Immunologic Occupational Asthma Research Articles

Incidence of Immunological Occupational Asthma in 2015–2022 by Occupation: Macedonian Experience

BACKGROUND: Immunologic occupational asthma (OA), a more prevalent OA type than non-immunologic OA, became an important public health problem in the last decades worldwide. AIM: To present the distribution of new diagnosed cases of immunologic OA in the RN Macedonia in the period 2015–2022 by occupation. METHODS: Immunologic OA was diagnosed by the serial measurement of peak expiratory flow rate (PEFR) at and away from work or by combination of serial PEFR measurement at and away from work and non-specific bronchial provocation at and away from work in workers with diagnosed asthma and work-relatedness of the symptoms. Sensitization to common inhalant and occupational allergens was evaluated by skin prick test. RESULTS: The annual incidence rate of the diagnosed immunologic OA in this period varied from 1.9 / 100,000 working population in 2015–2.6 / 100,000 in 2022 with a drop in 2020 and 2021, i.e. in the period of COVID-19 pandemic (0.6 and 0.5, respectively). Cleaning, bakery, cleaning, textile manufacture, wood industry, agriculture, and metal-parts manufacture were the most important occupations for the development of immunologic OA. More than a half of the new diagnosed immunologic OA cases were atopics. CONCLUSION: Our findings indicated the occupations with the highest incidence of immunologic OA that could enable targeting of preventive measures and activities to reduce the occurrence of immunologic OA as well as its adverse health outcomes.

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).

New causes of immunologic occupational asthma 2014-2020.

The purpose of this review was to list all new confirmed cases of immunological occupational asthma (IOA) described between mid-2014 and April 2020. Several new agents, both of high and low molecular weight, have been identified in the last 6 years as potential respiratory sensitizers being able to induce immunological occupational asthma. This review confirms that new causes of IOA are still identified regularly, particularly in subjects exposed to high molecular agents, in the food industry (farming, pest control, food processing), pharmaceutical industry (antibiotics, various drugs) and cosmetic environment (dyes, powders). It stressed the need for clinicians to stay alert and suspect occupational asthma in any adult with new onset asthma or newly uncontrolled asthma.

Causes and Phenotypes of Work-Related Asthma.

Work-related asthma (WRA) includes heterogeneous conditions, which have in common (i) symptoms and signs compatible with asthma and (ii) a relationship with exposures in the workplace. The types of WRA described in this review are distinguished by their etiology, comprising of work-exacerbated asthma (WEA), irritant-induced asthma (IIA), and immunologic occupational asthma (OA). There have been significant advances in the definition and characterization of the different forms of WRA by international panels of experts. The present review provides a comprehensive and updated view of the current knowledge on causes and phenotypes of WRA. Health care practitioners should consider WRA in any case of adult asthma, given that one fifth of workers with asthma report symptoms of WEA and it has been estimated that OA represents 10% to 25% of asthma in adulthood. The information provided in this review will facilitate the physician in the recognition of the different forms of WRA, since it has been established that five categories of agents are responsible for at least 60% of WEA cases and seven groups of agents are the cause of 70% of immunologic OA. In addition, there is agreement that IIA can be elicited not only by a single massive irritant exposure, but also by low/moderate repeated irritant exposures.

New causes of immunologic occupational asthma, 2012-2014.

The objective of this study was to review all new causes of well documented immunologic occupational asthma (IOA) published in the English and French medical literature between January 2012 and mid-2014. Ten case reports of new causes of IOA were reported during that period. The diagnosis was either confirmed by specific inhalation challenges (n = 5) or a combination of peak expiratory flow monitoring at and off work, confirmation of specific sensitisation, and asthma (n = 3). These involved both high (mites contaminating cured ham, various enzymes used as detergents and food additives, aquarium fish food, and orange allergens) and low-molecular-weight agents (spruce wood dust, a biocide, and an halogenated platinum compound used in cytotoxic drugs). Furthermore, eight studies reported cases of IOA with agents already known as airway sensitizers but in working environments that were unusual and reported for the first time. There are more than 400 known causes of IOA and the list grows continuously with the development of new technologies and better recognition of the diagnosis by physicians. IgE-mediated sensitization was confirmed in all new cases involving high-molecular-weight agents and in two of the three new cases involving low-molecular-weight agents. Symptoms of rhinitis were often associated with both types of agents. Physicians should stay alert and suspect occupational asthma in any adult with new-onset asthma or with newly uncontrolled asthma.

