Lower airway inflammation before and after house dust mite nasal challenge: an age and allergen exposure-related phenomenon.

BACKGROUND: Upper and lower airways allergic disease is currently considered unitarily. Allergic inflammation in one site can extend to other sites of the respiratory tract. OBJECTIVE: To evaluate bronchial inflammation before and after allergen-specific nasal challenge (ASNC) in rhinitic and asthmatic children, considering the different levels of allergen exposure, i.e. summer (low) and winter (high). METHODS: Fourteen children with rhinitis and 15 with rhinitis and asthma, all monosensitized to mites and 10 healthy controls were studied. Nasal IgE were measured before ASNC in summer and in winter season. Nasal clinical score, eosinophil cationic protein (ECP), nasal tryptase, bronchial clinical score, FEV(1), PEF, sputum ECP, sputum tryptase and exhaled nitric oxide (eNO) were evaluated before and after ASNC in summer and winter season. RESULTS: Nasal scores significantly increased after ASNC in rhinitic and asthmatic children in both seasons. Nasal IgE were significantly higher in summer compared to winter. Bronchial symptoms, FEV(1) and PEF showed no mean differences in rhinitic and asthmatic children after ASNC, with an increase of bronchial symptoms and a decrease of FEV(1) and PEF occurring in 3/15 asthmatic children. In both groups nasal tryptase and ECP after ASNC significantly increased in summer and winter, while sputum tryptase was undetectable before or after ASNC in both groups. Sputum ECP and eNO at baseline were significantly higher in patients than in controls (summer P=0.002, winter P=0.001). Sputum ECP significantly increased after ASNC in 3/15 asthmatics in summer and in 11/15 in winter, as well as in 3/14 rhinitics in summer and in 4/14 in winter. eNO significantly increased after ASNC in 3/15 asthmatics in summer and in 10/15 in winter, and in 1/14 rhinitics in summer and in 4/14 in winter. A significant median increase of sputum ECP (P=0.0007) and eNO (P=0.0012) after ASNC in asthmatic and of eNO (P=0.013) in rhinitic children was also found in winter. CONCLUSIONS: Basal sputum ECP and eNO values, significantly higher before ASNC in rhinitic patients compared to control subjects, confirm the inflammatory link of upper and lower airways. The more frequent detection of inflammatory changes induced by ASNC in winter suggests that allergen exposure favours the transfer of nasal inflammation to lower airways.

Measurement of nasal IgE in an epidemiological study: assessment of its diagnostic value in respiratory allergy.

BACKGROUND: Specific questionnaire and skin prick test (SPT) are the most used methods in epidemiological studies on respiratory allergy. SPT, however, can be positive in many subjects without evidence of any allergic disease. Nasal IgE determination has been suggested by some authors as a valuable diagnostic method, which may overcome this lack of specificity. OBJECTIVE: The aim of this study was to evaluate sensitivity and specificity of nasal specific IgE for the seven most common inhalant allergens in order to verify its reliability as a screening test. METHODS: 126 children, involved in an epidemiological study on prevalence of respiratory allergic disease, were evaluated. All children were assessed with a specific questionnaire, SPT and nasal specific IgE. Nasal specific IgE were determined with a previously described method modified for screening purposes, in order to test seven allergens at the same time. When discordant results were obtained between questionnaire, SPT and nasal IgE, an allergen specific nasal challenge (ASNC) was performed and nasal tryptase was also determined before and after challenge. RESULTS: The questionnaire was positive for respiratory allergy in 28/126 children. SPT was positive in 21 of the 28 children, but also in 5/10 children with atopic dermatitis (AD), and in 12/88 children without allergic symptoms. Nasal IgE were positive in 22/28 and also in 2/10 with AD. Nasal challenge and tryptase confirmed the negativity of nasal IgE in 12/17 children with positive SPT but totally negative for allergic respiratory disease. Moreover nasal IgE was found to be positive to dermatophagoides in one of seven children with negative SPT despite a clinical history suggestive for mite respiratory allergy. In this patient and in 2 of the 5 children with AD the positive nasal IgE to mites was confirmed by a positive ASNC and tryptase. CONCLUSIONS: Nasal IgE have shown a specificity significantly higher than SPT (98% vs. 83%) and a good sensibility. This screening test may also be useful to detect the beginning of upper airways sensitization in patients with AD.

