receptor signaling. We further outlined key features and functions of miRNAs and long non-coding RNAS (lncRNAs) and their interactions in children with asthma. This study identified DE miRNAs and lncRNAs in children with SAO when compared to those with NLF. Exosomal miRNAs show strong potential as non-invasive biomarkers for personalized asthma diagnosis, treatment, and monitoring. These RNA markers may also aid in tracking disease progression and response to therapy, thereby supporting the need for future studies aimed at applications in precision medicine. Full article

Background: Patients with mild coronavirus disease 2019 (COVID-19) are usually managed in an outpatient setting. Pulmonary functions in this setting have not been explored. This study aimed to determine abnormal lung functions in COVID-19 patients under a home isolation program. Methods: A prospective study was conducted in asymptomatic or mild COVID-19 patients with normal chest radiographs at two medical centers in Thailand. Spirometry data, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), forced expiratory flow at 25–75% of FVC (FEF25–75), and bronchodilator responsiveness (BDR), were collected. Spirometry was performed after disease resolution at baseline and 3-month follow-up. Abnormal lung functions were classified into airway obstruction, restrictive defect, mixed defect, small airway disease, and BDR. Results: A total of 250 patients (58% female) were included. The mean age was 37.4 ± 15.2 years. Asymptomatic patients accounted for 7.6%. Common symptoms included fever (55.6%) and cough (60.0%). Abnormal lung functions were observed in 28.4% of patients, with a restrictive lung pattern (14.4%), airway obstruction (4.8%), mixed defect (0.4%), small airway disease (8.4%), and BDR (2.8%). Significant changes from baseline were noted in FVC (1.21%), FEV₁/FVC (−1.51%predicted), PEF (0.06%), and FEF_25–75 (−2.76%). Logistic regression analysis indicated that a higher body mass index was associated with a lower risk of abnormal lung function. Conclusions: Ventilatory defects were observed in one-third of patients with mild COVID-19 who did not require hospitalization, mainly presenting as restrictive patterns and small airway disease. Even mild cases may have residual pulmonary impairment, warranting further long-term studies. Full article

Acute lower respiratory tract infections are a leading cause of death in individuals under the age of 5 years, mostly in low- and middle-income countries (LMICs). The lack of respiratory support systems contributes to the poor outcomes. Bubble CPAP is widely used for non-invasive respiratory support, but sicker children often require support over what CPAP provides in the form of BiPAP. We developed and tested a simple bubble-based bilevel ventilator (Bubble bi-vent) and compared it with a standard care BiPAP device. The bubble bilevel device consisted of a single tube submerged in a water-sealed column to maintain end-expiratory positive airway pressure. It moves vertically via an electric motor to also provide inspiratory positive airway pressure for augmentation of lung volumes, with the duration and frequency of breaths controlled by a microprocessor. We tested this novel device in passively breathing mechanical lung models for infants and small children. We compared pressure and tidal volume delivery between the novel device and a Trilogy BiPAP ventilator. The results showed that the Bubble bi-vent could deliver set pressures in a mechanical lung and was comparable to a standard Trilogy ventilator. While two different bubble-based bilevel pressure devices have been piloted for neonates and adults, our results demonstrate the feasibility of bubble bilevel ventilation for infants and small children with moderate to severe lung disease for whom this was previously not described. Full article

