Positive Specific Inhalation Challenge Research Articles

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 (sIgE) against wheat and rye flour, however, has not been thoroughly compared to other diagnostic procedures. 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. 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. 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. 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.

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...

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.

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

Occupational eosinophilic bronchitis (OEB) has been described only as anecdotal case reports. 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. 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. 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 negativeSIC was low, ranging from 43% to 24% using cutoff values of 8 ppb to 17.5 ppb, whereas the specificity was high (90%-97%). 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.

Severe Occupational Asthma: Insights From a Multicenter European Cohort

Although sensitizer-induced occupational asthma (OA) accounts for an appreciable fraction of adult asthma, the severity of OA has received little attention. The aim of this study was to characterize the burden and determinants of severe OA in a large multicenter cohort of subjects with OA. 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. 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). 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.

Occupational Asthma From Epoxy Compounds

Two-component epoxy resin systems (ERSs) composed of epoxy resin and polyamine hardeners are extensively used in industrial and construction coating. Triglycidyl isocyanurate (TGIC) is another type of epoxy derivative, mostly encountered in polyester powder paints. Epoxy compounds are well-known skin sensitizers, but their respiratory-sensitizing potential is largely unknown. To report patients examined for occupational asthma (OA) from epoxy compounds. We retrospectively reviewed patient files of cases tested with a placebo-controlled specific inhalation challenge (SIC) according to their workplace exposure-either by mixing epoxy resin and the polyamine hardener of a 2-component paint or by dusting or heating TGIC-containing powder paint. The data were collected from the Finnish Institute of Occupational Health, Helsinki, Finland, and at Fundación Jiménez Díaz Hospital, Madrid, Spain, during 1997 to 2018. We also measured airborne polyamine and solvent vapors at the workplace and during SIC with ERSs. Altogether 113 patients with work-related asthma symptoms underwent SIC with ERSs. Fifteen cases (13%) had positive SIC reactions confirming OA; in 12 cases reactions were late-type, in 1 case early, and in 2 cases combined. The median duration of exposure for patients with OA was 10 years; 2 of them (13%) had a diagnosis of allergic contact dermatitis from ERS compounds. In addition, 3 cases had a positive SIC reaction to TGIC. The airborne polyamine levels measured were low. ERSs and TGIC can cause sensitizer-induced OA in some exposed workers. Respiratory exposure to ERSs is difficult to demonstrate using air measurements.

Do laboratory challenge tests for occupational asthma represent what happens in the workplace?

Specific inhalation challenge (SIC) is the diagnostic reference standard for occupational asthma; however, a positive test cannot be considered truly significant unless it can be reproduced by usual work exposures. We have compared the timing and responses during SIC in hospital to Oasys analysis of serial peak expiratory flow (PEF) during usual work exposures.All workers with a positive SIC to occupational agents between 2006 and 2015 were asked to measure PEF every 2 h from waking to sleeping for 4 weeks during usual occupational exposures. Responses were compared between the laboratory challenge and the real-world exposures at work.All 53 workers with positive SIC were included. 49 out of 53 had records suitable for Oasys analysis, 14 required more than one attempt and all confirmed occupational work-related changes in PEF. Immediate SIC reactors and deterioration within the first 2 h of starting work were significantly correlated with early recovery, and late SIC reactors and a delayed start to workplace deterioration were significantly correlated with delayed recovery. Dual SIC reactions had features of immediate or late SIC reactions at work rather than dual reactions.The concordance of timings of reactions during SIC and at work provides further validation for the clinical significance of each test.

Assessment of eosinophilic airway inflammation as a contribution to the diagnosis of occupational asthma.

Ascertaining the presence of asthma through the assessment of nonspecific bronchial hyperresponsiveness (NSBH) is a key step in the diagnosis of occupational asthma (OA). We aimed at investigating whether indices of airway inflammation including fractional exhaled nitric oxide (FeNO) and sputum eosinophils would be useful adjuncts to the measurement of NSBH in diagnosing OA defined as a positive specific inhalation challenge (SIC). The study included 240 consecutive subjects with a suspicion of OA who completed a SIC, of whom 133 showed a positive response. The sensitivity, specificity, and predictive values of NSBH, and FeNO, as well as sputum eosinophil counts assessed at baseline of the SIC were determined. A concentration of histamine inducing a 20% decline in FEV1 (PC20 ) ≤16 mg/mL showed a sensitivity of 87% and a specificity of 36%. A FeNO level ≥25 ppb and a sputum eosinophil count ≥2% provided lower sensitivity rates (47% and 39%, respectively) than the PC20 value. Eight of the 17 subjects without baseline NSBH despite a positive SIC showed a sputum eosinophil count ≥2%, a FeNO level ≥25 ppb, or both outcomes. Combining either a PC20 value ≤16 mg/mL or a FeNO ≥25 ppb increased the sensitivity to 91%. Using either a PC20 ≤16 mg/mL or a sputum eosinophil count ≥1% increased the sensitivity to 94%. Adding the assessment of FeNO level and sputum eosinophils to NSBH improves the identification of subjects who may have OA and require further objective testing before excluding the possibility of OA.

