Grass Pollen Subcutaneous Immunotherapy: a Double-blind, Placebo-controlled Study in Elderly Patients With an Allergy to Grass Pollen

Methods Patients A total of 109 patients ranging from 60 to 70 years of age were recruited from the outpatient allergy clinic to assess their eligibility for inclusion in the study. The subjects had moderate or severe intermittent allergic rhinitis and fulfilled the ARIA criterion. Additionally, the patients included in the study all had a positive skin prick test (SPT), were positive for specific immunoglobulin E (sIgE), and had positive nasal provocation tests (NPTs) with grass pollen mixture allergens. Patients with any of the following characteristics were excluded from the study: hypersensitivity to other allergens, bronchial asthma, non-allergic rhinitis (especially senile or vasomotor rhinitis) and severe non-stable diseases. However, patients with stable coronary disease, diabetes, and arterial hypertension were permitted in the study. All subjects were required to abstain from anti-allergy drugs and glucocorticoid nasal drops for at least 6 weeks prior to the start of the study.

There were 62 patients individually randomized in comparable numbers to one of two "parallel" groups using a double-blind method. The groups were the active (n=33) treatment group and the placebo (n=29) group. There were 31 subjects in the SCIT group and 25 subjects in the placebo group that completed the three-year observation period. The groups were comparable at baseline.

Diagnostic procedures A careful examination of the eyes, ears, nose, and throat was performed on all patients. The severity of seasonal allergic rhinitis (SAR) was assessed using the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. The patients with other nasal problems such as chronic nasal obstruction, reduced olfaction, bacterial colonization, and chronic sinusitis were diagnosed based on a CT scan and nasal endoscopy. Several patients were excluded from further observation as a result of these problems. The subjects with other chronic or acute clinical disorders or with a history of respiratory tract infections within four weeks of the study initiation were also excluded. The SPT was performed using inhalant allergens (HAL Allergy B.V, Leiden, Netherlands) from the following panel: D. pteronyssinus, D. farinae, mixed 5 grasses (Phleum pratense, Dactylis glomerata, Anthoxanthum odoratum, Lolium perenne, and Poa pratensis), mixed tree, mugwort, Alternaria, Cladosporium, dog and cat allergens. There were also positive (10 mg/ml of histamine) and negative (saline) controls included. A grass pollen allergy was defined as having positive skin tests for 5 grass pollen allergens with a minimum wheal diameter of at least 3 mm greater than the negative control. The patients with negative tests for histamine sensitivity were excluded from further analyses. The sIgE reactivity to the single grass pollen allergen components (Phl p1, Phl p2, Phl p5, Phl p6, Phl p7 and Phl p12) was determined using ImmunoCAP (Phadia AB, Uppsala, Sweden) tests. The results were considered positive when the sIgE concentration was greater than 0.35 IU/ml (according to the manufacturer's instructions). NPTs were conducted using active anterior rhinomanometry with commercial grass pollen mixture allergens. The concentration was 10,000 AU/ml and the mixture was delivered as 1 puff per nostril (HAL Allergy B.V, Leiden, Netherlands) using the methods described by Bachert et al. and Dordal et al. A reduction in the peak nasal inspiratory flow greater than or equal to 40% and an increase in symptoms greater than or equal to 5 points were considered to be positive NPT criteria by Bachert et al. and Dordal et al. The NPTs were also repeated after three years of treatment. The patients monosensitized to grass pollen were included in this study.

Treatments The patients were randomly selected to receive Purethal Grasses 20,000 AUM/ml (pollen mixture extract solution of Agrostis stolonifera, Anthoxanthum odoratum, Arrhenatherum elatius, Dactylis glomerata, Festuca rubra, Holcus lanatus, Lolium perenne, Phleum pratense, Poa pratensis, Secale cereal, Loe edasi HAL Allergy B.V, Leiden, Netherlands) or placebo. The recruitment period was limited to three months (October-December). Purethal grasses (January-April) were administered as pre-seasonal therapy using the following regimen: 1 dose- 0.1 ml, 2 dose - 0.2 ml, 3 dose - 0.4 ml every week, and doses 4- 7 consisted of 0.5 ml every two weeks.

Using this schedule the average cumulative dose was 460,500 BAU (Bioequivalent Allergy Unit), which contains approximately 690 μg of Phl p5 administered to each patient undergoing active treatment for all three years of the study. The study consisted of two phases. The first phase was the baseline one season of follow-up visits without treatment and the second phase was three years of SCIT or placebo.