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Repeated aerosol exposure to small doses of allergen. A model for chronic allergic asthma
S H Arshad1, R G Hamilton, N F Adkinson
1Department of Medicine, Division of Allergy and Clinical Immunology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Abstract:
To improve our understanding of the pathophysiology of chronic allergic asthma, we mimicked natural allergen exposure by giving tiny doses of dust-mite extract (equivalent to estimated daily exposure in a typical bedroom) in three weekly sessions for 4 wk. Nine mild asthmatic adults who were highly sensitive to dust-mite allergen participated in the study. Serial assessments of bronchial reactivity by methacholine challenge, pulmonary function, symptoms, and bronchodilator requirements were obtained. Seven of nine subjects had a twofold or more (median: 6, range: 2.7 to 25) reduction (p = 0.008) in PC20, after which saline inhalations were substituted for dust-mite extract. Bronchial reactivity returned to normal within 2 to 3 wk after cessation of dust-mite inhalations in all but one subject. Predosing FEV1 dropped 10% over 4 wk of provocation (p = 0.001) and 7 of 9 returned to prestudy level within 2 wk after dosing was stopped. Late-phase responses were seen in 6 of 9 subjects. We conclude that repeated aerosol exposure to dust-mite allergen in doses comparable to natural bedroom exposure is sufficient to adversely affect pulmonary function and bronchial hyperractivity in sensitized individuals. These changes are rapidly reversible. This low-dose provocational strategy provides an attractive model for the experimental study of allergic asthma. Arshad SH, Hamilton RG, Adkinson NF, Jr. Repeated aerosol exposure to small doses of allergen: a model for chronic allergic asthma.
Insights
Repeated exposure to low-dose dust mite allergen, similar to bedroom levels, worsened asthma symptoms and bronchial reactivity in adults. These effects were reversible after stopping allergen exposure, suggesting a useful model for studying allergic asthma.
Area of Science:
- Allergy and Immunology
- Pulmonary Medicine
- Environmental Health
Background:
- Chronic allergic asthma pathophysiology requires better understanding.
- Natural allergen exposure, like dust mites in bedrooms, is a key factor.
- A controlled model for studying chronic allergic asthma is needed.
Purpose of the Study:
- To investigate the effects of low-dose, repeated dust mite allergen exposure on mild asthmatics.
- To establish a reproducible model for chronic allergic asthma research.
Main Methods:
- Nine mild asthmatic adults with dust mite sensitivity inhaled tiny doses of dust mite extract thrice weekly for 4 weeks.
- Assessments included methacholine challenge for bronchial reactivity, pulmonary function tests, symptom monitoring, and bronchodilator use.
- Saline inhalations replaced allergen after the provocation period.
Main Results:
- A significant reduction in bronchial reactivity (PC20) was observed in 7 out of 9 subjects (p = 0.008).
- Forced expiratory volume in 1 second (FEV1) decreased by 10% over 4 weeks (p = 0.001), returning to baseline in most subjects after cessation.
- Late-phase asthmatic responses occurred in 6 out of 9 subjects.
Conclusions:
- Repeated aerosolized dust mite allergen exposure, at levels comparable to natural environments, adversely affects pulmonary function and bronchial hyperreactivity in sensitized individuals.
- These asthma-related changes are rapidly reversible upon cessation of allergen exposure.
- This low-dose exposure method serves as a valuable model for experimental studies of allergic asthma.