Benefits of immunotherapy with a standardized Dermatophagoides pteronyssinus extract in asthmatic children: a three-year prospective study

BACKGROUND: Although widely practiced for over 80 years, the role of specific immunotherapy (SIT) in pediatric asthma treatment is still controversial. We assessed the effects of a 3-year period of subcutaneous administration of a standardized preparation of Dermatophagoides pteronyssinus (D pt) on the respiratory health in a group of asthmatic children monosensitized to house dust mite (HDM). METHODS: A randomized clinical trial was performed after 1-year run-in period. Fifteen children receiving SIT for HDM and 14 controls (four drop-outs), matched for age, allergen sensitization, asthma severity, lung function, and non-specific bronchial reactivity (BHR), were studied during the 3-year treatment period. During the whole trial, respiratory symptoms, pharmacological and respiratory function parameters were regularly evaluated. Skin prick tests and methacholine challenge were performed at the beginning and end of the study. RESULTS: In the SIT group significant improvement in asthmatic symptoms and marked reduction in drug intake was observed. The SIT group also showed a significant decrease in non-specific bronchial BHR. No new sensitivity occurred during the study period in the SIT group only. No major local or systemic side-effects were reported during the study. CONCLUSIONS: Our results confirm that SIT is effective in asthmatic children sensitive to mites. It is associated with a decrease in BHR and it may prevent the development of new sensitizations in monosensitized subjects.     

Parietaria pollinosis: a review

Species of the genus Parietaria (pellitory) are a prevalent cause of allergy in the Mediterranean area and the most important in some European regions such as southern Italy and coastal Spain (14, 26, 27, 29, 30, 31, 36, 59, 69). Up to now, however, Parietaria has received little attention in northern Europe and the US because of its limited regional distribution. Therefore, less is known about Parietaria allergy than about other inhalant allergens such as those of grasses, ragweed, and mites. During the last 5 years, only 31 reports on Parietaria allergy have appeared in the literature, as compared with 37 papers on birch pollen. This ratio may appear unbalanced, considering that millions of people suffer from pollinosis caused by Parietaria, while a much smaller number have rhinitis and/or asthma caused by birch pollen. The increasing movement of people throughout Europe and to and from the US is reason to broaden our knowledge of patterns of inhalant allergy in each geographic area, especially where tourism and immigration are high. This paper briefly reviews available data and personal studies on the botanical, aerobiological, immunochemical, and clinical features of Parietaria allergy.     

Post-marketing survey on the safety of sublingual immunotherapy in children below the age of 5 years

BACKGROUND: The age below 5 years is considered a prudential limit for immunotherapy in view of the possible severity of side-effects. Sublingual immunotherapy (SLIT) seems to be safe, but no study in very young children is available. We performed a safety post-marketing surveillance study in children below 5 years. METHODS: Children aged 3-5 years with respiratory allergy receiving SLIT were followed-up for at least 2 years. A diary card for side-effects was filled by parents at each dose given. Local and systemic side-effects were graded as: mild (no intervention, no dose adjustment), moderate (medical treatment and/or dose reduction), severe (life-threatening/hospitalization/emergency care). The comparative safety of different allergens and regimens was also assessed. RESULTS: One hundred and twenty-six children (mean age 4.2 years, 67 male) were included. Seventy-six (60%) had rhinitis with asthma, 34 (27%) rhinitis only and 16 (13%) only asthma. Immunotherapy was prescribed for mites (62%), grasses (22.2%), Parietaria (11.9%), Alternaria (2.4%) and olive (1.5%). Eighteen children underwent an accelerated build-up. The total number of doses was about 39,000. Nine side-effects were reported in seven children (5.6% patients and 0.2/1000 doses). Two episodes of oral itching and one of abdominal pain were mild. Six gastrointestinal side-effects were controlled by reducing the dose. All side-effects occurred during up-dosing phase. No difference in terms of safety among the allergens used was observed. CONCLUSION: SLIT is safe also in children under the age of 5 years.     

