Physician's appraisal vs documented signs and symptoms in the interpretation of food challenge tests: The EuroPrevall birth cohort.

BACKGROUND: Blinded food challenges are considered the current gold standard for the diagnosis of food allergies. We used data from a pan-European multicenter project to assess differences between study centers, aiming to identify the impact of subjective aspects for the interpretation of oral food challenges. METHODS: Nine study centers of the EuroPrevall birth cohort study about food allergy recruited 12 049 newborns and followed them for up to 30 months in regular intervals. Intensive training was conducted and every center visited to ensure similar handling of the protocols. Suspected food allergy was clinically evaluated by double-blind, placebo-controlled food challenges using a nine dose escalation protocol. The primary challenge outcomes based on physician's appraisal were compared to documented signs and symptoms. RESULTS: Of 839 challenges conducted, study centers confirmed food allergy in 15.6% to 53.6% of locally conducted challenges. Centers reported 0 to 16 positive placebo challenges. Worsening of eczema was the most common sign when challenged with placebo. Agreement between documented objective signs and the challenge outcome assigned by the physician was heterogeneous, with Cohen's kappa spanning from 0.42 to 0.84. CONCLUSIONS: These differences suggest that the comparison of food challenge outcomes between centers is difficult despite common protocols and training. We recommend detailed symptom assessment and documentation as well as objective sign-based challenge outcome algorithms to assure accuracy and comparability of blinded food challenges. Training and supervision of staff conducting food challenges is a mandatory component of reliable outcome data.

Urinary leukotriene E4 levels in atopic and non-atopic preschool children with recurrent episodic (viral) wheezing: a potential marker?

UNLABELLED: Backround: Reliable biological markers for the differentiation of asthma phenotypes in preschool children with wheezing are lacking. The purpose of the study is to assess the relationship of urinary Leukotriene E4 (U-LTE4) to particular asthma phenotypes in preschool children with recurrent episodic (viral) wheezing following upper respiratory tract infections with or without atopic predisposition. METHODS: Ninety-six preschool patients with recurrent episodic wheezing participated, 52 atopic and 44 non-atopic, during exacerbation and in remission. Exacerbation was defined on clinical basis (wheeze in the presence of coryzal symptoms). Atopy was determined by specific serum IgE measurement and skin-prick testing. U-LTE4 was determined by enzyme immunoassay. Thirty-six age-matched, non-asthmatic, non-atopic children served as controls. RESULTS: During exacerbation, U-LTE4 was significantly higher in all children with recurrent episodic wheezing in comparison to A: Remission: 642.20 ± 268 versus 399.45 ± 204, p value <0.001 and B: CONTROLS: 642.20 ± 268 versus 271.39 ± 83, p value <0.001. Atopic patients demonstrated significantly higher levels of U-LTE4 compared to non-atopic, both during exacerbation 872.13 ± 246 versus 613.15 ± 150, p value = 0.0013 and during remission 507.59 ± 182 versus 283.59 ± 160, p value <0.001. During remission, a highly significant difference of U-LTE4 was found when controls were compared to atopic patients: 271.39 ± 83 versus 507.59 ± 182, p value = 0.002 but not when compared to non-atopic ones: 271.39 ± 83 versus 283.59 ± 160, p value = 0.432. CONCLUSION: U-LTE4 is strongly associated with the acute wheeze episode in preschool children, more so in atopics. Increased basal levels of U-LTE4 occur only in atopics. This suggests a potential role of U-LTE4 as a marker of atopic, virus-induced asthma in preschool children.

Assessment of airflow limitation, airway inflammation, and symptoms during virus-induced wheezing episodes in 4- to 6-year-old children.

