Asthma, allergy and the Olympics: a 12-year survey in elite athletes.

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-γ/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.

Cigarette smoke and increased COX-2 and survivin levels in exhaled breath condensate of lung cancer patients: how hot is the link?

UNLABELLED: One of the most current intriguing hypotheses on lung cancerogenesis envisages a role for inflammation as a possible trigger of both epithelial-mesenchymal transition and cancer development. Cigarette smoke has been suggested to be the main factor underlying the inflammation of the airways described in lung cancer patients. Cycloxygenase and survivin, a COX-2 dependent factor of apoptosis resistance, seem to play a key role in this regard. PURPOSE: The aim of this study was to study COX-2 and survivin in the airways of lung cancer patients and in those of a group of smokers in a view to increasing our understanding of the link between smoking, airway inflammation and lung cancer. PATIENTS AND METHODS: 70 NSCLC patients (28 smokers, 26 ex-smokers and 16 non-smokers) and 30 healthy subjects (20 smokers and 10 non-smokers) were enrolled in the study. Both COX-2 and survivin concentrations were measured in the exhaled breath condensates of all the subjects under study using EIA kits. RESULTS: Higher levels of exhaled survivin and COX-2 were found in NSCLC patients compared to healthy smokers and non-smokers. These levels were observed to be significantly elevated in smokers (patients with lung cancer and healthy) and ex-smokers compared to non-smokers and exhibited a positive correlation with the number of cigarettes smoked expressed as pack/year. A correlation was also found between exhaled COX-2 and survivin and the progression of cancer. CONCLUSIONS: We support the hypothesis that cigarette smoke be strongly connected to the inflammation of the airways observed in lung cancer patients. On the basis of the results obtained the use of exhaled breath condensate COX-2 and survivin levels could be suggested as two potential markers within an early non-invasive screening of populations of smokers at risk of lung cancer.

AQUA: Allergy Questionnaire for Athletes. Development and validation.

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.

[New biomolecular methodologies in diagnosis of lung cancer]. / Attualità sui nuovi metodi biomolecolari nella diagnosi di neoplasie polmonari.

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.

Practical approach to diagnosis and treatment of ocular allergy: a 1-year systematic review.

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.

Development and testing of the quality of life in children with vernal keratoconjunctivitis questionnaire.

PURPOSE: To develop and validate a questionnaire that measures health-related quality of life (HRQoL) in children with vernal keratoconjunctivitis (VKC). DESIGN: Prospective, observational case series. METHODS: An initial list of 42 items was developed and administered to 30 children with active VKC (six girls and 24 boys; mean age, nine +/- two years). The 30 most significant items were selected and converted into questions on a three-step scale for validation in 41 children with active VKC (eight girls and 33 boys; mean age, 9.5 +/- 2.1 years). Twenty-two children also completed the generic KINDL questionnaire. Clinical signs were evaluated and scored and total sign scores (TSSs) were calculated. Validation was performed by factorial analysis and Pearson correlation. Internal consistency was computed by the Chronbach alpha on the extracted factors. RESULTS: Factorial analysis extracted two factors with good internal consistency: symptoms (12 items; alpha = 0.89) and daily activities (four items; alpha = 0.77). Correlations of Quality of Life in Children with Vernal Keratoconjunctivitis (QUICK) scores to KINDL scores were in the expected direction. Most patients reported itching (93%), burning (90%), redness (90%), the need to use eye drops (90%), tearing (83%), and photophobia (80%). The children's greatest concerns were limitations on going to the pool (71%), playing sports (58%), and meeting friends (58%). QUICK symptom scores were correlated significantly to conjunctival hyperemia (P < .001), secretion (P = .042), chemosis (P = .012), superficial punctate keratopathy (P < .001), and TSS (P = .010). CONCLUSIONS: The QUICK questionnaire is a new, simple instrument to measure HRQoL in children with severe allergic conjunctivitis. This test is effective for the global evaluation of the impact of VKC on children's daily lives.

Immunodysregulation of HIV disease at bone marrow level.

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.

Idiopathic CD4+ lymphocytopenia may be due to decreased bone marrow clonogenic capability.

BACKGROUND: Idiopathic CD4+ lymphocytopenia is defined by a stable decrease of CD4+ T cells in the absence of any known cause of immune deficiency. The mechanisms responsible for the immunological impairment are still unknown, but a regenerative failure of hematopoietic stem/progenitor cells has been hypothesized. METHODS: We evaluated in the bone marrow (BM) of 5 patients with idiopathic CD4+ lymphocytopenia the phenotype of BM progenitor cells, their differentiation capacity with colony-forming cells and long-term culture-initiating cell assays, in parallel with the spontaneous IL-7 production in the patient sera. RESULTS: Compared with controls, a regenerative failure of hematopoietic stem cells has been observed, both in 'committed' and in 'uncommitted' progenitor cells, despite high IL-7 serum levels. The percentage of phenotypically primitive CD34+CD38-DR+ cells (this includes the lymphoid precursor cells) was decreased, suggesting an involvement of the more primitive BM compartment in the de novo T cell generation. CONCLUSIONS: Despite the low number of patients, due to the low incidence of the disease, the decrease of primitive precursors sustains the possibility that diminished stem cell precursors might contribute to the development of CD4+ T cell depletion.