Monitoring of seasonal variability in bronchial hyper-responsiveness and sputum cell counts in non-asthmatic subjects with rhinitis and effect of specific immunotherapy

Bronchial hyper-responsiveness (BHR) is documented in a proportion of non-asthmatic individuals with allergic rhinitis (NAAR) and reflects inflammatory events in the lower airways. Natural exposure to allergens is known to modulate BHR and the level of airway inflammation in asthma, but less consistently in NAAR. Specific immunotherapy (SIT) attenuates symptoms possibly by reducing BHR and airway inflammation. The influence of natural exposure to Parietaria pollen on BHR and sputum cell counts of NAAR was investigated and the effect of Parietaria SIT examined. Thirty NAAR, monosensitized to Parietaria judaica, participated in a randomized, double-blind, placebo-controlled, parallel group study of the effects of a Parietaria pollen vaccine on symptoms/medication score, BHR to inhaled methacholine and adenosine 5'-monophosphate (AMP), and cell counts in the sputum collected out of and during the pollen seasons for 36 months. Seasonal variation in BHR to inhaled methacholine and AMP and changes in sputum cell counts were documented. Changes were consistent for AMP, but not methacholine, and invariably associated with modifications in sputum eosinophils and epithelial cells. The clinical efficacy of Parietaria SIT was associated with a decline in the seasonal deterioration of BHR to AMP, whereas no significant effect was observed on BHR to methacholine or sputum cell differentials. Between-groups comparison of the seasonal changes in PC15 methacholine values and sputum cell differentials calculated as the AUC were not statistically significant, whereas a significant difference in PC15 AMP was demonstrated throughout the study (P=0.029), the median (inter-quartile range) AUC values being 2478.5 (1153.3-3600.0) and 1545.5 (755.3-1797.9) for the SIT- and placebo-treated group, respectively. Bronchial airways of NAAR exhibit features of active inflammation that deteriorate during natural allergen exposure, particularly with regard to BHR to AMP. The clinical efficacy of Parietaria SIT was exclusively associated with attenuation in seasonal worsening of PC15 AMP, suggesting that AMP may be useful in monitoring changes in allergic inflammation of the airways.     

Cockroach allergy appears early in life in inner-city children with recurrent wheezing.

BACKGROUND: Cockroach allergy and exposure to high levels of this allergen are important in the increasing asthma-related health problems among young inner-city children. However, there are very little data regarding the prevalence of cockroach allergy in infants and young children with asthma. OBJECTIVE: This retrospective study was designed to test the hypothesis that cockroach allergy appears early in life in young children with recurrent wheezing. METHODS: We reviewed the medical records of all 196 children (ages 5 months to 16 years) evaluated between January 1995 and September 1997 at the Cook County Hospital Pediatric Allergy Clinic for recurrent wheezing. The patients were assigned into two age groups, less than 4 years old and 4 to 16 years old. The percentages of IgE skin tests positive for common aeroallergens were compared within and between the two age groups. All children in the younger age group were tested for cockroach and dust mites, cat, and dog when indicated by positive environmental history. All children in the older age group were tested for indoor and outdoor allergens. RESULTS: Sixty-three children were younger than 4 years of age, and of these, 15 (23.8%) had cockroach allergen sensitivity, compared with only eight patients (12.7%) who were skin test positive to dust mite allergen (P = .01). The youngest patient with a positive reaction to cockroach allergen was 6 months old. Patients with a single allergen skin reactivity were considered as monosensitized. Nine children younger than 4 years of age (14.3%) were monosensitized only to cockroach allergen in contrast to three children (4.8%) who were monosensitized to house-dust mites (P < .05). CONCLUSIONS: Our data suggest that cockroach allergen sensitivity starts early in life and may be the only sensitizing allergen in many young inner-city children.     

Allergy Induced by Parietaria officinalis Pollen in Southern Croatia

Pollen of Parietaria officinalis causes season-associated respiratory symptoms. In Southern Croatia (Yugoslavia) we found 65% patients with rhinitis and/or asthma to be allergic to this pollen. They showed positive cutaneous reactions and had specific IgE antibodies to the respective isolated allergen. The finding represents the first report on Parietaria officinalis-induced allergy on the east Adriatic coast.     

