Search Results (350)

Diagnosing and prognosing immune-mediated airway diseases, like hypersensitivity pneumonitis (HP) and sarcoidosis, is complicated due to their overlapping symptoms and the lack of definitive biomarkers. Hence, we wanted to compare bronchoalveolar lavage (BAL) cytokine and chemokine profiles from 92 patients with different immune-mediated and inflammatory airway diseases, namely, HP, sarcoidosis, non-allergic asthma, amiodarone lung, and EGPA. We also compared pulmonary function parameters, BAL’s cellularity, and lymphocyte immunophenotypes. We found significant differences across all measured lung functions (VC, VC%, FEV1, FEV1%, and Tiff%) and in the number of macrophages, lymphocytes, neutrophils, and eosinophils. Furthermore, we showed significant differences in CD4, CD8, and CD4/8 across all included ILDs and OLDs; however, no significant differences were found in CD3, CD19, NK, or NKT. We identified nine biomarkers (IL-1β, IL-6, IL-8, IL-13, VEGF, angiogenin, C4a, RANTES, and MCP-1) that significantly differ in the BAL of patients with HP and sarcoidosis and showed that RANTES and IL-6 are associated with fibrotic outcome. We have demonstrated that interstitial and obstructive lung diseases differ in cytokine and cellular lung imprint, which may, in the future, enable the determination of the disease subtype and thus the identification of targets for the treatment of individuals or subgroups within diseases. Full article

IgG antibodies, signaling via the inhibitory receptor, FcγRIIb, are potent inhibitors of IgE-mediated mast cell activation. We have previously reported that in addition to blocking mast cell degranulation, inhibitory IgG signals shut down a proinflammatory transcriptional program in which mast cells produce cytokines and chemokines known to drive type 2 tissue inflammation. To determine whether such effects of allergen-specific IgG can modulate allergic inflammation in vivo, we examined the airways of mice sensitized to ovalbumin (OVA) by intraperitoneal injection and then challenged with intranasal OVA. Pretreatment with allergen-specific IgG significantly reduced the recruitment of inflammatory cells, including macrophages and eosinophils, into the lungs of OVA-sensitized mice. The bronchoalveolar lavage fluid of OVA-challenged mice contained elevated levels of chemokine ligands (CCL2 and CCL24) and interleukin-5, a response that was markedly blunted in animals receiving allergen-specific IgG. IgG-treated animals exhibited attenuated allergen-induced production of IgE, IL-4, and IL-13, along with impaired OVA-induced goblet cell hyperplasia and Muc5ac expression and suppressed airway hyperresponsiveness, consistent with a shift away from a Th2 response. Using mice with a lineage-specific deletion of FcγRIIb, we demonstrated that each of these protective effects of IgG was dependent upon the expression of this receptor on mast cells. Overall, our findings establish that allergen-specific IgG can reduce allergen-driven airway inflammation and airway hyperresponsiveness and point to a mechanistic basis for the therapeutic benefit of aeroallergen-specific IgG therapy. Full article

Asthma is defined as a chronic respiratory disease, the processes of which are mainly related to the hyperreactivity of the immune system. Airway hyperresponsiveness and remodeling are other hallmarks of asthma that are strongly involved in the progression of the disease. Moreover, asthma is associated with the occurrence of atopic dermatitis, chronic sinusitis, allergic rhinitis, and a high profile of T2-type cytokines, such as IL-4, IL-5 and IL-13. The hyperresponsiveness of the immune system is a consequence of aberrant levels of alarmins, endogenous molecules that induce pro-inflammatory responses. They are released as a result of a defect or cell death, leading to the initiation of an inflammatory reaction. High-mobility group box 1 (HMGB1), S100 proteins, interleukin-33 (IL-33), thymic stromal lymphopoietin (TSLP), and IL-25 bind to various receptors, influencing the behavior of immune cells, resulting in stimulated migration and activation of these cells. In this review, we will discuss the potential role of alarmins in the pathogenesis of asthma. Full article