Distinct Clinical Phenotypes of Occupational Asthma due to Diisocyanates.

To assess whether diisocyanate occupational asthma represents a unique phenotype. We studied 187 patients with diagnosis of asthma due to diisocyanates confirmed by a positive specific inhalation challenge. The simplified algorithm from severe asthma research program (SARP) (Moore et al, 2010) was applied to classify patients into five clusters. Our patients were allocated in three of the five clusters described in common asthma, since the most severe Clusters (4 and 5) were not represented. Cluster 2 was the most populated, as in common asthma, and included the youngest patients with the shortest duration of exposure to the sensitizers. Cluster 3 included older men patients with worse lung function and longer occupational exposure. Diisocyanate asthma is a heterogeneous disease. Differences across clusters include demographic characteristics, lung function, and chronology of diisocyanate exposure.

Fractional Exhaled Nitric Oxide (FeNO) in the Screening and Diagnosis Work-Up of Occupational Asthma

FeNO is a simple non-invasive tool used as a surrogate marker of airway inflammation in the management of asthma. FeNO has been assessed in several populations of workers exposed to high- and low-molecular weight agents. However, there are many confounding factors to consider in the interpretation of FeNO. As such, its use in the investigation of occupational asthma (OA) has yielded inconsistent results. In screening studies of OA to high molecular weight (HMW) agents, an increase of FeNO over time has been associated with the development of bronchial hyperresponsiveness (BHR). When used in the investigation of OA, increases in FeNO show high positive predictive values for a positive specific inhalation challenge (SIC) to HMW agents. Subjects with high specific IgE to their workplace allergens seem to present higher increases in FeNO than subjects without specific IgE to causal agent. Changes in FeNO have less frequently been observed in studies of OA to low molecular weight (LMW) agents than OA to HMW agents, except for isocyanate-induced OA. Cluster analyses of patients exposed to various HMW and LMW agents have documented significant increases of FeNO in clusters of patients with OA to HMW agents, but not LMW. Recent studies have provided useful information for improving our understanding of the pathophysiology of exhaled NO in OA despite the previously reported conflicting results. Future studies are still required to clarify its role in the screening, investigation, and management of OA.

Occupational asthma caused by acrylic compounds from SHIELD surveillance (1989-2014).

Acrylic monomers (acrylates), methacrylates and cyanoacrylates all cause asthma by respiratory sensitization. Occupational inhalation exposures occur across a variety of industries including health care and dental work, beauty, laboratory science, assembly and plastic moulding. To examine notifications of occupational asthma caused by acrylic compounds from a UK-based regional surveillance scheme, in order to highlight prevalent exposures and trends in presentation. Retrospective review of all cases reported to the SHIELD surveillance scheme for occupational asthma, West Midlands, UK between 1989 and 2014. Patient data were gathered on demographics, employment, asthma symptoms and diagnostic investigations including serum immunological testing, serial peak flow analysis and specific inhalation challenge tests. Descriptive statistics were used to illustrate worker characteristics and evidence for sensitization to acrylic compounds. There were 20 affected patients out of 1790 total cases of occupational asthma (1%); all cases were confirmed by OASYS (Occupational Asthma SYStem) analysis of serial peak flow measurements, with three additional positive specific inhalation challenge tests. Three out of 20 (15%) patients were current smokers and 11/20 (55%) were atopic. A variety of exposures and industries were implicated including: manufacturing, health care, beauty and printing and a novel presentation seen in teachers exposed to floor adhesives. This is the largest reported series of occupational asthma caused by acrylic compounds, which remain an important aetiological factor in this disease. Exposure occurs in a variety of industries, particularly in manufacturing and is seen with other, perhaps better recognized sensitizing agents such as isocyanates and epoxy resins.