Multiple-allergen and single-allergen immunotherapy strategies in polysensitized patients: looking at the published evidence

In allergen immunotherapy there is debate as to whether polysensitized patients are best treated with many allergens simultaneously (chosen according to the sensitization profile, a predominantly North American approach) or a single allergen (chosen according to the most clinically problematic allergy, a predominantly European approach). In patients seeking treatment for moderate-to-severe respiratory allergies, polysensitization is more prevalent (range, 50% to 80%) than monosensitization in both the United States and Europe. Safe, effective, single-allergen preparations will most likely have been tested in polysensitized patients. In robust, large-scale clinical trials of grass pollen sublingual tablets, polysensitized patients benefited at least as much from allergen immunotherapy as monosensitized patients. A recent review of multiallergen immunotherapy concluded that simultaneous delivery of multiple unrelated allergens can be clinically effective but that there was a need for additional investigation of therapy with more than 2 allergen extracts (particularly in sublingual allergen immunotherapy). More work is also required to determine whether single-allergen and multiallergen immunotherapy protocols elicit distinct immune responses in monosensitized and polysensitized patients. Sublingual and subcutaneous multiallergen immunotherapy in polysensitized patients requires more supporting data to validate its efficacy in practice.     

Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six-year follow-up study.

BACKGROUND: Specific immunotherapy (SIT) is a recognized way of treating IgE-mediated respiratory diseases. The clinical outcome is usually better in allergic children than in adults. OBJECTIVE: To increase our knowledge of the ability of SIT to prevent the onset of new sensitizations in monosensitized subjects, so far poorly documented. METHODS: 134 children (age range 5-8 years), who had intermittent asthma with or without rhinitis, with single sensitization to mite allergen (skin prick test and serum-specific IgE), were enrolled. SIT was proposed to all the children's parents, but was accepted by only 75 of them (SIT Group). The remaining 63 children were treated with medication only, and were considered the Control Group. Injective SIT with mite mix was administered to the SIT Group during the first three years and all patients were followed for a total of 6 years. All patients were checked for allergic sensitization(s) by skin prick test and serum-specific IgE every year until the end of the follow-up period. RESULTS: Both groups were comparable in terms of age, sex and disease characteristics. 123 children completed the follow-up study. At the end of the study, 52 out of 69 children (75.4%) in the SIT Group showed no new sensitization, compared to 18 out of 54 children (33.3%) in the Control Group (P < 0.0002). Parietaria, Gramineae and Olea were the most common allergens responsible for the new sensitization(s). CONCLUSIONS: According to our data, SIT may prevent the onset of new sensitizations in children with respiratory symptoms monosensitized to house dust mite (HDM).     

Effects of sublingual immunotherapy for multiple or single allergens in polysensitized patients.

BACKGROUND: Sublingual immunotherapy (SLIT) has proven efficacy in treating respiratory allergy. OBJECTIVE: To compare the clinical and functional effects and the effect on nasal eosinophils of SLIT with either single or combination allergens. METHODS: We performed an open-labeled, controlled, 4 parallel-group randomized study with 58 patients sensitized to birch and grasses only who had rhinitis and bronchial hyperreactivity in both pollen seasons. Patients were recruited for the study from January 1, 1999, to June 30, 2001. The patients received SLIT for birch, SLIT for grass, SLIT for birch and grass, or drugs only. Symptom and medication scores, forced expiratory volume in 1 second, bronchial hyperreactivity, and nasal eosinophil counts were evaluated in both pollen seasons at baseline and after 2 and 4 years. RESULTS: Ten patients dropped out and 48 completed the study. No change in all the considered parameters vs baseline was seen in patients treated with drugs only. Those patients receiving SLIT for grass or birch had a significant clinical improvement and nasal eosinophil reduction vs baseline and vs patients who did not receive SLIT in the target season (P < .01) but also in the unrelated pollen season (P < .05). The patients receiving SLIT for grass and birch improved as well, and their improvement in clinical symptoms and inflammation was significantly greater than in patients treated with SLIT for the single allergens. Minor changes were seen in the forced expiratory volume in 1 second, since it remained within the reference range in the whole population. CONCLUSION: In patients sensitized to grass and birch, SLIT with the 2 allergens provided the best clinical results. Nevertheless, SLIT with birch only or grass only also provided a measurable improvement in the grass season and birch season, respectively.     