Asthma represents a heterogeneous disorder characterized by a dynamic balance between pro-inflammatory and anti-inflammatory forces, with allergic sensitization contributing substantially to airway hyperresponsiveness and remodeling. Central to its pathogenesis are cytokines such as IL-4, IL-5, IL-13, IL-17, and IL-33, which drive recruitment of eosinophils, neutrophils, and other effector cells, thereby precipitating episodic exacerbations in response to viral and environmental triggers. Conventional biomarkers, including blood and sputum eosinophil counts, IgE levels, and fractional exhaled nitric oxide, facilitate phenotypic classification and guide the emerging biologic era. Monoclonal antibodies targeting IgE (omalizumab) and IL-5 (mepolizumab, benralizumab, reslizumab, depemokimab) have demonstrated the ability to reduce exacerbation frequency and improve lung function, with newer agents such as depemokimab offering extended dosing intervals. Itepekimab, an anti-IL-33 antibody, effectively engages its target and mitigates tissue eosinophilia, while CM310-stapokibart, tralokinumab, and lebrikizumab inhibit IL-4/IL-13 signaling with variable efficacy depending on patient biomarkers. Comparative analyses of these biologics, encompassing affinity, dosing regimens, and trial outcomes, underscore the imperative of personalized therapy to optimize disease control in severe asthma. Full article

Hexokinase catalyzes the first rate-limiting step glycolysis. However, the roles of hexokinase 2 (HK2) in asthma remain incompletely understood. This study aimed to investigate metabolic alterations in asthma, focusing on the expression, function and regulation of HK2. In this study, non-targeted metabolomics analysis of 20 asthma patients and 15 healthy controls identified metabolic alterations in asthma, particularly in the glycolytic pathways. Consistently, HK2 expression was elevated in both asthma individuals and mice with allergic airway inflammation. Airway epithelium–specific HK2 knockdown and pharmacological inhibition with 2-deoxy-D-glucose (2-DG) significantly attenuated airway inflammation and hyperresponsiveness in mice induced by ovalbumin/ lipopolysaccharide. Mechanistic analyses demonstrated that HK2 regulates epithelial apoptosis and inflammation via interaction with peptidylprolyl isomerase F (PPIF), independent of voltage-dependent anion channel 1 (VDAC1). Asthma is associated with metabolic reprogramming, characterized by alterations in lipid and glucose metabolism. These findings establish HK2 plays a crucial role in asthma pathogenesis by promoting airway epithelial apoptosis and inflammation in asthma, suggesting its potential as a therapeutic target. Full article

Asthma is a chronic and heterogeneous inflammatory airway disease with diverse clinical endotypes and limited curative treatment options. Recent systems biology analyses identified four potential molecular triggers—AKT1, MAPK13, STAT1, and TLR4—as candidate regulators of asthma-associated signaling pathways. This study aimed to validate the expression of these four proteins and their downstream signaling elements in peripheral blood mononuclear cells (PBMCs) from patients with allergic asthma (AA), nonallergic asthma (NA), and healthy controls (HC), to explore their potential as biomarkers or therapeutic targets. For that, PBMC samples were collected from 45 AA patients, 17 NA patients, and 15 HC subjects. Gene and protein expression of AKT1, MAPK13, STAT1, and TLR4 were quantified using RT-qPCR and Western blotting. Expression patterns were compared across groups and stratified by asthma severity. Correlations with clinical parameters (FEV1, FVC, FeNO, IgE, eosinophil counts) and treatment regimens were also assessed. All four target genes showed significantly reduced expression in asthma patients compared to controls (p < 0.001), with the most marked downregulation in NA patients. At the protein level, MAPK13 and TLR4 showed significant differential expression. Stratification by severity revealed a stepwise reduction in gene expression in AA patients, correlating with disease severity, whereas NA patients showed uniformly low expression regardless of severity. Multiple pathway-related genes, including RELA, SMAD3, NFATC1, and ALOX5, were also downregulated, particularly in NA patients. Notably, differential correlations were observed between gene expression and lung function parameters in AA vs. NA groups. In conclusion, this study supports the potential involvement of AKT1, MAPK13, STAT1, and TLR4 in asthma pathogenesis and highlights differences between allergic and nonallergic asthma at the molecular level. These proteins and their associated pathways may serve as future targets for biomarker development or endotype-specific therapies. Further studies in larger and more diverse cohorts, including functional validation, are warranted. Full article

