Olle Zetterström

Improved asthma control with budesonide/formoterol in a single inhaler, compared with budesonide alone

Budesonide/formoterol in a single inhaler was compared with budesonide alone, and with concurrent administration of budesonide and formoterol from separate inhalers, in patients with asthma, not controlled with inhaled glucocorticosteroids alone. In this 12-week, double-blind, randomized, double-dummy study, 362 adult asthmatics (forced expiratory volume in one second 73.8% of predicted, inhaled glucocorticosteroid dose 960 microg x day(-1)) received single inhaler budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg, two inhalations b.i.d., or corresponding treatment with budesonide, or budesonide plus formoterol via separate inhalers. There was a greater increase in morning peak expiratory flow (PEF) with single-inhaler (35.7 L x min(-1)) and separate-inhaler (32.0 L x min(-1)) budesonide and formoterol, compared with budesonide alone (0.2 L x min(-1); p<0.001, both comparisons); the effect was apparent after 1 day (p<0.001 versus budesonide, both comparisons). Similarly, evening PEF, use of rescue medication, total asthma symptom scores and percentage of symptom-free days improved more with both single inhaler and separate inhaler therapy than with budesonide alone, as did asthma control days (approximately 15% more, p<0.001 versus budesonide, both comparisons, with a marked increase in the first week). All treatments were well tolerated and the adverse event profile was similar in all three treatment groups. It is concluded that single inhaler therapy with budesonide and formoterol is a clinically effective and well-tolerated treatment for patients with asthma that is not fully controlled by inhaled glucocorticosteroids alone.

Urticaria and asthma induced by food-and-drug additives in patients with aspirin hypersensitivity

Abstract Seven of 8 recently investigated aspirin-sensitive patients reacted with asthma, urticaria, or both after 1 to 2 mg. of the azobenzene dye, tartrazine. Tartrazine is commonly used as a food and drug color and a daily intake of several milligrams is possible. The patients also reacted to some benzoic acid derivatives. All of these food-and-drug additives may be difficult to avoid. It is important, therefore, that they are properly identified since they are dangerous for certain patients with asthma and urticaria. Administration of these drugs to patients with a history of reactivity is a procedure of considerable danger that should be done only with extreme caution and informed consent.

The leukotriene-antagonist ICI-204,219 inhibits the early airway reaction to cumulative bronchial challenge with allergen in atopic asthmatics

The hypothesis that cysteinyl-leukotrienes (LTC4, LTD4 and LTE4) are mediators of allergen-induced airway obstruction in asthmatics was tested with the specific receptor antagonist ICI-204,219, in a double-blind, placebo-controlled, randomized, cross-over bronchoprovocation study. On three occasions, cumulative bronchial challenge with specific allergen was performed in 10 males with mild allergic asthma. The first control session established the baseline provocative dose of allergen producing a decrease in forced expiratory volume in one second (FEV1) by 20% (PD20FEV1). The two rechallenges were performed 2 h after oral administration of placebo or 20 mg of ICI-204,219. The allergen dose-response relations were highly reproducible, producing PD20 values at the control session and after placebo treatment which varied by no more than 0.7-1.3 fold (95% confidence interval (95% CI)). After ICI-204,219, the median cumulated allergen dose was 5.5 fold higher, and the group geometric mean PD20 was increased 2.5 times. Furthermore, the recovery time after the immediate bronchoconstriction was shorter (40 vs 60 min). The wheal and flare responses to intradermally injected LTD4 were somewhat inhibited by ICI-204,219, whereas responses to histamine were unaffected. However, the findings suggest that skin testing with LTD4 is unlikely to predict the degree of leukotriene-antagonism in the airways. The findings confirm and extend the indications that cysteinyl-leukotrienes are important mediators of allergen-induced airway obstruction, and that leukotriene-antagonists should be evaluated as a potential new therapy in allergic asthma.

The impact of repeated spirometry and smoking cessation advice on smokers with mild COPD

Background. Smoking cessation is the most important therapeutic intervention in patients with chronic obstructive pulmonary diseases (COPD) and the health benefits are immediate and substantial. Major efforts have been made to develop methods with high smoking cessation rates. Objectives. To study whether a combination of spirometry and brief smoking cessation advice to smokers with COPD, annually for three years, increased their smoking cessation rate in comparison with groups of smokers with normal lung function. Method. Prospective, randomized study in primary care. Smoking cessation rates were compared between smokers with COPD followed-up yearly over a period of three years and smokers with normal lung function followed-up yearly for three years or followed-up only once after three years. Results. The point-prevalence abstinence rate and prolonged abstinence rate at 6 and 12 months increased yearly and in smokers with COPD at year 3 was 29%, 28%, and 25%, respectively. The abstinence rates were significantly higher in smokers with COPD than in smokers with normal lung function. Smoking cessation rates among smokers with normal lung function did not increase with increasing number of follow-ups. Conclusion. Smokers diagnosed with COPD stopped smoking significantly more often than those with normal lung function.

Anaphylactic reactions to sunflower seed

We report on four patients sensitized to sunflower seed. Three of them developed anaphylaxis and one chronic bronchial asthma. All four patients reacted the first time sunflower seeds were ingested, and all had kept cage birds fed on sunflower seeds. Therefore, the route of sensitization was probably by inhalation of airborne sunflower seed allergens. Investigation of this type of hypersensitivity in 84 atopic patients showed that only three patients were RAST‐positive, indicating that this allergy is fairly uncommon. On the other hand, when atopic persons are exposed to cage birds, the rate of sensitization is rather high, as indicated by the fact that in this category 79% were skin prick positive and 21% were unequivocably RAST positive to sunflower seed.