Occupational asthma follow-up — which markers are elevated in exhaled breath condensate and plasma?

To search for optimal markers in the exhaled breath condensate (EBC), plasma and urine that would reflect the activity/severity of occupational asthma (OA) after the withdrawal from the exposure to the allergen. Markers of oxidative stress: 8-iso-prostaglandin F2α (8-isoprostane, 8-ISO), malondialdehyde (MDA), 4-hydroxy-trans-2-nonenale (HNE), cysteinyl leukotrienes (LT) and LTB4 were determined using liquid chromatography and mass spectrometry in 43 subjects with immunological OA (49.3 ± 11.8 years), removed from the exposure to the sensitizing agent 10.5 ± 6.5 years ago; and in 20 healthy subjects (49.0 ± 14.9 years). EBC was harvested both before and after the methacholine challenge test. In parallel, identical markers were collected in plasma and urine. The results were analyzed together with forced expiratory volume in one second (FEV1), blood eosinophils, immunoglobulin E (IgE) and eosinophilic cationic protein (ECP) and statistically evaluated (Spearman rank correlation rS, two- or one-sample t tests and alternatively Kruskal Wallis or pair Wilcoxon tests). Several parameters of lung functions were lower in the patients (FEV1% predicted, MEF25% and MEF50%, Rtot%, p < 0.001). Shorter time interval since the removal from the allergen exposure correlated with higher ECP (rS = 0.375) and lower FEV1%, MEF25% and MEF50% after methacholine challenge (rS = -0.404, -0.425 and -0.532, respectively). In the patients, IgE (p < 0.001) and ECP (p = 0.009) was increased compared to controls. In EBC, 8-ISO and cysteinyl LTs were elevated in the asthmatics initially and after the challenge. Initial 8-ISO in plasma correlated negatively with FEV1 (rS = -0.409) and with methacholine PD20 (rS = -0.474). 8-ISO in plasma after the challenge correlated with IgE (rS = 0.396). The improvement in OA is very slow and objective impairments persist years after removal from the exposure. Cysteinyl LTs and 8-ISO in EBC and 8-ISO in plasma might enrich the spectrum of useful objective tests for the follow-up of OA.

Management of work-related asthma: guidelines and challenges

Asthma is one of the most common chronic diseases in working populations. Overall, ∼15% of all adult-onset asthma is estimated to be caused by occupational exposure to a respiratory sensitiser or irritant [1–3]. Although occupational asthma is probably the most frequently reported respiratory disorder in varying occupations [4, 5], the disease is still underdiagnosed. Systematic research on incidence rates, health impact and socioeconomic burden of occupational asthma is sparse and national estimates are difficult to compare [5–7]. Work-related asthma imposes a significant financial cost that is mainly borne by affected employees and government [8, 9]. On top of physical impairment, the patient faces problems regarding employment [10] and other psychosocial problems [11]. However, proper management is not expensive [12] and even a low reduction in disease burden would be cost effective [13]. Moreover, prevention management towards occupational asthma influences the health impact of diseases with overlapping risk factors, such as chronic obstructive pulmonary disease. Work-related asthma covers occupational asthma and work aggravated/exacerbated asthma. Occupational asthma includes asthma caused by (allergic) sensitisation to a workplace agent, with sensitisation occurring during an asymptomatic latency period via immunoglobulin (Ig)E-mediated mechanisms or other hitherto largely unknown mechanisms, and irritant-induced asthma which occurs without evidence of sensitisation to the offending agent [14]. The clinical course of immunological occupational asthma with latency period does not differ from non-occupational allergic asthma, where a low amount of allergen is sufficient to provoke symptoms and where an evolution towards persistent “nonspecific” asthma is possible if exposure persists. This clinical course and the high prevalence of occupational asthma underscore the need to invest further in the challenging prevention of occupational asthma at both the individual and …

