Detection and treatment of early asthma.

BACKGROUND: We sought answers to two questions: 1) how can mild, early asthma best be detected? 2) how should it be treated and the treatment effect monitored? METHODS: Eighty adult patients with early, mostly mild asthma and 30 control subjects were examined by lung-function and biochemical tests. Patients were randomly assigned to two treatment groups. One group was treated with an inhaled steroid (budesonide) for 6 weeks, and the other first with an inhaled beta2-agonist (terbutaline) for 6 weeks and then with an inhaled steroid for 2 weeks. RESULTS: Treatment with budesonide was effective: symptom scores, PEF, blood eosinophils, and sputum ECP values all improved. Terbutaline was ineffective by these criteria. For the detection of early asthma and for the following treatment effects, sputum and serum ECP assays are useful supplements to lung-function tests. CONCLUSIONS: Treatment of early, mild asthma with an inhaled steroid is effective and worthwhile. Detection of the disease remains a problem, as both lung-function and biochemical tests have low sensitivities.

Eosinophil cationic protein in induced sputum as a marker of inflammation in asthmatic children.

We evaluated the usefulness of eosinophil cationic protein (ECP) in induced sputum and in serum as markers of asthmatic inflammation in children. We measured ECP in serum and in total induced sputum samples from 14 children (7-11 years) with newly detected asthma before and after treatment, and from ten healthy non atopic controls of the same age. The patients inhaled budesonide, 800 micrograms/m2/day for the first month and 400 micrograms/ m2/day for the next 5 months, both divided into two doses, and nedocromil, 4 mg three times daily for the following 6 months. In both sputum and serum, ECP levels were higher in the patients than in the controls, but the difference was more distinct in sputum. Significant clinical improvement during the treatment was accompanied by a decrease in sputum ECP, whereas serum ECP did not change. The results suggest that induced sputum is useful as a non invasive source material for evaluating asthmatic inflammation in children, total sputum ECP being more sensitive than serum ECP for diagnosing and monitoring asthma.

Can early asthma be confirmed by laboratory tests?

We examined the performance of a number of laboratory tests in 23 patients who had had symptoms suggesting asthma, such as cough, sputum secretion, and chest tightness with wheezing, for less than a year. Even the best test, histamine challenge, had a sensitivity of only 48%. When more tests were added, sensitivity rose: with peak expiratory flow added, the sensitivity was 65%; with sputum eosinophil cationic protein (ECP) added, to 74%; and with serum ECP added, to 78%. Thus, a combination of tests measuring lung function and activation of eosinophils yielded fair, if not good, results. It appears that sensitivity could be increased further through the development of improved sputum tests.

Stability of cereal allergens.

BACKGROUND: Ingested cereals and inhaled cereal dusts can cause IgE-mediated allergy. Testing for these allergies yields variable, often undependable results, which could be due to the use of unsuitable or degraded testing materials. OBJECTIVE: We studied the effect of storage media, time and temperature on the stability of protein allergens extracted from wheat, rye, barley and oats flour. We also examined the effect of heat processing similar to that used when preparing foods on the stability of allergenic proteins present in wheat flour. METHODS: After storage experiments proteins in allergen extracts were separated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then visualized using immunoblotting or staining with Coomassie brilliant blue. After heat processing wheat flour proteins were extracted and their IgE-binding capacity was estimated. RESULTS: Extracted proteins from wheat, rye and barley flour appeared stable for at least 21 months when stored at 4 degrees C in an aqueous solution containing 50% glycerol and 0.45% sodium chloride. In a medium with 0.4% phenol and 0.9% sodium chloride degradation of many proteins became apparent already after 1 month of storage. Oats extracts lost their IgE-binding capacity more rapidly and the maximal storage time appeared to be 10 months at 4 degrees C in a solution containing 50% glycerol and 0.45% sodium chloride. The IgE-binding capacity of the allergenic proteins decreased as heat-processing temperature and heating time increased. No processing conditions entirely abolished IgE-binding. CONCLUSION: Cereal allergen preparations can be stored either in lyophilized form or at 4 degrees C in 50% glycerol. Unheated materials should be used also when testing for food allergy, as heating reduces allergenicity and thus sensitivity at testing.

