Effect of short-term, low-level nitrogen dioxide exposure on bronchial sensitivity of asthmatic patients.

Our purpose was to determine whether exposure to a realistic concentration of nitrogen dioxide (NO2) could increase the bronchial sensitivity of asthmatic patients to bronchoconstrictor agents. We established dose-response curves for changes in specific airway resistance (SRaw) in response to aerosolized carbachol in 20 asthmatics after each had spent 1 h in an exposure chamber breathing on one occasion unpolluted air and on a separate occasion 0.1 ppm NO2: sequence of exposures to unpolluted air and to low levels of NO2 were randomized in a single-blind fashion. NO2 induced a slight but significant increase in initial SRaw and enhanced the bronchoconstrictor effect of carbachol in 13 subjects: curves were shifted to the left and the mean dose of carbachol producing a twofold increase in initial SRaw was decreased from 0.66 mg to 0.36 mg (P less than 0.001). In contrast, NO2 neither modified the initial SRaw nor the bronchoconstrictor effect of carbachol in seven subjects. In 4 out of the 20 subjects, exposure to a higher concentration of NO2 (0.2 ppm) yielded variable results. Potentiation of the carbachol bronchoconstrictor response by NO2 could not be related to any physical or clinical characteristics of the subjects tested. Although the mechanisms underlying the NO2 effect remain controversial, the present results demonstrate that very low levels of NO2 can adversely affect some asthmatics.

The interaction between indomethacin and contractile agents on human isolated airway muscle.

1 Concentration-effect curves to acetylcholine and histamine were produced in fresh human bronchial muscle (2 to 4 h after removal from the patients) and in preparations previously stored at 4 degrees C for 12 h. 2 Sensitivities of fresh human airway muscle preparations to acetylcholine (pD2 value, 5.89 +/- 0.03; n = 4) and histamine (pD2 values, 5.41 +/- 0.03; n = 13) were similar. There was no significant difference in the sensitivities of stored preparations (acetylcholine: pD2 value, 5.70 +/- 0.06; n = 23 and histamine: pD2 value, 5.44 +/- 0.07; n = 16) when compared to the fresh preparations. 3 Indomethacin did not significantly change the basal tone in preparations of either fresh or stored human airway muscle. 4 A low concentration of indomethacin (0.17 muM) significantly reduced responsiveness and sensitivity to histamine in stored bronchi but not in fresh bronchi. The acetylcholine concentration-effect curves were unaltered by exposure to this concentration of indomethacin in either fresh or stored tissues. High concentrations (1.7 muM and 17 muM) depressed the maximal responsiveness of the bronchi to both agonists. 5 These results suggest indirectly that the regulatory role of prostaglandins in human airway muscle may be different from that in other species.

Left lung asthma.

The chest radiograph of a woman with acute asthma showed signs of obstructive emphysema of the left lung. Fiberoptic bronchoscopy excluded obstruction of a large bronchus. The signs disappeared after antiasthmatic treatment, suggesting that they were caused by airway closure. In usual asthma, airway closure affects both lungs; the reason for the unilateral predominance we observed is unknown.

Cholinergic responsiveness of respiratory and vascular tissues in two different rat strains.

The airway and systemic arterial smooth muscle responsiveness to cholinergic agents of two strains of rats, Rat Albino (RA) and Brown Norway (BN), was compared in vivo and in vitro. In vivo, we measured the doses of carbachol that induced a 100% increase in lung resistance (PD100 RL), a 50% decrease in dynamic lung compliance (PD50 Cdyn), and the value of systolic blood pressure at the carbachol dose of 10 micrograms (Pa 10 micrograms). In vitro airway smooth muscle and systemic arterial smooth muscle responsiveness was assessed by measuring the maximal response to acetylcholine, the slope of the linear portion of the dose-response curve, and the negative logarithm of the molar concentration of acetylcholine producing 50% of the maximal response (pD2). PD100 and PD50 were about four times greater in BN rats than in RA rats. In contrast, Pa 10 micrograms was 1.5 lower in the BN rats. These differences persisted after bivagotomy. Tracheal pD2 was 25% greater in the RA than in the BN strain. The mean dose-response curve of parenchymal strips of RA rats was situated upward and to the left of the BN curve, but the reverse was observed for aortic smooth muscle dose-response curves. Thus 1) airway smooth muscle responsiveness to cholinergic agents is greater in RA strain than in BN, but the reverse is true for systemic arterial smooth muscle responsiveness; and 2) these differences are not due to factors extrinsic to the smooth muscle, since they occurred in vitro and may depend on different densities of muscarinic receptors.

