J. G. R. De Monchy

Effects of inhaled budesonide on spirometric values, reversibility, airway responsiveness, and cough threshold in smokers with chronic obstructive lung disease.

Inhaled corticosteroids are known to reduce respiratory symptoms and airway responsiveness in allergic patients with asthma. The aim of the present randomised, double blind study was to assess the effect of eight weeks treatment with inhaled budesonide in non-allergic smokers with chronic obstructive lung disease. Twenty four subjects (23 male) entered the study. Their ages ranged from 40 to 70 (mean 57) years, with a mean of 35 (range 9-80) pack years of smoking; the mean FEV1 was 53% (range 32-74%) predicted and geometric mean PC20 (histamine concentration causing a 20% fall in FEV1) 0.96 (range 0.07-7.82) mg/ml. After a two week washout, single blind, placebo period, 12 patients were allocated to treatment with budesonide 1600 microgram/day and 12 to placebo for eight weeks. The only additional drug to be taken was ipratropium bromide if needed. Twenty one patients completed the study, 10 in the budesonide group and 11 in the placebo group. The standard deviation of the difference between duplicate measurements of PC20 histamine and citric acid cough threshold made two weeks apart was below one doubling dose step. There was a significant reduction in dyspnoea in the budesonide group, but otherwise no change in symptom scores or use of ipratropium bromide over the eight weeks of treatment within or between the two groups. No significant differences in spirometric values, peak expiratory flow, PC20 histamine, or citric acid cough threshold were found between the groups. Although differences were not significant, some of the changes showed a trend in favour of budesonide. Whether a longer observation period would show a significant influence of inhaled corticosteroids in patients with chronic obstructive lung disease remains to be determined.

Clinical evaluation of the effect of anti-allergic mattress covers in patients with moderate to severe asthma and house dust mite allergy: a randomised double blind placebo controlled study

Background: The use of anti-allergic mattress covers in patients with asthma can result in a large reduction in the level of house dust mite allergen in dust samples. Apart from a reduction in histamine induced bronchial hyperresponsiveness, there are few data on the effect of mattress covers on clinical efficacy and quality of life in patients with moderate to severe asthma. Methods: Thirty patients with asthma and house dust mite allergy were studied in a randomised, double blind, placebo controlled study. Before and after using anti-allergic covers for 1 year, dust was collected from the mattresses to determine concentrations of Dermatophagoides pteronyssinus (Der p 1), and bronchial hyperresponsiveness and quality of life were measured. The patients scored their symptoms (lungs and nose), morning and evening peak flow values, and rescue medication for 14 days before and after the intervention period. Results: There was a significant reduction in the concentration of Der p 1 in the dust collected from the mattresses in the actively treated group after 1 year compared with before treatment; no change was found in the placebo group. In both the actively treated and placebo groups there was no significant improvement in PC20 histamine. Quality of life improved similarly in both groups. The symptom score of the lower airways did not significantly change in either group. A significant decrease in nasal symptom score was seen in the actively treated group compared with before treatment, but there was no significant difference between the groups. No changes in morning and evening peak flow values, peak flow variability, nor in the use of rescue medication were found in either group. Conclusion: The use of anti-allergic mattress covers results in significant reductions in Der p 1 concentrations in carpet-free bedrooms. However, in patients with moderate to severe asthma, airways hyperresponsiveness and clinical parameters are not affected by this effective allergen avoidance.

The effect of anti-allergic mattress encasings on house dust mite-induced early- and late-airway reactions in asthmatic patients. A double-blind, placebo-controlled study

Background Anti‐allergic mattress encasing may provide clinical benefit in asthmatic patients. However, the effect of mattress encasings on allergen‐specific parameters, such as bronchial reactions to house dust mite (HDM) challenge, is not clear.

