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

BACKGROUND: 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 (sIgE) against wheat and rye flour, however, has not been thoroughly compared to other diagnostic procedures. OBJECTIVE: We sought to evaluate the diagnostic accuracy of sIgE against wheat and rye compared to specific inhalation challenge (SIC) with flour as the reference standard. METHODS: This retrospective multicenter study included 264 subjects who completed a SIC with flour in eight tertiary centers, of whom 205 subjects showed a positive SIC result. RESULTS: Compared with SIC, sIgE levels ≥0.35 kUA/L against wheat and rye provided similar sensitivities (84%-85%, respectively), specificities (71%-78%), positive predictive values (91%-93%), and negative predictive value (56%-61%). Increasing the threshold sIgE value to 5.10 kUA/L for wheat and to 6.20 kUA/L for rye provided a specificity ≥95% 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 post-challenge fractional exhaled nitric oxide as compared to the subjects with detectable sIgE. CONCLUSION: High levels of sIgE against wheat and/or rye flour strongly support a diagnosis of flour-induced occupational asthma without the need for performing a 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.

Long-term impairment from irritant-induced occupational asthma.

OBJECTIVE: To assess the long-term physical condition, health-related quality of life, employment, and work ability of irritant-induced asthma (IIA) patients. METHODS: Forty-three IIA patients completed a follow-up questionnaire a median of eight (interquartile range 4-11) years after asthma diagnosis. We compared their results with those of 43 low-molecular-weight (LMW) sensitizer-induced occupational asthma (OA) patients and those of 206 adult-onset asthmatics in the general population. RESULTS: Of the IIA patients, 40% reported depressive symptoms. Of the <65-year-olds, 56% were employed, of whom 39% assessed their work ability as limited. IIA patients had more difficulty climbing several flights of stairs than LMW-induced OA patients (70% vs. 47%, OR 4.83 95%CI 1.51-15.47). Most of the IIA patients' outcomes were inferior to those of the adult-onset asthmatics in the general population. CONCLUSION: IIA prognosis appeared poor but resembled that of LMW-induced OA.

Long-term outcome of occupational asthma with different etiology.

PURPOSE OF REVIEW: This review summarizes the recent literature on the long-term outcome of sensitizer-induced and irritant-induced occupational asthma. RECENT FINDINGS: Recent studies of sensitizer-induced occupational asthma show that after the offending exposure has ceased, most patients report at least partial relief of symptoms. However, in the long term, the diagnosis may negatively impact their careers, incomes, and quality of life. The studies also offer new insights into diisocyanate-induced occupational asthma phenotypes and asthma remission rates. One third of these cases were in remission in long-term after reduction or cessation of exposure. The long-term prognosis of irritant-induced occupational asthma was demonstrated to be poorer than sensitizer-induced occupational asthma. Older age, low fractional exhaled nitric oxide levels and uncontrolled asthma at the time of diagnosis predicted uncontrolled asthma in the long term in patients with irritant and low-molecular-weight sensitizer induced occupational asthma. SUMMARY: Recent studies provide further evidence of the long-term outcome of different occupational asthma phenotypes and the factors that affect them. These findings help us identify patients at risk of poor asthma outcomes, who need close monitoring and support. It should also be borne in mind that occupational asthma diagnosis may have wider-ranging negative impacts on patients' lives.

Occupational lung disease: when should I think of it and why is it important?

Exposure to toxic inhalants in the workplace has the potential to cause (in susceptible individuals) almost any major type of lung disease, such as asthma, COPD and interstitial lung diseases. Patients with occupational lung disease will often present to or will be managed by respiratory specialists without training in occupational respiratory medicine, and patients (or their clinicians) may not identify a link between their disease and their current or a past job. Without an awareness of the range of different occupational lung diseases that exist, their similarity to their non-occupational counterparts, and without directed questioning, these conditions may go unidentified. Patients with occupational lung diseases are often in lower paid work and are disproportionally affected by health inequality. Both clinical and socioeconomic outcomes generally improve if cases are identified early. This allows appropriate advice to be given about the risks of ongoing exposure, clinical management, occupational mobility and, in some cases, eligibility for legal compensation. As respiratory professionals, it is important that these cases are not missed, and if needed, are discussed with a physician with specialised expertise. Here we describe some of the most common occupational lung diseases and outline the diagnostic and treatment approach.

