Airway Hyperresponsiveness Research Articles

Exploring the effect of peppermint oil massage on pulmonary function in patients with bronchial asthma: insights from a case series

Bronchial asthma (BA) is a chronic inflammatory disorder characterized by airway hyperresponsiveness and obstruction, leading to symptoms such as coughing, wheezing, and shortness of breath. Management typically involves inhaled corticosteroids, but their adverse effects necessitate exploring alternative therapies. Aromatherapy massage, particularly using peppermint oil, may offer therapeutic benefits due to its anti-inflammatory and broncho dilatory properties. This study investigates the impact of upper back massage with peppermint oil on pulmonary function in BA patients. Three female patients with a history of poorly controlled BA participated in this case series. Each patient received a 20-minute upper back massage with peppermint oil daily for 10 days. Pulmonary function tests (PFTs) were conducted before and after the intervention, measuring forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), the FEV1/FVC ratio, peak expiratory flow rate (PEFR), and forced expiratory flow (FEF 25-75%). All patients showed improvement in pulmonary function post-intervention. Case 1: FVC increased from 80% to 97%, FEV1 from 67% to 82%, and PEFR from 72% to 93%. Case 2: FVC improved from 69% to 81%, FEV1 from 64% to 76%, and FEF 25-75% from 40% to 50%. Case 3: FVC rose from 74% to 78%, FEV1 from 55% to 60%, and PEFR from 56% to 63%. Upper back massage using peppermint oil appears to enhance pulmonary function in individuals with bronchial asthma.

Aging, brain-derived neurotrophic factor, and allergen-induced pulmonary responses in mice.

Asthma in the elderly is being recognized as more severe, resistant to standard therapies, and having greater morbidity. Therefore, it comes important to understand the impact of aging-associated airway structure and function changes towards pathogenesis of asthma in the elderly. Here, airway smooth muscle plays important roles in airway hyperreactivity and structural remodeling. The role of smooth muscle in asthma can be modulated by growth factors (including neurotrophins such as brain-derived neurotrophic factor (BDNF)) and pro-inflammatory senescence factors. In this study, we investigated aging effects on airway hyperreactivity, structural remodeling, inflammation, and senescence in a mouse model of allergic asthma. C57BL/6J wildtype mice or smooth muscle-specific BDNF knockout mice at 4, 18 and 24 months of age were intranasally exposed to mixed allergens (ovalbumin, aspergillus, Alternaria, and house dust mite) over 4 weeks. Assessing lung function by FlexiVent, we found that compared with 4 month old mice, 18 and 24 month old C57BL/6J mice showed decreased airway resistance and increased airway compliance after PBS or MA treatment. Deletion of smooth muscle BDNF blunted airway hyperreactivity in aged mice. Lung histology analysis revealed that aging increased bronchial airway thickness and decreased lung inflammation. Multiplex assays showed that aging largely reduced allergen-induced lung expression of proinflammatory chemokines and cytokines. By immunohistochemistry staining, we found that aging increased bronchial airway expression of senescence markers, including p21, phospho-p53 and phospho-gH2A.X. Our data suggest that aging associated increase of airway senescence in the context of allergen exposure may contribute to asthma pathology in the elderly.

Transforming Care in SEA: Evidence and Considerations for Evolution of the Current Treatment Paradigm

This article reviews an industry symposium held on 8 September 2024 as part of the European Respiratory Society (ERS) Congress 2024 in Vienna, Austria, which brought together four experts to discuss the current treatment paradigm for severe eosinophilic asthma (SEA), including the role of biologics and background medication tapering. Katrin Milger-Kneidinger, Professor of Respiratory Medicine at the University Hospital of the Ludwig Maximilian University Munich (LMU), in Germany, and the MedUni Graz, in Austria, explored the critical role eosinophils play in SEA pathology and how biologic therapies targeting eosinophils can address key disease features, including airway remodelling, airway hyperresponsiveness (AHR), and mucus production. Felix Herth, Professor of Pulmonary and Critical Care Medicine at Thoraxklinik Heidelberg, Heidelberg University Hospital, in Germany, discussed persistent airflow obstruction (PAO) in patients with SEA, focusing on a typical patient profile to understand the clinical manifestation and opportunities for management. Stephanie Korn, Professor of Pulmonary and Respiratory Medicine at Thoraxklinik Heidelberg, Heidelberg University Hospital, in Germany, and Head of the Clinical Research Centre, Institute für Klinische Forschung (IKP) Pneumologie in Mainz, Germany, presented on remission as a clinical target in SEA, focusing on how biologics can help achieve remission in some patients. Lastly, in a discussion led by symposium chair Stefano Del Giacco, Professor of Medicine, Allergy, and Clinical Immunology, at the University of Cagliari, Sardinia, in Italy, the experts agreed that a positive practice change would be to get more patients with relevant clinical manifestations on biologics, and that background medication tapering, when appropriate, could lead to improved patient outcomes and quality of life (QoL) in SEA.

