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Biomedical subjects

A F Henderson

Publications and source records attributed to A F Henderson.

26 records · Page 2Linked to original sources

Cold air as a bronchial provocation technique. Reproducibility and comparison with histamine and methacholine inhalation.

Bronchial provocation testing with cold air was carried out on 36 asthmatic and 13 normal subjects in order to assess the reproducibility and clinical relevance of the technique as a test of airways reactivity. Sixteen subjects underwent repeat testing after an interval of two to three weeks. Using a least squares linear regression analysis, the technique was highly reproducible, with a correlation of r = 0.93 (p less than 0.001). The 21 asthmatic subjects who had exercise-provoked symptoms required a significantly lower level of ventilation of cold air to produce a 35 percent drop in specific airways conductance (PD35) than did those who had no exercise-induced asthma (33.9 L min-1 vs 45.8 L min-1; p less than 0.02). Subjects requiring no regular treatment for their asthma had a geometric mean PD35 of 62.6 L min-1, significantly higher than those requiring inhaled therapy (44.9 L min-1; p less than 0.005). Subjects requiring oral in addition to inhaled treatment had the lowest PD35 (23.6 L min-1; p less than 0.02). Atopic status did not appear to influence the response. There was a strong correlation between the PD35 to cold air and to histamine (r = 0.92; p less than 0.001) and between the PD35 to cold air and to methacholine (r = 0.86; p less than 0.001). The three techniques of assessing bronchial reactivity were equally successful in separating the normal and asthmatic groups. The results indicate that cold air provocation may be reliably and reproducibly used to assess bronchial reactivity. The use of a naturally-occurring stimulus of asthma in all subjects has great potential as an investigational technique.

Adolescent↗

The influence of pretreatment with prostaglandin F2 alpha on bronchial sensitivity to inhaled histamine and methacholine in normal subjects.

The effect of pretreatment with prostaglandin F2 alpha (PGF2 alpha) on the bronchial sensitivity to histamine and methacholine has been studied in three groups of six normal subjects, and compared with the effect of citric acid aerosol as a non-specific stimulant of bronchial irritant receptors. Aerosols were generated by Wright's nebulizer and dose-response curves to histamine and methacholine constructed following preadministration of saline, prostaglandin F2 alpha or citric acid. Following prostaglandin F2 alpha pretreatment, the PC20 histamine fell from 12.9 mg/ml to 3.4 mg/ml (P less than 0.01), but the PC20 methacholine was unchanged. Citric acid was without effect. The results indicate that prostaglandin F2 alpha can increase bronchial sensitivity to inhaled histamine, possibly via a direct effect on the airway smooth muscle.

Adult↗

The bronchial response to cold air challenge: evidence for different mechanisms in normal and asthmatic subjects.

We have investigated possible mechanisms of response to airway cooling by studying the effects of sodium cromoglycate and ipratropium bromide on the changes in airways resistance that followed eucapnic hyperventilation with subfreezing air in a group of 12 patients with mild asthma and 10 normal subjects. We have also studied the period of refractoriness to repeated challenge. Maximum bronchoconstriction was not reduced after the second challenge, but in the asthmatics the one-second forced expiratory volume recovered more rapidly after the second challenge. The response in normal subjects was completely abolished by ipratropium bromide (p less than 0.0005) whereas sodium cromoglycate was without effect. In the asthmatics both ipratropium and cromoglycate were effective in attenuating the response (p less than 0.005). These results suggest that in normal subjects the response to airway cooling is produced predominantly via neural mechanisms, whereas in asthmatics there is an additional mechanism which can be abolished by sodium cromoglycate.

Adolescent↗

Effect of nifedipine on bronchoconstriction induced by inhalation of cold air.

The effect of nifedipine (20 mg sublingually) on the bronchial response to cold air was studied in eight asthmatic patients and eight normal subjects. Eucapnic hyperventilation with dry subfreezing air was performed for three minutes by each subject, with a minute volume of 30 X FEV1 for normal subjects and half that for the asthmatics. In the normal subjects there was no difference in the falls in the one-second forced expiratory volume (FEV1) and specific airways conductance (sGaw) produced by cold air inhalation on the days when they were pretreated with placebo and with nifedipine. In asthmatic patients, however, significant protection with nifedipine was demonstrated. The maximum recorded fall in FEV1 was reduced from 13% +/- 2% (SE) to 4% +/- 2% (p less than 0.005) and the maximum fall in sGaw from 35% +/- 5% to 17% +/- 4% (p less than 0.002). The possible causes of this difference are discussed. It is suggested that these results present further evidence for a different mechanism of response to cold air in asthmatic and normal subjects.

Adult↗

Effects of nifedipine on antigen-induced bronchoconstriction.

We have investigated the effects of the calcium antagonist nifedipine on antigen-induced bronchoconstriction in vivo and in vitro. Eight grass-pollen-sensitive asthmatics were given either nifedipine (20 mg sublingually) or placebo 30 min before antigen challenge. The fall in forced expiratory volume in one second after pretreatment with placebo was 42.8 +/- 10.1%. After nifedipine this fall was significantly reduced to 26.5 +/- 11.7% (p less than 0.005). Two in vitro models of allergic asthma have been studied: actively sensitized guinea pig tracheal strips (GPT) and passively sensitized human bronchial muscle (HBM). Contraction of GPT by acetylcholine, histamine, and antigen challenge was unaffected by nifedipine 10(-4)M. Contraction of HBM by acetylcholine, histamine and grass pollen antigen challenge was significantly reduced by nifedipine 10(-4)M and 10(-6)M. The magnitude of the reduction in contraction to antigen challenge was comparable to the inhibition of acetylcholine and histamine responses. It would appear most likely that nifedipine exerts its effect mainly on bronchial muscle contractility rather than by stabilizing mast cells.

Adult↗