Re Wiggans

UK asbestos imports and mortality due to idiopathic pulmonary fibrosis.

BACKGROUND Previous studies have demonstrated that the rising mortality due to mesothelioma and asbestosis can be predicted from historic asbestos usage. Mortality due to idiopathic pulmonary fibrosis (IPF) is also rising, without any apparent explanation. AIMS To compare mortality due to these conditions and examine the relationship between mortality and national asbestos imports. METHODS Mortality data for IPF and asbestosis in England and Wales were available from the Office for National Statistics. Data for mesothelioma deaths in England and Wales and historic UK asbestos import data were available from the Health & Safety Executive. The numbers of annual deaths due to each condition were plotted separately by gender, against UK asbestos imports 48 years earlier. Linear regression models were constructed. RESULTS For mesothelioma and IPF, there was a significant linear relationship between the number of male and female deaths each year and historic UK asbestos imports. For asbestosis mortality, a similar relationship was found for male but not female deaths. The annual numbers of deaths due to asbestosis in both sexes were lower than for IPF and mesothelioma. CONCLUSIONS The strength of the association between IPF mortality and historic asbestos imports was similar to that seen in an established asbestos-related disease, i.e. mesothelioma. This finding could in part be explained by diagnostic difficulties in separating asbestosis from IPF and highlights the need for a more accurate method of assessing lifetime occupational asbestos exposure.

Estimating Lifetime Asbestos Exposure in Patients With Idiopathic Pulmonary Fibrosis

We read with interest the article by van Oyen et al. (2015) relating to the production of a job-exposure matrix (AsbJEM) that allows lifetime occupational asbestos exposure to be estimated. We recently published an article highlighting a potential link between rising idiopathic pulmonary fibrosis (IPF) mortality in the UK and historic national asbestos imports (Barber et al., 2016). We identified a strong correlation between mesothelioma and IPF annual mortality between 1968 and 2012 in both males and females. Although this may be entirely coincidental, our article suggested a proportion of IPF deaths may in fact be due to unrecognized asbestosis. The two conditions can be clinically and radiologically indistinguishable and so rely heavily on the exposure history provided by the patient in order to differentiate them (Barber and Fishwick, 2012), raising the possibility of missed or inaccurate diagnosis. The difficulty of accurately estimating an individual patient’s asbestos exposure was recognized some years ago in the Netherlands, leading to the development of a risk matrix based on job titles. This information was then used to produce stepwise decision trees for mesothelioma and asbestosis, now used to assess whether agreed thresholds of exposure are likely to have been reached by individual patients (Burdorf and Swuste, 1999). Our study concluded that a similar asbestos JEM should be developed for the UK, to facilitate more valid case–control studies of asbestos as a risk factor in IPF. Our article referenced evidence from a case–control study of mesothelioma—published in 2009—that clearly demonstrated how common occupational asbestos exposure was historically among the working UK population (Rake et al., 2009). This study found that among 1420 age-matched controls (median age 58–68 years and randomly selected from Health Authority registers), 65% of men and 23% of women had worked in occupations that were classified as medium or high risk for asbestos exposure. Many of the male controls (1112 men) had worked in medium- or high-risk jobs for a significant duration of their employment—with 51, 42, and 28% having worked for at least 5, 10, and 20 years, respectively. Despite this, Rake et al. (2009) noted that many workers in medium-/high-risk exposure jobs were unable to provide a clear history of asbestos exposure. Possible explanations for this included the time elapsed since the exposure occurred, indirect exposure as a bystander, and handling materials that at the time were not identified as containing asbestos. As well as the valuable data on lifetime mesothelioma risk in different UK occupations, the study by Rake et al. (2009) confirmed that a substantial number of men in the current UK general population (of the same age-group at risk of IPF) have had significant and prolonged asbestos exposure in previous jobs and that in some cases this may only be apparent by considering their job titles. As well as having clear research benefits, a UK asbestos JEM could also assist in the management of individual patients being assessed for anti-fibrotic drug treatments (currently only licensed in the UK for IPF) and in assessing eligibility for government benefits. Although we accept population JEMs cannot calculate exact lifetime doses for each individual patient (Kottek and Kilpatrick, 2016), we believe a UK model based on years worked in different job titles will offer a more standardized and objective estimate than current practice. We wish to further highlight the possible link between asbestos exposure and IPF, and encourage van Oyen et al. (2015) to use their AsbJEM to carry out a case–control study of IPF in Australia. Hypothesizing a potential link between historic asbestos exposure and IPF has so far been controversial in the UK, and data from other countries would add greatly to the evidence base.

