Sublingual immunotherapy tablets in monosensitized and polysensitized adults with allergic rhinoconjunctivitis.

Background: Most patients with allergic rhinitis/conjunctivitis (AR/C) are sensitized to more than one allergen. An ongoing question is the efficacy of single-allergen immunotherapy in patients who are polysensitized. Objective: To evaluate the efficacy and safety of grass, ragweed, tree, and house-dust mite (HDM) sublingual immunotherapy (SLIT) tablets in adults with AR/C who are mono- or polysensitized. Methods: Data from adults (ages ≥ 18 years) with AR/C who participated in phase III double-blind, placebo controlled field trials (four grass, two ragweed, two HDM, one tree) were included in the post hoc analyses. Efficacy was assessed by the total combined score (TCS) (sum of AR/C daily symptom and medication scores) during the entire pollen season for grass and tree trials, and peak pollen season for ragweed trials versus placebo. Efficacy for the HDM SLIT-tablet was assessed by the total combined rhinitis score (TCRS) (sum of rhinitis daily symptom and medication scores) during the last 8 weeks of treatment versus placebo. Results: For the grass SLIT-tablet, TCS improved by 20% (mean difference 1.33 [95% confidence interval {CI}, 0.44-2.22]) in the subjects who were monosensitized (n = 442) and 20% (mean difference 1.28 [95% CI, 0.90-1.67]) in the subjects who were polysensitized (n = 1857). For the ragweed SLIT-tablet, TCS improved by 19% (mean difference 1.72 [95% CI, -0.20 to 3.63]) in the subjects who were monosensitized (n = 115) and 27% (mean difference 2.27 [95% CI, 1.28-3.27]) in the subjects who were polysensitized (n = 528). For the tree SLIT-tablet, TCS improved by 54% (mean difference 4.65 [95% CI, 2.48-6.82]) in the subjects who were monosensitized (n = 138) and 34% (mean difference 2.51 [95% CI, 1.34-3.69]) in the subjects who were polysensitized (n = 437). For the HDM SLIT-tablet, TCRS improved by 20% (mean difference 1.24 [95% CI, 0.48-1.99]) in the subjects who were monosensitized (n = 468) and 17% (mean difference 0.85 [95% CI, 0.43-1.28]) in the subjects who were polysensitized (n = 1294). The overall safety profile was not qualitatively different between the subjects who were monosensitized and the subjects who were polysensitized. Conclusion: Grass, ragweed, tree, or HDM SLIT-tablet treatment is effective for the specific allergen in question in adults with AR/C and who are monosensitized or polysensitized. Targeting one relevant allergen with SLIT-tablets induces a clinical effect for that allergen in patients who were polysensitized.

Allergy immunotherapy for allergic fungal respiratory diseases.

Background: Allergy immunotherapy (AIT) with fungal extracts is not as straight forward as that with other inhalants. The complexities relate to the number of airborne fungal spores, the limited data on the exposure to the spores of individual species of fungi and their clinical importance, the poor quality of the fungal allergen extracts that are available for the diagnosis and treatment, and the lack of controlled studies establishing dosing and efficacy of AIT with fungal extracts except for Alternaria. Objective: The objective was to review what is known with regard to the role of fungi in causing allergic respiratory diseases as well as the evidence that exists for the role of AIT as a treatment for these conditions. Methods: A search was conducted of PubMed, textbooks, known articles on immunotherapy with fungal extracts, and references derived from these primary sources. Results: Nine immunotherapy studies that used Alternaria or its major allergen Alt a 1 and two studies that used Cladosporium herbarum were identified. When a good quality extract was administered in adequate doses, immunotherapy with Alternaria was as effective as that with other inhalant allergens. There was a suggestion of efficacy with a specially prepared Cladosporium extract, but systemic reactions were common and limited the tolerated dose. The use of immunotherapy as an adjunct treatment for allergic fungal sinusitis is briefly reviewed, but controlled trials are lacking. Conclusion: Fungal immunotherapy should largely be limited to Alternaria alternata and perhaps C. herbarum. Under conditions of demonstrated exposure to a particular species of fungus and with symptoms that correlate with that exposure as well as availability of an apparently potent extract of that fungus to which the patient is sensitive that fungus may be considered for immunotherapy. Fungal (mold) mixes should not be used for diagnosis or therapy.

