Severe Occupational Asthma: Insights From a Multicenter European Cohort

doi:10.1016/j.jaip.2019.03.017

The Journal of Allergy and Clinical Immunology: In Practice

Volume 7, Issue 7, September–October 2019, Pages 2309-2318.e4

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https://doi.org/10.1016/j.jaip.2019.03.017 Get rights and content

Background

Although sensitizer-induced occupational asthma (OA) accounts for an appreciable fraction of adult asthma, the severity of OA has received little attention.

Objective

The aim of this study was to characterize the burden and determinants of severe OA in a large multicenter cohort of subjects with OA.

Methods

This retrospective study included 997 subjects with OA ascertained by a positive specific inhalation challenge completed in 20 tertiary centers in 11 European countries during the period 2006 to 2015. Severe asthma was defined by a high level of treatment and any 1 of the following criteria: (1) daily need for a reliever medication, (2) 2 or more severe exacerbations in the previous year, or (3) airflow obstruction.

Results

Overall, 162 (16.2%; 95% CI, 14.0%-18.7%) subjects were classified as having severe OA. Multivariable logistic regression analysis revealed that severe OA was associated with persistent (vs reduced) exposure to the causal agent at work (odds ratio [OR], 2.78; 95% CI, 1.50-5.60); a longer duration of the disease (OR, 1.04; 95% CI, 1.00-1.07); a low level of education (OR, 2.69; 95% CI, 1.73-4.18); childhood asthma (OR, 2.92; 95% CI, 1.13-7.36); and sputum production (OR, 2.86; 95% CI, 1.87-4.38). In subjects removed from exposure, severe OA was associated only with sputum production (OR, 3.68; 95% CI, 1.87-7.40); a low education level (OR, 3.41; 95% CI, 1.72-6.80); and obesity (OR, 1.98; 95% CI, 0.97-3.97).

Conclusions

This study indicates that a substantial proportion of subjects with OA experience severe asthma and identifies potentially modifiable risk factors for severe OA that should be targeted to reduce the adverse impacts of the disease.

Introduction

Severe asthma (SA) imposes a substantial public health burden because the condition has a major impact on patients' quality of life and accounts for a disproportionately large portion of health care costs associated with asthma.1, 2 Clinical practice guidelines advocate the identification and remediation of exposures contributing to asthma severity as a key step in disease management.1, 3 Among potentially modifiable exposures, the workplace environment is likely to hold a notable position because workplace exposures to high-molecular-weight (HMW) and low-molecular-weight (LMW) asthmagenic agents have been associated with an increased risk of poor asthma control and severe exacerbations.4, 5

Sensitizer-induced occupational asthma (OA), a distinguishable phenotype of work-related asthma, is characterized by the de novo inception of asthma or the recurrence of previously quiescent asthma induced by immunologically mediated sensitization to a specific agent at the workplace.6, 7 Enhancing our knowledge of the burden and determinants of severe OA may be relevant from both clinical and health-economic perspectives. Complete avoidance of exposure to the causal agent is the recommended treatment option for OA but is associated with a higher socioeconomic impact as compared with reduction of exposure.10, 11, 6, 8, 9 The severity of asthma at the time of diagnosis has been consistently identified as a risk factor for a worse outcome after removal from exposure.12, 6, 8 However, the determinants of OA severity have so far received little attention.13, 14

The aim of this study was to estimate the burden of severe OA and to identify its determinant factors in a large multicenter cohort of subjects with OA confirmed by specific inhalation challenge (SIC).

Section snippets

Study design and population

This retrospective, cross-sectional, observational study was conducted in an international, multicenter cohort of subjects with OA recruited from 20 tertiary centers in 11 European countries. Eligible subjects were those with a diagnosis of OA ascertained by a positive SIC completed between January 2006 and December 2015. From the 1180 eligible subjects with a positive SIC, 183 subjects with missing data pertaining to the variables used for assessing asthma severity and control were excluded

Population

The population included 997 patients with OA ascertained by a positive SIC result (see Appendix E1 and Figure 1). The demographic, clinical, and functional characteristics of the cohort are presented in Tables I and II. The occupational agents that induced a positive SIC response are summarized in Table E2 (available in this article's Online Repository at www.jaci-inpractice.org).

