OCCUPATIONAL ALLERGIES ALLSA Congress, Sept 2017, P/Elizabeth

Transcription

1 OCCUPATIONAL ALLERGIES ALLSA Congress, Sept 2017, P/Elizabeth Prof Mohamed F Jeebhay Head of Division Dr Shahieda Adams Director, Occupational Medicine Clinic, Groote Schuur Hospital Dr Amy Burdzik Occupational Medicine Consultant, Occupational Dermatology clinic Occupational Medicine Division School of Public Health and Family Medicine University of Cape Town

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3 OCCUPATIONAL ALLERGIES Diseases resulting from a hypersensitivity (exaggerated response) of the immune system to substances encountered in the work environment Constitute 15% of all occupational diseases (Finland data) Features: - initial contact with antigen - latent sensitisation period of weeks to years between first exposure and development of symptoms - temporal symptoms on exposure to very low doses of allergen - (exposure to non-specific irritants may trigger a reaction) ALLERGENS/SENSITISERS: - High Molecular weight agents - Proteins (animal, plant, microbial), enzymes (synthetic) - Low molecular weight agents - Chemicals

4 COMMON OCCUPATIONAL ALLERGIES Urticaria Rhinitis/Asthma Allergic alveolitis Contact dermatitis

5 OCCUPATIONAL RHINITIS AND ASTHMA Prof Mohamed F Jeebhay MBChB DOH MPhil (Epi) MPH (Occ Med) PhD OCCUPATIONAL MEDICINE DIVISION School of Public Health and Family Medicine University of Cape Town, South Africa ALLSA Congress, Sept 2017, Port Elizabeth

6 DEFINITION AND CLASSIFICATION

7 DEFINITIONS Work-related asthma includes occupational asthma and workexacerbated asthma: Occupational asthma (OA): asthma due to causes and conditions attributable to a particular occupational environment and not to stimuli encountered outside the workplace Work-exacerbated asthma (WEA): pre-existing asthma worsened by moderate-to-low level workplace exposures (e.g. dusts, smoke, fumes, sprays) and physical factors (e.g. cold air, humidity, strenuous work) but initially not caused by work At least 15% of adult asthma is work-related (Blanc and Toren, BMC Pulm Med, 2009) More than 25% of working adults with asthma have exacerbations of asthma at work (Fishwick, BMB, 2014)

8 CLASSIFICATION OF WORK-RELATED ASTHMA Work-related asthma (WRA) (PAF: 25%) Asthma caused by work: Occupational asthma (OA) (PAF: 15%) Pre-existing asthma exacerbated by work: Work-exacerbated asthma (WEA) (PAF: 25%) Sensitiser-induced (allergic) OA (80-85%) IgE-mediated asthma (HMW substances / protein allergens) (Jeebhay, CACI, 2012) Non-IgE mediated asthma (?LMW chemicals) Acute onset IIA Single high exposure to LMW chemicals (RADS) no latency, close temporal association Irritant-induced OA (5-15%) Subacute IIA Multiple high level symptomatic exposures to LMW chemicals (latency) Low-dose IIA Chronic moderate exposures

9 WORK-RELATED ASTHMA AND RHINITIS EAACI Consensus statement, Allergy, 2008

10 Common causes of occupational asthma in South Africa - Isocyanates - Cereal flour and grain - Natural rubber latex - Cleaning agents (instruments, surface) - Platinum salts - Laboratory animals (e.g. rat urinary proteins)

11 PATHOPHYSIOLOGICAL MECHANISMS

12 Allergens, particle size and lung deposition (EAACI Position Paper, Allergy, 2015)

13 ALLERGEN SOURCES AND ROUTES OF EXPOSURE Allergic reactions are the result of: de novo inhalation or skin contact/puncture with products containing single or multiple allergens (e.g. flour dust containing cereal flours, seafood, insect stings, isocyanates) re-exposure through an alternative route in a known food allergic individual (e.g. seafood) cross-reactivity to homologous protein allergens: - taxonomical homology (e.g. wheat vs. rye, shell-fish species, mites, latex-fruit) - structural similarities (e.g. profilins, cross-reactive carbohydrate determinants in pollen-food syndromes)

