Specific Inhalation Challenge Research Articles

Evaluation and Application of the Work-Related Asthma Screening Questionnaire—Long Version (WRASQ-L)

BackgroundThe Work-related Asthma (WRA) Screening Questionnaire (Long-Version)(WRASQ-L)TM is a screening questionnaire that could improve recognition of WRA. ObjectiveTo conduct a definitive evaluation of the WRASQ-LTM to justify its implementation in clinical settings. MethodsEmployed adults aged 18-75 years with asthma confirmed by objective measures and the ability to take time off work were eligible. Participants completed the WRASQ-LTM then monitored their peak expiratory flow at and away from work or completed a specific inhalation challenge test. Data were classified as WRA or non-WRA by two asthma specialists, blinded to WRASQ-LTM answers. Sensitivity (SN), specificity (SP), positive and negative predictive values (PPV and NPV, respectively) and Youden’s index were calculated for cut-offs of a positive screen. ResultsOf 106 participants (47.1±7.1 years (mean ± SD); 60 (57%) female), 14 (17%) were classified as WRA and were significantly younger in age than non-WRA participants (p=0.043). The questionnaire has high SN and NPV (90.9% and 93.1%, respectively), but low PPV and SP (32.1% and 26.0%, respectively). ConclusionsThe WRASQ-LTM has high SN and NPV. High SN is of primary interest to ensure that few false negative screens are missed and those with potential WRA are identified and continue to specialist care. The SN indicates utility of the questionnaire in clinical settings. Further benefits of the tool include its potential to prompt for education on the symptom-workplace relationship, workplace exposures, personal protective equipment use, and collect exposure and occupational history.

Der Nachweis beruflich verursachter Allergien ist ein komplexes Unterfangen: ein Fallbeispiel

The detection of occupational allergies is a complex undertaking: A case study According to the recommendations for the diagnosis of occupational asthma, suspected cases require a confirmed asthma diagnosis, work-associated symptoms, evidence of sensitization to an occupational allergen and a close relationship between the occupation and the symptoms. In addition to a detailed medical history, several examinations and tests and a differentiated consideration of them are required in order to arrive at a final expert assessment. We report the case of a 58-year-old butcher who had been complaining of shortness of breath and coughing at his workplace in a slaughterhouse for 5 years. It was only after extensive investigations and a detailed medical history that a powdered kebab spice used in an adjacent room was suspected as the potential allergen. Diagnostic tests showed that the patient was sensitized to the spice. While the specific inhalation challenge (SIC) with kebab spice did not elicit an asthmatic reaction, a non-specific bronchial hyperreactivity in the insured person was observed. On the day after the SIC, the bronchial hyperreactivity was increased by a factor of three and there were further indications of eosinophilic or allergic reaction. In summary, the individual diagnostic components led to the assessment of this case as allergic occupational asthma. This case illustrates that an assessment of the individual diagnostic components in the diagnosis of occupational asthma is quite complex and not without pitfalls. Keywords: occupational asthma – diagnosis – sensitization – bronchial hyperreactivity

Impact of Ongoing Treatment With Inhaled Corticosteroids During Specific Inhalation Challenges for Diagnosing Occupational Asthma

BackgroundSpecific inhalation challenge tests (SIC) are still the reference test for diagnosing sensitizer-induced occupational asthma (SIOA). The European Respiratory Society recommends the cessation of inhaled corticosteroids (ICS) 72h prior to SIC. ObjectiveTo assess the effect of an ongoing ICS treatment during SIC on the maximum fall in FEV1, change in methacholine PC20 as well as sputum eosinophil counts after exposure to the suspected agent. MethodsWe performed a retrospective analysis using a database of cases referred to our center for suspected SIOA from 1999 to 2022. The results of the SIC were compared between subjects treated with ICS during SIC and steroid-naïve subjects. ResultsSix-hundred and seventy-one individuals underwent SIC in the laboratory. Three hundred and eighteen were treated with ICS, whereas 353 were steroid naïve. The proportion of subjects with a positive SIC was greater among ICS treated subjects (39. 6%) compared to steroid-naïve subjects (27.5%, p<0.001). A treatment with ICS did not influence the outcome of the SIC. There was no difference in the change in PC20 or percentage of sputum eosinophils after SIC between steroid-treated and steroid-naïve subjects. ConclusionAn ongoing ICS treatment during a SIC did not affect the occurrence of an asthmatic reaction, the change in airway responsiveness or eosinophilic inflammation after exposure to the suspected agent in subjects who have been treated with ICS for a long period of time.

