DIAGNOSTIC TOOLS FOR OCCUPATIONAL

ASTHMA

Theerapan Songnuy M.D.

Overview

Definition Etiology Diagnosis Conclusion

Occupational Asthma ( OA)

Jean Luc Malo & Moira Chan-Yeung. Occupational Asthma. In Middleton 7th edition. 939-953.

-A type of asthma caused by the workplace-Classified into 2 types: 1. OA with a latency period need to get sensitized to an agent in the workplace 2. OA without a latency period, occur after accidentally inhale at work-Of the first type, mostly caused by high ( protein) molecular-weight agents-High-molecular weight agent induced by IgE- mediated mechanism- LMW agents act as hapten

lJean Luc Malo & Moira Chan-Yeung. Occupational Asthma. In Middleton 7th edition. 939-953.

l

Jean Luc Malo & Moira Chan-Yeung. Occupational Asthma. In Middleton 7th edition. 939-953.

JACI 2013; 131: 704-10

Aims

1. Compare the clinical , functional and inflammatory characteristics of workers with work-exacerbated asthma and occupational asthma2. Compare health care use and related costs between work-exacerbated asthma and occupational asthma, work-related asthma and non-work-related asthma

JACI 2013; 131: 704-10

Materials & Methods A prospective cohort study with a 2-year

follow-up Subjects: - Asthmatic patients referred for suspected work-related asthma - Two tertiary centers in Quebec, Canada - From 2003-2008 JACI 2013; 131: 704-10

Materials & Methods Subjects : - At first visit ; questionnaires, SPT, PFT, methacholine inhalation challenge test, sputum induction - Be classified as ; inflammatory phenotypes - Eosiophilic ( sputum EO > 3%) - Nutrophilic ( sputum N > 61%) - Paucigranulocytic ( sputum EO< 3%,N <

61%) - Mixed ( sputum EO> 3% , N > 61%)

Materials & Methods Severe asthma: an ER visit or a hospitalization Specific inhalation challenges to occupational agents

were done when asthma possibly related to work Asthma diagnosis: - FEV1<80% of predicted value - FEV1/FVC < 0.7 - improvement in FEV1 > 12% after bronchodilator - If absence of reversible airflow limitation, PC20 value should < 16 mg/ml JACI 2013; 131: 704-10

Materials & Methods Diagnosis of occupational asthma: - Positive specific inhalation challenge test - Worsening asthma symptoms while at work Diagnosis of work-exacerbation asthma: - Negative specific inhalation challenge test - Worsening asthma symptoms while at work

Materials & Methods

Health care use and related costs - From administrative database - Focusing on physician’s cost, ER

visit & hospitalization

JACI 2013; 131: 704-10

JACI 2013; 131: 704-10

JACI 2013; 131: 704-10

JACI 2013; 131: 704-10

JACI 2013; 131: 704-10

JACI 2013; 131: 704-10

Conclusion

Workers with WEA have more severe clinical than workers with occupational asthma

WEA is associated with a non-eosinophilic phenotype

Both WEA & occupational asthma have greater health care use & 10-fold higher direct costs than NWRA

Diagnostic tools for Occupational Asthma Specific inhalation challenge ( standard

test) Combination of Peak Expiratory Flow

Rate & sputum eosinophil count Exhaled Breath Condensate pH test

l

Aims

To characterize the threshold duration of exposure needed to elicit an asthmatic reaction during specific inhalation challenge with various occupational agents

To determine the duration of exposure that should be complete before the test can be considered negative

Materials & Methods

A retrospective study Centre Hospitalier Universitaire de Mont-

Godinne, Universite Catholique de Louvain, Yvain,Belgium

From Jan 1992-Dec 2011 Data records were reviewed All subjects investigated for possible

occupational asthma with positive test for specific inhalation challenge

Materials & Methods Specific Inhalation Challenge:

- Occupational agents were generated in five-cubic-meter cubicles using a realistic approach

- Asthma medications were stopped according to their duration of action

- Inhaled steroid was halted 72 hr prior to the test - The level of exposure during SICs was monitored only for isocyanates using an MDA 7100 monitor ( MDA Scienctific Inc, Glenview, IL) & was kept

below the ceiling value of 20 ppb.

