Sublingual immunotherapy tablets as a disease-modifying add-on treatment option to pharmacotherapy for allergic rhinitis and asthma

Allergic rhinitis (AR) with or without conjunctivitis (AR/C) is associated with a significant health and economic burden, and is often accompanied by asthma. Pharmacotherapies are the mainstay treatment options for AR and asthma, but guidelines also recommend allergy immunotherapy (AIT). Unlike pharmacotherapies, AIT has the ability to modify the underlying immunologic mechanisms of AR and asthma with the potential for long-term benefits after treatment is discontinued. Immunotherapy may also prevent progression of AR/C to asthma. Sublingual immunotherapy (SLIT)-tablets are a self-administered alternative to subcutaneous immunotherapy that provide the benefits of AIT without the cost and inconvenience of frequent office visits or the discomfort of injections. SLIT-tablets are also an option that can be utilized by primary care clinicians. Pharmacotherapies are generally effective in mild disease although a number of patients remain uncontrolled. SLIT-tablets have proven efficacy for AR in adults, children, and poly-sensitized allergic patients. Indirect comparisons indicate that SLIT-tablets have superior or comparable efficacy compared with traditional pharmacotherapies for seasonal AR, and superior efficacy for perennial AR. House dust mite (HDM) SLIT-tablets have also demonstrated clinically relevant benefits for asthma, with significant observed reductions in daily inhaled corticosteroid use, risk of asthma exacerbations, and asthma symptoms. SLIT-tablets are well tolerated, with minimal risk of systemic allergic reactions. The most common treatment-related adverse events are oral site reactions such as oral pruritus and throat irritation. Based on the favorable efficacy and safety profile, as well as the convenience of at-home oral administration and disease-modifying effects, SLIT-tablets should be considered as an alternative or add-on treatment to pharmacotherapy for AR/C, and as an add-on treatment for HDM allergic asthma.     

H1‐antihistamines and urticaria: how can we predict the best drug for our patient?

Urticaria, and especially chronic spontaneous urticaria (CSU), is a difficult condition to treat. Consequently, clinicians need to use the best H₁‐antihistamines currently available and the pharmaceutical industries need to keep developing H₁‐antihistamines that are more effective than the ones we have today. To do this we need to be able to compare the clinical efficacy of both established and new drugs. Obviously, the ideal way to do this is to use head‐to‐head studies in CSU. However, such studies are extremely expensive and, in the case of novel molecules, have ethical and logistical problems. Consequently, we need to have predictive models. Although determination of Ki, an indicator of the in vitro potency of an H₁‐antihistamine, may help in the initial selection of candidate molecules, the large differences in volume of distribution and tissue accumulation in humans, precludes this from being a good predictor of clinical efficacy in CSU. From the data reviewed in this article, especially the direct comparative data of desloratadine and levocetirizine in weal and flare studies and CSU, weal and flare response would appear to be the best indicator we have of effectiveness of H₁‐antihistamines in clinical practice. However, it must be pointed out that the conclusion is, essentially, based on detailed comparisons of two drugs in studies sponsored by pharmaceutical companies. Consequently, to confirm the conclusions of this review, a multicentre study independent from the influence of pharmaceutical companies should be commissioned to compare the speed of onset and effectiveness of desloratadine, fexofenadine and levocetirizine in chronic spontaneous urticaria and against histamine‐induced weal and flare responses in the same patients so that we have a clear understanding of the predictive value of our models.     

Urticaria and its subtypes: the role of second-generation antihistamines

Urticaria is a heterogeneous group of debilitating skin disorders characterized by wheals, pruritus, and frequently angioedema. The various forms of urticaria are often chronic and can exact a toll on quality of life. New diagnostic criteria and management guidelines are available to assist primary care physicians in the identification and proper treatment of different subtypes of urticaria. Second-generation antihistamines are recommended as first-line therapy because of their high degree of efficacy and safety. It is important to note, however, that European indications for most agents in this class are limited to specific forms of urticaria. The exception is desloratadine, the only second-generation antihistamine approved for the treatment of all urticaria subtypes in the European Union. Guidelines and best practice suggest that doses of antihistamines up to 4 times higher than those normally recommended for urticaria may benefit patients who do not respond to standard doses of antihistamines. Adjunctive therapy with leukotriene receptor antagonists may be advantageous in certain subgroups of patients who have suboptimal responses to antihistamine monotherapy. In all cases, physicians should work closely with patients to ensure proper adherence to prescribed regimens—a component that is often lacking but holds the key to successful outcomes.     