P223 Update of the british occupational health foundation (bohrf) evidence-based guidelines on the prevention and management of occupational asthma

Introduction and Objectives Occupational asthma (OA) can be prevented by eliminating or at least minimising exposures to the causal agents at work. However, the rapid development of industrial technologies constantly introduces new potential asthmagens at work and therefore up-to-date knowledge of these changes is pivotal to diagnose and prevent new OA cases. The current evidence-based guidance on the prevention and management of OA was commissioned by the British Occupational Health Foundation (BOHRF) in 2010.1 Our aim was to update these guidelines to help stakeholders reducing the incidence of OA by improved prevention, and the severity of individual cases of disease by earlier identification and better management. Methods We conducted a literature systematic review according to state-of-the-art methods via search of two electronic database (Embase and Medline), using the Ovid interface, from January 2009 to November 2016. Both MeSH and free-text terms were used for combinations of ‘work’ and ‘asthma’. The retrieved references were managed using EndNote software and evaluated blindly by paired reviewers. Critical appraisal of the included articles was performed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) scoring system to link evidence-quality evaluations to clinical recommendations. Results From the 2424 references retrieved, 133 met the inclusion criteria (see attached PRISMA flow-chart diagram). Briefly, in terms of occupations, many previously identified were confirmed, such as bakers, and painters, but new ones emerged such as cleaners, suggesting also underlying irritative-mediated causal mechanisms. Not substantial changes in the diagnosis of OA emerged, but new potential frameworks for better management and health surveillance of OA arose. Conclusions Exposure to respiratory hazards at work is still an important cause of asthma worldwide and in the UK, with important costs for both the individual and the society. Updated evidence-based guidelines on the prevention and management of OA are key to guide healthcare workers’ decision-making in their routine clinical practice. Abstract P223 Figure 1 PRISMA flow diagram. Reference British Occupational Health Research Foundation. Occupational Asthma – Identification, Management and Prevention: Evidence Based Review and Guidelines 2010. Available at http://www.bohrf.org.uk/downloads/Occupational AsthmaEvidenceReview-Mar2010.pdf

S105 Respiratory symptoms, lung function and sensitisation across different exposure groups of british woodworkers

