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Objective: There are no comprehensive surveys relating the reported high prevalence of asthma and allergic diseases in athletes to comorbidities and immune changes associated with intense chronic exercise. This 12-year survey aims to evaluate several clinical, functional and immunological parameters in order to assess features, trend and burden of asthma, allergy, infections and autoimmune diseases, in a large homogeneous population of Olympic athletes. Methods: Six hundred and fifty-nine Italian Olympic athletes were studied through four cross-sectional surveys performed between 2000 and 2012 before the Summer and Winter Olympics. Clinical diagnosis of allergic, autoimmune and infectious diseases was complemented by: skin-prick tests (n = 569); pulmonary function tests (n = 415); total (n = 158) and specific (n = 72) serum IgE; serum autoantibodies (n = 30), cytokines and growth factors (n = 92); flow cytometry (n = 135). Results: The prevalence of asthma and/or exercise-induced bronchoconstriction was 14.7%, with a significant increase (P = 0.04) from 2000 (11.3%) to 2008 (17.2%). The prevalence of rhinitis, conjunctivitis, skin allergic diseases and anaphylaxis was 26.2%, 20.0%, 14.8% and 1.1%, respectively. Sensitization to inhalant allergens was documented in 49.0% of athletes, being 32.7% in 2000 and 56.5% in 2008 (P < 0.0001). Food, drug and venom allergy was present in 7.1%, 5.0% and 2.1% of athletes, respectively. The high prevalence of asthma and allergy was associated with recurrent upper respiratory tract (10.3%) and herpes (18.2%) infections, an abnormal T cell subset profile and a general down-regulation of serum cytokines with a significantly lower IFN-[gamma]/IL-4 ratio. Conclusion: A chronic and intense physical exercise may cause a transient immunodepression with a preferential shift to a Th2 response, associated with abnormalities of the respiratory tract.

Back ground and objectives : Nerve grow th facto r (NG F) and NGF recept ors have be en shown to be express ed by struc tural and infilt rating inflamm atory cells in the huma n alle rgic bron chial mucosa and conjuncti va. In the nose, a positive imm unostain ing for NGF was recent ly repo rted in bio psies of subject s unde r-going surger y for refractor y nasal obstruc tion. This study was aimed at studyi ng by immu nohisto chemistry NGF exp ression and localizat ion in the nasal mucosa from sub jects wi th moderat e/sev ere persi stent allergic rh initis and natural allergen expo sure. Method s: Imm unostai ning for NGF, trypt ase an d eo sinophi l cation ic protei n was perfor med in human nasal turbinate sections of 25 patie nts affected by persi stent allergic rhini tis and sensitiza tion to Dermat ophagoi des ptero nyssinus . Resu lts: NGF was co nsistentl y exp ressed in the epithe lium and in the submucosa of allergic rhinitic su bjects, pr eferential ly local ized in eosinop hils and mast cell s. A strong NGF immuno staining was found in mucou s cells of the epithelial lining and in the submuco sal glands. Conc lusions: As previou sly shown for alle rgic asthm a and alle rgic conjuncti vitis, NGF is also detect able in the na sal mucosa of patie nts with persistent alle rgic rhini tis. The prefer ential NGF local ization in mucou s cells of the ep ithelial lining and in the submuco sal glands sugge sts a possibl e role for NGF in mod ulating secret ion in allergic rhini tis and possibly other allergic diseas es.

The number of allergens to be tested in order to identify sensitized patients is important in order to have the most cost-effective approach in epidemiological studies.To define the minimal number and the type of skin prick test (SPT) allergens required to identify a patient as sensitized using results of the new Pan-European GA(2)LEN skin prick test study.In a large Pan-European multicenter (17 centers in 14 countries) patient based study, a standardized panel of 18 allergens has been prick tested using a standardized procedure. Conditional approach allowed to determine the allergens selection.Among the 3034 patients involved, 1996 (68.2%) were sensitized to at least one allergen. Overall, eight allergens (grass pollen, Dermatophagoides pteronyssinus, birch pollen, cat dander, Artemisia, olive pollen, Blatella and Alternaria) allowed to identified more than 95% of sensitized subjects. However, differences were observed between countries, two allergens being sufficient for Switzerland (grass pollen and cat dander) as opposed to nine for France (grass pollen, Dermatophagoides pteronyssinus, olive pollen, cat dander, Blatella, cypress, dog dander, alder and [Artemisia or Alternaria]). According to country, up to 13 allergens were needed to identify all sensitized subjects.Eight to ten allergens allowed the identification of the majority of sensitized subjects. For clinical care of individual patients, the whole battery of 18 allergens is needed to appropriately assess sensitization across Europe.

