Asthma related to cleaning agents: a clinical insight.

OBJECTIVE: To determine the agents causing asthmatic reactions during specific inhalation challenges (SICs) in workers with cleaning-related asthma symptoms and to assess the pattern of bronchial responses in order to identify the mechanisms involved in cleaning-related asthma. DESIGN: A retrospective case series analysis. SETTING: The study included all participants who completed an SIC procedure with the cleaning/disinfection products suspected of causing work-related asthma over the period 1992-2011 in a tertiary centre, which is the single specialised centre of the French-speaking part of Belgium where all participants with work-related asthma are referred to for SIC. RESULTS: The review identified 44 participants who completed an SIC with cleaning/disinfection agents. Challenge exposure to the suspected cleaning agents elicited a ≥20% fall in forced expiratory volume in 1 s (FEV1) in 17 (39%) participants. The cleaning products that induced a positive SIC contained quaternary ammonium compounds (n=10), glutaraldehyde (n=3), both of these agents (n=1) and ethanolamines (n=2). Positive SICs were associated with a significant decrease in the median (IQR) value of the provocative concentration of histamine causing a 20% fall in FEV1 (PC20) from 1.4 (0.2-4.2) mg/mL at baseline to 0.5 (0.4-3.0) mg/mL after the challenge and a significant increase in sputum eosinophils from 1.8 (0.8-7.2)% at baseline to 10.0 (4.1-15.9)% 7 h after the challenge exposure while these parameters did not significantly change in participants with a negative SIC. Overall, 11 of 17 participants with positive SICs showed greater than threefold decrease in postchallenge histamine PC20 value, a >2% increase in sputum eosinophils, or both of these outcomes. CONCLUSIONS: These data indicate that a substantial proportion of workers who experience asthma symptoms related to cleaning materials show a pattern of bronchial reaction consistent with sensitiser-induced occupational asthma. The results also suggest that quaternary ammonium compounds are the principal cause of sensitiser-induced occupational asthma among cleaners.

The effect of clinical covariates on the diagnostic and prognostic value of soluble mesothelin and megakaryocyte potentiating factor.

BACKGROUND: Soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF) are serum biomarkers of mesothelioma. This study examined the effect of clinical covariates on biomarkers levels and their diagnostic and prognostic value. METHODS: Five hundred ninety-four participants were enrolled in a multicenter study, including 106 patients with mesothelioma and 488 control subjects. Multiple linear regression analyses were used to identify which covariates were independently associated with SM and MPF levels. The effect of these covariates on the diagnostic accuracy was evaluated with receiver operating characteristics curve analysis. In patients with mesothelioma, survival analysis was performed with Cox regression. RESULTS: SM and MPF levels were independently associated with age, glomerular filtration rate (GFR), and BMI in control subjects and with GFR and tumor stage in patients with mesothelioma. The diagnostic accuracy of SM and MPF was significantly affected by the distribution of these covariates in the study population. The patients with mesothelioma were best discriminated from the control subjects with either the youngest age, the highest GFR, or the largest BMI. Furthermore, the control subjects were significantly better differentiated from stage II to IV than from stage I mesothelioma. MPF, not SM, was an independent negative prognostic factor, but only if adjusted for the biomarker-associated covariates. CONCLUSIONS: SM and MPF levels were affected by the same clinical covariates, which also had a significant impact on their diagnostic and prognostic value. To improve the interpretation of biomarker results, age, GFR, and BMI should be routinely recorded. Approaches to account for these covariates require further validation, as does the prognostic value of SM and MPF.

Time trends in occupational asthma in Belgium.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Serial measurements of mesothelioma serum biomarkers in asbestos-exposed individuals: a prospective longitudinal cohort study.

