Asthma is a chronic inflammation of lower airway disease, characterized by bronchial hyperresponsiveness. Type I hypersensitivity underlies all atopic diseases including allergic asthma. However, the role of neurotransmitters (NT) and neuropeptides (NP) in this disease has been less explored in comparison with inflammatory mechanisms. Indeed, the airway epithelium contains pulmonary neuroendocrine cells filled with neurotransmitters (serotonin and GABA) and neuropeptides (substance P[SP], neurokinin A [NKA], vasoactive intestinal peptide [VIP], Calcitonin-gene related peptide [CGRP], and orphanins-[N/OFQ]), which are released after allergen exposure. Likewise, the autonomic airway fibers produce acetylcholine (ACh) and the neuropeptide Y(NPY). These NT/NP differ in their effects; SP, NKA, and serotonin exert pro-inflammatory effects, whereas VIP, N/OFQ, and GABA show anti-inflammatory activity. However, CGPR and ACh have dual effects. For example, the ACh-M3 axis induces goblet cell metaplasia, extracellular matrix deposition, and bronchoconstriction; the CGRP-RAMP1 axis enhances Th2 and Th9 responses; and the SP-NK1R axis promotes the synthesis of chemokines in eosinophils, mast cells, and neutrophils. In contrast, the ACh-α7nAChR axis in ILC2 diminishes the synthesis of TNF-α, IL-1, and IL-6, attenuating lung inflammation whereas, VIP-VPAC1, N/OFQ-NOP axes cause bronchodilation and anti-inflammatory effects. Some NT/NP as 5-HT and NKA could be used as biomarkers to monitor asthma patients. In fact, the asthma treatment based on inhaled corticosteroids and anticholinergics blocks M3 and TRPV1 receptors. Moreover, the administration of experimental agents such as NK1R/NK2R antagonists and exogenous VIP decrease inflammatory mediators, suggesting that regulating the effects of NT/NP represents a potential novel approach for the treatment of asthma.
Allergen immunotherapy (AIT) is the sole disease-modifying treatment for allergic rhinitis; it prevents rhinitis from progressing to asthma and lowers medication use. AIT against mites, insect venom, and certain kinds of pollen is effective. The mechanism of action of AIT is based on inducing immunological tolerance characterized by increased IL-10, TGF-β, and IgG4 levels and Treg cell counts. However, AIT requires prolonged schemes of administration and is sometimes associated with adverse reactions. Over the last decade, novel forms of AIT have been developed, focused on better allergen identification, structural modifications to preserve epitopes for B or T cells, post-traductional alteration through chemical processes, and the addition of adjuvants. These modified allergens induce clinical-immunological effects similar to those mentioned above, increasing the tolerance to other related allergens but with fewer side effects. Clinical studies have shown that molecular AIT is efficient in treating grass and birch allergies. This article reviews the possibility of a new AIT to improve the treatment of allergic illness.
Background Adenoviruses are highly contagious pathogens which cause respiratory disease particularly in children; they may induce severe disease in infants. Human neutrophil peptides (HNPs) have been found to exhibit antiadenoviral activity. Thus, we have investigated HNPs in nasal aspirates (NAs) of children suffering from adenoviral common cold. Objective To investigate the release of HNP-1–4 in adenovirus infection and the relationship with self-limiting upper respiratory tract infections. Methods Nasal aspirate samples (n=14) were obtained from children (aged 6–12 years) infected with adenovirus between June 2012 and December 2015. Control samples were taken 4 weeks after infection when the children were asymptomatic. Levels of HNPs were measured using an enzyme-linked immunosorbent assay (ELISA). Results There were increased levels of HNP-1, -3, and -4, but not HNP-2, in nasal aspirates (NAs) during adenovirus infections compared to healthy specimens (p ≤ 0.01). Moreover, there was also increase in the neutrophil count, which is a known cell source of HNPs. Conclusion Our finding supports the involvement of HNP-1, -3, and -4 in naturally occurring cold in children infected with adenovirus. Because of their known antiviral properties, it is tempting to hypothesize that HNPs might play a protective role in adenovirus-induced respiratory disease; however, this remains to be shown.