Severe OA while at work

The prevalence rates of high-level treatment, poor symptom control, 2 or more SA exacerbations during the last 12

Prevalence of severe OA

This cohort study indicates that a substantial fraction of subjects with OA (16.2%; 95% CI, 14.0%-18.7%) experience SA according to the multidimensional European Respiratory Society/American Thoracic Society consensus definition of the disease.¹ This estimate is higher than those found in the general adult asthma population in 2 studies that applied the same definition of SA: 4.5% (95% CI, 3.9%-5.1%)²¹ and 6.3%.²² The prevalence of SA in the general adult asthma population remains, however,

Conclusions

This study shows that the determinants of severe OA include not only potentially modifiable factors (ie “unchanged/persistent” exposure to the causal agent and duration of symptomatic exposure before diagnosis) but also a low sociodemographic status and clinical characteristics (ie, childhood asthma and daily sputum production). Interestingly, data collected in the subset of subjects removed from the causal agent at the time of the diagnostic evaluation suggest that the persistence of SA was

Acknowledgments

European Network for the Phenotyping of Occupational Asthma (E-PHOCAS) investigators: Olivier Vandenplas and Catherine Rifflart (Department of Chest Medicine, Centre Hospitalier Universitaire UCL Namur, Université Catholique de Louvain, Yvoir, Belgium); Pavlina Klusackova (Department of Occupational Medicine, General University Hospital, Charles University, Prague, Czech Republic); David Sherson (Department of Pulmonary Medicine and Occupational Medicine, Odense University Hospital, Odense,

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Asthma in the workplace is an important occupational health issue. It comprises various subtypes: occupational asthma (OA; both allergic asthma and irritant-induced asthma) and work-exacerbated asthma (WEA). Current regulatory paradigms for the management of OA are not fit for purpose. There is therefore an important unmet need, for the purposes of both effective human health protection and appropriate and proportionate regulation, that sub-types of work-related asthma can be accurately identified and classified, and that chemical respiratory allergens that drive allergic asthma can be differentiated according to potency. In this article presently available strategies for the diagnosis and characterisation of asthma in the workplace are described and critically evaluated. These include human health studies, clinical investigations and experimental approaches (structure-activity relationships, assessments of chemical reactivity, experimental animal studies and in vitro methods). Each of these approaches has limitations with respect to providing a clear discrimination between OA and WEA, and between allergen-induced and irritant-induced asthma. Against this background the needs for improved characterisation of work-related asthma, in the context of more appropriate regulation is discussed.
Disposition of Work-Related Asthma in a Spanish Asthma Cohort: Comparison of Asthma Severity Between Employed and Retired Workers
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Exposure to certain agents in the workplace can trigger occupational asthma or work-exacerbated asthma, both of which come under the heading of work-related asthma (WRA). Understanding the burden that WRA represents can help in the management of these patients.
To assess the influence of occupation on asthma in real life and analyze the characteristics of patients with WRA included in an asthma cohort.
This was a prospective multicenter study of a cohort of consecutive patients with asthma. A standardized clinical history was completed. Patients were classified as having WRA or non-WRA. All patients underwent respiratory function tests, FeNO test, and methacholine challenge (methacholine concentration that causes a 20% drop in FEV₁) at the beginning of the study. They were classified into two groups, depending on their employment status: employed (group 1) or unemployed (group 2).
Of the 480 patients included in the cohort, 82 (17%) received the diagnosis of WRA. Fifty-seven patients (70%) were still working. Mean age (SD) was 46 (10.69) years in group 1 and 57 (9.91) years in group 2 (P < .0001). Significant differences were observed in adherence to treatment (64.9% in group 1 vs 88% in group 2; P = .0354) and in severe asthma exacerbations (35.7% in group 1 vs 0% in group 2; P = .0172). No significant differences were observed in the rest of the variables analyzed.
The burden of WRA in specialized asthma units is not negligible. The absence of differences in the severity of asthma, the treatment administered, alterations in lung function, and the number of exacerbations in those working versus not working may support the idea that advice regarding changing jobs should be customized for individual patients.
Level of knowledge on occupational asthma and asthmagens: Assessment among healthcare workers by a validated questionnaire
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Le système de santé est l’un des secteurs professionnels à risque d’asthme professionnel. L’objectif de ce travail est d’évaluer le niveau des connaissances des professionnels de santé sur l’asthme professionnel et les agents asthmogènes afin de planifier une action éducative sur ce sujet.
Étude transversale multicentrique réalisée entre juillet et décembre 2020, incluant 180 personnels de santé. On a utilisé un questionnaire validé abordant quatre dimensions : connaissances sur la maladie asthmatique, connaissances sur l’asthme professionnel, connaissance sur le pronostic de l’asthme professionnel et connaissance sur la prévention de l’asthme professionnel.