Salivary and serum IgA antigliadin antibodies in dermatitis herpetiformis.

Serum IgA class antigliadin antibodies (IgA-AGA) are increased in untreated patients with coeliac disease and dermatitis herpetiformis (DH), and it has been suggested that salivary IgA-AGA measurements could be used as a non-invasive screening test for gluten-sensitive enteropathy. In the present study salivary and serum IgA-AGA were measured by an ELISA test in 10 untreated patients with DH. The results were compared to IgA-AGA levels in nine patients with DH on a long-term gluten-free diet (GFD) and in 20 healthy control subjects on an ordinary diet. The mean serum but not salivary IgA-AGA concentrations were significantly higher in the untreated than in the patients with DH on a long-term GFD. When the 10 untreated patients with DH adhered to a GFD for 3 months, the rash disappeared and the mean serum IgA-AGA decreased to normal levels, but no change was found in the mean salivary IgA-AGA concentration. These results show that serum but not salivary IgA-AGA measurements are suitable for monitoring GFD treatment in patients with DH. The discrepancy between the serum and salivary IgA-AGA concentrations suggests that systemic and salivary IgA-AGA responses are controlled separately.

Mast cells and histamine in adenoid tissue and middle ear.

Biopsy specimens from middle ear mucosa of patients with secretory (SOM) and chronic (COM) otitis media as well as specimens of adenoid and tonsil tissue were studied for mast cells. Effusion fluid, nasopharyngeal secretion and supernatant of crushed adenoid tissue were analyzed for histamine with a radioenzymatic method. Astra blue (AB) safranine stained highly significantly more mast cells than did toluidine blue. Mast cell counts in SOM and COM were similar. There were significantly more mast cells in adenoid subepithelial tissue than in middle ear mucosal subepithelial layer. For epithelium the counts were within the same range in adenoids and middle ear mucosa. Histamine concentrations were significantly higher than plasma levels for SOM fluid and nasopharyngeal secretion. Crushed adenoid tissue showed values over 100 times higher than the histamine level in the secretion.

Prevalence of asthma in Finnish young men.

OBJECTIVE: To determine the prevalence of asthma in cohorts of Finnish young men in the period 1926-89. DESIGN: A retrospective analysis using reports and statistics of Finnish defence forces. SETTING: Call up examinations of candidates for military conscription and examination of conscripts discharged because of poor health. SUBJECTS: Roughly 900,000 men--that is, 98% of men of conscription age--examined in 1966-89 and a proportional but unknown number examined in 1926-61. MAIN OUTCOME MEASURES: Asthma recognised at call up examination, exemption from military service, and discharge from military service because of asthma. RESULTS: During 1926-61 the prevalence of asthma recorded at call up examinations remained steady at between 0.02% and 0.08%. Between 1961 and 1966, however, a continuous, linear rise began, the prevalence increasing from 0.29% in 1966 to 1.79% in 1989--that is, representing a sixfold increase. Compared with 1961 the rise was 20-fold. From 1966 to 1989 the sum of exemptions and discharges from military service due to asthma increased analogously sixfold. CONCLUSIONS: If the apparent increase in asthma detected in Finnish young men was due entirely to improved diagnostic methods and other confounding effects then some 95% of cases must have gone undiagnosed in the years before 1966. This seems inconceivable, which suggests that much of the increase was real. This conclusion is strengthened by the observed rise in exemptions and discharges due to asthma.

A simplified Boyden chamber assay for neutrophil chemotaxis based on quantitation of myeloperoxidase.

Cell locomotion and chemotaxis are usually assayed by the Boyden chamber technique, in which the response is measured by microscopical counting of the cells migrated into a micropore filter. We report a simplified Boyden chamber method which utilizes myeloperoxidase (MPO) specific to neutrophilic and monocytic leukocytes. The chamber is incubated for a period long enough for the neutrophils to migrate through the first of two superimposed filters. The cells entering the second filter are then lysed and the released MPO activity is quantitated. Random migration, chemokinesis, and chemotaxis measurements of neutrophils were compared by the enzymatic and the conventional cell count methods. There was good agreement between the two methods (0.84 less than r less than 0.98). The intraassay precision of the enzymatic and the cell count methods was equal; the coefficients of variation were 14 and 15%, respectively. The enzymatic method provides a more objective, reliable, and rapid modification of the Boyden chamber assay for analysis of neutrophil chemotaxis.

