Early Compliance and Efficacy of Sublingual Immunotherapy in Patients with Allergic Rhinitis for House Dust Mites

Objectives. Sublingual immunotherapy (SLIT) has recently received much attention around the world as a treatment for allergic rhinitis. This study aimed to investigate the efficacy and adverse effects of SLIT in Korean patients with allergic rhinitis caused by house dust mites. The treatment compliance and the patient satisfaction with SLIT were also assessed. Methods. The patients who were sensitized to Dermatophagoides pteronyssinus and Dermatophagoides farinae and who started SLIT between November 2007 and July 2008 were included in this study. The symptom questionnaires, which included items on rhinorrhea, sneezing, nasal obstruction, itchy nose, olfactory disturbance, eye discomfort and sleep disturbance, were obtained before and 6 months after SLIT. The patient satisfaction and the adverse effects were also investigated. Results. One hundred forty-two patients started SLIT and 98 of them continued SLIT for 6 months or more. Ninety-two of the 98 patients completed the questionnaires. The duration of receiving SLIT was 9.8 months on average (range, 6 to 13 months). All the symptoms of allergic rhinitis were improved with SLIT. Forty-five percent of the patients were satisfied for SLIT, while 12% were unsatisfied. The incidence of adverse effects was 12% during maintenance therapy, although it was 48% during the up-dosing phase. The drop-out rate of SLIT was 31.0%. Conclusion. The subjective symptoms were improved with SLIT in Korean patients with allergic rhinitis for house dust mites. Yet the drop out rate was high despite of the symptomatic improvement.Roder E, 2008, CLIN EXP ALLERGY, V38, P1659, DOI 10.1111/j.1365-2222.2008.03060.xEsch RE, 2008, CURR OPIN OTOLARYNGO, V16, P260Frew AJ, 2008, NEW ENGL J MED, V358, P2259BOUSQUET J, 2008, ALLERGY S, V86, P8Eifan AO, 2007, ALLERGY, V62, P567, DOI 10.1111/j.1398-9995.2006.01301.xDunsky EH, 2006, ALLERGY, V61, P1235, DOI 10.1111/j.1398-9995.2006.01137.xAntico A, 2006, ALLERGY, V61, P1236, DOI 10.1111/j.1398-9995.2006.01155.xDahl R, 2006, J ALLERGY CLIN IMMUN, V118, P434, DOI 10.1016/j.jaci.2006.05.003Durham SR, 2006, J ALLERGY CLIN IMMUN, V117, P802, DOI 10.1016/j.jaci.2005.12.1358Passlacqua G, 2006, J ALLERGY CLIN IMMUN, V117, P946, DOI 10.1016/j.jaci.2005.12.1312Canonica GW, 2006, ALLERGY, V61, P20PASSALACQUA G, 2006, INFLAMM ALLERGY DRUG, V5, P43RIENZO VD, 2005, CLIN EXP ALLERGY, V35, P560KIM DY, 2004, KOREAN J OTOLARYNGOL, V47, P132WILSON DR, 2003, COCHRANE DB SYST REV, P2893NUHOGLU Y, 2003, J INVESTIG ALLERGOL, V17, P375Lombardi C, 2001, ALLERGY, V56, P989Guez S, 2000, ALLERGY, V55, P369, DOI 10.1034/j.1398-9995.2000.00413.xPurello-D`Ambrosio F, 1999, ALLERGY, V54, P968Pradalier A, 1999, ALLERGY, V54, P819Durham SR, 1996, J ALLERGY CLIN IMMUN, V97, P1356CASANOVAS M, 1994, J INVEST ALLERG CLIN, V4, P305

