Occupational asthma: a practical approach.

Although evaluation of possible occupational asthma may be complex, it can be pursued systematically by first assessing whether asthma is present, and then determining whether asthma is caused or triggered by the workplace or by alternative or confounding nonoccupational explanations. A detailed history is of great importance in raising suspicion of occupational asthma, but studies have shown that even detailed histories obtained by experienced specialists can lead to inaccurate conclusions about the presence or absence of occupational asthma. Consequently, objective measurements should be performed to establish the diagnosis of occupational asthma whenever possible. If the patient is still working in the workplace, work-related changes in spirometry or peak flow measurements can confirm the diagnosis. For occupational asthma from some airborne sensitizers, immediate-type skin testing or in vitro tests for specific IgE may establish sensitization. However, there is evidence that for some isocyanates, in vitro tests for specific IgG serum antibody levels correlate better with documented bronchospasm from isocyanate exposure, even though the IgG antibody is not thought to be pathogenic. Controlled, specific inhalation tests may be valuable, but they should be performed only under experienced medical supervision. Intervention should be focused on reducing or avoiding harmful workplace exposures so that permanent lung impairment and need for chronic medical treatment are avoided. Assessment of permanent impairment/disability from occupational asthma optimally should be determined 2 years after the removal from occupational exposure, when improvement has been shown to plateau and the patient will likely have reached maximal medical improvement.     

Diagnosis of Occupational Asthma: An Update

Work-related asthma (WRA) includes patients with sensitizer- and/or irritant-induced asthma in the workplace, as well as patients with preexisting asthma that is worsened by work factors. WRA is underdiagnosed; thus, the diagnosis is critical to prevent disease progression and its potential for morbidity and mortality. The interview is the first diagnostic tool to be used by physicians, and the question, “Does asthma improve away from work?” is of the highest sensitivity. However, history can show numerous false positives, and the relationships between asthma worsening and work should be confirmed by objective methods such as peak expiratory flow (PEF) at and away from work. PEF sensitivity and specificity can be enhanced in combination with nonspecific bronchial hyperresponsiveness to histamine/methacholine (NSBP) before and after 2 weeks at work and a similar period off work. Immunologic testing, especially skin prick test (SPT) or specific IgE, is useful for high molecular weight allergens and some low molecular weight agents. Other immunologic tests, as well as induced sputum, measurement of exhaled nitric oxide, exhaled breath condensate, and specific inhalation challenge (SIC) are methods that contribute to the diagnosis and are typically performed at specialized facilities. A diagnosis of occupational asthma (OA) should no longer be based on a compatible history only but should be confirmed by means of objective testing. SIC is the diagnostic gold standard. When SIC is not available, the combination of PEF measurement, NSBP test , a specific SPT, or specific IgE may be an appropriate alternative in diagnosing OA.     

Asthma from inhalation of Triplochiton scleroxylon (Samba) wood dust.

The inhalation of wood dust may produce allergic rhinitis, asthma, or contact dermatitis in sensitized patients. We describe a patient with occupational asthma induced by the inhalation of samba (Triplochiton scleroxylon) wood dust. A specific bronchial provocation test was conducted, and the patient showed a significant decrease in forced-expiratory volume in first second (FEV1) after the inhalation of nebulized samba wood allergens. We suggest an IgE-mediated mechanism since the patient had a positive skin test and positive specific IgE determinations using an extract of samba wood. SDS-PAGE immunoblots revealed IgE binding to proteins with molecular weights of 17 kDa, 28 kDa and less intense binding to a band with an approximate molecular weight of 60 kDa. Two asymptomatic skin test-negative subjects, also occupationally exposed to samba, did not show any signs of bronchoconstriction when challenged with the samba wood extracts. We conclude that the occupational asthma suffered by this patient is related to sensitization and occupational exposure to samba wood dust.     

Advances in methods used in evaluation of occupational asthma

PURPOSE OF REVIEW: Diagnosing occupational asthma (OA) is a complex undertaking, the primary goal of which is to demonstrate a causal relation between exposure to a specific agent encountered at work and asthmatic responses. Recent development or refinement of diagnostic tools may improve the diagnostic accuracy, which may have important economic and social consequences for both employers and workers. RECENT FINDINGS: Although specific inhalation challenge (SIC) testing is the gold standard for diagnosis of OA, these tests are not widely available in many countries. Thus, new less invasive techniques used in the measurement of airway inflammation, such as exhaled nitric oxide and induced sputum are highlighted as are recent developments in both in vivo and in vitro immunologic testing. SUMMARY: Although new perspectives are being evaluated, the diagnosis of occupational asthma still relies mostly on specific inhalation challenge. Further studies are required to confirm the utility of these new techniques in the diagnosis of OA.     