Diagnostic Accuracy of Specific IgE Against Wheat and Rye in Flour-Induced Occupational Asthma

Assessment of IgE-mediated sensitization to flour allergens is widely used to investigate flour-induced occupational asthma. The diagnostic efficiency of detecting specific IgE antibodies (sIgEs) against wheat and rye flour, however, has not been thoroughly compared with other diagnostic procedures. We sought to evaluate the diagnostic accuracy of sIgE against wheat and rye compared with specific inhalation challenge (SIC) with flour as the reference standard. This retrospective multicenter study included 264 subjects who completed an SIC with flour in eight tertiary centers, of whom 205 subjects showed a positive SIC result. Compared with SIC, sIgE levels of 0.35 kUA/L or greater against wheat and rye provided similar sensitivities (84% to 85%, respectively), specificities (71% to 78%), positive predictive values (91% to 93%), and negative predictive values (56% to 61%). Increasing the threshold sIgE value to 5.10 kUA/L for wheat and to 6.20 kUA/L for rye provided a specificity of 95% or greater and further enhanced the positive predictive value to 98%. Among subjects with a positive SIC, those who failed to demonstrate sIgE against wheat and rye (n= 26) had significantly lower total serum IgE level and blood and sputum eosinophil counts and a lesser increase in postchallenge FeNO compared with subjects with a detectable sIgE. High levels of sIgE against wheat and/or rye flour strongly support a diagnosis of flour-induced occupational asthma without the need to perform an SIC. The absence of detectable sIgE against wheat and rye in subjects with a positive SIC seems to be associated with lower levels of TH2 biomarkers.

Occupational asthma, rhinitis and contact urticaria from greenhouse work.

The current knowledge about occupational allergic diseases among greenhouse workers is scant. To describe greenhouse workers' occupational allergic diseases. We identified 28 greenhouse workers with occupational allergic diseases in 2002-2020 by conducting a systematic search in the patient register of the Finnish Institute of Occupational Health. All the patients worked in tomato- or cucumber-growing greenhouses and showed immunoglobulin-E-mediated sensitization to occupational agents. Specific inhalation challenges or workplace peak expiratory flow monitoring confirmed occupational asthma (OA), nasal allergen challenges confirmed occupational rhinitis (OR) and open skin tests confirmed occupational contact urticaria (OCU). Most patients had more than one occupational disease and were sensitized to several workplace agents. Tomato plants were the most common cause of occupational diseases and induced 22 allergic diseases in 14 patients. Cucumber plants caused occupational diseases in 10 patients (3 OA, 7 OR and 6 OCU). The pest control mite Amblyseius swirskii and a mixture of parasitic wasps Encarsia formosa and Eretmocerus eremicus both induced two OA cases. Three patients had an occupational disease caused by storage mites and three others had a work-related systemic reaction to a bumblebee sting. The greenhouse workers typically suffered from several occupational allergic diseases and were sensitized to cultivated plants, various pest control organisms and storage mites. All these can cause OA and OR, but in this study, OCU was only induced by cultivation plants. Cucumber plant is a novel cause of OA and OR, and A. swirskii is a novel cause of OA.

Hypersensitivity pneumonitis: Principles in diagnosis and management.

Hypersensitivity pneumonitis: Principles in diagnosis and management.

Serial fractional exhaled nitric oxide measurements at and off work may help to identify immunologic occupational asthma in cases with complex exposures

Serial measurements of fractional exhaled nitric oxide (FeNO) at home and at work have been described to provide complementary information for the diagnosis of occupational asthma (OA) when specific inhalation challenge (SIC) is missing or doubtful. We describe two cases in which serial FeNO measurements enabled the detection of probable OA after complex exposures. A 25-year-old industrial painter with exposure to a variety of paints suffered from work-related airway symptoms for five years. Lung function was normal, and she was not atopic. SIC with hexamethylene diisocyanate was negative. A 47-year-old sign maker (screen printing, foils) suffering from work-related dyspnoea for seven years. Moderate airway obstruction, but no atopy was detectable. Due to the complex exposures SIC was not performed. Both patients performed FeNO measurements once daily during a 2–week-holiday and a subsequent 2–week-work period. In both cases elevated baseline FeNO decreased to normal (25 ppb) during holidays and increased after resuming work (case 1: 125 ppb, case 2: 45 ppb).

