Nogrady, S G, and Bevan, C (1978). Thorax, 33,[700][701][702][703][704]. Inhaled antihistaminesbronchodilatation and effects on histamine-and methacholine-induced bronchoconstriction. To assess further the bronchodilator activity of inhaled antihistamines ten stable asthmatic subjects inhaled aerosols of clemastine, 1 mg/ml, and saline placebo administered double blind. Subjects underwent bronchial challenge with increasing concentrations of histamine and methacholine, and specific airways conductance was measured by whole body plethysmography at each concentration. There was a significant 21-9% increase in specific airways conductance after inhalation of clemastine. Subjects could tolerate significantly higher mean concentrations of histamine when treated with clemastine than with saline. The shift of the cumulative log histamine dose-response curve suggests that such protection is due to competitive antagonism to the inhaled clemastine. Clemastine did not protect subjects against methacholine-induced bronchoconstriction, which suggests that its bronchodilator properties are not related to any anticholinergic action.

. (1975). Thorax, 30,[663][664][665][666][667][668]. A community survey of asthmatic characteristics. A survey was undertaken among adults aged 20-44 years in a South Wales town. Persons with a history of wheezing with breathlessness and in the absence of a cold were identified by postal questionnaires and seen at a clinic, together with a sample of subjects without these symptoms. The response rates for the first and second stages of the survey were 99 6 % and 91 0 % respectively, and 574 subjects were ultimately seen.Asthmatic patients (those receiving treatment within the previous year) had some airways obstruction at rest, which increased after exercise. They also had strong allergic tendencies, as shown by personal and family history, skin tests, and serum IgE levels. The ex-asthmatics (those not receiving treatment within the previous year) showed these tendencies to a lesser extent. A larger group gave a history of wheezing but stated that they had never had asthma; in their response to exercise and allergic traits they resembled the control group rather than the asthmatics, and appeared to have the features of chronic bronchitis. Asthma and chronic bronchitis would therefore seem to be distinct clinical entities within the population studied.

Bronchial hyper-responsiveness is a particular feature of asthma, but also occurs in normal subjects after a viral upper the second by saline as placebo. The study was performed double-blind and in random order. After pretreatment with PGF2ot the histamine dose-response curve was significantly shifted to the left in a parallel fashion (p < 0-001). There was a significant decrease in the doses of histamine required to cause a 20 fall in sGaw (p < 00015) but no significant change in the slopes of the dose-response regression lines, indicating that bronchial muscle sensitivity rather than reactivity had been predominantly affected.

Sixty staff working in a hospital operating theatre, where a case of humidifier fever had been identified, were studied together with 49 subjects working in other parts of the hospital. They each had a blood test for serology, a skin test, and a chest radiograph and completed a questionnaire. The theatre staff also had pulmonary function tests. The theatre humidifier was found to contain several organisms including amoebae and antigens cross-reacting highly with those implicated in previous outbreaks of humidifier fever. Of the 60 exposed subjects, 25 had developed antibodies, nine had probable symptoms of humidifier fever, and six possible symptoms. There was a strong association between symptoms and antibodies (p = 6 x 10-5 by Fisher Four subjects reacted to the challenge, including both those with antibodies and previous symptoms.

Studies were performed to investigate whether hyperresponsiveness of the airways could be induced in normal subjects by inhalation of prostaglandin E2 (PGE2). During the initial bronchodilator phase of PGE2 action the bronchoconstrictor effect of inhaled histamine was significantly antagonised. When bronchoconstrictor challenges were started shortly after the end of the bronchodilator response to PGE2, however, significant enhancement of the effects of both inhaled histamine and methacholine occurred. It was predominantly sensitivity to these agents that was increased, with a parallel shift of the dose-response curves towards increased bronchoconstriction. Thus PGE2 may be protective in the acute phase of a bronchoconstrictor challenge, but in a chronic inflammatory condition its net effect may be a balance between this beneficial action and a non-specific potentiation of the activity of bronchoconstrictor agents.Inflammatory conditions of the airways are associated with increased responsiveness to bronchoconstrictor agents such as histamine and methacholine. This occurs classically in asthma' 2 but also in atopic subjects, particularly after exposure to specific allergen,3 and in normal subjects shortly after an upper respiratory tract infections 6 or inhalation of noxious fumes.7 Prostaglandin F2a (PGF2G) and its metabolites, which are associated with such allergic and inflammatory responses, induce hyperresponsiveness in bronchial smooth muscle in vitro to several bronchoconstrictor stimuli.1'0 We have recently shown in vivo that normal human subjects will develop hyperresponsiveness to inhaled histamine after inhaling small doses of PGF2a which themselves have no demonstrable effect on airways calibre."I An increase in responsiveness of bronchial smooth muscle has been shown in vitro after brief contact with PGE2 metabolites.'2 In this study we have investigated whether previous inhalation of the bronchodilator PGE2, another product of inflammation, also induces a change in the bronchoconstrictor response to subsequent inhalation of histamine and methacholine.