[The Incidence of occupational asthma in Alsace from 2001 to 2002. Results of intensification of the ONAP project in Alsace (2001-2002). Regional specificities]. / L'asthme professionnel en Alsace: quelques particularités régionales. Résultats de l'intensification locale de l'ONAP en 2001-2002.

INTRODUCTION: A national surveillance programme (ONAP project) was created in France in 1996 by two professional societies to estimate the incidence and identity the characteristics of occupational asthma. MATERIALS AND METHODS: In 2001 and 2002 chest physicians and occupational physicians in Alsace were intensively solicited for better voluntary reporting of cases of occupational asthma. The objective of this study was to evaluate the consequences of such a procedure on the number of cases reported, with a view to collecting comprehensive data. RESULTS: The mean annual incidence of occupational asthma was estimated at 126 cases per million workers with a female predominance (52.4%). Flours and isocyanates represented 40% of the suspected agents. Isocyanate asthma (21% of the total) was reported mainly in workers in the car supply industry, and seems to be a specific feature of the region. Persulfates represented 5.3% of the cases; latex and aldehydes 2.6%. The study also points to emergent aetiologies and work risks, i.e. quaternary ammonium compounds in disinfecting detergent products used by cleaners and healthcare workers. CONCLUSION: This study, which allowed better assessment of the real incidence of OA in Alsace and better detection of substances and occupations at risk, is an incentive to continue our Surveillance programme.

[The diagnosis and management of occupational asthma]. / Diagnostic et prise en charge de l'asthme professionnel.

INTRODUCTION: Occupational asthma (OA), with a latency period induced by multiple exposures, is characterized by immunological sensitization to the responsible agent, based on both an IgE mediated mechanisms and non specific bronchial hyper responsiveness. DIAGNOSTIC METHODS: In the diagnosis of OA, the medical history is obviously the starting-point. Onset of respiratory symptoms at work and resolution on vacation are indications of the diagnosis. After analysis of several publications, this element appears to have the best level of proof (grade 2+) according to the criteria of evidence-based medicine. A visit of the workplace, with the cooperation of the industrial physician, is essential to characterize the nature of the exposure. Positive immunological tests (skin tests and/or specific IgE) associated with objective criteria of symptoms related to work (modification of PEFR, lung function and/or nonspecific bronchial hyper responsiveness) will confirm the aetiological diagnosis of OA. Specific bronchial provocation tests performed in the laboratory allow the identification of new agents involved in OA and are necessary when other investigations are discordant or unavailable. OA needs a stepwise approach including induced sputum eosinophilic counts and measurements of exhaled nitric oxide. MANAGEMENT OF OA: OA requires removal from the workplace because persistence of exposure to respiratory sensitisers may lead to an increase and prolongation of asthma symptoms. However, removal from the workplace can have tremendous professional, financial and social consequences, and sometimes a compromise must be found with reduction of exposure by various methods combined with adequate treatment. The pharmacological treatment of patients with OA should be the same as for patients with non OA, the use of bronchodilators and corticoids depending on the severity of asthma. Concerning the medico-legal aspects, OA can be recognised as an occupational disease. In France OA is included in several tables of work-related diseases.

Reported incidence of occupational asthma in France, 1996-99: the ONAP programme.

AIMS: To estimate the general and specific incidence of occupational asthma in France in 1996-99; and to describe the distribution of cases by age, sex, suspected causal agents, and occupation. METHODS: New cases of occupational asthma were collected by a national surveillance programme, based on voluntary reporting, named Observatoire National des Asthmes Professionnels (ONAP), involving a network of occupational and chest physicians. For each case, the reporting form included information on age, sex, location of workplace, occupation, suspected causal agent, and methods of diagnosis. Estimates of the working population, used to calculate incidence rates by age, sex, region, and occupation, were obtained from the Institut National de la Statistique et des Etudes Economiques (INSEE) and from the French Securite Sociale statistics. RESULTS: In 1996-99, 2178 cases of occupational asthma were reported to the ONAP, giving a mean annual rate of 24/million. Rates in men were higher than rates in women (27/million versus 19/million). The highest rate was observed in the 15-29 years age group (30/million). The most frequently incriminated agents were flour (20.3%), isocyanates (14.1%), latex (7.2%), aldehyde (5.9%), persulphate salts (5.8%), and wood dusts (3.7%). The highest risks of occupational asthma were found in bakers and pastry makers (683/million), car painters (326/million), hairdressers (308/million), and wood workers (218/million). CONCLUSION: Despite likely underreporting, the number of cases of occupational asthma reported to the ONAP was approximately twice the number of compensated cases over the same period. The relevance of the programme is confirmed by the reproducibility of the results year after year, and its consistency with other surveillance programmes. The ONAP programme is useful for the identification of targets for primary prevention.