Diagnostic Accuracy of Inflammatory Markers for Diagnosing Occupational Asthma

The assessment of airway responsiveness andinflammation is key to the investigation of occupational asthma (OA). We sought to assess and compare the diagnostic accuracies of the blood and sputum eosinophil counts and the methacholine challenge for the diagnosis of OA. We conducted a retrospective study assessing 618 patients who underwent specific inhalation challenges (SICs) for symptoms suggestive of OA between 2000 and 2015. A sputum induction and a methacholine challenge were performed before and after SICs. Blood samples were collected in all subjects before the SICs and in 100 subjects before and after SICs. The diagnostic accuracies of blood and sputum eosinophil counts and methacholine challenge were calculated for diagnosing OA. The change in blood eosinophil count failed to differentiate workers with positive and negative SICs. The change in sputum eosinophil counts induced by the exposure to the offending agent had the highest diagnostic accuracy (receiver operating characteristic area under the curve: 86% [95% confidence interval: 0.8-0.9, P < .001]) for diagnosing OA compared with changes in concentration of methacholine inducing a 20% fall in forced expiratory volume in 1 second (PC20) and blood eosinophils. Combining a 2-fold or greater decrease in PC20 or a 3% or greater increase in sputum eosinophil count achieved a sensitivity of 84% and a specificity of 74% with a negative predictive value of 91% for the diagnosis ofOA. Blood eosinophil counts do not appear to be an effective aid for diagnosing OA. The performance of both sputum cell count analysis and a methacholine challenge before and after exposure to the offending agent may represent an effective alternative in diagnosing OA when SICs are unavailable.

Specific inhalation challenge: the relationship between response, clinical variables and lung function

IntroductionThe specific inhalation challenge (SIC) is considered the gold standard for the diagnosis of occupational asthma (OA). However, its use is not standardised, and the intensity of exposure is regulated...

Do Low Molecular Weight Agents Cause More Severe Asthma than High Molecular Weight Agents?

IntroductionThe aim of this study was to analyse whether patients with occupational asthma (OA) caused by low molecular weight (LMW) agents differed from patients with OA caused by high molecular weight (HMW) with regard to risk factors, asthma presentation and severity, and response to various diagnostic tests.MethodsSeventy-eight patients with OA diagnosed by positive specific inhalation challenge (SIC) were included. Anthropometric characteristics, atopic status, occupation, latency periods, asthma severity according to the Global Initiative for Asthma (GINA) control classification, lung function tests and SIC results were analysed.ResultsOA was induced by an HMW agent in 23 patients (29%) and by an LMW agent in 55 (71%). A logistic regression analysis confirmed that patients with OA caused by LMW agents had a significantly higher risk of severity according to the GINA classification after adjusting for potential confounders (OR = 3.579, 95% CI 1.136–11.280; p = 0.029). During the SIC, most patients with OA caused by HMW agents presented an early reaction (82%), while in patients with OA caused by LMW agents the response was mainly late (73%) (p = 0.0001). Similarly, patients with OA caused by LMW agents experienced a greater degree of bronchial hyperresponsiveness, measured as the difference in the methacholine dose-response ratio (DRR) before and after SIC (1.77, range 0–16), compared with patients with OA caused by HMW agents (0.87, range 0–72), (p = 0.024).ConclusionsOA caused by LMW agents may be more severe than that caused by HMW agents. The severity of the condition may be determined by the different mechanisms of action of these agents.

The role of allergen components for the diagnosis of latex-induced occupational asthma.

Recombinant Hevea brasiliensis (rHev b) natural rubber latex (NRL) allergen components have been developed to assess the patients' allergen sensitization profile and to improve the diagnosis of NRL allergy. To examine whether the determination of specific IgE (sIgE) reactivity to a panel of recombinant allergen components would be helpful for diagnosing NRL-induced occupational asthma (OA) in predicting the outcome of a specific inhalation test. sIgE levels to NRL extract and 12 recombinant NRL allergen components were assessed in 82 subjects with OA ascertained by a positive specific inhalation challenge (SIC) with NRL gloves and in 25 symptomatic subjects with a negative challenge. The sensitivity, specificity, positive predictive value, and negative predictive value of a NRL-sIgE level ≥0.35 kUA /l as compared to the result of SICs were 94%, 48%, 86%, and 71%, respectively. The positive predictive value increased above 95% when increasing the cutoff value to 5.41 kUA /l. Subjects with a positive SIC showed a significantly higher rate of sIgE reactivity to rHev b 5, 6.01, 6.02, and 11 than those with a negative SIC. A sIgE sum score against rHev b 5 plus 6.01/6.02 ≥ 1.46 kUA /l provided a positive predictive value >95% with a higher sensitivity (79%) and diagnostic efficiency (Youden index: 0.67) as compared with a NRL-sIgE ≥5.41 kUA /l (49% and 0.41, respectively). In suspected OA, high levels of sIgE against rHev b 5 combined with rHev b 6.01 or 6.02 are the most efficient predictors of a bronchial response to NRL.