Inhalation challenge with bovine dander allergens: who needs it?

STUDY OBJECTIVES: To identify which tests would be useful in selecting patients for a specific inhalation challenge with bovine dander allergens (bSIC). DESIGN: A prospective study. SETTING: A university hospital. PATIENTS: Thirty-seven dairy farmers with a clinical suspicion of occupational asthma due to bovine allergens. INTERVENTIONS: Each patient (n = 27) underwent histamine challenge, mannitol challenge, exhaled nitric oxide (NO) measurement, bovine-specific serum IgE measurement, and skin-prick test (SPT) with bovine allergens prior to undergoing a bSIC. RESULTS: Eleven patients responded to the inhalation challenge with bovine allergens. The sensitivity and specificity of the tests, based on this response, were 82% and 65%, respectively, for the histamine challenge; 20% and 94%, respectively, for the mannitol challenge; 27% and 77%, respectively, for the NO measurement; 82% and 100%, respectively, for the bovine-specific serum IgE measurement; and 100% and 50%, respectively, for the SPT. Multiple regression analysis revealed that only IgE-mediated sensitivity to bovine allergens, but neither bronchial hyperreactivity nor exhaled NO concentration, contributed significantly to the response. CONCLUSION: Only the SPT with bovine allergens and bovine-specific serum IgE measurements were useful in selecting patients for the bSIC. This challenge should not be performed in SPT-negative subjects. A diagnosis of occupational asthma due to bovine dander allergens could be made without an inhalation challenge test in asthmatic patients with high bovine-specific serum IgE levels. This practice would eliminate the need for the majority of bSICs.     

Occupational asthma related to mouse allergen exposure and rhinoconjunctivitis due to collagenase inhalation in a laboratory technician

We describe the case of a 27-year-old patient working in a research laboratory, who developed occupational asthma to mouse proteins and presented symptoms of rhinoconjunctivitis caused by manipulation of collagenase. Specific inhalation challenge confirmed the diagnosis of occupational asthma to mouse proteins, whereas specific challenge with collagenase only evoked symptoms of rhinitis and conjunctivitis. SDS-PAGE and Western blot analysis for collagenase showed that the patient's IgE antibodies bound specifically to a protein with a molecular weight of 92 kDa. Hence, this was an unusual case of double sensitization. The sensitization to collagenase presented in this report may represent a new occupational disease in technicians working in medical or research laboratories.     

Bronchial asthma due to sensitization to chloramine T.

Chloramine T, an organic, highly reactive derivative of chlorine with potent bactericidal properties, is used as a disinfectant in the food industry. Described as an occupational sensitizer in 1945 for the first time, it produces late or dual asthma, occasionally accompanied by fever and leukocytosis, which is mediated by IgE. We present the case of a male dairy worker who, after 4 years of exposure to the product, developed rhinitis and asthma. Skin tests with chloramine T were positive at a concentration of 10 mg/ml, while all other allergens tested negative. RAST detected specific IgE at 12 PRU and bronchial provocation induced immediate and late bronchoconstriction.     

Evaluation of occupational asthma from airborne egg protein exposure in multiple settings

We previously reported IgE-mediated occupational asthma among workers exposed to airborne egg protein at a plant that produces liquid and dried powdered egg products. To demonstrate that our original observations are generalizable to other facilities that process eggs, and to estimate the prevalence of IgE-mediated occupational asthma among egg-exposed workers, we conducted surveys at two additional plants. We administered a questionnaire to 188 employees to identify workers with symptoms suggestive of occupational asthma. We further evaluated 88 workers with and without symptoms by a clinical examination by a physician blinded to results of other tests, serial peak expiratory flow rate (PEFR) determinations every three hours while awake for one week, and skin prick tests and serum specific IgE levels to extracts of factory egg products, commercial egg test reagents, and egg white protein fractions. Fourteen workers had work-related asthmalike symptoms by questionnaire, a physician diagnosis of occupational asthma, and evidence of IgE-mediated sensitization to one or more egg proteins. Workers exposed exclusively to liquid egg aerosol, as well as workers exposed primarily to dried airborne egg protein, developed occupational asthma. This study replicated our original observations and demonstrated that workers in all areas of liquid and powdered egg production are at risk of developing occupational asthma from exposure to airborne egg proteins.     