[Asthma from tropical abachi wood]. / L'asthme au bois d'abachi.

We report the case of a 28-year old man suffering from rhinitis and asthma which appeared 8 years after exposure to different woods, especially abachi wood. Serial PEFR monitoring at work and away from work were consistent with occupational asthma. Spirometry showed an airway obstruction, and metacholine inhalation test was positive. Skin prick-tests performed with different woods were only positive to abachi wood extract. The search for specific IgE was positive to abachi wood (4, 98 KU/l, class 3). The diagnosis of occupational asthma caused by exposure to abachi wood was established, the mechanism underlying this asthma was IgE mediated. Despite respiratory protection measures, the patient had persisting symptoms and was laid off. The German service for social cover asked for an expert evaluation: specific nasal and inhalation provocation tests performed by exposure to fine abachi wood dust were positive. This is an observation with a double significance: first, although the mechanisms underlying wood occupational asthma remain largely unknown, an IgE mechanism for abachi wood was demonstrated; second, legislation is different in France and Germany where occupational asthma will only be acknowledged if inhalation tests are positive.

Occupational asthma in France: a 1-yr report of the observatoire National de Asthmes Professionnels project.

Observatoire National des Asthmes Professionnels (ONAP) was created in 1996 by two French professional societies to estimate the incidence of occupational asthma and to promote preventive measures against it. Occupational and chest physicians were asked to report newly diagnosed cases of work-related asthma and reactive airway dysfunction syndrome (RADS), the information collected included age, sex, occupation, suspected causal agents and diagnostic methods. In 1997, 82.3% of 559 cases reported (64% males, mean age 36 +/- 13 yrs) involved occupational asthma, 4.7% RADS and 12.7% atypical asthma syndromes. Incidence rates (expressed as number of cases per million workers) showed a regional variation that ranged from 4 to 73 (national mean: 25.7). The most frequently suspected agents were flour (23.3%), followed by isocyanates (16.6%), latex (7.5%), aldehydes (5.5%), and persulphates (4.1%). Occupations at risk were bakers (23.9%), healthcare workers (12%), painters (9.1%), hairdressers (5.2%), wood industry workers (4.8%) and cleaners (3.5%). These results are compared to those of other systems set up in Europe and North America. Because of the considerable bias inherent in a surveillance system based on voluntary, reporting, the number of occupational asthma cases reported is probably lower than the real incidence. Nevertheless, the French National Observatory for Occupational Asthma encourages physician awareness of occupational asthma and provides an estimate of its incidence and aetiologies in France.

Quaternary ammonium compounds and occupational asthma.

OBJECTIVE: Quaternary ammonium compounds, among which benzalkonium chloride is one of the best-known, are commonly used as antiseptics, disinfectants, detergents and preservatives. They can cause occupational asthma, which however, has been rarely reported so far, despite wide use of these products. We report three such cases. Possible mechanisms causing asthma are discussed, taking into account their characteristics. METHODS AND RESULTS: Our patients, all female nurses, manifested asthma symptoms upon handling disinfectant solutions containing benzalkonium chloride. Work-related fall in PEFR was observed in all of them. The diagnosis was confirmed by challenge tests where the patients were exposed, in a closed chamber, to suspected disinfectant contained in a tray. All of the women developed early or delayed symptoms upon exposure. Similar challenge tests to placebo or other disinfectants devoid of quaternary ammonium compound were negative. CONCLUSION: These three cases, in addition to others reported in the literature, point out an as yet poorly known etiology of occupational asthma to quaternary ammonium compounds in hospital employees. The exact mechanism of the action remains unexplained.

