In animals, histamine inhalation is known to increase either respiratory frequency or respiratory drive by stimulation of airway vagal sensitive endings. However, it is not well known whether these changes are concomitant in man. In order to elucidate this point, we carried out the present investigation in thirty-five asthmatic patients who underwent bronchial provocation test by progressively doubling the dose ofinhaled histamine. Bronchial reactivity to histamine allowed two populations of patients to be defined: group I with moderate and group II with mild, increased reactivity. In the twenty-three group I patients, neuromuscular inspiratory drive, assessed by mouth occlusion pressure (Poi), was found to be significantly increased while no significant changes in breathing pattern were noted. In the twelve group 11 patients histamine did not modify Po i or breathing pattern. However, we were able to separate in group I a sub-group often patients, as with atopic asthma, in which histamine-induced increase in Poi was paralleled by rapid and shallow breathing (RSB). Changes in P,, i and breathing pattern did not depend on baseline airway calibre. In group 1, after bronchoconstriction had been reversed by inhaling a /fragonist bronchodilator agent {fenoterol), Po i decreased significantly and RSB was found to be reversed; however, these changes were not interrelated. We concluded that: (i) in asthmatics, histamineinduced increase in Po i is not necessarily paralleled by, nor related with, change in breathing pattern and (ii) in atopies a "sensitization' of vagal receptors could account for the concomitance of enhanced Po i with RSB.

In order to evaluate the separate effects of aminophylline on the neural and muscular components of the respiratory control system, assessed by electromyographic activity of the diaphragm (EMGd) and mouth occlusion pressure (P0.1), respectively, 6 normal subjects and 14 patients with mild or moderate chronic airflow obstruction (8 asthmatics and 6 COPD) were studied during CO2 rebreathing, before and after administration of a therapeutic dose of aminophylline 5.6 mg/kg. Compared to normal subjects, before aminophylline administration both asthmatic and COPD patients exhibited a significantly greater value in EMGd response slope to CO2. In no group did aminophylline modify P0.1 or EMGd activity response slope to CO2, nor did it significantly affect neuromuscular coupling, assessed by plotting change in P0.1 against change in EMGd activity with increasing CO2. The data appear to indicate that aminophylline in therapeutic concentrations does not modify respiratory drive or neuromuscular coupling in normal subjects, or in patients with mild or moderate chronic airflow obstruction.

A functional evaluation was performed in 9 non-smoking patients suffering from sarcoidosis characterized, on chest roentgenograms, by hilar adenopathies (stage I). Frequency dependence of compliance (5 cases) and decreased conductance of the upstream segment (3 cases) were the major findings. From this it is concluded that, even at stage I, small-airway impairment may be documented in some patients, suggesting the existence of peribronchiolar granulomatous infiltration.

Histamine inhalation provocation tests were performed in 18 asymptomatic asthmatic patients with progressively increasing doses of a pressurized aerosol of histamine phosphate. Forced expiratory volume in 1 s (FEV₁), total neuromuscular output, assessed by mouth occlusion pressure (P_0.1), mean inspiratory flow (VT/Ti), and the P_0.1/(VT/Ti) ratio, which represents an index of effective inspiratory impedance of the respiratory system, were measured. With histamine, compared to control, FEV₁ decreased and P_0.1/(VT/Ti) increased (p < 0.01 for both). After bronchoconstriction was reversed by administration of a β₂-agonist bronchodilator (fenoterol), a significant decrease in P_0.1/(VT/Ti) (p < 0.001) and a significant increase in FEV₁ (p < 0.01) were noted as compared to histamine. With histamine, change in P_0.1 /(VT/Ti) was found to be related to its pre-histamine value (p < 0.01). Furthermore, with histamine and fenoterol, changes in P_0.1/(VT/Ti) and concurrent changes in FEV₁ were found to be significantly related (p < 0.001). From these data we calculated that the P_0.1 /(VT/Ti) ratio provides a useful tool in the clinical assessment of histamine-induced bronchospasm

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