The burden of chronic obstructive pulmonary disease (COPD) is increasing, especially for women in low-to-middle income countries. Biomarkers provide ever-increasing diagnostic precision for COPD and show promise for primary, secondary, and tertiary disease prevention. This review describes emerging applications for biomarkers in COPD, especially as they align with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) emphasis on prevention, early diagnosis, and response to therapy. These biomarkers include blood eosinophils; IgE; C-reactive protein; fibrinogen; procalcitonin; interleukins 6, 8, and 33; tumor necrosis factor alpha; and soluble receptor for advanced glycated products (sRAGE). They have been used in various ways to identify COPD endotypes, predict exacerbations, predict mortality, and monitor the response to therapy. The fraction of exhaled nitric oxide (FENO) is increasingly studied in eosinophilic COPD endotypes and can be a diagnostic and predictive non-invasive biomarker. Imaging biomarkers, especially the quantitative computerized tomography (QCT) assessment of airway remolding, functional small airway disease, air trapping, lung function, and volume surrogates, all serve as non-invasive biomarkers for screening, early detection, and disease progression. Biomarkers facilitate all the phases of COPD care from detecting early airflow obstruction to predicting exacerbation and mortality. Biomarkers will be increasingly used as precise diagnostic tools to improve the COPD outcomes. The aim of this narrative review is to summarize the recent investigations in COPD biomarkers and their clinical applications. Full article

Airborne diseases pose a significant challenge in intensive livestock farming due to their rapid transmission. Aerosols facilitate the spread of pathogens, introducing external infections to farms and enabling cross-transmission within barns. To address knowledge gaps in aerosol dynamics in animal respiratory tracts and enhance understanding of airborne disease transmission, this study employed CT scanning, 3D printing, and CFD technologies to develop and validate a pig respiratory model. Qualitative and quantitative results from the present study reveal spatiotemporal heterogeneity in aerosol deposition and transmission. Under rest conditions, for aerosols with D ≤ 5.0 μm, 21.1% of inhaled aerosols were deposited in the lung by the end of a respiratory cycle. Doubling the respiratory cycle or the inhalation rate could further increase the penetration ability of small-sized aerosols by approximately 60% to 70%. Moreover, the asymmetric distribution of airflow between the left and right halves of the lower respiratory tract (Q_L/R = 0.89) resulted from the leftward position of the pig’s heart and consequently led to a deposition ratio of about 0.83 between the left and right bronchial airways. These findings provide fundamental scientific data for the development and application of aerosolized vaccines and offer insights into optimizing respiratory intervention strategies. Full article

Lung cancer is one of the deadliest forms of cancer. Its prognosis becomes even worse when it co-occurs with other diseases, such as chronic obstructive pulmonary disease (COPD). Both illnesses have numerous shared risk factors, including the use of tobacco smoke, and have similar underlying mechanisms like long-term inflammation. There are some other less studied but equally important molecules, like small extracellular vesicles (sEVs), that have been shown to mediate effective communication at the cellular level and may affect the progression of a disease or cause resistance to therapies. In sEVs from lung cancer tumors, there are onco-proteins (e.g., tumor initiator EGFR mutations, onco-miR, miR-21), while in sEVs from patients with COPD, there are pro-inflammatory cytokines like IL-6 and TNF-α that enhance airway inflammation. These potential biomarkers of sEVs from chronic lung disease have great value in defense against emerging health problems; however, limitations in sample extraction and analysis are obstacles that hinder clinical enhanced applicability. This review focuses on sEV-derived biomarkers in lung cancer and COPD for diagnostic, prognostic, and therapeutic monitoring purposes. To make these molecules more useful in real-life therapy and determine their signature’s role, further investigation with a high-scale study is necessary. Full article

This case report highlights the management of a delayed bronchopleural fistula (BPF) following salvage pulmonary resection to achieve local control and no radiographic evidence of disease in a patient treated with serial tyrosine kinase inhibitors (TKIs) for stage IV anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC). The initial pulmonary resection was complicated by dense adhesions and an abnormally torturous pulmonary artery. Six weeks after the index surgery, the patient presented with a delayed BPF requiring decortication, repair of airway, and coverage of the bronchial stump with a serratus anterior muscle flap. Full article

