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.

Adherence to inhaled corticosteroids and long-acting ß2-agonists in asthma: A MASK-air study.

INTRODUCTION: Adherence to controller medication is a major problem in asthma management, being difficult to assess and tackle. mHealth apps can be used to assess adherence. We aimed to assess the adherence to inhaled corticosteroids+long-acting ß2-agonists (ICS+LABA) in users of the MASK-air® app, comparing the adherence to ICS+formoterol (ICS+F) with that to ICS+other LABA. MATERIALS AND METHODS: We analysed complete weeks of MASK-air® data (2015-2022; 27 countries) from patients with self-reported asthma and ICS+LABA use. We compared patients reporting ICS+F versus ICS+other LABA on adherence levels, symptoms and symptom-medication scores. We built regression models to assess whether adherence to ICS+LABA was associated with asthma control or short-acting beta-agonist (SABA) use. Sensitivity analyses were performed considering the weeks with no more than one missing day. RESULTS: In 2598 ICS+LABA users, 621 (23.9%) reported 4824 complete weeks and 866 (33.3%) reported weeks with at most one missing day. Higher adherence (use of medication ≥80% of weekly days) was observed for ICS+other LABA (75.1%) when compared to ICS+F (59.3%), despite both groups displaying similar asthma control and work productivity. The ICS+other LABA group was associated with more days of SABA use than the ICS+F group (median=71.4% versus 57.1% days). Each additional weekly day of ICS+F use was associated with a 4.1% less risk in weekly SABA use (95%CI=-6.5;-1.6%;p=0.001). For ICS+other LABA, the percentage was 8.2 (95%CI=-11.6;-5.0%;p<0.001). CONCLUSIONS: In asthma patients adherent to the MASK-air app, adherence to ICS+LABA was high. ICS+F users reported lower adherence but also a lower SABA use and a similar level of control.

Identification by cluster analysis of patients with asthma and nasal symptoms using the MASK-air® mHealth app.

BACKGROUND: The self-reporting of asthma frequently leads to patient misidentification in epidemiological studies. Strategies combining the triangulation of data sources may help to improve the identification of people with asthma. We aimed to combine information from the self-reporting of asthma, medication use and symptoms to identify asthma patterns in the users of an mHealth app. METHODS: We studied MASK-air® users who reported their daily asthma symptoms (assessed by a 0-100 visual analogue scale - "VAS Asthma") at least three times (either in three different months or in any period). K-means cluster analysis methods were applied to identify asthma patterns based on: (i) whether the user self-reported asthma; (ii) whether the user reported asthma medication use and (iii) VAS asthma. Clusters were compared by the number of medications used, VAS asthma levels and Control of Asthma and Allergic Rhinitis Test (CARAT) levels. FINDINGS: We assessed a total of 8,075 MASK-air® users. The main clustering approach resulted in the identification of seven groups. These groups were interpreted as probable: (i) severe/uncontrolled asthma despite treatment (11.9-16.1% of MASK-air® users); (ii) treated and partly-controlled asthma (6.3-9.7%); (iii) treated and controlled asthma (4.6-5.5%); (iv) untreated uncontrolled asthma (18.2-20.5%); (v) untreated partly-controlled asthma (10.1-10.7%); (vi) untreated controlled asthma (6.7-8.5%) and (vii) no evidence of asthma (33.0-40.2%). This classification was validated in a study of 192 patients enrolled by physicians. INTERPRETATION: We identified seven profiles based on the probability of having asthma and on its level of control. mHealth tools are hypothesis-generating and complement classical epidemiological approaches in identifying patients with asthma.

Gibberellin-regulated proteins: Emergent allergens.