Nonasthmatic Eosinophilic Bronchitis: A Systematic Review of Current Treatment Options.

Nonasthmatic eosinophilic bronchitis is characterized by persistent dry or barely productive cough and bronchial eosinophilia without airway obstruction or bronchial hyperreactivity. It is primarily a chronic disease, in which some patients have clinical and pathophysiological relapses, while others progress to asthma or chronic obstructive pulmonary disease. It accounts for 5% to 30% of cases referred for chronic cough. Exposure to common inhalants and occupational sensitizers has been proposed as a possible cause of the disease, although the etiology and underlying mechanisms are uncertain. Some features are similar to those of asthma, such as airway eosinophilia, inflammatory mediator levels, and airway remodeling. Differences in airway pathophysiology, such as the location of airway inflammation and levels of IL-13 and PGE-2, have been reported. Sputum cell count is the gold standard test for diagnosis, and other biomarkers, such as exhaled nitric oxide, could support the diagnosis. A systematic review of treatments for the disease shows that while inhaled corticosteroids are the primary option, the appropriate dose, the type of corticosteroid, and the duration of treatment remain unknown. Treatment duration is inversely correlated with the relapse rate. Increased doses of inhaled corticosteroids, oral corticosteroids, and leukotriene receptor antagonists are recommended in persistent disease. Anti-IL-5 biologics could be promising in this disease. Studies that investigate biomarkers for diagnosis and prognosis are necessary, as are randomized controlled studies for second-line treatments.

Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism.

Asthma is an inflammatory disease where the balance between Th1/Th2 and Th17/Treg plays a crucial role in its pathogenesis. Shikonin is used to treat a variety of autoimmune diseases due to its good anti-inflammatory activity. However, the effect and mechanism of shikonin on asthma remain unknown. Mice were sensitized with ovalbumin (OVA)/house dust mite (HDM) and treated with shikonin. Lung inflammation was assessed histologically and via flow cytometry. Bronchoalveolar lavage fluid (BALF) was analyzed for cell counts and cytokines. Shikonin's impact on p-STAT3 was studied in vivo and in vitro. Shikonin inhibited OVA or HDM-induced inflammation and airway hyperresponsiveness. Upon treatment, a restoration of the Th1/Th2 and Th17/Treg balance was observed, evidenced by a reduction in IL-4 and IL-17A levels in BALF, alongside an elevation in interferon-gamma and IL-10. Furthermore, shikonin impeded the infiltration of eosinophils, neutrophils, macrophages, and lymphocytes into lung tissue. The observed decrease in STAT3 phosphorylation and diminished nuclear translocation of p-STAT3 confirmed that shikonin promotes the balance of Th1/Th2 and Th17/Treg by regulating airway epithelial STAT3. Shikonin mitigates asthma symptoms through a STAT3-dependent mechanism, indicating its potential as an anti-asthmatic therapeutic agent.

Role of Thymic Stromal Lymphopoietin in the Pathophysiology of Asthma and Clinical and Biological Effects of Blockade With Tezepelumab.

The airway epithelium is the first line of defense of the respiratory system against the external environment. It plays an active role in the initiation of immune and allergic responses against potential hazards. Among the various specialized cells and cytokines that participate in epithelium-induced responses, alarmins are particularly interesting, given their ample role in mediating T2 and non-T2 inflammatory mechanisms involved in the pathogenesis of asthma. Thymic stromal lymphopoietin (TSLP) is an alarmin with broad effects in asthma that result from its widespread action on multiple cell types, including eosinophils, mast cells, dendritic cells, and group-2 innate lymphoid cells. Its role in allergy-mediated responses, eosinophilic inflammation, airway hyperresponsiveness, mucus hyperproduction, viral tolerance, and airway remodeling is of the utmost importance, as more comprehensive asthma assessments have been developed to explore these pathogenic features. Therefore, blockade with targeting molecules, such as monoclonal antibodies, has emerged as a promising therapeutic option, particularly in patients with multiple pathogenic pathways. In this review, we examine the roles of alarmins (mainly TSLP) in the pathogenesis of asthma and clinical expression and discuss the effects of inhibiting TSLP on several inflammatory and clinical outcomes. We also review the literature supporting treatment with anti-TSLP biologics and the unanswered questions and unmet needs associated with targeting alarmins in asthma.

