Bronchial hyperresponsiveness (BHR) is a typical feature of asthma, and is, at least in part, related to the chronic inflammation. Allergen exposure is a major trigger and cause of allergic inflammation. The possible relationship between the degree of bronchial reactivity and the number of positive skin test was studied. One hundred and one patients with allergic asthma (and rhinitis) underwent skin-prick tests and methacholine bronchial challenge according to standard protocols. No significant relation was found between the degree of BHR and age or sex. Conversely, it was found that the number of positive skin tests correlated well with the degree of BHR (p = 0.046); in particular, those patients with three or more sensitivities showed greater bronchial reactivity. The present data support the hypothesis that allergic polysensitized patients may exhibit greater bronchial hyperresponsiveness, possibly due to an enhanced inflammatory component related to the exposure to multiple allergens.

Adolescent↗

PubMed1999

Clinical and immunologic effects of a rush sublingual immunotherapy to Parietaria species: A double-blind, placebo-controlled trial.

BACKGROUND: The local (noninjection) routes of immunotherapy are presently regarded as viable therapeutic options for respiratory allergy, and their mechanisms of action are currently undergoing investigation. OBJECTIVE: We evaluated the clinical efficacy of a preseasonal rush sublingual-swallow immunotherapy and its effects on allergic inflammation in patients with seasonal rhinoconjunctivitis caused by Parietaria species. METHODS: Thirty patients with Parietaria species-induced rhinoconjunctivitis (13 with mild intermittent asthma) were randomly assigned sublingual-swallow immunotherapy or placebo in a rush preseasonal course. We assessed the seasonal symptom-drug intake score by diary card and the inflammatory infiltration and the intercellular adhesion molecule 1 expression on nasal epithelium after specific allergenic challenge before and after treatment. RESULTS: The investigated immunotherapy was well tolerated, and no side effects were recorded. A significant reduction of the symptom score (P =.016) and drug intake score (P =. 008) after immunotherapy was observed only in the active group. A decrease of the cumulative score was observed also in the placebo group (P =.046), but the significance was clearly higher (P =.006) in the active group. In the active group a reduction of neutrophils (P =.001), eosinophils (P =.01), and intercellular adhesion molecule 1 expression (P =.04) after specific nasal challenge was also detected. CONCLUSION: The present results suggest that this sublingual-swallow immunotherapy administered through a rush schedule is clinically effective and safe and that it decreases the immune-mediated inflammatory responses to the allergen.

Administration, Sublingual↗

PubMed1999

Post-marketing surveillance study on the safety of sublingual immunotherapy in pediatric patients.

BACKGROUND: Immunotherapy (IT) is the only causal treatment for allergic subjects recognized to be effective and to offer long-lasting efficacy. The noninjective routes, aimed at improving the safety of the treatment, have been validated as effective in adults, but documentation of their safety in children is still poor. The aim of the present survey study was to assess the safety of sublingual immunotherapy in pediatric patients, by evaluating a large population. METHODS: A total of 268 children (aged 2-15 years), receiving sublingual IT for respiratory allergy, were followed-up over a period ranging from 3 months to 7 years (mean 34 months). The side-effects possibly due to the treatment were recorded on a proper diary card; self-assessment of the clinical outcome was also evaluated. RESULTS: About 96000 doses of extract were globally administered. Local side-effects were of no clinical relevance. Eight side-effects were reported (3% of patients; 0.083 per 1000 doses). Seven systemic side-effects (abdominal pain, conjunctival itching, and rhinitis) were mild and required no treatment. One case of urticaria was well controlled with oral antihistamines. No life-threatening event occurred. The clinical outcome was judged excellent or good by 80% of the patients. CONCLUSIONS: The sublingual IT herein investigated appeared to be well tolerated and safe in pediatric patients. The risk/benefit ratio was therefore favorable.

Administration, Sublingual↗

PubMed1999

Unconventional medicine: a risk of undertreatment of allergic patients.

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Adolescent↗

PubMed1999

Long-term treatment with allergoid immunotherapy with Parietaria. Clinical and immunologic effects in a randomized, controlled trial.

