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In six subjects with intrinsic asthma in clinical remission, time-structure of ventilatory parameters has been evaluated in order to evaluate: 1) which indexes present statistically significant circadian fluctuations; 2) if phase-shifts occur in comparison with normal subjects. After a period of synchronization of 7 days (L/D: 07.30-23.00; meal timing at 08.00, 13.00 and 20.30) all subjects have been studied by spirometry, flow-volume loop and Raw determination 6 times in a 24-hr period at constant intervals of 4 hrs. The results have been evaluated by macroscopic and microscopic analysis statistical significant fluctuations have been shown in these functional indexes: MEF50, Raw, SRaw, SGaw, FRC and RV; no phase-shifts occurred in comparison with normal subjects. On the contrary a circadian rhythm has not been shown in FVC, FEV1, and PEF. Therefore only the effort-independent test should be used to study correctly the bronchial tone.

The aim of the investigation was to demonstrate the existence of cyclic variations of bronchial tone, correlated with the increase of vagal tone during nocturnal hours and with the increase of adrenergic tone in the late morning and afternoon. Twenty-five healthy subjects were tested, utilizing forced expiration curve (V/V loop), Raw and SGaw. We did not detect a statistically significant rhythm for FVC, FEV1, PEF, because they are effort-dependent parameters. On the contrary, we demonstrated significant fluctuations for V max50, FEF25.75 (acrophase in the later morning and early afternoon), for Raw (acrophase in late evening) and for SGaw (Acrophase in antiphase with Raw); these parameters are effort-independent as well as direct and sensitive indexes of the tone of peripheral and central airways.

Seventeen asthmatic, non-atopic patients (aged 15-48 years) were studied at different hours of the day. On 3 different days, they were submitted to a fog-test at 03:00 p.m. and at 03:00 a.m. On 2 different days, they were given fenoterol (200 micrograms) or Duovent (fenoterol 200 micrograms plus ipratropium bromide 80 micrograms). We were able to demonstrate significant inter-hour differences of the basal values of all parameters, except FVC, in all patients at 03:00 p.m. and at 03:00 a.m. We did not observe any inter-hour difference after the fog-test. Both fenoterol and Duovent improved challenge-induced bronchoconstriction. After the fog-test, both drugs showed an inter-hour variability of ventilatory parameters, which was not significant without drugs because it was masked by the magnitude of the obstructive response to challenge.