14 Mechanisms Involved in Sensitizer-Induced Asthma and Irritant-Induced Asthma. Tarlo and Lemiere, N Engl J Med 2014

15 NATURAL HISTORY OF OCCUPATIONAL ALLERGY AND ASTHMA

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17 EPIDEMIOLOGY OF OCCUPATIONAL ASTHMA

18 The incidence of OA in developing countries appears to be lower than industrialised countries (Jeebhay&Quirce, IJTlD, 2007) Under-detection or under-reporting or low risk populations? Occupational asthma in Great Britain, (HSE)

19 Patterns of atopy and allergic sensitisation in working adults in epidemiological studies of the Western Cape urban and rural differences West coast seafood workers (n=575) Overberg grape farm workers (n=207) Cape Town bakery workers (n=517) Common inhalants (SPT) House dust mite Cockroach Rye grass Bermuda grass Mouldmix Dog Cat (Jeebhay et al, Am J Ind Med, 2008 Jeebhay et al, Int Arch Allergy Immunol, 2007 Baatjies et al, Eur Resp J, 2009)

20 (Jeebhay & Quirce, IJTLD, 2007) Jeebhay CACI, 2012

21 RISK FACTORS FOR OCCUPATIONAL ALLERGY AND ASTHMA

22 Non work-related Asthma Younger age Female Risk factors for WRA and non-wra (Jeebhay et al, COACI, 2014) Family history of allergy/asthma Atopy Obesity Current/previous history of rhinitis or allergy Previous bronchial hyperresponsiveness Some serious childhood respiratory diseases (e.g. viral infections) Active and passive smoking Low household income Home environmental factors (e.g. fuel combustion, dampness, mould, environmental tobacco smoke) Exposure to cleaning sprays at home Host Risk Factors Behavioural and Social Factors Environmental Risk Factors Work-related Asthma (sensitizer-induced) Younger age Female (gendered distribution of work) Family history of allergy/asthma Atopy (for HMW protein agents) Obesity Current/previous history of work-related rhinitis Previous bronchial hyperresponsiveness Active smoking Low household income (association with greater risk of work exposure to sensitizers) HMW (protein) or LMW (chemical) sensitizing agents at work Cleaning/disinfectant agents at work Air pollution.

23 RISK FACTORS FOR SENSITISATION AND INHALANT OCCUPATIONAL ALLERGIC REACTIONS Environmental factors: Exposure to the causative agent/substance (allergen) Elevated dose (duration and level of exposure) Host-related factors: Atopy and genetic predisposition Cigarette smoking as a contributory factor Upper airway symptoms Pre-existing food/pollen allergy Dietary intake (?)

24 (Source: Cullinan, Panminerva Med, 2006)

25 Exposure-response relationships for wheat allergen exposure and asthma (Baatjies et al, OEM, 2015) 0.6 Sensitisation to wheat Work-related allergic rhinitis Prevalence (%) Allergic Work-related ocular-nasal allergic symptoms chest symptoms Baker s asthma Sensitisation to wheat Allergic chest symptoms Probable occupational asthma Allergic ocular-nasal symptoms Probable occupational asthma Average current wheat exposure g/m 3

26 Cross-reactivity between taxonomically-related inhalant allergens of food origin Pilchard antigen concentration Anchovy antigen concentration Fitted values ng/m3 Pilchard and anchovy environmental antigen concentrations highly correlated Spearman r = 0.74 (p<0.001) (Jeebhay et al, Ann Occ Hyg, 2005) Wheat and rye flour environmental antigen concentrations highly correlated Spearman r = 0.97 (p<0.001) (Baatjies et al, Ann Occ Hyg, 2010)