Occupational asthma caused by Ipe (Tabebuia spp) dust.

BACKGROUND: Ipe is a resistant hardwood that contains naphtoquinones. It is easily found and frequently used in South and Central America. Naphtoquinones are skin sensitizers. OBJECTIVE: To describe a case of occupational asthma related to Ipe wood dust. METHODS: The patient was submitted to a clinical evaluation consisting of a respiratory symptom questionnaire, occupational history, serial measurements of lung function by spirometry, skin prick tests, patch tests, specific IgE and specific bronchial provocation tests to Ipe dust. RESULTS: Serial lung function measurements showed sustained regression of obstruction following removal from exposure. Skin prick tests, but not patch tests, were positive to Ipe, and a specific bronchial challenge showed a late asthmatic reaction. Specific IgE search was negative. CONCLUSIONS: Exposure to Ipe wood dust can lead to occupational asthma. The underlying mechanism should be investigated.     

Sensitivity of the skin prick test and specificity of the serum-specific IgE test for airway responsiveness to house dust mites in asthma.

BACKGROUND: The concept that asthma diagnosis based on allergen-specific IgE levels in serum is more accurate than diagnosis based on skin test reactivity is controversial. OBJECTIVE: To determine the atopy parameter that correlates most closely with airway reactivity to house dust mites in asthma. METHODS: Forty-three asthma cases were examined retrospectively for data on Dermatophagoides farinae-specific bronchoprovocation, serum-specific IgE, and skin prick tests. RESULTS: The maximal decreases in FEV1 following bronchoprovocation were correlated significantly with both the IgE levels and skin test scores. The accuracies of the tests were highest at a cutoff value of class 4 or higher for the IgE and of 3+ or higher for the skin test. At the cutoff values, the accuracies of both tests were similar (70% vs. 70%). The sensitivity of the skin test (81%) was higher than that of the IgE test (67%), whereas the specificity of the IgE test (71%) was higher than that of the skin test (52%). The sensitivity of the skin test was 91% at 2+ or higher, and the specificity of the IgE test was 95% at class 6 or higher. CONCLUSION: These results suggest that both the specific IgE level and the skin test reactivity are useful parameters in the prediction of positive airway responses to house dust mites in asthma. However, the skin test is more sensitive, whereas the IgE test is more specific. Therefore, these tests can be used in a complementary fashion (i.e., the skin test for screening and the specific IgE test for confirmation of the relevant allergen).     

Occupational asthma from natural rubber latex. Specific inhalation challenge test and evolution.

BACKGROUND: Natural rubber latex (NRL) is the most frequent cause of occupational respiratory problems in hospital workers. OBJECTIVE: To describe the diagnostic methodology, including the specific inhalation challenge (SIC), used on patients diagnosed as having occupational asthma due to NRL in our Allergy Department during a 6-year period from 1989 to 1995. METHODS: In 19 patients diagnosed as having occupational asthma due to NRL, clinical severity was assessed with a combined score for symptoms and medication use. Skin prick tests with aeroallergens, latex, papain, kiwi and chestnut, total IgE, serum-specific latex IgE, respiratory function study, methacholine test, specific conjunctival test, and SIC test with latex were done. RESULTS: All but three patients worked in hospitals. All presented urticaria and rhinoconjunctivitis, and six also suffered anaphylaxis, usually preceded by asthma. Clinical fruit allergy was present in eight patients. The latency period was variable (0.25-27 years). The intensity of symptoms was low to moderate. Specific IgE, skin prick, and conjunctival tests to latex were positive in all cases. SICs were done in 12 patients. All of them presented isolated immediate reactions. No adverse reactions were observed. Duration of follow-up ranged from 1 to 7 years. Twenty-six percent of the patients kept their job, 26% changed jobs but remained in health care, and 48% switched to jobs unrelated to health care. Only 16% were free of symptoms without treatment, while 32% needed bronchodilators and 52% needed inhaled steroids. The specific bronchial challenge test was safe, but it did not predict the course of the illness. Duration of exposure and intensity of symptoms did correlate with prognosis, however. CONCLUSIONS: NRL acts as a common aerollergen. Minor symptoms often precede occupational asthma. The SIC test was safe in the hands of trained technicians. Occupational asthma due to NRL seems to have a poor prognosis.     