Occupational allergy and asthma among salt water fish processing workers

Background Fish processing is a common economic activity in Southern Africa. The aim of this study was to determine the prevalence and host determinants of allergic symptoms, allergic sensitization, bronchial hyper-responsiveness and asthma among workers processing saltwater fish. Methods A cross-sectional study was conducted on 594 currently employed workers in two processing plants involved in pilchard canning and fishmeal processing. A modified European Community Respiratory Health Survey (ECRHS) questionnaire was used. Skin prick tests (SPT) used extracts of common airborne allergens, fresh fish (pilchard, anchovy, maasbanker, mackerel, red eye) and fishmeal. Spirometry and methacholine challenge tests (MCTs; tidal breathing method) used ATS guidelines. Results Work-related ocular-nasal symptoms (26%) were more common than asthma symptoms (16%). The prevalence of atopy was 36%, while 7% were sensitized to fish species and 26% had NSBH (PC 20  ≤ 8 mg/ml or ≥12% increase in FEV 1 post-bronchodilator). The prevalence of probable occupational asthma was 1.8% and fish allergic rhino-conjunctivitis 2.6%. Women were more likely to report work-related asthma symptoms (OR = 1.94) and have NSBH (OR = 3.09), while men were more likely to be sensitized to fish (OR = 2.06) and have airway obstruction (OR = 4.17). Atopy (OR = 3.16) and current smoking (OR = 2.37), but not habitual seafood consumption were associated with sensitization to fish. Conclusions Based on comparison with previous published studies, the prevalence of occupational asthma to salt water fish is lower than due to shellfish. The gendered distribution of work and exposures in fish processing operations together with atopy and cigarette smoking are important determinants of occupational allergy and asthma. Am. J. Ind. Med. 51:899–910, 2008. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61335/1/20635_ftp.pd

Mometasone and desloratadine additive effect on eosinophil survival and cytokine secretion from epithelial cells

Although antihistamines and topical corticosteroids are used in combination to treat allergic rhinitis, their additive effect has not been yet demonstrated. The aim was investigate the antiinflammatory additive effect of mometasone and desloratadine on cytokine and sICAM-1 secretion by epithelial cells, and on eosinophil survival stimulated by human epithelial cells secretions from nasal mucosa and polyps. Methods Epithelial cells obtained from nasal mucosa or polyps were stimulated with 10% fetal bovine serum in presence of mometasone (10-11M-10-5M) with/without desloratadine (10-5M). Cytokine and sICAM-1 concentrations in supernatants were measured by ELISA. Peripheral blood eosinophils were incubated during 4 days with epithelial cell secretions with (10-11M-10-5M) and/or desloratadine (10-5M) and survival assessed by Trypan blue. Results are expressed as percentage (mean ± SEM) compared to control. Results Fetal bovine serum stimulated IL-6, IL-8, GM-CSF and sICAM-1 secretion. In mucosa and polyp epithelial cells, mometasone inhibited this induced secretion while desloratadine inhibited IL-6 and IL-8. The combination of 10-5M desloratadine and 10-9M mometasone reduced IL-6 secretion (48 ± 11%, p < 0.05) greater extent than mometasone alone (68 ± 10%) compared to control (100%). Epithelial cell secretions induced eosinophil survival from day 1 to 4, this effect being inhibited by mometasone. At day 4, the combination of mometasone (10-11M) and desloratadine (10-5M) provoked an increased inhibition of eosinophil survival induced by cell secretions (27 ± 5%, p < 0.01) than mometasone (44 ± 7%) or desloratadine (46 ± 7%) alone. Conclusions These results suggest that the combination of desloratadine and mometasone furoate have a greater antinflammatory effect in an in vitro model of eosinophil inflammation than those drugs administered alone

Allergen immunotherapy for the prevention of allergy:a systematic review and meta-analysis

Background: there is a need to establish the effectiveness, cost-effectiveness, and safety of allergen immunotherapy (AIT) for the prevention of allergic disease.Methods: two reviewers independently screened nine international biomedical databases. Studies were quantitatively synthesized using random-effects meta-analyses.Results: a total of 32 studies satisfied the inclusion criteria. Overall, meta-analysis found no conclusive evidence that AIT reduced the risk of developing a first allergic disease over the short term (RR = 0.30; 95% CI: 0.04-2.09) and no randomized controlled evidence was found in relation to its longer-term effects for this outcome. There was, however, a reduction in the short-term risk of those with allergic rhinitis developing asthma (RR = 0.40; 95% CI: 0.30-0.54), with this finding being robust to a pre-specified sensitivity analysis. We found inconclusive evidence that this benefit was maintained over the longer term: RR = 0.62; 95% CI: 0.31-1.23. There was evidence that the risk of new sensitization was reduced over the short term, but this was not confirmed in the sensitivity analysis: RR = 0.72; 95% CI: 0.24-2.18. There was no clear evidence of any longer-term reduction in the risk of sensitization: RR = 0.47; 95% CI: 0.08-2.77. AIT appeared to have an acceptable side effect profile.Conclusions: AIT did not result in a statistically significant reduction in the risk of developing a first allergic disease. There was, however, evidence of a reduced short-term risk of developing asthma in those with allergic rhinitis, but it is unclear whether this benefit was maintained over the longer term. We are unable to comment on the cost-effectiveness of AIT