27 Host-related predictors of flour dust-related allergy and asthma phenotypes in bakers (Baatjies et al, Eur Resp J, 2009)

28 Atopy is an effect modifier for wheat sensitisation among bakers (Baatjies et al, OEM, 2015) Atopic ATOPIC Prevalence (%) Non-atopic NON-ATOPIC Sensitisation in atopics Sensitisation in non-atopics Sensitisation in all workers Average current wheat exposure g/m 3 Relationship between wheat sensitisation and wheat allergen concentration among supermarket bakery workers, stratified by atopic status

29 Smoking modifies the risk of sensitisation with exposure to platinum salts - hexachloroplatinic acid (Calverly et al, Occ Env Med, 1995) Platinum refinery salts: 14%/100 PYR sensitised (20% symptoms)

30 DIAGNOSTIC APPROACH: EVALUATION OF THE PATIENT

31 CASE STUDY A 42 year old man complains of a chronic cough and tight chest for the past six months. He is an exsmoker. He has been a baker for the past five years and prior to this he worked as a clerk in a joinery, which assembled furniture. He feels that his chest problem was caused by his work, but he is reluctant to report this to his employer for fear of losing his job

32 Diagnostic approach based on pathophysiological mechanisms involved Occupational history Environmental monitoring Serial PEF Spirometry NSBH FeNO Specific Challenge ImmunoCAP, Immunoblot SPT, CAST / Basophil Activation test Molecular markers (cytokines) (Jeebhay, CACI, 2011)

33 STEP I. Clinical and occupational exposure history Work-related asthma should be considered in all adult patients with new-onset or worsening asthma through taking an appropriate history Assess the probability of work-related asthma based on clinical history: Absence of symptoms prior to working in the current job Changes in work processes in the period prior to the onset of symptoms Unusual work exposure within 24 hours before the onset of initial asthma symptoms Asthma symptoms differ during times away from work such as weekends, holidays or other extended times away from work Symptoms of allergic rhinitis and/or conjunctivitis that worsen with work Increased probability of work-related symptoms in the first 2 years of employment high risk

34 An occupational exposure history is crucial in assessing the probability of exposure to potential asthmagenic agents Ascertain the nature and degree of exposure to a respiratory sensitiser or irritant to assess level of risk: A history of the job duties and duration Assess the level of airborne exposures of the job (degree of perceived dustiness) and exposure duration Use and adequacy of control measures and use of protective devices/equipment (respirators, goggles, gloves) A list of the hazardous exposures (obtain chemical safety data sheets of agents used from workplace) and cross-check against a list of known agents causing OA from reliable electronic databases, e.g. or Assess sensitising potential of the agent (QSAR Hazard Index for LMW agents) - epidemiology/coeh/research/workrelatedillhealth/asthma

35 Work activities that generate excessive aerosolisation of particulates dusts, vapours and fumes pose a higher risk Fish gutting Bread dough mixing Spice blending Fish cooking Dusting dough table Spice mix packing

36 Quantitative Structural Activity Relationship (QSAR) Hazard Index for occupational asthma causation (Jarvis et al, OEM, 2005)

37 Confirm the diagnosis of asthma using any one of the ff: Spirometry: a post-bronchodilator increase of 12% accompanied by a 200 ml increase in FEV 1 Serial peak expiratory flow (PEF) monitoring over a 2-week period: diurnal variation of 20% (especially useful for low molecular weight exposures) Steroid trial: > 20% improvement in FEV 1 after 2 weeks Non-specific challenge test with methacholine/histamine: PC 20 < 8mg/ml (A negative methacholine challenge (PC 20 >16mg/ml) in a subject still exposed to the causative agent at work makes the diagnosis of occupational asthma very unlikely) Differential diagnosis: Irritable larynx syndrome Eosinophilic bronchitis STEP II. Confirmation of asthma Asthma-like syndromes (e.g. byssinosis, aluminium potroom asthma, grain dust COPD) It is best to complete the evaluation of the patient and/or refer to an occupational medicine specialist before removing the patient from work