BACKGROUND: It is disputed whether recurrent episodes of wheeze in preschool-aged children comprise a distinct asthma phenotype. OBJECTIVE: We sought to prospectively assess airflow limitation and airway inflammation in children 4 to 6 years old with episodic virus-induced wheeze. METHODS: Ninety-three children 4 to 6 years old with a history of mild, virus-induced episodes of wheeze who were able to perform acceptable fraction of exhaled nitric oxide (Feno) maneuvers and spirometry (with forced expiratory time ≥0.5 seconds) were followed prospectively. Lung function and Feno values were measured every 6 weeks (baseline) within the first 48 hours of an acute wheezing episode (day 0) and 10 and 30 days later. Symptom scores and peak flow measurement were recorded daily. RESULTS: Forty-three children experienced a wheezing episode. At day 0, Feno values were significantly increased, whereas forced expiratory volume at 0.5 seconds (FEV(0.5)) significantly decreased compared with baseline (16 ppb [interquartile range {IQR}, 13-20 ppb] vs 9 ppb IQR, 7-11 ppb] and 0.84 L [IQR, 0.75-0.99 L] vs 0.99 L [IQR, 0.9-1.07 L], respectively; both P < .001). Airflow limitation at day 0 was reversible after bronchodilation. FEV(0.5) and Feno values were significantly associated with each other and with lower and upper respiratory tract symptoms when assessed longitudinally but not cross-sectionally at all time points independently of atopy. Feno and FEV(0.5) values returned to baseline levels within 10 days. CONCLUSIONS: Mild episodes of wheeze in preschoolers are characterized by enhanced airway inflammation, reversible airflow limitation, and asthma-related symptoms. Feno values increase significantly during the first 48 hours and return to personal baseline within 10 days from the initiation of the episode. Longitudinal follow-up suggests that symptoms, inflammation, and lung function correlate well in this phenotype of asthma.

A 5-year venom immunotherapy protocol with 50 µg maintenance dose: safety and efficacy in school children.

BACKGROUND: Venom immunotherapy (VIT) has been shown to be an effective and safe treatment for preventing sting-induced anaphylaxis in patients with systemic reactions to hymenoptera stings. A remaining problem is the relative effectiveness and safety of different immunotherapy protocols used with respect to maintenance dose, injection interval, and duration. OBJECTIVE: We aimed to describe a modified cluster VIT protocol with a maintenance dose of 50 µg lasting 5 yr and to evaluate retrospectively its safety and efficacy in children. PATIENTS AND METHODS: Fifty four children 9.5±3.2 yr old with a history of at least one anaphylactic reaction to hymenoptera stings underwent VIT between 1995 and 2006. The identification of the offending insect(s) was based on patient's report and documented with in-vivo (SPTs and IDs) and in-vitro (RAST/CAP) test results. A modified cluster outpatient protocol lasting 5 wks, reaching a maintenance dose of 50 µg was followed according to clinical history and test results. After the maintenance dose was achieved, the followed injection-intervals were 4 wks for the first year, 5 wks for the 2nd year and 3rd year, and 6 wks for the last 2 yr. RESULTS: Of the 54 children, 52 tolerated the 50 µg VIT protocol without side effects. Twenty one of them reported at least one field sting from at least one of the culprit, for their allergy, insects, 6±3.5 yr after they have started VIT treatment. In 11 of them, sting occurred 3.5±2.9 yr after the VIT was completed, whereas the other 10 of them during immunotherapy, 3.2±1.4 yr after they have started VIT. In the remaining two children, the maintenance dose was increased to 100 µg due to systemic reactions from the VIT. The data reflect outcomes 6-16 yr after the patients' initial allergic reaction. CONCLUSION: VIT with 50 µg maintenance dose lasting 5 yr appears to be safe and effective enough to induce tolerance in children with hymenoptera venom hypersensitivity.

Comparison of natural and recombinant forms of the major fish allergen parvalbumin from cod and carp.

Allergic reaction following fish consumption can trigger life-threatening reactions in predisposed individuals. Parvalbumins from different species have been identified as the major fish allergens. There are two distinct phylogenetic lineages of parvalbumins, alpha and beta. Most allergic reactions are caused by beta-parvalbumins. We cloned and expressed cDNAs encoding cod (Gadus morhua) and carp (Cyprinus carpio) beta-parvalbumins and purified natural cod beta-parvalbumin. CD spectra of the purified proteins showed that their overall secondary structure contents were very similar. No differences in thermal stability were monitored in the calcium-bound or calcium-depleted form of natural cod parvalbumin. IgE reactivity was assessed using 26 sera of fish allergic patients from Spain, The Netherlands, and Greece in immunoblot and ELISA experiments. Twenty-five of the 26 patients with IgE reactivity to native and recombinant cod parvalbumin also reacted to the recombinant carp parvalbumin. IgE inhibition assays were performed using cod and carp extracts and purified recombinant parvalbumin of cod and carp. High crossreactivity among cod and carp parvalbumins was observed in immunoblots as well as in fluid phase assays. Natural and recombinant parvalbumins gave comparable results when performing various in vitro diagnostic assays.

Reintroduction of cow's milk in milk-allergic children: safety and risk factors.

