U. G. Svendsen

Allergen skin test reactivity in an unselected Danish population.: The Glostrup Allergy Study, Denmark

The aim of this study was to assess the distribution of allergen skin test reactivity in an unselected Danish population. A total of 793 subjects, aged 15–69 years, were invited, and 599 (75.5%) attended. The skin prick test was performed with standardized allergen extracts of high potency. Skin reactivity occurred in 28.4% of the subjects. The frequency of skin reactivity to the specific allergens ranged from 1.5% (Cladosporium) to 12.5% (Dermatophagoides pteronyssinus), and the frequencies of skin reactivity to the allergen groups (pollen, animal dander, house‐dust mites, and molds) were 17.6%, 8.7%, 14.0%, and 3.2%, respectively. Young women appeared to reflect the average skin reactivity. When compared with young women, skin reactivity to animal dander was more probable in young men (odds ratio (OR) value = 2.6; 95% confidence interval (CI) of odds ratio value = 1.1–6.1). Current smokers were less likely than nonsmokers to be skin‐reactive to pollen (OR = 0.4; 95%, CI = 0.3–0.7). In conclusion, allergen skin test reactivity was common, and was related to sex, age, smoking history, and probably genetic predisposition.

High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.

Svendsen UG, Frølund L, Heinig JH, Madsen F, Nielsen NH, Weeke B. High‐dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.

Effect of a non-sedative antihistaminic (loratadine) in moderate asthma: a double-blind controlled clinical crossover-trial

Seventeen patients with perennial asthma, stable on a moderate dose of inhaled steroid, participated in a crossover study comparing the clinical effect of a non‐sedative, potent and highly selective H1 antagonist (loratadine 10 mg) with placebo. Each treatment period began with 2 weeks run‐in followed by 8 weeks on either antihistamine or placebo. During the 8‐week periods inhaled steroid was gradually tapered according to a fixed scheme. One patient was withdrawn from active treatment and three from placebo periods because of decreasing lung function (P > 0.1). Among the remaining 13 patients there was a threefold (1.8–4.8) decrease in the bronchial sensitivity to histamine during treatment with antihistamine compared to placebo (P < 0.01). There was a trend in favour of active treatment with regard to changes in all symptom scores, lung function and use of escape medication, but these differences were not statistically significant. The increase in FEV, was < 5% of predicted normal (P < 0.05). We concluded that the bronchial response to histamine can be attenuated by loratadine, an oral H1 receptor antagonist, but further studies are necessary to assess the clinical usefulness and place of loratadine in the therapy of asthma.

Hyposensitization in asthmatics with mPEG-modified and unmodified house dust mite extract. IV: Occurrence and prediction of side effects

A double‐blind study on hyposensitization (HS) with two extracts prepared from the house dust mite Dermatophagoides pteronyssinus (Dp) was performed on a group of asthmatics with bronchial sensitivity to Dp. In 18 patients, aluminiumhydroxide was added to the Dp‐extract to give a depot effect (Dp‐group). Nineteen patients were treated with a similar extract in which allergenicity had been reduced by coupling to monomethoxy‐polyethylene glycol (mPEG‐Dp‐group). This extract had previously been shown to have less effect on clinical symptoms and skin sensitivity compared to the Dp‐extract. In the Dp‐ and mPEG‐Dp‐groups, 778 and 675 injections were administered. Fifteen and 12 patients in the Dp‐ and mPEG‐Dp‐groups had systemic reactions (P > 0.05). The frequency of injections giving systemic reactions was reduced in the mPEG‐Dp‐group: 5.1 % compared to 9.0% in the Dp‐group (P < 0.01). In the mPEG‐Dp‐group, reactions were mild to moderate, mainly late‐occurring asthma and urticaria, whereas two episodes of anaphylaxis and four of severe asthma occurred in the Dp‐group. The reduction in side effects seems promising, but a further dose increase in the mPEG‐Dp‐group would be necessary to compare the side effects of doses with equal therapeutic effectiveness. High frequency of late local reactions made dose increase impossible with the present slightly modified extract. The systemic side effects occurred more frequently in patients highly skin test‐sensitive to Dp prior to treatment. All patients skin test‐positive to: ≤ 100 BU had systemic reactions. Systemic side effects could not be predicted from the size of previous local reactions.

Duration of the inhibitory activity on histamine‐induced skin weals of sedative and non‐sedative antihistamines

The inhibitory effect of orally administered dexchlorfeniramine (4 mg/day), cyproheptadine (8 mg/day), astemizole (20 mg/day), loratadine (40 mg/day) and terfenadine (120 mg/day) on the size of histamine‐induced weals was tested by skin prick test with histamine in an open study including 23 healthy individuals. The antihistamines were administered for 2 days in the nationally recommended therapeutic doses. For all drugs the maximal weal suppression with the dosage chosen was recorded the day after the last dosage, being 29% (for dexchlorfeniramine), 72% (for cyproheptadine), 50% (for astemizole), 62% (for loratadine), and 56% (for terfenadine) of the baseline value. For the drugs in the same order the duration of the inhibitory effect of the drugs after the last dose administered was between 3–4, 7–11, 17–28, 4–7, and 4–7 days, respectively.

