Identification of late asthmatic reactions following specific inhalation challenge.

Specific inhalation challenge (SIC) is the reference standard for the diagnosis of occupational asthma. Current guidelines for identifying late asthmatic reactions are not evidence based. OBJECTIVES: To identify the fall in forced expiratory volume in 1 s (FEV1) required following SIC to exceed the 95% CI for control days, factors which influence this and to show how this can be applied in routine practice using a statistical method based on the pooled SD for FEV1 from three control days. METHODS: Fifty consecutive workers being investigated for occupational asthma were asked to self-record FEV1 hourly for 2 days before admission for SIC. These 2 days were added to the in-hospital control day to calculate the pooled SD and 95% CI. RESULTS: 45/50 kept adequate measurements. The pooled 95% CI was 385 mL (SD 126), or 14.2% (SD 6.2) of the baseline FEV1, but was unrelated to the baseline FEV1 (r=0.06, p=0.68), or gender, atopy, smoking, non-specific reactivity or treatment before or during SIC. Thirteen workers had a late asthmatic reaction with ≥2 consecutive FEV1 measurements below the 95% CI for pooled control days, 4/13 had <15% and 9/13 >15% late fall from baseline. The four workers with ≥2 values below the 95% CI all had independent evidence of occupational asthma. CONCLUSION: The pooled SD method for defining late asthmatic reactions has scientific validity, accounts for interpatient spirometric variability and diurnal variation and can identify clinically relevant late asthmatic reactions from smaller exposures. For baseline FEV1 <2.5 L, a 15% fall is within the 95% CI.

Hospital Attendances and Acute Admissions Preceding a Diagnosis of Occupational Asthma.

PURPOSE: Occupational exposures are a common cause of adult-onset asthma; rapid removal from exposure to the causative agent offers the best chance of a good outcome. Despite this, occupational asthma (OA) is widely underdiagnosed. We aimed to see whether chances of diagnosis were missed during acute hospital attendances in the period between symptom onset and the diagnosis of OA. METHODS: Patients diagnosed with OA at the regional occupational lung disease service in Birmingham between 2007 and 2018 whose home address had a Birmingham postcode were included. Emergency department (ED) attendances and acute admission data were retrieved from acute hospitals in the Birmingham conurbation for the period between symptom onset and diagnosis. RESULTS: OA was diagnosed in 406 patients, 147 having a Birmingham postcode. Thirty-four percent (50/147) had acute hospital attendances to a Birmingham conurbation hospital preceding their diagnosis of OA, including 35 (24%) with respiratory illnesses, which resulted in referral for investigation of possible OA in 2/35. The median delay between symptom onset and diagnosis of OA was 30 months (IQR = 13-60) and between first hospital attendance with respiratory illness and diagnosis 12 months (IQR = 12-48, range 3-96 months) CONCLUSIONS: The chance to reduce the delay in the diagnosis of OA was missed in 33/35 patients admitted or seen in ED with respiratory symptoms in the period between symptom onset and diagnosis of OA. The diagnosis of OA was delayed by a median of 12 months by failure to ask about employment and work relationship of symptoms.

Occupational asthma; the limited role of air-fed respiratory protective equipment.

BACKGROUND: Evidence-based reviews have found that evidence for the efficacy of respiratory protective equipment (RPE) in the management of occupational asthma (OA) is lacking. AIMS: To quantify the effectiveness of air-fed RPE in workers with sensitizer-induced OA exposed to metal-working fluid aerosols in a car engine and transmission manufacturing facility. METHODS: All workers from an outbreak of metal-working fluid-induced OA who had continuing peak expiratory flow (PEF) evidence of sensitizer-induced OA after steam cleaning and replacement of all metal-working fluid were included. Workers kept 2-hourly PEF measurements at home and work, before and after a strictly enforced programme of RPE with air-fed respirators with charcoal filters. The area-between-curve (ABC) score from the Oasys plotter was used to assess the effectiveness of the RPE. RESULTS: Twenty workers met the inclusion criteria. Records were kept for a mean of 24.6 day shifts and rest days before and 24.7 after the institution of RPE. The ABC score improved from 26.6 (SD 16.2) to 17.7 (SD 25.4) l/min/h (P > 0.05) post-RPE; however, work-related decline was <15 l/min/h in only 12 of 20 workers, despite increased asthma treatment in 5 workers. CONCLUSIONS: Serial PEF measurements assessed with the ABC score from the Oasys system allowed quantification of the effect of RPE in sensitized workers. The RPE reduced falls in PEF associated with work exposure, but this was rarely complete. This study suggests that RPE use cannot be relied on to replace source control in workers with OA, and that monitoring post-RPE introduction is needed.

