Christopher M. Barber

Standards of care for occupational asthma

Occupational asthma remains a common disease in the UK with up to 3000 new cases diagnosed each year. The Health and Safety Executive (HSE) estimates the cost to our society to be over £1.1 billion for each 10-year period.1 In October 2001 the Health and Safety Commission agreed a package of measures aimed at reducing the incidence of asthma caused by exposure to substances in the workplace by 30% by 2010. Key to this aim are primary prevention by proper risk assessment and exposure control, together with secondary prevention to ensure reduction in the delay between the development of allergic symptoms at work (normally nasal or respiratory) and appropriate advice to the affected worker and workplace. Conservative estimates suggest that one in 10 cases of adult onset asthma relate directly to sensitisation in the workplace,2 with a smaller subset of workers with acute irritant induced asthma. The latter—formerly termed reactive airway dysfunction syndrome (RADS)—relates to asthma caused by exposure to high levels of airborne irritants. The prognosis of individuals with occupational asthma is better if they are removed from exposure quickly, particularly within a year of first symptoms.3–5 However, removing individuals often leads to unemployment. If the diagnosis of occupational asthma is incorrect, advising individuals whose asthma is not caused by work to be removed from exposure may have unnecessary financial and social consequences. The intent of this article is not to document the entire current evidence base related to occupational asthma, as the British Occupational Health Research Foundation (BOHRF) recently completed such an evidence review.7 The key points of this article are summarised in box …

Standards of care for occupational asthma: an update

Background The British Thoracic Society (BTS) Standards of Care (SoC) Committee produced a standard of care for occupational asthma (OA) in 2008, based on a systematic evidence review performed in 2004 by the British Occupational Health Research Foundation (BOHRF). Methods BOHRF updated the evidence base from 2004–2009 in 2010. Results This article summarises the changes in evidence and is aimed at physicians, nurses and other healthcare professionals in primary and secondary care, occupational health and public health and at employers, workers and their health, safety and other representatives. Conclusions Various recommendations and evidence ratings have changed in the management of asthma that may have an occupational cause.

Hypersensitivity pneumonitis due to metalworking fluid exposures.

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Systematic review of respiratory case definitions in metalworking fluid outbreaks

BACKGROUND Since the mid-1990s, outbreaks of asthma and extrinsic allergic alveolitis (EAA) have been identified in workers exposed to metalworking fluids (MWFs). The cause of these outbreaks remains to be determined. AIMS To identify and review all previously published occupational lung disease case definitions and diagnostic criteria that have been utilized during MWF outbreak investigations. METHODS Respiratory outbreaks due to MWFs were identified by a systematic literature search for articles published between 1990 and October 2011. Investigations reporting the usage of disease case definitions or diagnostic criteria for respiratory disease were reviewed and summarized. RESULTS The literature search identified 35 papers relating to 27 outbreaks of respiratory disease in MWF-exposed workers. Fourteen case definitions for MWF-related respiratory disease were identified: seven for EAA, five for occupational asthma and one each for humidifier fever and industrial bronchitis. A single paper was identified where any comparison of different disease case definitions (for EAA) had been performed. CONCLUSIONS A range of case definitions and diagnostic criteria for MWF respiratory disease have been utilized in outbreak investigations, but the majority have been produced for individual outbreak investigations without previous validation. It may be difficult to compare the findings of future workplace studies without a more standardized approach to case identification and diagnosis.

Metal worker’s lung: spatial association with Mycobacterium avium

Background Outbreaks of hypersensitivity pneumonitis (HP) are not uncommon in workplaces where metal working fluid (MWF) is used to facilitate metal turning. Inhalation of microbe-contaminated MWF has been assumed to be the cause, but previous investigations have failed to establish a spatial relationship between a contaminated source and an outbreak. Objectives After an outbreak of five cases of HP in a UK factory, we carried out blinded, molecular-based microbiological investigation of MWF samples in order to identify potential links between specific microbial taxa and machines in the outbreak zone. Methods Custom-quantitative PCR assays, microscopy and phylogenetic analyses were performed on blinded MWF samples to quantify microbial burden and identify potential aetiological agents of HP in metal workers. Measurements and main results MWF from machines fed by a central sump, but not those with an isolated supply, was contaminated by mycobacteria. The factory sump and a single linked machine at the centre of the outbreak zone, known to be the workstation of the index cases, had very high levels of detectable organisms. Phylogenetic placement of mycobacterial taxonomic marker genes generated from these samples indicated that the contaminating organisms were closely related to Mycobacterium avium. Conclusions We describe, for the first time, a close spatial relationship between the abundance of a mycobacterium-like organism, most probably M. avium, and a localised outbreak of MWF-associated HP. The further development of sequence-based analytic techniques should assist in the prevention of this important occupational disease.