Effects of Nedocromil Sodium and Placebo Delivered by Pressurised Aerosol in Bronchial Antigen Challenge

Nedocromil sodium (Tilade*) is the disodium salt of a pyranoquinoline dicarboxylic acid developed for the treatment of chronic obstructive airways disease (2). The new compound has been shown to inhibit the immediate bronchoconstrictor response induced by exercise (4, 5) and sulfur dioxide (1) challenge and early clinical studies indicate that nedocromil sodium is an effective drug for the treatment of extrinsic and intrinsic asthma (3, 6). The aini of the present study was to compare the protective effect of nedocromil sodium (4 mg administered by pressurised aerosol) and placebo, against the allergen-induced early asthmatic reaction. A double blind crossover design was employed, with patients randomly assigned to active or placebo treatment according to a latin square design.

The predictive value of bronchial histamine challenge in the diagnosis of bronchial asthma

A prospective survey aiming to study the predictive value of bronchial histamine challenge was performed on 151 patients with a forced expiratory volume1 (FEV1) above 60% of predicted. According to variations in peak expiratory flow rate (PEFR) and medical history the patients were classified as asthmatics (n = 97) or non-asthmatics (n = 54). The diagnostic properties of the challenge were calculated using the statement of Baye. Considering PC20 values below 4.00 mg/ml as positive, the predictive value of a positive test was about 0.80 and the predictive value of a negative about 0.76. When PC20 was below 0.125 mg/ml the predictive value of a positive test was 1.00, but an increase in PC20 in the range from 4.00 to 16 mg/ml did not increase the predictive value of a negative test. In this study the prevalence of asthma was about 0.6. We therefore conclude that bronchial histamine challenge is a valuable test for detection and exclusion of bronchial asthma, when the prevalence of the disease is high. In populations with a lower frequency of bronchial asthma the diagnostic value of a positive bronchial challenge will be negligible.

Bronchial Histamine Challenge in the Diagnosis of Asthma The Predictive Value of Changes in Airway Resistance Determined by the Interrupter Method

The predictive value of a bronchial challenge with histamine was determined in a prospective survey on a population with a high prevalence of asthma (0.62). Without knowledge of the bronchial responsiveness 133 patients were classified as asthmatics (83) or non‐asthmatics (50) according to variation in peak expiratory flow rate and medical history. Response to challenge was determined by the interrupter method, and the concentration of histamine inducing a 40% increase in resistance to breathing (PC40‐Rt) was calculated from the log dose response curve. When defining a positive test as a test giving PC40‐Rt‐values below 2.00 mg/ml, the predictive value of a positive test was 0.75 and the predictive value of a negative test was 0.72. By decreasing the limit for a positive test to 0.25 mg/ml the corresponding predictive value was increased to 0.91. When further increasing the limit to 4.00 mg/ml the predictive value of a negative test in the diagnosis of asthma was increased to 0.81. The interrupter technique is suitable for diagnostic purposes in the detection and exclusion of bronchial asthma.

A comparison of two RAST methods and skin prick testing in the diagnosis of wasp venom allergy

With the aim of evaluating the correlation between skin prick test and two radio‐allergosorbent tests (RAST) using paper (P‐RAST) and Al (OH)3 (Al‐RAST) as sorbent materials, 45 consecutive patients known to have been stung by wasp within 6 months were examined. Four patients had a normal reaction, four a large local reaction and 37 a systemic reaction. We found a good correlation between a systemic reaction and a positive P‐RAST. Fifty‐one per cent of patients with a systemic reaction had a negative Al‐RAST, whereas only 8% had a negative P‐RAST. Eight per cent of patients with a systemic reaction had a negative SPT. In the eight patients without a systemic reaction, the same patient reacted positively in Al‐RAST and P‐RAST.

A rapid challenge protocol for determination of non-specific bronchial responsiveness

A rapid method for determination of non-specific bronchial hyperreactivity was developed. Resistance to breathing was determined by a modified expiratory airway interrupter technique and combined with a dosimeter-controlled nebulizer which made continuous determination of response possible during challenge. The patients inhaled histamine chloride 8 mg/ml at every eighth breath until resistance to breathing (Rt) was increased by 60%. The number of inhalations (NI) or the provocative concentration (PC60-Rt) of histamine increasing Rt by 60% were determined in 68 patients. The new method correlated well to a non-cumulative standard protocol and could be terminated either within 10 min or within 20 inhalations. The results of this new challenge procedure enables us to predict the responsiveness to inhaled histamine precisely enough to separate patients into hyperreactive or normal reactive patients. Furthermore, the repeatability of the new method is comparable or superior to that of standard methods. The 95% confidence interval for the difference between replicates was the observed value +/- 2.4 NI. Thus this new method will be suited for studies of drug modifying effect on bronchial hyperreactivity since individual dose titration is easily performed, and the method could be valuable in epidemiological and occupational surveys as well.