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.

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.

Do long periods off work in peak expiratory flow monitoring improve the sensitivity of occupational asthma diagnosis?

INTRODUCTION: Serial peak expiratory flow (PEF) monitoring is a useful confirmatory test for occupational asthma diagnosis. As weekends off work may not be long enough for PEF records to recover, this study investigated whether including longer periods off work in PEF monitoring improves the sensitivity of occupational asthma diagnosis. METHODS: Serial PEF measurements from workers with occupational asthma and from workers not at work during their PEF record, containing minimum data amounts and at least one rest period with > or = 7 consecutive days off work, were analysed. Diagnostic sensitivity and specificity of the area between the curves (ABC) score from waking time and Oasys score for occupational asthma were calculated for each record by including only consecutive rest days 1-3 in any rest period, including only consecutive rest days from day 4 onwards in any rest period or including all available data. RESULTS: Analysing all available off work data (including periods away from work of > or = 7 days) increased the mean ABC score by 17% from 35.1 to 41.0 l/min/h (meaning a larger difference between rest and work day PEF values) (p=0.331) and the Oasys score from 3.2 to 3.3 (p=0.588). It improved the sensitivity of the ABC score for an occupational asthma diagnosis from 73% to 80% while maintaining specificity at 96%. The effect on the Oasys score using discriminant analysis was small (sensitivity changed from 85% to 88%). CONCLUSIONS: Sensitivity of PEF monitoring using the ABC score for the diagnosis of occupational asthma can be improved by having a longer period off work.

Functions of actin in endocytosis.

Endocytosis is a fundamental eukaryotic process required for remodelling plasma-membrane lipids and protein to ensure appropriate membrane composition. Increasing evidence from a number of cell types reveals that actin plays an active, and often essential, role at key endocytic stages. Much of our current mechanistic understanding of the endocytic process has come from studies in budding yeast and has been facilitated by yeast's genetic amenability and by technological advances in live cell imaging. While endocytosis in metazoans is likely to be subject to a greater array of regulatory signals, recent reports indicate that spatiotemporal aspects of vesicle formation requiring actin are likely to be conserved across eukaryotic evolution. In this review we focus on the 'modular' model of endocytosis in yeast before highlighting comparisons with other cell types. Our discussion is limited to endocytosis involving clathrin as other types of endocytosis have not been demonstrated in yeast.

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 (FEV(1)) 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 FEV(1) for four logging meters and to determine the sensitivity of meters to detect FEV(1) and PEF diurnal changes. METHODS: Thirteen assessors (all hospital staff members) were asked to record 1 week of 2-hour PEF and FEV(1) measurements using four portable lung function meters. Within-session variability of PEF and FEV(1) 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 FEV(1) 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 FEV(1). PEF was also slightly more variable between days, but not significantly different than FEV(1) (p = 0.409). PEF and FEV(1) diurnal variability did not differ between the 4 meters (p = 0.154 and 0.882 respectively), but within-session FEV(1) COV differed between meters (p = 0.009). CONCLUSION: PEF was marginally more sensitive to within-day variability than FEV(1) but was less repeatable. Overall, differences between the 4 meters were small, suggesting that all meters are clinically useful.

Diesel exhaust causing low-dose irritant asthma with latency?