The return of the mixed respiratory bacterial vaccine.

Background: Orally or sublingually administered lysates of mixed respiratory pathogenic bacteria have been used in Europe, Asia, and other parts of the world, but not the United States, since the mid 1950s, first to prevent recurrent respiratory tract infections, later to prevent wheezing and asthma exacerbations associated with respiratory infections, and, more recently, for the treatment of allergic rhinitis. The apparent success of this treatment contrasts with the negative experience of treating with injections of similar mixed respiratory bacterial vaccines (MRBV or BV) to prevent asthma exacerbations associated with respiratory infections that was once common practice but abandoned ∼50 years ago. Methods: Textbooks and articles on the use of injected BVs to prevent asthma exacerbations associated with respiratory infections were reviewed, including a number of, randomized, double-blind, placebo controlled (RDBPC) studies the results of which were predominantly negative that contributed to the abandonment of this treatment. Also reviewed were more recent articles from Europe and China, which report both clinical and immunologic support for the use of the orally and sublingually administered mixed respiratory bacterial lysates (MRBL or BL). Results: A review of five RDBPC studies of the parenteral use of BVs for prevention of asthma exacerbations conducted by leading international allergists in the 1950s and 1960s showed, in a combined 532 patients, an overall reduction of asthma attacks by 4.9% over placebo. However, in five studies in 1126 patients of oral or sublingual treatment with BLs, the reduction in respiratory infections, wheezing episodes, and asthma exacerbations was 42.6% over placebo. Conclusion: Reported results with oral and sublingual BLs are far superior to the historical performance of injected BVs. Possible reasons for this difference are discussed, but none is clearly responsible for the difference in clinical results.

Standardized allergen extracts for allergen immunotherapy.

Nineteen U.S. allergen extracts were standardized by the U.S. Food and Drug Administration (FDA) between 1987 and 1998, including of two house-dust mites, short ragweed, cat hair and cat pelt, seven temperate and one southern grass, and six Hymenoptera venom preparations. Relevant literature was reviewed. For each allergen, a "representative" extract was established; the potency of each representative extract was determined by measurement of the total protein content (Hymenoptera venom), radial diffusion measurement of the dominant allergen (short ragweed and cat), or, if there was no dominant allergen, then by quantitative skin testing by using the ID50EAL (intradermal dilution for 50 mm sum of erythema determines the bioequivalent allergy units) method. In vitro tests were developed to allow the manufacturer to demonstrate that each lot of its extract was statistically identical, within defined limits, to the FDA reference extract. These tests included radial immunodiffusion, competitive enzyme-linked immunosorbent assay, and isoelectric focusing. The standardized extracts offer the advantage of consistent potency from lot to lot for each manufacturer and also from manufacturer to manufacturer, and assure the presence of recognized significant allergens within the extract. Therefore, standardized extracts offer improved safety and efficacy over their nonstandardized predecessors.

Future directions in allergen immunotherapy.

Both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are effective clinically against allergic rhinitis and allergic asthma, and modify the underlying immunologic abnormalities. Despite this, many patients who could benefit from receiving SCIT and SLIT do not because of concerns about safety and the inconvenience in receiving SCIT, and the long duration of treatment with both, 3-4 years being required for lasting benefit. Attempts to improve the efficacy and safety, and to shorten the course of allergen immunotherapy have taken many approaches. Some approaches have generated great enthusiasm, only to fail in larger trials and be discarded. Other approaches show some promise but perhaps not enough to achieve regulatory approval. Those approaches that seem to have the best chance of becoming available in the next few years include the following: intralymphatic and epicutaneous immunotherapy, vitamin D in patients with insufficient serum 25 hydroxy vitamin D, probiotics, and allergoids, but all require further studies before being ready for nonexperimental use or, where necessary, for regulatory approval.