Genetic association research in AERD has evaluated studies of SNPs in metabolic pathways related to arachidonic acid. Recently, whole genome analysis strategies have allowed the detection of new genetic variants that were previously not considered. Furthermore, these studies have identified SNPs that are associated with inflammatory processes, which could serve as diagnostic markers or predictors of the therapeutic response.
Introduction: Subcutaneous allergen-specific immunotherapy (SCIT) is one of the main cornerstones in the treatment of allergic rhinitis in pediatric patients. It has demonstrated symptoms and quality of life improvement, but it is not exempt from adverse reactions (ADVrs). Nevertheless, there are a few reports that have evaluated their safety. Our objective was to evaluate the ADVr to SCIT in pediatric patients. Methods: We reviewed 786 clinical records with SCIT from 2005 to 2018, comparing the clinical characteristics of patients with ADVrs with SCIT versus a group of a similar number of patients who completed SCIT (control group, CG). The analysis of ADVrs was according to the World Allergy Organization (WAO) 2010 grading system by frequency analysis, survival curve, and log rank. Results: Of 786 patients, 106 (13.4%) presented ADVrs, and the patients with ADVr had sensitivity and immunotherapy with at least 2 allergens versus CG p < 0.001, containing a combination of standardized and nonstandardized allergens (p = 0.003). The ADVrs were in the buildup phase (p < 0.001). The survival curve showed that 50% had some reaction at 12 weeks of SCIT. The most frequent ADVr was grade 1 in 73/106 patients (68.8%) and grade 2 in 33/106 (31.1%). The log-rank analysis between the grades of the WAO grading system showed a statistically significant difference (p = 0.02). Conclusions: The SCIT is safe in pediatric patients. The ADVrs are infrequent, grade 1 being the most reported; however, at >12 weeks, the risk of ADVrs that involve 2 organs systems increases.
Aspirin exacerbated respiratory disease (AERD) is a set of diseases of the unified airway, and its physiopathology is related to disruption of the metabolism of arachidonic acid (AA). Genetic association studies in AERD had explored single nucleotide polymorphism (SNPs) in several genes related to many mechanisms (AA metabolism, inflammation, drug metabolism, etc.) but most lack validation stages in second populations. Our aim is to evaluated whether contribution to susceptibility of SNPs reported in other populations are associated with AERD in Mexican Mestizo patients. We developed a replicative study in two stages. In the first, 381 SNPs selected by fine mapping of associated genes, (previously reported in the literature), were integrated into a microarray and tested in three groups (AERD, asthma and healthy controls -HC-) using the GoldenGate array. Results associated to risk based on genetic models [comparing: AERD vs. HC (comparison 1, C1), AERD vs. asthma (C2), and asthma vs. HC (C3)] were validated in the second stage in other population groups using qPCR. In the first stage, we identified 11 SNPs associated with risk in C1.The top SNPs were ACE-rs4309C (p = 0.0001) and MS4A2-rs573790C (p = 0.0002). In C2, we detected 14 SNPs, including ACE-rs4309C (p = 0.0001). In C3, we found MS4A2-rs573790C (p = 0.001). Using genetic models, C1 MS4A2-rs57370 CC (p = 0.001), and ACE-rs4309 CC (p = 0.002) had associations. In C2 ACE-rs4309 CC (p = 0.0001) and C3 MS4A2-rs573790 CC (p = 0.001) were also associate with risk. In the second stage, only MS4A2-rs573790 CC had significance in C1 and C3 (p = 0.008 and p = 0.03). We concluded that rs573790 in the MS4A2 gene is the only SNP that supports an association with AERD in Mexican Mestizo patients in both stages of the study.
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