Do tryptase, ECP and specific IgE measurement by nasal incubation increase the specific nasal provocation test sensitivity?

The specific Nasal Provocation Test (sNPT) is a third level diagnostic tool. Fitted to reproduce natural exposure condition to pick the responsible allergen for nasal symptoms out, it is applied when prick test and RAST responses are doubtful. SNPT results have been evaluated measuring nasal resistance (anterior rhinomanometry) and nasal symptoms (clinical score), reaching 50% of sensitivity. This study focused on the determination of allergic response markers, triggered by nasal challenge: tryptase levels in the nose, specific IgE and ECP (Eosinophil Cationic Protein). The aim was to increase sNPT sensitivity. Twenty patients suffering from allergic rhinitis and 16 age-matched-nonallergic subjects were enrolled in the study. Tryptase, specific IgE and ECP were determined in nasal mucosa applying a new method, based on in situ incubation, before and after sNPT. The latter was performed following a standardized method. Tryptase levels increased in 13 patients (65%), were unchanged in four patients (20%), and slightly decreased in three patients (15%). The increase recorded was significant in mite allergic patients (p=0.005), but not significant (p> 0.05) in pollen allergic patients. ECP values increased in 13 patients (65%), were unchanged in two patients (10%), and highly decreased in five patients (25%). ECP increase was not significant (p> 0.05). Specific IgE levels increased in seven patients (35%), were unchanged in 11 patients (55%) and decreased in two patients (10%). The IgE increase was significant in pollen-allergic patients (p<0.05), while it was not significant in mite-allergic patients (p>0.05). Tryptase, ECP, and specific IgE were not detected in the control group. The data obtained showed a positive sNPT response in 12 patients (60%). Comparing our results with those derived from classical-parameter employment, we gathered an improvement of 10%. On the basis of the usual parameters, in fact, we recorded 50% positivity, while the use of mediators provided an additional 10% improvement in sNPT sensitivity: taking together the usual parameters and nasal allergic mediators values, we reached an sNPT over-all sensitivity of 85%.

Low-dose local nasal immunotherapy in children with perennial allergic rhinitis due to Dermatophagoides.

BACKGROUND: Allergen specific immunotherapy was known to be useful in the treatment of respiratory allergic disease. Local nasal immunotherapy (LNIT) offers advantages such as a good efficacy/safety ratio and a more convenient allergen delivery. The aim of this study was to assess the safety and clinical efficacy of a modified scheduling of LNIT in 32 children with allergic rhinitis due to Dermatophagoides. METHODS: A multicentre, randomized, double-blind placebo controlled study carried out for two years, with a modified schedule of LNIT treatment: a build-up phase at increasing dosages from 2.5 AU to 80 AU and a maintenance period at low dosage (80 AU) once a week. Symptom and medication scores. threshold dose with specific nasal provocation test (NPT) and immunological parameters (IgE and IgG4) were evaluated. RESULTS: No important local or systemic side-effects were observed in children who completed the study. Compared to placebo, the active treatment group showed significant improvement in rhinitis symptoms and a reduction of drug consumption after 18 months of LNIT. These results were confirmed by a significant reduction of allergen specific nasal reactivity. Serum and nasal specific IgE and IgG4 did not show any difference in the two groups. CONCLUSIONS: The safety and clinical efficacy of low-dose LNIT suggests that this therapy may be useful in the treatment of allergic rhinitis disease in children.

Eosinophil cationic protein and specific IgE in serum and nasal mucosa of patients with grass-pollen-allergic rhinitis and asthma.