About 10 years ago, a protein family was shown for the first time to contain allergenic members, gibberellin-regulated protein (GRP). The first reported member was from peach, Pru p 7. One can hypothesize that it was not detected before because its physicochemical characteristics overlap with those of lipid transfer protein (LTP), a well-known allergen, or because the exposure to GRP increased due to an increase in the gibberellin phythormone level in plant food, either exogenous or endogenous. Like LTPs, GRPs are small cationic proteins with disulfide bridges, are resistant to heat and proteolytic cleavage, and are involved in the defense of the plant. Besides peach, GRP allergens have been described in Japanese apricot (Pru m 7), sweet cherry (Pru av 7), orange (Cit s 7), pomegranate (Pun g 7), bell pepper (Cap a 7), strawberry (Fra a GRP), and also in pollen with a restriction to Cupressaceae tree family (Cup s 7, Cry j 7, and Jun a 7). IgE cross-reactivities were described between GRPs, and the reported peach/cypress and citrus/cypress syndromes may therefore be explained because of these GRP cross-reactivities. GRPs are clinically relevant, and severe adverse reactions may sometimes occur in association with cofactors. More than 60% and up to 95% sequence identities are calculated between various allergenic GRPs, and three-dimensional models show a cleft in the molecule and predict at least three epitopic regions. The structure of the protein and its properties and the matrix effect in the original allergenic source should be unraveled to understand why, despite the ubiquity of the protein family in plants, only a few members are able to sensitize patients.

[The use of anti-pollution masks in daily life - a review]. / Masques anti-pollution.

INTRODUCTION: "Anti-pollution" masks are a form of personal protective equipment intended to ensure filtration of ambient particulate air pollution. STATE OF THE ART: Although according to tests performed in the lab, their filtration power is high, the filtering efficiency of these masks in real conditions of use, that is to say, during physical effort, is generally lower than that established in the laboratory and this information is rarely available on commercial products on sale. Clinical studies, which are rarely double-blind, demonstrate a lower incidence of symptoms and a somewhat better cardiac performance when exercise is performed while wearing a mask. For short-term use, the tolerance of these masks is fair. PERSPECTIVES: There is room for technical improvements in mask design improved fitting to the face, lowering inspiratory resistance and dead space, as well as preventing the accumulation of humidity on the mask. Manufacturers should include information in their packaging on the filtering power and design masks usable by children. Clinical studies should be performed to assess the long-term safety and effectiveness of mask in susceptible populations, especially people with asthma. CONCLUSION: Anti-pollution filtering face piece respirators have a theoretical high filtering power towards particles, but their efficiency in real-life conditions is more limited. Because such devices may confer to users a false sense of protection, the French agency on environment and health do not support their use.

Altitude healing effect in severe asthmatic children.

BACKGROUND: The beneficial effect of a climatic treatment in children with asthma was established quite some time ago, but the mechanism of this beneficial effect has not been fully elucidated. We investigated the role of the cytokines of the TH2 pathway, reactive oxygen species (ROS) and reactive nitrogen species (RNS) over the course of a high-altitude climatic therapy. METHODS: A group of 67 children originating from various French towns suffering from uncontrolled severe asthma was sent via their medical specialists, to the Briançon climatic area. They were monitored over the course of an entire school year. During this time, they returned home for 15 days during the Christmas holidays. At each stage, assessment of asthma control, lung function examination (peak flow meter and spirometry), and measurement of exhaled NO, ROS and RNS in exhaled breath condensate (EBC), and the level of cytokines in the plasma of the TH2 pathway were carried out. RESULTS: The degree of asthma control improved at high altitude and worsened upon returning home. The average value of the peak expiratory flow also improved during the first 3 months but then worsened upon returning home, while the other spirometric parameters did not change. The level of expired NO and the scores for quality of life underwent a similar change. The level of RNS and ROS in the EBC did not change significantly. Besides, a marked and statistically significant decrease in the level of IL-13 and IL-10 was noted. CONCLUSION: The beneficial effect of a climatic stay of children suffering from allergic asthma at altitude appears to be linked with less allergenic stimulation.

Eating fish and fruits are associated with lower prevalence of allergic diseases.

BACKGROUND: Allergic diseases are recognized as a burden on the public health. They stand as one of the most common chronic diseases, especially in developed countries. Therefore, the objective of this study is to evaluate the association between the development of atopic allergy and the presence of food allergy in children, and food consumption. METHODS: This multidisciplinary cross-observational epidemiological study was conducted among 1199 schoolchildren who were recruited in 4th grade and 5th grade (9-11 years old from Marseille). Data were collected by means of a standardized epidemiological questionnaire with a medical assessment focusing on allergic diseases, and questions on lifestyle and child nutrition (FFQ). RESULTS: During the last 12 months, prevalence of allergic diseases were shown as follows: 41% of children presented allergic rhinitis symptoms, 24% reported having asthma related symptoms, while 28% suffered of eczema and 7% complained of food allergy. There was a significant association between food allergy and asthma symptoms (P-value<0.001, IC=[2.29-7.69]), eczema (P-value<0.001, IC=[2.37-8.32]) and allergic rhinitis (P-value<0.001, IC=[2.32-8.17]). Regarding dietary habits, the multivariate analysis shows that the consumption of vegetables (ORa=0.72 [0.64-0.74]) and fish (ORa=0.74 [0.50-1.09], ORa=0.66 [0.47-0.94] respectively) are associated decreased risk of developing asthma and allergic rhinitis symptoms, while fruit consumption (ORa=0.68 [0.45-1.03]) is associated with a decrease in eczema symptoms. CONCLUSION: This study shows that the presence of a food allergy is strongly associated with allergic diseases. Indeed, the consumption of vegetables, fruits and fish seems to have a protective effect on the occurrence of these diseases.

