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Effect of chronic theophylline treatment on the methacholine dose-response curve in allergic asthmatic subjects. 1998

C P Page, and T Cotter, and S Kilfeather, and P Sullivan, and D Spina, and J F Costello
The Sackler Institute of Pulmonary Pharmacology, Dept of Respiratory Medicine, King's College School of Medicine and Dentistry, London, UK.

Theophylline is a bronchodilator and immunomodulator drug which has recently been demonstrated to attenuate the recruitment and activation of inflammatory cells into lungs of asthmatics. This study investigated the effect of chronic treatment with theophylline for its ability to alter airway responsiveness, as indicated by changes in airway sensitivity and reactivity to inhaled methacholine. The subjects studied were mild asthmatics who relied on beta-agonist medication only and who were randomized into two groups, one receiving theophylline (median dose 250 mg twice daily; range 250-375 mg twice daily) and the other placebo. A number of parameters was measured before and after treatment, including baseline forced expiratory volume in one second (FEV1), the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20; sensitivity), dose-response slope (reactivity) and percentage eosinophils, eosinophil cationic protein and T-cell markers in peripheral blood (by flow cytometry). After 2 months of treatment with theophylline there was a significant lowering of airway reactivity (slope) to methacholine and improvement in methacholine sensitivity (PC20). However, such changes were not associated with any significant change in the number or activation status of eosinophils and lymphocytes in peripheral blood. In conclusion, chronic treatment with theophylline reduces the reactivity of the airways to methacholine, which might be beneficial in the treatment of persistent asthma. The cellular mechanisms of this improvement remain to be clarified.

UI MeSH Term Description Entries
D008134 Long-Term Care Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. Care, Long-Term,Long Term Care
D008297 Male Males
D012130 Respiratory Hypersensitivity A form of hypersensitivity affecting the respiratory tract. It includes ASTHMA and RHINITIS, ALLERGIC, SEASONAL. Airway Hyperresponsiveness,Hypersensitivity, Respiratory,Airway Hyper-Responsiveness,Airway Hyper Responsiveness,Airway Hyperresponsivenesses,Hyper-Responsiveness, Airway,Hyperresponsiveness, Airway,Respiratory Hypersensitivities
D001985 Bronchial Provocation Tests Tests involving inhalation of allergens (nebulized or in dust form), nebulized pharmacologically active solutions (e.g., histamine, methacholine), or control solutions, followed by assessment of respiratory function. These tests are used in the diagnosis of asthma. Allergen Bronchial Provocation Tests,Allergen Challenge, Endobronchial,Antigen Bronchial Provocation Tests,Bronchial Allergen Challenge,Bronchial Challenge Tests,Inhalation Provocation Tests,Provocation Tests, Bronchial,Endobronchial Challenge Tests,Allergen Challenge, Bronchial,Allergen Challenges, Bronchial,Allergen Challenges, Endobronchial,Bronchial Allergen Challenges,Bronchial Challenge Test,Bronchial Provocation Test,Challenge Test, Bronchial,Challenge Test, Endobronchial,Challenge Tests, Bronchial,Challenge Tests, Endobronchial,Challenge, Bronchial Allergen,Challenge, Endobronchial Allergen,Challenges, Bronchial Allergen,Challenges, Endobronchial Allergen,Endobronchial Allergen Challenge,Endobronchial Allergen Challenges,Endobronchial Challenge Test,Inhalation Provocation Test,Provocation Test, Bronchial,Provocation Test, Inhalation,Provocation Tests, Inhalation,Test, Bronchial Challenge,Test, Bronchial Provocation,Test, Endobronchial Challenge,Test, Inhalation Provocation,Tests, Bronchial Challenge,Tests, Bronchial Provocation,Tests, Endobronchial Challenge,Tests, Inhalation Provocation
D001993 Bronchodilator Agents Agents that cause an increase in the expansion of a bronchus or bronchial tubes. Bronchial-Dilating Agents,Bronchodilator,Bronchodilator Agent,Broncholytic Agent,Bronchodilator Effect,Bronchodilator Effects,Bronchodilators,Broncholytic Agents,Broncholytic Effect,Broncholytic Effects,Agent, Bronchodilator,Agent, Broncholytic,Agents, Bronchial-Dilating,Agents, Bronchodilator,Agents, Broncholytic,Bronchial Dilating Agents,Effect, Bronchodilator,Effect, Broncholytic,Effects, Bronchodilator,Effects, Broncholytic
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D005260 Female Females
D005541 Forced Expiratory Volume Measure of the maximum amount of air that can be expelled in a given number of seconds during a FORCED VITAL CAPACITY determination . It is usually given as FEV followed by a subscript indicating the number of seconds over which the measurement is made, although it is sometimes given as a percentage of forced vital capacity. Forced Vital Capacity, Timed,Timed Vital Capacity,Vital Capacity, Timed,FEVt,Capacities, Timed Vital,Capacity, Timed Vital,Expiratory Volume, Forced,Expiratory Volumes, Forced,Forced Expiratory Volumes,Timed Vital Capacities,Vital Capacities, Timed,Volume, Forced Expiratory,Volumes, Forced Expiratory
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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