Impact of occupational asthma on health and employment status: a long-term follow-up study

ObjectivesThe aim of this study was to assess the predictors of a favourable prognosis of occupational asthma (OA) and the employment status of patients with OA at least 2 years...

Reported Cases and Diagnostics of Occupational Insect Allergy: A Systematic Review.

A significant part of adult-onset asthma is caused by occupational exposure to both high- and low-molecular-mass agents. Insects are occasionally described to cause occupational allergy in professions including anglers and fishers, laboratory workers, employees of aquaculture companies, farmers, bakers, sericulture workers and pet shop workers. Occupational insect allergies are often respiratory, causing asthma or rhinoconjunctivitis, but can be cutaneous as well. The European Union recently approved three insect species for human consumption, enabling an industry to develop where more employees could be exposed to insect products. This review overviews knowledge on occupational insect allergy risks and the tools used to diagnose employees. Despite the limited availability of commercial occupational insect allergy diagnostics, 60.9% of 164 included reports used skin prick tests and 63.4% of reports used specific IgE tests. In 21.9% of reports, a more elaborate diagnosis of occupational asthma was made by specific inhalation challenges or peak expiratory flow measurements at the workplace. In some work environments, 57% of employees were sensitized, and no less than 60% of employees reported work-related symptoms. Further development and optimization of specific diagnostics, together with strong primary prevention, may be vital to the health conditions of workers in the developing insect industry.

The antioxidant, tert-butylhydroquinone: a new cause of asthma.

The antioxidant, tert-butylhydroquinone (TBHQ), a common additive in food and cosmetics can cause allergic contact dermatitis. A 49-year-old non-atopic male factory worker developed asthma in connection with cleaning mixing drums containing TBHQ. Due to the suspicion that TBHQ might be the cause of asthma, a specific inhalation challenge was carried out. Lactose was used as a control agent. The following day he developed asthma symptoms with a 41% drop in FEV1 after 30-min exposure to small amounts of TBHQ and water. Methacholine reactivity increased 5-fold after TBHQ exposure compared to pre-exposure reactivity. This suggests that TBHQ may be the cause of asthma in this case. Due to this case respirators were introduced in the factory to reduce TBHQ exposure. TBHQ has not previously been shown to cause asthma.

Occupational asthma in office workers.

Office work has a relative perception of safety for the worker. Data from surveillance schemes and population-based epidemiological studies suggest that office work carries a low risk of occupational asthma (OA). Office workers are frequently used as comparators in studies of occupational exposure and respiratory disease. We aimed to describe and illustrate our tertiary clinical experience of diagnosing OA in office workers. We searched the Birmingham NHS Occupational Lung Disease Service clinical database for cases of occupational respiratory disease diagnosed between 2002 and 2020, caused by office work or in office workers. For patients with OA, we gathered existing data on demographics, diagnostic tests including Occupational Asthma SYStem (OASYS) analysis of serial peak expiratory flow and specific inhalational challenge, and employment outcome. We summarised data and displayed them alongside illustrative cases. There were 47 cases of OA (5% of all asthma) confirmed using OASYS analysis of PEFs in the majority. Sixty percent of cases occurred in healthcare, education and government sectors. The most frequently implicated causative exposures or agents were: indoor air (9), printing, copying and laminating (7), cleaning chemicals (4), mould and damp (4), and acrylic flooring and adhesives (4). Exposures were grouped into internal office environment, office ventilation-related and adjacent environment. Clinicians should be vigilant for exposures associated with OA in office workers who present with work-related symptoms, where respiratory sensitizing agents may be present. A structured approach to assessment of the workplace is recommended.

Utilization of Predictive Models for Diagnosis of Occupational Diseases

Predictive models have long been used to assist clinical decision-making in medicine. Predictive models are made to estimate how likely a person is to have a disease (diagnostic model) or will experience a disease (prognostic model). In the field of occupational health, for example, diagnostic models can be used to increase the efficiency of surveillance programs by identifying groups of workers with occupational diseases without using complex and expensive diagnostic tests.Work-related asthma (WRA) is the most common occupational lung disease in industrialized countries and the second most common in developing countries. Around the world, especially in developing countries, diagnosing WRA is still difficult due to the limitations of available diagnostic tests. Specific inhalation challenge (SIC), the best test for diagnosing occupational asthma, is only available in several research centres worldwide.Several questionnaire-based models have been developed to diagnose work-related asthma at both the primary (general practitioner) and secondary (specialist) levels of care. A recent model for diagnosing occupational asthma was developed using data from Canada and has been validated using data from several European countries. A collaboration has been initiated to assess the application of this model among Indonesian workers.