[Non-allergenic impact of indoor mold exposure]. / Effets non allergiques des moisissures domestiques sur la santé.

The proportion of moldy housing in France is around 20%. It is not simple to establish that a health impact of mold is not allergic, because the identification of allergy is itself difficult. Moreover, exposure to molds and their metabolites may have a protective effect. Non-allergic health impacts may occur due to the multiple aerocontaminants found in damp or mold-containing dwellings: glucans, microbial volatile organic compounds, mycotoxins, bacteria and endotoxins. The heath impacts of indoor mold have been addressed by numerous toxicologic and epidemiologic investigations, the results of which have been summarized in three notable reports. These conclude that mold exposure is linked to a risk of ENT and bronchial symptoms, both the genesis and exacerbation of asthma and, lastly, hypersensitivity pneumonitis. Finally, other studies highlight the protective role of fungal metabolites with respect to asthma and allergy. Pulmonologists should be aware of these data, which can be useful in clinical practice and also in legal work.

[Neurofibromatosis as a cause of breathlessness]. / La neurofibromatose rend souvent essoufflé.

INTRODUCTION: Type 1 neurofibromatosis, also called "Recklinghausen's disease" is among the most frequent autosomal dominant genetic disorders, with an incidence of 1:3500 births. It mainly affects the skin and peripheral nervous system. However, in its less frequent manifestations, are tumors such as meningocele and skeletal dysplasias leading to severe clinical presentation. CASE REPORT: We report the case of a 55-year-old patient with type 1 neurofibromatosis and dyspnea due to a large left thoracic meningocele combined with a significant kyphoscoliosis, causing a severe restrictive ventilatory defect, complicated by chronic respiratory failure and pulmonary hypertension. Symptomatic treatment with non-invasive ventilation permitted an improvement of the clinical situation. CONCLUSIONS: Our observation shows the complexity of the therapeutic support of the neurofibromatosis of type 1. The contribution of non-invasive ventilation was illustrated by the arterial blood gas and clinical improvements as well as improved quality of life, with an acceptable level of inconvenience to the patient.

[Occurrence of delayed symptoms after a challenge test with methacholine]. / Survenue de symptômes tardifs après un test de provocation par la méthacholine.

There are few prospective studies available on the development of delayed symptoms following challenge tests with methacholine (MCT) at the currently recommended doses. The objective of this study was to describe the nature and frequency of respiratory symptoms suggestive of bronchospasm developing within 24hours after a MCT. The study was offered to adult patients who underwent MCT seen consecutively between June and October 2015. Following the test, a questionnaire adapted from the GINA asthma control questionnaire bearing on diurnal and nocturnal symptoms (cough, dyspnoea, wheeze and tightness), was delivered to the patient and the replies collected by telephone 24hours later. Of the 101 patients included (initial FEV1 2.82±0.79L), 46 (46 %) were MCT+ and 55 (54 %) MCT-. Among the MCT-, 4 (7 %) presented with immediate symptoms (S+) and 4 (7 %) with delayed symptoms. Among the MCT+ patients, 36 (78 %) presented with immediate symptoms (P<0.001 compared with the MCT- patients), and 39 (85 %) with delayed symptoms (P<0.001 compared with the MCT- patients). Delayed symptoms developed with a mean of 5h30 after the provocation test. Immediate and delayed symptoms were more frequent in subjects having significant non-specific bronchial hyper-reactivity. Informing patients of the risk of developing delayed symptoms seems useful and allows optimization of their management after a MCT.

[Outdoor moulds and respiratory health]. / Moisissures extérieures et santé respiratoire.

