Notes: In a 2-year double-blind placebo controlled study an immunological evaluation was carried out on 33 patients (15 males, 18 females, mean age 29.2 years) with mite-induced perennial rhinitis who were submitted to specific immunotherapy (IT) with an alginate-conjugated extract of D. pteronyssinus. The behaviour of IgE, IgG, IgG1, and IgG4, antibodies specific to D. pteronyssinus and its major allergen Der p1, was characterized by assessment of their changes m serum, and changes in IgG in nasal secretions during the treatment. The placebo-treated patients did not show any significant variation in the levels of specific antibodies, while in the actively treated patients we found; a statistically significant decrease (P 〈 0.005) of specific IgE, a statistically significant increase of specific IgG (P 〈 0.005), IgG1, (P 〈 0.005) and IgG4 (P 〈 0.005) in serum and a statistically significant increase (P 〈 0.001) of specific IgG in nasal secretions. The IgG response showed an early relative predominance of the IgG1 subclass and a late absolute predominance of IgG4 subclass, that confirmed the model of IgG4 restriction in prolonged allergen stimulation. No correlation was found between immunological and clinical data.

Notes: The effects of three oral doses of a new compound KW 4679 thought to have both antihistaminic and antiallergic properties were compared with terfenadine and placebo in a double-blind cross-over trial in 15 volunteers with seasonal allergic rhinitis. Comparison of the effect of the treatments with either 2.5, 5 or 10mg b.i.d. of KW 4679, 60 mg b.i.d. of terfenadine or placebo was made on the response to histamine and grass pollen skin-prick testing. Nasal provocation testing with grass pollen was performed on the eighth day of treatment. Nasal airway resistance (NAR) was measured using active posterior rhinomanometry and the dose of grass pollen which caused a 200% increase in NAR was determined. The number of sneezes in the first 12min was counted. Compared with placebo all doses of KW 4679 and terfenadine significantly inhibited the skin weal response to histamine and grass pollen (P 〈 0.001). The inhibitory effect of KW 4679 on both histamine and allergen induced skin weals was significantly greater than that of terfenadine (P= 0.001 and P= 0.049 respectively). The results of nasal challenges with grass pollen showed that all doses of KW 4679 and terfenadine were effective in reducing sneeze counts (P 〈 0.001), though there were no significant effects on allergen induced increase in NAR. All three doses of KW 4679 were generally well tolerated. Drowsiness was reported by some of the volunteers on KW 4679 and one volunteer reported drowsiness whilst taking placebo. Slight and reversible rises in AST and ALT concentrations were observed; these were not considered clinically significant.

Notes: Standardization of allergen provocation tests of the airways requires standardization of each of the steps involved, including standardization of the extracts used. The value of international standards is emphasized and so is the determination of a clinically relevant potency. The allergen extracts used for bronchial provocation tests must be compared with qualitatively and quantitatively clinically relevant standards using complementary immunochemical and biological methods. Ideally the same extracts should be used for diagnosis (skin test, specific IgE determinations, provocations) and treatment (immuno-therapy). The importance of the biological compared with the non-biological methods is that the biological methods are established in allergenic patients in order to select a clinically relevant potency of the allergen in question, and this potency ought to be confirmed in clinical trials. Once established the biological potency of an in-house preparation can be reproduced by supplementary in vitro methods. Very few commercial allergen preparations are available which fulfil the above-mentioned criteria.

Notes: The effect of single dose topical nasal therapy with azelastine hydrochloride (azelastine) on the response of nasal airways resistance (NAR) to provocation testing was studied in 36 patients with seasonal allergic rhinitis. Nasal provocation testing (NPT) with histamine or grass pollen was performed after a single dose of azelastine, 0.28 mg to each nostril, or placebo. NAR was assessed by rhinomanometry for 10 hr following NPT. Compared to placebo the NAR response to histamine was inhibited at both 1 and 2 hr following azelastine administration, significant at 1 hr (P 〈 0.02) and 2 hr (P 〈 0.0001). No such effect was observed in relation to allergen-induced changes in NAR. Azelastine also inhibited numbers of sneezes for up to 10 hr following both histamine NPT (P 〈 0.02) and allergen NPT (P 〈 0.05), when compared to placebo. Forty-seven per cent of participants experienced bitter or unpleasant taste sensations after azelastine administration but no other unwanted effects were clearly related to azelastine therapy.