[Occupational asthma caused by a coloring reagent]. / Asthme et rhinite professionnels à un colorant réactif.

A case of occupational asthma associated with rhinitis and conjunctivitis occurred in a patient working in a textile factory and exposed to different coloring reagents is reported. Symptoms appeared in phases correlated with changes in the use of the coloring reagents. Prick tests were carried out with the different coloring reagents and were positive for the yellow color. The test was followed by a clear increase in bronchial hyperreactivity to methacholine. Some individual preventive measures, such as wearing a face mask, led to reduction then disappearence of the symptoms.

Increase in non-specific bronchial hyperresponsiveness without specific response to isocyanate in isocyanate-induced asthma: a pilot study.

Increased non-specific bronchial hyperresponsiveness (BHR) has been reported after positive reaction to isocyanates in patients with isocyanate-sensitive asthma. The increased responsiveness may, however, also precede the asthma attack. We therefore compared non-specific BHR to a cholinergic agent before and after exposure to toluene-diisocyanate (TDI) that induced no asthma symptoms in 11 workers with isocyanate-related asthma. Patients were exposed for 3 consecutive days to progressively increasing doses of TDI (5, 10, and 20 ppb min-1 for 20 min) in an exposure chamber with continuous TDI monitoring. No immediate nor late asthmatic bronchial reaction was observed in any patient after any dose of TDI during or after challenge. A significant increase in non-specific BHR was noted 24 h after the last dose of TDI challenge, however. This increase was at least one doubling dose for seven of 11 patients. In conclusion, our study shows that, in patients with isocyanate-induced asthma, exposure to TDI induces a slight but significant increase in non-specific BHR in the absence of any immediate or late bronchial response to isocyanate. This result, which requires further confirmation, may justify a proposal to measure non-specific BHR, even after a negative specific inhalation test to TDI, as an additional diagnostic element for TDI-induced occupational asthma, to help lower the percentage of the undetected occupational asthma cases.

Lung auscultation in airway challenge testing.

The appearance of wheezes and changes in inspiratory breath (vesicular) sound intensity (BSI) were monitored in patients undergoing routine methacholine challenge test (MCT). The results were compared with changes in spirometry and to airway hyper-responsiveness (AH). Fifty-four patients were examined. Spirometry was performed before and after the inhalation of cumulative doses of methacholine starting from 25 micrograms; a fall in forced expiratory volume in 1 s (FEV1) by 20% or more was considered as significant. Lung auscultation was performed by two observers simultaneously using a special stethoscope placed sequentially over the posterior right and left upper (interscapular region, 5 cm from the fourth thoracic vertebra) and lower lung zones (5 cm below the scapulae). Symptoms were recorded by the patients on a visual analogue scale. In 27 patients, the MCT was positive (MCT+) and in 27 patients it was negative (MCT-). Wheezes were identified at PD20 in 12 MCT+ patients while reduced BSI alone was found in 11 patients; in four patients, auscultation was normal. In 20 MCT+ patients, either wheezes, diminished BSI or both were heard, one to several steps before reaching PD20. In the MCT- group, wheezes were detected in two patients and diminished BSI in four. In MCT+ patients, the mean (+/-SD) perception of symptoms at end-challenge was 33% (+/-26), whereas in MCT- patients, it was 13.6% (+/-22). Complete inter-observer agreement was found in 95.7% of auscultations performed (Kappa coefficient = 0.846). Coupled to spirometry, lung auscultation may prove useful in airway challenge testing provided the concept is accepted that wheeze appearance and, by extension, an acute decrease in BSI, is as legitimate a manifestation of AH as a fall in FEV1.

[Is the bronchial provocation test justified in occupational respiratory disease?]. / L'épreuve de provocation bronchique est-elle justifiée en pathologie respiratoire professionnelle?

