Recognizing and preventing Occupational asthma and lung diseases:Recognizing and preventing Occupational asthma and lung diseases Moira Chan-Yeung, University of British Columbia


Diseases associated with occupational exposure :Diseases associated with occupational exposure Clinical manifestations of lung diseases are the same irrespective of the etiology Airway diseases Asthma (reversible) Chronic obstructive lung disease (irreversible) Cancer Parenchymal diseases Hypersensitivity pneumonitis (reversible) Diffuse fibrosis (irreversible) eg. silicosis, asbestosis


Occupational asthma:Occupational asthma Disease characterized by variable airflow obstruction and/or airway hyperresponsiveness due to causes and conditions attributable to a particular working environment and not to stimuli encountered outside the workplace


% occupational asthma in occupational lung diseases:% occupational asthma in occupational lung diseases UK BC, Canada (1989) (1992) Asthma 26.4 52.0 Pneumoconiosis 15.4 17.8 Others 58.2 30.2


Attributable risk (AR) of occupation for adult onset asthma by source of data:Attributable risk (AR) of occupation for adult onset asthma by source of data AR Population-based studies 15 (2-20) Medical practice data 9 (2-33) Surveillance or registry data 4 (2-17) Medicolegal data 5 (3-8) Overall Median 9 (2-45) Blanc and Toren 1999


Recognise and establish work-relatedness :Recognise and establish work-relatedness Aware and suspect Occupational history Medical history suggesting work-relatedness Symptoms started after employment Improvement of symptoms during weekends and holidays Worsening of symptoms on returning to work Objective testing


History:History A history suggestive of work-relatedness is very sensitive but…: Predictive value of questionnaire positive = 63% / negative = 83% A history of asthma at work, even in the presence of a known sensitizer, does not confirm the diagnosis of occupational asthma The diagnosis needs to be confirmed objectively


Objective testing to confirm work-relatedness:Objective testing to confirm work-relatedness Pre and post-shift measurement of lung function Monitoring of PEF at and off work, each for a period of 2 weeks with and without measurement of NSBH Specific inhalation challenges or occupational type of exposure tests - "gold standard"


Slide 9:Exposure to nickel dust


Slide 10:Spirometry at and away from work cross-shift Exposure challenge testing


Monitoring of PEF - How to do it ?:Monitoring of PEF - How to do it ? At least 2 weeks at work and off work (often longer...) At least 4 times daily, preferably every 2 hours Medication allowed: keep constant & at minimum dose... beta-2 agonist on demand only continue inhaled steroids/theophylline avoid, if possible, long-acting beta-2-agonist


Slide 12:Serial monitoring of PEF in the diagnosis of OA


PEF monitoring :PEF monitoring False positive Subject not exposed during monitoring Poor compliance False negative Change in medication (inhaled steroids) Bronchitis Malingering (falsification of results)


Slide 15:Serial monitoring of PEF in the diagnosis of OA


Slide 16:Exposure chamber


Methods- exposure testing:Methods- exposure testing


Typical patterns of response:Typical patterns of response


Skin tests & serology:Skin tests & serology Valid for HMW allergens (eg. baker’s asthma) & rarely for LMW agents (eg. diisocyanates) Requires good allergen extracts Frequently not available commercially When positive, means presence of sensitization


Slide 21:Compatible clinical history and exposure Skin testing and/or specific IgE (if possible) Assessment of NSBH Normal Increased Subject still at work Subject no longer at work Subject still at work Laboratory challenge tests Positive Negative Consider return to work Workplace challenge tests PEF monitoring, or both Positive Negative No asthma Occupational asthma Non occcupational asthma Use of other means (induced sputum, exhaled NO) Chan Yeung M, Malo JL. NEJM 1995; 333:107 Algorithm for investigation of occupational asthma


Slide 22:Occupational agents known to cause OA


Identifying a novel agent suspected for causing occupational asthma:Identifying a novel agent suspected for causing occupational asthma


