Olivier Vandenplas

Health and socioeconomic impact of work-related asthma

There is accumulating evidence that the workplace environment contributes significantly to the general burden of asthma. The purpose of this review is to explore the respiratory health and socioeconomic consequences of work-related asthma by addressing a series of controversial issues: 1) what is the natural history of occupational asthma and in what ways does ongoing exposure to the causal agent impact clinical outcomes?; 2) how does the natural history of irritant-induced asthma differ in its health outcomes from immunologically-mediated occupational asthma?; 3) do working conditions have a significant impact on asthma regardless of the aetiology of the disease?; 4) what is the scope of work disability from work-related-asthma in social and economic terms?; 5) what is the clinicians role in reducing the respiratory health consequences of work-related asthma? 6) to what extent do existing compensation and other social insurance schemes successfully address occupational asthma and work-aggravated asthma?

Occupational asthma and extrinsic alveolitis due to isocyanates: current status and perspectives

Isocyanates are used for the large scale production of polyurethane polymers, which have an almost endless variety of applications in the manufacture of flexible and rigid foams, elastomers, adhesives, and surface coatings.1 Acute or chronic exposure to high concentrations of isocyanates can result in res piratory health hazards through a direct irritant effect.23 Isocyanates are of special interest, how ever, because, in some exposed workers, they can cause occupational asthma or extrinsic alveolitis through an apparently sensitising mechanism.23 Because of their wide industrial use, isocyanates are the principal cause of occupational asthma which is now the most common respiratory disease linked to the working environment.4 5 This review focuses on recently studied aspects of occupational asthma and extrinsic alveolitis related to exposure to iso cyanates.

Inhalation challenges with agents causing occupational asthma

Occupational asthma (OA) is steadily emerging as the principal cause of respiratory disease due to the workplace environment. One of the key means to ascertain diagnosis of OA is specific inhalation challenge (SIC) with occupational agents. This review: 1) describes the methodology of SIC, with a special emphasis on procedures aimed at increasing the safety and validity of these tests; and 2) outlines the roles of SIC in the diagnosis of OA in clinical and medicolegal assessment, epidemiological studies, surveillance programmes and the investigation of the pathophysiological mechanisms of asthma and OA. We discuss areas of future development, including the development of apparatus which allows exposure of subjects to low and stable concentrations of the occupational agent and the assessment of preventive procedures.

An Official American Thoracic Society Statement: Work-Exacerbated Asthma

RATIONALE Occupational exposures can contribute to the exacerbation as well as the onset of asthma. However, work-exacerbated asthma (WEA) has received less attention than occupational asthma (OA) that is caused by work. OBJECTIVES The purpose of this Statement is to summarize current knowledge about the descriptive epidemiology, clinical characteristics, and management and treatment of WEA; propose a case definition for WEA; and discuss needs for prevention and research. METHODS Information about WEA was identified primarily by systematic searches of the medical literature. Statements about prevention and research needs were reached by consensus. MEASUREMENTS AND MAIN RESULTS WEA is defined as the worsening of asthma due to conditions at work. WEA is common, with a median prevalence of 21.5% among adults with asthma. Different types of agents or conditions at work may exacerbate asthma. WEA cases with persistent work-related symptoms can have clinical characteristics (level of severity, medication needs) and adverse socioeconomic outcomes (unemployment, reduction in income) similar to those of OA cases. Compared with adults with asthma unrelated to work, WEA cases report more days with symptoms, seek more medical care, and have a lower quality of life. WEA should be considered in any patient with asthma that is getting worse or who has work-related symptoms. Management of WEA should focus on reducing work exposures and optimizing standard medical management, with a change in jobs only if these measures are not successful. CONCLUSIONS WEA is a common and underrecognized adverse outcome resulting from conditions at work. Additional research is needed to improve the understanding of the risk factors for, and mechanisms and outcomes of, WEA, and to inform and evaluate preventive interventions.

Definitions and types of work-related asthma: a nosological approach

The workplace can trigger or induce asthma and cause the onset of different types of work-related asthma. Analysis of previous definitions of occupational asthma (OA) led to the conclusion that evidence of a direct causal relationship between workplace exposure and the development of asthma remains the key element for defining OA. Based on clinical features and pathophysiological mechanisms, the following conditions should be distinguished in the spectrum of work-related asthma: 1) immunological OA characterised by a latency period necessary to acquire immunologically induced sensitisation; 2) nonimmunological OA characterised by the rapid onset of asthma following single or multiple exposures to high concentrations of irritant compounds; 3) work-related asthma defined by exacerbation of symptoms in workers with pre-existing or coincident asthma; and 4) variant syndromes including eosinophilic bronchitis, potroom asthma, and asthma-like disorders caused by organic dusts. The issues and controversies relating to this approach are critically reviewed in order to stimulate the consensus development of operational definitions of work-related asthma.

Socioeconomic outcome of subjects experiencing asthma symptoms at work.

The aim of this study was to investigate the socioeconomic outcomes of subjects who experienced workrelated asthma symptoms in the absence of demonstrable occupational asthma (OA) and to compare these outcomes with those found in subjects with documented OA. Subjects (n=157) who were being investigated for workrelated asthma, were surveyed. Of these 86 had OA, ascertained by a positive specific inhalation challenge (SIC), and 71 subjects had a negative SIC response. After a median interval of 43 months (range 12–85 months), the subjects were interviewed to collect information on employment status, income changes, and asthmarelated work disability. Rates of work disruption and income loss at followup were similar in subjects with negative SIC (46% and 59%, respectively) and in those with OA (38% and 62%). The median loss as a percentage of initial income was 23% in subjects with negative SIC and 22% in subjects with OA. Asthmarelated work disability, defined as any job change or work loss due to asthma, was slightly more common in subjects with OA (72%) than in those with negative SIC (54%). This study shows that, even in the absence of demonstrable occupational asthma, workrelated asthma symptoms are associated with considerable socioeconomic consequences.