High-CBD Extract (CBD-X) in Asthma Management: Reducing Th2-Driven Cytokine Secretion and Neutrophil/Eosinophil Activity.

Asthma is a chronic inflammatory disorder of the airways affecting over 10% of the global population. It is characterized by airway inflammation, mucus hypersecretion, and bronchial hyperresponsiveness, driven predominantly by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s) in a subset of patients. However, a significant portion of asthmatic individuals present with "type 2-low" asthma that is often refractory to standard inhaled corticosteroid (ICS) therapy. Therefore, developing innovative therapeutic strategies has become essential. Recent studies have highlighted cannabidiol (CBD) as a promising anti-inflammatory agent capable of modulating immune responses. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in asthma. We evaluated the effects of CBD-X on cells involved in asthma pathogenesis using primary human Th2 cells, neutrophils, and asthma mouse model. Our findings indicate that CBD-X extract inhibits Th2 differentiation and reduces the secretion of IL-5 and IL-13, which are crucial cytokines in asthma. Additionally, CBD-X significantly reduces pro-inflammatory cytokines IL-8 and IL-6 in neutrophils and impairs their migration, a critical step in airway inflammation. In a murine asthma model, CBD-X administration led to marked downregulation of IgE and pro-asthmatic cytokines, along with reduced leukocyte, eosinophil, and neutrophil infiltration in lung tissues. These results suggest that CBD-X extract could offer a novel and complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune cell behavior.

MrgprC11+ Jugular Neurons Control Airway Hyperresponsiveness in Allergic Airway Inflammation.

The lung is densely innervated by sensory nerves, the majority of which are derived from the vagal sensory neurons. Vagal ganglia consist of two different ganglia, termed nodose and jugular ganglia, with distinct embryonic origins, innervation patterns, and physiological functions in the periphery. Since nodose neurons constitute the majority of the vagal ganglia, our understanding of the function of jugular nerves in the lung is very limited. This study aims to investigate the role of MrgprC11+ jugular sensory neurons in a mouse allergic asthma model. Our previous study has shown that MrgprC11+ jugular neurons mediate cholinergic bronchoconstriction. In this study, we found that in addition to MrgprC11, several other Mrgpr family members including MrgprA3, MrgprB4, and MrgprD are also specifically expressed in the jugular sensory neurons. MrgprC11+ jugular neurons exhibit dense innervation in the respiratory tract including the larynx, trachea, proximal, and distal bronchus. We also found that receptors for IL-4 and oncostatin M, two critical cytokines promoting allergic airway inflammation, are mainly expressed in jugular sensory neurons. Both IL-4 and oncostatin M can sensitize the neuronal responses of MrgprC11+ jugular neurons. Moreover, ablation of MrgprC11+ neurons significantly inhibited airway hyperresponsiveness in the asthmatic lung, demonstrating the critical role of MrgprC11+ neurons in controlling airway constriction. Our results emphasize the critical role of jugular sensory neurons in respiratory diseases.

Exposure to toluene diisocyanate induces dysbiosis of gut-lung homeostasis: Involvement of gut microbiota