Mepolizumab represents an effective strategy for severe eosinophilic asthma. Small airways disease (SAD) defines a peculiar asthma phenotype related to worse disease control. Limited and indirect findings are currently available on the effect of mepolizumab on SAD. Objectives: We investigated the impact of mepolizumab on SAD assessed through impulse oscillometry (IOS) and spirometry. As secondary outcomes, we tested the correlation between SAD and clinical, functional and inflammatory parameters. Methods: This is a prospective cohort study including severe eosinophilic asthmatics eligible for mepolizumab performed between 2021 and 2023. IOS (R5–R20) and spirometry (FEF25-75%, TLC%, RV/TLC%) parameters were assessed at baseline and over 1 year of mepolizumab. Other functional (FEV1%), clinical (ACT, number of asthma exacerbations/previous year, use of OCS) and inflammatory data (BEC and FeNO) were concomitantly collected for correlations. Results: A total of 18 patients (mean age 61.1 ± 12.0 y; 10 (55.5%) female) were included. Longitudinal data from 16 patients showed that R5–R20 significantly improved after 12-months treatment (p: 0.03), as well as FEF25-75% (p: 0.04) and TLC% (0.04). FEV1% and ACT showed a concomitant improvement (p: 0.03 and <0.01, respectively). All the steroid-dependent subjects discontinued OCS after 3 months and the percentage of subjects experiencing exacerbations significantly decreased (p: <0.01). As per drug effect, BEC consistently decreased (p: <0.01). The decrease in R5–R20 correlated with an improvement in FEF25-75% (r: −0.40 p: 0.048) and ACT at T12 (r: −0.59 p: 0.02). Conclusions: Twelve months treatment with mepolizumab improved R5–R20, suggesting its additional role as a targeted treatment for distal lung regions. This improvement also correlated with a clinically relevant amelioration of asthma symptoms. Full article

Study Objectives: This review aims to explore the epidemiology, pathophysiology, risk factors, and diagnostic approaches of obstructive sleep apnea syndrome and small airway disease, emphasizing their interrelationship and implications for clinical management. Methods: A comprehensive analysis of the literature was conducted to examine shared and distinct characteristics of obstructive sleep apnea syndrome and small airway disease. Risk factors, clinical presentations, diagnostic tools, and management strategies were reviewed to identify potential areas for improvement in care. Results: Obstructive sleep apnea syndrome, characterized by intermittent upper airway obstruction during sleep, contributes to fragmented sleep and systemic diseases. Small airway disease involves inflammation and obstruction of the small airways, impairing airflow and gas exchange. Shared risk factors, such as obesity, smoking, and age, were identified as contributors to the development and progression of both conditions. The co-occurrence of obstructive sleep apnea syndrome and small airway disease exacerbates respiratory symptoms and increases the risk of comorbidities, such as pulmonary hypertension, heart failure, and respiratory failure. Recognition of their interplay highlights the need for integrated diagnostic and therapeutic strategies. Conclusions: The interrelationship between obstructive sleep apnea syndrome and small airway disease underscores the importance of integrated management approaches to improve patient outcomes. Addressing shared risk factors and understanding the interplay between these conditions are crucial for optimizing care. This review identifies key knowledge gaps, including the need for precise diagnostic tools and targeted therapies, which are essential for advancing personalized treatment strategies for individuals with obstructive sleep apnea syndrome and small airway disease. Full article