BACKGROUND: Although development of clinical tolerance is the rule in allergy to cow's milk (CM), food challenges are required in order to reintroduce CM into the patient's diet. Less 'invasive' procedures able to predict tolerance would be useful as clinical tools. The purpose of this study was to identify potential risk factors for clinical reactivity in CM-allergic children assessed for CM reintroduction. METHODS: One hundred and sixteen open challenges performed in children 10-47 months old with IgE-mediated allergy to CM, in order to reintroduce CM into the diet, were retrospectively evaluated. Specific IgE (sIgE) levels assessed by the CAP System FEIA and skin prick tests (SPT) were obtained at diagnosis and prechallenge. Demographic parameters and measures of sIgE were evaluated as potential predictors of a positive challenge in univariate and multivariate logistic regression models. RESULTS: Twenty-four out of 116 challenges were positive, 9 of which required the use of adrenaline. In order of performance, prechallenge sIgE <3.94 kU/l, the combination of SPT and sIgE or an SPT wheal <4 mm could correctly predict a negative challenge outcome, whereas values of SPT >7.5 mm or sIgE >25.4 kU/l, or their combination, had a high positive predictive value. The presence of atopic dermatitis did not affect the predictive accuracy of these values. CONCLUSIONS: Milk sIgE level prechallenge is a useful predictor of challenge outcome in patients with milk allergy. SPT do not offer an additional predictive value, but can be used when sIgE is not available.

Optimized techniques for the extraction of grape allergens appropriate for in vivo and in vitro testing and diagnosis.

Standardized allergen extracts are needed for diagnosis and therapy purposes. For grapes, standardization is hampered by low protein and high tannin and pectin concentrations. The aim of the current study was to develop an optimized method for the extraction of grape proteins and possibly extend this to other fruits. Several existing or modified extraction methods were compared by means of protein concentration determination, SDS-PAGE, immunoblotting and radioallergosorbent test (RAST). An optimized extraction protocol was obtained in which we combined a high concentration of plant tissue, a concentrated, enriched and neutral buffer able to remove sugars and keep proteins soluble and a bivalent buffer for pectin removal. Both the quantitative (protein concentration) and qualitative parameters (SDS-PAGE protein patterns and IgE reactivity) were compared to standard protocols and commercial extracts used as diagnostic tools in the clinical practice. This method proved to be the most efficient mainly compared to the standard Björksten protocol in extracting the low molecular weight proteins, including the major grape allergen (lipid transfer protein, Vit v 1). It proved to be an easy, low cost and reproducible method proposed to prepare grape extracts that could replace the commercially available ones, used for diagnosis and possibly extend the method to other fruits especially in extracting LTPs.

Severe immediate allergic reactions to grapes: part of a lipid transfer protein-associated clinical syndrome.

BACKGROUND: Grape allergy is considered rare; grape lipid transfer protein (LTP; Vit v 1), an endochitinase and a thaumatin-like protein (TLP) have been reported as grape allergens. A considerable number of patients have referred to our department for severe reactions to grapes, and several IgE binding proteins were detected. OBJECTIVES: The aim of this study was to identify and characterise the allergens involved in severe allergic reactions to grapes and describe the population in which they occur. METHODS: Patients with reported severe allergic reactions to grapes (n = 37) are described. Grape allergens were purified/fractionated by a combination of chromatographic techniques, identified by proteomic analysis and biochemically characterised. Immunoreactivity was assessed by blot (inhibitions) and RAST (inhibitions), and skin prick tests were performed with the isolated allergens. RESULTS: All subjects were polyallergic, sensitised and reactive to several additional foods and pollen. All patients were sensitised to grape LTP. A 28-kDa expansin, a 37.5-kDa polygalacturonase-inhibiting protein, a 39-kDa beta-1,3-glucanase and a 60-kDa protein were identified as minor grape allergens. Endochitinase and TLP did not play a role. Inhibition experiments revealed the possible cross-reactive role of LTP for clinical sensitivities to other LTP-containing plant foods, but also the involvement of cross-reactive carbohydrate determinants of minor allergens in IgE cross-reactivity. CONCLUSIONS: LTP is the major grape allergen, while additional minor allergens may contribute to clinical reactivity. Severe grape allergy presents in atopic patients who frequently react to other LTP-containing, plant-derived foods. The 'LTP syndrome' is the appropriate term to describe this condition.