Slide 24:Thuja plicata Western red cedar


Slide 25:Inhalation challenge test with dust of Western red cedar induced a late asthmatic reaction


Slide 27:Inhalation challenge with aqueous Western red cedar extract and with plicatic acid induced biphasic asthmatic reaction


Hypersensitivity pneumonitis- definition:Hypersensitivity pneumonitis- definition Hypersensitivity pneumonitis is a spectrum of granulomatous, interstitial, and alveolar-filling lung diseases that result from repeated inhalation of and sensitization to a wide variety of organic dusts


Slide 30:Mushroom Workers’ Lung (Thermoactinomyces vulgaris) Acute onset of fever, malaise, and shortness of breath after spawning Chest- diffuse crackles


Hypersensitivity pneumonitis (HP)Diagnosis:Hypersensitivity pneumonitis (HP)Diagnosis Diagnosis of HP: Compatible clinical picture (symptoms, chest x-ray or CT, lung function changes) of HP Presence of precipitating antibodies Bronchoalveolar lavage Lung biopsy Objective testing to establish work-relatedness: Returning to work induce similar symptoms and signs Specific challenge tests – more difficult to do


Hypersensitivity pneumonitis - microorganisms (1):Hypersensitivity pneumonitis - microorganisms (1)


Hypersensitivity pneumonitis - microorganisms (2):Hypersensitivity pneumonitis - microorganisms (2)


Hypersensitivity pneumonitis – (3):Hypersensitivity pneumonitis – (3)


Bronchiolitis obliterans:Bronchiolitis obliterans Narrowing of the small airways as a result of inhalation of toxins Patients present with progressive shortness of breath on exertion over a period of weeks or months Lung function tests show irreversible airflow obstruction Chest x-ray normal


Clinical bronchiolitis obliterans in workers in a microwave-popcorn plant- Kreiss et al:Clinical bronchiolitis obliterans in workers in a microwave-popcorn plant- Kreiss et al May 2000, eight former employees of a microwave-popcorn plant were reported to have severe bronchiolitis obliterans (between 1993-2000) A survey was carried out in the plant 117/135 took part


Slide 37:Workers in the popcorn plant had significantly higher prevalence of symptoms than expected irrespective of smoking habit


Slide 39:Strong relation between the quartile of estimated cumulative exposure to diacetyl (butter-flavouring agent) and the frequency and extent of airway obstruction.


Difficulties in recognizing disease related to work exposure :Difficulties in recognizing disease related to work exposure No distinct episode of over-exposure that preceded the onset of symptoms No temporal relationship existed between working at the plant and the severity of symptoms over the course of the workday or workweek Association of this disease with exposures in the workplace was largely unsuspected by the workers, their physicians and the plant managers


Clinical bronchiolitis obliterans in workers in a microwave-popcorn plant- Kreiss et al:Clinical bronchiolitis obliterans in workers in a microwave-popcorn plant- Kreiss et al Distribution of health-related conditions among workers and over time; Excess prevalence of respiratory disease in the current workers Estimated cumulative exposure to diacetyl direct inverse correlation with lung function Rats exposed to diacetyl levels of 352 ppm had damage to respiratory epithelium, higher level damage the area below the epithelium


Chronic obstructive pulmonary disease (COPD):Chronic obstructive pulmonary disease (COPD) COPD is a disease characterized by airflow obstruction that is not reversible. The airflow obstruction is usually progressive and associated with abnormal inflammatory response of the lungs to noxious particles and gases. COPD should be considered in any patient presenting with cough, sputum production and breathlessness. The diagnosis is confirmed by spirometry. The presence of post bronchodilator FEV1 of < 80% the predicted and FEV/FVC of <70% confirms the presence of airflow limitation that is not reversible. GOLD 2001


Occupational contribution to the burden of COPD:Occupational contribution to the burden of COPD ATS position statement 2003