Materials & Methods Spirometry was obtained at: - baseline, q 15 min * 4 times q 30 min * 2 times q 1 hr for a total of 6 hr after the end of exposure - The baseline level of BHR to histamine & sputum eosinophil

count were assessed at the end of control day

- Re-assessed 6 & 24 hr after the active challenge

- Degree of non-specific BHR was assessed as provocative concentration of histamine causing a 20% fall in FEV1

( PC20)

- Positive SIC : sustained > 20% fall in FEV1 was recorded on 2 consecutive assessments

Materials & Methods On the first day : - Using “ control” agent for 30 min to ensure FEV1 fluctuation < 12% of baseline - “ control” agent according to the nature of occupational agent suspected causing

asthma ( ie ; use lactose powder for flour)

Materials & Methods The second day: - Use a suspected agent - A duration of exposure gradually increased from 1 , 4, 10, 15, 30, 60 min until a > 20% fall in FEV1 occurred or 2 hr was reached

- Who did not show a >20% fall in FEV1, had to repeat for 3 hr on the next day

- Negative test : challenging at least 240 min without significant change

- If > 3-fold decrease in post-challenge PC20 or increase in sputum > 3% compared to control value, further challenge will be repeated

Conclusion

Sensitivity of Specific Inhalation Challenge for diagnosis occupational asthma depend on duration of challenge exposure

Need markers such as post-challenge level of non-specific bronchial responsiveness to histamine , sputum eosinophil count

Aim

To evaluate the utility of exhaled breath condensate ( EBC) pH for the diagnosis of occupational asthma

Materials & Methods

A prospective study Total of 37 patients suspected

occupational asthma Exclusion criteria: - Seasonal asthma - Can not join PEF, SIC, EBC pH * Allow to take asthma medication

but don’t change type or dose

Materials & Methods Spirometry & Methacholine Test

- A Datospir 200 system ( Sibel, Barcelona, Spain) used for spirometry

- A Mefar MB3 dosimeter ( Ele H2O, Medically, Brescia, Italy) for Methacholine test

- Increasing dose of methacholine ( 0.03-16 mg/ml) were inhaled at 3-min intervals until FEV1 fell by 20% of baseline or max dose was inhaled ( PC 20)

- Negative test defined as PC20 > 16 mg/ml - Dose response rate : last FEV1 decline ( %) / last dose administered

Materials & Methods Monitoring Peak Expiratory Flow Rates

- Serial PEF during 2 wk at work & 2 wk off work - A Mini-Wright portable peak flow meter ( Clement

Clarke International, UK) & diary cards

- Record 4 times a day - PEF graphs were interpreted by 3 experienced

independent readers

- Positive test : evidence changes between exposure period

- PEF recording was computerized by Oasys-2 software

- Suggestive Occupational asthma : score > 2.51

Materials & Methods Exhaled Breath Condensate Collection & pH

Measurement

- Collecting during tidal breating with a commercially condensor ( EcoScreen; Jaeger,Wurzburg, Germany)

- To determine ventilatory pattern, spirometer ( EcoVent; Jaeger ) was connected

- Patients were prohibited from foods 2 hr before sample collection

- A fixed volume of 150 liters of exhaled breath was collected per patient

- Sample was divided into 500 ul aliquots in 2-4 plastic tubes

Materials & Methods pH was measured in 1 aliquot after

collection immediately Another one was measured after de-

aeration with helium ( 350ml/min for 10 min)

Using a model GLP 21 calibrated Ph meter

( Crison Instruments SA, Barcelona, Spain) with an accuracy of +- 0.01 pH

A probe ( Crison 5028) was calibrated daily with standard Ph 7.02 & 4.00 buffers

N

Materials & Methods Specific Inhalation Challenge:

- Standard test for diagnosis - Using substances suspected the cause of the

patient’s asthma*

- A placebo was done before an actual test - Measuring FEV1, FVC q 10 min during first hr

following exposure & q 1 hr until 15 hr post-inhalation

- Positive test : FEV1 decrease > 20% baseline

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Conclusion

SIC is a gold standard to diagnosis occupational asthma

EBC pH is an easily performed, inexpensive, & noninvasive method

If SIC can’t be done, PEF & induced sputum eosinophil count are chosen

EBC pH alone or combine with PEF may be a good option

Thank You Very Much