BACKGROUND: After allergen exposure, IgE-bearing mast cells surface in respiratory mucosa. Eosinophils are also recruited locally by chemotactic mediators; they are the main cell directly involved in the late phase of allergic inflammation. IgE antibody and eosinophil cationic protein (ECP) are routinely determined mainly in serum although they exert their pathogenetic role more directly on mucosal surfaces. METHODS: We performed a comparative study of IgE antibody to grass and ECP on nasal mucosa and blood samples in order to evaluate the relevance of monitoring allergic inflammation in the target organ. Thirty-one patients and 10 nonatopic controls were enrolled in the protocol. Twenty-six subjects allergic to grass, 11 with rhinitis (group 1) and 15 with asthma and rhinitis (group 2), completed the study. Five patients dropped out. Specific IgE to grass and ECP was determined in nasal mucosa by our method based on in situ incubation. RESULTS: Serum IgE to grass did not increase during the pollen peak, as did nasal IgE, in group 1 from before the pollen peak, from 2.3 to 3.2 kU/l (P=0.02), and in group 2 at the pollen peak, from 4.8 to 12.2 kU/l (P=0.01). Serum ECP did not show any significant variation in group 1, but it increased at pollen peak from 6 to 11.2 microg/l (P=0.01) in group 2. Nasal ECP increased significantly in both groups even before the pollen peak. In group 1, ECP values rose from 15 to 39.9 microg/l (P=0.01). In group 2, ECP increase was much higher than in group 1, from 9 to 213 microg/l (P=0.001). Serum eosinophils, like nasal ECP, showed a significant increase of values from before the pollen peak in both groups, without correlation with serum ECP in rhinitic patients. CONCLUSIONS: Both specific IgE and ECP in the nasal mucosa showed a better correlation with allergen exposure than serum evaluations. With an appropriate method, allergic inflammation may be best monitored in the nasal mucosa.

Preseasonal local allergoid immunotherapy to grass pollen in children: a double-blind, placebo-controlled, randomized trial.

BACKGROUND: We assessed the efficacy of preseasonal local allergoid immunotherapy in a group of children with asthma and/or rhinitis and/or rhinoconjunctivitis due to grass pollen. METHODS: We randomly assigned 24 children allergic to grass pollen to receive local allergoid immunotherapy for 3 months before the pollen season and 24 such patients to receive identically appearing placebo. The immunotherapy consisted of tablets of monomeric allergoid grass pollen allergens held in the mouth until they dissolved and then swallowed. The study was double-blind. Symptoms and medications were scored on diary cards during the pollen season. Nasal eosinophil cationic protein levels were measured by the monoclonal antibodies EG1 and EG2 outside the pollen season and at low and at high pollen concentration during the pollen season. RESULTS: The active-treatment group had a statistically significant reduction of total symptoms (P<0.05), especially bronchial symptoms (P<0.05), in comparison with the placebo group. Immunotherapy was well tolerated and compliance was good. Nasal levels of EG2 and EG1 increased significantly during the pollen season, but there was no difference between groups. EG2/EG1 increased significantly only in the placebo group during natural allergen exposure (P<0.01). CONCLUSIONS: Our results suggest that this immunotherapy is effective for the treatment of asthma due to grass pollen in children.

Allergic rhinitis in children: effects of flunisolide and disodium cromoglycate on nasal eosinophil cationic protein.

