Despite optimum drug delivery and good compliance with inhaled corticosteroids, many patients experience symptoms and exacerbations. Dose–response studies using inhaled corticosteroids have generally been unable to demonstrate any significant difference between individual doses of inhaled corticosteroids. For example, a metaanalysis evaluated eight studies (2324 asthmatics) where the effects of at least two doses of inhaled fluticasone were measured. (more…)

The immunologic mechanisms of sublingual immunotherapy are less established. In Cochrane analysis, the authors concluded that there was an increase in IgG4 but no stable effect on IgE levels in adults. In addition, the induction of allergen-specific IgA has been reported. There are conflicting data concerning lympho-proliferative responses. So far the evidence on changes in Th1/Th2/Treg activity induced by sublingual immunotherapy need to be confirmed. The effects on T-cell reactivity and cytokine secretion show strong variation in a number of studies. (more…)

Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunctivitis, asthma, and venom allergy hypersensitivity. It is the only treatment that leads to lifelong tolerance against previously disease-causing allergens due to restoration of the normal immunity. (more…)

The intracellular forkhead winged transcription factor Foxp3 (forkhead box P3) appears to be specifically expressed by naturally occurring Treg cells, particularly in mice, although in humans there is evidence of upregulation of Foxp3 in all T cells on activation. Foxp3 is required for the development and function of naturally occurring regulatory t cells (treg) and expression is sufficient to convert non-regulatory CD4+CD25T cells into cells with regulatory activity. Conversion of peripheral CD4+CD25 naive T cells to Foxp3+CD4+CD25 foxp3+ Treg cells can be induced by TGF-ß. In a murine asthma model, these TGF-ß-induced Treg prevented house-dust mite-induced allergic pathogenesis or infection pathogenesis in lungs. A single independent report has suggested that IL-4 and IL-13 also induce Foxp3+CD25+ Treg from CD4+CD25precursors. (more…)

A variety of proinflammatory cells, mediators, and cytokines orchestrate the development of airway hyperresponsiveness, which results in the episodic airflow obstruction characteristic of asthma. As a consequence, modulation of the underlying disease process with antii-nflammatory agents is firmly established as being the cornerstone of successful management. Inhaled corticosteroids are the most potent antiinflammatory agents available and satisfactorily suppress underlying airway inflammation in most individuals. (more…)

Normally present at very low levels in plasma, antibodies of the immunoglobulin E (IgE) isotype were first discovered in 1967, decades after the description of IgA, IgG, and IM. IgE antibodies are produced primarily by plasma cells in mucosal-associated lymphoid tissue and their levels are uniformly elevated in patients suffering from atopic conditions like allergic rhinitis, asthma and atopic dermatitis. Production of allergen-specific IgE in atopic individuals is driven both by a genetic predisposition to the synthesis of this isotype as well as by environmental factors, including chronic allergen exposure. (more…)

This study was similar to the study of Harrison and colleagues, which looked at doubling the dose of inhaled corticosteroid during an asthma exacerbation. This study investigated whether doubling the dose of budesonide inhalation in patients on regular inhaled budesonide would be beneficial during an asthma exacerbation. (more…)

Maintenance of asthma control by once-daily inhaled ciclesonide nasal spray in adults with persistent asthma. Ciclesonide is an inhaled corticosteroid that is converted to an active metabolite, desisobutyryl ciclesonide, in the lungs, thereby minimizing effects on endogenous cortisol inflammation. The goal of finding newer, safer corticosteroids for the management of asthma has led to the development of this inhaled corticosteroid.

This 12-week, double-blind, randomized, parallel-group, placebo-controlled study evaluated the efficacy and safety of ciclesonide in adults with persistent asthma. Efficacy was monitored with asthma symptom scores, rescue medication use, morning and evening peak expiratory flow rate (PEF) measurements, spirometry, and the probability of study completion without experiencing lack of efficacy. It was concluded that ciclesonide (160 or 640 µg) once daily in the morning maintains asthma control effectively, does not affect cortisol levels, and has an adverse event profile comparable with that of placebo in adults with primarily mild to moderate asthma.

It has been reported previously that, compared with fluticasone, ciclesonide possesses equivalent anti-inflammatory efficacy, through pulmonary activation, with a significantly improved safety profile. Since it has low bioavailability because it is metabolized by the lung, it is believed to cause minimal systemic adverse effects. It was found that the morning peak expiratory flow rate (PEF) and FEV 1 values from patient diaries decreased significantly in patients switched from their usual inhaled corticosteroids therapy to placebo but remained stable in patients switched to either dose of ciclesonide (160 or 640 µg). Furthermore, in patients switched to placebo there were significant increases in daily asthma symptoms and the use of rescue medication, with no significant changes from baseline in patients switched to either dose of ciclesonide. Mean changes from baseline in serum and urinary cortisol levels were not statistically significant in any of the treatment groups. Adverse effects were mild, with no reported cases of oral candidiasis.

In conclusion, once-daily inhaled ciclesonide nasal spray (160 or 640 µg) was superior to placebo in the maintenance of asthma control in adult patients previously treated with moderate doses of inhaled corticosteroids, without any significant adverse effects.

Allergic rhinitis and asthma are common comorbidities. Like asthma, the presence of a genetic component in allergic rhinitis has been well established. To identify genetic linkage regions unique to allergic rhinitis, as well as those shared by allergic rhinitis and asthma, a genome screen study was conducted. A total of 295 families in the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) containing 1317 subjects were genotyped for 396 microsatellite markers. The families included had two siblings with DNA available and at least one asthmatic subject. Three definitions of allergic rhinitis were used, two binary and one categorical. To investigate linkages specific to allergic rhinitis (without asthma), linkage analyses were also conducted in 185 families with at most one asthmatic sib. (more…)

Asthma control is improved by combining inhaled corticosteroids with long acting beta-agonists but patients still require reliever medication for breakthrough symptoms. Periodic fluctuations in symptoms and airway inflammation are characteristics of asthma, which means that treatment requirements, especially reliever use, can vary over time. (more…)