Long-Term Outcome of Occupational Asthma From Irritants and Low-Molecular-Weight Sensitizers.

BACKGROUND: The short-term asthma outcome of irritant-induced asthma (IIA) is poorer than that of low-molecular-weight (LMW) sensitizer-induced occupational asthma (OA). OBJECTIVES: To evaluate the long-term asthma outcome of IIA and LMW-induced OA and to determine which baseline features are associated with a poor long-term outcome. METHODS: This follow-up questionnaire study assessed 43 patients diagnosed with IIA and 43 patients with LMW-induced OA at the Finnish Institute of Occupational Health in 2004-2018. The baseline results were analyzed to detect features associated with uncontrolled asthma (Asthma Control Test [ACT] score of ≤19, or ≥2 exacerbations or ≥1 serious exacerbation within 1 year) at follow-up. RESULTS: The median interval since OA diagnosis was 6.3 years (interquartile range [IQR]: 4.4-11.3 years). Uncontrolled asthma was more frequent with IIA than with LMW-induced OA (58% vs 40%, adjusted odds ratio [OR]: 3.60, 95% confidence interval [CI]: 1.20-10.81). Poor symptom control was the main factor for this difference (median [IQR] ACT score of 18 [15-22] vs 21 [18-23], P = .036, respectively). Among all participants, older age (OR: 1.08 per year, 95% CI: 1.02-1.15), a fractional exhaled nitric oxide (FeNO) value <20 ppb (OR: 5.08, 95% CI: 1.45-17.80), and uncontrolled asthma at baseline (OR: 3.94, 95% CI: 1.31-11.88) were associated with uncontrolled asthma at follow-up. CONCLUSIONS: Long-term asthma control of IIA appears to be inferior to that of LMW-induced OA. Older age, a low FeNO value, and uncontrolled asthma at baseline might indicate a worse long-term outcome among those with IIA and LMW-induced OA.

Clinical Characteristics of Irritant-Induced Occupational Asthma.

BACKGROUND: 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. OBJECTIVES: To evaluate whether the clinical picture of IIA differs from that of sensitizer-induced OA. METHODS: 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. RESULTS: Six months after the diagnosis, 30% of the patients with IIA needed daily short-acting ß-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). CONCLUSIONS: 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.

Transcriptomic Profiling of Adult-Onset Asthma Related to Damp and Moldy Buildings and Idiopathic Environmental Intolerance.

A subset of adult-onset asthma patients attribute their symptoms to damp and moldy buildings. Symptoms of idiopathic environmental intolerance (IEI) may resemble asthma and these two entities overlap. We aimed to evaluate if a distinct clinical subtype of asthma related to damp and moldy buildings can be identified, to unravel its corresponding pathomechanistic gene signatures, and to investigate potential molecular similarities with IEI. Fifty female adult-onset asthma patients were categorized based on exposure to building dampness and molds during disease initiation. IEI patients (n = 17) and healthy subjects (n = 21) were also included yielding 88 study subjects. IEI was scored with the Quick Environmental Exposure and Sensitivity Inventory (QEESI) questionnaire. Inflammation was evaluated by blood cell type profiling and cytokine measurements. Disease mechanisms were investigated via gene set variation analysis of RNA from nasal biopsies and peripheral blood mononuclear cells. Nasal biopsy gene expression and plasma cytokine profiles suggested airway and systemic inflammation in asthma without exposure to dampness (AND). Similar evidence of inflammation was absent in patients with dampness-and-mold-related asthma (AAD). Gene expression signatures revealed a greater degree of similarity between IEI and dampness-related asthma than between IEI patients and asthma not associated to dampness and mold. Blood cell transcriptome of IEI subjects showed strong suppression of immune cell activation, migration, and movement. QEESI scores correlated to blood cell gene expression of all study subjects. Transcriptomic analysis revealed clear pathomechanisms for AND but not AAD patients. Furthermore, we found a distinct molecular pathological profile in nasal and blood immune cells of IEI subjects, including several differentially expressed genes that were also identified in AAD samples, suggesting IEI-type mechanisms.