Patterns of improvement in spirometry, bronchial hyperresponsiveness, and specific IgE antibody levels after cessation of exposure in occupational asthma caused by snow-crab processing

Thirty-one workers with occupational asthma caused by snow-crab processing were assessed by a long-term follow-up on three occasions at mean +/- SD intervals of 12.8 +/- 5.4, 31.4 +/- 6.3, and 64.4 +/- 6.3 months after leaving work. The diagnosis of work-related asthma was initially confirmed in all of them by specific inhalation challenges at the workplace or by laboratory inhalation of snow-crab boiling water (n = 24) or by serial monitoring of airway caliber and bronchial responsiveness to histamine at work and off work (n = 7). Total duration of work-related exposure was 12.8 +/- 5.6 months (range, 3 to 21 months), and the duration of symptoms after onset was 6.8 +/- 4.2 months (range, 1 to 18 months). At the time of diagnosis, all 31 subjects required medication for asthma, 11 had a FEV1 less than or equal to 85% predicted, and all subjects had a PC20 less than or equal to 16 mg/ml. Twelve of 25 serum samples assessed showed high levels of specific immunoglobulin E (IgE) antibodies to crab meat and/or boiling water. At the time of the first follow-up, there was a reduction in the number of subjects still requiring medication, with a significant reduction in FEV1, and a PC20 less than or equal to 16 mg/ml. However, no further change was observed afterwards. Similarly, the mean FEV1 and FEV1/FVC improved significantly from the time of diagnosis to the first follow-up (p less than 0.01), with a plateau thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Occupational rhinitis due to pepsin.

A woman presented work-related rhinoconjunctivitis due to inhalation of pepsin used in a slaughterhouse. Prick tests and conjunctival challenge were positive to pepsin. Serum specific IgE to pepsin was 5.58 kU/L and an IgE-binding band of 43 kDa was detected in SDS-PAGE Immunoblotting. Rhinoconjunctivitis improved clearly when the patient was assigned to another place without contact with pepsin. Pepsin has been previously reported to cause occupational allergic asthma on three occasions. As far as we know, this is the first reported case in which an IgE-immunoblot has been performed.     

A 38-year-old hairdresser with irritant-associated vocal cord dysfunction

The present case study reports the first case of a 38-year-old hairdresser with irritant-associated vocal cord dysfunction (VCD) due to alkaline persulfate, who was referred on suspicion of occupational asthma. Several tests were performed, including specific inhalation challenge and upper airway endoscopy. During the specific inhalation challenge to alkaline persulfate, the patient experienced dysphonia and a non-significant decrease in forced expiratory volume in 1 second on spirometry. Upper airway endoscopy was then performed and revealed VCD. A specific inhalation challenge test is therefore essential in cases of VCD to exclude possible concomitant occupational asthma.     

Diagnosing occupational asthma: how, how much, how far?

Diagnosing occupational asthma is still a challenge because it is based on a stepwise approach in which the depth of investigative means may vary depending on resources. The authors herewith review the existing investigative means from the approach of outlining controversies and queries. There is no validated clinical questionnaire for diagnosing occupational asthma. Immunological investigation is limited by the lack of standardised extracts for skin-prick testing and specific immunoglobulin E assessments. Criteria for interpretation of changes in peak expiratory flow rates and bronchial responsiveness to pharmacological agents are still open to discussion. It is worth improving the methodology of specific inhalation challenges, either in the laboratory or in the workplace, to facilitate more extensive use of these tests. Validation of new means that assess airway inflammation, such as exhaled nitric oxide and induced sputum, needs to be performed. There is a need to increase the use of these diagnostic tests because the diagnosis is still too often based on "clinical impression".     

Occupational asthma: validity of monitoring of peak expiratory flow rates and non-allergic bronchial responsiveness as compared to specific inhalation challenge.