Randomized double-blind placebo-controlled trial of sublingual immunotherapy in children with house dust mite allergy in primary care: study design and recruitment

Background. For respiratory allergic disorders in children, sublingual immunotherapy has been developed as an alternative to subcutaneous immunotherapy. Sublingual immunotherapy is more convenient, has a good safety profile and might be an attractive option for use in primary care. A randomized double-blind placebo-controlled study was designed to establish the ef

EAACI Guidelines on Allergen Immunotherapy:Prevention of allergy

Allergic diseases are common and frequently coexist. Allergen immunotherapy (AIT) is a disease-modifying treatment for IgE-mediated allergic disease with effects beyond cessation of AIT that may include important preventive effects. The European Academy of Allergy and Clinical Immunology (EAACI) has developed a clinical practice guideline to provide evidence-based recommendations for AIT for prevention of i) development of allergic comorbidities in those with established allergic diseases, ii) development of first allergic condition and iii) allergic sensitization. This guideline has been developed using the Appraisal of Guidelines for Research &amp; Evaluation (AGREE II) framework, which involved a multi-disciplinary expert working group, a systematic review of the underpinning evidence and external peer-review of draft recommendations. Our key recommendation is that a three year course of subcutaneous or sublingual AIT can be recommended for children and adolescents with moderate to severe allergic rhinitis (AR) triggered by grass/birch pollen allergy to prevent asthma for up to two years post-AIT in addition to its sustained effect on AR symptoms and medication. Some trial data even suggest a preventive effect on asthma symptoms and medication more than two years post AIT. We need more evidence concerning AIT for prevention in individuals with AR triggered by house dust mites or other allergens and for the prevention of allergic sensitization, the first allergic disease or for prevention of allergic co-morbidities in those with other allergic conditions. Evidence for the preventive potential of AIT as disease modifying treatment exists but there is an urgent need for more high-quality clinical trials

Allergen-specific immunotherapy provides immediate, long-term and preventive clinical effects in children and adults: the effects of immunotherapy can be categorised by level of benefit -the centenary of allergen specific subcutaneous immunotherapy

Allergen Specific Immunotherapy (SIT) for respiratory allergic diseases is able to significantly improve symptoms as well as reduce the need for symptomatic medication, but SIT also has the capacity for long-term clinical effects and plays a protective role against the development of further allergies and symptoms. The treatment acts on basic immunological mechanisms, and has the potential to change the pathological allergic immune response. In this paper we discuss some of the most important achievements in the documentation of the benefits of immunotherapy, over the last 2 decades, which have marked a period of extensive research on the clinical effects and immunological background of the mechanisms involved. The outcome of immunotherapy is described as different levels of benefit from early reduction in symptoms over progressive clinical effects during treatment to long-term effects after discontinuation of the treatment and prevention of asthma. The efficacy of SIT increases the longer it is continued and immunological changes lead to potential long-term benefits. SIT alone and not the symptomatic treatment nor other avoidance measures has so far been documented as the therapy with long-term or preventive potential. The allergic condition is driven by a subset of T-helper lymphocytes (Th2), which are characterised by the production of cytokines like IL-4, and IL-5. Immunological changes following SIT lead to potential curative effects. One mechanism whereby immunotherapy suppresses the allergic response is through increased production of IgG4 antibodies. Induction of specific IgG4 is able to influence the allergic response in different ways and is related to immunological effector mechanisms, also responsible for the reduced late phase hyperreactivity and ongoing allergic inflammation. SIT is the only treatment which interferes with the basic pathophysiological mechanisms of the allergic disease, thereby creating the potential for changes in the long-term prognosis of respiratory allergy. SIT should not only be recognised as first-line therapeutic treatment for allergic rhinoconjunctivitis but also as secondary preventive treatment for respiratory allergic diseases

Sublingual immunotherapy for asthma.