Occupational exposure and chronic obstructive pulmonary disease (COPD):Occupational exposure and chronic obstructive pulmonary disease (COPD) Long-term exposure to Inorganic dust Organic dust Chemicals - vapors, irritants, fumes


Slide 46:Area sampling of grain elevators 1974-1989


Slide 47:Respiratory symptoms in grain workers and controls


Slide 48:Cumulative exposure and lung function in grain workers


Slide 49:Lung function of retired grain and civic workers


Establish work-relatedness of COPD :Establish work-relatedness of COPD Mostly based on epidemiological evidence In an individual patient, work-relatedness of COPD is difficult to establish Diagnosis is by exclusion, easier if patient is a nonsmoker In a smoker, it is often not possible to apportion effect of smoking from effect of occupational exposure


Prevention of occupational lung disease:Prevention of occupational lung disease


Primary prevention of OA:Primary prevention of OA Reduce exposure Pre-employment screening Atopy Genetic factors Education Screen for potential respiratory sensitizers


Slide 53:Accepted claims for diisocyanate-induced and other types of OA in Ontario, 1980-93 Tarlo and Liss 2002 Annual incidence of incident reports and allergy clinic visits of hospital staff relating to perceived NRL allergy


HLA and occupational sensitizers:HLA and occupational sensitizers Agent HLA class OR Western red cedar DQB1 *0501 0.3 DQB1 *0302 4.9 Horne et al ERJ; 2000 Diisocyanates DQB1 *0501 0.14 DQB1 *0503 9.8 Bignon et al ARJCCM; 1994


Structure of the occupational agent:Structure of the occupational agent Some agents are potent respiratory sensitizers: HMW – those with enzymatic activity eg. detergent enzymes LMW compounds – those with N=C=O eg. isocyanates


Summary:Summary Awareness of occupational exposure as a cause of disease is important Occupational history is mandatory To establish a work relationship, objective evidence of exposure and occurrence of symptoms or changes in lung function is necessary Reduction of exposure is the key to prevention


Slide 58:Asbestos exposure and recognition of asbestos-related diseases


Employment based risk factors :Employment based risk factors Size of business Region Age of employees most at risk Income


Slide 60:Sensitivity and specificity of various diagnostic methods – specific challenge test as gold standard


Slide 61:Improvement of PEF when away from work and deterioration of PEF on returning to work


Slide 62:Cases of OA in selected countries


Atypical patterns of response:Atypical patterns of response


Slide 65:Improvement of PEF when away from work and deterioration of PEF on returning to work Serial PEF monitoring


Exposure-response relationships:Exposure-response relationships Substance Lowest effective dose Flour 1-2.4 mg/m3 Fungal amylase 0.25 ng/m3 Red cedar dust 1 mg/m3 Natural rubber latex 0.6 ng/m3 Cow dander 1-29 ug/g dust Rat urine 0.1 – 68 u/m3 Acid anhydride - TMA 0.82 mg/m3 Isocyanates 5-10 ppb Baur et al. Clin Exp Allergy 1998


Prevention of CAO :Prevention of CAO Prohibition of smoking in the workplace Reduction of exposure Education


Slide 68:Grain elevator workers 5 cross-sectional study 1974-1989 …. Cross-sectional study ___ Longitudinal study


Slide 69:Changing trend in OA


Slide 71:Non Smokers Ex- Smokers Moderate Smokers Heavy Smokers (31) (51) (20) (48) (88) (156) (48) (132) ( ) No of men No Yes Occupational exposure FEV1 slope (ml/a) FEV1 slope according to smoking habits and occupational exposure


Slide 72:Prevalence of respiratory symptoms in nonsmoking grain and civic workers 1974-1989


Slide 73:1e+0 1e+1 1e+2 1e+3 1e+4 1e+5 Log (allergen concentration) (ng/m3) Dose-response relationship for sensitization to occupational allergens


Slide 74:%