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.

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.

P3 COPD causation; an assessment of agreement between expert clinical raters

Introduction and Objectives Epidemiological studies consistently find that up to 15% of COPD is attributable to occupational exposures. Despite growing recognition that such exposures are associated with COPD, very little is known about how clinicians weight such attributions against cigarette smoking causation in individual cases. Methods In order to assess attribution of causative factors in COPD by clinicians, we used 15 hypothetical cases of COPD, structured to represent a broad range of smoking and occupational exposure histories. Cases were developed a priori into nine categories: combinations of low, medium and high tobacco smoking and low, medium, and high COPD-risk occupational exposures. Twelve general experts in COPD and 12 specifically in occupational lung disease were invited to rate the cause of COPD in each case, attributing a percentage contribution to the harm caused by three categories: (i) smoking, (ii) occupational exposures and (iii) other causes. Results To date, responses have been received from nine raters (seven occupational and two general). Ratings from a selected spectrum of cases are shown in Abstract P3 Table 1, expressed as median and IQR. Attribution varied with the degree of exposures, but even light smoking (less than 15 pack years) was weighted more heavily than substantial occupational exposure. Abstract P3 Table 1 Selected case scenarios by attribution mix Causal attribution by physician case raters Smoking % (median, IQR) Occupation%(median, IQR) Other % (median, IQR) Case 1 (Heavy smoker, heavy occupational exposure – 43 years foundry and scrap metal work, paint fume exposure) 73 (62.5–90) 10 (10–31) 0 (0–10) Case 2 (Heavy smoker, light occupational exposure – 9 years grain dust exposure 90 (80–96.5) 10 (0–12.5) 0 (0–10) Case 3 (Medium smoker, medium occupational exposure – 28 years, scrap metal and cotton dust exposure) 70 (60–87.5) 20 (7.5–40) 0 (0–15) Case 4 (Light smoker, heavy occupational exposure – 45 years as a stonemason) 50 (32.5–75) 40 (15–67.5) 0 (0–15) Conclusions There was a wide range of estimates relating to causative factors in COPD documented by experienced clinicians. These findings are consistent with the a priori assumption that attributing COPD causation in an individual case is difficult, as a sparse evidence base exists to guide clinicians. Further work is needed to allow translation of epidemiological findings to attribution in individual COPD cases, to better facilitate the screening, identification and management of occupational COPD.

A Male with Pleuritic Chest Pain, Dry Cough, Progressive Dyspnoea, and Weight Loss

A 39-year-old white male presented with a 2-day history of severe right-sided pleuritic pain. He was unwell for 6 months prior to this, reporting a dry cough, exertional dyspnoea, night sweats, and 10-kg weight loss. He was a non-smoker, and had no recent foreign travel. He was a heavy goods vehicle driver, and had no known exposures to chemicals, fumes or dust. He had no prior medical history and was on no medication. Physical examination revealed normal vital signs, and SaO 2 was 96% on room air. He had no fever, clubbing, skin lesions, cervical lymphadenopathy or joint swelling. Auscultation of the lungs revealed diminished breath sounds bilaterally with crepitations over the posterior left chest. Cardiovascular, abdominal and neurological system examinations were unremarkable. A chest X-ray showed a spontaneous rightsided pneumothorax, with bilateral peripheral infi ltrates ( fi g. 1 ). A computerized tomographic scan of the chest, performed on the same day as the chest X-ray, showed the bilateral peripheral infi ltrates to represent subpleural consolidation. No mediastinal lymphadenopathy or pleural effusion was seen ( fi g. 2 ). The parameters of his laboratory test results including a full blood count and differential, renal and liver function tests, and measurement of serum calcium level were all normal. The erythrocyte sedimentation rate was 37 mm/h and C-reactive protein 50 mg/l. What is your diagnosis? What is your next diagnostic step? Received: November 14, 2005 Accepted after revision: December 21, 2005 Published online: March 31, 2006