Comparison of Specific Inhalation Challenge Test Results in Occupational and Non- Occupational Asthma Patients: Is Monitoring Peak Expiratory Flow Rate Sufficient for Diagnosis?

Comparison of Specific Inhalation Challenge Test Results in Occupational and Non- Occupational Asthma Patients: Is Monitoring Peak Expiratory Flow Rate Sufficient for Diagnosis?

The Effect of Seasonal Priming on Specific Inhalation Challenges With Birch and Grass Allergen Among Persons With Allergic Rhinitis.

Objectives: Allergic diseases are prevalent in the working population, and work-related airborne pollen exposure might be substantial, especially among outdoor workers, resulting in work-exacerbated effects. Seasonal exposure to pollen may induce a priming effect on the allergic bronchial response resulting in exaggerated effects at the end of the natural pollen season. This was previously observed among people with asthma but may also be of importance for persons with allergic rhinitis. In this study, we examined the effect of seasonal priming on bronchial responsiveness among young adults with allergic rhinitis and no or mild asthma. In addition, we explored the association between the baseline characteristics of participants and the severity of bronchoconstriction. Finally, we evaluated the application of a novel non-linear regression model to the log-dose-response curves.Material and methods: In a crossover design, 36 participants underwent specific inhalation challenges (SICs) with either grass or birch allergen outside and at the end of the pollen season. The differences in bronchial response were evaluated by comparing the dose-response profiles and PD20 estimates derived by applying a non-linear regression model.Results: The results showed that 12 of the 19 grass pollen-exposed participants had a lower PD20 at the end of the season compared with the outside season. For birch, this was true for nine out of the 17 participants. However, no statistically significant effects of the seasonal pollen exposure were found on neither the shape nor the magnitude of the modeled dose-response curves for either birch allergen, p = 0.77, or grass allergen, p = 0.45. The model depicted a good fit for the data. Among the baseline characteristics, only the size of the skin prick test for grass allergen was associated with PD20.Conclusion: This study does not support a priming effect of pollen exposure on the bronchial response from the natural seasonal exposure levels of grass or birch allergens among young adults with allergic rhinitis.

Serial measurements of fractional exhaled nitric oxide at home and at work: A useful tool for monitoring workers with platinum salt allergy after exposure reduction.

Serial measurements of fractional exhaled nitric oxide at home and at work: A useful tool for monitoring workers with platinum salt allergy after exposure reduction.

Long-Term Follow-Up of Cluster-Based Diisocyanate Asthma Phenotypes

Data on the outcome of occupational asthma (OA) are heterogeneous. To assess the impact of being part of a specific cluster at diagnosis on the long-term outcome of diisocyanate-induced OA. We collected data from 56 patients who had a diagnosis of OA confirmed by a positive specific inhalation challenge. Patients sensitized to toluene diisocyanate were allocated to cluster 1 or 2 based on a tree analysis, using the 3 variables relevant for cluster segregation identified in a previous study: age, body mass index, and forced expiratory volume in 1 second/forced vital capacity at diagnosis. Patients sensitized to methylene diisocyanate were allocated to cluster 3, as in previous study. We defined OA remission when a patient had met a total of 3 criteria: no asthma symptoms and no antiasthma therapy for the last year, as well as having normal lung function. At follow-up, 16 patients showed OA remission. They exhibited better lung function, less bronchial hyperreactivity, as well as younger age at diagnosis. Twenty-eight patients were allocated to cluster 1, 10 to cluster 2, and 18 to cluster 3. The percentage of patients with OA remission was higher in cluster 2 (50% vs 25% in cluster 1 and 22.5% in cluster 3), although the difference was not statistically significant (P= .2789). Age at diagnosis was a strong predictor of OA remission. The outcome of diisocyanate OA tended to be more favorable for patients with toluene diisocyanate OA allocated in cluster 2, but this finding needs to be validated by further data.