Time trends in occupational asthma in Belgium

There is little information on the changes in the pattern of occupational asthma (OA) over time. The objective of this study was to evaluate the time trends in the incidence and causes of immunological OA in Belgium using workers' compensation data. Cases of OA were identified through a retrospective review of all claims submitted by salaried workers to the Belgian Workers' Compensation Board from 1993 to 2002. The likelihood of OA was categorized as definite, probable, or possible based upon the results of from diagnostic procedures. Time trends were evaluated using Spearman's rank correlation for crude numbers of cases and through the negative binomial regression for incidence rates of OA per industry. From a total of 1852 claims, 971 were categorized as having definite, probable, or possible OA. There was a downward trend in the annual number of cases due to the main causes of OA (i.e. flour, isocyanates, woods, and enzymes) and an apparent increase in cases of latex-induced OA. The estimated average annual incidence of OA was 29.4 (95% CI: 27.6-31.3) new cases per million salaried workers during the 1993-2002 period. There was a significant decline in the overall incidence rate of OA throughout the study period from 35.5 new cases per million salaried workers in 1993 to 25.8 in 2002. These compensation-based data indicate that there has been a global downward trend in the incidence of OA during the nineties, although the factors that determined this reduced incidence should be further investigated.

Occupational asthma caused by triglycidyl isocyanurate

Several cases of allergic contact dermatitis, two cases of occupational asthma from over one decade ago and one case of hypersensitivity pneumonitis have been documented in painters who use polyester powder paint containing triglycidyl isocyanurate (TGIC). We report a 28-year-old female who, 4 months after beginning work in a powder-coating factory, developed asthma-like symptoms. In her workplace, aluminium frames were treated with an electrostatic powder paint containing 2.5-10% TGIC. Serial peak-flow measurements performed during both working and non-working periods demonstrated peak-flow variability of up to 46% on work days. Bronchial methacholine test results also varied between times at work and away from work. PC(20) methacholine was 0.32 mg/ml and fraction of exhaled nitric oxide (FENO) was 18 ppb. A controlled exposure challenge was performed with a placebo yielding no changes in FEV(1) over a 24-hour period. On visit 2, the patient was placed in the chamber and exposed to TGIC (4% in lactose) at a mean concentration of 3.61 mg/m(3) for a total of 15 min. A 20% fall in FEV(1) from baseline was elicited at 10 min, together with cough and wheezing. No late response was demonstrated. Twenty-four hours after the challenge, neither methacholine PC(20) nor FENO levels varied from baseline values. No IgE was detected by ELISA testing and no IgE-binding bands were found by immunoblot analysis of patient and control serum. The aforementioned results demonstrate that TGIC inhalation induced immunologic occupational asthma, although no IgE mechanism was evidenced.

Occupational Asthma

Substantial epidemiologic and clinical evidence indicates that agents inhaled at work can induce asthma. In industrialized countries, occupational factors have been implicated in 9 to 15% of all cases of adult asthma. Work-related asthma includes (1) immunologic occupational asthma (OA), characterized by a latency period before the onset of symptoms; (2) nonimmunologic OA, which occurs after single or multiple exposures to high concentrations of irritant materials; (3) work-aggravated asthma, which is preexisting or concurrent asthma exacerbated by workplace exposures; and (4) variant syndromes. Assessment of the work environment has improved, making it possible to measure concentrations of several high- and low-molecular-weight agents in the workplace. The identification of host factors, polymorphisms, and candidate genes associated with OA is in progress and may improve our understanding of mechanisms involved in OA. A reliable diagnosis of OA should be confirmed by objective testing early after its onset. Removal of the worker from exposure to the causal agent and treatment with inhaled glucocorticoids lead to a better outcome. Finally, strategies for preventing OA should be implemented and their cost-effectiveness examined.

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.