Mould spores constitute the largest portion of biologic particulate matter suspended in the outdoor atmosphere. There is no universal method for collecting airborne mould spores. The most used sampler, Hirst's apparatus, operates continuously and gives results in individual spores per cubic metre of air. Spore concentrations depend on available substrates, human activities such as agriculture, season, diurnal meteorological variations and climate changes. Under natural conditions, concentrations of over 100,000 spores per cubic metre are not exceptional. Cladosporium is the most commonly identified outdoor mould. The association between respiratory health and outdoor mould spore exposure has been assessed in clinical studies, and also by cross-sectional, and less often longitudinal, epidemiological studies. The relationship between asthma exacerbations and specific mould spores has been demonstrated in longitudinal studies. Cross sectional studies have related measurements of mould spore concentrations to severity of bronchial symptoms, drug consumption and peak-flow measurements in groups of asthmatic subjects. Ecological time-series studies use daily indicators of asthma exacerbations (emergency room visits, hospitalizations) within the general population. The moulds mainly incriminated are Cladosporium and Alternaria. They are associated with seasonal, but also perennial, asthma and rhinitis. Further studies are needed to better assess the impact of outdoor moulds on health, particularly basidiomycetes. Studies with molecular biology tools are probably a way forward.

Cypress pollen allergy is responsible for two distinct phenotypes of allergic rhinitis different from other pollinosis.

Summary: Different phenotypes of allergic rhinitis have been identified based on the seasonality of the allergen involved. Within pollinosis, importance has to be paid to the responsible pollen species. Guidelines for clinical management are mostly based on studies performed in patients with grass pollen allergy. Only few data is available on tree pollen allergy and more specifically on cypress pollen allergy. We focused on the clinical and biological features of cypress pollen allergy to determine whether it is associated with a specific phenotype of allergic rhinitis or not. Our results suggest that cypress pollen can be responsible for two distinct phenotypes of rhinitis, both different from other pollinosis. In the most common phenotype, cypress pollen was not responsible for bronchial hyperresponsiveness or systemic inflammation. Close attention has to be paid to the allergen involved in allergic rhinitis. Different phenotypes leading to different pharmacological strategies may apply.

Identification of a polygalacturonase (Cup s 2) as the major CCD-bearing allergen in Cupressus sempervirens pollen.

As IgE glyco-epitopes, also referred to as cross-reactive carbohydrate determinants (CCDs), can share significant structural homologies between different plants, they are prone to extensive cross-reactivity among allergen pollen extracts. Here, cypress pollen allergens, especially a polygalacturonase (PG), were further characterized using double one-dimensional electrophoresis (D1-DE). The presence of specific IgE directed against CCDs was investigated by bromelain IgE inhibition and concanavalin A binding assays using sera of cypress pollen-sensitized patients. Our results showed that IgE reactivity to CCDs in Cupressus sempervirens pollen extracts is mainly related to bromelain-type epitopes of a newly identified cypress PG. This glycoprotein has been further characterized through an immunoproteomic approach and officially indexed as Cup s 2 by the WHO/IUIS allergen nomenclature. Cup s 2 could thus be associated with the increased prevalence of IgE reactivity to cypress pollen extracts because of CCD interference.

Static and elevated pollen traps do not provide an accurate assessment of personal pollen exposure.

SUMMARY: Background. Volumetric pollen traps are commonly used to assess pollen exposure. These traps are well suited for estimating the regional mean airborne pollen concentration but are likely not to provide an accurate index of personal exposure. In this study, we tested the hypothesis that hair sampling may provide different pollen counts from those from pollen traps, especially when the pollen exposure is diverse. Methods. We compared pollen counts in hair washes to counts provided by stationary volumetric and gravimetric pollen traps in 2 different settings: urban with volunteers living in short distance from one another and from the static trap and suburban in which volunteers live in a scattered environment, quite far from the static trap. Results. Pollen counts in hair washes are in full agreement with trap counts for uniform pollen exposure. In contrast, for diverse pollen exposure, .individual pollen counts in hair washes vary strongly in quantity and taxa composition between individuals and dates. These results demonstrate that the pollen counts method (hair washes vs. stationary pollen traps) may lead to different absolute and relative contributions of taxa to the total pollen count. Conclusions. In a geographic area with a high diversity of environmental exposure to pollen, static pollen traps, in contrast to hair washes, do not provide a reliable estimate of this higher diversity.