38 STEP III. Confirmation of work-related bronchoconstriction Establish the work-relatedness of asthma using objective tests: Serial PEF testing using a portable peak flow meter (at work and away from work 4 per day for 4 weeks) in patients who are still working in the job OASYS Graph of a worker handling cellulose fibre: AWAY FROM WORK >20% variability in PEF measurements Work effect Index (WEI) = 3.8 (Cut off = <2.5) ( Serial PEF measurement is a feasible, sensitive (82%), and specific (88%) test for the diagnosis of occupational asthma, when potential sources of error are understood (Moore et al, AoRM 2009)

39 STEP IV. Confirmation of sensitisation to occupational allergens Immunologic assessment aims to: - Identify presence of atopy as a risk factor Atopic workers exposed to high molecular weight agents (proteins) are at increased risk of becoming sensitised to occupational allergens - Support the diagnosis of occupational allergic rhinitis/asthma in symptomatic patients exposed to respiratory sensitisers Various techniques are used: Skin prick tests Allergen-specific IgE (ImmunoCAP) ( Information/Occupational-Allergens/) Immunoblots Basophil activation / CAST ELISA assay

40 Skin Prick Testing SPT results of a supermarket bakery worker: Atopic (HDM, rye grass, cockroach) Occupational allergens + (wheat, rye, corn flour) Positive test: wheal >3mm than negative control

41 Allergen-specific serum IgE testing

42 Asymptomatic IgE reactivity vs. true latex allergy in dental health care workers (n = 41) relevance of cross-reactive carbohydrate determinants (CCDs) (Ratshikhopha et al, Occ Health SA, 2016) Prevalence of true latex allery = ~ 50% of initial 9.7% on K82 ImmunoCAP for latex

43 Increased probability of clinical reactivity with elevated levels of IgE antibodies Williams et al, Clin Exp Immunol, 2009

44 Immunoblot Testing (Van der Walt et al, Int Arch Allerg Immunol, 2010) 150kDa 100kDa 75kDa 50kDa 37kDa ImmunoCAP and Immunoblot results of a spice mill worker: - Garlic and onion IgE kDa protein binding to serum IgE 25kDa 20kDa 1 = molec. weight marker 2 = maize meal 3 = garlic powder 4 = raw garlic 5 = onion flakes 6 = raw onion Serum specific IgE (ku/l) Patient Ref garlic 2.37 <0.35 onion 2.05 <0.35

45 CAST ELISA Test (Lopata et al, Int Arch Allergy Immunol, 2007) PATIENT A PATIENT B CONTROL Serum specific IgE (ku/l) Patient A Patient B Latex Patient Ref (k82) 1.70 <0.35 Latex (k82) 11.6 <0.35 ImmunoCAP and CAST ELISA test of 2 garment workers: - sulphidoleukotriene release

46 STEP V. Specific bronchial challenge test the gold standard Confirmation of the causal role of occupational agent (Jeebhay, et al, JACI, 1996) Meranti wood dust (control) Imbuia dust (causative agent) SBT results of a furniture joinery worker: - >15% decline in FEV 1 post challenge (Vandenplas, ERS Taskforce on OA, 2014)

47 Assessment and diagnosis of Irritant-induced Occupational Asthma Acute onset IIA / RADS: diagnosis of asthma onset of asthma after a single exposure or accident to an irritant vapour, gas, fumes or smoke in very high concentrations (within mins. to <24 hrs) exclusion of pre-existent asthma Asthma symptoms and NSBH persistence (> few weeks) after exposure Subacute IIA (multiple high level exposures): Similar to above except that there is evidence of multiple symptomatic exposures to irritant vapours, gas, fumes or smoke with latency Subacute IIA (multiple low level exposures): Chronic low dose exposures to chemicals with latency (EAACI Position Paper, Allergy, 2014)