Background Wood dust is a leading cause of occupational asthma (OA) in the UK, with over 2 00 000 people exposed annually. There have been no recent studies examining respiratory health in British woodworkers. Aim We surveyed British woodworkers to examine how respiratory symptoms, airway inflammation, lung function and sensitisation relate to wood dust exposure. Methods British woodworkers were recruited to a cross-sectional study. All workers underwent a validated respiratory symptom questionnaire, job history and exposure measurement. Spirometry and fractional exhaled nitric oxide (FENO) were recorded to American Thoracic Society (ATS) standards. Blood was taken for total and specific IgE to hard and soft wood. Results 269 workers participated (Table 1). Most were men (n=261, 97%), with a mean age of 42.4 years (SD 12.6) and 18.9 (12.8) years woodworking. Mean current wood dust exposure was 1.9 mg/m3 (SD 0.9, IQR 1.4). Current asthma symptoms (CAS, defined as wheezing, nocturnal chest tightness, exertional/nocturnal/resting breathlessness, or asthma medication use within the last 12 months) were common, reported by 123 (46%). Work-related respiratory symptoms were less common, reported by 29 (11%). Forty one (18%) people had a FENO ≥40 ppb. Only one worker had a positive IgE to soft wood. Ten (4%) had an FEV1/FVC less than the lower limit of normal (<LLN). In adjusted regression models, workers in the highest exposure quartile were at lower risk of work-related respiratory symptoms (WRRS) than those in the lowest quartile (OR 0.16 , 95% CI 0.03–0.81). Workers in the low exposure group were more likely to have a FENO ≥40 ppb (OR 3.59, 95% CI 1.09–11.77). However, there was no clear exposure response relationship when looking at percent predicted FEV1 or FVC (for FEV1β=0.05, p=0.41). Conclusion CAS are common among British woodworkers, reported by nearly half. One fifth fulfilled BTS criteria for high FENO despite low sensitisation rates. The highest exposed were at lower risk for WRRS, suggesting a healthy worker effect. No clear relationship between exposure and lung function was identified. Mechanisms for asthma among woodworkers may not be IgE mediated, and longitudinal studies are needed to clarify the exposure response relationship. Abstract S105 Table 1 Table showing population characteristics of 269 British woodworkers across exposure quartiles Total (n=269) Lowest exposure (0–1.19 mg/m3) n=67 Low exposure (1.20–2.00 mg/m3) n=72 Medium exposure (2.01–2.32 mg/m3) n=63 Highest exposure (2.33–5.44 mg/m3) n=67 Demographics Age, years (SD) 42.4 (12.6) 42.45 (10.51) 44.64 (13.69) 41.31 (13.00) 40.93 (12.68) Sex, m (%) 261 (97) 65 (97) 71 (99) 62 (98) 63 (94) Current smoker (%) 70 (26) 17 (25) 22 (30) 14 (22) 17 (25) Ever smoked more than 1 pack year (%) 140 (52) 34 (51) 46 (64) 27 (43) 33 (49) Exposure Currently uses RPE (%) 207 (77) 44 (66) 55 (76)* 51 (81)* 57 (85)* Mean current exposure, mg/m3 (SD) 1.9 (0.9) 0.69 (0.37)** 1.74 (0.27)** 2.12 (0.09)** 2.98 (0.80)** Total time in woodworking industry, years (SD) 18.9 (12.8) 17.95 (11.03) 19.71 (12.52) 20.86 (14.58) 17.11 (12.90) Health Current asthma symptoms (%) 123 (46) 34 (50) 34 (47) 29 (46) 26 (39) Any work-related respiratory symptom (%) 29 (11) 11 (16) 8 (11) 8 (13) 2 (3) Work-related nasal symptoms (%) 35 (13) 5 (8) 8 (11) 11 (18) 11 (16) Work-related ocular symptoms (%) 37 (14) 6 (9) 13 (18) 3 (5) 15 (22)* Physician diagnosed asthma (%) 22 (8) 6 (9) 10 (14) 4 (6) 2 (3) Current asthma under ECRHS (%) 40 (15) 11 (16) 16 (22) 8 (13) 5 (8) FEV1/FVC<LLN (%) 10 (4) 4 (7) 3 (5) 1 (2) 2 (4) Physician diagnosed COPD (%) 4 (2) 3 (5) 0 (0) 1 (2) 0 (0) Positive IgE to hardwood (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Positive IgE to softwood (%) 1 (1) 0 (0) 0 (0) 1 (2) 0 (0) TIgE, kU (SD) 133.5 (632.2) 138.72 (305.23) 95.95 (148.18) 236.75 (1223.90) 61.40 (108.90) Atopic (%)+ 53 (20) 13 (21) 17 (26) 16 (27) 7 (13) AM FEno# 27.2 (27.7) 24.40 (23.90) 32.45 (32.31) 24.90 (20.29) 26.39 (32.45) FENO>40 ppb (%) 41 (18) 7 (13) 15 (25) 9 (17) 10 (16) Mean FEV1 (%)^ 99.8 (12.7) 99.90 (13.45) 98.61 (12.34) 99.35 (12.25) 101.41 (13.09) Mean FVC (%) 102.9 (12.8) 103.48 (12.52) 101.16 (12.16) 101.63 (12.81) 105.41 (13.59) Mean PEF (%) 108.5 (15.9) 108.16 (16.91) 109.80 (16.63) 107.56 (13.86) 108.27 (16.14) Mean FEV1, mls (SD) 3824 (699) 3809 (658) 3697 (720) 3823 (656) 3986 (739) Mean FVC, mls (SD) 4813 (854) 4825 (818) 4658 (899) 4759 (750) 5027 (905) Mean PEF, mls (SD) 588 (102) 584 (116) 587 (98) 581 (95) 588 (102) *p<0.05, **p<0.01 +atopy was defined as total IgE >100 kU/L # Valid FENOmeasurements were made in 225 workers. ^ Valid spirometry was measured in 228 workers.

P252 Accurate measurement of lung function in the workplace and potential effects of underestimation

Introduction Accurate workplace spirometry measurement is key to giving workers the best clinical assessment of their respiratory health. We were interested in the underestimation of spirometry that occurs if best practice is not adhered to and the significance of this on assessment of health at work. Methods 667 stone, brick and foundry workers (with varying spirometry experience), carried out lung function testing as part of a larger cross sectional workplace study. Each performed a minimum of 3 forced expirations. Testing continued until each worker had met the ATS/ERS guidance. The final FEV1 and FVC recorded was the maximum value attained from 3 technically acceptable blows, and that the two highest FEV1 and FVC values were within 150 mls. Using the final FEV1 and FVC for each worker, it was then possible to calculate the underestimate of both measures, had only the first blow, or the maximum of the first two blows, been used for interpretation. Results 613 of the 669 (91.6%) attained the ATS/ERS criteria based on FEV1. Analysis of the first actual blow, regardless of technical quality, showed an FEV1 mean underestimate of 250 mls (median = 80 mls, IQR = 210 mls). If only the first technically acceptable blow had been carried out, the FEV1 would have been underestimated by a mean of 114 mls (60 mls, 150 mls). If only two technically acceptable blows had been carried out, and the maximum of these used, the FEV1 would have been underestimated by a mean of 36 mls (0 mls, 50 mls). Similarly, the FVC would have been underestimated by a mean of 131 mls (75 mls, 180 mls) if only the first technically acceptable blow had been used for interpretation. If only two technically acceptable blows were carried out, the FVC would have been underestimated by a mean of 43 mls (0 mls, 50 mls). Conclusion Non adherence to ATS/ERS lung function testing guidance at work can cause the FEV1 and FVC to be underestimated by clinically significant amounts.

