P. Sherwood Burge

Specific IgE to isocyanates: A useful diagnostic role in occupational asthma

BACKGROUND Isocyanates are the most frequent cause of occupational asthma in industrialized countries. OBJECTIVE We sought to investigate the utility of specific IgE measurement in the diagnosis of isocyanate-induced asthma. METHODS Fifty-eight of 101 patients referred for investigation were diagnosed as having isocyanate-induced occupational asthma by means of history, serial peak flow records, and bronchial provocation tests. Specific IgE antibodies to toluene diisocyanate:human serum albumin (HSA), diphenylmethane diisocyanate:HSA, and hexamethylene diisocyanate: HSA were measured in all patients by Phadebas RAST. RESULTS Twenty patients had a RAST ratio of 2 or greater to at least one isocyanate. Thirteen (28%) of the 46 patients with a positive provocation test response had a RAST ratio of 2 or greater, and nine (20%) had a RAST ratio of 3 or greater. Raising the RAST cut-off from 2 or greater to 3 or greater reduced its sensitivity but increased the specificity of the test to 100%. RAST measurement was most likely to be positive within 30 days of exposure. Serial measurements suggested that the half-life of the IgE antibodies was approximately 6 months. Evidence of cross-reactivity between isocyanate RAST responses was found in eight subjects. CONCLUSION Specific IgE to isocyanates is a more specific than sensitive index of occupational asthma. With a RAST score of 3 or greater, it is wholly specific and therefore diagnostic of isocyanate-induced asthma. The sensitivity of specific IgE measurement is highest when blood is taken less than 30 days from last exposure, which is consistent with the observed half-life.

A pooled analysis of FEV1, decline in COPD patients randomized to inhaled corticosteroids or placebo

BACKGROUND There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV(1). METHODS The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting >/= 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV(1) decline in COPD patients, and whether this relationship is modified by gender and smoking. RESULTS There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (+/- SE) relative increase in FEV(1) of 2.42 +/- 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV(1) decline (-0.01 +/- 0.09%; p = 0.86). The initial treatment effect was dependent on smoking status and gender. Smokers who continued to smoke had a smaller increase in FEV(1) during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV(1) with ICS therapy than did male ex-smokers. CONCLUSIONS We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV(1) among those who completed these randomized clinical trials.

A New Diagnostic Score for Occupational Asthma: The Area Between the Curves (ABC Score) of Peak Expiratory Flow on Days at and Away From Work

BACKGROUND Evidence-based guidelines recommend serial measurements of peak expiratory flow (PEF) on days at and away from work as the first step in the objective confirmation of occupational asthma. The aim of this study was to improve the diagnostic value of computer-based PEF analysis by using the program Oasys-2 to calculate a score from the area between the curves (ABC) of PEF on days at and away from work. METHODS Mean 2-hourly PEFs were plotted separately for workdays and rest days for 109 workers with occupational asthma and 117 control asthmatics. A score based on the ABC was computed from records containing >or= 4 day shifts, >or= 4 rest days, and >or= 6 readings per day. Patients were randomly classified into two data sets (analysis and test sets). Receiver operator characteristic (ROC) curve analysis determined a cutoff point from set 1 that best identified those with occupational asthma, which was then tested in set 2. RESULTS Logistic regression analysis showed that all ABC PEF scores were significant predictors of occupational asthma, with the best being ABC per hour from waking (odds ratio, 11.9 per 10 L/h/min; 95% confidence interval, 10.8 to 13.1). ROC curve analysis showed that a difference of 15 L/min/h provided a high specificity without compromising sensitivity in diagnosing occupational asthma. Analysis of data set 2 confirmed a specificity of 100% and sensitivity of 72%. CONCLUSION The ABC PEF score is sensitive and specific for the diagnosis of occupational asthma and can be calculated from a shorter PEF surveillance than is needed for the current Oasys-2 work effect index.