Effect of in vitro gastric and duodenal digestion on the allergenicity of grape lipid transfer protein.

BACKGROUND: Severe grape allergy has been linked to lipid transfer protein (LTP) sensitization. LTPs are known to be resistant to pepsin digestion, although the effect of gastroduodenal digestion on its allergenicity has not been reported. OBJECTIVE: We sought to investigate the effect of gastric and gastroduodenal digestion on the allergenic activity of grape LTP. METHODS: The proteolytic stability of grape LTP was investigated by using an in vitro model of gastrointestinal digestion. The allergenicity of LTP and its digesta was assessed in vitro by means of IgE immunoblotting, RASTs, and in vivo skin prick tests in the same patients with grape allergy. RESULTS: Grape LTP was resistant to gastric digestion, and yielded a 6000-d relative molecular mass C-terminally trimmed fragment after duodenal digestion. This fragment retained the in vitro IgE reactivity of the intact protein. Inclusion of phosphatidylcholine during gastric digestion protected the LTP to a limited extent against digestion. Digestion did not affect the in vivo (skin prick test) biologic activity of LTP. CONCLUSION: The allergenic activity of grape LTP was highly resistant to in vitro digestion. This property might facilitate sensitization through the gastrointestinal tract and might also potentiate the ability of LTPs to elicit severe allergic reactions in sensitized individuals. CLINICAL IMPLICATIONS: Purified natural allergens will facilitate the development of component-resolved diagnostic approaches, including allergen chips. This study contributes to our understanding of the role digestion plays in symptom elicitation in true food allergy.

Association of weather conditions with childhood admissions for wheezy bronchitis or asthma in Athens.

BACKGROUND: The association between asthma morbidity and meteorological conditions is well documented, but it is not clear to what extent more specific meteorological variables are implicated. OBJECTIVES: This study was aiming to investigate whether there is any association between specific meteorological conditions and the seasonal variation and the rate of asthma admissions among children in Athens. METHODS: Data were obtained retrospectively from hospital registries of the three main Children's Hospitals in Athens during a 23-year period (1978-2000). The meteorological database consisted of mean monthly values of eight meteorological variables. The whole period studied was divided into three time periods: 1978-1987, 1988-1993 and 1994-2000. RESULTS: A clear seasonal trend with a permanent pattern was detected. There were more monthly asthma admissions in winter-spring and autumn for younger children, as well as a lower peak in winter and autumn and a major one in May for older children, without significant differences in between the three time periods. The results of a multiple regression analysis revealed that relative humidity and atmospheric pressure were predictors of up to 56.7% (1988-1993) and 59.2% (1994-2000) monthly asthma admissions among younger children. No relation of the time trend in asthma admissions during the periods studied for any age group with any of the meteorological variables was detected. CONCLUSIONS: Our results indicate a constant seasonal variability in asthma admissions among children in Athens, whereas relative humidity and atmospheric pressure are the more implicated meteorological variables for younger asthmatic children.

Efficacy and safety of mometasone furoate vs nedocromil sodium as prophylactic treatment for moderate/severe seasonal allergic rhinitis.

BACKGROUND: The preventive use of medications has been proposed to be effective in the treatment of seasonal rhinitis. OBJECTIVE: To evaluate the efficacy and safety of mometasone furoate and nedocromil sodium nasal sprays as prophylactic treatment for moderate to severe seasonal allergic rhinitis (SAR). PATIENTS: Sixty-one patients were recruited from 3 referral allergy centers. Inclusion criteria were history of SAR for 2 years or longer, sensitization to relevant local pollen (grasses, Parietaria, and olive), and age older than 12 years. METHODS: An open-label, randomized, parallel-group, "real-life" study design was used. Patients received mometasone furoate nasal spray once daily or nedocromil sodium nasal spray 3 times daily starting 2 to 4 weeks before the pollen season and continuing for up to 4 months. Instructions regarding the use of additional medications were given. Diary cards recording symptoms, use of medication, and adverse events were kept by the patients. RESULTS: All 61 patients completed the study. The prophylactic use of mometasone furoate vs nedocromil sodium led to significantly more days without symptoms (75.1% vs 54.5%; P < .001). The mometasone furoate group also had lower nasal symptom scores (mean, 1.4 vs 2.9; median, 0 vs 2; P < .001) and was more satisfied (93.1% vs 43.5%; P < .001). No serious adverse event was recorded, and there was no difference between the treatments in any adverse event. CONCLUSIONS: Prophylactic administration of mometasone furoate before the pollen season is safe and may lead to improved control of SAR compared with the use of nedocromil sodium.