Le score total moyen était de 13,71 sur un total de 18. Le taux de réponses justes était de 76,17 %. Il n’y avait pas de corrélation entre le score total moyen et l’âge, le niveau éducationnel, l’ancienneté, les grades du personnel paramédical. Les scores totaux moyens étaient significativement plus élevés pour les participants sans horaire de travail fixe, le personnel exerçant aux structures non universitaires. Les indices de difficulté des dimensions étaient respectivement de 82,22 %, 77,56 %, 53,52 % et 66,67 %.
Les lacunes de connaissances intéressent toutes les catégories professionnelles à des degrés variables. La pertinence et la personnalisation du contenu de la formation médicale continue garantissent une amélioration. L’évaluation du niveau de connaissance pour chaque catégorie professionnelle constitue la première étape pour planifier une action éducative.
The health system is one of the professional sectors perhaps most at risk of occupational asthma. The aims of this study were to evaluate the level of knowledge of health care workers (HCWs) on occupational asthma and asthmogenic agents and to pave the way to effective educational action on the subject.
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The average total score was 13.71/18 (76.17%). There was no correlation between average total score and age, educational level, seniority or status of paramedical staff. Mean total scores were significantly higher for participants with no fixed work schedule and those practicing in non-university structures. The difficulty indexes for the four aforementioned dimensions were 82.22%, 77.56%, 53.52% and 66.67% respectively.
Knowledge gaps affect all professional categories but to different degrees. A review of the level of knowledge of persons in each category would be the first step on the road to planned educational action.
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Work is a substantial contributing factor of adult-onset asthma. A subtype of occupational asthma (OA) is caused by irritant agents, but knowledge of the clinical outcomes of irritant-induced asthma (IIA) is incomplete.
To evaluate whether the clinical picture of IIA differs from that of sensitizer-induced OA.
This retrospective study analyzed acute and subacute IIA patients diagnosed in an occupational medicine clinic during 2004 to 2018. Sixty-nine patients fulfilled the inclusion criteria, and their characteristics were analyzed at the time of the diagnosis and 6 months later. The results were compared with those of 2 subgroups of sensitizer-induced OA: 69 high-molecular-weight (HMW) and 89 low-molecular-weight (LMW) agent-induced OA patients.
Six months after the diagnosis, 30% of the patients with IIA needed daily short-acting β-agonists (SABA), 68% were treated with Global Initiative for Asthma, 2020 report (GINA) step 4-5 medication, and 24% of the patients had asthma exacerbation after the first appointment. IIA depicted inferiority to LMW-induced OA in daily need for SABA (odds ratio [OR]: 3.80, 95% confidence interval [CI]: 1.38-10.46), treatment with GINA step 4-5 medication (OR: 2.22, 95% CI: 1.08-4.57), and exacerbation (OR: 3.85, 95% CI: 1.35-11.04). IIA showed poorer results than HMW-induced OA in the latter 2 of these features (OR: 2.49, 95% CI: 1.07-5.79 and OR: 6.29, 95% CI: 1.53-25.83, respectively).
Six months after the OA diagnosis, a significant proportion of the patients with IIA remain symptomatic and the majority of these patients use asthma medications extensively suggesting uncontrolled asthma. The short-term outcomes of IIA appear poorer than that of sensitizer-induced OA.
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Compared with the healthy controls, the welding asthma patients had more differentially expressed genes than the flour asthma and isocyanate asthma patients, both in the airway epithelia and in the blood immune cells. In the airway epithelia, active inflammation was detected only in welding asthma patients. In contrast, many differentially expressed genes were detected in blood cells in all 3 asthma groups. Disease-related immune functions in blood cells, including leukocyte migration and inflammatory responses, and decreased expression of upstream cytokines such as TNF and IFN-γ were suppressed in all the asthma groups. In transcriptome-phenotype correlations, hyperresponsiveness (R ∼ |0.6|) had the highest clinical relevance and was associated with a set of exposure group–specific genes. Finally, biomarker subsets of only 5 genes specifically distinguished each of the asthma exposure groups.
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: This work was funded in part by a Task Force of the European Academy of Allergy and Clinical Immunology. O.V. and C.R. were supported by a grant from the Fondation Mont-Godinne. J.S. was supported in part by CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Spain.

: Conflicts of interest: The authors declare that they have no relevant conflicts of interest.

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Original ArticleSevere Occupational Asthma: Insights From a Multicenter European Cohort

Background

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Study design and population

Population

Severe OA while at work

Prevalence of severe OA

Conclusions

Acknowledgments

Chest

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Respir Med

J Allergy Clin Immunol Pract

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol Pract

J Allergy Clin Immunol

J Allergy Clin Immunol Pract

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

Eur Respir J

Severe and difficult-to-treat asthma in adults

N Engl J Med

Global strategy for asthma management and prevention 2015

Asthma severity and exposure to occupational asthmogens

Am J Respir Crit Care Med

Occupational exposures and uncontrolled adult-onset asthma in the European Community Respiratory Health Survey II

Eur Respir J

Occupational asthma

N Engl J Med

Occupational asthma: prevention, identification & management: systematic review & recommendations

Management of occupational asthma: cessation or reduction of exposure? A systematic review of available evidence

Eur Respir J

Original Article
Severe Occupational Asthma: Insights From a Multicenter European Cohort