Asthma is a chronic inflammatory airway disease that can be aggravated by metabolic comorbidities such as type 2 diabetes mellitus (DM2) and obesity. Elevated levels of methylglyoxal (MGO), a reactive glycolysis byproduct, have been associated with exacerbation of allergic airway disease. SGLT2 inhibitors have been successfully employed in DM2 treatment. Here, we hypothesized that elimination of MGO might be a potential anti-inflammatory mechanism of SGLT2 inhibitors. This study aimed to evaluate the effects of empagliflozin on ovalbumin (OVA)-induced airway inflammation in mice chronically exposed to MGO. Male C57BL/6 mice sensitized with OVA were exposed to 0.5% MGO for 12 weeks and treated with empagliflozin (10 mg/kg, gavage, two weeks). MGO exposure significantly enhanced airway eosinophil infiltration, mucus production and collagen deposition, as well as levels of IL-4, IL-5, eotaxin and TNF-α. Empagliflozin treatment significantly reduced OVA-induced airway disease, which was accompanied by reductions in IgE, IL-4, IL-5, eotaxin, and TNF-α levels. Empagliflozin significantly reduced the MGO levels in serum, and immunohistochemical staining, and protein expression of MGO-hydroimidazolone (MG-H1), while increasing IL-10 levels and glyoxylase-1 (GLO 1) activity in lungs. In conclusion, empagliflozin efficiently removes MGO from circulation, while increasing the MGO detoxification by GLO 1, thereby mitigating the OVA-induced inflammation in MGO-exposed mice. Full article

Allergic diseases share a type 2 immune reaction and elevated oxidative stress, contributing to disease pathogenesis and exacerbations. Vitamin C (ascorbic acid), a fundamental exogenous antioxidant, has been hypothesized to attenuate these pathological mechanisms. This narrative review critically examined the most recent evidence concerning the role of vitamin C in preventing and managing allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis. This narrative review consisted of three steps: conducting the search, reviewing abstracts and full texts, and discussing results. For this reason, we consulted the PubMed database to detect the pertinence of studies according to the review’s conduct. The final search ended in March 2025 and included English-language-based international articles, online reports, and electronic books. The keywords “vitamin C and allergic disease” and “vitamin C and immune system” were used. After the complete search, we read the abstracts to ensure that they concerned the topic of interest. Recent evidence suggests a protective role for vitamin C in asthma, with several studies reporting reduced oxidative stress markers, improved lung function, and decreased airway inflammation following regular intake or supplementation. Higher dietary vitamin C intake correlates with lower asthma prevalence and severity, particularly in pediatric populations. Conversely, the findings regarding allergic rhinitis and atopic dermatitis are heterogeneous. While topical ascorbic acid derivatives show promise in atopic dermatitis models, oral vitamin C intake does not appear to affect allergic rhinitis or dermatitis risk significantly. Vitamin C demonstrates potential as an add-on therapy in asthma management by attenuating oxidative stress and type 2 respiratory inflammation. However, its role in allergic rhinitis and atopic dermatitis remains less clear. Further multicentric, well-designed clinical trials are necessary to establish definitive guidelines for vitamin C supplementation in allergic disease management. Full article

Asthma is a chronic and multifaceted respiratory condition that affects over 300 million individuals across the globe. It is characterized by persistent inflammation of the airways, which leads to episodes of wheezing, breathlessness, chest tightness, and coughing. The most prevalent form of asthma is classified as Type 2 or T2-high asthma. In this variant, the immune response is heavily driven by eosinophils, mast cells, and T-helper 2 (Th2) cells. These components release a cascade of cytokines, including interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13). This release promotes several processes: the production of immunoglobulin E (IgE), which is integral to allergic responses; the recruitment of eosinophils—white blood cells that contribute to inflammation and tissue damage. Conversely, non-Type 2 or T2-low asthma is typically associated with a different inflammatory profile characterized by neutrophilic inflammation. This type of asthma is driven by T-helper 1 (Th1) and T-helper 17 (Th17) immune responses, which are often present in older adults, smokers, and those suffering from more severe manifestations of the disease. Among asthmatic patients, approximately 80–85% of cases are classified as T2-high asthma, while only 15–20% are T2-low asthma. Treatment of asthma focuses heavily on controlling inflammation. Inhaled corticosteroids remain the cornerstone therapy for managing T2-high asthma. For more severe or treatment-resistant cases, biologic therapies targeting specific inflammatory pathways, such as anti-IgE (omalizumab), anti-IL-5 (mepolizumab, benralizumab), and anti-IL-4/IL-13 (dupilumab), have shown great promise. For T2-low asthma, macrolide antibiotics like azithromycin and other novel therapies are being explored. This article reviews the safety, efficacy, and indications of the currently approved biologics and discusses potential novel biologics for asthma. Full article