Specific bronchial provocation tests can confirm the diagnosis of occupational respiratory disease and also identify the causal agent of occupational asthma. The changes in French regulations established in 1993 which allow other agents to be recognized as causal in compensation for occupational diseases has increased interest in these tests. The different diagnostic methods used for occupational asthma are discussed here with special emphasis on limitations in each case: history taking, immunological investigations, respiratory function tests, measurement of peak flow during occupational activity and holidays, sequential measurements of non-specific bronchial hyperreactivity. The difficulty in standardizing specific provocation tests used for occupational asthma is related to the wide variety of causal agents which can be inhaled as gas, aerosols or powders. Because of the required precautions, these tests must be performed by specialized personnel in hospital units. There are also limitations to specific provocation tests. False positives require placebo tests and false negatives may result from insufficient identification of the causal agent. Exposure time may be too short or concentrations too low, and may depend on how long the causal agent has been evicted. Specific provocation tests may be avoided when the clinical history reveals a typical situation due to an agent known to cause occupational asthma and repeated peak flow measurements at the working site and/or immunological sensitisation tests provide objective evidence. But in a certain number of cases, specific investigations are required to obtain the precise etiological diagnosis required to evict the allergen rapidly and avoid chronic asthma.

[Occupational asthma: medical and social prognosis]. / Asthme professionnel: pronostic médical et social.

The medical and social prognosis of occupational asthma has only been assessed with retrospective studies. The main findings are analyzed here. The wide range of methods used to obtain a positive diagnosis of occupational asthma and more or less complete eviction of the causal agent hinder interpretation of the results. Nevertheless, the findings reported in 15 studies focusing on the medical prognosis have shown that in 70% of the cases, occupational asthma remains symptomatic after eviction. The number of years the asthma existed at diagnosis is higher in subjects who remain symptomatic after eviction. In most patients with occupational asthma, the absence of eviction leads to accentuation of the obstructive syndrome and non-specific bronchial hyperreactivity. When the occupational disease has been recognized, the social-professional consequences unfortunately often include loss of employment and lower revenue.

[Study by questionnaire of the influence of weather conditions, particularly fog, on the symptomatology of asthmatic subjects]. / Etude par questionnaire de i'influence des conditions météorologiques, en particulier du brouillard sur la symptomatologie des sujets asthmatiques.

The role of fog in the symptomatology in asthmatic subjects has been assessed by a questionnaire concerning respiratory complaints linked to meteorological conditions and to non-specific irritant factors. In a population of 121 asthmatics (59 men and 62 women) 74.4% complained that fog was a factor aggravating their symptoms while only 3% of a group of 30 non-asthmatic subjects expressed discomfort during episodes of fog. The chemical analysis of fog during 32 episodes of local fog (pH, chloride, nitrate, sulphate, sodium, ammonia, potassium, magnesium, calcium) has shown a greater concentration of pollutants and greater acidity in the smaller particles (2-6 microns) which are able to penetrate the bronchial tree. This acidity could explain the role of fog in respiratory physiology. Certain authors have suggested that the aggravation of respiratory symptoms observed during peaks of pollution could be induced by aerosols containing sulphuric acid while others have described effects on respiratory function at the time of exposure to acid aerosols in asthmatic subjects but the results of the different studies have not all been concordant. Putting aside the role of the susceptible individual, other factors may intervene at the time inhalation of pollutants, notably the ambient humidity, the neutralising effect of endogenous ammonia and the synergystic effect between acid aerosols and atmospheric pollutants.

Breath sound intensity in patients with airway provocation challenge test positive by spirometry but negative for wheezing: a preliminary report.

Wheeze detection has been proposed as an indicator of bronchial responsiveness during airway provocation challenge (APC) test. However, there is evidence that wheeze may be occasionally absent in subjects whose APC is positive by spirometry. We tested the hypothesis that, in this case, inspiratory breath sound intensity (BSI) over the chest is noticeably decreased. Six patients (3 asthmatics and 3 patients with atopic rhinitis) were selected, whose forced expiratory volume in 1 s (FEV1) fell by 20% or more at the end point of the challenge in the absence of concurrent wheezing. Lung sounds were recorded at the right posterior lung base and analysed by computer. Inspiratory BSI at the end point of the challenge was markedly decreased in all patients, a change almost completely reverted by the inhalation of 200 micrograms of salbutamol in all of them but one. These results support the view that BSI monitoring is potentially useful as an indicator of bronchoconstriction during bronchial provocation testing. However, further studies are necessary to confirm this hypothesis.