Utility of Exhaled Nitric Oxide Fraction for the Diagnosis of Hypersensitivity Pneumonitis

There is very little evidence of the utility of the exhaled fraction of NO (FeNO) for the diagnosis of interstitial lung disease and nearly all of it is related with connective tissue disease. Some authors have suggested that in patients with hypersensitivity pneumonitis (HP), evolution to pulmonary fibrosis may be mediated by a Th2 mechanism, which could redound in a potential utility of FeNO. The aim of this study was to investigate the values of FeNO before and after antigenic exposure with the specific inhalation challenge (SIC) and to analyze its potential utility for the diagnosis of HP. It was a prospective, cross-sectional study of all patients older than 18 years referred to our center for suspected chronic HP between May 2012 and May 2014 and who underwent a SIC. FeNO was collected before and after SIC. The study sample comprised 25 patients. Eleven were diagnosed with chronic HP; six had been exposed to avian proteins and five to fungal agents. Of these 11 patients, seven had positive SICs. In the 14 patients with diagnoses other than HP, all the SICs were negative. No significant differences in baseline characteristics were observed according to HP diagnosis, except in the BAL lymphocyte count. No differences were found after the test in patients diagnosed with HP; nor were there differences in baseline FeNO in patients diagnosed with HP and those who received alternative diagnoses. The results suggest that FeNO measurement is not useful for the diagnosis of chronic HP.

Importance of specific inhalation challenge in the diagnosis of occupational asthma induced by quaternary ammonium compounds

Importance of specific inhalation challenge in the diagnosis of occupational asthma induced by quaternary ammonium compounds

Is the analysis of histamine and/or interleukin-4 release after isocyanate challenge useful in the identification of patients with IgE-mediated isocyanate asthma?

Isocyanates are a well-known and frequent cause of occupational asthma. The implementation of specific inhalation challenges (SICs) is the gold standard in asthma diagnosis supporting occupational case history, lung function testing, specific skin prick tests and the detection of specific IgE. However, the diagnosis is not always definitive. An interesting new approach, analyses of individual genetic susceptibilities, requires discrimination between a positive SIC reaction arising from IgE-mediated immune responses and one from other pathophysiological mechanisms. Hence, additional refinement tools would be helpful in defining sub-classes of occupational asthma and diagnosis. We used total IgE levels, specific IgE and SIC results for sub-classification of 27 symptomatic isocyanate workers studied. Some mutations in glutathione S-transferases (GSTs) are suspected either to enhance or to decrease the individual risk in the development of isocyanate asthma. Our patient groups were assessed for the point mutations GSTP1*I105V and GSTP1*A114V as well as deletions (null mutations) of GSTM1 and GSTT1. There seems to be a higher risk in developing IgE-mediated reactions when GSTM1 is deleted, while GSTT1 deletions were found more frequently in the SIC positive group. Blood samples taken before SIC, 30–60min and 24h after SIC, were analyzed for histamine and IL-4, classical markers for the IgE-mediated antigen-specific activation of basophils or mast cells. We suggest that the utility of histamine measurements might provide an additional useful marker reflecting isocyanate-induced cellular reactions (although the sampling times require optimization). The promising measurement of IL-4 is not feasible at present due to the lack of a reliable, validated assay.

Investigation of occupational asthma: Do clinicians fail to identify relevant occupational exposures?

Specific inhalation challenges (SIC) enable the identification of the agent responsible of occupational asthma (OA). A clinician may fail to identify a specific agent in the workplace, which may potentially lead to a misdiagnosis. The expert assessment method performed by an occupational hygienist has been used to evaluate occupational exposures in epidemiological studies. The broad aim of the present study was to evaluate the contribution of an expert assessment performed by an occupational hygienist to the diagnosis of OA. The specific aim was to compare workplace exposures identified by an occupational hygienist and by chest physicians in subjects with positive SICs and subjects with asthma, but with a negative SIC. SICs were performed in 120 cases: 67 were positive and 53 were negative. A clinician assessed occupational exposures to sensitizers during a routine clinical evaluation preceding the performance of the SIC. An expert assessment of occupational exposures was performed by an occupational hygienist blind to the result of the SIC. The occupational hygienist identified the causal agent in 96.7% of the 61 cases of positive SIC. In 33 (62.3%) cases of negative SICs, the occupational hygienist identified ≥1 sensitizing agent(s) that had not been identified by the clinician. The hygienist identified the causal agent in almost all subjects with OA. In contrast, the clinician failed to identify potential exposures to sensitizers in >60% of the negative SIC subjects, which may have resulted in some subjects being misdiagnosed as not having OA.