Fractional exhaled nitric oxide in the interpretation of specific inhalational challenge tests for occupational asthma.

PURPOSE: Fractional exhaled nitric oxide (FENO) measurements are recommended for the assessment of eosinophilic airway inflammation in asthma. Clinically relevant increases in FENO have been reported 24 h after positive specific inhalational challenge (SIC) tests in occupational asthma. We aimed to determine whether positive SICs could be discriminated from control tests, on the basis of change in FENO. METHODS: We reviewed all positive SICs to a variety of agents performed at our institution 2008-2012 and gathered data on age, sex, asthmatic response (immediate/dual/late), smoking status, inhaled corticosteroid usage, and FENO pre- and 24-h postcontrol and positive SIC from each worker. Changes in FENO after positive SICs were compared with control SICs from each worker, by using paired Student's t tests. RESULTS: In 16 workers, negative control challenges were associated with mean changes in FENO of 9 % (95 % CI -1.14 to 19.01) or 1.1 ppb (95 % CI -3.59 to 5.84); 2 of 16 (13 %) workers tested showed increases in FENO that were clinically relevant based on recent guidelines. Subsequent positive SICs were associated with mean changes in FENO of 7 % (95 % CI −15.73 to 29.6) or 2.1 ppb (95 % CI -6.07 to 10.19), which were not significantly different to controls; only 2 of 16 (13 %) workers had FENO changes that were clinically relevant. CONCLUSIONS: FENO changes above the upper confidence limits of ≥20 % or ≥6 ppb may be considered to be outside the range of normality. However, the majority of workers who had clearly positive SICs to common low molecular weight agents also had no statistically or clinically relevant increase in FENO. Therefore, change in FENO does not predict a positive SIC in this group.

Differences in serial lung function recorded on four data-logging meters.

OBJECTIVE: Lung function measurements performed several times daily are useful for the diagnosis of occupational asthma. Patient fabrication of hand-recorded charts can limit confidence in the results; this is overcome using electronic meters that log time and measurement. We have compared individual and meter differences in FEV1 and PEF recorded by hand and from meter logs using expert subjects on four data-logging spirometers with different methods of measurement and different quality control software. METHODS: Eight workers in a respiratory physiology department were asked to record FEV1 and PEF 2-hourly from waking for 7 days using four electronic meters (Easyone, Micro DL, Vitalograph Diary card 2110 and Piko-1) in random order. Subjects hand-recorded the best FEV1 and PEF from each session, this was compared with the logged data. RESULTS: Discordant measurements from individuals were lower for FEV1 than PEF and differed from 4.4-19.1% for FEV1 (mean 9.4%, p < 0.0001) and 6-23.3% for PEF (mean 12.6, p < 0.0001). There were also significant differences between meters for both variables (p < 0.0001). The magnitude of the differences in PEF was highest for the Easyone (34l/min) and lowest for the Vitalograph Diary card 2110 (14l/min) and varied significantly between meters (mean 22l/min, p = 0.002). CONCLUSIONS: Differences between hand-recorded and logged measurements are unlikely to be due solely to patient fabrication and can be due to quality criteria or other unclear software requirements applied after the results are shown on the meter screen; they differ between meters. Whether the differences shown affect clinical outcome will require further investigation.

COPD causation and workplace exposures: an assessment of agreement among expert clinical raters.

BACKGROUND: Although occupational exposure is a known risk factor for Chronic Obstructive Pulmonary Disease (COPD), it is difficult to identify specific occupational contributors to COPD at the individual level to guide COPD prevention or for compensation. The aim of this study was to gain an understanding of how different expert clinicians attribute likely causation in COPD. METHODS: Ten COPD experts and nine occupational lung disease experts assigned occupational contribution ratings to fifteen hypothetical cases of COPD with varying combinations of occupational and smoking exposures. Participants rated the cause of COPD as the percentage contribution to the overall attribution of disease for smoking, occupational exposures and other causes. RESULTS: Increasing pack-years of tobacco smoking was associated with significantly decreased proportional occupational causation ratings. Increasing weighted occupational exposure was associated with increased occupational causation ratings by 0.28% per unit change. Expert background also contributed significantly to the proportion of occupational causation rated, with COPD experts rating on average a 9.4% greater proportion of occupational causation per case. CONCLUSION: Our findings support the notion that respiratory physicians are able to assign attribution to different sources of causation in COPD, taking into account both smoking and occupational histories. The recommendations on whether to continue to work in the same job also differ, the COPD experts being more likely to recommend change of work rather than change of work practice.

Current topics in occupational asthma.

