Allergen immunotherapy for respiratory allergy: to what extent can the risk of systemic reactions be reduced?

Introduction: Allergen immunotherapy is an effective treatment for respiratory allergy, but the administration to patients of extracts of the causative allergen may elicit systemic reactions, which include, particularly with subcutaneous immunotherapy (SCIT), anaphylaxis. In the past, the occurrence (tough rare) of fatal reactions has represented a serious problem that has limited the prescription of SCIT. Areas covered: The authors analyzed in this review the safety data of SCIT, especially concerning the years following the identification of uncontrolled asthma at the moment of allergen injection as the major risk of life-threatening reactions and fatalities. The safety of SLIT, which is far better than SCIT, was analyzed and its specific risk factors for systemic reactions were highlighted. Expert opinion: Presently, the safety profile of SCIT and SLIT is satisfactory, provided the treatment is administered by physicians experienced in this treatment, who are aware of the known risk factors for severe reactions and who implement all measures to avoid them. For SLIT, which is self-administered by the patient, receiving the first dose under medical control is recommended

Sublingual reactivity to rBET V1 and rPHL P1 in patients with oral allergy syndrome.

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The role of allergoids in allergen immunotherapy: from injective to sublingual route

SummaryAllergen immunotherapy (AIT) is aimed at inducing tolerance to allergens, such as pollens, dust mites or moulds, by administering increasing amounts of the causative allergen through subcutaneous or sublingual route. The evidence of efficacy of AIT is high, but the issue of safety, especially for the subcutaneous route, must be taken into account. The search for safer AIT products aimed at reducing the allergenicity, and thus adverse reactions, while maintaining the immunogenicity, that is essential for effectiveness, gave rise to the introduction of allergoids, which were conceived to fulfill these requirements. In the first allergoids glutaraldehyde or formaldehyde were used as cross-linking agent to polymerize allergens, this resulting in high molecular weight molecules (200,000 to 20,000,000 daltons) which were significantly less allergenic due to a decreased capacity to bridge IgE on its specific receptor, while maintaining the immunogenicity and thus the therapeutic efficacy. In recent years further agents, acting as adjuvants, such as L-tyrosine, monophosphoryl lipid A, aluminium hydroxide, were added to polymerized extracts. Moreover, a carbamylated monomeric allergoid was developed and, once adsorbed on calcium phosphate matrix, used by subcutaneous route. At the same time, in virtue of its peculiarities, such allergoid revealed particularly suitable for sublingual administration. A lot of clinical evidences show that it is well tolerated, largely safer and effective. Importantly, the higher safety of allergoids allows faster treatment schedules that favor patient compliance and, according to pharmaco-economic studies, they might be more cost-effective than other AIT options

Effectiveness of omalizumab in a patient with severe asthma and atopic dermatitis

The anti-IgE antibody omalizumab is currently indicated in severe asthma not controlled by standard drug therapy. Recently, new indications for omalizumab were suggested, which include atopic dermatitis (AD), a skin disorder characterized by elevated levels of IgE. We report the case of a 39-year old woman with severe asthma and severe AD, both resistant to conventional drug treatment. The patient had a IgE level of 1304 kU/L, which exceeded the recommended maximum level for treating asthma with omalizumab (stated in 700 Ku/L) but was far lower than previously reported in cases of AD treated with anti-IgE. The treatment consisted of a dose of omalizumab 375 mg every two weeks, and induced a rapid improvement of asthma, with no need of other drugs after three months, along with a progressive decline of severity of AD, which after five months was completely cured. These findings suggest the usefulness of omalizumab in patients with concomitant severe asthma and AD, also considering the pharmaco-economic balance obtained by withdrawing the multiple drugs used to treat both diseases

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

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

Effectiveness of high dose sublingual immunotherapy to induce a stepdown of seasonal asthma: a pilot study

There is ample evidence to support the efficacy of sublingual immunotherapy (SLIT) on allergic rhinitis, while there is less solid data regarding asthma. We evaluated the effects of a high dose birch SLIT on birch-induced rhinitis and asthma in a controlled study