Vascular endothelial growth factor-mediated induction of angiogenesis by human rhinoviruses.

BACKGROUND: Human rhinoviruses, major precipitants of asthma exacerbations, infect the lower airway epithelium inducing inflammation. The possibility that viral infection may mediate angiogenesis, thus contributing to airway remodeling, has not been evaluated. OBJECTIVE: To investigate whether epithelial infection with rhinovirus mediates angiogenesis in vitro, evaluate possible modulation by an atopic environment, and confirm angiogenic factor induction after in vivo rhinovirus infection. METHODS: Bronchial epithelial cells were infected with rhinovirus and levels of vascular endothelial growth factor (VEGF), and angiopoietins were measured. The angiogenic effect of epithelial products was assessed in in vitro models of angiogenesis. PBMCs, obtained from patients with atopic asthma and normal controls, were exposed to rhinovirus; the ability of supernatants from these cultures differentially to affect rhinovirus-mediated epithelial VEGF production was evaluated. VEGF levels were measured in respiratory secretions from patients with asthma, before and during rhinovirus-induced exacerbations. RESULTS: Epithelial infection with rhinovirus specifically stimulated mRNA expression and release of VEGF, but not angiopoietins, in a time-dependent and dose-dependent manner. Supernatants from these cultures were able to induce angiogenesis in vitro, significantly inhibited by a neutralizing anti-VEGF antibody. When bronchial cells were exposed to supernatants of rhinovirus-infected mononuclear cells from normal subjects or atopic patients with asthma, VEGF induction was significantly higher under the influence of the atopic environment. VEGF was elevated during rhinovirus-associated asthma exacerbations. CONCLUSION: Rhinovirus infection, a frequent event, induces VEGF production in bronchial epithelial cells and human airways, an effect enhanced in an atopic environment. Rhinovirus-associated, VEGF-mediated angiogenesis may contribute to airway remodeling in asthma.

Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells.

BACKGROUND: Human rhinoviruses (RV), the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro. METHODS: Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxicity was assessed chromatometrically. Epithelial monolayers were mechanically wounded, exposed or not to RV and the repopulation of the damaged area was assessed by image analysis. Finally epithelial cell proliferation was assessed by quantitation of proliferating cell nuclear antigen (PCNA) by flow cytometry. RESULTS: RV1b, RV5, RV7, RV14 and RV16 were able to induce considerable epithelial cytotoxicity, more pronounced in less dense cultures, in a cell-density and dose-dependent manner. RV9 was not cytotoxic. Furthermore, RV infection diminished the self-repair capacity of bronchial epithelial cells and reduced cell proliferation. CONCLUSION: RV-induced epithelial cytotoxicity may become considerable in already compromised epithelium, such as in the case of asthma. The RV-induced impairment on epithelial proliferation and self-repair capacity may contribute to the development of airway remodeling.

Duration of postviral airway hyperresponsiveness in children with asthma: effect of atopy.

BACKGROUND: Respiratory viruses induce asthma exacerbations and airway hyperresponsiveness (AHR). Atopy is an important risk factor for asthma persistence. OBJECTIVE: We sought to evaluate whether atopy is a risk factor for prolonged AHR after upper respiratory tract infections (URIs). METHODS: Twenty-five children (13 atopic and 12 nonatopic children) with intermittent virus-induced asthma were studied. Clinical evaluation, skin prick tests, methacholine bronchoprovocation, questionnaires, and a nasal wash specimen were obtained at baseline. For 9 months, subjects completed diary cards with respiratory symptoms. During their first reported cold, a nasal wash specimen was obtained. Methacholine provocation was performed 10 days and 5, 7, 9, and 11 weeks later. In case a new cold developed, the provocation schedule was followed from the beginning. RESULTS: Viruses were detected in 17 (68%) of 25 patients during their first cold, with rhinovirus being most commonly identified (82%). AHR increased significantly 10 days after the URI, equally in both groups (P = .67), and remained so up to the fifth week. Duration of AHR in subjects experiencing a single URI ranged from 5 to 11 weeks, without a significant difference between groups. In the duration of the study, atopic children experienced more colds and asthma exacerbations than nonatopic children. Thus for duration of AHR, significant prolongation was noted in the atopic group when assessed cumulatively. CONCLUSION: In asthmatic children the duration of AHR after a single natural cold is 5 to 11 weeks. However, an increased rate of symptomatic cold and asthma episodes in atopic children is associated with considerable cumulative prolongation of AHR, which might help explain the role of atopy as a risk factor for asthma persistence.