Association of oral almitrine and medroxyprogesterone acetate: effect on arterial blood gases in chronic obstructive pulmonary disease.

Almitrine (A) and medroxyprogesterone acetate (MA) given separately improve arterial blood gases in some patients with chronic obstructive pulmonary disease (COPD); the aim of this study was to assess the effect of the two drugs given together. Forty-eight patients with irreversible COPD and hypoxaemia were prospectively enrolled into a 14-day run-in period and received single-blind oral treatment with double placebo. Patients whose PaO2 remained stable (less than 10% change; n = 29, 25 males, mean age 65.6 years) were included in a 14-day active treatment period and randomly assigned to three groups. They received double-blind oral treatment with: A (50 mg bid, group A, n = 10); MA (20 mg tid, group MA, n = 9); A (50 mg bid) and MA (20 mg tid, group A+MA, n = 10). Anthropometric and spirometric measurements were similar in the three groups and so were the arterial blood gas values at the beginning and the end of the run-in period. At the end of the active treatment period, blood gas changes (mean+/-SE) were significantly different between groups (P<0.05, Kruskal-Wallis test), with improvement in both hypoxaemia and hypercapnia in group A+MA only: delta PaO2 = 7.4+/-1.9 mmHg, delta PaCO2 = -5.1+/-1.7 m mHg (P<0.05, Wilcoxon test). In short-term treatment, the association of A and MA is more efficient than either drug alone at improving arterial blood gases in COPD patients.

[Measurement of the effect of a bronchodilator using FEV1: how to express it?]. / Mesure d'un effet bronchodilatateur par le VEMS: comment l'exprimer?

An assessment of the effect of a bronchodilator on VEMS (FEV1) is based on a "before and after" comparison with the chosen drug. Most often the percentage rise in FEV1 compared to the initial value is calculated (I), and a minimum of 20% reversibility is expected for asthma. But the change of FEV1 expressed as a percentage of predicted theoretical value (II) may also be calculated. With the help of 50 cases of asthma selected by the first criteria (I) after an inhalation of an adrenergic stimulant the following changes were shown: That the first method (I) is biased, over estimating for low initial values; That the second method (II) was not inconvenient and furnished all the information derived. It shows in particular that 14/50 subjects have a variation of FEV1 less than 10% of their theoretical value, which has considerable therapeutic interest and merits further discussion.

[Medical history of severe respiratory insufficiency]. / Histoire médicale des insuffisants respiratoires graves.

To evaluate retrospectively health care in severe chronic respiratory failure, we interviewed 38 patients, admitted for the first time to a pulmonary intensive care unit for an acute episode. A standardised questionnaire was devoted to establishing if the patients were aware of chronic respiratory disease prior to admission, if they had visited a general practitioner or a chest clinic, and had undergone a lung function evaluation. Six patients were unaware of any respiratory disease prior to the acute episode. Six others realised they had suffered from a respiratory disease, but had failed to visit a physician. Among the remaining 26 patients, two-thirds had visited a chest physician. Fourteen of them had undergone spirometry and arterial blood gas measurements. One third had visited a general practitioner but spirometry was performed in only 3 and arterial blood gas analysis in only 1. Thus, chronic respiratory failure is sometimes ignored, and most of the time diagnosed with delay and inadequately evaluated.

[Bronchodilator effects of an atropinic compound: oxitropium pressurized aerosol. Comparison with theophylline in asthma]. / Effets bronchodilatateurs d'un atropinique: l'oxitropium aérosol-doseur. Comparaison avec la théophylline dans l'asthme.

Oxitropium bromide (Tersigat pressurized aerosol) is a new anticholinergic agent. Two puffs of 100 micrograms given in 27 adult patients with asthma produced a 33% mean increase in FEVI, significantly bigger than the 20.9% increase obtained by an intra-muscular injection of theophylline (240 mg) in the same patients.