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With the forced pseudo-random noise oscillation technique (FOT), resistance (Rrs) and reactance (Xrs) of the respiratory system can be measured simultaneously over a frequency spectrum of 2-26 Hz. As only passive cooperation of the child is needed, FOT is suitable for lung function measurements from the age of 2 1/2 years. Hence bronchial responsiveness can be measured in children who are not yet able to perform spirometry or flow-volume curves. We compared bronchial responsiveness to histamine and methacholine obtained with FOT. Threshold dose or provocative dose to histamine and methacholine showed a close correlation in asthmatic children aged 3.6 to 7.8 years. The 24 hour interval within-subject reproducibility of threshold dose and provocative dose to histamine in asthmatic children aged 3.9 to 8.5 years proved to be good. Bronchial responsiveness to histamine or methacholine measured by FOT was not influenced by baseline lung function or by bronchial smooth muscle tone.

A number of studies have shown that children who had infantile bronchiolitis are at increased risk of recurrent episodes of wheezing. A genetic predisposition to atopy is mentioned in some studies and is contested by others. Lung function abnormalities and increased bronchial responsiveness (BR) have been described after infantile bronchiolitis. We investigated children who had had the clinical syndrome of bronchiolitis during infancy and compared them with asthmatic and healthy children of the same age regarding bronchial caliber, smooth muscle tone, and responsiveness to histamine. Lung function was measured by forced oscillometry. We found that most children with current symptoms had either decreased baseline bronchial caliber, increased bronchial smooth muscle tone, or increased BR. These patients are comparable to mild asthmatics. The children without current symptoms are comparable to healthy children in these respects. Recurrent respiratory symptoms after bronchiolitis should be regarded as mild asthma and treated as such.

The difference between isometric and isotonic responses of human small airway smooth muscle to a number of pharmacological agonists was studied. The isotonically measured sensitivity to methacholine was 1.4 times less than the isometrically measured value (p less than 0.05), and similar small discrepancies were found for histamine, leukotriene, prostaglandin F2 alpha, isoproterenol, and theophylline. Maximal isometric force and isotonic shortening after methacholine were linearly related (p less than 0.01). The between-methods difference is relatively small. Because the difference was of similar magnitude and in the same direction in all tissues studied, it is of little practical importance for conventional pharmacological experiments.

The technique by which human bronchiolar strips are prepared is described in detail. The biological viability of the preparations after storage at 4 degrees C overnight and the reproducibility of contractile responses to KCl and methacholine were examined in lung tissue from six patients. Measurements were performed on the first and second day after surgical resection. On both days, most bronchioles showed an increase in contractility. The responses on the first day were not different from those on the second day. No significant changes in time were found for pD2 and slope of the methacholine dose-response curves. The variability of responses between patients was significantly larger than between strips within patients. The pD2 was the best reproducible parameter.

A study was carried out to test the hypothesis that chronic inflammation is associated with increased sensitivity or contractility of human airway smooth muscle. Bronchiolar strips from 30 patients, 12 of whom had chronic bronchitis, were examined in the organ bath for their responses to histamine, methacholine, and leukotriene (LT) C4. The same airways were also studied histologically and small airway disease was quantified by subjective grading of the degree of inflammatory cell infiltration, smooth muscle hypertrophy, fibrosis, and goblet cell hyperplasia. The degree of small airway disease varied widely among patients both with and without chronic bronchitis. Multiple regression analysis failed to show increased sensitivity (-log EC50) to histamine, methacholine, or LTC4 in relation to small airway disease. In contrast, the only significant correlations found were between a decreased -log EC50 to histamine and methacholine and an increased small airway disease score. Contractile responses (Tmax) to histamine and methacholine in peripheral airways tended to be higher in patients with chronic bronchitis than in those without. Tmax was not related to small airway disease scores. These results suggest that chronic airway inflammation does not cause in vitro hyperresponsiveness of human small airway smooth muscle.