A mutant of the major apple allergen, Mal d 1, demonstrating hypo-allergenicity in the target organ by double-blind placebo-controlled food challenge

BACKGROUND: Allergen-specific immunotherapy for food allergy has been hindered by severe side-effects in the past. Well-characterized hypo-allergenic recombinant food allergens potentially offer a safe solution. OBJECTIVE: To demonstrate hypo-allergenicity of a mutated major food allergen from apple, Mal d 1, in vitro and in vivo. METHODS: A mutant of the major apple allergen, Mal d 1, was obtained by site-directed mutagenesis exchanging five amino acid residues. Fourteen patients with combined birch pollen-related apple allergy were included in the study. Hypo-allergenicity of the mutant rMal d 1 (rMal d 1mut) compared with rMal d 1 was assessed by in vitro methods, i.e. RAST (inhibition), immunoblotting and basophil histamine release (BHR) and in vivo by skin prick test and double-blind placebo-controlled food challenge (DBPCFC). RESULTS: RAST analysis (n = 14) revealed that IgE reactivity to rMal d 1mut was twofold lower than that of the wild-type molecule (95% confidence interval (CI): 1.7-2.4). RAST inhibition (n = 6) showed a 7.8-fold decrease in IgE-binding potency (95% CI: 3.0-12.6). In contrast to this moderate decrease in IgE-binding potency, the biological activity of rMal d 1mut assessed by SPT and BHR decreased 10-200-fold. Hypo-allergenicity was confirmed by DBPCFC (n = 2) with both recombinant molecules. CONCLUSION: A moderate decrease in IgE-binding potency translates into a potent inhibition of biological activity. This is the first study that confirms by DBPCFC that a mutated recombinant major food allergen is clinically hypo-allergenic. This paves the way towards safer immunotherapy for the treatment of food-allergic patients.     

Nasal resistance and allergic inflammation depend on allergen type

BACKGROUND: Allergic rhinitis is characterized by inflammatory cell infiltrate and increased nasal airflow resistance. OBJECTIVE: The aim of this study was to evaluate the relationship between sensitization type, inflammatory cell pattern, and nasal airflow resistance in a group of rhinitics with monosensitization. METHODS: Seventy-seven subjects (40 males and 37 females, with a mean age of 33 +/- 4.4 years) suffering from allergic rhinitis were studied. Skin prick test, nasal cytology and electronic rhinomanometry were assessed in all subjects. RESULTS: The number of subjects monosensitized to house dust mites was 23, to grasses 20, to cypress 17, to Parietaria 11, and to olive tree 6. Significant differences were observed between each type of allergen sensitization concerning both the nasal airflow resistance (p = 0.002) and the nasal cytology pattern: eosinophils (p = 0.004), degranulated eosinophils (p = 0.002), mast cells (p = 0.006) and degranulated mast cells (p = 0.008). Furthermore, goblet cells were higher in house dust mite-sensitized subjects compared with the pollen-sensitized group (p = 0.018), in which a prevalence of eosinophils, degranulated eosinophils, mast cells and degranulated mast cells was observed (p = 0.049, p < 0.001, p = 0.022 and p = 0.007, respectively). Nasal resistances were higher in the pollen group (p = 0.001). CONCLUSIONS: This study provides evidence that inflammatory cell pattern and nasal resistance depend on the type of allergen sensitization.     

Immunotherapy in children with allergic asthma: effect on bronchial hyperreactivity and pharmacotherapy

BACKGROUND: Immunotherapy has been shown to reduce allergen sensitivity to allergens such as cat and dust mite. The aim of this study was to investigate the effect of cat or dust mite immunotherapy on bronchial hyperreactivity and the need for inhaled corticosteroids in children with asthma, cat or dust mite allergy, and hay fever. SUBJECTS: Twenty-nine children, 7 to 16 years old, completed the 3-year study. They were randomly allocated to receive cat/dust mite or placebo and birch/timothy immunotherapy. METHODS: Before immunotherapy was begun and then once each year, bronchial histamine challenges were performed. Bronchial allergen challenge with the perennial allergen was done before and after the 3-year study. Pharmacotherapy was given according to a standardized protocol. RESULTS: PC20 allergen increased significantly in both the active immunotherapy group (P <.001) and in the placebo-pollen group (P <.05). PC20 histamine increased continuously in the active immunotherapy group (P <.05 and P =.002 after 1 and 3 years, respectively) and had also increased after 3 years in the placebo-pollen group (P <.05). The difference between the 2 groups was significant for PC20 allergen (P =.001) but not for PC20 histamine. There was no significant change in the dose of inhaled budesonide needed for symptom control in either of the groups. CONCLUSION: Pollen immunotherapy combined with inhaled corticosteroids results in improvement of both cat/dust mite bronchial sensitivity and hyperresponsiveness to histamine. The combination of cat or dust mite, pollen immunotherapy, and inhaled budesonide enhances this improvement. Cat immunotherapy also induces cat allergen tolerance.     