Curcumin does not significantly affect immediate skin tests.

Background: Curcumin has been shown to decrease allergic symptoms and biomarkers in some animal and human studies. Objective: Our study aimed to determine if curcumin affects immediate skin-prick testing. Methods: We enrolled 34 participants sensitized to select antigens. The participants were randomized to treatment with curcumin or placebo in a double-blind fashion. The participants underwent titrated skin-prick testing before and after 1 week of treatment, and the pre- and posttreatment skin test wheals and flares were compared. Results: Curcumin did not have a statistically significant effect on immediate skin-prick test wheal or flare size. Conclusion: Although curcumin may attenuate allergic symptoms and biomarkers, it does not have a significant effect on immediate skin-prick test results and does not need to be discontinued before testing.

The evolution of allergy immunotherapy.

OBJECTIVE: The objective of this review is to trace the evolution of the art and science of allergy immunotherapy (AIT). DATA SOURCES: Original reports relating to the evolution of the concept of respiratory allergy and its specific treatment were identified by following references in journal articles, review articles, and allergy textbooks from the mid-20th century to the present. STUDY SELECTIONS: Studies highlighting substantial milestones in the evolution of the practice of allergy immunotherapy were included. RESULTS: The story of AIT begins with the recognition of hay fever as a distinct entity and subsequent studies that established grass pollen as one of the causes. This knowledge led several investigators, most notable Leonard Noon and John Freeman who worked at St. Mary's Hospital in London, to attempt to induce tolerance giving grass pollen extract by injection to their patients. After the publication of the work of Noon and Freeman in 1911, the practice of AIT spread rapidly and was applied to many other pollen allergens besides grass and for perennial rhinitis and asthma. The early studies were largely anecdotal, but over the past 60 to 70 years, studies of AIT have been conducted with increasingly sophisticated scientific methods. Nowadays, not only is the practice of AIT based on carefully conducted studies, but the underlying immunologic basis of allergy and the response to AIT have also been and still are being firmly established. CONCLUSION: Both the art and the science behind the practice of AIT have been established by a solid base of clinical and immunologic studies.

How important is proper dosing for subcutaneous and sublingual allergy immunotherapy?

Background: Results of surveys report that allergists use a wide range of doses for allergy immunotherapy; however, results of randomized, double-blind, placebo controlled studies suggest that the range of the optimum effective dosing is relatively narrow. Objective: To review studies that established effective or less than fully effective doses for allergy immunotherapy. Methods: Studies were reviewed that established effective and ineffective subcutaneous and sublingual immunotherapy doses. Only those studies that expressed dosing in terms of the content of a major allergen in the maintenance doses were included in defining effective and ineffective doses. Results: Studies were identified that showed effective doses for subcutaneous injection, established in randomized, double-blind, placebo controlled trials, for short ragweed, timothy grass, house-dust mites, cat and dog dander, birch, and Alternaria. For short ragweed, timothy grass, Dermatophagoides pteronyssinus, and cat and dog dander, less-effective doses were determined, along with effective doses; the less-effective doses were only one-fifth to one-tenth less in allergen content than were the effective doses. Effective doses of cockroach and all fungal extracts except Alternaria have not been established. Information is available on the mean major allergen content of U.S. standardized and a few nonstandardized extracts, which allows the information on effective and ineffective dosing to be used in prescribing subcutaneous allergy immunotherapy. With sublingual allergy immunotherapy, all the approved tablets had multidose studies that determined the optimal dose. For the U.S. liquid extracts, to my knowledge, there are no studies to define effective doses except for ragweed. Conclusions: Although a wide range of doses are prescribed by U.S. allergists, analysis of available data suggests that effective doses fall within a narrow range and that use of doses one-fifth or one-tenth of the effective doses may sacrifice most or all of the potential efficacy of the treatment.