BACKGROUND: Asthma is a common long-term respiratory disease affecting approximately 300 million people worldwide. Approximately half of people with asthma have an important allergic component to their disease, which may provide an opportunity for targeted treatment. Sublingual immunotherapy (SLIT) aims to reduce asthma symptoms by delivering increasing doses of an allergen (e.g. house dust mite, pollen extract) under the tongue to induce immune tolerance. However, it is not clear whether the sublingual delivery route is safe and effective in asthma. OBJECTIVES: To assess the efficacy and safety of sublingual immunotherapy compared with placebo or standard care for adults and children with asthma. SEARCH METHODS: We identified trials from the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov (www.ClinicalTrials.gov), the World Health Organization (WHO) trials portal (www.who.int/ictrp/en/) and reference lists of all primary studies and review articles. The search is up to date as of 25 March 2015. SELECTION CRITERIA: We included parallel randomised controlled trials (RCTs), irrespective of blinding or duration, that evaluated sublingual immunotherapy versus placebo or as an add-on to standard asthma management. We included both adults and children with asthma of any severity and with any allergen-sensitisation pattern. We included studies that recruited participants with asthma, rhinitis, or both, providing at least 80% of trial participants had a diagnosis of asthma. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results for included trials, extracted numerical data and assessed risk of bias, all of which were cross-checked for accuracy. We resolved disagreements by discussion.We analysed dichotomous data as odds ratios (ORs) or risk differences (RDs) using study participants as the unit of analysis; we analysed continuous data as mean differences (MDs) or standardised mean differences (SMDs) using random-effects models. We rated all outcomes using GRADE (Grades of Recommendation, Assessment, Development and Evaluation) and presented results in the 'Summary of findings' table. MAIN RESULTS: Fifty-two studies met our inclusion criteria, randomly assigning 5077 participants to comparisons of interest. Most studies were double-blind and placebo-controlled, but studies varied in duration from one day to three years. Most participants had mild or intermittent asthma, often with co-morbid allergic rhinitis. Eighteen studies recruited only adults, 25 recruited only children and several recruited both or did not specify (n = 9).With the exception of adverse events, reporting of outcomes of interest to this review was infrequent, and selective reporting may have had a serious effect on the completeness of the evidence. Allocation procedures generally were not well described, about a quarter of the studies were at high risk of bias for performance or detection bias or both and participant attrition was high or unknown in around half of the studies.One short study reported exacerbations requiring a hospital visit and observed no adverse events. Five studies reported quality of life, but the data were not suitable for meta-analysis. Serious adverse events were infrequent, and analysis using risk differences suggests that no more than 1 in 100 are likely to suffer a serious adverse event as a result of treatment with SLIT (RD 0.0012, 95% confidence interval (CI) -0.0077 to 0.0102; participants = 2560; studies = 22; moderate-quality evidence).Within secondary outcomes, wide but varied reporting of largely unvalidated asthma symptom and medication scores precluded meaningful meta-analysis; a general trend suggested SLIT benefit over placebo, but variation in scales meant that results were difficult to interpret.Changes in inhaled corticosteroid use in micrograms per day (MD 35.10 mcg/d, 95% CI -50.21 to 120.42; low-quality evidence), exacerbations requiring oral steroids (studies = 2; no events) and bronchial provocation (SMD 0.69, 95% CI -0.04 to 1.43; very low-quality evidence) were not often reported. This led to many imprecise estimates with wide confidence intervals that included the possibility of both benefit and harm from SLIT.More people taking SLIT had adverse events of any kind compared with control (OR 1.70, 95% CI 1.21 to 2.38; low-quality evidence; participants = 1755; studies = 19), but events were usually reported to be transient and mild.Lack of data prevented most of the planned subgroup and sensitivity analyses. AUTHORS' CONCLUSIONS: Lack of data for important outcomes such as exacerbations and quality of life and use of different unvalidated symptom and medication scores have limited our ability to draw a clinically useful conclusion. Further research using validated scales and important outcomes for patients and decision makers is needed so that SLIT can be properly assessed as clinical treatment for asthma. Very few serious adverse events have been reported, but most studies have included patients with intermittent or mild asthma, so we cannot comment on the safety of SLIT for those with moderate or severe asthma. SLIT is associated with increased risk of all adverse events