BACKGROUND: Specific immunotherapy (SIT) is a valuable treatment for respiratory allergy, and the use of chemically modified allergens (allergoids) has improved its safety, as testified by several studies. We evaluated the effects of a SIT course with an allergoid extract of Parietaria pollen in a double-blind, placebo-controlled trial. METHODS: The study was double-blind in the first year; then it was prolonged up to 3 years with all patients on active treatment. Clinical effectiveness, safety, skin reactivity, systemic immunologic parameters, and subjective assessment were evaluated. We also had available a self-evaluation recorded in a follow-up visit 4 years after the discontinuation of SIT. RESULTS: A significant reduction of the symptoms plus drug intake scores during the pollen seasons was observed in the patients receiving active SIT. The placebo patients, after switching to active SIT, also showed significant clinical improvement. The clinical efficacy persisted during years 2 and 3 of treatment. After year 1, the actively treated patients reported a significant subjective improvement (frequency of symptoms, P = 0.001; duration of symptoms, P = 0.024; physical performance, P = 0.043) compared with the placebo group. The self-evaluation by visual analog scale showed that all patients maintained a significant clinical improvement up to 4 years after discontinuing SIT (year 1: active=+31.6%, placebo=-15.7%; year 7: active=+35.8%, placebo=+31.3%). The systemic immunologic changes after active SIT paralleled those described elsewhere (IgE decreased from 22 to 9 and from 21 to 8 IU/ml; IgG4 increased from 43 to 87 and from 18 to 60 IU/ml). A significant decrease in skin reactivity to three different allergen concentrations was observed at year 3 compared with pretreatment values (P<0.05). CONCLUSIONS: The investigational SIT with Parietaria appeared to be effective and safe; a 3-year course of treatment achieved a long-lasting efficacy.

Adolescent↗

PubMed1999

Continuous antihistamine treatment controls allergic inflammation and reduces respiratory morbidity in children with mite allergy.

BACKGROUND: Allergic reaction is characterized by a complex inflammatory process. Some of the new antihistamines have antiallergic effects and can affect the inflammatory cell recruitment via adhesion molecule downregulation. We aimed to assess in a 12-month study whether continuous treatment with an antihistamine (terfenadine) can reduce respiratory symptoms and local inflammation in children with mite allergy. METHODS: The study was double-blind and placebo-controlled: it involved two parallel groups of children suffering from rhinoconjunctivitis and/or mild intermittent asthma due to mite allergy. They received either terfenadine (1 mg/kg per body weight per day) or placebo for 1 year. Nasal, conjunctival, and bronchial symptoms were recorded by diary cards; at each of the programmed control visits, a nasal scraping for inflammatory cells and ICAM-1 was performed. Some additional clinical parameters were also recorded: days of school absence, extra visits for acute respiratory symptoms, and days of hospital admission. RESULTS: Only children treated with terfenadine achieved significant control of symptoms (P<0.05 in 8 out of 12 months) and allergic inflammation, as shown by inflammatory cell infiltrate and ICAM-1 expression at nasal level (P<0.001), and had significantly fewer extra visits and school absences than the placebo group (P<0.03). No side-effects were reported in either group. CONCLUSIONS: The present study demonstrates that continuous terfenadine treatment (1 mg/kg body weight per day) could decrease respiratory symptoms and allergic inflammation, and it had an additional antiallergic effect in reducing ICAM-1 expression on nasal epithelial cells. Therefore, the present results confirm the efficacy of a long-term therapeutic strategy in controlling allergic inflammation.

Adolescent↗

PubMed1999

Prevalence of latex-specific IgE in blood donors: an Italian survey.

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Antibody Specificity↗

PubMed1999

Effects of H1 antihistamines on adhesion molecules: a possible rationale for long-term treatment.

Our knowledge of the mechanisms underlying the allergic reaction has increased rapidly and has revealed a complex network of cells, mediators and cytokines. The intercellular adhesion system (and the ICAM-1 molecule in particular) appeared to play a pivotal role in the accumulation of inflammatory cells at the site of allergic reaction. The new antihistamines have been demonstrated to be capable of affecting several phenomena of the allergic inflammation, including mediator release, cellular activation and adhesion molecule expression. Taking into consideration the central role of adhesion molecules, the modulation of their expression may represent an important therapeutic target. The nasal and the conjunctival challenges represent two useful models for the in vivo study of the antiallergic activity of drugs, as they allow investigation of a wide variety of parameters: inflammatory infiltrate, ICAM-1 expression, concentration of soluble mediators.

Animals↗

PubMed1999

Oral and sublingual immunotherapy: general aspects and critical considerations.