Allergic rhinitis and asthma are common chronic airway diseases that present significant public health challenges. Previous research has shown how the nasal and oral mycobiomes influence the onset, progression and severity of these two conditions, but no study so far has directly compared those mycobiomes within the same cohort during health and disease. To address this gap, I analyzed next-generation fungal ITS sequence data from 349 participants, including individuals with allergic rhinitis, asthma, and healthy controls. The nasal and oral mycobiomes showed a great overlap in composition but differed significantly (p < 0.04) in the relative abundance of several dominant genera. Moreover, only 18.6% of the fungal amplicon variants were shared among cavities. Microbial alpha-diversity was significantly higher (p < 0.05) in the nasal cavity, while beta-diversity varied significantly (p < 0.045) across all indices and clinical groups. Fungal networks were largely fragmented and showed relatively low ecological niche specialization, which contrasts with a previous study of bacteriomes from the same cohort. These networks also differed in structure, complexity and keystone nodes across clinical phenotypes. Overall, these findings highlight that the nasal and oral mycobiomes play distinct yet interconnected roles in allergic rhinitis and asthma. Full article

TGF-β is a central mediator of pulmonary allergic inflammation recently associated with lung metastasis of osteosarcoma. Given the controversial links between cancer and allergic diseases, this study aimed to evaluate the effects of allergic airway inflammation—particularly TGF-β—on osteosarcoma lung metastasis using a comorbidity mouse model. Osteosarcoma cells were implanted in BALB/c mice with induced allergic airway inflammation. Lung metastasis was quantified, while PCNA/TGF-β expression was assessed by immunohistochemistry and digital pathology. Bioinformatic analyses of patient datasets compared TGF-β and PCNA expression in metastatic vs. normal tissues, and their association with survival. Mice with allergic inflammation showed increased lung metastases associated with TGF-β production. In patient samples, both TGF-β and PCNA were upregulated in metastatic tissues and correlated with poor overall survival. PCNA was also linked to genes involved in cell proliferation, DNA replication, and repair. Our results show an association between allergic airway inflammation and extensive lung metastasis of osteosarcoma in a comorbidity mouse model with elevated expression of TGF-β and PCNA. Full article

The global prevalence of asthma is approximately 4.3%, and current asthma treatments focus on reducing symptoms, maintaining normal activity levels, and preventing the deterioration of lung function, rather than achieving a cure or complete prevention. We identified isochlorogenic acid C (ICGAC) as a potential natural medicine for the treatment of asthma. However, the bioavailability of ICGAC was low, ranging from 14.4% to 16.9%, suggesting the involvement of the gut microbiota. The full spectrum of ICGAC’s anti-asthmatic mechanism remains to be elucidated. This study investigated the mechanism by which ICGAC alleviates allergic asthma through the gut–lung axis. We discovered anti-asthma pathways and targets based on the selective regulation of lipid peroxidation and employed pharmacological tools to preliminarily validate their mechanisms and efficacy. To study the role of ICGAC in regulating the gut microbiota, we performed 16S rRNA gene sequencing and metabolite analysis. Furthermore, by combining molecular biology and lipid metabolomics, we elucidated the underlying anti-asthma mechanisms of ICGAC. The effective form of ICGAC varies between single and long-term administration. The oral administration of ICGAC enhances the gut-microbiota-derived production of short-chain fatty acids (SCFAs) as the active substances, modulates immune cell activity, influences the differentiation of T- and B-cells, and reduces airway inflammation. ICGAC also regulates the metabolic network of lipid mediators (LMs) and polyunsaturated fatty acids (PUFAs), thus exerting anti-inflammatory effects by modulating arachidonate lipoxygenase (ALOX) activity and LM levels. In addition, ICGAC enhanced the antioxidant response by upregulating the expression of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and nuclear factor erythroid 2-related factor 2 (Nrf2), while inhibiting the release of interleukin-4 (IL-4), thereby suppressing asthma inflammation and IgE production. The anti-asthmatic mechanism of oral ICGAC involves the inhibition of lipid peroxidation by chlorogenic acid (CGA) and SCFAs produced by the gut microbiota. ICGAC suppresses asthma-associated inflammatory and oxidative stress responses through the upregulation of GPX4, SLC7A11, and Nrf2 in lung tissue. This study not only provides a solid foundation for the potential clinical use of ICGAC in asthma treatment but also offers novel insights for future research and therapeutic strategies targeting asthma. Full article

