The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA—disseminated and implemented in over 70 countries globally—is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.

Background: The association between sensitizations and severity of allergic diseases is controversial. Objective: This study was to investigate the association between severity of asthma and rhinitis and degree of specific allergic sensitization in allergic patients in China. Method: A cross-sectional survey was performed in 6304 patients with asthma and/or rhinitis from 4 regions of China. Patients completed a standardized questionnaire documenting their respiratory and allergic symptoms, their impact on sleep, daily activities, school and work. They also underwent skin prick tests with 13 common aeroallergens. Among the recruited subjects, 2268 provided blood samples for serum measurement of specific IgE (sIgE) against 16 common aeroallergens. Results: Significantly higher percentage of patients with moderate-severe intermittent rhinitis were sensitized to outdoor allergens while percentage of patients sensitized to indoor allergens was increased with increasing severity of asthma. Moderate-severe intermittent rhinitis was associated with the skin wheal size and the level of sIgE to Artemisia vulgaris and Ambrosia artemisifolia (p < 0.001). Moderate-severe asthma was associated with increasing wheal size and sIgE response to Dermatophagoides (D.) pteronyssinus and D. farinae (p < 0.001). Moderate-severe rhinitis and asthma were also associated with increase in number of positive skin prick test and sIgE. Conclusions: Artemisia vulgaris and Ambrosia artemisifolia sensitizations are associated with the severity of intermittent rhinitis and D. pteronyssinus and D. farinae sensitizations are associated with increasing severity of asthma in China. Increase in number of allergens the patients are sensitized to may also increase the severity of rhinitis and asthma.

Background: It is now recognized that asthma can present in different forms. Typically, asthma present with symptoms of wheeze, breathlessness and cough. Atypical forms of asthma such as cough variant asthma (CVA) or chest tightness variant asthma (CTVA) do not wheeze. We hypothesize that these different forms of asthma may have distinctive cellular and molecular features. Methods: 30 patients with typical or classical asthma (CA), 27 patients with CVA, 30 patients with CTVA, and 30 healthy control adults were enrolled in this prospective study. We measured serum IgE, lung function, sputum eosinophils, nitric oxide in exhaled breath (FeNO). We performed proteomic analysis of induced-sputum supernatants by mass spectrometry. Results: There were no significant differences in atopy and FEV₁ among patients with CA, CVA, and CTVA. Serum IgE, sputum eosinophil percentages, FeNO, anxiety and depression scores were significantly increased in the three presentations of asthmatic patients as compared with healthy controls but there was no difference between the asthmatic groups. Comprehensive mass spectrometric analysis revealed more than a thousand proteins in the sputum from patients with CA, CVA, and CTVA, among which 23 secreted proteins were higher in patients than that in controls. Conclusions: Patients with CA, CVA, or CTVA share common clinical characteristics of eosinophilic airway inflammation. And more importantly, their sputum samples were composed with common factors with minor distinctions. These findings support the concept that these three different presentations of asthma have similar pathogenetic mechanism in terms of an enhanced Th2 associated with eosinophilia. In addition, this study identified a pool of novel biomarkers for diagnosis of asthma and to label its subtypes. Trial registrationhttp://www.chictr.org.cn (ChiCTR-OOC-15006221)

Migraine is a complex neurological disorder with high prevalence but unclear pathogenesis. Numerous studies have suggested that migraine is associated with alterations in brain imaging phenotypes (BIPs) and dysregulation of cerebrospinal fluid (CSF) and brain metabolism; however, causal evidence remains limited. Mendelian randomization (MR) offers a powerful approach for inferring causality using genetic instruments. Firstly, we conducted linkage disequilibrium score regression (LDSC) to evaluate genetic correlations between migraine, including the migraine with aura (MA) and migraine without aura (MO) subtypes, and BIPs, CSF, and brain metabolites. Traits that showed genetic correlations with migraine, MA, or MO were retained for subsequent MR analysis with the corresponding migraine phenotype. Traits showing significant correlations were analyzed using bidirectional two-sample MR (TSMR), followed by two-step TSMR to identify cross-omics mediation effects. Additionally, We also applied summary-data-based MR (SMR) to detect brain-region-specific genes with potential causal effects. Enrichment analyses (KEGG, GO, PPI, transcription factor, and miRNA networks) were conducted to further explore underlying mechanisms. LDSC identified significant genetic correlations with 73 BIPs and 40 metabolites for overall migraine, 71 BIPs and 37 metabolites for MA, and 49 BIPs and 62 metabolites for MO. Enrichment analysis revealed that genetically associated metabolites were predominantly involved in amino acid metabolic pathways. TSMR identified 6 BIPs and 2 metabolites causally linked to overall migraine, 3 BIPs and 3 metabolites to MA, and 2 BIPs and 5 metabolites to MO. Most migraine-related BIPs mapped to the parietal lobe. Reverse MR analysis showed that overall migraine causally influenced 4 BIPs and 3 metabolites, while MA and MO affected 1 BIP and 1 metabolite, and 3 BIPs and 1 metabolite, respectively. Mediation analysis revealed five significant mediation pathways were identified. SMR analysis identified FAM83B and CIB2 consistently showing inhibitory effects across most regions. Enrichment analysis showed that these genes were predominantly involved in immune activation and cell adhesion. Our study integrates cross-omics analyses to investigate the causal links between brain structure, metabolic alterations, gene expression, and migraine including its MA and MO subtypes. These findings provide novel insights into the pathophysiological mechanisms and potential targets for intervention across migraine subtypes.