右美沙芬缓释混悬液治疗慢性咽炎所致咳嗽90例的临床观察

目的：研究右美沙芬缓释混悬液治疗成人慢性咽炎所致咳嗽的临床效果。方法：将90例慢性咽炎咳嗽患者随机分为3组,对照组给予万应胶囊治疗,治疗组l给予万应胶囊联合右美沙芬缓释混悬液治疗,治疗组2给予万应胶囊联合右关沙芬缓释混悬液及抗组胺药治疗,疗程均为14d。结果：治疗组1及治疗组2在7d、14d时疗效均优于对照组,差异有统计学意义（P〈O．01）;治疗组2在7d时疗效优于治疗组1,差异有统计学意义（P〈O．01）。结论：右美沙芬缓释混悬液用于成人慢性咽炎所致咳嗽临床效果良好,右关沙芬缓释混悬液联合抗组胺药对成人慢性咽炎所致咳嗽的临床疗效更快、更好。     

Cyproheptadine is an effective appetite stimulant in cystic fibrosis

Chronic pulmonary infection and intestinal malabsorption often lead to malnutrition in children and adults with cystic fibrosis (CF). Appetite stimulants, along with provision of adequate calories, may aid in overcoming nutritional deficits, allowing a better prognosis. We undertook a trial of cyproheptadine hydrochloride (CH) to determine its effectiveness as an appetite stimulant in 18 adults and children with CF. This was a 12-week, randomized, double-blind, controlled trial of CH vs. placebo. Eighteen subjects with documented CF (sweat or genetics positive), minimum age of 5 years, and ideal body weight for height <100% were entered, and 16 completed the study. Subjects were seen at baseline and every 4 weeks. Measures included baseline demographics, Shwachman score, anthropometrics (weight, height, body mass index, skin folds, and body composition by bioelectric impedance analysis), spirometry, caloric intake, days of oral (PO) and intravenous (IV) antibiotics, and a symptom and satisfaction survey. Subjects in the CH group showed significant increases in weight (mean 3.45 kg vs. 1.1 kg in the placebo group), height, BMI percentiles, ideal body weight/height, weight for age z-scores, and fat and fat-free mass. There were no changes or differences in PO or IV antibiotic use or spirometric changes. No significant side effects except transient mild sedation occurred in the CH group. Patient acceptance was good. In conclusion, CH appears to be an effective appetite stimulant with minimal side effects in children and adults with CF.     

Management of anaphylaxis: a systematic review

To establish the effectiveness of interventions for the acute and long‐term management of anaphylaxis, seven databases were searched for systematic reviews, randomized controlled trials, quasi‐randomized controlled trials, controlled clinical trials, controlled before–after studies and interrupted time series and – only in relation to adrenaline – case series investigating the effectiveness of interventions in managing anaphylaxis. Fifty‐five studies satisfied the inclusion criteria. We found no robust studies investigating the effectiveness of adrenaline (epinephrine), H1‐antihistamines, systemic glucocorticosteroids or methylxanthines to manage anaphylaxis. There was evidence regarding the optimum route, site and dose of administration of adrenaline from trials studying people with a history of anaphylaxis. This suggested that administration of intramuscular adrenaline into the middle of vastus lateralis muscle is the optimum treatment. Furthermore, fatality register studies have suggested that a failure or delay in administration of adrenaline may increase the risk of death. The main long‐term management interventions studied were anaphylaxis management plans and allergen‐specific immunotherapy. Management plans may reduce the risk of further reactions, but these studies were at high risk of bias. Venom immunotherapy may reduce the incidence of systemic reactions in those with a history of venom‐triggered anaphylaxis.     

Ethylenediamine contact dermatitis

A retrospective study of 50 patients with ethylenediamine allergy revealed that 2 topical products containing ethylenediamine as a stabiliser are the main sources of sensitization in Italy. Some of these patients cross-reacted to piperazine and diethylenetriamine, but none to ethylenediamine tetracetic acid.     

Topical treatment of rhinosinusitis

We reviewed current clinical evidence for the use of topical treatments in pediatric rhinosinusitis. Repeated Entrez PubMed searches were done using the template algorithm [rhinosinusitis AND (…)] with the settings: [Humans; English; All Child 0–18; Clinical trial; Last 10 yr] for the following comparators: steroid, irrigation, saline, antihistamine, decongestant, antibiotic, antimycotic, fungicide. The authors' clinical experience in the pediatric allergy unit of a university hospital was also drawn upon. Pediatric studies were retrieved but only one satisfied current evidence-based medicine standards for reporting clinical trials. Studies could not be systematized because of methodological, analytical, and interpretation biases. While saline irrigation, nasal decongestants, steroids, antibiotics, antihistamines and fungicides are all in widespread pediatric use, comparing studies from the literature for evidence of efficacy implied subjective appraisal, except in the case of topical steroids. Evidence for the efficacy of topical treatment for pediatric rhinosinusitis is narrative albeit this modality cannot be excluded from individualized patient protocols on the basis of the clinical literature alone. With the exception of topical steroids, no weighable evidence of effectiveness supports the premise that topical treatments actually serve the purpose for which they are widely prescribed in pediatrics.