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Biomedical subjects

L Frølund

Publications and source records attributed to L Frølund.

At least 19 recordsLinked to original sources

Bronchial allergen challenge: dose versus concentration.

This study was designed to investigate if two equivalent doses of allergen administered by different dosing regimes--two breaths and 10 breaths of each concentration--would result in the same magnitude of the early and late asthmatic response. Fifteen patients with extrinsic allergic asthma were challenged twice with either two or 10 breaths of twofold increasing allergen concentrations. The challenge was continued until a 20% decrease in FEV1 had been achieved. A non-cumulative PC20FEV1 allergen was derived, and the cumulative dose of allergen given was similarly derived. In order to assess the reproducibility of the challenge, seven patients were challenged twice with two-breath regime. The mean value of allergen PC20 obtained by the two-breath regime was 4.1 fold (95% CI: 2.3-7.1 fold) greater than those obtained by the 10-breath regime (P less than 0.05), whereas the difference was 1.4 fold (95% CI: -3.3-0.5 fold) for the cumulative dose (P greater than 0.05). A statistically significant larger magnitude of the early asthmatic response, as determined by the maximum per cent fall in FEV1, and late asthmatic response determined by the maximum per cent fall in peak expiratory flow domiciliary recorded during the following 24 hr after challenge, was observed in favour of the 10-breath regime compared to the two-breath regime (mean difference 6%, 95% CI: 0.6-11%). The reproducibility of the provocation test was acceptable (+/- 1.8 two-fold concentration difference). These results confirm the 'equivalent dose hypothesis', and demonstrates that dosage rather than concentration appears to determine the early and late asthmatic response after bronchial allergen challenge.

Adolescent

Aeroallergen analyses and their clinical relevance. II. Sampling by high-volume airsampler with immunochemical quantification versus Burkard pollen trap sampling with morphologic quantification.

A comparison was made between the amount of airborne pollen collected by Burkard airsampler and the allergenic activity of particles trapped on glass fibre filters in an Accu-Vol high-volume airsampler. The comparison was made throughout the pollen seasons 1986 to 1989. Both airsamplers were operated 24 h a day. They were placed less than 5 m apart, and estimation of the pollen amount was made on a day-to-day basis during the pollen seasons, and on a weekly basis outside the seasons. The occurrence of the 3 clinically most important allergenic types of pollen, birch, grass, and mugwort, was analysed, and close correlations between the 2 sampling techniques were found (rs 0.5-0.8, p < 0.001). The detected range of counted pollens/m3 was: birch 0-1075, grass 0-156, and mugwort 0-44. By immunochemical analysis we found the corresponding amounts to be 0-80, 0-8, and 0-1 SQ-U/m3, respectively. Pollen counts and immunochemical estimation were compared with the symptom score recordings of allergic persons for birch season 1989 and for grass seasons 1986, 1988, and 1989. A close correlation was found for both sampling techniques for the grass seasons in 1986 and 1989 (rs 0.51-0.61, p < 0.001-0.0001), but a less significant correlation was found for the 1988 grass season, and for birch in 1989 (rs 0.24-0.34, p < 0.001-0.05).

Air Pollutants

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.

The efficacy of budesonide (800 micrograms b.d.) and beclomethasone dipropionate (750 micrograms b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV1, FVC, PEF or the histamine PC20. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.

Administration, Inhalation

Airway calibre as a confounder in interpreting bronchial responsiveness in asthma.

BACKGROUND: The relation between airway responsiveness to constrictor agents and forced expiratory volume in one second (FEV1) is important when interpreting change in airway responsiveness after an intervention. The aim of the study was to analyse the relation between FEV1 as a percentage of predicted values (% predicted) and airway responsiveness between and within asthmatic subjects. METHODS: Results of non-specific bronchial challenge tests were pooled from two randomised crossover studies comparing the effect of a non-sedative antihistamine with placebo in 35 patients with moderate asthma. The design of the two studies was similar: the provocative concentration of either histamine (first study) or methacholine (second study) resulting in a 20% decrease in ventilatory capacity (PC20) was repeated at two week intervals while patients were treated with the antihistamine or placebo. The dose of inhaled corticosteroid was gradually reduced during the study. Data were analysed with PC20 as the dependent variable in a general linear model so that the influence on PC20 of inhaled corticosteroid dose, antihistamine, and choice of bronchoconstricting agent could be separated from the influence of FEV1% predicted. RESULTS: The correlation coefficient between mean PC20 and mean prechallenge FEV1 for each patient was 0.45. In the general linear model two thirds (65%) of the variation in PC20 was due to variation between subjects. One third of the within subject variation in PC20 could be explained by variation in prechallenge FEV1% predicted (a change in FEV1 of 27% predicted was associated with one doubling or halving of PC20). Treatment with the antihistamine had no influence on PC20, except when histamine was used as the bronchoconstricting agent. The dose of inhaled corticosteroid had a small but significant effect. CONCLUSIONS: The variation in a patient's PC20 over time (several months) is related to changes in FEV1% predicted. Variation in FEV1% predicted explains less of the variation in bronchial responsiveness between subjects where a patient specific factor, which is probably related to the pathogenesis of bronchial asthma, seems to dominate.