Prevention of new sensitizations in monosensitized subjects submitted to specific immunotherapy or not. A retrospective study

BACKGROUND: Specific immunotherapy is the only currently available allergen-orientated treatment able to modify the natural history of respiratory allergic diseases. Safety and clinical efficacy of this treatment are well documented, but evidence about the ability to reduce new sensitizations is still poor. OBJECTIVE: We report a retrospective study conducted in order to assess the prevention of new sensitizations in monosensitized subjects treated with specific immunotherapy vs. monosensitized patients treated with anti-allergic drugs. METHODS: 8396 monosensitized patients with respiratory symptoms were selected according to an open, retrospective design. Group A included 7182 patients submitted to specific immunotherapy (and anti-allergic drugs when needed) for 4 years and then treated with drugs for at least 3 years. Group B included 1214 patients treated only with drugs for at least 7 years. All patients underwent prick test with a standard panel of allergens and total and specific IgE determination before and after 4 years of treatment and again 3 years later. RESULTS: Groups were well balanced. Polysensitized subjects were 23.75% in Group A and 68.03% in Group B after 4 years (P < 0.0001) and 26.95% and 76.77%, respectively, after 7 years (P < 0.0001). Asthmatic subjects were more prone to develop polysensitization in comparison to subjects suffering only from rhinitis (32.14% instead of 27.29% after 4 years, 36.5% instead of 31.33% after 7 years; P < 0.0001). Specific IgE decreased by 24.11% in Group A and increased by 23.87% in Group B (P < 0.0001). Total IgE decreased by 17.53% in Group A and increased by 13.71% in Group B (P < 0.0001). CONCLUSIONS: Specific immunotherapy was observed retrospectively to reduce new sensitizations in monosensitized subjects suffering from respiratory allergic diseases.     

The allergic march in pollinosis: natural history and therapeutic implications

BACKGROUND: That specific immunotherapy (SIT) can slow the march of allergy has been confirmed in controlled clinical trials. However, an assessment of its effects in everyday life, in a large cohort of patients, might provide further useful information. METHODS: This observational study comprised 3,643 patients allergic to pollens; 1,620 with pure allergic rhinitis or rhinitis and intermittent or mild-persistent bronchial asthma, responding poorly to standard pharmacological therapy (SPT), were treated for 3 years with SPT alone (pure rhinitis, n = 890), or combined with continuous SIT (rhinitis and asthma, n = 730). Symptom/drug scores were recorded, respiratory function and skin tests were done, and methacholine challenge was scheduled at the beginning and end of the study. A series of 2,023 patients with pure rhinitis, responsive to SPT, were asked to 'self-medicate' as needed, serving as a control group to check the incidence of asthma. RESULTS: The incidence of rhinitis-asthma co-morbidity was highest in the self-medication group (50.8%). Persistent rhinitis was associated with asthma more often than the intermittent form, regardless of the severity of the symptoms that led to progression to asthma in patients with intermittent rhinitis. Treatment with SIT combined with SPT always slowed the allergic march which, however, was not influenced by drugs alone. CONCLUSIONS: In routine clinical practice, SIT is effective in preventing the allergic march. Patients with persistent rhinitis, who are at greatest risk of progression to asthma, appear to be the most logical candidates.     

