In anesthetized cats, breathing spontaneously, increase in lung resistance (RL) was induced by either external resistive loads (ERL) or internal loading produced by dense gas breathing (sulfur hexafluoride, SF6) or serotonin (5-HT)-induced bronchoconstriction. The 3 test agents were used in each animal. Arterial blood gases were maintained in the normal range. Ventilatory and cardiovascular responses were studied in 3 groups of animals: intact, vagotomized, or spinalized at C8 level, a condition that preserved diaphragmatic afferents. In intact or spinal animals, ERL as well as SF6 inhalation lengthened the inspiratory and/or the expiratory periods, whereas 5-HT injections elicited rapid shallow breathing. The changes in ventilatory timing with either type of load were not observed in vagotomized cats. In all animals, ERL breathing or 5-HT injections increased the moving-time average of diaphragmatic EMG measured at constant time (Edi 0.1 and 0.5 secs), but this was not observed during SF6 inhalation, a condition in which the magnitude of RL increase was less than in the 2 other situations. The changes in systemic arterial blood pressure and/or cardiac frequency were mostly associated with 5 HT-induced bronchoconstriction. They persisted in spinalized cats, but were not observed or reversed in vagotomized ones. These observations demonstrate that vagal afferents play a major role in the changes in ventilatory timing and cardiovascular function in response to both external or internal moderate resistive loading. The existence of Edi changes in the 3 groups of cats suggests also that diaphragmatic afferents, preserved in both situations, are involved in this response.

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There are few prospective studies available on the development of delayed symptoms following challenge tests with methacholine (MCT) at the currently recommended doses. The objective of this study was to describe the nature and frequency of respiratory symptoms suggestive of bronchospasm developing within 24hours after a MCT. The study was offered to adult patients who underwent MCT seen consecutively between June and October 2015. Following the test, a questionnaire adapted from the GINA asthma control questionnaire bearing on diurnal and nocturnal symptoms (cough, dyspnoea, wheeze and tightness), was delivered to the patient and the replies collected by telephone 24hours later. Of the 101 patients included (initial FEV1 2.82±0.79L), 46 (46 %) were MCT+ and 55 (54 %) MCT-. Among the MCT-, 4 (7 %) presented with immediate symptoms (S+) and 4 (7 %) with delayed symptoms. Among the MCT+ patients, 36 (78 %) presented with immediate symptoms (P<0.001 compared with the MCT- patients), and 39 (85 %) with delayed symptoms (P<0.001 compared with the MCT- patients). Delayed symptoms developed with a mean of 5h30 after the provocation test. Immediate and delayed symptoms were more frequent in subjects having significant non-specific bronchial hyper-reactivity. Informing patients of the risk of developing delayed symptoms seems useful and allows optimization of their management after a MCT.

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