BACKGROUND: Eosinophil cationic protein (ECP) is one of the major, cytotoxic molecules produced by eosinophils, which can be used as a marker of allergic inflammation. OBJECTIVE: In this placebo-controlled study we measured nasal and serum ECP levels to verify their possible role in monitoring the efficacy of anti-inflammatory therapy in allergic chronic rhinitis in 38 children aged from 4 to 14yr, allergic to house dust mites. METHOD: Nasal ECP, by the method of direct incubation on nasal mucosa, and serum ECP were determined before and after 3 weeks of treatment with flunisolide nasal spray 50 micrograms twice/daily (13 cases, Group 1), disodium cromoglycate (DSCG) 10.4 mg three times/day (15 cases, Group 2) and placebo (10 cases, Group 3). The effectiveness of therapy was evaluated clinically and correlated to serum and nasal ECP values. RESULTS: Before treatment no significant difference emerged in the clinical scores of the three groups of patients. Before and after treatment serum ECP levels were not statistically different from normal controls. Before treatment nasal ECP was significantly higher in all patients compared with controls (P < 0.001). Nasal ECP decreased significantly in flunisolide-treated patients (P < 0.01) (before therapy: median 111 micrograms/L, range from 33.6 to 200 micrograms/L; after therapy: median 36.8 micrograms/L, range from 2.6 to 196 micrograms/L), but not in DSCG-treated patients, (before therapy: median 66.2 micrograms/L, range from 32.3 to 200 micrograms/L; after therapy: median 60.4 micrograms/L, range from 7.9 to 144 micrograms/L). No significant variation was present in the placebo group. Clinical improvement was statistically significant after flunisolide therapy (P < 0.05), less evident after DSCG (P = 0.06). CONCLUSION: Serum ECP in chronic allergic rhinitis has been shown to be not useful in monitoring allergic inflammation, but nasal ECP, determined by mucosal incubation, may be used to evaluate the activity of eosinophils and monitor the anti-inflammatory efficacy of therapy in chronic rhinitis.

Changes in nasal specific IgE to mites after periods of allergen exposure-avoidance: a comparison with serum levels.

Variations of serum and nasal specific IgE to Dermatophagoides pteronyssinus (Der p) during alternate periods of antigen avoidance-exposure have been evaluated with an open design in a group of allergic children with asthma and rhinitis at the residential house Istituto Pio XII (Misurina, BL, Italy), at 1756 m, in the Italian Dolomites. A method based on direct incubation of allergen coupled substrate on the nasal mucosa has been employed to evaluate the levels of nasal IgE. Serum specific IgE decreased respectively from (median) 117-89.3 kU/l (P < 0.001) during an initial period of 3 months of allergen avoidance and from 88.2 to 78.4 kU/l (P < 0.0002) during a subsequent period of allergen avoidance. No significant increase in serum specific IgE was, in contrast, observed during two periods, 22 and 9 days, of antigen exposure, changing respectively from 89.3 to 88.2 and from 78.4 to 89.1 kU/l. In contrast, nasal IgE has been significantly influenced by the alternate periods of antigen exposure-avoidance, showing a decrease from 19.75 to 4.01 kU/l (P < 0.0001) after the initial period of avoidance, followed by an increase to 9.95 kU/l (P < 0.0001) after 22 days of exposure. A significant decrease to a value of 2.37 kU/l (P < 0.0001) was also observed during the subsequent period of avoidance, followed again by an increase to 7.87 kU/l (P < 0.002) after 9 days of exposure. The evaluation of the kinetics of changes in nasal specific IgE revealed a significant decrease (P < 0.01) as soon as antigen avoidance was implemented for 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Specific IgE to food and inhalant allergens in intestinal washings of children affected by atopic eczema.

Serum and rectal total and specific IgE were measured in eleven children with atopic dermatitis and eight with atopic dermatitis and associated wheezing. Specific IgE to food and inhalant allergens in rectal washings were found in fourteen patients. Of the seventy-six allergens which gave positive results, twenty were positive in both serum and intestine, thirty in serum alone and twenty-six in intestines alone. Specific intestinal IgE were confirmed by food challenge in three out of four patients whose skin-prick test and serum RAST were both negative. Local production of these antibodies was demonstrated by the 'double ratio' of Deuschl and Johansson, and the 'specific activity ratio' of Platts-Mills. Positive ratios (greater than 1) were obtained with both formulas for twelve of fourteen allergens tested. These data suggest that gut-associated lymphoid tissue may play a role in the pathogenesis of atopic disease.