Adrenal Cortex Hormones

Efficacy of an oral antihistamine, loratadine, as compared with a nasal steroid spray, beclomethasone dipropionate, in seasonal allergic rhinitis.

The aim of the study was to compare the efficacy and side-effects of oral antihistamine and nasal glucocorticoid therapy in seasonal allergic rhinitis. In a double-blind, double-dummy, group-comparative study, 60 birch and grass pollen allergic patients were treated with either loratadine (10 mg daily) or beclomethasone dipropionate (BDP) (100 micrograms in each nostril twice daily) during a 3 weeks' study period. Grading of 4 nasal and 3 non-nasal symptoms was performed at 4 weekly visits, and patients recorded daily symptoms and possible adverse experiences in a diary. Patients treated with BDP showed significantly less nasal blockage than those receiving loratadine (P less than 0.05), but there was no difference (P greater than 0.05) in other nasal symptoms (sneezing, itching and discharge). Patients treated with loratadine showed a statistically significantly greater relief in eye symptoms as compared with BDP (P less than 0.05). The side-effects caused by the 2 treatments were few and insignificant. We conclude that loratadine and intranasal BDP were effective in the treatment of seasonal allergic rhinitis, but the spectrum of individual symptoms controlled was different for the 2 drugs.

Administration, Intranasal

Immunological and physical properties of allergen solutions. Effects of nebulization.

Lyophilised birch pollen allergen extracts, reconstituted with different diluents (H2O, saline, Albumin diluent (AD] were investigated to determine whether the allergen activity and quality of the extracts deteriorated by nebulization with different nebulizers (Pari, Wright, and Sandoz). Allergen activity was measured by IgG4 RAST inhibition technique and allergen quality was analysed by crossed immunoelectrophoresis (CIE). The distribution of particle sizes of aerosols of different allergen solutions was determined by a TSI Aerodynamic Particle Sizer. A significant difference (P less than 0.05) in allergen activity was found between the AD and H2O diluents before and after using a Sandoz nebulizer and a Wright nebulizer equipped with a small chamber. This suggested greater allergen activity in AD-diluted solutions, and the pattern was repeated with the other two nebulizers, but was not statistically significant. The samples diluted with saline showed no significant differences in quality after nebulization except for the impacted aerosol in which one of the precipitates was slightly diminished. In the AD-diluted sample one of the precipitates disappeared from the impacted aerosol and from the nebulization chamber after 2 min nebulization. To elucidate whether the extract proteins had been bound by albumin, samples were submitted to CIE with rabbit anti-human albumin in an intermediate gel. By this procedure one precipitate was transformed to a precipitate in the intermediate gel, indicating that one or more proteins in the extracts may associate with albumin. No significant difference in output was observed between the nebulizers. The particle size distribution curves for each diluent (saline, AD) were identical for the Wright nebulizer with 99% of the dry particles distributed within 0.5-2.0 microns.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens

Reproducibility of leukotriene D4 inhalation challenge in asthmatics. Effect of a novel leukotriene D4/E4-antagonist (SR 2640) on leukotriene D4-induced bronchoconstriction.

We have studied the reproducibility of a bronchial leukotriene (LT) provocation test in asthmatics, and the effect of prior treatment with an oral leukotriene D4/E4 antagonist (SR 2640) on LTD4-induced bronchoconstriction in nine asthmatics in a double-blind placebo-controlled randomized cross-over trial. The reproducibility of the bronchial leukotriene provocation test was high. For a specific patient, the replication variance is 0.2303, and the standard deviation is thus 0.4799, corresponding to 48%, i.e. one halving of the dose or half doubling of the dose. SR 2640 antagonised LTD4 induced bronchoconstriction causing a mean shift of 48% to the right of the dose-response curve as compared with placebo (95% confidence interval being 11-137%). This study demonstrates that bronchial LTD4 provocation test is a safe and reproducible method in asthmatics, and that the method can be used to detect LT-antagonism; furthermore that SR 2640 is a weak LTD4-antagonist in asthmatics.

Adult

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, aluminium-hydroxide 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 monomethoxypolyethylene 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 greater than 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 less than 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 less than or equal to 100 BU had systemic reactions. Systemic side effects could not be predicted from the size of previous local reactions.

Animals

Methylprednisolone pulse therapy in acute severe asthma. A randomized, double-blind study.