Background: Sputum immunoglobulin G (Sp-IgG) has been discovered to induce cytolytic extracellular trap cell death in eosinophils, suggesting a potential autoimmune mechanism contributing to asthma. This study aimed to explore the potential origin of Sp-IgG and identify clinically relevant subtypes of Sp-IgG that may indicate autoimmune events in asthma.Methods: This study included 165 asthmatic patients and 38 healthy volunteers. We measured Sp-IgG and its five subtypes against eosinophil inflammatory proteins (Sp-IgG_EPs), including eosinophil peroxidase, eosinophil major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and Charcot-Leyden Crystal protein in varying asthma severity. Clinical and Mendelian randomization (MR) analyses were conducted. A positive Sp-IgG_EPs signature (Sp-IgG_EPs+) was defined when any of the five Sp-IgG_EPs values exceeded the predefined cutoff thresholds, calculated as the mean values of healthy controls plus twice the standard deviation.Results: The levels of Sp-IgG and Sp-IgG_EPs were significantly elevated in moderate/severe asthma than those in mild asthma/healthy groups (all p < 0.05). Sp-IgG levels were positively correlated with airway eosinophil and Sp-IgG_EPs. MR analysis showed causality between eosinophil and IgG (OR = 1.02, 95%CI = 1.00-1.04, p = 0.020), and elevated IgG was a risk factor for asthma (OR = 2.05, 95%CI = 1.00-4.17, p = 0.049). Subjects with Sp-IgG_EPs+ exhibited worse disease severity and served as an independent risk factor contributing to severe asthma (adjusted-OR = 5.818, adjusted-95% CI = 2.193-15.431, adjusted-p < 0.001). Receiver operating characteristic curve analysis demonstrated that the combination of Sp-IgG_EPs+ with non-allergic status, an ACT score < 15, and age ≥ 45 years, effectively predicted severe asthma (AUC = 0.84, sensitivity = 86.20%, specificity = 67.80%).Conclusion: This study identifies a significant association between airway eosinophilic inflammation, Sp-IgG, and asthma severity. The Sp-IgG_EPs panel potentially serves as the specific biomarker reflecting airway autoimmune events in asthma.

Emerging research indicates that bronchiectasis often coexists with a range of allergic illnesses. The pathogenesis of both conditions is highly complex, involving a variety of interconnected factors, such as immune responses, metabolic pathways, and gut microbiota. However, the precise causal relationship between bronchiectasis and allergy-related conditions remains poorly understood. We obtained published GWAS datasets for 5 allergic disorders (allergic asthma, allergic rhinitis, atopic conjunctivitis, atopic dermatitis, and chronic rhinosinusitis) and bronchiectasis, along with data on 731 immune cells, 91 inflammatory proteins, 1400 plasma metabolites, and 473 gut microbiotas. Using bi-directional two-sample Mendelian Randomization (TSMR), we explored causal relationships between allergic diseases and bronchiectasis and validated these findings in a replication cohort. We also applied Linkage Disequilibrium Score Regression (LDSC) to assess genetic correlations between the conditions. Additionally, the mediating effects of immune cells, inflammatory proteins, metabolites, and gut microbiota on the relationship between allergic disorders and bronchiectasis were assessed through two-step TSMR and multivariate MR analysis. Our study revealed that allergic asthma, allergic rhinitis, atopic conjunctivitis, and atopic dermatitis all increased the risk of developing bronchiectasis, with no causal relationship identified in the reverse direction. Additionally, positive genetic associations were observed between allergic asthma, allergic rhinitis, atopic dermatitis, and bronchiectasis, respectively. We identified a total of forty immune cells, 5 inflammatory proteins, ninety plasma metabolites, and nineteen gut microbiota species as causal factors contributing to bronchiectasis onset. In mediation analysis, we found that the metabolic ratio of Retinol (Vitamin A) to oleoyl-linoleoyl-glycerol (18:1 to 18:2) was a risk factor for allergic asthma developing bronchiectasis, while the level of CD14 on CD33dim HLA-DR + CD11b + cells was a risk factor for allergic rhinitis. Two specific metabolic ratios—the Aspartate to N-acetylglucosamine to N-acetylgalactosamine ratio and the Methionine to phosphate ratio—served as, respectively, risk and protective factors for atopic dermatitis-developing bronchiectasis. Our findings suggest that allergic asthma, allergic rhinitis, atopic conjunctivitis, and atopic dermatitis increase the risk of developing bronchiectasis, with no evidence of a reverse causal relationship. Specifically, 3 metabolic ratios were identified as mediators between allergic diseases and bronchiectasis. Further studies are needed to clarify the underlying mechanisms.