Toluene diisocyanate (TDI) is a major industrial compound that induces occupational asthma with steroid-resistant properties. Recent studies suggest that the gastrointestinal tract may be an effective target for the treatment of respiratory diseases. However, the alterations of the gut-lung axis in TDI-induced asthma remain unexplored. Therefore, in this study, a model of stable occupational asthma caused by TDI exposure was established to detect the alteration of the gut-lung axis. Exposure to TDI resulted in dysbiosis of the gut microbiome, with significant decreases in Barnesiella_intestinihominis, Faecalicoccus_pleomorphus, Lactobacillus_apodemi, and Lactobacillus_intestinalis, but increases in Alistipes_shahii and Odoribacter_laneus. The largest change in abundance was in Barnesiella_intestinihominis, which decreased from 12.14 per cent to 6.18 per cent. The histopathological abnormalities, including shorter length of intestinal villi, thinner thickness of muscularis, reduced number of goblet cells and inflammatory cell infiltration, were found in TDI-treated mice compared to control mice. In addition, increased permeability (evidenced by significantly reduced levels of ZO-1, Occludin and Claudin-1) and activation of TLR4/NF-κB signaling were observed in the intestine of these TDI-exposed mice. Concurrently, exposure to TDI resulted in airway hyperresponsiveness, overt cytokine production (e.g., IL-4, IL-5, IL-13, IL-25, and IL-33), and elevated IgE level within the respiratory tract. The expression of tight junction proteins is reduced and TLR4/NF-κB signaling is activated in the lung following TDI treatment. In addition, correlation analyses showed that changes in the gut microbiota were correlated with TDI exposure-induced airway inflammation. In conclusion, the present study suggests that the immune gut-lung axis may be involved in the development of TDI-induced asthma, which may have implications for potential interventions against steroid-resistant asthma.

Chrysene contribution to bronchial asthma: Activation of TRPA1 disrupts bronchial epithelial barrier via ERK pathway

BackgroundElevated polycyclic aromatic hydrocarbon (PAH) levels are associated with exacerbation of asthma. Chrysene is one of the most prevalent unsubstituted PAHs in the environment. Transient receptor potential ankyrin 1 (TRPA1) can be used as a chemoreceptor to detect inhaled stimuli and plays an important role in the occurrence and deterioration of asthma. Whether exposure to a high concentration of chrysene in the environment can activate TRPA1 and contribute to the development of asthma, potentially through the dysfunction of the bronchial epithelial barrier, remains unclear. MethodsA cell-based assay was performed to verify the downregulation of the expression of E-cadherin and tight junction (TJ) proteins by chrysene in bronchial epithelial cells to explore the role of chrysene-mediated TRPA1 activation in the regulation of TJ protein expression through the extracellular signal-regulated protein kinase (ERK) pathway. Animal tests were conducted to determine whether chrysene could enhance airway hyperresponsiveness (AHR) induced by house dust mites (HDMs) and disrupt barrier function, thereby contributing to asthma. ResultsThe cell-based assay revealed that chrysene could disrupt the function of the bronchial epithelial barrier and decrease the expression levels of E-cadherin, zonula occludens-1 (ZO-1), occludin, and claudin-5 through the ERK pathway. Chrysene induced airway epithelial barrier dysfunction primarily through TRPA1 instead of transient receptor potential vanilloid 1. TRPA1 knockdown was able to attenuate chrysene-induced downregulation of TJ protein expression and downregulate ERK activation (p-ERK). Compared with exposure to HDM alone, coexposure to chrysene and HDM resulted in an increased incidence of AHR, disruption of barrier function, and eosinophilic inflammatory responses in a mouse model of asthma. Coexposure to chrysene and HDM increased TRPA1 expression. The animal test verified that the TRPA1 inhibitor HC030031 could suppress chrysene and HDM-induced asthma in mice. ConclusionsOur findings showed that chrysene contributed to the breakdown of the function of the bronchial epithelial barrier through the TRPA1–ERK axis and therefore acted as an adjuvant to contribute to asthma.

Roles of noncoding RNA in allergic rhinitis.

Allergic rhinitis (AR) is one of the most common respiratory noninfectious diseases and chronic inflammatory diseases, the incidence of which has been increasing in recent years. The main pathological characteristics of AR are repeated inflammation, airway hyperreactivity, mucus hypersecretion, and reversible airway obstruction due to inflammatory cell response. AR occurrence is associated with various factors, including those of genetic and environmental origins. Noncoding RNAs (ncRNAs) are a group of RNA molecules that cannot be converted into polypeptides. The three main categories of ncRNAs include microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs). NcRNAs play a crucial role in controlling gene expression and contribute to the development of numerous human diseases. Articles are selected based on Pubmed's literature review and the author's personal knowledge. The largest and highest quality studies were included. The search selection is not standardized. Several recent studies have indicated the relationship of ncRNAs with the development of respiratory allergic diseases. NcRNAs, including miRNAs, lncRNAs, and circRNAs, are important gene expression regulatory factors. We review the expression and function of ncRNAs in AR, their role as disease biomarkers, and their prospective applicability in future research and clinically. We also discuss interactions between ncRNAs and their influence on AR comprehensively, these interactions are essential for determining the underlying pathological mechanisms further and discovering new drug therapeutic targets. NcRNAs can be used as biomarkers for early AR diagnosis, disease surveillance and prognosis assessment. Various categories of ncRNAs play distinct yet interconnected roles and actively contribute to intricate gene regulatory networks. They are also therapeutic targets and biomarkers in other allergic diseases. This article demonstrates ncRNAs have a wide range of applications in AR treatment. The database covers three key areas: miRNAs, lncRNAs, and circRNAs. Additionally, potential avenues for future research to facilitate the practical application of ncRNAs as therapeutic targets and biomarkers will be explore. With further research and technological development, ncRNAs may provide additional innovative, effective solutions for AR treatment.