Late asthmatic reactions and bronchial variability after challenge with low doses of allergen

Late allergic inflammatory reactions are probably of major importance for the development of asthma. In order to study the occurrence of early and late asthmatic reactions after challenge with different doses of allergen, inhalation provocation tests were performed in 13 patients with mild or moderate symptoms of allergic asthma. The provocation series was started with a low allergen dose (0.1–10 BU), which was then increased in successive ten‐fold increments at intervals of 1 week until a pronounced bronchial reaction developed. Three different reaction patterns were observed. Six patients showed an isolated late reaction to relatively low doses of allergen. In four patients an immediate reaction was followed by a late reaction—a so‐called dual response, and in three patients only an immediate reaction occurred. In four of the six patients who showed only a late reaction a higher allergen dose was given and this resulted in dual reactions in all four. One patient was challenged with an even higher dose, to which she reacted with an immediate response alone. After a late reaction, bronchial variability with low PEF values was observed over a period of several days. It is thus possible for an isolated late asthmatic reaction to be provoked by a low dose of inhaled allergen. This can be of clinical importance, repeated small doses of allergen may be unnoticed but still give bronchial inflammation and asthmatic symptoms.

Coffee worker's allergy.

Workers in the coffeee industry were investigated. Study I comprised 50 selected cases of whom 25 had work‐related symptoms and 25 had not. Prick tests and RAST investigations with different factory dust extracts were performed. Study II was a cross‐sectional study comprising 129 workers who were prick‐tested with one factory dust extract and with castor bean (CB). More than 40% described occupationally related asthma, rhintis, and in about half of these cases sensitization with one or two allergens found. One allergen comes from coffee beans and is found in the factory dust, mainly where the raw coffee is handled. This allergen is destroyed in the roast other allergen is identical with the allergen from castor bean and is presumed to enter the plant via the sacks. Predisposing factors to developing sensitization were atopic status, degree and length of exposure, and smoking habits.

Formoterol as needed with or without budesonide in patients with intermittent asthma and raised NO levels in exhaled air: a SOMA study

Patients with mild intermittent asthma sometimes show signs of inflammation, and guidelines suggesting bronchodilator therapy alone as needed may be questioned. The current study compared as-needed use of a rapid-acting β2-agonist with as-needed use of a β2-agonist and corticosteroid combination as the only medication in asthma patients with intermittent symptoms. A total of 92 nonsmoking asthma patients (of 187 screened) using only an inhaled β2-agonist as needed (28 males, 64 females; mean age 37 yrs; mean forced expiratory volume in one second (FEV1) 101% predicted, mean reversibility 6.5% pred and fractional exhaled nitric oxide (FeNO) ≥20 parts per billion (ppb)) were randomised to treatment with formoterol (Oxis® Turbuhaler®) 4.5 μg as needed (n = 47) or budesonide/formoterol (Symbicort® Turbuhaler®) 160/4.5 μg as needed (n = 45) in a double-blind, parallel-group 24-week study. The primary variable of efficacy was change in FeNO. Baseline FeNO was 60 ppb and 59 ppb in the budesonide/formoterol and formoterol groups, respectively. Mean reductions in FeNO in the budesonide/formoterol and formoterol groups were 18.2 ppb and 2.8 ppb, respectively (95% confidence interval (CI) 7.5–23.5 ppb). The reduction in the budesonide/formoterol group occurred during the first 4 weeks of treatment and remained at this low level. Mean FEV1 increased by 1.8% pred normal value in the budesonide/formoterol group and decreased by 0.9% pred normal value in the formoterol group (95% CI -4.7– -0.7). In the budesonide/formoterol group, use of ≥4 inhalations·day-1 of study medication was seen on 21 treatment days compared with 74 in the formoterol group. In conclusion, as-needed use of an inhaled corticosteroid together with a rapid-acting bronchodilator may be more beneficial than a β2-agonist alone in patients with intermittent asthma and signs of airway inflammation. The long-term benefits are unknown.

Occupational Allergy in Nurses to a Bulk Laxative

Finely ground psyllium (Plantago ovata) seeds, so‐called ispaghula powder is used in bulk laxatives. During the dispensing of these medicines some dust is generated. Allergic symptoms from exposure to this dust was reported by two nurses, one of whom was working in a department where exposure to the powder could be considered high. Nineteen other subjects working in the same department were investigated with regard to allergy to ispaghula powder.

AN INVESTIGATION OF POLLEN EXTRACTS FROM DIFFERENT DECIDUOUS TREES IN PATIENTS WITH SPRINGTIME ALLERGY IN SWEDEN

Allergy to pollen from deciduous trees is a common cause of allergic rhinitis and asthma during the spring in Sweden. Juhlin-Dannfelt discovered (z) that patients with these disorders often get allergic symptoms from eating nuts or raw fruits. Using intracutaneous tests (i. c. tests) and, in some cases, provocation tests and Prausnitz-Kiistner tests, he could also detect the kind of tree pollen which usually caused the symptoms, i. e. mainly hirch but also hazel, alder, ash, sailowwillow and oak. Humoral reagins of the IgE class directed against different allergens can be detected with the radioallergosorbent test (RAST) (4). This test can also be used to study allergenic activities and to obtain information on relationships between various allergens. In the present investigation the RAST, i. c. tests and provocation tests have been used to study pollen extracts from different deciduous trees. The present study has been made in order to compare the extracts and illustrate whether they have any allergens in common.