Background: Within a large prospective study, the Global Asthma and Allergy European Network (GA2LEN) has collected skin prick test (SPT) data throughout Europe to make recommendations for SPT in clinical settings. Objective: To improve clinical interpretation of SPT results for inhalant allergens by providing quantitative decision points. Methods: The GA2LEN SPT study with 3068 valid data sets was used to investigate the relationship between SPT results and patient-reported clinical relevance for each of the 18 inhalant allergens as well as SPT wheal size and physician-diagnosed allergy (rhinitis, asthma, atopic dermatitis, food allergy). The effects of age, gender, and geographical area on SPT results were assessed. For each allergen, the wheal size in mm with an 80% positive predictive value (PPV) for being clinically relevant was calculated. Results: Depending on the allergen, from 40% (blatella) to 87-89% (grass, mites) of the positive SPT reactions (wheal size ≥ 3 mm) were associated with patient-reported clinical symptoms when exposed to the respective allergen. The risk of allergic symptoms increased significantly with larger wheal sizes for 17 of the 18 allergens tested. Children with positive SPT reactions had a smaller risk of sensitizations being clinically relevant compared with adults. The 80% PPV varied from 3 to 10 mm depending on the allergen. Conclusion: These 'reading keys' for 18 inhalant allergens can help interpret SPT results with respect to their clinical significance. A SPT form with the standard allergens including mm decision points for each allergen is offered for clinical use. © 2013 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Background: Skin prick testing is the standard for diagnosing IgE-mediated allergies. However, different allergen extracts and different testing procedures have been applied by European allergy centres. Thus, it has been difficult to compare results from different centres or studies across Europe. It was, therefore, crucial to standardize and harmonize procedures in allergy diagnosis and treatment within Europe. Aims: The Global Asthma and Allergy European Network (GALEN), with partners and collaborating centres across Europe, was in a unique position to take on this task. The current study is the first approach to implement a standardized procedure for skin prick testing in allergies against inhalant allergens with a standardized pan-European allergen panel. Methods: The study population consisted of patients who were referred to one of the 17 participating centres in 14 European countries (n = 3034, median age = 33 years). Skin prick testing and evaluation was performed with the same 18 allergens in a standardized procedure across all centres. Results: The study clearly shows that many allergens previously regarded as untypical for some regions in Europe have been underestimated. This could partly be related to changes in mobility of patients, vegetation or climate in Europe. Conclusion: The results of this large pan-European study demonstrate for the first time sensitization patterns for different inhalant allergens in patients across Europe. The standardized skin prick test with the standardized allergen battery should be recommended for clinical use and research. Further EU-wide monitoring of sensitization patterns is urgently needed. © 2009 John Wiley & Sons A/S.

Background: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA2LEN) study with data on clinical relevance was used to determine the clinical relevance of sensitizations against the 18 most frequent inhalant allergens in Europe. The study population consisted of patients referred to one of the 17 allergy centres in 14 European countries (n = 3034, median age = 33 years). The aim of the study was to assess the clinical relevance of positive skin prick test reactions against inhalant allergens considering the predominating type of symptoms in a pan-European population of patients presenting with suspected allergic disease. Methods: Clinical relevance of skin prick tests was recorded with regard to patient history and optional additional tests. A putative correlation between sensitization and allergic disease was assessed using logistic regression analysis. Results: While an overall rate of ≥60% clinically relevant sensitizations was observed in all countries, a differential distribution of clinically relevant sensitizations was demonstrated depending on type of allergen and country where the prick test was performed. Furthermore, a significant correlation between the presence of allergic disease and the number of sensitizations was demonstrated. Conclusion: This study strongly emphasizes the importance of evaluating the clinical relevance of positive skin prick tests and calls for further studies, which may, ultimately, help increase the positive predictive value of allergy testing. © 2009 John Wiley & Sons A/S.

PURPOSE: Despite the high and increasing prevalence of allergic diseases in athletes, allergy diagnostics is not part of the routine medical examination in sports medicine. This study reports the development and validation of an easy and reliable questionnaire for screening allergy in athletes. METHODS: AQUA was derived from the European Community Respiratory Health Survey Questionnaire. On the basis of open interviews with team doctors, coaches, and athletes, questions were added about: the type, duration, and intensity of training; exercise-related allergic and infectious symptoms; social habits (smoking); drug and food supplements intake; antidoping regulations. The final version of the questionnaire, made of 25 selected questions, was validated in 128 professional soccer players who underwent accurate history taking, medical examination, skin prick testing, and/or specific IgE determination. On the basis of the correlation with objective allergy (positive skin tests to at least one allergen), questions were scored from 1 to 5 according to their positive likelihood ratio. RESULTS: Skin tests (gold standard for validation) were positive in 46.8% of soccer players. Mean total AQUA score was 9.4 +/- 7.8 in allergic athletes versus 1.3 +/- 2.3 in nonallergic athletes. A total AQUA score of >or=5 was shown to have the best positive predictive value for allergy (0.94) with a specificity of 97.1% and a sensitivity of 58.3%. CONCLUSIONS: AQUA, produced in 10 European languages, is a validated, easy, and reliable tool for calling attention on the high prevalence of allergy in athletes.