The study of occupational asthma (OA) provides insights into asthma in general, as the cause is known. The relationships between the cause and response can be measured and modifying factors can be identified and their influence quantified. Developing OA has much more serious consequences for the patient than new onset asthma unrelated to work exposures, as the patient's livelihood is nearly always affected. Many healthcare professionals are more ready to accept and act on asthmatic symptoms when they are unrelated to work than when work may be the cause; antagonism can also occur in the workplace. This article reviews some of the areas where development and controversy enrich the study of OA. It makes no attempt to be comprehensive.

Concise guidance: diagnosis, management and prevention of occupational asthma.

This concise guidance, prepared for physicians, summarises the British Occupational Health Research Foundation guideline for the prevention, identification and management of occupational asthma. Approximately one in six people of working age who develop asthma have work-related asthma, where work has either caused or aggravated their disease. Physicians who assess working adults with asthma need to ask the patient about their job and the materials they work with, and be aware of those that carry particular risks; they should also ask whether symptoms improve regularly on days away from work. A diagnosis of occupational asthma (ie asthma caused by work) should not be made on the basis of history alone, but be supported by immunological and physiological investigations of proven diagnostic benefit. Following a validated diagnosis of occupational asthma, physicians should recommend early avoidance of further exposure, because this offers the best chance of complete recovery. If appropriate and timely interventions are not taken, the prognosis of occupational asthma is poor, with only approximately one-third of workers achieving full symptomatic recovery.

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.

Are we failing workers with symptoms suggestive of occupational asthma?

AIMS: To assess the route to secondary care for patients with possible occupational asthma, and to document the duration of workrelated symptoms and referral times. METHODS: Consecutive patients with suspected occupational asthma were recruited to a case series from six secondary care clinics with an interest in occupational asthma. Semi-structured interviews were performed and hospital case notes were reviewed to summarise relevant investigations and diagnosis. RESULTS: 97 patients were recruited, with a mean age of 44.2 years (range 24-64), 51 of whom (53%) had occupational asthma confirmed as a diagnosis. Most (96%) had consulted their general practitioner (GP) at least once with work-related respiratory symptoms, although these had been present for a mean of 44.6 months (range 0-320 months) on presentation to secondary care. Patients experienced a mean delay for assessment in secondary care of 4 years (range 1-27 years) following presentation in primary care. CONCLUSIONS: Significant diagnostic delay currently occurs for patients with occupational asthma in the UK.

Occupational asthma: an assessment of diagnostic agreement between physicians.

OBJECTIVES: To investigate the levels of agreement between expert respiratory physicians when making a diagnosis of occupational asthma. METHODS: 19 cases of possible occupational asthma were identified as part of a larger national observational cohort. A case summary for each case was then circulated to 12 physicians, asking for a percentage likelihood, from the supplied information, that this case represented occupational asthma. The resulting probabilities were then compared between physicians using Spearman's rank correlation and Cohen's kappa coefficients. RESULTS: Agreement between the 12 physicians for all 19 cases was generally good as assessed by Spearman's rank correlation. For all 66 physician-physician interactions, 45 were found to correlate significantly at the 5% level. The agreement assessed by kappa analysis was more variable, with a median kappa value of 0.26, (range -0.2 to +0.76), although 7 of the physicians agreed significantly (p<0.05) with >or=5 of their colleagues. Only in one case did the responses for probability of occupational asthma all exceed the "on balance" 50% threshold, although 12 of the 19 cases had an interquartile range of probabilities not including 50%, implying "on balance" agreement. The median probability values for each physician (all assessing the identical 19 cases) varied from 20% to 70%. Factors associated with a high probability rating were the presence of a positive serial peak expiratory flow Occupation Asthma SYStem (OASYS)-2 chart, and both the presence of bronchial hyper-reactivity and significant change in reactivity between periods of work and rest. CONCLUSIONS: Despite the importance of the diagnosis of occupational asthma and reasonable physician agreement, certain variations in diagnostic assessment were seen between UK expert centres when assessing paper cases of possible occupational asthma. Although this may in part reflect the absence of a normal clinical consultation, a more unified national approach to these patients is required.

An outbreak of extrinsic alveolitis at a car engine plant.

BACKGROUND: Twelve workers from a car engine-manufacturing plant presented with extrinsic allergic alveolitis (EAA), with heterogeneous clinical, radiological and pathological findings. They were exposed to metalworking fluids (MWF) that cooled, lubricated and cleaned the machines. METHODS: They were characterized by history, examination, lung function testing, radiology, bronchoscopic lavage, lung biopsy and serology. Sera were tested for precipitins to a crude extract of used MWF and to reference cultures of bacteria suspected to be implicated. RESULTS: All were males and none were current smokers. All had dyspnoea, many had weight loss and cough, but only half had influenza-like symptoms. Only half had auscultatory crackles. Five had peak flow variability, four with an occupational component. There was overall restrictive spirometry, decreased lung volumes and reduced gas transfers. Ten had radiological evidence of interstitial lung disease. Seven (of eight) had lymphocytosis on bronchial lavage, including the two with inconclusive radiology. Seven (of 11) had lung biopsies showing inflammatory infiltrates, two with fibrosis and one with granulomas. Three (of 11) had strong positive precipitins to an extract of the used MWF from the plant. Molecular biological analysis of the MWF revealed Acinetobacter and Ochrobactrum. Precipitins to Acinetobacter were detected in seven of 11 workers tested (and four of 11 control workers). Precipitins to Ochrobactrum were detected in three of 11 workers tested (and three of 11 control workers). CONCLUSION: This is the largest series reported in Europe of EAA due to an aerosol of microbiologically contaminated MWF in heavy manufacturing industry.