High Prevalence of Sensitization to Mites and Insects in Greenhouses Using Biologic Pest Control.

BACKGROUND: Mites and insects are widely used as biologic pest control in greenhouses. A few studies have reported sensitization to mites among greenhouse workers, but the prevalence of sensitization to pest control insects is not known. OBJECTIVE: We aimed to determine the prevalence of IgE-mediated sensitization to pests and their control organisms in the population of exposed greenhouse workers and the relationship between sensitization and allergic symptoms. METHODS: In a cross-sectional study, we interviewed 117 tomato and cucumber greenhouse workers from eight companies that use biologic pest control. Sensitization to nine organisms was assessed by serum-specific IgE measurement. We also measured fractional exhaled nitric oxide. RESULTS: The prevalence of specific sensitization to pests and pest control organisms was 50%; to mites, 29%; and to insects, 46%. Of the individual species, Macrolophus pygmaeus insect sensitization had the highest prevalence (46%). Asthma symptoms were significantly associated with sensitization to pest and pest control organisms (odds ratio [OR] = 3.9; 95% confidence interval [CI], 1.2-12.5) and with a fractional exhaled nitric oxide level of 25 ppb or greater (OR = 4.8; 95% CI, 1.7-13.8), indicating eosinophilic airway inflammation. Southeast Asian origin was significantly associated with sensitization (OR = 5.1; 95% CI, 2.1-12.1) and rhinitis (OR = 2.8; 95% CI, 1.2-6.3). CONCLUSIONS: Tomato and cucumber greenhouse workers were commonly sensitized to predatory insect M pygmaeus and pest control mites. Our findings stress the importance of surveilling and preventing work-related allergic diseases among greenhouse workers.

Endotyping asthma related to 3 different work exposures.

BACKGROUND: Work exposures play a significant role in adult-onset asthma, but the mechanisms of work-related asthma are not fully elucidated. OBJECTIVE: We aimed to reveal the molecular mechanisms of work-related asthma associated with exposure to flour (flour asthma), isocyanate (isocyanate asthma), or welding fumes (welding asthma) and identify potential biomarkers that distinguish these groups from each other. METHODS: We used a combination of clinical tests, transcriptomic analysis, and associated pathway analyses to investigate the underlying disease mechanisms of the blood immune cells and the airway epithelium of 61 men. RESULTS: 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. CONCLUSIONS: This study provides novel data on the molecular mechanisms underlying work-related asthma. We identified a set of 5 promising biomarkers in asthma related to flour, isocyanate, and welding fume exposure to be tested and clinically validated in future studies.

Occupational Asthma Caused by Quaternary Ammonium Compounds: A Multicenter Cohort Study.

BACKGROUND: 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). OBJECTIVE: To examine the clinical, functional, and inflammatory profile of QAC-induced OA compared with OA caused by other low-molecular weight (LMW) agents. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Occupations and exposure events in acute and subacute irritant-induced asthma.