Methylprednisolone pulse therapy (MPPT) has been shown to possess a long-lasting effect in other immune-inflammatory diseases without the well-known side effects caused by long-term treatment with glucocorticosteroids. In an attempt to reduce the long-term use of oral steroids in asthmatics, we conducted this double-blind, double-dummy study to compare the use of MPPT (1 g of methylprednisolone intravenously) (8 patients) with a short course of oral prednisolone (10 patients) in asthmatics presenting with acute severe asthma. Both treatments were effective in relieving the acute attack of asthma. The MPPT-treated patients did not show a faster resolution than did the orally treated group. No patients needed assisted ventilation, and no deaths occurred. One week after the treatment FEV1 tended to decrease in the methylprednisolone group compared with the oral prednisolone group (P = 0.06). The patients initially receiving MPPT needed supplementary prednisolone earlier and in higher doses than did the patients receiving oral prednisolone as initial treatment. At the end of the 12 weeks' study period, the groups reached identical FEV1. In conclusion, we did not find intravenous methylprednisolone superior to oral prednisolone in the treatment of acute attacks of severe asthma, but methylprednisolone pulse therapy had a shorter duration as regards protection against future asthma attacks.

Acute Disease

A multicentre study of loratadine, clemastine and placebo in patients with perennial allergic rhinitis.

This multicentre, double-blind, randomized parallel-group study compared 3 weeks' treatment with either loratadine (Clarityn) 10 mg once daily, or clemastine (Tavegyl) 1 mg twice daily, and placebo in outpatients with active perennial allergic rhinitis. 155 patients were evaluated for efficacy and safety. Grading of four nasal and three non-nasal symptoms, rhinoscopy signs, and therapeutic response was performed on treatment days 6, 13, and 20. Patients recorded daily symptoms and possible adverse experiences in a diary, also indicating when symptoms of active rhinitis were relieved. Loratadine and clemastine were statistically significantly superior to placebo throughout the study (P less than 0.05), based on assessment of patients' nasal and eye symptoms, patients' diary scores, rhinoscopy signs of symptoms, and onset of relief. The loratadine group showed a statistically significantly (P less than 0.05) faster onset of relief of symptoms compared with the group treated with clemastine. Concerning nasal stuffiness, loratadine was significantly (P less than 0.05) superior to clemastine after 1 week's treatment. Reports of adverse reactions showed that significantly (P less than 0.05) more patients complained of sedation in the clemastine than in the loratadine group. Regarding other adverse experiences and laboratory tests, the three treatment groups were statistically comparable (P less than 0.05). The study showed that compared with placebo both loratadine and clemastine were effective in relieving nasal and eye symptoms in patients with perennial allergic rhinitis. Loratadine was safe and well tolerated and was significantly less sedative than clemastine; loratadine may therefore possess an advantage in clinical use in the treatment of perennial allergic rhinitis.

Adolescent

A comparison of the effects of nedocromil sodium and beclomethasone dipropionate on pulmonary function, symptoms, and bronchial responsiveness in patients with asthma.

The efficacy of nedocromil sodium (NED) (4 mg twice daily) and beclomethasone dipropionate (BDP) (200 micrograms twice daily) in controlling the symptoms of asthma, the pulmonary function, and bronchial responsiveness to histamine was assessed in a double-blind, double-dummy, crossover study of 39 adult patients with chronic asthma. The patients, most of whom were assessed to be affected to a moderate degree, were insufficiently controlled in their current regimen of inhaled and/or oral bronchodilators. A 2-week baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups demonstrated improvements from baseline in clinical assessment of lung function performed after the first 6 weeks of treatment. No significant differences were observed when the effects of the treatments were compared on FEV1, FVC, and peak expiratory flow. Bronchial reactivity to histamine, measured as the amount of histamine causing a 20% fall in FEV1 (PC20), decreased significantly (p less than 0.05) after 6 weeks of treatment with BDP compared to the effect of NED treatment. Asthma severity, symptom score, and inhaled bronchodilator use demonstrated significantly better results with BDP. After crossover of treatment, the group transferring from NED to BDP continued to improve, whereas the group crossing from BDP to NED tended to demonstrate a major deterioration during the first 3 weeks, after which a stabilization or an increase in FEV1, FVC, and ln PC20 appeared to occur. It is concluded that NED for inhalation is a potent new drug for treatment of both atopic and nonatopic subjects with asthma. With the number of patients and dosages used, the effect on the pulmonary function was not significantly different from that of BDP after the initial 6 weeks of treatment, but BDP had a better effect on asthma severity, overall opinions, symptom score, bronchodilator use, ln PC20, and morning peak expiratory flow.

Adult

Beclomethasone dipropionate versus flunisolide as topical steroid treatment in patients with perennial rhinitis.

After a 2-week run-in period 23 atopics and non-atopics with perennial rhinitis were treated with intranasally nebulized aqueous flunisolide or aqueous beclomethasone dipropionate in a randomized, double-blind cross-over study, each treatment period being 4 weeks. Before and after each treatment period daily rhinitis symptoms were recorded, and additional determination of nasal airway resistance was performed by posterior rhinomanometry. No statistically significant difference between drugs was observed for any effect parameter recorded, and furthermore no difference in patient preference for either drug was found. It is concluded that both steroids are effective for the improvement of nasal airway in patients with perennial, atopic and non-atopic rhinitis.

Administration, Intranasal

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 radioallergosorbent 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.

Adolescent