(FEV3-FEV1)/FVC: A Terminal-Airflow Variable for Airway Hyperresponsiveness and Inflammation Prediction in Patients With Symptoms Despite Preserved Spirometry

BackgroundSmall-airway function assessment is crucial for asthma diagnosis and management. Abnormalities in terminal airflow deserve attention. ObjectiveThis study investigated whether the ratio of forced expiratory volume in the second and third seconds to forced vital capacity ([FEV3-FEV1]/FVC) correlates with airway hyperresponsiveness (AHR) and inflammation in patients with preserved spirometry. MethodsThis cross-sectional study enrolled patients with FEV1 ≥ 80% predicted, FEV1/FVC ≥ 0.7, and recurring asthma-like symptoms. Data included demographics, fractional exhaled nitric oxide (FeNO), impulse oscillometry, and spirometry. Univariate and combined models predicting AHR was analyzed in 553 patients and validated in 561. Correlations between sputum inflammation and spirometrics were also assessed. ResultsAHR+ patients exhibited higher (FEV3-FEV1)/FVC ratios compared to AHR-. This ratio showed the strongest association with the methacholine dose causing a 20% FEV1 decrease (PD20) and the response dose ratio (RDR)(r = -0.26 and 0.39, respectively; P < .001, both). The area under the receiver operating characteristic curve for AHR diagnosis using (FEV3-FEV1)/FVC was 0.751, increasing to 0.821 when combined with FeNO, confirmed in the validation cohort. (FEV3-FEV1)/FVC was superior to maximal expiratory flow at 50% of forced vital capacity for identifying eosinophilic airway inflammation characterized by elevated FeNO levels. It correlated better with sputum eosinophil count than with the other spirometrics. ConclusionElevated (FEV3-FEV1)/FVC were evident in AHR+ patients with preserved FEV1/FVC ratios. It serves as a sensitive marker of AHR and airway inflammation correlating with RDR, PD20, and sputum eosinophils, suggesting its utility in monitoring patients at risk for uncontrolled asthma.

Curcumin Alleviates Airway Inflammation in Cough-Variant Asthmatic Rats by Modulating M1/M2 Macrophage Polarization.

With the increase of environmental pollution and atypical pathogen infections, the incidence of cough variant asthma (CVA) has been increasing annually, making it a pressing issue of the medical community. This study aims to observe the ameliorative effect of curcumin on a rat model of cough variant asthma. A rat model of cough variant asthma was induced by sensitization with ovalbumin combined with aluminum hydroxide (Al(OH)3), followed by repeated excitations. The drug was administered on the day of the initial nebulized attack, and gavage was administered for 14 d. Pathological changes in the lung tissues were observed, along with the assessment of cough susceptibility and airway resistance. The number of inflammatory cell eosinophils and leukocytes were determined in alveolar lavage fluid. Additionally, serum inflammatory factors and lung tissues Matrix Metalloproteinase-9 (MMP-9) protein were assessed. The level of M1/M2 macrophages was also detected. Following the administration of curcumin, there was reduced inflammatory infiltration, less disordered arrangement of the lung tissue, and decreased abnormal proliferation of lung tissues in cough variant asthma rats compared to the model group. Curcumin treatment led toa notable reduction in cough frequency, a significant decrease in pro-inflammatory factor concentration levels in serum and inflammatory cell counts in the alveolar lavage fluid, and a marked increase in anti-inflammatory factor levels (p < 0.05). Additionally, curcumin administration led to a significant increase in M2-type macrophage levels, while simultaneously decreasing the levels of M1-type macrophages (p < 0.05). The administration of curcumin effectively ameliorates ovalbumin-induced airway inflammation in cough-variant asthma rats. This effect is attributed to modulating macrophage polarization towards the anti-inflammatory M2 phenotype, thereby reducing airway inflammation, airway hyperresponsiveness, and lung tissue injury.