Background: The number of allergens to be tested in order to identify sensitized patients is important in order to have the most cost-effective approach in epidemiological studies. Objective: To define the minimal number and the type of skin prick test (SPT) allergens required to identify a patient as sensitized using results of the new Pan-European GA2LEN skin prick test study. Method: In a large Pan-European multicenter (17 centers in 14 countries) patient based study, a standardized panel of 18 allergens has been prick tested using a standardized procedure. Conditional approach allowed to determine the allergens selection. Result: Among the 3034 patients involved, 1996 (68.2%) were sensitized to at least one allergen. Overall, eight allergens (grass pollen, Dermatophagoides pteronyssinus, birch pollen, cat dander, Artemisia, olive pollen, Blatella and Alternaria) allowed to identified more than 95% of sensitized subjects. However, differences were observed between countries, two allergens being sufficient for Switzerland (grass pollen and cat dander) as opposed to nine for France (grass pollen, Dermatophagoides pteronyssinus, olive pollen, cat dander, Blatella, cypress, dog dander, alder and [Artemisia or Alternaria]). According to country, up to 13 allergens were needed to identify all sensitized subjects. Conclusion: Eight to ten allergens allowed the identification of the majority of sensitized subjects. For clinical care of individual patients, the whole battery of 18 allergens is needed to appropriately assess sensitization across Europe. © 2009 John Wiley & Sons A/S.

Lung cancer remains the most frequent tumour and cause of cancer death in worldwide. Unfortunately most of patients still discover their tumour in advanced stage. Lung cancer results from the occurrence of a number of genetic alterations in oncogenes and tumour suppressor genes that are potential markers either for screening procedures or for earlier detection in patients with non small-cell lung cancer (NSCLC). It was estimated that about 10 to 20 genetic events are required for lung tumorigenesis. These genetic changes are triggered by smoking and persist for many years after smoking cessation. Continuously, more sophisticated methods for the analysis of these genetic alterations involved in lung cancer become available. Several molecular alterations involved in lung cancer have been already identified in different biological samples (biopsy, BAL) that are collected with highly invasive techniques that make them poorly suitable for wider screening. Recently the DNA has been extracted from exhaled breath condensate, demonstrating the suitability of this sample for the study of genetic alterations and its potential role in screening programs of subjects at risk of lung cancer.

Background: There is evidence that selenium levels are relatively low in Europe and may be falling. Low levels of selenium or low activity of some of the enzymes dependent on selenium have been associated with asthma. Methods: The GA2LEN network has organized a multicentre case-control study in Europe to assess the relation of plasma selenium to asthma. The network compared 569 cases in 14 European centres with a diagnosis of asthma and reporting asthma symptoms in the last 12 months with 576 controls from the same centres with no diagnosis of asthma and no asthmatic symptoms in the last 12 months. Results: All cases and controls were selected from the same population defined by age and place of residence. Mean plasma selenium concentrations among the controls ranged from 116.3 μg/l in Palermo to 67.7 μg/l in Vienna and 56.1 μg/l among the children in Oslo. Random effects meta-analysis of the results from the centres showed no overall association between asthma and plasma selenium [odds ratio (OR)/10 μg/l increase in plasma selenium: 1.04; 95% confidence interval (CI): 0.89-1.21] though there was a significantly protective effect in Lodz (OR: 0.48; 95% CI: 0.29-0.78) and a marginally significant adverse effect in Amsterdam (OR: 1.68; 95% CI: 0.98-2.90) and Ghent (OR: 1.35; 95% CI: 1.03-1.77). Conclusion: This study does not support a role for selenium in protection against asthma, but effect modification and confounding cannot be ruled out. © 2008 The Authors.