[The pertinence of bronchial provocation tests to allergens]. / Pertinence des tests bronchiques à l'allergène.

The contribution and the relevance of bronchial provocation tests to allergens have been evaluated in the realm of clinical research and in the diagnosis of the aetiology of asthma. These tests enable the recognition or to confirm the role of certain allergens in asthma, as well as to study the delayed reaction which occurs in some cases after the inhalation of an allergen as well as the relations existing between HRBNS and bronchial provocation tests to allergens. They also can show the preventative action of certain drugs on the immediate and/or delayed reaction induced by allergens. The methodology of bronchial provocation tests to allergens, notably their variability and their reproductibility, as well as the initial and maximal inhaled doses that can be realistically used, are discussed. The final point touched upon concerns the justification of bronchial provocation tests to allergens in the aetiological diagnosis of asthma. The indications of these tests have been restricted, they seen nonetheless always to be of interest in cases of discordance with the clinical history, cutaneous tests and/or measures of specific serum IgE.

Protective effect of nedocromil sodium on the dual asthmatic response to bronchial antigen challenge.

The effects of nedocromil sodium and placebo on the asthmatic response to antigen bronchial provocation were studied in a double-blind, randomized, crossover trial. Twelve subjects sensitized to Dermatophagoides pteronyssinus were challenged with successive doubling doses of this allergen (1.25-80 x 10(-3) mg) on two separate occasions, at least 15 days apart. A single dose of either nedocromil sodium 4 mg, or, a matching placebo was given 30 min before challenge. Forced expiratory volume in 1 s (FEV1) was measured 5, 10 and 15 min after challenge. Early asthmatic response was analyzed using three indices: dose producing a 20% decrease in FEV1 (PD20), the slope of and area under the dose-response curve. Nedocromil sodium was significantly superior to placebo with respect to all three indices, providing significant inhibition of the early asthmatic responses. Seven of the 12 patients showed a late asthmatic response. There was no significant difference between the effects of nedocromil sodium and placebo treatments on the decline in peak expiratory flow rate (PEFR) during the late asthmatic response but it should be noted that when patients had been treated with nedocromil sodium they were receiving two to eight times the dose of allergen given after placebo treatment.

[Occupational asthma caused by ebony wood]. / Asthme professionnel au bois d'ébène.

A case of occupational asthma to ebony wood dust is described in a violin and stringed instrument maker, who was sanding and filing ebony to make the finger boards of violins and cellos. The diagnosis was confirmed using a realistic provocation test; after sanding and smoothing the ebony for 20 minutes the patient developed bronchial spasm with fall of the force expired volume in one second (VMS) of 45% which was reversible following the inhalation of beta 2 agonists. A delayed reaction was seen at 3 hours and 6 hours and at 20 hours after the test. The observations of occupational asthma or rhinitis to ebony wood are very rare. To our knowledge there are two publications at the present time. It has been recognised as an occupational disease (see table 47 of occupational diseases) and an exclusion order has been effected.

[Specific provocation tests]. / Les tests de provocation spécifiques.

The authors describe the methodology of allergen challenge tests, with special attention to some particular aspects, such as the allergenic extracts and their biological activity, and the methods used in aerosol administration and in measurements of bronchial obstruction. They present the results of their personal experience, concerning interindividual variations in a sensitized population and the reproducibility of the immediate reaction revealed by dose-response curves. Comparisons of allergen tests with exposure to allergens under physiological conditions are discussed. In occupational asthma the exposure tests sometimes constitute the only diagnostic method, owing to ignorance of the responsible mechanisms and to the multiplicity of incriminated substances. However, these tests are not without danger and must be performed by well-trained medical and paramedical teams.