Local receptor-interacting protein kinase 2 inhibition mitigates house dust mite-induced asthma.

House dust mite is the most frequent trigger of allergic asthma, with innate and adaptive immune mechanisms playing critical roles in outcomes. We recently identified the nucleotide-binding oligomerisation domain 1 (NOD1)/receptor-interacting serine/threonine protein kinase 2 (RIPK2) signalling pathway as a relevant contributor to murine house dust mite-induced asthma. This study aimed to evaluate the effectiveness of a pharmacological RIPK2 inhibitor administered locally as a preventive and therapeutic approach using a house dust mite-induced asthma model in wild-type and humanised NOD1 mice harbouring an asthma-associated risk allele, and its relevance using air-liquid interface epithelial cultures from asthma patients. A RIPK2 inhibitor was administered intranasally either preventively or therapeutically in a murine house dust mite-induced asthma model. Airway hyperresponsiveness, bronchoalveolar lavage composition, cytokine/chemokine expression and mucus production were evaluated, as well as the effect of the inhibitor on precision-cut lung slices. Furthermore, the inhibitor was tested on air-liquid interface epithelial cultures from asthma patients and controls. While local preventive administration of the RIPK2 inhibitor reduced airway hyperresponsiveness, eosinophilia, mucus production, T-helper type 2 cytokines and interleukin 33 (IL-33) in wild-type mice, its therapeutic administration failed to reduce the above parameters, except IL-33. By contrast, therapeutic RIPK2 inhibition mitigated all asthma features in humanised NOD1 mice. Results in precision-cut lung slices emphasised an early role of thymic stromal lymphopoietin and IL-33 in the NOD1-dependent response to house dust mite, and a late effect of NOD1 signalling on IL-13 effector response. RIPK2 inhibitor downregulated thymic stromal lymphopoietin and chemokines in house dust mite-stimulated epithelial cultures from asthma patients. These data support that local interference of the NOD1 signalling pathway through RIPK2 inhibition may represent a new therapeutic approach in house dust mite-induced asthma.

Bronchial asthma with normal forced expiratory volume in 1 second (FEV1) compared with low FEV1.

Cough variant asthma (CVA) is characterized by cough as a sole symptom and normal pulmonary function. However, it is unclear whether CVA really common among asthmatic patients with normal forced expiratory volume in 1 second (FEV1). The aim of this study was to evaluate the incidence of cough alone symptom among the subjects with normal FEV1 and to evaluate their differences from ordinary asthmatic subjects. We defined normal FEV1 as ≥90% predicted based on the article of Kotti GH. Of the patients with normal FEV1, we chose subjects without wheeze, and the duration of cough was not to ask, since the symptoms often occurred with acute exacerbation and timing of visiting a doctor depended on each patient's perception. Test for airway hyperresponsiveness was not performed in this study. Visual analogue scale (VAS) scores for cough and dyspnea, FEV1, and fractional exhaled nitric oxide (FeNO) responsiveness to inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) treatment were compared in patients with normal FEV1 and with low FEV1 <90%. Correlations of changes in symptoms with changes of FEV1, FeNO, peripheral eosinophil count, and serum immunoglobulin E (IgE) at single time point were also examined in each group and in overall patients. The participants were 329 physician-diagnosed treatment-naive patients with asthma who were divided into 187 in normal FEV1 and 142 in low FEV1 groups. Cough without dyspnea was present in 16 patients (8.6%) in the normal FEV1 group, suggesting candidates for CVA in this analysis were quite few. Improvement in symptoms after treatment was similar between both groups. But VAS scores of dyspnea were still higher in the low FEV1 group. The degree of improvement in FEV1 after ICS/LABA treatment was less in the normal FEV1 group than in the low FEV1 group, but was still evident. Peripheral eosinophil count, serum IgE, and FeNO values before treatment were lower in the normal FEV1 group. In overall patients, improvements of symptoms after treatment were significantly correlated with FEV1 changes. Improvement of dyspnea was also significantly related to peripheral eosinophil count and change of FeNO, whereas improvement of cough was not related to these T helper 2 (Th2) response markers. Candidates for CVA among the patients with asthma with predicted FEV1 ≥90% were few. Participants with normal FEV1 respond well to ICS/LABA treatment for improvement of symptom. The change of FEV1 after treatment, and the pre-treatment blood eosinophil count, serum IgE, and FeNO were lower in normal FEV1 cases than in low FEV1 cases. These observations suggest asthmatic patients with normal FEV1, including candidates for CVA having just common mild asthma. In overall participants, symptoms of cough and dyspnea were similar, but were not identical in relation to the Th2 background.

