Airway Inflammatory Responses Following Exposure to Occupational Agents

doi:10.1378/chest.11-1134

Chest

Volume 141, Issue 6, June 2012, Pages 1522-1527

https://doi.org/10.1378/chest.11-1134 Get rights and content

Background

Airway inflammatory responses to specific inhalation challenges (SICs) with low-molecular-weight (LMW) and high-molecular-weight (HMW) agents have not been studied thoroughly. We assessed the changes in airway inflammatory cells following SIC in sensitized workers, and looked at the influence of various factors on the pattern of inflammatory responses to SIC.

Methods

Induced sputum analysis was performed in workers sensitized to LMW (n = 41) or HMW agents (n = 41) after a control day and after a positive SIC. Cell counts were compared with lung function and various clinical parameters.

Results

In the LMW group, eosinophils were increased following late asthmatic responses (median [interquartile range], 0.02 [0.04] × 10⁶ cells/g vs 0.30 [0.80] × 10⁶ cells/g and 1.0% [3.5] vs 8.9% [8.0], P < .05), as were neutrophil numbers (0.8 [1.3] × 10⁶ cells/g vs 2.3 [5.4] × 10⁶ cells/g, P = .04). In the HMW group, eosinophil percentages increased both after early (1.0% [2.2] vs 5.5% [14.5], P = .003) and dual asthmatic responses (4.5% [3.7] vs 15.0% [13.7], P = .02). In the LMW group, the increases in neutrophils were higher in current smokers than in ex-smokers or nonsmokers. The length of exposure to the agent, tobacco use, and baseline percentage of eosinophils were independent predictors of the change in eosinophils, whereas age and baseline neutrophil percentage were predictors of the change in neutrophils.

Conclusions

This study confirms that eosinophils and neutrophils are increased after SIC, whatever the causal agent. The type of agent is not predictive of the inflammatory response to SIC. Smoking is associated with a more neutrophilic response after SIC with an LMW agent.

Section snippets

Subjects and Design

In this retrospective study, data obtained from the charts of subjects with OA confirmed with a positive SIC between 2001 and 2008 in two Canadian referral centers for OA (Institut universitaire de cardiologie et de pneumologie de Québec, Quebec City, and Hôpital du Sacré-Cœur, Montreal, Quebec) were analyzed. At that time, the investigation for OA included a first visit to collect baseline information, and subsequent visits for performing SIC. The SIC was performed in the laboratory and was

Subjects' Characteristics

The subjects' characteristics are summarized in Table 1. Among the 82 subjects evaluated, 41 were sensitized to LMW and 41 to HMW agents. LMW substances included mainly isocyanates, plicatic acid, and other chemicals, whereas the most prevalent HMW agents were flour and seafood. There was no difference in ICS use between the two groups (LMW, 63% vs HMW, 51%; P = .3). Following the SIC, the types of reaction were different between the two groups, with mostly LAR in the LMW group and EAR in the

Discussion

This retrospective study provides original information on inflammatory changes following exposure to workplace sensitizers, in relation to the pattern of change in expiratory flows following bronchoprovocation with the offending agent, in a large number of subjects. It confirms that airway eosinophils increase significantly following SIC, whatever the type of asthmatic response to the offending agent. Other studies22, 23 showed that most workers with a positive SIC had higher sputum eosinophil

Acknowledgments

Author contributions: Mr Prince: contributed to the data collection, analysis, and writing of the manuscript.

Dr Lemière: contributed to the study protocol and writing of the manuscript.

Dr Dufour: contributed to the data collection, analysis, and writing of the manuscript.

Ms Chaboillez: contributed to the data collection, analysis, and writing of the manuscript.

Dr Boulet: contributed to the study protocol and writing of the manuscript, and as the guarantor of the manuscript.

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Cited by (25)

