Bulletin europeen de physiopathologie respiratoire最新文献

The effect of inhaling 0.25 and 2.0 mg of terbutaline sulphate, a beta-2-stimulant, from a metered dose aerosol was studied in five asthmatic patients during two periods of five days each. During the first period, the patients used a good spontaneous inhalation technique; during the second period, the inhalation technique was optimized and controlled. The variation of basal FEV1 and of the increase (delta FEV1) caused by 0.25 mg of inhaled terbutaline was considerable. The effect was only slightly better and the variation only slightly smaller when the controlled inhalation technique was used. The differences were not significant. In individual patients, there was no or negative correlation between delta FEV1 and the corresponding basal FEV1 value. Accordingly, the most commonly used way of expressing delta FEV1 as a percentage of basal FEV1 value was found to be insensitive. Delta FEV1, expressed as a percentage of the maximum available FEV1 increase on the same day after 2.25 mg terbutaline sulphate, was found to be most sensitive. This way of expressing delta FEV1 will increase the possibilities of detecting differences between treatments in clinical trials.

Personal experience and analysis of the medical literature on isocyanate asthma shows, that the reported incidence of this disease varies between 0 and 25%. Reasons for differences in observed incidence are intensity of isocyanate exposure, criteria for diagnosis, mode of calculation, sensitizing capacity of different isocyanates, individual predisposition and confounding factors (adjuvants). There is no geographical or ethnical prevalence. Work places at risk are those with isocyanate concentrations above 20 ppb (ceiling).

A shortened protocol was developed for the epidemiological measurement of bronchial responsiveness to methacholine without compromising sensitivity, power, precision or safety, and without distorting the numerical value of the PD20.FEV1 (the cumulative dose from a doubling incremental sequence which provokes a 20% decrement in FEV1). It was used in a survey of 254 polyurethane workers (83% of the eligible workforce) exposed occupationally to toluene diisocyanate. The mean duration of each test proved to be 38 min, it was well tolerated and 64 workers (25%) proved to be reactors. PD20.FEV1 appeared to be distributed unimodally. It was significantly correlated with questionnaire records of shortness of breath, chest tightness, and wheeze; and with pre-shift FEV1 and FEF25-75. Even the reactors requiring the highest dose of 640 cumulative inhalation units (1 unit = one 8.9 microliters inhalation of methacholine 1 mg.ml-1) to generate a PD20 measurement reported significantly more wheeze than the non-reactors. This indicates that the test had clinical meaning throughout its dose range of 0.3-640 units. No correlation was found between PD20 and individual changes in ventilatory function across the working shift, but mean shift changes were negligible and not statistically significant. PD20 was also found to be unrelated to age, sex, race, smoking, cough and atopy.

In December, 1984, in Bhopal, India, a massive leak of methyl isocyanate (MIC) resulted from operational and equipment malfunctions in a pesticide plant. Many thousands of residents of the city, most in proximity to the plant, suffered sublethal and lethal respiratory injuries, the expected consequences of high-level exposure to this type of potent irritant chemical vapour. Animal toxicologic information was limited prior to the accident, but has since confirmed that the lung is the major target of these lethal injuries, invariably with pulmonary oedema. Early concerns regarding acute cyanide intoxication were not supported by subsequent scientific inquiry. Superficial corneal erosions did not result in permanent eye injury. The primary medical (and, presumably, legal) issue which is unresolved, and perhaps unresolvable, is the incidence and determinants of long-term respiratory injury in the survivors. Available evidence, which is limited, suggests that chronic damage, when present, is, or resembles, fibrosing bronchiolitis obliterans, the expected consequence when permanent injury results from acute, high-level irritant gas exposure. Definition of the follow-up population is uncertain, and exposure information is lacking. Dose-response relationships are not likely to emerge from follow-up studies.

The temporal and quantitative relationship between increases in airway responsiveness and late asthmatic reactions provoked by inhalation challenge with occupational agents was studied in nine individuals who underwent a total of thirteen active inhalation challenge tests with one of the following agents: toluene diisocyanate (TDI), maleic anhydride (MA), trimellitic anhydride (TMA), carmine, or colophony (pine wood resin). Airway responsiveness to inhaled histamine (histamine PC20) was measured before and at approximately 3 and 24 h after control and active challenge exposure, when, on all but four occasions, FEV1 was within 10% of pre-challenge values. Significant increases (p less than 0.02) in histamine responsiveness were present at 3 h following challenge exposures which subsequently provoked a definite late asthmatic reaction (FEV1 decrease greater than 15% 3-11 h post challenge). These increases in histamine responsiveness were significantly greater than those at 3 h following the challenges which provoked an isolated early (FEV1 decrease less than 6% 3-11 h post-challenge) or equivocal late asthmatic reaction (FEV1 decrease 6-15% 3-11 h post-challenge) (p less than 0.03). Although histamine responsiveness remained high at 24 h after challenges provoking late asthmatic reactions (p less than 0.05), this was less than the increase at 3 h and not significantly different from the PC20 at 24 h after challenges provoking either single early or equivocal late asthmatic reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Although TDI asthma has been recognised for more than twenty years, the mechanism of the reaction is still highly controversial. To assist in elucidation of the mechanism, an animal model has been developed which displays many of the characteristics of the response including immediate- and late-onset pulmonary reactions, cytophilic antibody production, and dermal sensitivity. This communication traces the development of the guinea pig model, describes the rationale behind its methodology, and presents evidence for validation of the model. Concepts derived from the model regarding factors promoting sensitization are discussed.