Diagnostic Challenges and Pathogenetic Differences in Biomass-Smoke-Induced versus Tobacco-Smoke-Induced COPD: A Comparative Review.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a major global health challenge, primarily driven by exposures to tobacco smoke and biomass smoke. While Tobacco-Smoke-Induced COPD (TSCOPD) has been extensively studied, the diagnostic challenges and distinct pathogenesis of Biomass-Smoke-Induced COPD (BSCOPD), particularly in low- and middle-income countries, remain underexplored. Objective: To explore the differences in clinical manifestations, pulmonary function, and inflammatory profiles between BSCOPD and TSCOPD and highlight the diagnostic complexities of BSCOPD. Methods: This review analyzes the current literature comparing BSCOPD with TSCOPD, focusing on distinctive pathophysiological mechanisms, inflammatory markers, and oxidative stress processes. Results: BSCOPD presents differences in clinical presentation, with less emphysema, smaller airway damage, and higher rates of pulmonary hypertension compared to TSCOPD. BSCOPD is also characterized by bronchial hyperresponsiveness and significant hypoxemia, unlike TSCOPD, which exhibits severe airflow obstruction and emphysema. Additionally, the inflammatory profile of BSCOPD includes distinct mucous hypersecretion and airway remodeling. Conclusions: The unique genetic, epigenetic, and oxidative stress mechanisms involved in BSCOPD complicate its diagnosis and management. Biomass smoke's underrecognized impact on accelerated lung aging and exacerbation mechanisms emphasizes the need for targeted research to refine diagnostic criteria and management strategies for BSCOPD. Future directions: Further research should focus on identifying specific biomarkers and molecular pathways to enhance early diagnosis and improve clinical outcomes in populations exposed to biomass smoke.

Perinatal administration of Saccharomyces cerevisiae UFMG A-905 prevents asthma development in the offspring of mice.

Asthma prevalence has been increasing in communities that become more urbanised. Our previous results showed that Saccharomyces cerevisiae UFMG A-905 prevented the development of asthma symptoms and characteristics in a dose-dependent manner. Perinatal programming theory proposes that early exposure to some stimuli may have a protective effect in adult life. The aim of this study was to evaluate the effects of perinatal administration of S. cerevisiae UFMG A-905 in the prevention of asthma in the offspring of mice. S. cerevisiae UFMG A-905 was cultured in YPD broth medium and administered to three groups of mice: before conception, during gestation and lactation (CGL group); during gestation and lactation (GL group); and only during lactation (L group). The offspring of these animals were sensitised and challenged with ovalbumin. Two control groups received saline in the same periods. After, in vivo measurements of airway hyperresponsiveness (AHR) were performed. Total and differential cell count in bronchoalveolar lavage (BAL); ELISA for interleukin (IL)-4, IL-5, IL-10, IL-13, and IL-17A in the lung homogenate or BAL; and ELISA for ovalbumin (OVA)-specific immunoglobulin E (IgE) were performed. The animals of the CGL, GL, and L group, when compared to the OVA group, presented a significant reduction of AHR ( P < 0.01), levels of IL-5 ( P < 0.001) in BAL, and IL-4 ( P < 0.05) and IL-13 ( P < 0.01) in the lung homogenate. Serum IgE levels were significantly higher ( P < 0.05) in CGL and GL groups when compared to the OVA group, but not in the L group. Only in the group L, there was a significant decrease in the number of total cells ( P < 0.01) and eosinophils ( P < 0.05). Perinatal administration of S. cerevisiae UFMG A-905 prevented the development of asthma-like characteristics and may be an option for asthma management. The protective effects on the offspring were more prominent when the yeast was given during lactation.

