Exacerbations Among Patients With Asthma Are Largely Dependent on the Presence of Multimorbidity.

BACKGROUND AND OBJECTIVE: Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions. To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort. METHODS: The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient. RESULTS: The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC. CONCLUSION: Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern.

Serum microRNAs Catalog Asthma Patients by Phenotype.

BACKGROUND AND OBJECTIVES: Asthma is a chronic inflammatory condition of the airways with a complex pathophysiology. Stratification of asthma subtypes into phenotypes and endotypes should move the field forward, making treatment more effective and personalized. Eosinophils are the key inflammatory cells involved in severe eosinophilic asthma. Given the health threat posed by eosinophilic asthma, there is a need for reliable biomarkers to identify affected patients and treat them properly with novel biologics. microRNAs (miRNAs) are a promising diagnostic tool. The aim of this study was to identify serum miRNAs that can phenotype asthma patients. METHODS: Serum miRNAs of patients with eosinophilic asthma (N=40) and patients with noneosinophilic asthma (N=36) were evaluated using next-generation sequencing, specifically miRNAs-seq, and selected miRNAs were validated using RT-qPCR. Pathway enrichment analysis of deregulated miRNAs was performed. RESULTS: Next-generation sequencing revealed 15 miRNAs that were expressed differentially between eosinophilic and noneosinophilic asthma patients, although no differences were observed in the miRNome between atopic and nonatopic asthma patients. Of the 15 miRNAs expressed differentially between eosinophilic and noneosinophilic asthma patients, hsa-miR-26a-1-3p and hsa-miR-376a-3p were validated by RT-qPCR. Expression levels of these 2 miRNAs were higher in eosinophilic than in noneosinophilic asthma patients. Furthermore, expression values of hsa-miR-26a-1-3p correlated inversely with peripheral blood eosinophil count, and hsa-miR-376a-3p expression values correlated with FeNO values and the number of exacerbations. Additionally, in silico pathway enrichment analysis revealed that these 2 miRNAs regulate signaling pathways associated with the pathogenesis of asthma. CONCLUSIONS: hsa-miR-26a-1-3p and hsa-miR-376a-3p could be used to differentiate between eosinophilic and noneosinophilic asthma.

Delayed Hypersensitivity Reactions Caused by Drug Excipients: A Literature Review.

The European Medicines Agency (EMA) defines excipients as the constituents of a pharmaceutical form apart from the active substance. Delayed hypersensitivity reactions (DHRs) caused by excipients contained in the formulation of medications have been described. However, there are no data on the prevalence of DHRs due to drug excipients. Clinical manifestations of allergy to excipients can range from skin disorders to life-threatening systemic reactions. The aim of this study was to perform a literature review on allergy to pharmaceutical excipients and to record the DHRs described with various types of medications, specifically due to the excipients contained in their formulations. The cases reported were sorted alphabetically by type of medication and excipient, in order to obtain a list of the excipients most frequently involved for each type of medication.

Immediate Hypersensitivity Reactions Caused by Drug Excipients: A Literature Review.

The European Medicines Agency defines excipients as the constituents of a pharmaceutical form apart from the active substance. Immediate hypersensitivity reactions (IHRs) caused by excipients contained in the formulation of medications have been described. However, there are no data on the prevalence of IHRs due to drug excipients. Clinical manifestations of allergy to excipients can range from skin disorders to life-threatening systemic reactions. The aim of this study was to review the literature on allergy to pharmaceutical excipients and to record the IHRs described with various types of medications, specifically reactions due to the excipients contained in their formulations. The cases reported were sorted alphabetically by type of medication and excipient in order to obtain a list of the excipients most frequently involved for each type of medication.

IgE, IgG1 and IgG4 response to specific allergens in sensitized subjects showing different clinical reactivity to Anisakis simplex.

SUMMARY: Background. Anisakis simplex hypersensitive subjects may be sensitized without clinical allergy, or experience acute symptoms or chronic urticaria induced by raw fish. We studied whether the 3 subgroups differ in IgE, IgG1 or IgG4 reactivity to specific Anisakis simplex allergens. Methods. 28 Anisakis simplex-hypersensitive adults, 11 with acute symptoms, 9 with chronic urticaria, and 8 sensitized were studied. IgE, IgG1 and IgG4 to rAni s 1, 5, 9 and 10 were sought by ELISA. IgE and IgG4 to nAni s 4 were determined by WB. Results. IgE to Ani s 1, 4, 5, 9, and 10 were found in 8, 3, 2, 5, and 9 sera, respectively. Nine sera did not react to any allergen. IgG1 to Ani s 1, 5, 9, and 10 were detected in 5, 16, 14, and 4 sera, respectively. Four sera did not react to any of the 4 allergens. IgG4 to Ani s 1, 4, 5, 9, and 10 were detected in 10, 0, 2, 6 and 1 sera, respectively. Fifteen subjects did not react to any of the 5 allergens. On ELISA sensitized subjects showed lower IgE and IgG1 levels than patients. IgG4 levels were highest in the sensitized group. The prevalence of IgE, IgG1 or IgG4 reactivity to any of the studied allergens did not differ between the 3 subgroups. Conclusion. The clinical expression of Anisakis simplex sensitization does not seem to depend on IgE reactivity to a specific allergen of the parasite, nor on the presence of IgG antibodies possibly related with blocking activity.