Airborne pollen concentrations and the incidence of allergic asthma and rhinoconjunctivitis in northern Italy from 1992 to 2003

BACKGROUND: Aeroallergens and the environment play an important role in the pathogenesis of respiratory allergies. In a 12-year study carried out in Northern Italy (geographic area of Parma), the effects of airborne pollen and meteorological conditions on the incidence of allergic asthma and rhinoconjunctivitis were evaluated. PATIENTS AND METHODS: Among 9,060 subjects examined for respiratory pathologies at our Allergy Unit, Parma Hospital, Italy, from 1992 to 2003, only 1,054 positive to only one type of inhalant allergen in the skin prick test were studied, to avoid bias of cross-reactivity. Allergy and clinical aspects were compared with the duration of the pollination period, and peaks and total concentrations of airborne pollen. RESULTS: Our data showed a significantly growing trend of allergy to mites, pets and birch pollen and a significant increase in asthma, and a significantly decreasing trend of positive reactions to grasses and a decrease in rhinoconjunctivitis. At the same time, there was a significant decrease in total pollen counts, concentration peaks and pollination period of grasses. A significant increase was only observed in ragweed and ash-olive total and peak pollen concentrations. CONCLUSIONS: Significant correlations between the increasing incidence in asthma and allergy to mites, pets and birch pollen are shown. The decrease in the total pollen count and concentration peaks of grass pollen was correlated to the decreasing trend of rhinoconjunctivitis. The trend of increasing concentrations of ash-olive and ragweed pollen was not accompanied by an increase in the related allergy.     

Age at symptom onset and distribution by sex and symptoms in patients sensitized to different allergens

The aim of our study was to analyze the clinical features, particularly the age at symptom onset, of allergic subjects (asthma and/or rhinitis) on the basis of the etiologic elements (sensitization to various allergens). We identified a group of monosensitized patients and a group of polysensitized patients. Within these groups, we identified subgroups of subjects monosensitized to one of the five main allergenic mixes (mites, Gramineae, trees, Parietaria, and Artemisia) and five subgroups of patients sensitized nonexclusively, that is, polysensitized, to the same allergens. The comparison between the two groups and among the various subgroups enabled us to conclude that:

• 1)

  mono- and polysensitized patients present some clinical features so different as to constitute two clearly distinct clinical groups
• 2)

  analysis of the clinical features associated with the sensitization to a specific allergen brings us to significantly different conclusions when we consider subgroups of monosensitized or polysensitized patients
• 3)

  the parameter "age at symptom onset" shows great heterogeneity among both the mono- and the polysensitized subgroups - in particular, the great differences in mean age among the monosensitized subgroups (trees>y4rtemi.s(fl>Pflrie/flria>Gramineae>mites) appear very interesting and are open to various interpretative hypotheses
• 4)

  unlike the polysensitized group, in the monosensitized group and subgroups, mean age is similar between men and women and, only for tree- and parietaria -monosensitive patients, also between asthmatic and rhinitic subjects.

     

Impact of allergic rhinitis on asthma: effects on bronchial hyperreactivity

Background:  Remarkable relationship exists between upper and lower airways. Bronchial hyperreactivity (BHR) is a paramount feature of asthma and may be considered a strong risk factor for the onset of asthma in patients with allergic rhinitis.
Objective:  This study is aimed at evaluating the presence of BHR in a large group of patients with moderate-severe persistent allergic rhinitis alone, and at investigating possible risk factors related to severe BHR.
Methods:  Three hundred and forty-two patients with moderate-severe persistent allergic rhinitis were prospectively and consecutively evaluated. Clinical examination, skin prick test, spirometry and bronchial methacholine (MCH) test were performed in all patients.
Results:  Twenty-two (6.4%) patients had severe BHR, 74 (21.6%) patients had mild BHR and 192 (56.2%) had borderline BHR; 54 (15.8%) patients had a negative MCH test. The logistic regression analysis evidenced that trees and house dust mites sensitization (OR_Adj: 8.1), rhinitis duration > 5 years (OR_Adj: 5.4) and FEV₁ ≤ 86% of predicted (OR_Adj: 4.0) were significantly associated with severe BHR. The discriminative ability of this model is appreciably satisfactory, being the AUC = 0.90.
Conclusion:  This study highlights the close link between upper and lower airways and the role of some risk factors, such as tree and mite sensitization, > 5-year duration, and ≤ 86% FEV₁ values, as risk factors for severe BHR in patients with moderate-severe persistent allergic rhinitis alone. Therefore, BHR is frequently present in patients with chronic rhinitis and should be suspected in the presence of defined risk factors.     