Allergy immunotherapy: Future directions for the 2020s.

Allergy immunotherapy (AIT), whether administered as subcutaneous immunotherapy or as sublingual immunotherapy (SLIT), is an effective treatment for sensitization to inhalant allergens. There remain, however, some important unresolved issues, such as the need for compelling evidence for or against the efficacy of treatment with multiple unrelated allergen extracts and optimal dosing with SLIT-liquid preparations. Both methods of AIT involve prolonged periods of treatment to achieve persisting benefit. This can be inconvenient and expensive, and failure to complete the period of prescribed treatment is common with both methods. New approaches are being developed and studied to make AIT more effective, safer, or more convenient. Among these approaches are using alternative routes of administration; using adjuvants, including vitamin D, Toll-like receptor ligand agonists, biologics, or probiotics; introducing additional SLIT tablets; defining the patterns of major and minor allergen sensitivity of patients and the content of allergen extracts to better match sensitization with treatment; and treating cats to reduce their allergen release. The allergen molecules themselves are being altered to make them less reactive with specific immunoglobulin E, both by creating allergoids and by using recombinant technology to produce modified allergen molecules. Which, if any, of these new approaches will become part of AIT practice in the next decade depends in part on their efficacy and in part on the availability of the resources to adequately study them.

Allergy immunotherapy for inhalant allergens: Strategies to improve efficacy.

Background: Allergy immunotherapy (AIT), both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), is an effective and safe treatment for allergic rhinitis and allergic asthma due to inhalant allergens. However, there are many variables in how it is administered. Objective: To review the evidence that suggests the optimum practices to enhance the efficacy of AIT. Methods: Articles that reported the results of various approaches to the practice of AIT and evidence-based guidelines were consulted for guidance on what approaches would enhance the efficacy of AIT. Results: Evidence is presented that supports optimum dosing for SCIT, a discussion of dosing with liquid SLIT, the management of the patient who is polyallergic, considerations in mixing allergen extracts, advantages and disadvantages of different up-dosing regimens with SCIT, the optimum duration of AIT, the comparative efficacy of SCIT and SLIT, and improving adherence to AIT. Also reviewed were two approaches, the use of adjuvants and of alternative routes of administration of currently available extracts, which may be useful in the future after further studies have defined their effectiveness. Conclusion: Although there is still controversy about some aspects of AIT, there is literature to support approaches that enhance the efficacy of both SCIT and SLIT.

Allergy immunotherapy for inhalant allergens: Strategies to minimize adverse reactions.

Background: Allergy immunotherapy (AIT), both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), is an effective and safe treatment for allergic rhinitis and allergic asthma due to inhalant allergens. However, there are many variables in how it is administered. Objective: To review the evidence that suggests the optimal practice(s) to minimize adverse reactions to AIT. Methods: Articles that reported the results of various approaches to the practice of AIT and evidence-based guidelines were consulted for guidance about approaches that would minimize adverse reactions to AIT. Results: Evidence is presented that supports care in the preparation of allergy extracts for treatment; use of modified extracts; location for administration of SCIT and SLIT; risk factors for systemic reactions; AIT in patients on adrenergic blocking agents and angiotensin-converting enzyme inhibitors; use of premedication; the need for prescription of epinephrine autoinjectors; adjustments in dose for pollen seasons, interruptions in treatment, and for local and systemic reactions; and the safety in patients with autoimmune diseases and during pregnancy. Conclusion: Although some of these variables have not been adequately studied, there are many studies that indicate practices that minimize the risk of adverse reactions for both SCIT and SLIT.

SQ house dust mite sublingual immunotherapy tablet subgroup efficacy and local application site reaction duration.