Pulmonary homeostasis can be agitated either by external environmental insults or endogenous factors produced during respiratory/pulmonary diseases. The lungs counter these insults by initiating mechanisms of inflammation as a localized, non-specific first-line defense response. Cytokines are small signaling glycoprotein molecules that control the immune response. They are formed by numerous categories of cell types and induce the movement, growth, differentiation, and death of cells. During respiratory diseases, multiple proinflammatory cytokines play a crucial role in orchestrating chronic inflammation and structural changes in the respiratory tract by recruiting inflammatory cells and maintaining the release of growth factors to maintain inflammation. The issue aggravates when the inflammatory response is exaggerated and/or cytokine production becomes dysregulated. In such instances, unresolving and chronic inflammatory reactions and cytokine production accelerate airway remodeling and maladaptive outcomes. Pro-inflammatory cytokines generate these deleterious consequences through interactions with receptors, which in turn initiate a signal in the cell, triggering a response. The cytokine profile and inflammatory cascade seen in different pulmonary diseases vary and have become fundamental targets for advancement in new therapeutic strategies for lung diseases. There are considerable therapeutic approaches that target cytokine-mediated inflammation in pulmonary diseases; however, blocking specific cytokines may not contribute to clinical benefit. Alternatively, broad-spectrum anti-inflammatory approaches are more likely to be clinically effective. Herein, this comprehensive review of the literature identifies various cytokines (e.g., interleukins, chemokines, and growth factors) involved in pulmonary inflammation and the pathogenesis of respiratory diseases (e.g., asthma, chronic obstructive pulmonary, lung cancer, pneumonia, and pulmonary fibrosis) and investigates targeted therapeutic treatment approaches. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory disease of the upper airway, contributing significantly to the global disease burden. CRSwNP is characterized by sustained and exaggerated inflammation, accompanied by marked changes in gene and protein expression regulated through intricate molecular mechanisms. MicroRNAs (miRNAs), small single-stranded RNA molecules that regulate gene expression at transcriptional and post-transcriptional levels, have emerged as pivotal players in CRSwNP pathophysiology. Dysregulated miRNA expression is implicated in numerous human diseases, including cancer, asthma, and inflammatory disorders, highlighting their broad clinical relevance. In CRSwNP, miRNAs influence important inflammatory pathways, including T2 immune responses and epithelial–mesenchymal transition (EMT), which leads to chronic inflammation and tissue remodeling. Profiling studies have identified specific miRNAs as potential biomarkers for disease severity, prognosis, and therapeutic response, offering a pathway to personalized medicine. Furthermore, advances in small extracellular vesicles (sEVs) and exosomes, which naturally transport miRNAs, provide innovative avenues for targeted miRNA delivery, minimizing systemic side effects. This review explores current knowledge on miRNA expression and function in CRSwNP, emphasizing their role in disease pathogenesis and their potential as biomarkers and therapeutic targets. Full article

Background: Small airway dysfunction (SAD) is associated with impaired asthma control, but small airway physiology is not routinely assessed in clinical practice. Previously, we demonstrated impulse oscillometry (IOS)-defined small airway dysfunction (SAD) in dual responders (DRs) upon bronchoprovocation with various allergens. Aim: To compare lung physiology using spirometry and IOS following bronchoprovocation with methacholine (M) and inhaled house dust mite (HDM) extract in corticosteroid-naïve asthmatic subjects. Methods: Non-smoking, clinically stable HDM-allergic asthmatic subjects (18–55 years, FEV₁ > 70% of pred.) underwent an M and inhaled HDM challenge on two separate days. Airway response was measured by IOS and spirometry, until a drop in FEV₁ ≥ 20% (PC₂₀) from post-diluent baseline (M), and up to 8 h post-allergen (HDM). Early (EAR) and late asthmatic response (LAR) to HDM were defined as ≥20% and ≥15% fall in FEV₁ from post-diluent baseline during 0–3 h and 3–8 h post-challenge, respectively. IOS parameters (Rrs5, Rrs20, Rrs5-20, Xrs5, AX, Fres) were compared between mono-responders (MRs: EAR only) and dual responders (EAR + LAR). Correlations between maximal % change from baseline after the two airway challenges were calculated for both FEV₁ and IOS parameters. Results: A total of 47 subjects were included (11 MRs; 36 DRs). FEV₁ % predicted did not differ between MR and DR at baseline, but DR had lower median PC₂₀M (0.84 (range 0.07–7.51) vs. MR (2.15 (0.53–11.29)); p = 0.036). During the LAR, DRs had higher IOS values than MRs. For IOS parameters (but not for FEV₁), the maximal % change from baseline following M and HDM challenge were correlated. PC₂₀M was inversely correlated with the % change in FEV₁ and the % change in Xrs5 during the LAR (r= −0.443; p = 0.0018 and r= −0.389; p = 0.0075, respectively). Conclusions: During HDM-induced LAR, changes in small airway physiology can be non-invasively detected with IOS and are associated with increased airway hyperresponsiveness and changes in small airway physiology during methacholine challenge. DRs have a small airways phenotype, which reflects a more advanced airway disease. Full article