PEF analysis requiring shorter records for occupational asthma diagnosis

BACKGROUND The Oasys programme plots serial peak expiratory flow (PEF) measurements and produces scores of the likelihood that the recordings demonstrate occupational asthma. We have previously shown that the area between the mean workday and rest day PEF curves [the area between the curves (ABC) score] has a sensitivity of 69% and specificity of 100% when plotted from waking time using a cut-off score of 15 l/min/h. AIMS To investigate the minimum data requirements to maintain the sensitivity and specificity of the ABC score. METHODS A total of 196 sets of measurements from workers with occupational asthma confirmed by methods other than serial PEFs and 206 records from occupational and non-occupational asthmatics who were not at work at the time of PEF monitoring were analysed according to their mean number of readings per day. Measurements from work and rest days were sequentially removed separately and the ABC score calculated at each reduction. The sensitivity and specificity of the ABC score (using a cut-off of 15 l/min/h) was calculated for each duration. RESULTS Two-hourly measurements (approximately 8 readings per day) with eight workdays and three rest days had 68% sensitivity and 91% specificity for occupational asthma diagnosis. As readings decreased to <or=4 readings per day, >or=15 workdays were required to provide a specificity above 90%. CONCLUSIONS To be sensitive and specific in the diagnosis of occupational asthma, the ABC score requires 2-hourly PEF measurements on eight workdays and three rest days. This is a short assessment period that should improve patient compliance.

Serial lung function variability using four portable logging meters.

Objective. Portable lung function logging meters that allow measurement of peak expiratory flow (PEF) and forced expiratory volume in 1 second (FEV1) are useful for the diagnosis and exclusion of asthma. The aim of this study was to investigate the within and between-session variability of PEF and FEV1 for four logging meters and to determine the sensitivity of meters to detect FEV1 and PEF diurnal changes. Methods. Thirteen assessors (all hospital staff members) were asked to record 1 week of 2-hour PEF and FEV1 measurements using four portable lung function meters. Within-session variability of PEF and FEV1 were compared for each meter using a coefficient of variation (COV). Between-session variability was quantified using parameter estimates from a cosinor analysis which modeled diurnal change for both lung function measures and also allowed for variation between days for individual sessions. Results. The mean within-session COV for FEV1 was consistently lower than that for PEF (p < 0.001). PEF showed a higher but not significantly different (p = 0.068) sensitivity for detecting diurnal variation than FEV1. PEF was also slightly more variable between days, but not significantly different than FEV1 (p = 0.409). PEF and FEV1 diurnal variability did not differ between the 4 meters (p = 0.154 and 0.882 respectively), but within-session FEV1 COV differed between meters (p = 0.009). Conclusion. PEF was marginally more sensitive to within-day variability than FEV1 but was less repeatable. Overall, differences between the 4 meters were small, suggesting that all meters are clinically useful.

Hypersensitivity pneumonitis in workers exposed to metalworking fluids

Background This study used data from a large UK outbreak investigation, to develop and validate a new case definition for hypersensitivity pneumonitis due to metalworking fluid exposure (MWF-HP). Methods The clinical data from all workers with suspected MWF-HP were reviewed by an experienced panel of clinicians. A new MWF-HP Score was then developed to match the “gold standard” clinical opinion as closely as possible, using standard diagnostic criteria that were relatively weighted by their positive predictive value. Results The new case definition was reproducible, and agreed with expert panel opinion in 30/37 cases. This level of agreement was greater than with any of the three previously utilized case definitions (agreement in 16–24 cases). Where it was possible to calculate, the MWF-HP Score also performed well when applied to 50 unrelated MWF-HP cases. Conclusions The MWF-HP Score offers a new case definition for use in future outbreaks. Am. J. Ind. Med. 57:872–880, 2014.

Obliterative bronchiolitis in fibreglass workers: a new occupational disease?

