Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study.

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.

F12-46C/T polymorphism as modifier of the clinical phenotype of hereditary angioedema.

The factors influencing the heterogeneous clinical manifestation of hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) represent one of the oldest unsolved problems of the disease. Considering that factor XII (FXII) levels may affect bradykinin production, we investigated the contribution of the functional promoter polymorphism F12-46C/T in disease phenotype. We studied 258 C1-INH-HAE patients from 113 European families, and we explored possible associations of F12-46C/T with clinical features and the SERPING1 mutational status. Given that our cohort consisted of related subjects, we implemented generalized estimating equations (GEEs), an extension of the generalized linear model accounting for the within-subject correlation. F12-46C/T carriers exhibited a significantly delayed disease onset (P < 0.001) and did not need long-term treatment (P = 0.02). In a GEE linear regression model, the presence of F12-46C/T was significantly associated with a 7-year delay in disease onset (P < 0.0001) regardless of SERPING1 mutational status. It is concluded that F12-46C/T carriage acts as an independent modifier of C1-INH-HAE severity.

Modulation of the epithelial inflammatory response to rhinovirus in an atopic environment.

BACKGROUND: Immune responses to rhinovirus (RV) as well as direct effects of RV on respiratory epithelium may contribute to the induction of asthma exacerbations. OBJECTIVE: To evaluate the effect of the environment resulting from an atopic immune response on RV-induced epithelial inflammation, replication and cytotoxicity. METHODS: Peripheral blood mononuclear cells (PBMC) from atopic asthmatic subjects and matched controls (12 pairs) were isolated and stimulated by RVs. Human bronchial epithelial (BEAS-2B) cells were infected with RV in the presence of conditioned media from RV-stimulated PBMC cultures. IL-6, IL-8, RANTES and TGF-beta1 levels were measured by ELISA, RV-induced cytotoxicity by a colorimetric method and RV titres on Ohio-HeLa cells. RESULTS: RV-induced epithelial production of IL-6, IL-8 and RANTES was significantly lower, while TGF-beta1 was higher when cells were exposed to conditioned media from atopic asthmatic subjects compared with those from normal controls. Exposure to the 'atopic' environment also resulted in elevated RV titres and increased RV-induced cytotoxicity. CONCLUSIONS: Under the influence of an atopic environment, the epithelial inflammatory response to RV is down-regulated, associated with increased viral proliferation and augmented cell damage, while TGF is up-regulated. These changes may help explain the propensity of atopic asthmatic individuals to develop lower airway symptoms after respiratory infections and indicate a mechanism through which viral infections may promote airway remodelling.

Expression of costimulatory molecules in peripheral blood mononuclear cells of atopic asthmatic children during virus-induced asthma exacerbations.

BACKGROUND: Respiratory viruses are the most frequent triggers of acute asthma exacerbations. Herein we investigate costimulatory molecule expression on peripheral blood mononuclear cells (PBMC) during such exacerbations. METHODS: Eleven children with atopic asthma were followed prospectively and respiratory symptoms were recorded on diary cards. A blood sample and nasopharyngeal wash (NPW) were obtained at baseline and subsequently during an exacerbation. PBMC were immunophenotyped using flow cytometry. NPW samples were examined for the presence of respiratory viruses by RT-PCR. RESULTS: A virus was detected in 73% of exacerbations and none at baseline. A drop of NK cells and a marginal increase of monocytes were the only changes of cell count during the exacerbation. A significant downregulation of B7-2 on NK cells and of B7-1 on monocytes was also observed during exacerbations. CONCLUSIONS: The above observations are in contrast to in vitro findings showing an upregulation of costimulatory molecules after exposure of blood cells to viruses or allergens. It is possible that activated immune cells leave the blood stream to migrate to the inflammation site during acute asthma exacerbations.