CUTANEOUS REACTIONS TO CAPTOPRIL - PREDICTIVE VALUE OF SKIN-TESTS

Cutaneous reactions associated with captopril treatment occurred in fifteen out of eighty‐nine patients (17%). Dose reduction invariably led to improvement of the reaction but later recurrences were frequent (six patients). In four out of the fifteen patients captopril withdrawal ultimately was necessary. Skin tests and in vitro lymphocyte transformation tests with captopril were performed in these fifteen patients and also in nine captopril‐treated control patients without adverse reactions.

Citric acid cough threshold and airway responsiveness in asthmatic patients and smokers with chronic airflow obstruction.

The relation between citric acid cough threshold and airway hyperresponsiveness was investigated in 11 non-smoking patients with allergic asthma (mean FEV1 94% predicted) and 25 non-atopic smokers with chronic airflow obstruction (mean FEV1 65% predicted). Cough threshold was determined on two occasions by administering doubling concentrations of citric acid. Seven of the 11 asthmatic subjects and 14 of 25 smokers with chronic airflow obstruction had a positive cough threshold on both test days. Cough threshold measurements were reproducible in both groups (standard deviation of duplicate measurements 1.2 doubling concentrations in asthma, 1.1 doubling concentrations in chronic airflow obstruction). Citric acid provocation did not cause bronchial obstruction in most patients, though four patients had a fall in FEV1 of more than 20% for a short time on one occasion only. No significant difference in cough threshold was found between the two patient groups despite differences in baseline FEV1 values. There was no significant correlation between cough threshold and the provocative concentration of histamine causing a 20% fall in FEV1 (PC20) histamine in either group. Thus sensory nerves can be activated with a tussive agent in patients with asthma and chronic airflow obstruction without causing bronchial smooth muscle contraction.

Occupational asthma due to IgE mediated allergy to the flower Molucella laevis (Bells of Ireland)

Background: About 25% of greenhouse flower and/or ornamental plant growers sensitised to workplace flowers or moulds have occupational asthma, a disease that is suffered by 8% of the growers who cultivate these crops. Aim: To document a case of occupational asthma due to IgE mediated allergy to the flower Molucella laevis. Methods and Results: There was a history of work related seasonal asthmatic and rhinoconjunctivitis symptoms in a Molucella laevis grower. Bronchial obstruction following exposure to Molucella laevis was documented by a fall in FEV1 from 89% to 73% of predicted during seasonal exposure to Molucella laevis. Daily PEF measurements showed a fall from 500 to 250 l/min during this period following withdrawal of inhaled steroids. Bronchial reactivity to inhaled methacholine was increased (PC20 1.45 mg/ml). Confirmation of sensitisation to Molucella laevis flower pollen extract was done using an SPT and by demonstration of Molucella laevis specific serum IgE (18 IU/ml; class 4). Specific inhalation challenge with Molucella laevis extract provoked an early and late asthmatic reaction (EAR and LAR) with a fall in FEV1 compared with control day of 40% and 53% respectively, with associated 5.1-fold increase in absolute sputum eosinophil cell counts and 2.9-fold increase in neutrophil cell counts.

Effect of local allergen priming on early, late, delayed-phase, and epicutaneous skin reactions

Allergic disease is reflected in a chronic inflammatory response to an allergen. It is thought that local allergen priming underlies this chronicity. To assess the effect of allergen priming on the amplitude and histologic effect of the allergic reaction, four sequential, intracutaneous skin tests were done with 48‐h intervals in 13 patients allergic to the house‐dust mite Dermatophagoides pteronyssinus (Dpt). Reactions were measured at 15 min, and at 6, 24. and 48 h. Subsequently, epicutaneous tests were done on Dpt‐primed spots (n= 5). At 6, 24, and 48 h, reactions increased after priming (P < 0.006), with unaltered early reactions. Epicutaneous reactions to Dpt on primed spots were larger than in epicutaneous controls on similarly primed skin. Local intradermal priming results in greater inflammatory responses at both intra‐ and epicutaneous challenge. This mechanism may explain the chronicity of allergic reactions at epithelial surfaces.

Follow up investigation of workers in synthetic fibre plants with humidifier disease and work related asthma.