Rationale and objectives Obliterative bronchiolitis (OB) is a rare disease with a small number of established occupational aetiologies. We describe a case series of severe OB in workers making glass-reinforced plastics. Methods Workplace exposures were the likely cause after the independent diagnosis of OB in two workers laying up the fibreglass hulls of yachts; the second worker took over the job of the first after he left following a lung transplant. Presentation of these two cases at international meetings led to others identifying similar workers. Main results We identified six workers with good evidence of OB. All were involved in preparing fibreglass with styrene resins, five as boat builders laying up fibreglass hulls and one during cooling-tower fabrication. The disease came on rapidly without unusual acute exposures. Two patients had lung transplants, while another died while waiting for one. Histology confirmed OB in the four with biopsies/post-mortem examinations or explanted lungs. Conclusions A rare, potentially fatal disease occurring in six workers laying up fibreglass with styrene resins from five different worksites suggests that work exposures were the cause of their OB. The precise agent responsible awaits identification.

Two variants of occupational asthma separable by exhaled breath nitric oxide level

UNLABELLED Exhaled nitric oxide (FE(NO)) has been used as a marker of asthmatic inflammation in non-occupational asthma, but some asthmatics have a normal FE(NO). In this study we investigated whether, normal FE(NO) variants have less reactivity in methacholine challenge and smaller peak expiratory flow (PEF) responses than high FE(NO) variants in a group of occupational asthmatics. METHODS We measured FE(NO) and PD(20) in methacholine challenge in 60 workers currently exposed to occupational agents, who were referred consecutively to a specialist occupational lung disease clinic and whose serial PEF records confirmed occupational asthma. Bronchial responsiveness (PD(20) in methacholine challenge) and the degree of PEF change to occupational exposures, (measured by calculating diurnal variation and the area between curves score of the serial PEF record in Oasys), were compared between those with normal and raised FE(NO). Potential confounding factors such as smoking, atopy and inhaled corticosteroid use were adjusted for. RESULTS There was a significant correlation between FE(NO) and bronchial hyper-responsiveness in methacholine challenge (p = 0.011), after controlling for confounders. Reactivity to methacholine was significantly lower in the normal FE(NO) group compared to the raised FE(NO) group (p = 0.035). The two FE(NO) variants did not differ significantly according to the causal agent, the magnitude of the response in PEF to the asthmagen at work, or diurnal variation. CONCLUSIONS Occupational asthma patients present as two different variants based on FE(NO). The group with normal FE(NO) have less reactivity in methacholine challenge, while the PEF changes in relation to work are similar.

Peak expiratory flow analysis in workers exposed to detergent enzymes

AIMS To study serial peak expiratory flow (PEF) responses in a group of symptomatic detergent enzyme-exposed workers. METHODS Workers were recruited from a biological detergent formulating and packaging company. Those with occupational asthma symptoms and/or specific IgE to a detergent enzyme were asked to complete 2 hourly PEF measurements for 4 weeks. Outputs from the Oasys program (Oasys score, rest-work score and rest-work difference in diurnal variation) assessed PEF response. These were then related to the levels of sensitization and current occupational exposure to detergent enzymes. RESULTS In all, 67/72 workers returned PEF records; 97% were able to return a record with at least four readings per day and 87% at least 3 weeks in length. Of total, 79% (n = 27) of those with a final diagnosis of occupational asthma had peak flow records confirming the disease using Oasys. PEF response was similar in those with high, medium and low levels of exposures and those with negative, low-moderate and high specific IgE levels. CONCLUSIONS The Oasys program is a sensitive tool for the diagnosis of detergent enzyme occupational asthma, but the levels of exposure and specific IgE sensitization to enzymes do not affect the magnitude of PEF response in symptomatic workers.

Environmental, Psychological and Organizational Correlates of Employee Health in Offices: A Proposed Model

In a survey of 4373 office workers, sampled from 47 office sites across the U.K., correlates of work-related illness were investigated. Results showed that a variety of factors influence the prevalence of 10 work-related symptoms which are characteristic of the “sick building syndrome”. Path analysis was used to develop a model to represent causal associations. This model proposes that work-related illness is affected by architectural/environmental factors, individual/psychological factors, and occupational/organizational factors. The implications of this for health promotion are outlined.