48 Assessment and diagnosis of Work Exacerbated Asthma Suspect work exacerbated asthma (WEA) in individuals with: pre-existing asthma moderate-to-low level workplace exposures to dusts, smoke, fumes, sprays or extreme physical factors (e.g. cold air, humidity, strenuous work) worsening of asthma symptoms (increase in doctor visits or medication use) or deterioration of lung function no documented workplace exposure to agents known to induce occupational asthma (OA) OA and WEA are managed differently - OA patients need to be removed from the specific exposure as soon as possible, whereas WEA patients may continue to work in current job provided there is close environmental control and asthma treatment is optimised

49 EVALUATION OF THE WORK ENVIRONMENT

50 Evaluation of allergen content of manufactured products Underwear manufacture (Lopata, et al, Int Arch Allergy Immunol, 2007) Glove evaluation prior to purchase (Ratshikhopha et al, SAMJ, 2015)

51 MANAGEMENT

52 MANAGEMENT 1. Exposure avoidance Patients with allergic OA should be relocated to a job without exposure, or if this is not possible they should be moved to an area of low exposure The use of respirators is usually ineffective in preventing exposure and exacerbations Irritant-induced OA or WEA: optimise asthma treatment and reduce exposure to relevant workplace triggers, and if not successful change job to a workplace with fewer triggers in order to control asthma. RADS: patients can continue to work in the same job provided measures are taken to prevent further exposures to high concentrations of irritant agents Early diagnosis and early avoidance of further exposure are key to the management occupational asthma

53 Recommendations of the Scandinavian workshop on the management of baker s allergy and asthma following surveillance SYMPTOMS SENSITISATION Asthmatics sensitised to flour or fungal -amylase MANAGEMENT Change to non-bakery work Asthmatics without sensitisation Relocate to less exposed bakery tasks Bakers with rhinitis and sensitisation Bakers sensitised but without respiratory symptoms Bakers with rhinitis only but without sensitisation Investigate closely and consider relocation to less exposed tasks Re-examine annually Do not warrant re-examination unless symptoms worsen

54 2. Optimise asthma treatment Pharmacological treatment of WRA does not differ from therapy of other types of asthma, and should comply with the asthma treatment guidelines Treat co-morbid conditions, e.g. allergic rhinitis Counsel on cessation of smoking and avoidance of exposure to common environmental irritants or aeroallergens to which patients may also be sensitised Early use of inhaled corticosteroids after the diagnosis may improve symptoms, but insufficient evidence whether pharmacological treatment alters course of asthma in subjects who remain exposed

55 3. Ongoing follow up and assessment of impairment and disability Evaluate degree of impairment (presence of symptoms and exacerbations, post-bronchodilator FEV 1, degree of reversibility or NSBH, type and dose of medication needed for control) and disability evaluation (in relation to job) Assessment is done three weeks after removal from exposure and after two years when the asthma is stabilised Asthma symptoms and airway hyperresponsiveness persist in ~70% of patients with occupational asthma, even after several years of removal from exposure Good prognostic factors for outcome of occupational asthma: - early diagnosis - cessation of exposure to the offending agent - asthma is not yet severe (lung function preserved at diagnosis) Monitor patient and if asthma severe or worsens consider job change if still exposed

56 SUMMARY: Diagnosis and management of occupational asthma in the South African setting

57 TAKE HOME MESSAGES Work-related asthma should be considered in all adult patients with new-onset or worsening asthma Early diagnosis and early avoidance of further exposure are key to the management occupational asthma

58 Referral/advice centres for assistance with occupational diseases Cape Town Occupational Medicine Clinic (E16), Groote Schuur Hospital, (021) Respiratory Clinic, Tygerberg Hospital, (021) Johannesburg National Institute of Occupational Health, Braamfontein, (011) Medical Bureau for Occupational Diseases, Braamfontein, (011) Durban Occupational Medicine Clinic, King Edward Hospital, (031) /3 or (031)