Effect of inhaled histamine on occlusion pressure and breathing pattern in asthmatic patients.

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 of inhaled 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 (P0.1), was found to be significantly increased while no significant changes in breathing pattern were noted. In the twelve group II patients histamine did not modify P0.1 or breathing pattern. However, we were able to separate in group I a sub-group of ten patients, as with atopic asthma, in which histamine-induced increase in P0.1 was paralleled by rapid and shallow breathing (RSB). Changes in P0.1 and breathing pattern did not depend on baseline airway calibre. In group I, after bronchoconstriction had been reversed by inhaling a beta 2-agonist bronchodilator agent (fenoterol), P0.1 decreased significantly and RSB was found to be reversed; however, these changes were not interrelated. We concluded that: in asthmatics, histamine-induced increase in P0.1 is not necessarily paralleled by, nor related with, change in breathing pattern and in atopics a 'sensitization' of vagal receptors could account for the concomitance of enhanced P0.1 with RSB.

Control of breathing in normal subjects and in patients with chronic airflow obstruction.

In order to assess ventilatory control in patients with chronic airflow obstruction (CAO), the present study was carried out in nine patients with chronic obstructive pulmonary disease (COPD), eight asthmatics and nine normal subjects. We analysed the components of the respiratory control system at three levels: neural, assessed by diaphragmatic electromyography (EMGd), muscular, assessed by mouth occlusion pressure (P0.1), and ventilatory, assessed by mean inspiratory flow (VT/TI). EMGd was recorded by surface electrodes. During a CO2 rebreathing test, patients showed a normal or greater EMGd response slope (EMGdS), while for a given degree of EMGdS, P0.1 response slope (P0.1S) was found to be significantly reduced; in contrast, for a given degree of P0.1S, VT/TI response slope (VT/TIS) was found to be significantly reduced in COPD patients only. These data show that, compared to normal subjects, patients with CAO have a normal or increased neural component of the respiratory activity (EMGdS) and a relatively lower neuromuscular coupling (P0.1S/EMGdS). Probably due to different parenchymal and airway involvement, musculoventilatory transfer (VT/TIS/P0.1S) was found to be reduced in COPD patients but not in asthmatics. A complementary study, showing a good agreement between surface and oesophageal EMGd seems to confirm that surface EMGd is a useful and promising tool for clinical investigation.

Inspiratory impedance during histamine-induced bronchoconstriction in patients with bronchial asthma.

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 (P0.1), mean inspiratory flow (VT/Ti), and the P0.1/(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 P0.1/(VT/Ti) increased (p less than 0.01 for both). After bronchoconstriction was reversed by administration of a beta 2-agonist bronchodilator (fenoterol), a significant decrease in P0.1/(VT/Ti) (p less than 0.001) and a significant increase in FEV1 (p less than 0.01) were noted as compared to histamine. With histamine, change in P0.1/(VT/Ti) was found to be related to its pre-histamine value (p less than 0.01). Furthermore, with histamine and fenoterol, changes in P0.1/(VT/Ti) and concurrent changes in FEV1 were found to be significantly related (p less than 0.001). From these data we calculated that the P0.1/(VT/Ti) ratio provides a useful tool in the clinical assessment of histamine-induced bronchospasm.

Effects of aminophylline on respiratory drive and neuromuscular coupling in normal man and in patients with chronic airflow obstruction.

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.

Effects of histamine and reproterol inhalation on mouth occlusion pressure in patients with bronchial asthma.

Both vagal and non-vagal afferences from the lung or chest wall contribute to increasing neural drive to the respiratory muscles, but only the former are known to change the breathing pattern by increasing respiratory frequency (RF) during bronchoconstriction. In order to evaluate the relative contribution of vagal and non-vagal afferences to increasing neural drive to the respiratory muscles in 14 asymptomatic asthmatic patients known to be responsive (decrease in FEV1 greater than 20% of the control values) to previous bronchial provocation test (BPT) with aerosolized histamine, we evaluated FEV1, breathing pattern and neuromuscular drive, as assessed by mouth occlusion pressure (PO.1), under control conditions, during BPT with progressive doubling doses of inhaled histamine (H) and 5 min after inhalation of a bronchodilator agent (Reproterol) (B). During HBPT FEV1 exhibited a significant decrease (p less than 0.01) while PO.1 was found to increase significantly (p less than 0.01). However, no significant changes were noted in breathing pattern. After B FEV1 returned to control values while PO.1, even if significantly reduced (p less than 0.01), did not. Changes in PO.1 were found to be significantly related to changes in FEV1 both during HBPT and B (p less than 0.05). The data suggest that in these patients non-vagal afferences, linked to the abnormalities of thoraco-pulmonary mechanics, could play a major role in changing neural drive to the respiratory muscles.

Functional evaluation in stage I pulmonary sarcoidosis.

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.