Role of fractional exhaled nitric oxide in patients with sickle cell disease

IntroductionPatients with sickle cell disease exhibit different patterns in pulmonary function tests. In particular, there is little evidence on the fractional exhaled nitric oxide (FeNO) test, and its value ranges and its interpretation in these patients have been under debate in recent years. MethodsWe conduced a cross-sectional, observational and descriptive study between November 2021 and January 2023 including patients aged 6–18 years with sickle cell disease able to perform the FeNO test. We applied the GLI-2012 reference values and the ERS/ATS standards. We defined statistical significance as P < 0.05. ResultsThe sample included 43 patients with a median age of 12 years (IQR, 10−15). We did not find an association between significantly elevated FeNO (≥25 ppb) and the diagnosis of asthma (P = 0.37), an obstructive pattern in spirometry (P = 0.67), a positive bronchodilator test (P = 0.53), clinical bronchial hyperreactivity in the context of cold or flu-like symptoms (P = 0.48), cough with exercise (P = 0.42) or nocturnal cough (P = 1.0), but found an association with peripheral eosinophilia (P < 0.01). ConclusionsWe found no association between FeNO values and the classic features of asthma (clinical or spirometric) in patients with sickle cell disease. Therefore, airway inflammation mechanisms are probably different in these patients.

Nobiletin, as a Novel PDE4B Inhibitor, Alleviates Asthma Symptoms by Activating the cAMP-PKA-CREB Signaling Pathway.

Asthma is a chronic airway inflammation that is considered a serious public health concern worldwide. Nobiletin (5,6,7,8,3',4'-hexamethyl flavonoid), an important compound isolated from several traditional Chinese medicines, especially Citri Reticulatae Pericarpium, is widely used for a number of indications, including cancer, allergic diseases, and chronic inflammation. However, the mechanism by which nobiletin exerts its anti-asthmatic effect remains unclear. In this research, we comprehensively demonstrated the anti-asthmatic effects of nobiletin in an animal model of asthma. It was found that nobiletin significantly reduced the levels of inflammatory cells and cytokines in mice and alleviated airway hyperresponsiveness. To explore the target of nobiletin, we identified PDE4B as the target of nobiletin through pharmacophore modeling, molecular docking, molecular dynamics simulation, SPR, and enzyme activity assays. Subsequently, it was found that nobiletin could activate the cAMP-PKA-CREB signaling pathway downstream of PDE4B in mouse lung tissues. Additionally, we studied the anti-inflammatory and anti-airway remodeling effects of nobiletin in LPS-induced RAW264.7 cells and TGF-β1-induced ASM cells, confirming the activation of the cAMP-PKA-CREB signaling pathway by nobiletin. Further validation in PDE4B-deficient RAW264.7 cells confirmed that the increase in cAMP levels induced by nobiletin depended on the inhibition of PDE4B. In conclusion, nobiletin exerts anti-asthmatic activity by targeting PDE4B and activating the cAMP-PKA-CREB signaling pathway.

Eosinophils prevent diet-induced airway hyperresponsiveness in mice on a high-fat diet.

Eosinophils contribute to metabolic homeostasis and airway hyperresponsiveness, but their specific role in obesity-related airway hyperresponsiveness remains unclear. To address this, we used transgenic mice that overexpress interleukin-5 (IL-5) in peripheral T cells (+IL-5T) and wild-type controls. On a normal diet, +IL-5T and wild-type mice have similar body weight, body fat, and airway nerve-mediated reflex bronchoconstriction in response to inhaled serotonin. Feeding wild-type mice a 61.6% high-fat diet resulted in significantly increased body weight, body fat, fasting glucose, fasting insulin, and reflex bronchoconstriction induced by serotonin, which was blocked by vagotomy. In contrast, +IL-5T mice on a high-fat diet gained less body weight and fat than wild-type mice on the same diet and did not exhibit potentiation in fasting glucose, fasting insulin, or reflex bronchoconstriction induced by serotonin. Compared with wild-type mice, +IL-5T mice on normal diet had significantly more adipose tissue eosinophils, and this was further increased by high-fat diet. High-fat diet did not increase adipose tissue eosinophils in wild-type mice. Our findings suggest that adipose tissue eosinophils may play a role in regulating body fat, thereby reducing insulin, which is a mediator of obesity-related airway hyperresponsiveness. Thus, our data indicate adipose tissue eosinophils may be an important avenue for research in obesity-related asthma.NEW & NOTEWORTHY This study investigates how eosinophils influence systemic metabolism and airway function in obesity. Known for their immune functions, eosinophils also mitigate obesity-related hyperinsulinemia, reducing airway hyperresponsiveness in obese mice models. The findings suggest potential therapeutic strategies targeting the intricate interplay among neurons, eosinophils, and the endocrine system to alleviate asthma in obesity. This research provides novel insights into the critical neuro-immune-endocrine interactions essential for managing obesity-related asthma.