The sensitivity and specificity of monitoring peak expiratory flow rates (PEFR) and bronchial responsiveness to the provocative concentration of histamine or methacholine (PC20) has been determined as compared to specific inhalation challenges in the diagnosis of occupational asthma. A prospective study of 61 subjects referred for occupational asthma to various agents was performed. PEFR was assessed every 2 h during a period away from work for at least 2 weeks. The period at work was 2 weeks, or less if there was increased symptomatology or marked changes in PEFR. At least one PC20 assessment was obtained at work and away from work. Graphs of PEFR and PC20 values were interpreted in blind fashion by three experienced readers. There was complete agreement among the three in 54 out of 61 instances (78%). Twenty five out of 61 subjects (41%) had positive specific inhalation challenges. The best index for comparing results of PEFR with specific inhalation challenges was the visual analysis of PEFR with sensitivity and specificity of 81% and 74%. All of the numerical indices were significantly less satisfactory. We conclude that visual analysis of PEFR is an interesting tool for investigating occupational asthma, although sensitivity and specificity values do not seem satisfactory enough to warrant using it alone.     

The diagnosis and management of occupational asthma

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.     

Occupational asthma in food packers

This report describes the case of a 26-year-old woman working in a fish-processing factory who developed bronchial asthma when transferred to the packing department. Various tests, including a specific bronchial challenge test, confirmed a diagnosis of occupational asthma. While polyvinyl chloride (PVC) appeared to be the causal agent in this case, the possible role of other etiological agents is also discussed. Although occupational asthma in food packers is rare, we nonetheless consider it important to recognize this type of asthma given the widespread use of PVC.     

Contact urticaria, rhinoconjunctivitis and bronchial asthma from occupational use of papain

Papain is a plant protein with a wide pharmacological, domestic and industrial use. It leads a high sensitisation, being the most common rotue of entry the inhalation. The occupational allergy to papain in exposed workers was described some years ago, being presented with bronchial asthma, rhinitis or both. In most of the cases, the specific IgE was positive. We present a case contact urticaria, rhinoconjunctivitis and bronchial asthma per papain of occupational origin. Papain prick test, specific IgE and nasal challenge were positive. The peak flow record showed diary decreases during the working week and the basal spirometry showed obstruction to the airflow. The patient was moved away the place where papain was handled and this resolved the clinical symptoms and the spirometry returns to the normal values. We present a case of IgE-mediated allergy, vehicled by tow routes: contact and airborne. The latest produced clinical manifestations later. Papain was used as Cephalopoda softening, because of that it worth emphasising its seasonal use.     

The "egg-egg" syndrome: occupational respiratory allergy to airborne egg proteins with consecutive ingestive egg allergy in the bakery and confectionery industry.

Allergies to various inhalative allergens are a serious problem in the bakery and confectionery industry. Sensitization to wheat flour and enzymes such as alpha-amylase are a frequent cause of occupational asthma. Airborne egg allergens have been reported as another cause of respiratory allergy. We examined bakery and confectionery workers with respiratory symptoms due to egg aerosols. Skin tests (SPT), scratch tests (ST), nasal provocation tests (NPT) and serological examinations (IgE) were performed. Lung function was assessed by spirometry, and continuous registration of aerosols and particulates as well as gravimetric sampling was done at the workplace. Four bakery and two confectionery workers intensively exposed to airborne egg proteins suffered from conjunctivitis and rhinitis, four also from asthma. Subsequently, three of these four workers reported symptoms after ingestion of food that contained egg. SPT with commercial egg white and egg yolk extracts were negative in four cases. Only two employees had clearly positive SPT to commercial egg allergens and reacted also to wheat flour extracts. Scratch tests with native egg proteins were positive in four employees. Specific IgE to egg white and egg yolk were positive (CAP > or = 2) in three and in four cases, respectively, whereas they were negative in two cases. Elevated levels of specific IgE to lysozyme were detected in four employees. Two workers were sensitized to lysozyme but not to other egg proteins. The clinical relevance of egg sensitization was confirmed by continuous air sampling and by correlating the onset of the respiratory symptoms which were reflected by a significant decline (> or = 30%) of the forced one second capacity (FEV1) in two workers. Sieving of egg white powder and an inadequate spray station for liquid eggs were identified as sources of excessive allergen exposure. Bakery and confectionery workers exposed to airborne egg proteins are at risk of developing occupational asthma and subsequent nutritive egg allergy. To our knowledge, these are the first cases of inhalative egg allergy and subsequent nutritive egg allergy reported in the literature, which we refer to as the "egg-egg syndrome" in analogy to the already known "bird-egg" and "egg-bird" syndromes.