Patient attitudes to clinical trials: development of a questionnaire and results from asthma and cancer patients.

OBJECTIVE: To develop a questionnaire to assess patients' views of clinical trials, and to report the results from the questionnaire in two patient groups: asthma and cancer. DESIGN: A 43 item questionnaire asking patients about their views to clinical trials was developed on the basis of interviews with trialists and focus groups with patients. The questionnaire was mailed to patients with a diagnosis of either asthma or cancer. A set of items was then selected, via statistical analyses, to form the core of the questionnaire. PARTICIPANTS: Patients with a diagnosis of cancer in one NHS Hospital Trust, and patients with a diagnosis of asthma in two NHS Hospital Trusts. RESULTS: Completed questionnaires were received from 353 cancer patients and 578 asthma patients. Factor analyses of the data indicated that 22 items contributed to five dimensions: 'positive beliefs', 'safety', 'information needs', 'negative expectations' and 'patient involvement'. Differences between asthma and cancer patients on these dimensions were small. A regression of these dimension scores against a variable asking if patients would be willing to take part in trials found that 'safety' and 'information needs' did not contribute significantly to the model for either asthma or cancer patients. CONCLUSIONS: A questionnaire has been developed for use in assessing patients' views towards clinical trials. Results from the surveys reported here suggest that patient views about the importance of trials and beliefs about the value of patient involvement are likely to be predictive of whether or not patients will agree to take part in a study.

Improving the quality of peak flow measurements for the diagnosis of occupational asthma.

INTRODUCTION: Serial measurements of peak expiratory flow (PEF) are recommended in the evidence-based review list as the first stage in objective confirmation of occupational asthma. Different centres have reported widely different success in obtaining records of sufficient data quantity for diagnosis. We investigated different methods of instruction and determined the return rate and quality of the resulting record for the diagnosis of occupational asthma. METHODS: Consecutive new referrals were recruited from a specialized occupational lung disease clinic and requested to carry out serial PEFs for the assessment of suspected occupational asthma. Requests to carry out the records were either from written postal instructions or personal instruction from a PEF specialist. Record quality received from other clinicians was also analysed separating those using dedicated occupational forms, and those submitting on graph type forms. RESULTS: The postal return rate was 56% and the personal rate 85%. The number of records fulfilling all the data quality criteria were similar in the postal and personal groups (55 and 59%, respectively). Pre-existing records from other clinics plotted from graph charts (fulfilling all criteria) were only adequate in 23%, compared with 61% adequate for pre-existing records plotted from occupational forms. Failure of the record to contain consecutive work periods of > or =3 workdays was the most common failure. CONCLUSION: The return rate of PEFs for diagnosing occupational asthma is better when patients have been given specific instructions from a PEF specialist and the data quantity better when recorded on a dedicated form.

Specific IgE to colophony?

BACKGROUND: Colophony (rosin) is a natural product obtained from coniferous trees. It is used in a diverse range of products such as adhesives, ink, paints and soldering fluxes. Some workers exposed to colophony during soldering can develop occupational asthma; at present, no specific IgE test is available to assess sensitization to colophony. METHODS: Serum samples were obtained from exposed symptomatic individuals (n = 7), some with a likely diagnosis of occupational asthma, exposed asymptomatic individuals (n = 10) and unexposed individuals (n = 11). Serum was tested for specific IgE antibodies against a protein extract produced following in vitro challenge of mono-mac-6 cells with colophony extract. RESULTS: Serum from exposed symptomatic individuals showed increased binding of specific IgE antibodies to a range of colophony-cell protein conjugates [29% (2/7) of samples tested when cut-off > 0.1 or 86% (6/7) of samples tested when cut-off > 0%] compared with both the exposed asymptomatic [0% when cut-off > 0.1, or 20% when cut-off > 0% (2/10)] and the non-exposed control populations [0% when cut-off > 0.1, or 27% when cut-off > 0% (3/11)]. CONCLUSIONS: This novel approach for the production of conjugates to assess sensitization to colophony was able to detect specific IgE in colophony-exposed workers with a likely diagnosis of occupational asthma.