S118 Can fractional exhaled nitric oxide help predict asthma in british foundry workers

Background Foundry work may involve exposure to respiratory sensitisers and irritants. There is limited evidence for the use of FENO in occupational settings, and particularly in foundries. Aim To examine the usefulness of FENO in identifying foundry workers at risk of asthma. Methods Foundry workers undertook a respiratory questionnaire. Spirometry (Ndd Easy on-PC Spirometer, Zurich) and FENO (NOBreath, Bedfont Scientific, Kent) were measured to ATS/ERS standards. The ATS upper limit of normal (ULN) of 50 parts per billion (ppb), or 45.9ppb for current smokers, determined the high FENO category (FENO >ULN). Workers with FENO >ULN were compared with those with at least one work-related respiratory symptom (WRRS) and those with obstructive lung function (FEV1/FVC <0.7) using Chi Square and Fisher’s Exact Tests. Results 351 workers (350 men, 99%) participated. 350 workers had a valid FENO performed. Arithmetic mean FENO was 30.2ppb (95% CI: 27.3–33.2); geometric mean (GM) FENO20.8 (18.9–22.9) ppb. FENO exceeded the ULN in 61 (17%) workers. Average age for the FENO >ULN group was 41.5 (95% CI: 38.3–44.7), with a mean of 15.8 (12.4 – 19.2) years working in the foundry industry. Workers in the FENO >ULN group were significantly more likely to have a current diagnosis of asthma (12% vs 5%, p < 0.05), have ever suffered allergies (55% vs 31%, p < 0.01), or report work-related shortness of breath (3% vs 0%, p < 0.05). Fourteen workers (4%) had a FENO >ULN and WRRS (Figure1). Of these 14, only 2 (14%) had a current diagnosis of asthma (Fisher’s p = 0.20). Eight (2%) workers had a FENO > ULN and FEV1/FVC <0.7, though only 2 (25%) had a current asthma diagnosis (Fisher’s p = 0.08). Conclusion A significant proportion of foundry workers have FENO levels that exceed the ATS cut point for likely eosinophilic airway inflammation. Of these workers, most had a raised FENO but no WRRS or obstructive lung disease. Only a minority of workers with FENO >ULN and either WRRS or obstruction had a current diagnosis of asthma. FENO may be useful in identifying foundry workers at risk of asthma and warrants further study. Abstract S118 Figure 1 Overlap between FENO>ULN, work-related respiratory symptoms and obstructive spirometry in foundry workers. Total numbers in each group (%of total): FENO >ULN: n=61 (17%); >1 WRRS: n = 69(20%); FEV1/FVC <0.7 = n = 34 (10%). FENO>ULN = FENO above 50ppb or 45.9ppb in current smokers; WRRS = at least one work-related respiratory symptom