BACKGROUND: Allergic rhinitis with or without conjunctivitis (AR/C) is common, necessitating evaluation of SQ house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet efficacy in various subgroups. OBJECTIVE: To evaluate 12 SQ-HDM efficacy and safety across subgroups, and the onset, duration, and recurrence of local application site reactions. METHODS: Subgroup (age, sex, race, asthma status, and allergen sensitization) efficacy was assessed using pooled data from 2 previously described trials of daily 12 SQ-HDM vs placebo for AR/C (n = 2,138). Efficacy was measured by average total combined rhinitis score (TCRS; rhinitis daily symptom plus medication score) during the last 8 weeks of treatment. Safety in subgroups and local application site reaction onset, duration, and recurrence were evaluated using pooled data from 5 previously described trials of SQ HDM SLIT-tablet (n = 2,923). RESULTS: Significant (based on 95% confidence intervals [CIs]) reduction in TCRS was seen with 12 SQ-HDM relative to placebo across all subgroups, with TCRS improvements ranging from 15% to 25%. The AE profile was generally similar within subgroups. Approximately 95% of local application site reactions were mild to moderate in severity. Median duration on day 1 of treatment for the most common local application site reactions (throat irritation, oral pruritus, ear pruritus, and lip swelling) ranged from 30 to 60 minutes; median first day of onset ranged from days 1 to 4 of treatment; median days that reactions recurred ranged from 3 to 12 days. CONCLUSION: Treatment with 12 SQ-HDM consistently improved symptoms and was well tolerated in relevant subgroups of subjects with HDM AR/C. Local application site reactions to 12 SQ-HDM were typically mild to moderate and transient.

Immunotherapy for house-dust mite allergy.

BACKGROUND: Since the discovery of house-dust mites (HDM) in the 1960's, allergy immunotherapy trials that used extracts of these mites have been conducted, first by subcutaneous (SCIT) and later by the sublingual (SLIT) route. When reviewed in 2013, published studies of HDM immunotherapy were found to often be characterized by small sample size, widely varying doses, and poorly defined disease severity and outcomes. These trials were thought to to support the efficacy of HDM subcutaneous allergy immunotherapy but the evidence for efficacy of sublingual immunotherapy was less firm. METHODS: This report will review a large number of well-designed studies reported since 2013, mostly of SLIT, and in particular, of two newly developed HDM sublingual tablets. In addition, other aspects of HDM immunotherapy will be addressed, including use in atopic dermatitis, optimum duration of treatment, evidence for disease modification and use with adjuvants. RESULTS: Seventeen reports on 15 randomized, double-blind, placebo-controlled trials were identified as having been published since the cut-off date of the 2013 systematic review. Twelve of these reported results with the 2 HDM SLIT-tablets. These studies clearly established the appropriate doses and the efficacy and safety of these tablets in treating allergic rhinitis and asthma. Other reports offered support for use of HDM immunotherapy in selected patients with atopic dermatitis, for administration of HDM immunotherapy for 3 to 5 years, for anticipating disease modification after 3-5 years of treatment, and for the use of vitamin D and selected probiotics to enhance its efficacy. CONCLUSION: HDM SCIT and SLIT-tablet therapy have demonstrated effectiveness in allergic rhinitis and asthma. Appropriate dosing with HDM SLIT-liquid has not been established although a limited number of studies suggest it can be effective as well. HDM SCIT and HDM SLIT share efficacy in allergic rhinitis and asthma, disease modification and the duration of treatment required to produce persisting benefit.

Pooled efficacy and safety data for house dust mite sublingual immunotherapy tablets in adolescents.

