SQ-standardized house dust mite immunotherapy as an immunomodulatory treatment in patients with asthma.

BACKGROUND: Specific immunotherapy is the only treatment with the potential to prevent progression of the allergic disease and the potential to cure patients. The immunomodulatory ability of SQ-standardized house dust mite (HDM) subcutaneous immunotherapy (SCIT) was investigated in patients with allergic asthma. METHODS: Fifty-four adults with HDM-allergic asthma were randomized 1:1 to receive SQ-standardized HDM SCIT (ALK) or placebo for 3 years. At baseline, and after 1, 2 and 3 years of treatment, the lowest possible inhaled corticosteroid dose required to maintain asthma control was determined, followed by determinations of nonspecific and HDM-allergen-specific bronchial hyperresponsiveness, late asthmatic reaction (LAR), immediate and late-phase skin reactions, and immunological response. RESULTS: SQ-standardized HDM SCIT provided a statistically significantly higher HDM-allergen tolerance (P<0.05 vs placebo) in terms of a 1.6-fold increase in PD(20) (HDM-allergen inhalation challenge), a 60-fold increase in skin test histamine equivalent HDM-allergen concentrations, reduced immediate- and reduced or abolished late-phase skin reactions, as well as fewer patients with LAR. PD(20) (methacholine inhalation challenge) increased initially and was similar between groups. House dust mite SCIT induced an initial increase in serum HDM-allergen-specific IgE (P=0.028 vs placebo), which then declined to baseline value. House dust mite SCIT induced an increase in components blocking IgE binding to allergen [ΔIgE-blocking factor: 0.31; 95% CI of (0.26; 0.37)] after 1 year that remained constant after 2 and 3 years (P < 0.0001 vs placebo). CONCLUSION: SQ-standardized HDM SCIT induced a consistent immunomodulatory effect in adults with HDM-allergic asthma; the humoral immune response was changed and the HDM-allergen tolerance in lung and skin increased.

Steroid-sparing effect of subcutaneous SQ-standardised specific immunotherapy in moderate and severe house dust mite allergic asthmatics.

BACKGROUND: The present study evaluated the steroid-sparing effect of subcutaneous SQ-standardized specific immunotherapy (SIT) in moderate and severe house dust mite (HDM) allergic asthmatics. METHODS: Fifty-four adult asthmatics allergic to HDM requiring at least inhaled corticosteroids (ICS) doses equivalent to 500 microg fluticasone propionate daily were randomized to subcutaneous SIT or placebo injections for a period of 3 years. The minimum required ICS dose, 4 week diary of asthma symptom score, use of rescue medication, peak expiratory flow (PEF) measurements and visual analog scale for asthma symptoms were assessed before start of treatment and after 1, 2 and 3 years of treatment. RESULTS: In patients with moderate and severe asthma, the reduction in ICS was statistical significant after 2 years of treatment (P = 0.03) but not after 3 years. The median reductions were 82% and 42% after the third year for active and placebo respectively. In patients with moderate persistent asthma the reduction was statistical significant larger for those treated with SIT compared with placebo after year 2 and year 3. The median reductions after 3 years were 90% for SIT and 42% for placebo (P = 0.04). Despite significant steroid reduction, there was no difference in asthma assessments between the two groups. No serious reactions related to SIT injections were seen. CONCLUSION: This study shows that SIT with a SQ-standardized HDM extract is safe. An ICS sparing effect was evident in patients with moderate persistent asthma.

Mode of action of intranasal corticosteroids.

The mode of action of intranasal corticosteroids (INCS) is complex. It is not known whether INCS penetrate the nasal mucosa or act on target cells; however, their low systemic activity supports the concept of local action on nasal mucosa. This local effect can nonetheless influence a variety of inflammatory cells and their mediators such as epithelial cells, lymphocytes, basophils, mast cells, and Langerhans cells. Corticosteroid-induced inhibition of immunoglobulin E-dependent release of histamine is a possible but unproven mode of action. Epithelial cells are an important target for corticosteroids, and INCS concentration is high at the epithelial surface. INCS may combine with the corticosteroid receptors in epithelial cells, which are then expelled into the airway lumen together with the dead epithelial cells or migrating inflammatory cells. A reduced influx of mediator cells may explain some of the effects of INCS on rhinitis symptoms, but it cannot explain all of the effects because INCS also reduce the early-phase sneezing and rhinorrhea after an allergen challenge outside the pollen season. In this situation, the number of surface mast cells/basophils is very low, as it is in the absence of allergic rhinitis. The mechanism by which INCS treatment of allergic rhinitis reduces itching, sneezing, and rhinorrhea, the characteristic symptoms of an early-phase response involving mast cell release of histamine, remains to be determined. Studies should be conducted to characterize the broad range of mechanisms by which INCS produce their therapeutic effects in allergic rhinitis.