BACKGROUND: Diesel exhaust exposure may cause acute irritant-induced asthma and potentiate allergen-induced asthma. There are no previous reports of occupational asthma due to diesel exhaust. AIMS: To describe occupational asthma with latency in workers exposed to diesel exhaust in bus garages. METHODS: The Shield database of occupational asthma notifications in the West Midlands, UK, was searched between 1990 and 2006 for workers where diesel exhaust exposure was thought to be the cause of the occupational asthma. Those without other confounding exposures whose occupational asthma was validated by serial peak expiratory flow (PEF) analysis using Oasys software were included. RESULTS: Fifteen workers were identified with occupational asthma attributed to diesel exhaust. Three had validated new-onset asthma with latency. All worked in bus garages where diesel exhaust exposure was the only likely cause of their occupational asthma. Occupational asthma was confirmed by measures of non-specific reactivity and serial measurements of PEF with Oasys scores of 2.9, 3.73 and 4 (positive score > 2.5). CONCLUSIONS: The known non-specific irritant effects of diesel exhaust suggest that this is an example of low-dose irritant-induced asthma and that exposures to diesel exhaust in at least some bus garages are at a sufficient level to cause this.

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=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.

Characteristics of hypersensitivity pneumonitis diagnosed by interstitial and occupational lung disease multi-disciplinary team consensus.

INTRODUCTION: The causes of hypersensitivity pneumonitis (HP) in the UK are changing as working practices evolve, and metalworking fluid (MWF) is now a frequently reported causative exposure. We aimed to review and describe all cases of HP from our UK regional service, with respect to the causative exposure and diagnostic characteristics. METHODS: In a retrospective, cross-sectional study, we collected patient data for all 206 cases of HP diagnosed within our UK-based regional NHS interstitial and occupational lung disease service, 2002-17. This included demographics, environmental and occupational exposures, clinical features, and diagnostic tests (CT imaging, bronchiolo-alveolar cell count, lung function, histology). We grouped the data by cause (occupational, non-occupational and unknown) and by presence or absence of fibrosis on CT, in order to undertake hypothesis testing. RESULTS: Cases were occupational (n = 50), non-occupational (n = 56) or cryptogenic (n = 100) in aetiology. The commonest causes were birds = 37 (18%) and MWF = 36 (17%). Other occupational causes included humidifiers and household or commercial waste, but only one case of farmers' lung. Cryptogenic cases were associated with significantly older age, female gender, lower lung function parameters, fewer alveolar lymphocyte counts >20%, and fibrosis on CT; exposure information was missing in 22-33% of cryptogenic cases. CONCLUSION: MWF is the commonest occupational cause of HP, where workers usually present with more acute/subacute features and less fibrosis on CT; refuse work is an emerging cause. Cryptogenic HP has a fibrotic phenotype, and a full occupational history should be taken, as historical workplace exposures may be relevant.

Understanding health beliefs and behaviour in workers with suspected occupational asthma.

INTRODUCTION: Long delays from symptom onset to the diagnosis of occupational asthma have been reported in the UK, Europe and Canada and workers are often reluctant to seek medical help or workplace solutions for their symptoms. Reducing this delay could improve workers' quality of life, and reduce the societal cost of occupational asthma. This study aimed to explore reasons behind such delays. METHODS: A purposive sample of 20 individuals diagnosed with, or under investigation for, occupational asthma (median age = 52; 70% male; 80% white British) undertook a single semi-structured interview. Interviews were transcribed verbatim and thematic analysis was undertaken in order to explore health beliefs and identify barriers to diagnosis. RESULTS: Four themes were identified: (1) workers' understanding of symptoms, (2) working relationships, (3) workers' course of action and (4) workers' negotiation with healthcare professionals. Understanding of symptoms varied between individuals, from a lack of insight into the onset, pattern and nature of symptoms, through to misunderstanding of what they represented, or ignorance of the existence of asthma as a disease entity. Workers described reluctance to discuss health issues with managers and peers, through fear of job loss and a perceived lack of ability to find a solution. The evolution of workers' understanding depended upon how actively they looked to define symptoms or seek a solution. Proactive workers were motivated to seek authoritative help and negotiate inadequate healthcare encounters with GPs. CONCLUSION: Understanding workers' health beliefs will enable policy makers and clinicians to develop better workplace interventions that may aid diagnosis and reduce delay in identifying occupational asthma.