Allergic sensitization to indoor and outdoor allergens and relevance to bronchial hyperresponsiveness in younger and older subjects

BACKGROUND: Most previous epidemiological studies on the relationship between allergy and bronchial hyperresponsiveness (BHR) have made no distinction between sensitization to indoor and outdoor allergens. We studied the relationship between specific sensitization to allergen and BHR and further assessed whether this was different in young adults and older subjects. METHODS: Specific IgE to indoor allergens (house dust mite and cat) and outdoor allergens (timothy grass and birch) were measured using the CAP System. BHR was defined as PD20 /= 3). Young adults with multiple sensitization had the highest risk of BHR. Subjects who were exclusively sensitized to pollen did not show increased BHR in both age groups. Total IgE had, independently of sensitization, only a significant dose-response relationship with BHR in the oldest age group. CONCLUSIONS: The association between sensitization and BHR is dependent on the nature of the allergen and the level of specific IgE. Furthermore, this study shows for the first time that total IgE is associated with BHR at older ages, independently of sensitization.     

Birch and ragweed pollinosis north of Milan: a model to investigate the effects of exposure to "new" airborne allergens

BACKGROUND: The effects of sudden and massive exposure of the general population to novel airborne allergens are not known. This study aimed to investigate the clinical effects of two "new" allergens, ragweed and birch, in an area north of Milan during the last 15 years. METHODS: We reviewed the records of 2571 monosensitized patients seen during the last 10 years in two allergy units north of Milan. Data included age at onset of allergic symptoms, and family history of allergic diseases. In this sample, 500 were allergic to grass, mite, birch, and ragweed; 293 to pellitory; 167 to mugwort; 100 to Alternaria; and 11 to plantain. RESULTS: Birch pollen-allergic patients and ragweed pollen-allergic patients showed a similar mean age at onset (35.3 years vs. 35.1 years; P = NS), but were significantly older than all other groups of patients (P < 0.001). Patients allergic to ragweed and birch pollen, 304 and 323 respectively, were >30 years at the onset of allergic symptoms. A family history of allergic disorders among first degree relatives was far less frequent among patients allergic to birch pollen (29%) or ragweed pollen (27%) than among patients sensitive to all other airborne allergens, except those allergic to mugwort pollen (P < 0.001). In both ragweed and birch groups, a positive family history was significantly more common among subjects < 30 years than in those > 30 years at onset of respiratory allergy (81/196 (41%) vs. 54/304 (18%), P < 0.001 for the ragweed group; 80/177 [45%]vs. 65/323 (20%), P < 0.001 for the birch group). CONCLUSION: Exposure of the general population of this area to two new airborne allergens resulted in the onset of respiratory allergy in many older people who lacked any relevant predisposing factor. Although we cannot exclude the possibility that those who became allergic had been exposed to birch or ragweed pollen elsewhere, a more likely explanation is a specific susceptibility that remains viable until the subject encounters the "right" allergen.     

Preventive effects of sublingual immunotherapy in childhood: an open randomized controlled study

BACKGROUND: Sublingual immunotherapy (SLIT) has been proved to be effective in allergic rhinitis and asthma, but there are few data on its preventive effects, especially in children. OBJECTIVE: To evaluate the clinical and preventive effects of SLIT in children by assessing onset of persistent asthma and new sensitizations, clinical symptoms, and bronchial hyperreactivity. METHODS: A total of 216 children with allergic rhinitis, with or without intermittent asthma, were evaluated and then randomized to receive drugs alone or drugs plus SLIT openly for 3 years. The clinical score was assessed yearly during allergen exposure. Pulmonary function testing, methacholine challenge, and skin prick testing were performed at the beginning and end of the study. RESULTS: One hundred forty-four children received SLIT and 72 received drugs only. Dropouts were 9.7% in the SLIT group and 8.3% in the controls. New sensitizations appeared in 34.8% of controls and in 3.1% of SLIT patients (odds ratio, 16.85; 95% confidence interval, 5.73-49.13). Mild persistent asthma was less frequent in SLIT patients (odds ratio, 0.04; 95% confidence interval, 0.01-0.17). There was a significant decrease in clinical scores in the SLIT group vs the control group since the first year. The number of children with a positive methacholine challenge result decreased significantly after 3 years only in the SLIT group. Adherence was 80% or higher in 73.8% of patients. Only 1 patient reported systemic itching. CONCLUSIONS: In everyday clinical practice, SLIT reduced the onset of new sensitizations and mild persistent asthma and decreased bronchial hyperreactivity in children with respiratory allergy.