Notes: The role of pyroglyphid mites in house dust allergy is well established and the major allergens from the common house dust mites (Dermatophogoides species) have been characterized. There is, however, relatively little progress in the understanding of the human IgE response to non-pyroglyphid storage mites, allergenic crossreactivity with other mite species and extent of environmental exposure. We studied 196 individuals from an urban environment who were not occupationally exposed to storage mites and found a 24% prevalence of specific IgE antibody to Dermatophagoides pteronyssinus and a 14% prevalence of RAST positivity to at least one of three storage mites, Acarus siro, Lepidoglyphus destructor and Tyrophagus longior. All individuals with a positive RAST to storage mites had specific IgE to D.pteronyssinus. RAST inhibition studies with the eight sera with greater than 2% RAST binding to both families of mites showed considerable crossreactivity between D. pteronyssinus and the storage mites A.siro and T. longior and limited crossreactivity between D. pteronyssinus and L. destructor. This suggests that at least some of the response to storage mites observed by direct RAST is a consequence of crossreactivity with the more abundant D. pteronyssinus.

Notes: Evidence suggests that allergic disease is becoming more common, particularly in industrialized societies. Two studies of schoolchildren from Aberdeen, Scotland aged 8–13 years were undertaken in 1964 and 1989 using identical questionnaires, and found that the reported prevalence of asthma had risen from 4.1% to 10.2% during this period, hay fever from 3.2% to 11.9% and eczema from 5.3% to 12%. Indication that air pollution may contribute to this increase has come from several studies. In Japan, allergic rhinoconjunctivitis was found to be more prevalent in individuals living near motorways than in cedar forests. Severe asthma also occurs more commonly than mild asthma in children living in polluted areas. Exercise-induced asthma and the use of asthma medication were twice as high in a town near two power stations compared with a non-polluted town. A recent study in Finland showed that admissions to hospital with severe asthma correlated with atmospheric levels of nitrogen dioxide. Deterioration in peak flow recordings in asthmatics and exacerbations of symptoms in hay fever sufferers correlate with ambient levels of ozone. Elucidation of the mechanisms by which exposure to air pollutants may influence the frequency of allergic disease or exacerbate symptoms has come from in vitro and in vivo experiments in animals and man. Animals exposed to ozone, sulphur dioxide, nitrogen dioxide and particles from diesel exhaust, together with allergens, show more ready development of allergic sensitization compared with those exposed to allergen alone. The dose of allergen necessary to produce a 20% fall in FEV1 (forced expiratory volume in 1 second) in mild asthmatics is reduced by previous exposure to ozone or a mixture of nitrogen dioxide and sulphur dioxide. It has also been suggested that the allergic potency of pollen grains may be increased when they are coated in pollutants. Bronchial and nasal lavage studies have shown that air pollutants can induce an influx of inflammatory cells and proinflammatory cytokines into the respiratory tract. Studies on human epithelial cells cultured to confluence in vitro have indicated that exposure to nitrogen dioxide can decrease ciliary beat frequency which would, in theory, reduce allergen clearance and increase the risk of sensitization. Further, exposure of these cells to either ozone or nitrogen dioxide induces the release of inflammatory mediators, such as leukotriene C4, and proinflammatory cytokines, including granulocyte-macrophage colony-stimulating factor, tumour necrosis factor-α and interleukin-8. This effect can be attenuated by the use of anti-inflammatory drugs.