Obstructive sleep apnoea (OSA) is associated with airways inflammation; a key role in this regard seems to be played by nitric oxide (NO). The aim of this study was to measure exhaled NO and expression of its enzyme, the inducible nitric oxide synthase (iNOS) in cells of induced sputum in OSA patients and in obese subjects without sleep apnoea and to correlate these inflammatory markers with severity of OSA.We enrolled 18 obese patients with OSA (10 men, age 48.2 +/- 8.4 years), 15 obese patients without OSA (eight men, age 52.8 +/- 11 years) and 10 healthy subjects (five men, age 42 +/- 4 years). Exhaled NO was measured using a chemiluminescence analyser; iNOS expression was measured in the sputum cells by immunocytochemistry.Exhaled NO resulted significantly increased in OSA and in obese patients (23.1 +/- 2.1 and 17.9 +/- 2.1 p.p.b.) than in healthy subjects (7.2 +/- 0.6 p.p.b.; P0.001). OSA and obese patients showed a higher percentage of neutrophils and a lower percentage of macrophages in the induced sputum compared to healthy subjects. In addition, OSA and obese patients showed higher iNOS expression in neutrophils and in macrophages with respect to healthy subjects. A positive correlation between exhaled NO, iNOS expression and AHI was observed.These data confirm the presence of airway inflammation in OSA and in obese patients, and suggest the possible role for NO and iNOS expression in neutrophils of the induced sputum as noninvasive markers to identify and monitor the airway inflammation in these subjects.

It is widely accepted that nonspecific tissue reactivity is a distinct pathophysiological hallmark of allergic diseases, influenced by genetic and environmental factors different from those involved in causing sensitization and allergen response of target organs. This consensus document aims at reviewing procedures currently used for nonspecific provocation of the bronchi, nose and eye and for measuring their responsiveness to nonspecific stimuli.

Udgivelsesdato: July BACKGROUND: There is evidence that selenium levels are relatively low in Europe and may be falling. Low levels of selenium or low activity of some of the enzymes dependent on selenium have been associated with asthma. METHODS: The GA(2)LEN network has organized a multicentre case-control study in Europe to assess the relation of plasma selenium to asthma. The network compared 569 cases in 14 European centres with a diagnosis of asthma and reporting asthma symptoms in the last 12 months with 576 controls from the same centres with no diagnosis of asthma and no asthmatic symptoms in the last 12 months. RESULTS: All cases and controls were selected from the same population defined by age and place of residence. Mean plasma selenium concentrations among the controls ranged from 116.3 microg/l in Palermo to 67.7 microg/l in Vienna and 56.1 microg/l among the children in Oslo. Random effects meta-analysis of the results from the centres showed no overall association between asthma and plasma selenium [odds ratio (OR)/10 microg/l increase in plasma selenium: 1.04; 95% confidence interval (CI): 0.89-1.21] though there was a significantly protective effect in Lodz (OR: 0.48; 95% CI: 0.29-0.78) and a marginally significant adverse effect in Amsterdam (OR: 1.68; 95% CI: 0.98-2.90) and Ghent (OR: 1.35; 95% CI: 1.03-1.77). CONCLUSION: This study does not support a role for selenium in protection against asthma, but effect modification and confounding cannot be ruled out.

Purpose of review A 1-year systematic review in the field of ocular allergy was carried out to select new information which may be useful for a practical approach to allergic conjunctivitis. Recent findings Out of the 56 articles listed by PubMed, 27 papers were included in the review following a consensus achieved among the authors who had independently reviewed all abstracts. Selected articles were classified according to their main focus: antihistamines, omalizumab, new treatments for vernal keratoconjunctivitis and inflammatory ocular disorders, and sublingual immunotherapy. Summary The data reviewed are discussed with the aim of underlining unmet needs and making recommendations for future studies on diagnosis and treatment of ocular allergy which may better guide clinical practice in this important area of allergy and clinical immunology.

Hematological abnormalities frequently occur in patients infected with HIV-1. Increasing evidence indicates that bone marrow (BM) suppression results from viral infection of accessory cells, with impaired stromal function and alteration of hematopoietic growth factor network. We investigated the effects of antiretroviral therapy on cytokine and chemokine production by BM cells and stromal cells, in a group of HIV-1-infected subjects before and during treatment. Compared with uninfected controls, an altered cytokine and chemokine production by BM cells has been observed before treatment, characterised by decreased IL-2 and elevated TNF-alpha, MIP-1alpha, MIP-1beta, and RANTES levels, along with a defective BM clonogenic activity. Antiretroviral therapy determined an amelioration of stem cell activity, a restoration of stromal cell pattern and functions, and an increased IL-2 production at BM level and a decrease of Fas expression on progenitor cells, in parallel with the diminution of TNF-alpha levels. HIV-1 protease inhibitors (PIs) may improve hematopoietic functions owing to their direct effects on the BM progenitor cells. Ritonavir and indinavir increased the colony growth of BM obtained either from HIV-1-infected patients or from normal individuals, in parallel with the normalization of functional and morphologic characteristics of stromal cells.