Formulation considerations of intranasal corticosteroids for the treatment of allergic rhinitis.

OBJECTIVE: To examine how various aspects of an intranasal corticosteroid (INS) formulation may influence the efficacy, tolerability, and patient preference and adherence to INS therapy. DATA SOURCES: A PubMed search of the literature was conducted for studies on allergic rhinitis published between January 1977 and January 2006 using the keywords intranasal corticosteroid, preservatives, benzalkonium chloride, and tonicity. STUDY SELECTION: Prospective studies, retrospective studies, and case reports were selected for inclusion in this review. RESULTS: Currently available INSs are effective first-line treatments for allergic rhinitis. Differences in patient preference for a particular INS are largely attributable to sensory attributes of the nasal spray, which arise from characteristics of the formulation. Additives and preservatives can cause tolerability issues by irritating the mucosal membranes and causing nasal drying, or they can confer an unpleasant odor or taste to an INS formulation. The relative osmotic pressure, or tonicity, of an INS can modulate nasal absorption and retention, thereby potentially influencing the clinical efficacy. Characteristics such as delivery device and spray volume can affect a patient's perception and experience with a particular INS. Newer INSs, such as ciclesonide, are in development for the treatment of allergic rhinitis, and consideration of the formulation characteristics of these agents is an important part of the development process. CONCLUSIONS: INSs are an effective treatment option for patients with allergic rhinitis; however, there is room for formulation improvement. Optimization of formulation may increase the efficacy, tolerability, and patient preference and adherence to INSs.

[Treatment strategies in rhinoconjunctivitis and asthma during pregnancy]. / Estrategias de tratamiento de la rinoconjuntivitis y el asma durante el embarazo.

BACKGROUND: The incidence of asthma is high, especially in young people, a population group that includes women of reproductive age. We reviewed recent publications on asthma control during pregnancy to avoid undesired effects on both the mother and fetus. The prevalence of rhinoconjunctivitis is also high, although this disease is often under-treated by physicians. The use of beta2-agonists, corticoids (systemic/inhaled/nebulized), epinephrine and specific allergen immunotherapy is discussed. METHODS: We reviewed recent publications on asthma during pregnancy as well as other articles of interest. Articles providing data on drug therapy, overall strategies and patient education were selected. Sufficient drugs are available for the management of this disease and under-treatment cannot be justified. CONCLUSIONS: Pregnancy is not a disease, but constitutes a period when special care must be taken with underlying diseases. The aim of asthma treatment during pregnancy is to prevent fetal complications due to the effects of medication and asthma crises by keeping the mother symptom free and preventing possible exacerbations. Almost all authors agree that asthma crises in pregnant women should be treated no differently from those in non-pregnant women. Treatment of rhinoconjunctivitis should not be stopped during pregnancy since a wide variety of FDA category B drugs is available. Specific allergen immunotherapy should not be suspended during pregnancy as it is not contraindicated. However, this therapy should not be initiated during pregnancy.

Clinical trial design, nasal allergen challenge models, and considerations of relevance to pediatrics, nasal polyposis, and different classes of medication.

Clinical trials in allergic rhinitis present several specific difficulties. In seasonal pollen-related disease, there are variations between subjects in the extent of pollen sensitization, individual variations in exposure to pollen even within a set area because of lifestyle differences, and variations between different areas in pollen counts and weather patterns. Thus, large patient numbers are needed in multicenter trials to account for such variations when the standard endpoint is symptom reporting. Furthermore, a pollen season may be relatively short (eg, lasting 6-8 weeks), and the pollen count is inconsistent during this period. Crossover study designs are thus inappropriate, and trials are usually conducted with a parallel-group design. This further increases the trial sample size as it reduces statistical power. These large patient numbers must be recruited over a very short period. Perennial house dust mite-sensitive allergic rhinitis presents other problems. Although there is less disease variation, it is appreciated that symptoms may be induced by nonallergic as well as allergic mechanisms because of the nasal hyperresponsiveness. The nonallergic symptoms may not be modified by treatments based on allergic disease mechanisms. Thus, symptom outcomes--although relevant to the patient--may not adequately reflect the pharmacologic efficacy of the specific intervention. To control variability and focus on allergic disease mechanisms, nasal allergen challenge has been used in drug development. Single-dose challenges in the laboratory or in a pollen chamber, which allow many volunteers to be studied at the same time, have proven useful in the evaluation of drugs that afford acute symptom relief. However, such challenges incompletely model naturally occurring disease, in which the repeated daily exposure to allergen modifies the mucosal inflammatory cell profile and in particular promotes the epithelial accumulation of effector cells. This alters the response to allergen exposure. To model this, repeated low-dose daily allergen exposure has been used to generate these mucosal changes artificially, and early studies suggest that this may be a more valid model for the evaluation of anti-inflammatory therapy. However, little has been published with this model. Different disease groups are associated with their own specific issues in clinical trials. The pediatric population, in which allergic rhinitis is common, has different requirements for education, quality of life evaluation, and adverse-event monitoring; nasal polyposis, because of the nature of the disease, requires additional means of assessment, such as nasal endoscopy and imaging (eg, computerized tomography scanning), as well as attention to additional outcome measures (eg, the measurement of sense of smell). Within clinical trial design, there are important questions to be considered in relationship to the therapeutic intervention. Should this be given topically or systemically? What are the appropriate timing and frequency of medication? Does the disease itself modify the treatment efficacy, and does combination therapy afford better clinical outcome than single-modality therapy? These issues are discussed, and the influences of current therapies on objective outcome measures in allergic rhinitis are reviewed.

[Anti-allergy therapy in children]. / Les thérapeutiques anti-allergiques chez l'enfant.

The discovery of the physiopathological mechanisms of asthma and the diseases of allergy has allowed the development of many symptomatic therapeutical perspectives. We review below the mechanisms of actions, routes of administration, secondary effects, dosages and indications for different commercialised anti-allergy medications. A better understanding of the pharmacology of the different medications should produce optimisation of the treatment of the allergic child.