INTRODUCTION: Soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF) are serum biomarkers of mesothelioma. This study aims to examine the longitudinal behavior of SM and MPF in controls to gain insight in the optimal use of these biomarkers in screening. METHODS: Asbestos-exposed individuals, with no malignant disease at inclusion, were surveilled for 2 years with annual measurements of SM and MPF. Fixed thresholds were set at 2.10 nmol/L for SM and 13.10 ng/ml for MPF. Longitudinal biomarker analysis, using a random intercept model, estimated the association with age and glomerular filtration rate (GFR), and the intraclass correlation. The latter represents the proportion of total biomarker variance accounted for by the between-individual variance. RESULTS: A total of 215 participants were included, of whom 179 and 137 provided a second sample and third sample, respectively. Two participants with normal SM and MPF levels presented afterward with mesothelioma and lung cancer, respectively. Participants with elevated biomarker levels were typically older and had a lower GFR. During follow-up, biomarker levels significantly increased. Longitudinal analysis indicated that this was in part due to aging, while changes in GFR had a less pronounced effect on serial biomarker measurements. SM and MPF had a high intraclass correlation of 0.81 and 0.78, respectively, which implies that a single biomarker measurement and fixed threshold are suboptimal in screening. CONCLUSIONS: The longitudinal behavior of SM and MPF in controls indicates that a biomarker-based screening approach can benefit from the incorporation of serial measurements and individual-specific screening rules, adjusted for age and GFR. Large-scale validation remains nevertheless mandatory to elucidate whether such an approach can improve the early detection of mesothelioma.

Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma.

RATIONALE: Soluble mesothelin (SM) is currently the reference serum biomarker of malignant pleural mesothelioma (MPM). Megakaryocyte potentiating factor (MPF), which originates from the same precursor protein, is potentially more sensitive, yet lacks validation. OBJECTIVES: To analyze the diagnostic performance of MPF as an MPM biomarker and compare this performance with SM. METHODS: A total of 507 participants were enrolled in six cohorts: healthy control subjects (n = 101), healthy asbestos-exposed individuals (n = 89), and patients with benign asbestos-related disease (n = 123), benign respiratory disease (n = 46), lung cancer (n = 63), and MPM (n = 85). Sera were analyzed for SM and MPF levels using the Mesomark and Human MPF ELISA kit, respectively. MEASUREMENTS AND MAIN RESULTS: SM and MPF levels differed significantly between patients with MPM and participants from each other cohort (P < 0.001). Receiver operating characteristics curve analysis did not reveal a significant difference between both markers in area under curve (AUC) for distinguishing MPM from all cohorts jointly (SM = 0.871, MPF = 0.849; P = 0.28). At 95% specificity, SM and MPF had a sensitivity of 64% (cutoff = 2.00 nmol/L) and 68% (cutoff = 12.38 ng/ml), respectively. Combining both markers did not improve the diagnostic performance. CONCLUSIONS: In this prospective multicenter study, MPF is validated as a highly performant MPM biomarker. The similar AUC values of SM and MPF, together with the limited difference in sensitivity, show that both serum biomarkers have an equivalent diagnostic performance.

Rhinitis in subjects with work-exacerbated asthma.

OBJECTIVES: This study aimed at characterizing the nature, severity, and timing of nasal and ocular symptoms in subjects with work-exacerbated asthma (WEA). METHODS: Among the 363 subjects referred to a tertiary-care hospital for the investigation of work-related asthma symptoms, 105 subjects who demonstrated non-specific bronchial hyperresponsiveness to histamine, but a negative response to a specific inhalation challenge with the suspected occupational agent(s) were considered as having WEA. Their characteristics were compared with those of 172 subjects with occupational asthma (OA), ascertained by a positive response to a specific inhalation challenge. RESULTS: A high proportion of subjects with WEA (83%) and OA (90%) reported at least one nasal symptom at work. Sneezing/itching and rhinorrhea were more frequent in subjects with OA (78% and 70%, respectively) than in those with WEA (61%, p = 0.004 and 57%, p = 0.038, respectively), while post-nasal discharge was more common in WEA (30%) than in OA (18%, p = 0.019). Nasal symptoms were less severe in WEA (median [25th-75th percentiles] global severity score: 4 [2-6]) as compared to OA (5 [4-7], p < 0.001). Nasal symptoms preceded less frequently those of asthma in subjects with WEA (17%) than in subjects with OA (43%, p = 0.001). CONCLUSIONS: Nasal symptoms are highly prevalent in subjects with WEA, although their clinical pattern differs from that found in OA. Further investigations of the health and socio-economic impacts of upper airways symptoms in WEA are required to improve the understanding and management of this common condition.