Relationships between T cell and IgE/IgG4 epitopes of the Anisakis simplex major allergen Ani s 1.

BACKGROUND: Anisakiasis is a global disease caused by the consumption of raw or lightly cooked fish parasitized with third-stage Anisakis larvae. Anisakis simplex allergens may cause severe allergic reactions including angio-oedema, urticaria and anaphylaxis. Approximately 80% of allergic patients have allergen-specific IgE against Ani s 1, and the diagnostic value of testing for antibodies to Ani s 1 has been extensively demonstrated. However, no previous studies have investigated the molecular aspects of the allergic response to Ani s 1. Knowledge of allergen-specific T cell and B cell (IgE and IgG4) epitopes is important for elucidating the immunological mechanisms underlying allergic responses, and for understanding why particular proteins behave as allergens. OBJECTIVE: To elucidate the main T cell- and B cell (IgE and IgG4)- binding regions of Ani s 1. METHODS: T cell epitopes were identified by peptide proliferation assays using T cell lines derived from peripheral blood mononuclear cells of 11 patients with Anisakis allergy, and IgE and IgG4 epitopes were identified by microarray immunoassay using sera from a different group of 11 patients with Anisakis allergy. RESULTS: Several T cell epitopes of Ani s 1 were identified, of which Ani s 1145-156 , Ani s 1151-162 and Ani s 1163-171 located at the C-terminal end of the protein were the most relevant. IgE and IgG4 recognized largely the same peptides, including Ani s 122-41 , Ani s 125-44 , Ani s 127-47 , Ani s 137-56 and Ani s 194-113 . CONCLUSIONS AND CLINICAL RELEVANCE: This is the first report describing the T cell epitopes of an important allergen of A. simplex, and the first B cell epitope study of this allergen in the Spanish population. This information can help to elucidate the mechanisms underlying the allergic response to Ani s 1, potentially leading to therapeutic and diagnostic advances.

Contact angioedema and rhinoconjunctivitis caused by Dendrobaena species and Sarcophaga carnaria used as fishing bait.

The flesh fly Sarcophaga carnaria is commonly used as fishing bait. Immunoglobulin (Ig) E-mediated reactions caused by the handling of this bait have been reported. The earthworm Dendrobaena species is increasingly being used as fishing bait but there have been no reported cases of allergy to this species to date. We studied a 26-year-old amateur angler who presented rhinoconjunctivitis, urticaria, and angioedema on handling S carnaria. He started to use Dendrobaena species instead but developed the same symptoms. The aim of this study was to identify the allergens involved in the patient's clinical reactions. The study was performed using immunoglobulin (Ig) E immunoblotting and immunoblotting inhibition assays.The patient's serum detected allergens from Dendrobaena species (of an apparent molecular weight of approximately 150, 60, 37, 24, 21 and 19 kDa) and S. carnaria (approximately 70 kDa and a smear ranging from 50 to 40 kDa). The patient was diagnosed with allergy to both Dendrobaena species and 5 carnaria. This is the first case describing Dendrobaena species as an allergic agent.

Mexican Trypanosoma cruzi T. cruzi I strains with different degrees of virulence induce diverse humoral and cellular immune responses in a murine experimental infection model.

It is has been shown that the majority of T. cruzi strains isolated from Mexico belong to the T. cruzi I (TCI). The immune response produced in response to Mexican T. cruzi I strains has not been well characterized. In this study, two Mexican T. cruzi I strains were used to infect Balb/c mice. The Queretaro (TBAR/MX/0000/Queretaro)(Qro) strain resulted in 100% mortality. In contrast, no mortality was observed in mice infected with the Ninoa (MHOM/MX/1994/Ninoa) strain. Both strains produced extended lymphocyte infiltrates in cardiac tissue. Ninoa infection induced a diverse humoral response with a higher variety of immunoglobulin isotypes than were found in Qro-infected mice. Also, a stronger inflammatory TH1 response, represented by IL-12p40, IFNgamma, RANTES, MIG, MIP-1beta, and MCP-1 production was observed in Qro-infected mice when compared with Ninoa-infected mice. We propose that an exacerbated TH1 immune response is a likely cause of pathological damage observed in cardiac tissue and the primary cause of death in Qro-infected mice.