BACKGROUND: House dust mite (HDM) respiratory allergy is a common and burdensome disease in children and adolescents. There are few HDM allergy immunotherapy trials in children with perennial allergic rhinitis. This post hoc analysis used pooled data to evaluate efficacy and safety of the SQ HDM sublingual immunotherapy (SLIT) tablet in adolescents (12-17 years). METHODS: In two double-blind, placebo-controlled trials conducted in North America and Japan, respectively, subjects aged 12+ years with HDM allergic rhinitis were randomized to up to 1 year of treatment. The primary end-point in both trials was the average total combined rhinitis score (TCRS) during the last 8 weeks of treatment in the active group compared with placebo. Data from subjects aged 12-17 years were pooled (N=395). RESULTS: In the pooled adolescent subpopulation, average TCRS improved 22% with 12 SQ HDM vs placebo (absolute treatment difference of 1.04; P<.01). Rhinitis daily symptom score (DSS), conjunctivitis DSS and rhinitis daily medication score (DMS) were also significantly improved vs placebo in the pooled adolescent subpopulation (all P<.05). There were no new safety signals for adolescents. The frequency of adverse events was similar in adolescents and adults with the majority being mild application site-related events. CONCLUSIONS: Treatment with 12 SQ HDM appears to be effective and well tolerated in adolescents with HDM allergic rhinitis.

Allergen Immunotherapy Clinical Trial Outcomes and Design: Working Toward Harmonization of Methods and Principles.

Progress has been made in the harmonization of efficacy and safety outcome measures for allergen immunotherapy (AIT) trials, but unresolved issues still remain. Furthermore, there are discrepancies in recommendations from professional medical societies and regulatory agencies regarding requirements for AIT trials. In this article, we reviewed published recommendations and current data from recent clinical trials, as well as the criteria applied by regulatory authorities for approval of AIT products, to provide updated considerations for conducting phase 3 AIT trials. Topics discussed include analysis of outcomes and trial designs for pediatric and asthma indications, as well as trial designs for perennial allergic rhinoconjunctivitis. In addition, the need for harmonization of safety reporting is emphasized. Considerations presented in this article may further effort to find common ground among professional medical societies and government agencies in developing future recommendations for AIT trial design.

Treatment effect of sublingual immunotherapy tablets and pharmacotherapies for seasonal and perennial allergic rhinitis: Pooled analyses.

BACKGROUND: Data comparing the treatment effect of allergy immunotherapy and pharmacotherapy are lacking. OBJECTIVE: We sought to indirectly compare the treatment effect of sublingual immunotherapy (SLIT)-tablets with pharmacotherapy for seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR). METHODS: Pooled data from randomized, double-blind, placebo-controlled trials for the clinical development programs of selected allergic rhinitis treatments were evaluated. Total nasal symptom scores (TNSSs) relative to placebo were compared. Subjects scored symptoms daily during entire pollen seasons in 6 timothy grass SLIT-tablet trials (n = 3094) and 2 ragweed SLIT-tablet trials (n = 658) and during the last 8 weeks of treatment in 2 house dust mite (HDM) SLIT-tablet trials (n = 1768). Subjects scored symptoms daily in 7 montelukast (10 mg, n = 6799), 9 desloratadine (5 mg, n = 4455), and 8 mometasone furoate nasal spray (MFNS; 200 µg daily, n = 2140) SAR or PAR trials. SLIT-tablet trials allowed rescue medication use, whereas most pharmacotherapy trials did not. A fixed-effect meta-analysis method estimated differences in on-treatment average TNSSs. RESULTS: In grass and ragweed SLIT-tablet trials, overall improvement in TNSSs relative to placebo was 16.3% and 17.1%, respectively. In HDM SLIT-tablet trials, TNSS overall improvement relative to placebo was 16.1%. In the montelukast, desloratadine, and MFNS trials, TNSS overall improvement relative to placebo was 5.4%, 8.5%, and 22.2%, respectively, for SAR trials, and 3.7%, 4.8%, and 11.2%, respectively, for PAR trials. CONCLUSIONS: Although comparisons were limited by study design heterogeneity and use of rescue medications in SLIT-tablet trials, effects on nasal symptoms with timothy grass and ragweed SLIT-tablets were nearly as great as with MFNS and numerically greater than with montelukast and desloratadine for SAR. HDM SLIT-tablet effects were numerically greater than all pharmacotherapies for PAR. SLIT-tablets offer the additional benefit of long-term efficacy.

