Clinical and anti-inflammatory effects of ultra-short preseasonal vaccine to Parietaria in asthma

We present data showing that a Th1-inducing adjuvant can reduce the number of injections required for allergy vaccination. Allergy vaccination is the only treatment for type 1 hypersensitivity that can alter the underlying disease process. A switch of specific T-cell activity from Th2 >Th1 to Th1 >Th2 is believed to be an important change seen after long-term vaccination therapy. An immunologic adjuvant that enhances such a switch could be used to reduce the number of injections required. This would improve compliance with the treatment and provide pharmacoeconomic advantages. Such an adjuvant is 3-deacylated monophosphoryl lipid A (MPL adjuvant, Corixa). A multicentre, placebo-controlled, randomized, double-blind clinical study was performed with a new standardized allergy vaccine comprising a tyrosine-adsorbed glutaraldehyde-modified grass pollen extract containing MPL adjuvant. Four subcutaneous injections of the active product were given preseasonally to 81 grass pollen-sensitive subjects, and 60 received placebo injections (tyrosine alone). Diary cards were used to record symptoms and medication taken during approximately 30 days of the grass pollen season. There was a statistical advantage in favour of the active treatment for nasal (P = 0.016) and ocular (P = 0.003) symptoms and combined symptom and medication scores (P=0.013). Titrated skin prick testing revealed a significant reduction of skin sensitivity in the active group compared to placebo (P = 0.04). Grass-pollen-specific IgG antibody was raised by active treatment (P < 0.01). A rise in IgE antibody was seen in the placebo group during the season (P < 0.01). The first year's treatment rise of IgE was not seen in the active group, and no rise occurred during the pollen season. More local adverse events were seen in the active group. There was no difference in generalized adverse events. A new, well-tolerated allergy vaccine, incorporating a Th1-inducing adjuvant, MPL, was efficacious and after only four preseasonal injections produced antibody changes normally associated with long injection schedules. This may encourage wider application of allergy vaccination. The vaccine is now available in a number of countries as Pollinex Quattro.

To date we have available specific instruments assessing health-related quality of life (HRQL) in rhinoconjunctivitis or in asthma, but not instruments evaluating rhinitis and asthma together, although they often coexist. The aim of our study was to develop and validate a specific quality of life (QoL) questionnaire for adult patients with rhinoconjunctivitis, asthma or both. A pool of 42 items covering the main symptoms and problems related to respiratory allergy, was generated based on literature review and clinical experience. The items were randomly listed and presented to 148 consecutive outpatients 46 suffering from asthma (age 32.9 +/- 14.3 years), 53 suffering from rhinoconjunctivitis (age 32.6 +/- 11.5 years) and 49 from asthma and rhinoconjunctivitis (age 35.6 +/- 12.2 years). The patients were asked to indicate which item they had directly experienced and for each of them, its importance on a four-point scale (1 = not important; 4 = very important). Twelve items were cancelled from the list, because of low importance or redundance. In the instrument validation phase, 104 patients (42 with rhinoconjunctivitis alone and 62 with asthma and rhinoconjunctivitis) were evaluated with the generic instrument SF-36 and the new questionnaire (RHINASTHMA). RHINASTHMA was able to differentiate patients with rhinitis from those with both rhinitis and asthma. In stable condition, RHINASTHMA showed good reliability. The factor analysis extracted three factors with a good reliability (0.93, 0.87, 0.76). RHINASTHMA is the first tool aimed at evaluating HRQL impairment in patients with rhinitis and/or asthma. It provides a short and simple assessment, and has overall psychometric properties. This is of relevance because of the frequent asthma-rhinitis comorbidity.

Specific immunotherapy is a well-established treatment for allergic rhinoconjunctivitis; conventional regimens are lengthy, however, reducing convenience and cost-effectiveness. This study evaluated the efficacy and safety of an ultrashort course (four doses) of the immunotherapy Grass Modified Allergen Tyrosine Adsorbate (Allergy Therapeutics, Worthing, U.K.) monophosphoryl lipid A (MATA MPL). Subjects were randomized to receive four injections of either Grass MATA MPL (n = 514; 300-2000 standardized units/injection) or placebo (n = 514) before the grass pollen season. They used electronic diaries to record allergy symptoms and medication use during the pollen season. The primary end point was the difference between the mean combined symptom and medication scores in the Grass MATA MPL and placebo groups during the 4 local peak pollen weeks. The injection course was completed by 95.3 and 97.7% of the Grass MATA MPL and placebo groups, respectively, and was well tolerated. Grass MATA MPL treatment afforded a 13.4% benefit over placebo in the 4 peak pollen weeks (p = 0.0038). The benefit in subjects with 28 complete diary entries during the 4 peak pollen weeks was 26.9% (p = 0.0031). Significant benefits over placebo were observed in subjects with severe symptoms (17.1%; p = 0.0023), in those who had a history of allergic rhinoconjunctivitis for up to 35 years (up to 37.2%; p = 0.0059) and at sites with a higher burden of disease (38.3%; p < 0.0001). The ultrashort course of Grass MATA MPL was well tolerated and provided a significant benefit over placebo in relieving allergy symptoms.