Cluster analysis of phenotypes, job exposure, and inflammatory patterns in elderly and nonelderly asthma patients
2024, Allergology International
Asthma has been identified as different phenotypes due to various risk factors. Age differences may have potential effects on asthma phenotypes. Our study aimed to identify potential asthma phenotypes among adults divided by age as either younger or older than 65 years. We also compared differences in blood granulocyte patterns, occupational asthmagens, and asthma control-related outcomes among patient phenotype clusters.
We recruited nonelderly (<65 years old) (n = 726) and elderly adults (≥65 years old) (n = 201) with mild-to-severe asthma. We conducted a factor analysis to select 17 variables. A two-step cluster analysis was used to classify subjects with asthma phenotypes, and a discriminant analysis was used to verify the classification of cluster results.
There were three clusters with different characteristics identified in both the nonelderly and elderly asthmatic adults. In the nonelderly patient group, cluster 2 (obese, neutrophilic phenotypes) had a 1.85-fold significantly increased risk of asthma exacerbations. Cluster 3 (early-onset, atopy, and smoker with an eosinophil-predominant pattern) had a 2.37-fold risk of asthma exacerbations and higher oral corticosteroid (OCS) use than cluster 1 (late-onset and LMW exposure with paucigranulocytic blood pattern). Among elderly patients, cluster 2 had poor lung function and more ex-smokers. Cluster 3 (early-onset, long asthma duration) had the lowest paucigranulocytic blood pattern percentages in the elderly group.
The novelty of the clusters was found in age-dependent clusters. We identified three distinct phenotypes with heterogeneous characteristics, asthma exacerbations and medicine use in nonelderly and elderly asthmatic patients, respectively. Classification of age-stratified asthma phenotypes may lead to precise identification of patients, which provides personalized disease management.
Occupational Asthma Caused by Quaternary Ammonium Compounds: A Multicenter Cohort Study
2021, Journal of Allergy and Clinical Immunology: In Practice
Citation Excerpt :
Although a number of reports documented asthmatic reactions after challenge exposure to QACs,3-7 the inflammatory pattern induced by these chemicals has not been specifically investigated. Previous studies reported an increase in sputum eosinophils after challenge exposure to the causal agent in subjects with OA independently of the type of agent (ie, LMW vs high–molecular weight agents) and the pattern of asthmatic reaction (ie, late vs early reactions).20,28 Nevertheless, a previous analysis of the E-PHOCAS cohort demonstrated that BPTs with acrylate compounds were more frequently associated with a significant increase in sputum eosinophils (88%) compared with other LMW agents (48%).19
Quaternary ammonium compounds (QACs) are used extensively for cleaning and disinfection and have been documented in scattered reports as a cause of occupational asthma (OA) through bronchoprovocation tests (BPTs).
To examine the clinical, functional, and inflammatory profile of QAC-induced OA compared with OA caused by other low–molecular weight (LMW) agents.
The study was conducted in a retrospective multicenter cohort of 871 subjects with OA ascertained by a positive BPT. Subjects with QAC-induced OA (n = 22) were identified based on a positive BPT to QACs after exclusion of those challenged with cleaning products or disinfectants that contained other potential respiratory sensitizers. They were compared with 289 subjects with OA caused by other LMW agents.
Most subjects with QAC-induced OA were working in the health care sector (n = 14). A twofold or greater increase in the postchallenge level of nonspecific bronchial hyperresponsiveness was recorded in eight of 11 subjects with QAC-induced OA (72.7%) and in 49.7% of those with OA caused by other LMW agents. Although sputum assessment was available in only eight subjects with QAC-induced OA, they showed a significantly greater median (interquartile) increase in sputum eosinophils (18.1% [range, 12.1% to 21.1%]) compared with those with OA caused by other LMW agents (2.0% [range, 0% to 5.2%]; P < .001).
This study indicates that QAC-induced OA is associated with a highly eosinophilic pattern of airway response and provides further evidence supporting the sensitizing potential of QACs. The findings highlight the heterogeneous nature of the pathobiologic pathways involved in OA caused by LMW agents.
Long-Term Follow-Up of Cluster-Based Diisocyanate Asthma Phenotypes
2021, Journal of Allergy and Clinical Immunology: In Practice
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.
Assessment and Management of Occupational Asthma
2020, Journal of Allergy and Clinical Immunology: In Practice
Citation Excerpt :
HMW proteins and a few LMW compounds (eg, platinum salts, reactive dyes, acid anhydrides, sulfonechloramide, and some wood species) act through a demonstrable type I IgE-associated hypersensitivity mechanism, but for most LMW agents, the immunologic mechanisms leading to airway sensitization remain poorly elucidated.9 Although asthmatic reactions induced by both HMW and LMW agents are characterized by a predominant eosinophilic airway inflammation,10 there are differences in the clinical characteristics of OA caused by these 2 broad categories of causal agents.8 OA caused by HMW agents is more frequently associated with work-related rhinitis/conjunctivitis, atopy, and early asthmatic reactions on exposure to the causal agent, whereas OA due to LMW agents is associated with a higher prevalence of daily sputum production and late asthmatic reactions.8
Exposures at work can give rise to different phenotypes of “work-related asthma.” The focus of this review is on the diagnosis and management of sensitizer-induced occupational asthma (OA) caused by either a high- or low-molecular-weight agent encountered in the workplace. The diagnosis of OA remains a challenge for the clinician because there is no simple test with a sufficiently high level of accuracy. Instead, the diagnostic process combines different procedures in a stepwise manner. These procedures include a detailed clinical history, immunologic testing, measurement of lung function parameters and airway inflammatory markers, as well as various methods that relate changes in these functional and inflammatory indices to workplace exposure. Their diagnostic performances, alone and in combination, are critically reviewed and summarized into evidence-based key messages. A working diagnostic algorithm is proposed that can be adapted to the suspected agent, purpose of diagnosis, and available resources. Current information on the management options of OA is summarized to provide pragmatic guidance to clinicians who have to advise their patients with OA.
Occupational Rhinitis
2020, Journal of Allergy and Clinical Immunology: In Practice
Citation Excerpt :
Such LMW agents causing OA and OR are typically highly reactive electrophilic compounds that are capable of combining with amino acid residues on airway proteins.52,53 The resulting airway inflammatory process seems similar for OR and OA and is predominantly characterized by the presence of eosinophils.54 An influx of eosinophils in the nasal mucosa has been demonstrated in nasal lavage fluid or nasal blown secretions after specific nasal provocation tests (sNPTs) with both HMW55-57 and LMW38,58,59 agents in subjects with OR.
There is convincing evidence that tight relationships between the upper and lower airways also apply to the workplace context. Most patients with occupational asthma (OA) also suffer from occupational rhinitis (OR), although OR is 2 to 3 times more common than OA. OR most often precedes the development of OA, especially when high-molecular-weight protein agents are involved, and longitudinal cohort studies have confirmed that OR is associated with an increased risk for the development of OA. The level of exposure to sensitizing agents at the workplace is the most important determinant for the development of IgE-mediated sensitization and OR. Atopy is a risk factor for the development of IgE-mediated sensitization only to high-molecular-weight agents. In workers with work-related rhinitis symptoms, documentation of IgE-mediated sensitization to a workplace agent via skin prick testing or serum specific IgE confirms a diagnosis of probable OR, whereas specific nasal provocation testing in the laboratory remains the reference method to establish a definite diagnosis of OR. Complete avoidance of exposure to the causal agent is the most effective therapeutic option for controlling work-related nasal symptoms and preventing the development of OA. If complete elimination of exposure is expected to induce meaningful adverse socioeconomic consequences, reduction of exposure can be considered as an alternative approach, but it is important to consider the individual risk factors for the development of OA to implement a more personalized management of OR.
Developing and emerging clinical asthma phenotypes
2014, Journal of Allergy and Clinical Immunology: In Practice
For more than a century, clinicians have attempted to subdivide asthma into different phenotypes based on triggers that cause asthma attacks, the course of the disease, or the prognosis. The first phenotypes that were described included allergic asthma, intrinsic or nonallergic asthma, infectious asthma, and aspirin-exacerbated asthma. These phenotypes are being reviewed elsewhere in this issue of the journal. The present article focuses on developing and emerging clinical asthma phenotypes. First, asthma phenotypes that are associated with environmental exposures (occupational agents, cigarette smoke, air pollution, cold dry air); second, asthma phenotypes that are associated with specific symptoms or clinical characteristics (cough, obesity, adult onset of disease); and third, asthma phenotypes that are based on biomarkers. This latter approach is the most promising because it attempts to identify asthma phenotypes with different underlying mechanisms so that therapies can be better targeted toward disease-specific features and disease outcomes can be improved.