Immune modulator pidotimod decreases the in vitro expression of CD30 in peripheral blood mononuclear cells of atopic asthmatic and normal children.

Recurrent viral infections are frequently observed in children with atopic asthma. In this study we investigated the ability of the synthetic immunomodulator pidotimod to affect in vitro the phenotype and/or cytokine profile of blood cells in relation to atopic asthma. Peripheral blood mononuclear cells were isolated from 13 atopic asthmatic and 9 normal children and stimulated in culture with mitogen either in the presence or not of the drug. Expression of surface markers was evaluated by flow cytometry, and production of interleukin-4 and interferon-gamma was measured in supernatants. Pidotimod was able to down-regulate the expression of CD30 on cells from both atopic and normal subjects. Because CD30 has been associated with Th-2 cells, this observation supports the possibility of pidotimod being able to affect the Th-1/Th-2 balance in atopic asthma.

The role of respiratory viruses in the origin and exacerbations of asthma.

PURPOSE OF REVIEW: The present review focuses and comments on the increasing body of evidence correlating respiratory viral infections with asthma onset and exacerbations. RECENT FINDINGS: Recent data suggest multiple and some time contrasting roles for viral infection in the origin of asthma. These data also indicate that the immune status of the host, including atopy, may interactively contribute to this process, conferring susceptibility or even resistance to the development of asthma in virus-infected individuals. In the presence of asthma, the role of viral infection in triggering exacerbations is clearly established. Chemokine and cytokine responses of the respiratory epithelium, a biased type 1/type 2 cytokine balance, defective costimulation, as well as abnormal neural control have been suggested as possible mechanisms. The importance of concurrent or synergistic effects of allergen exposure is currently under scrutiny. SUMMARY: Viruses may initiate and certainly exacerbate asthma. Mild repeated infections early in life could also stimulate type 1 immune responses conferring protection from atopy and asthma. The host's immune status, the type of viral infection and the timing of exposure to various environmental stimuli are probably the key factors in this process. Mechanistic insights deduced from recent work should allow for the development of intervening strategies in the near future.

Skin-prick test findings in atopic asthmatic children: a follow-up study from childhood to puberty.

In a prospective cohort study we investigated the course of allergic sensitization from childhood to puberty in a group of children with atopic asthma. An attempt was made to correlate the findings with the persistence of asthma. A total of 150 children with atopic asthma established at 7 years of age were evaluated when 8-10 years of age. A battery of skin-prick tests (SPTs) to common environmental allergens, a detailed clinical history for asthma severity classification, and spirometric analyses, were performed. In 127 of these children a re-evaluation was performed at puberty. A variety of statistical methods were used to analyze the results regarding changes in skin test reactivity to individual aeroallergens and atopic index (degree of atopy), as well as to determine any correlation between these changes and the persistence of asthma in puberty. A wide spectrum of modification in skin reactivity to common environmental allergens was observed, including the complete loss of sensitization to some allergens or the development of a new one to others. Specifically, 34% of asthmatic children sensitive to Dermatophagoides pteronyssinus and 52.7% sensitive to cat lost their sensitivity in puberty, while only 7.5% and 11.1%, respectively, became sensitized (p = 0.03 and p = 0.001, respectively). In contrast, regarding pollen sensitivity, 30.2% and 24% of asthmatic children became sensitive in puberty to olive pollen and grasses mix, respectively, and only 11.7% and 12.5%, respectively, lost their sensitivity to these allergens (p = 0.04). No correlation was shown between the skin test reactivity changes to individual allergens and the persistence of asthma, but a significant correlation was found between atopic index to indoor allergens in childhood and the persistence of asthma at puberty (p = 0.04). Interestingly, multi-sensitivity to allergens (>/= 4 allergens) in childhood was also found to correlate with the persistence of asthma at puberty [p = 0.05, odds ratio (OR) = 2.65, 95% confidence interval (CI) 1.2-7.2]. Our findings indicate that significant modification of skin reactivity to common environmental allergens in atopic children with asthma in puberty can occur. However, no association between these changes and the persistence of asthma could be demonstrated, although children with indoor allergic sensitization and multi-reactivity were found to have a higher probability of maintaining their asthma in puberty.