BACKGROUND: Exposures leading to irritant-induced asthma (IIA) are poorly documented. METHODS: We retrospectively screened the medical records of patients with IIA diagnosed in an occupational medicine clinic during 2000-2018. We classified the cases into acute (onset after single exposure) and subacute (onset after multiple exposures) IIA. We analysed in detail, occupations, causative agents and their air levels in the workplace, exposure events and the root causes of high exposure. RESULTS: Altogether 69 patients were diagnosed with IIA, 30 with acute and 39 with subacute IIA. The most common occupational groups were industrial operators (n=23, 33%), metal and machinery workers (n=16, 11%) and construction workers (n=12, 8%). Among industrial operators significantly more cases had subacute IIA than acute IIA (p=0.002). Forty cases (57%) were attributable to some type of corrosive acidic or alkaline chemical. Acute IIA followed accidents at work in different types of occupation, while subacute IIA was typical among industrial operators performing their normal work tasks under poor work hygiene conditions. The most common root cause was lack of information or false guidance in acute IIA (n=11, 36%) and neglect of workplace hygiene measures in subacute IIA (n=29, 74%). CONCLUSIONS: Accidents are the main causes of acute IIA, whereas subacute IIA can develop in normal work in risk trades with poor work hygiene. Airborne strong acids or bases seem to be the most important causative agents of acute and subacute IIA. The different risk profiles of acute and subacute IIA should be considered in the prevention and identification of the cases.

Characterization of Occupational Eosinophilic Bronchitis in a Multicenter Cohort of Subjects with Work-Related Asthma Symptoms.

BACKGROUND: Occupational eosinophilic bronchitis (OEB) has been described only as anecdotal case reports. OBJECTIVE: We investigated the clinical and inflammatory characteristics of subjects with OEB identified in a cohort of subjects who completed a specific inhalation challenge (SIC) with occupational agents. METHODS: In this retrospective multicenter study, OEB was defined by (1) a fall in FEV1 less than 15% during the SIC and the absence of nonspecific bronchial hyperresponsiveness both before and after the SIC and (2) a postchallenge increase of 3% or more in sputum eosinophils. The subjects who fulfilled these criteria were compared with 226 subjects with a negative SIC and 30 subjects with a positive SIC who failed to show baseline nonspecific bronchial hyperresponsiveness. RESULTS: An isolated increase in postchallenge sputum eosinophils was documented in 33 of 259 subjects (13%) with a negative SIC. These subjects reported significantly more often an isolated cough at work compared with the negative and positive SIC controls. When compared with positive SIC controls, the subjects with OEB experienced less frequently work-related wheezing and reported a shorter duration of symptoms at work. The sensitivity of the post-SIC increase in fractional exhaled nitric oxide in identifying OEB among subjects with a negative SIC was low, ranging from 43% to 24% using cutoff values of 8 ppb to 17.5 ppb, whereas the specificity was high (90%-97%). CONCLUSIONS: This study highlights the relevance of induced sputum analysis in the investigation of work-related asthma symptoms to identify isolated increases in sputum eosinophils that are consistent with a diagnosis of OEB.

Asthma onset after exposure to fluorinated hydrocarbons in the presence of combustion.

Fluorinated hydrocarbons, which can thermally degrade into toxic hydrofluoric acid, are widely used as, for example, cooling agents in refrigerators and air conditioning systems and as medical aerosol propellants. Hydrofluoric acid is a known causative agent of irritant-induced asthma. We report on two patients with asthma initiation shortly after exposure to fluorinated hydrocarbon-based cooling agents while welding or smoking cigarettes in a confined space. Both cases developed respiratory symptoms and headache and later demonstrated nonspecific bronchial hyperresponsiveness. In follow-up, asthma was persistent and responded poorly to asthma medication. Exposure to the fluorinated hydrocarbons themselves is unlikely to have caused asthma due to their low toxicity. Instead, exposure to small amounts of hydrofluoric acid via the thermal degradation of the fluorinated hydrocarbons was considered the most likely cause of asthma onset. This is supported by the typical clinical picture of irritant-induced asthma and acute symptoms resembling hydrofluoric acid poisoning. When fluorinated hydrocarbons are used in the presence of combustion, thermal degradation may lead to the formation of hydrofluoric acid. In confined spaces, this exposure may induce asthma via irritation. Welding, smoking, and other sources of combustion in confined spaces may be a risk in workplaces and other places in which fluorinated hydrocarbons are used.