OBJECTIVE: To investigate the clinical and sociomedical outcome in patients with various clinical manifestations of humidifier disease and work related asthma after removal from further exposure. METHODS: Follow up investigation (range 1-13 years) of respiratory symptoms, spirometry, airway responsiveness, sickness absence, and working situation in patients with (I) humidifier fever (n = 12), (II) obstructive type of humidifier lung (n = 8), (III) restrictive type of humidifier lung (n = 4), and (IV) work related asthma (n = 22). All patients were working at departments in synthetic fibre plants with microbiological exposure from contaminated humidification systems or exposure to small particles (< 1 micron) of oil mist. RESULTS: At follow up patients with work related asthma were less often symptom free (37%, 7/19) than patients with humidifier disease (I, II, III) (67%, 16/24). Mean forced expiratory volume in one second (FEV1) of patients with obstructive impairment had been increased significantly at follow up but still remained below the predicted value. Mean forced vital capacity (FVC) of patients with initially restrictive impairment had returned to normal values at follow up. Airway hyperresponsiveness at diagnosis persisted in patients with obstructive impairment (II + IV 14/17, but disappeared in patients with humidifier fever (3/3) and restrictive type of humidifier lung (2/2). In patients with obstructive impairment (II + IV), FVC and FEV1 at diagnosis were negatively associated with the duration between onset of symptoms and diagnosis and the number of years of exposure. Those with positive pre-employment history of respiratory disease had a lower FEV1 at diagnosis. Sickness absence due to respiratory symptoms decreased in all groups of patients after removal from further exposure, but this was most impressive in patients with the humidifier lung (II, III) and patients with work related asthma (IV). At follow up 83% of the patients were still at work at the same production site, whereas 11% received a disability pension because of respiratory disease. CONCLUSION: In patients with work related respiratory disease caused by exposure from contaminated humidification systems or oil mist, removal from further exposure resulted in clinical improvement, although, especially in those with obstructive impairment, signs persisted. Because of the possibility of transferring patients to exposure-free departments most patients could be kept at work.

HLA-DR EXPRESSION IS INDUCED ON KERATINOCYTES IN DELAYED-HYPERSENSITIVITY BUT NOT IN ALLERGEN-INDUCED LATE-PHASE REACTIONS

In view of increasing evidence suggesting an active immunoregulatory role of the skin keratinocytes and the observation that the differentiation of allergen specific T lymphocytes is critical in the development of allergy, we evaluated epidermal expression of HLA‐DR antigen in skin reactions induced with an atopen (house dust mite) and with an non‐atopic antigen (Hemocyanin). Two groups of patients with house dust mite (Dermatophagoides pteronyssinus [Der p]) allergy were compared, one group was skin tested with Der p, the other group was immunized and subsequently skin tested with Helix pomatia Hemocyanin (HPH), Biopsy specimens taken at 48 h after the HPH (n= 11) and Der p (n= 11) tests were analysed immunohistologically. Reactions in both groups were comparable in size. Immunohistological analysis showed domination by CD4 + lymphocytes. Expression of HLA‐DR antigen by epidermal keratinocytes was observed in six out of 11 of the HPH induced reactions, but in none of the Der p induced reactions. Eosinophils were spotted only throughout the Der p induced reactions, showing a good correlation with the number of CD4 positive lymphocytes. The lack of HLA‐DR expression by keratinocytes during the allergen‐induced reaction, compared with the Hemocyanin induced reaction can be the result of a difference in cytokine profile of the lymphocytes dominating the dermal infiltrate. On the other hand evidence exists that defective HLA‐DR expression by keratinocytes enhances antigen induced lymphocyte activation, and may thus contribute to the development of allergen‐specific T‐lymphocytes.

Determination of the stability of diluted allergen extracts using a concentration step prior to EAST inhibition

Background Generally the stability of diluted allergen extracts, as used for skin testing, provocation testing und immunotherapy can not be tneasured using a normal enzyme allergosorbent test (EAST) inhibition method.