Adherence issues related to sublingual immunotherapy as perceived by allergists

Sublingual immunotherapy (SLIT) is a viable alternative to subcutaneous immunotherapy to treat allergic rhinitis and asthma, and is widely used in clinical practice in many European countries. The clinical efficacy of SLIT has been established in a number of clinical trials and meta-analyses. However, because SLIT is self-administered by patients without medical supervision, the degree of patient adherence with treatment is still a concern. The objective of this study was to evaluate the perception by allergists of issues related to SLIT adherence.We performed a questionnaire-based survey of 296 Italian allergists, based on the adherence issues known from previous studies. The perception of importance of each item was assessed by a VAS scale ranging from 0 to 10.Patient perception of clinical efficacy was considered the most important factor (ranked 1 by 54\% of allergists), followed by the possibility of reimbursement (ranked 1 by 34\%), and by the absence of side effects (ranked 1 by 21\%). Patient education, regular follow-up, and ease of use of SLIT were ranked first by less than 20\% of allergists.These findings indicate that clinical efficacy, cost, and side effects are perceived as the major issues influencing patient adherence to SLIT, and that further improvement of adherence is likely to be achieved by improving the patient information provided by prescribers

Economic evaluation of sublingual immunotherapy vs. symptomatic treatment in allergic asthma

The worldwide increased prevalence of allergic diseases, and especially of respiratory allergy, is paralleled by increased health costs. This requires consideration of the cost to efficacy ratio of the available treatment to identify the optimal choice

Sublingual immunotherapy: administration, dosages, use

Allergen extracts for sublingual immunotherapy (SLIT) are currently marketed by several manufacturers, with administration schedules and amount of allergen(s) quite variable in the different products, although almost all are standardized biologically or immunologically. The allergen extracts for SLIT are available in two main pharmaceutical forms: solution to be delivered by drop-counters, pre-dosed actuators (mini-pumps) or disposable single-dose vials; tablets with appropriate composition that allows a slow (1-2 minutes) dissolution in the mouth in contact with saliva. In Europe, SLIT is prescribed in general for one or a few allergens, and mixtures are less used, though there is no immunological contraindication to give multiple allergens. SLIT traditionally involves a build-up phase and a maintenance phase with the top dose. The build-up phase has usually the duration of 4 - 6 weeks. The patient must start with the lowest concentration and gradually increase, using the different dosage preparations, until the maintenance dose is reached. Rush and ultra-rush inductions have been introduced, based on the safety profile of SLIT that is very favorable. For these reasons it has been suggested that an updosing phase maybe even not necessary. The no-updosing approach would result in a treatment that is more patient-friendly and convenient to manage. Indeed, the most recent randomized trials were performed with the no-updosing regimen and their results in term of safety were as favorable as the studies performed with the traditional updosing approach. The currently recommended duration of SLIT is comprised between 3 and 4 years depending on the clinical response in single patients

Different outcomes of pulmonary rehabilitation in patients with COPD with or without exacerbations

Background. Pulmonary rehabilitation is recognised as an effective treatment in reducing disability and improving the quality of life in patients with COPD. We evaluated the effects of a course of pulmonary rehabilitation in improving the physical performance and lung function in patients with or without COPD exacerbations. Methods. 74 patients with COPD were enrolled, 37 (24 males and 13 females, mean age 74.6 years) without exacerbations (group A), and 37 (23 males, 14 females, mean age 73.9 years) with exacerbations (group B). The latter must have had the latest exacerbation at least one month before the inclusion. All patients underwent to a rehabilitation programme of 8 visits in 4 weeks in a day-hospital setting, with exercise training, respiratory muscle training and education on COPD. The changes in physical performance and lung function in respect to baseline were measured by a 6-minute walking test, using phethysmography, and by an analogic manometer measuring maximal inspiratory and expiratory pressures (MIP, MEP). Results. Patients of group A showed a mean increase in timed walk distance of 58.38 ± 57.46 m, compared to a mean increase of 31.38 ± 44.78 m in group B patients (p = 0.028). As to lung function, a mean increase of 178.92 ± 132.28 ml in FEV1 in group A versus 67.84 ± 102.04 ml in group B (p < 0.0001) and a mean increase of 22.36 ± 25.06 cm H2O in MEP in group A versus 7.70 ± 12.28 cm H2O in group B (p = 0.002) was found. Conclusions. These findings indicate that patients with COPD with exacerbations achieve a less favourable outcome of pulmonary rehabilitation, with a significantly lower improvement of physical performance, respiratory muscle strength and lung function in respect to subjects without exacerbations