Background: Information is limited regarding the role of impulse oscillometry (IOS) for the detection of preserved ratio impaired spirometry (PRISm). Therefore, we aimed to study the diagnostic ability of IOS in differentiating between PRISm and healthy subjects. Methods: This retrospective data collection was done at the Lung Health Center, Faculty of Medicine, Chiang Mai University, Thailand between July 2019 and April 2022. The potential diagnostic possibilities of difference in resistance at 5 Hz (R5) and resistance at 20 Hz (R20) (R5-R20) for PRISm detection were analyzed. Results: The prevalence of PRISm was higher when using the fixed ratio (FR) criteria (FEV₁/FVC ≥0.7 with FEV₁ < 80% of predicted value) compared to the lower limit of normal (LLN) criteria (FEV₁/FVC ≥ LLN and FEV₁ < LLN) (10.0% vs. 4.2%). The %prediction for R5-R20 provided an acceptable area under the curve (AUC) for PRISm, defined by the LLN and the FR criteria (AuROC = 0.75 (95%CI; 0.64, 0.85) and 0.72 (95%CI; 0.63, 0.81), respectively). The cut-off value of %predicted R5-R20 ≥120% resulted in the highest sensitivity and specificity for detecting PRISm. Conclusions: The %predicted of R5-R20 ≥ 120% showed an acceptable performance for PRISm detection and PRISm may be detected by IOS. Full article

Background: Chronic obstructive pulmonary disease (COPD) is characterized by progressive and incurable airflow obstruction and chronic inflammation. Both TGF-β1 and CXCL8 have been well described as fundamental to COPD progression. DNA methylation and histone acetylation, which are well-understood epigenetic mechanisms regulating gene expression, are associated with COPD progression. However, a deeper understanding of the complex mechanisms associated with DNA methylation, histone post-translational changes and RNA methylation in the context of regulatory pathways remains to be elucidated. We here report on how DNA methylation and histone acetylation inhibition differentially affect CXCL8 signaling in primary human non-COPD and COPD airway cells. Methods: Airway smooth muscle (ASM) cells, a pivotal cell type in COPD, were isolated from the small airways of heavy smokers with and without COPD. Histone acetylation and DNA methylation were inhibited before the TGF-β1 stimulation of cells. Subsequently, CXCL8 production and the abundance and activation of pertinent transcription regulatory proteins (NF-κB, p38 MAPK and JNK) were analyzed. Results: TGF-β1-stimulated CXCL8 release from ASM cells from ‘healthy’ smoker subjects was significantly modulated by DNA methylation (56.32 pg/mL and 56.60 pg/mL) and acetylation inhibitors (27.50 pg/mL and 48.85 pg/mL) at 24 and 48 h, respectively. However, modulation via the inhibition of DNA methylation (34.06 pg/mL and 43.18 pg/mL) and acetylation (23.14 pg/mL and 27.18 pg/mL) was observed to a lesser extent in COPD ASM cells. These changes were associated with differences in the TGF-β1 activation of NF-κB and MAPK pathways at 10 and 20 min. Conclusions: Our findings offer insight into differential epigenetics in controlling COPD ASM cells and provide a foundation warranting future studies on epigenetic differences associated with COPD diagnosis. This would provide a scope for developing therapeutic interventions targeting signaling and epigenetic pathways to improve patient outcomes. Full article