Efficacy of house dust mite sublingual immunotherapy tablet in North American adolescents and adults in a randomized, placebo-controlled trial.

BACKGROUND: The house dust mite (HDM) sublingual immunotherapy (SLIT) tablet (MK-8237; Merck & Co, Kenilworth, NJ/ALK-Abelló, Hørsholm, Denmark) has demonstrated beneficial effects on allergic rhinoconjunctivitis and asthma outcomes in European trials. OBJECTIVE: This is the first trial to assess the efficacy/safety of HDM SLIT-tablets in North American subjects with HDM-induced allergic rhinitis with or without conjunctivitis (AR/C). METHODS: In this double-blind, multicenter trial (NCT01700192) 1482 subjects (aged ≥12 years) with HDM-induced AR/C with or without asthma were randomized to a daily SQ HDM SLIT-tablet (12 SQ-HDM dose) or placebo for up to approximately 52 weeks. A rhinitis daily symptom score (DSS; 4 nasal symptoms, maximum score = 12) of 6 or greater, or 5 or greater with 1 symptom being severe, on 5 of 7 consecutive days before randomization was required. The primary end point was the average total combined rhinitis score, which was defined as the rhinitis DSS plus rhinitis daily medication score (DMS), during the last 8 treatment weeks. RESULTS: Treatment with 12 SQ-HDM improved the total combined rhinitis score by 17% (95% CI, 10% to 25%) versus placebo. Improvements versus placebo in the secondary end points of average rhinitis DSS, rhinitis DMS, total combined rhinoconjunctivitis score, and visual analog scale-assessed AR/C symptoms were 16%, 18%, 17%, and 16%, respectively. All nominal P values were less than .001 versus placebo, except rhinitis DMS (P = 0.15). No treatment-related adverse events meeting the International Council on Harmonization definition of a serious adverse event were reported; 1 nonserious treatment-related systemic allergic reaction occurred (assessed as moderate intensity) at first administration under medical supervision and was treated with epinephrine. CONCLUSIONS: In the first North American trial of use of a SLIT-tablet for HDM allergy, 12 SQ-HDM was well tolerated and improved HDM-induced rhinitis symptoms in adults and adolescents.

Inhalation devices, delivery systems, and patient technique.

BACKGROUND: In real-life clinical settings, physicians often consider the properties of various inhaled corticosteroids (ICSs), but typically little consideration is given to the properties of different inhalers and formulations. OBJECTIVE: To discuss the effects of inhalation devices and user technique on efficacy, safety, and adherence with the aim of improving asthma management. METHODS: Relevant publications were selected to augment discussion. RESULTS: There are many types of devices available, each with advantages, disadvantages, ease of use, and rate of misuse. Aerosol particle size influences the deposition pattern of a drug in the lungs, and the optimal particle size range is 1 to 5 µm. Retrospective reviews suggest that smaller particles (1-2 µm) could provide improved asthma control, but randomized, prospective studies are needed. Multiple studies have demonstrated high misuse rates in patients for pressurized metered-dose inhalers and dry powder inhalers. Because of this, repeated education should include physical demonstrations of using the device, checking the patient's technique, correcting the technique, and rechecking the technique. This also means that dedicated, trained staff and placebo devices should be available for instructing patients. Furthermore, the device should be selected to be cost effective and to fit the patient's preference and ability to use it correctly to enhance compliance. Asthma management guidelines and algorithms are available to guide the clinician. CONCLUSION: The choice of inhaler device should depend on cost effectiveness and the patient's preference and ability to use it correctly. Patient inhaler technique should be checked and, if necessary, corrected and rechecked, with retraining if needed, at every opportunity.