Biomaterial Database

Acute bronchial obstruction following inhalation of PAF in asthmatic and normal subjects: comparison with methacholine. 1996

R E Louis, and M F Radermecker

Dept. of Pneumology, CHU Sart-tilman, Liege, Belgium.

Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma but controversies exist about bronchial responsiveness toward this mediator in asthma. We have compared the variations in the specific conductance (sGaw) and forced expiratory volume in one second (FEV1) in 12 asthmatics and 12 normal subjects after inhalation of doubling doses of PAF (15-120 micrograms) and methacholine (18 to at least 144 micrograms). In order to take into account a possible tachyphylaxis, we compared PAF dose-response curves performed on one day with the curves obtained by giving the same doses separately on different days. Repeated inhalations of doubling doses of PAF caused sGaw and FEV1 to plateau after the second dose in each group, whereas methacholine provoked a dose-related decrease in sGaw and FEV1. A dose-dependent decrease in the functional indices was restored when the different doses of PAF were administered on separate days. In both groups, the fall in sGaw after inhalation of 60 micrograms as a single dose was higher than that achieved when this dose was given during a full bronchial challenge. The falls in sGaw and FEV1 after PAF inhalation were significantly higher in the asthmatics than in the normal subjects. The provocative dose of PAF causing a 35% fall in sGaw (PD35,sGaw) PAF was only twofold lower in the asthmatics than in the normal subjects (p < 0.05), while it was 11 fold lower for methacholine (p < 0.001). When the PD35,sGaw values were compared, PAF was found on a molar basis to be 33 fold more potent than methacholine in the normal subjects, but only fivefold more potent in the asthmatics (p < 0.05). The percentage falls in FEV1 (calculated by interpolation) for a 35% fall in sGaw, were greater in asthmatics than in normals both for methacholine (p < 0.05) and PAF (p = 0.09). Our results demonstrate a tachyphylaxis after inhalation of platelet-activating factor in normal subjects and asthmatics, and show that asthmatics develop a greater bronchial obstruction than normal subjects even if methacholine is more sensitive than platelet-activating factor at discriminating between the two groups.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010972	Platelet Activating Factor	A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.	AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
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
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
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000280	Administration, Inhalation	The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract.	Drug Administration, Inhalation,Drug Administration, Respiratory,Drug Aerosol Therapy,Inhalation Drug Administration,Inhalation of Drugs,Respiratory Drug Administration,Aerosol Drug Therapy,Aerosol Therapy, Drug,Drug Therapy, Aerosol,Inhalation Administration,Administration, Inhalation Drug,Administration, Respiratory Drug,Therapy, Aerosol Drug,Therapy, Drug Aerosol
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D001249	Asthma	A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).	Asthma, Bronchial,Bronchial Asthma,Asthmas
D013618	Tachyphylaxis	Rapidly decreasing response to a drug or physiologically active agent after administration of a few doses. In immunology, it is the rapid immunization against the effect of toxic doses of an extract or serum by previous injection of small doses. (Dorland, 28th ed)