Serial peak flow measurements in allergic alveolitis

Dear Sir, We read with interest the recent article by Burge et al. comparing serial peak flow [peak expiratory flow (PEF)] changes in occupational asthma (OA) and extrinsic allergic alveolitis (EAA) in workers exposed to metalworking fluids (MWFs) [1]. The exact cause of the allergic lung disease seen during MWF outbreaks remains to be determined despite several decades of workplace investigations [2]. It is clear, however, that re-circulated water-soluble MWFs contain chemical asthmagens and are prone to microbial contamination with bacteria, fungi and opportunistic mycobacteria linked to the development of EAA. Burge et al. found that work-related changes in PEF were demonstrated in workers with EAA and hypo thesized that this might reflect falls in PEF that occurred in parallel with falls in FEV1 (forced expiratory volume in 1 s) and FVC (forced vital capacity) due to the pulmonary restriction expected in alveolitis. We would like to propose a different hypothesis, that their findings are more likely to relate to the reversible airflow obstruction that has been previously noted in a proportion of those with EAA. Although alveolar inflammation and fibrosis most commonly result in restrictive lung disease in EAA, obstructive spirometry may be found in up to 16% of individuals in case series [3]. In addition, biopsy evidence of bronchiolitis can be found in up to 50% of cases with active disease [4]. This small airway involvement is responsible for the air trapping and mosaic attenuation that are common high-resolution computed tomography findings in EAA [5], and in some cases, this is the only radiological finding [6]. An increased risk of asthma diagnosis following acute episodes of EAA was recognized by Jack Pepys as long ago as the 1960s, with an estimated 10% of workers with Farmer’s Lung (FL) being expected to later develop asthma [7]. Evidence to support this came from a small UK study of FL, where 14% of affected workers developed asthma over the 10-year follow-up period [8]. A much larger Finnish study (1031 patients with FL) also found a marked increase in the prevalence of asthma following a diagnosis of EAA. The prevalence of chronic asthma was 1% in the year prior to diagnosis of FL, rising to 7% in the 5 years post-diagnosis. In this study, asthma cases had to have been confirmed by a physician, requiring objective evidence of asthma with a 15% improvement in FEV1 following inhaled bronchodilator, a 15% fall in FEV1/PEF on exercise testing, or at least 20% diurnal variation in peak flow monitoring [9]. Although the development of acute and reversible airflow obstruction in response to histamine or methacholine challenge is used as a diagnostic test in asthma, it is also seen in up to 50% of workers with FL [10]. Bronchial hyper-reactivity has been demonstrated to be transient in most FL patients, fluctuating with exacerbations of symptoms [11]. Workers with airway hyper-responsiveness due to EAA would therefore develop airflow obstruction when exposed to irritants or allergens in the workplace, which would be expected to result in a work-related fall in PEF. Further related evidence can be found from specific inhalation challenge (SIC) in FL. Although isolated late reactions are most commonly seen, there have also been reports of early and dual responses in SIC with agricultural dusts [12,13], patterns more typical of OA [14]. In summary, there is a body of evidence that has established the importance of airway disease in EAA, and that asthmatic features are to be expected in a proportion of affected patients. For occupational EAA, it is our view that this would manifest as PEF variability and a positive work-effect index. We agree therefore that serial PEF analysis offers an important diagnostic tool in symptomatic MWF-exposed workers, to identify those with OA or extrinsic allergic bronchiolitis. From a practical point of view however, the key management principles for both conditions remain broadly the same, with prognosis dependant on early recognition of disease, and cessation of further exposure to the cause.

Impaired Quality of Life in Chronic Hypersensitivity Pneumonitis

We read with interest in an issue of CHEST (June 2014) the article by Lubin et al, 1 who compared Short Form-36 quality of life (QOL) among patients with idiopathic pulmonary fi brosis (IPF) and chronic hypersensitivity pneumonitis (CHP). Th e authors noted that they were surprised to fi nd that QOL scores were signifi cantly better in IPF than CHP in seven of eight domains. Th ey demonstrated that this fi nding did not relate to age or severity of lung function impairment, and they discussed possible explanations.

P127 Copd And The Workplace; Attitudes Of Those With And Without The Condition In A Population Based Study

Background Current estimates support 15% of the total population burden of chronic obstructive pulmonary disease (COPD) to be associated with harmful inhaled occupational exposures. Despite a now substantial body of evidence relating to causation, remarkably little is known about the consequences of these inhaled exposures at an individual level, and the attitudes of workers with and without COPD to these issues. Aim The aim of this work was to explore attitudes to workplaces, and to other aspects of the management of long-term respiratory problems, from individuals within a large population study with and without COPD. Methods The primary aim of this population-based study was to assess the contribution made by inhaled occupational exposures to the development of COPD. The study was based in Sheffield, historically an industrialised part of the UK. A sub sample of cases of self reported COPD (n = 66) and non cases of COPD (n = 224) were asked to rate their views to a set of 36 pre defined statements, each rated between “don’t agree” and “completely agree” on a five point scale. Statements included enquiry about attitudes to chronic respiratory ill health, smoking, general health issues and the influences of the workplace on health. Results 290 individuals, all 55 years old or greater, participated, 172 (59%) of whom were male. The majority of participants generally agreed or completely agreed with most statements, although various differences emerged between those with and without COPD. For example, those with self reported COPD were more likely, as anticipated, to identify this condition as a longer term health problem, but less likely to agree that workers with possible breathing problems should talk to their employer about these or undergo regular spirometry to identify these. Conclusions This study has identified a set of attitudes and beliefs from those with and without COPD relating to chronic respiratory problems at work. Knowledge of these semi-quantitative data will assist the development of better workplace interventions to reduce the burden of this condition.