Francesco Marcucci

Long‐lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10‐year prospective study

Background Subcutaneous immunotherapy for respiratory allergy has shown a long‐lasting efficacy after its discontinuation, whereas this evidence is still lacking for sublingual immunotherapy, despite the fact that it is widely used.

The safety of sublingual-swallow immunotherapy: an analysis of published studies

Background As the main target of sublingual immunotherapy (SLIT) is to reduce at most the occurrence of adverse events (AE), safety represents a critical issue. This aspect deserves particular mention when a higher dose of allergen extract than traditional subcutaneous immunotherapy (SCIT) is required to be effective: that may be up to 500 times that employed for SCIT.

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.

Safety of sublingual-swallow immunotherapy in children aged 3 to 7 years

BACKGROUND The minimum age to start specific immunotherapy with inhalant allergens in children has not been clearly established, and position papers discourage its use in children younger than 5 years. OBJECTIVE To assess the safety of high-dose sublingual-swallow immunotherapy (SLIT) in a group of children younger than 5 years. METHODS Sixty-five children (51 boys and 14 girls; age range, 38-80 months; mean +/- SD age, 60 +/- 10 years; median age, 60 months) were included in this observational study. They were treated with SLIT with a build-up phase of 11 days, culminating in a top dose of 300 IR (index of reactivity) and a maintenance phase of 300 IR 3 times a week. The allergens used were house dust mites in 42 patients, grass pollen in 11 patients, olive pollen in 5 patients, Parietaria pollen in 4 patients, and cypress pollen in 3 patients. All adverse reactions and changes in the treatment schedule were compared in 2 subgroups: children 38 to 60 months old and children 61. to 80 months old. RESULTS The average cumulative dose of SLIT was 36,900 IR. Adverse reactions were observed in 11 children, none of them severe enough to require discontinuation of immunotherapy. Six reactions occurred in the 60 months or younger age group and 7 in the older than 60 months age group, with no differences between these 2 groups. CONCLUSION High-dose immunotherapy in children younger than 5 years does not cause more adverse reactions than in children aged 5 to 7 years. There is no reason to forbear studies on safety and efficacy of these preparations in young children.

Allergy and the gastrointestinal system

The gastrointestinal system plays a central role in immune system homeostasis. It is the main route of contact with the external environment and is overloaded every day with external stimuli, sometimes dangerous as pathogens (bacteria, protozoa, fungi, viruses) or toxic substances, in other cases very useful as food or commensal flora. The crucial position of the gastrointestinal system is testified by the huge amount of immune cells that reside within it. Indeed, gut‐associated lymphoid tissue (GALT) is the prominent part of mucosal‐associated lymphoid tissue (MALT) and represents almost 70% of the entire immune system; moreover, about 80% of plasma cells [mainly immunoglobulin A (IgA)‐bearing cells] reside in GALT. GALT interacts strictly with gastrointestinal functions in a dynamic manner; for instance, by increasing intestinal permeability in replay to particular stimulations, or orientating the immune response towards luminal content, allowing either tolerance or elimination/degradation of luminal antigens, or sometimes provoking damage to the intestinal mucosa, such as in coeliac disease or food allergy. The immune mechanisms implicated in these actions are very complex and belong to both innate and adaptive immunity; innate immunity supplies an immediate non‐specific response that is indispensable before specific adaptive immunity, which needs 7–10 days to be efficacious, takes place. The results of their interactions depend upon different contexts in which contact with external agents occurs and may change according to different genetic settings of the hosts.

Sublingual tryptase and ECP in children treated with grass pollen sublingual immunotherapy (SLIT): safety and immunologic implications.

Background: The clinical safety of sublingual immunotherapy (SLIT) has been repeatedly confirmed; nevertheless, the possible onset of local oral symptoms is still a concern, and nothing is known about the pathogenesis of this effect. We aimed to determine whether the administration of SLIT in allergic children can evoke an IgE‐mediated reaction, by measuring the levels of sublingual tryptase and ECP.

Three-year follow-up of clinical and inflammation parameters in children monosensitized to mites undergoing sub-lingual immunotherapy

Parallel follow‐up of clinical and inflammatory markers during sub‐lingual immunotherapy (SLIT) is highly beneficial. Twenty‐four children (age 4–16) monosensitized to house dust mite were randomized to receive either active or placebo SLIT for 1 yr in a double‐blind placebo controlled design (Marcucci et al., Allergy 2003: 58: 657–62). Thereafter, for 2 yr they all received active treatment. Symptom scores for rhinitis, asthma, and drug usage were daily recorded. Eosinophil cationic proten (ECP) and tryptase in sputum and nasal secretions, serum and nasal mite‐specific immunoglobulin E (IgE) were recorded before treatment and at 10–12 months intervals. Nasal ECP and nasal tryptase after specific nasal provocation tests were significantly reduced as compared to baseline values (p = 0.0043 and 0.0195, respectively) in the third year of active treatment. None of the other inflammatory parameters was increased. In placebo treated patients all these parameters tended to decrease only after switching to active treatment. Clinical scores did not improve in treated vs. placebo patients in the double‐blind placebo‐controlled phase of the study. In both cohorts a clinical benefit was observed as intra‐group score reduction as compared to baseline. A significant difference was reached in patients treated for 2 yr for rhinitis and asthma (p = 0.0009 and 0.0019, respectively) but not for drug usage and in patients treated for 3 yr for rhinitis, asthma, and drug usage (p = 0.0105, 0.0048, and 0.02, respectively). SLIT in children monosensitized to mites reverted the spontaneous increase in nasal IgE and in local parameters of allergic inflammation. These outcomes were followed by a consolidated clinical improvement in the second and third year of treatment.

Effects on inflammation parameters of a double-blind, placebo controlled one-year course of SLIT in children monosensitized to mites.

Background: Clinical documentation about effects on local markers of inflammation of sublingual immunotherapy (SLIT) in children is still poor.

Dose dependence of immunological response to sublingual immunotherapy

Background:  Sublingual‐swallow immunotherapy (SLIT) is an accepted treatment for allergic rhinitis but its optimal dosage is scantly investigated. We studied the dose dependence of clinical efficacy and immunological response to SLIT by administering two different dosages of the same allergen in rhinitic children monosensitized to grass pollen.

Infant swimming in chlorinated pools and the risks of bronchiolitis, asthma and allergy

Recent studies suggest that swimming in chlorinated pools during infancy may increase the risks of lower respiratory tract infection. The aim of the present study was to assess the influence of swimming in chlorinated pools on the risks of bronchiolitis and its late consequences. A total of 430 children (47% female; mean age 5.7 yrs) in 30 kindergartens were examined. Parents completed a questionnaire regarding the child’s health history, swimming practice and potential confounders. Attendance at indoor or outdoor chlorinated pools ever before the age of 2 yrs was associated with an increased risk of bronchiolitis (OR 1.68; 95% CI 1.08–2.68; p = 0.03), which was exposure-dependent for both types of pool (p-value for trend <0.01). Associations persisted, and were even strengthened, by the exclusion of other risk factors. Among children with no parental antecedents of atopic disease or no day-care attendance, odds ratios for bronchiolitis amounted to 4.45 (1.82–10.9; p = 0.001) and 4.44 (1.88–10.5; p = 0.007) after >20 h spent in chlorinated pools during infancy. Infant swimmers who developed bronchiolitis also showed higher risks of asthma and respiratory allergies later in childhood. Swimming pool attendance during infancy is associated with a higher risk of bronchiolitis, with ensuing increased risks of asthma and allergic sensitisation.