Allergic rhinitis and asthma are significant public health concerns worldwide. While previous studies have explored how nasal and buccal bacteriotas influence these conditions, few have directly compared their bacteriomes within the same cohort. To bridge this gap, I analyzed 16S rRNA next-generation sequencing data from 347 individuals, including participants with allergic rhinitis, asthma and healthy controls. The nasal and buccal bacteriomes shared all dominant bacterial taxa but differed significantly in their phylum- and genus-level relative abundances. Alpha-diversity was significantly higher in the buccal cavity, while beta-diversity varied significantly across all indices and clinical groups. Over 80% of the predicted metabolic pathways were differentially regulated between the two cavities, yet these functional differences remained fairly consistent across clinical groups. Naso-buccal bacterial networks exhibited striking differences in structure, complexity and hub nodes. Notably, the network of healthy controls showed a clear segregation between nasal and buccal bacteria, with 93.5% of the interactions occurring within each respective cavity, and contained few pathogenic keystone taxa. In contrast, bacterial networks from diseased individuals exhibited reduced ecological specialization and more pathogenic keystone taxa linked to airway disease. These findings, thus, demonstrate that the naso-buccal bacteriome plays distinct yet interconnected roles in allergic rhinitis and asthma. Full article

Airway defensive reflexes, such as pharyngeal swallowing, coughing, and sneezing, play a pivotal role in maintaining airway homeostasis. These reflexes are controlled by complex mechanisms primarily governed by specific neuronal circuitry in the brainstem, referred to as central pattern generators. These behaviors also require optimal conditions for the peripheral organs within the airway and alimentary tracts, including the nose, pharynx, larynx, and trachea, which are vital for ensuring appropriate responsiveness and motor outputs. Oxidative stress is linked to the development and progress of impaired functions of those behaviors. Dysphagia caused by central or peripheral impairments, such as neurodegeneration of related neuronal networks and laryngeal desensitization, is likely associated with an increased level of oxidative stress. Chronic inflammation and allergic airway sensitization in the lower airways, including asthma, elevate oxidative stress levels and diminish the activity of antioxidant defense enzymes, which exacerbate the severity of respiratory conditions. Antioxidant supplements offer promising therapeutic benefits by facilitating the recovery of distorted airway defensive reflexes, although limited information has been provided concerning therapeutic strategies. Further studies are necessary to enhance our understanding of the pathophysiology of dysphagia and airway diseases related to oxidative stress, as well as to develop new treatment strategies for these disorders. Full article

Phellodendri cortex (PC), the dried trunk bark of Phellodendron amurense RUPR, has traditionally been used to treat patients who suffer from gastroenteritis, abdominal pain or diarrhea. Its major bioactive compounds include alkaloids and limonin, and many physiological activities including anti-microbial, anti-ulcer and anti-cancer as well as anti-inflammation have been reported. Although PC is an effective anti-inflammatory natural substance that inhibits the inflammatory response, its effect on allergic asthma has not yet been investigated. The aim of this study was to evaluate the anti-asthmatic effects of PC in an ovalbumin (OVA)-induced murine model of asthma. As a result, PC inhibited airway eosinophil accumulation, the influx of inflammatory cells, airway hyperresponsiveness (AHR), production of Th2 cytokines (IL-4, IL-5 and IL-13) and tumor necrosis factor-α (TNF-α) in the bronchoalveolar lavage fluid and/or lung, as well as OVA-specific immunoglobulin E (IgE) in the serum. Furthermore, PC suppressed the gene expression of IL-4, IL-5, IL-13, TARC and CCR3, and attenuated unique histological changes that are associated with airway inflammatory reactions including the infiltration of various inflammatory cells, collagen deposition and goblet cell hyperplasia in lung tissues. These results indicate that PC may have preventive and/or therapeutic effects for allergic asthma via the inhibition of cytokines, chemokines and chemokine receptors associated with allergic inflammation. Full article