Phénotypage de l’asthme professionnel par la réalisation d’expectoration induite après test d’exposition spécifique

RationaleAlthough the non-invasive assessment of airway inflammation through the induced sputum (IS) technique identified distinct asthma phenotypes, there is few information on the determinants of airway inflammatory pattern in sensitizer-induced occupational asthma (OA). AimTo investigate whether the pattern of airway inflammation in IS is associated with distinct clinical phenotypes of OA. MethodsThis retrospective multicentric study was conducted among 372 patients with OA confirmed by a positive specific inhalation challenge (SIC) who were recruited in the European network for the Phenotyping of OCupational Asthma cohort (2006–2018). Each patient underwent an analysis of IS before and 24 hours after the SIC. Sputum eosinophilia and neutrophilia were defined by the presence of≥3% eosinophils and≥76% neutrophils in sputum samples collected after the SIC. ResultsIn total, 268 (72%) and 42 patients (11%) exhibited sputum eosinophilia and neutrophilia, respectively. Multivariate logistic regression analysis revealed that eosinophilia was associated with exposure to a high molecular weight agent (odds ratio [OR], 1.89; 95% CI, 1.18–3.04), moderate asthma (OR, 3.17; 95% CI, 1,43–7.0) and severe asthma (OR, 2.39; 95% CI, 1.06–5.43). Sputum neutrophilia was associated with age (OR for each additional year, 1.04; 95% CI, 1.01–1.08), male gender (OR, 2.74; 95% CI, 1,21–6.8), mild asthma (OR, 3.26; 95% CI, 1.24–8.88), and dysphonia (OR, 2.83; 95% CI, 1.14–6.87). ConclusionsSputum eosinophilia post-SIC was predominant in OA patients. Sputum eosinophilia and neutrophilia were associated with distinct clinical phenotypes of OA, especially in terms of causal agents and asthma severity.

Inhalation Challenge Tests in Occupational Asthma: Why Are Multiple Tests Needed?

Occupational and environmental lung diseases are on the rise because of the widespread use of various toxic agents in industry. Asthma etiopathogenesis is unclear because of exposure to high and low molecular agents in workplaces. Approximately 15-25% of asthma in adults is reported to be related to occupational exposure. The prevalence of occupational asthma (OA) is predicted to be high. The difficulties in diagnosing OA results in inadequate treatment, permanent airway damage, and medicolegal and social problems. As with other occupational diseases, it is necessary to demonstrate a direct causal relationship between the suspected agent and OA. Spirometry, peak expiratory flow rate, and/or non-specific bronchial hyperresponsiveness are frequently used to show airway hyperresponsiveness at the workplace and away from work. However, there are some controversies about the specificity and sensitivity of these test methods. Furthermore, these tests do not identify the exposure agent, which could be the causative agent. Specific inhalation challenge (SIC) tests that demonstrate the direct causal relationship are currently the gold standard. However, their positive and negative predictive values have not yet been established; therefore, many low molecular weight agents could cause late or atypical reactions. Therefore, a negative SIC test cannot exclude the disease. This review describes the procedures for the SIC test and discusses the importance of using the combined test methods with the SIC test.

Pulmonary Function Testing in Work-Related Asthma: An Overview from Spirometry to Specific Inhalation Challenge.

Work-related asthma (WRA) is a very frequent condition in the occupational setting, and refers either to asthma induced (occupational asthma, OA) or worsened (work-exacerbated asthma, WEA) by exposure to allergens (or other sensitizing agents) or to irritant agents at work. Diagnosis of WRA is frequently missed and should take into account clinical features and objective evaluation of lung function. The aim of this overview on pulmonary function testing in the field of WRA is to summarize the different available tests that should be considered in order to accurately diagnose WRA. When WRA is suspected, initial assessment should be carried out with spirometry and bronchodilator responsiveness testing coupled with first-step bronchial provocation testing to assess non-specific bronchial hyper-responsiveness (NSBHR). Further investigations should then refer to specialists with specific functional respiratory tests aiming to consolidate WRA diagnosis and helping to differentiate OA from WEA. Serial peak expiratory flow (PEF) with calculation of the occupation asthma system (OASYS) score as well as serial NSBHR challenge during the working period compared to the off work period are highly informative in the management of WRA. Finally, specific inhalation challenge (SIC) is considered as the reference standard and represents the best way to confirm the specific cause of WRA. Overall, clinicians should be aware that all pulmonary function tests should be standardized in accordance with current guidelines.

Workplace-related inhalation test (AIT) – Specific inhalation challenge (SIC) – S2k Guideline of the German Society for Occupational and Environmental Medicine e.V. (DGAUM), the German Society for Pneumology and Respiratory Medicine e.V. (DGP)

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