Spice allergy: results of skin prick tests and RAST with spice extracts.

Skin prick tests (SPT) with freeze-dried spices and 5% (w/v) spice extracts were performed on 50 patients with 2+ or stronger SPT reactions to spices per se, and RAST were performed on 10 of them. Freeze-dried extracts produced mostly equal or stronger SPT reactions than corresponding whole spices, but 5% (w/v) extracts produced weaker reactions and also remained totally negative in some patients. Positive RAST results were seen in all 10 patients tested. The correlation between the RAST and SPT results was good for mustard and paprika, but poor for cayenne, coriander, caraway and white pepper. Five patients with positive SPT and RAST for spices contracted rhinitis from powdered spices in their working environments, and one patient suffered from gastrointestinal pains caused by spiced food. The others had noticed no clinical symptoms caused by spices. The present results thus indicate that both SPT and RAST should include purified spice extracts.

Monitoring of theophylline treatment by saliva and plasma concentrations.

The interdependence of serum and saliva theophylline concentrations was studied in a group of 79 children. Our results indicate that the measurement of saliva theophylline concentration, when the excretion of saliva is not stimulated, is reliable. The saliva theophylline concentration should be multiplied with the factor 1.6 to give an estimated serum concentration. Our results indicate that the use of saliva theophylline determination is comparable with the determination of serum concentration. The collection of saliva sample is painless compared with drawing a blood sample and the method is recommended, especially in pediatric use. The use of a slow-release theophylline preparation (Theo-Dur) was studied and compared with the use of ordinary theophylline in a group of asthmatic children. It was shown that the use of slow-release theophylline preparation (Theo-Dur) in a dose of 16-18 mg/kg/day divided in two daily doses gave a stable and safe serum concentration compared with ordinary theophylline in doses about 18-21 mg/kg/day divided in three doses.

Percutaneous absorption of hydrocortisone during exacerbation and remission of atopic dermatitis in adults.

Percutaneous absorption of hydrocortisone was studied in 18 young adults during and after the acute phase of atopic dermatitis using the direct hydrocortisone absorption test. In the acute phase the post-application increase in serum cortisol concentration ranged between 18 and 711 nmol/l (median 125 nmol/l). In remission the increase in serum cortisol ranged between 0 and 114 nmol/l (median 16 nmol/l), which was significantly lower than the rise in the acute phase. In the acute phase of dermatitis, topical hydrocortisone treatment has both a local and a systemic effect, due to percutaneous absorption.

Comparison of atracurium and vecuronium in anaesthesia for renal transplantation.

In a controlled study, equipotent doses of atracurium (20 patients) or vecuronium (22 patients) were given randomly to patients with chronic renal failure anaesthetized for renal transplantation. There were no statistically significant differences in the degree of muscle relaxation (electromyographic twitch response) and circulatory parameters. Plasma histamine concentration increased in three patients after the first dose of atracurium, but in none of the patients could any signs of allergic reactions be observed. Tracheal intubation was difficult in six patients of the atracurium group, all of whom had diabetes mellitus and varying degrees of neck stiffness. The neuromuscular block response in diabetic uraemic patients was similar to that in other uraemic patients.

Allergic conjunctivitis, total and specific IgE in the tear fluid.

Twenty-three patients with allergic conjunctivitis caused by birch, timothy or mugwort pollen were examined for the presence of total and specific IgE in the tear fluid. In thirteen of the 23 patients IgE could be shown in the tears. Specific IgE antibodies against the causative pollens were present in the tear fluid of 8 of the patients. The relation between serum and tear IgE on one hand and serum and tear albumin on the other hand suggests local production of the specific IgE antibody.