Guidelines for the management of work-related asthma

Work-related asthma, which includes occupational asthma and work-aggravated asthma, has become one of the most prevalent occupational lung diseases. These guidelines aim to upgrade occupational health standards, contribute importantly to transnational legal harmonisation and reduce the high socio-economic burden caused by this disorder. A systematic literature search related to five key questions was performed: diagnostics; risk factors; outcome of management options; medical screening and surveillance; controlling exposure for primary prevention. Each of the 1,329 retrieved papers was reviewed by two experts, followed by Scottish Intercollegiate Guidelines Network grading, and formulation of statements graded according to the Royal College of General Practitioners’ three-star system. Recommendations were made on the basis of the evidence-based statements, which comprise the following major evidence-based strategic points. 1) A comprehensive diagnostic approach considering the individual specific aspects is recommended. 2) Early recognition and diagnosis is necessary for timely and appropriate preventative measures. 3) A stratified medical screening strategy and surveillance programme should be applied to at-risk workers. 4) Whenever possible, removing exposure to the causative agent should be achieved, as it leads to the best health outcome. If this is not possible, reduction is the second best option, whereas respirators are of limited value. 5) Exposure elimination should be the preferred primary prevention approach.

What are the questionnaire items most useful in identifying subjects with occupational asthma

The present study assessed the usefulness of key items obtained from a clinical “open” questionnaire prospectively administered to 212 subjects, referred to four tertiary-care hospitals for predicting the diagnosis of occupational asthma (OA). Of these subjects, 72 (34%) were diagnosed as OA (53% with OA due to high-molecular-weight agents) according to results of specific inhalation challenges, and 90 (42%) as non-OA. Wheezing at work occurred in 88% of subjects with OA and was the most specific symptom (85%). Nasal and eye symptoms were commonly associated symptoms. Wheezing, nasal and ocular itching at work were positively, and loss of voice negatively associated with the presence of OA in the case of high-, but not low molecular-weight agents. A prediction model based on responses to nasal itching, daily symptoms over the week at work, nasal secretions, absence of loss of voice, wheezing, and sputum, correctly predicted 156 out of 212 (74%) subjects according to the presence or absence of OA by final diagnosis. In conclusion, key items, i.e. wheezing, nasal and ocular itching and loss of voice, are satisfactorily associated with the presence of occupational asthma in subjects exposed to high-molecular-weight agents. Therefore, these should be addressed with high priority by physicians. However, no questionnaire-derived item is helpful in subjects exposed to low-molecular-weight agents.

Pathogenesis of occupational asthma

The development of occupational asthma (OA) is likely to result from the complex interaction of environmental and host factors. This article addresses a series of issues relating to the multiple environmental factors that could affect the initiation of OA, including the intrinsic characteristics of causative agents, as well as the influence of the level, mode and route of exposure. Although the clinical and pathological features of OA caused by low molecular weight agents resemble those of immunoglobulin (Ig)E-mediated asthma, the failure to detect specific IgE antibodies against most of these agents and/or poor association with disease status have resulted in intense speculation about alternative or complementary physiopathological mechanisms leading to airway sensitisation. In this contribution, the roles of specific immunoglobulin E and G antibodies, cell-mediated immunity and inflammatory effector cells are critically reviewed. Recent advances in the characterisation of the molecular interactions between chemical sensitisers and human airway proteins provide promising avenues for elucidating the immunological basis of occupational asthma caused by low molecular weight agents.

Prepolymers of hexamethylene diisocyanate as a cause of occupational asthma

BACKGROUND Occupational asthma (OA) caused by products that contain hexamethylene diisocyanate (HDI) has been ascribed to the highly volatile monomer of HDI. Most two-component paints are now made up primarily of nonvolatile prepolymers of HDI (30% to 60%) with only trace amounts (< 0.1%) of the monomer. The respective role of the two chemical forms of HDI in causing OA has never been investigated. METHODS Twenty workers who were consecutively referred for possible OA that resulted from exposure to spray paints underwent inhalation challenges on separate days with pure HDI monomer and the commercial formulation of HDI prepolymers to which they had been exposed at work. RESULTS Specific inhalation challenges elicited a positive asthmatic reaction in 10 of the 20 subjects. Among these subjects, four had positive bronchial reactions (two early, one late, and one dual) to both the monomer and the prepolymers. Four other subjects had asthmatic reactions (two early, one late, and one dual) after exposure to the prepolymers but not after exposure to the monomer. The discordance in bronchial response elicited by the monomer and the prepolymers could not be due to differences in the level of baseline nonspecific bronchial reactivity or in HDI concentrations during the tests. One subject showed an atypical progressive reaction after exposure to the monomer but not after exposure to the prepolymer. In this case, the discordant response could be explained by differences in HDI concentration. CONCLUSION These observations show that, although they are nonvolatile, the prepolymers of HDI can induce OA and that asthmatic reactions as a result of exposure to prepolymers but not the monomer is not a rare occurrence.