Local routes for immunotherapy (IT) such as oral (OIT) and sublingual (SLIT) have the primary aim of avoiding or minimizing the risk of adverse events and of improving the compliance of the patients with IT itself. About the possible mechanisms of action, only few information are available since local IT has been deeply studied only in the last ten years. The current data about pharmacokinetics are controversial and not conclusive, since they are mostly derived from animal models. However, very recent studies have demonstrated that the sublingual/swallow modality is the most promising way of mucosal immunotherapy. Thus, SLIT could be shown to lead to systemic immunological effects and to a decreased responsiveness of target organs. Furthermore, no severe adverse events were reported in the SLIT-studies. Some studies indicate that SLIT is as effective as subcutaneous IT, whilst OIT is not recommended for the clinical practice. SLIT would appear particularly suitable for pediatric patients. Administration schedules include a build-up phase and a maintenance phase which can be administered either preseasonally or continuously, and rush schedules for preseasonal IT are also available. Furthermore, SLIT reduces time and money expenses usually required by SIT since it is self-administered.

Administration, Oral↗

PubMed1998

Randomised controlled trial of local allergoid immunotherapy on allergic inflammation in mite-induced rhinoconjunctivitis.

BACKGROUND: Non-injective routes of immunotherapy are thought to be valuable therapeutic options for respiratory allergy. We investigated the clinical efficacy and the effects of sublingual/oral immunotherapy on conjunctival allergic inflammation in patients with mite-induced respiratory allergy. METHODS: We used a double-blind placebo-controlled design. 20 patients with mite-induced rhinoconjunctivitis (six of whom also had mild asthma) were randomly assigned sublingual/oral immunotherapy (n=10) or placebo (n=10) for 2 years. We assessed symptom score by diary cards and inflammatory-cell infiltrate, and expression of intercellular adhesion molecule 1 (ICAM-1) in the conjunctiva after specific allergen challenge at enrollment and after 12 and 24 months of treatment. FINDINGS: We found significantly lower symptom scores in the immunotherapy group than in the placebo group in most of the winter months (p=0.05). Compared with the placebo group, inflammatory-cell infiltration after conjunctival challenge, and ICAM-1 expression on conjunctival epithelium decreased significantly in the first year of treatment in the immunotherapy group (p=0.04 and p=0.02, respectively). These effects were also seen for the minimum persistent inflammation, in symptom-free patients exposed constantly to allergens (p=0.02). Serum concentrations of eosinophil cationic protein decreased significantly (p=0.04). Immunotherapy was well tolerated and compliance was good. INTERPRETATION: Our results suggest that this immunotherapy is clinically effective in rhinoconjunctivitis and that it decreases the immune-mediated inflammatory responses to the allergen.

Administration, Sublingual↗

PubMed1998

Cytokines and Airways: Recent Insights and Therapeutic Implications.

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Journal Article↗

PubMed1998

Intranasal fluticasone propionate reduces ICAM-1 on nasal epithelial cells both during early and late phase after allergen challenge.

BACKGROUND: Allergen specific nasal challenge (ASNC) is an optimal method to study the pathophysiological mechanisms sustaining the allergic inflammation and in particular the adhesion molecule system, which is involved in cellular infiltration of nasal mucosa. Topical steroids have been accepted as a highly effective anti-inflammatory therapy for allergic rhinitis. OBJECTIVE: The aim of this double-blind placebo- controlled study was the evaluation of clinical and cytological parameters, including ICAM-1 expression on nasal epithelial cells, after a 4 week treatment with nasal fluticasone propionate (200 microg/daily) or placebo, using the model of ASNC. METHODS: Twenty allergic rhinitics underwent nasal challenge before and after treatment. The following parameters were evaluated: (i) nasal symptoms (rhinorrhoea, itching, sneezing, obstruction), (ii) inflammatory cells (eosinophils and neutrophils), (iii) ICAM-1 expression on nasal epithelial cells at baseline, 30 min (early phase) and 6 h (late phase) after ASNC. RESULTS: Fluticasone propionate was capable of reducing: (i) clinical symptoms during both early (P<0.001) and late phase (P<0.04), (ii) eosinophil (P<0.002) and neutrophil (P<0.001) infiltrate during late phase, and (iii) ICAM-1 expression on nasal epithelial cells during both early (P < 0.01) and late phase (P < 0.03). CONCLUSIONS: The present results demonstrate that fluticasone propionate exerts a significant action on early and late phase clinical events following specific nasal challenge, reducing also the cellular influx during the late phase. This event is likely due to the modulation of ICAM-1 expression on epithelial cells.

Adolescent↗