View all citing articles on Scopus

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Funding/Support: The authors have reported to CHEST that no funding was received for this study.

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Chest

Original ResearchOccupational and Environmental Lung DiseasesAirway Inflammatory Responses Following Exposure to Occupational Agents

Background

Methods

Results

Conclusions

Section snippets

Subjects and Design

Subjects' Characteristics

Discussion

Acknowledgments

Chest

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Chest

Chest

Chest

American Thoracic Society Statement: occupational contribution to the burden of airway disease

Am J Respir Crit Care Med

Occupational asthma

Am J Respir Crit Care Med

Asthma in the Workplace

Definition and diagnosis of occupational asthma

Eur Respir J

Proceedings of the first Jack Pepys Occupational Asthma Symposium

Am J Respir Crit Care Med

Directives de la Societe canadienne de thoracologie pour l'asthme professionnel canadian thoracic society guidelines for occupational asthma

Can Respir J

Bronchoalveolar neutrophilia during late asthmatic reactions induced by toluene diisocyanate

Am Rev Respir Dis

Outcome of occupational asthma after removal from exposure: a follow-up study

Can Respir J

Comparative airway response to high- versus low-molecular weight agents in occupational asthma

Eur Respir J

Original Research
Occupational and Environmental Lung Diseases
Airway Inflammatory Responses Following Exposure to Occupational Agents