Phase III Establishing the work-relatedness of asthma Population

5.6.1

Subjects whose methacholine tests suggested asthma (i.e. PD20 ≤ 1600 µg) were chosen.

Tests of work-relatedness 5.6.2

To investigate whether asthma was work related or not, asthmatic subjects were further investigated by serial monitoring of PEF and serial methacholine tests. In addition, these subjects undertook a clinical interview.

Serial PEF

Mini-Wright Digital meters (Clement Clarke, Inc) equipped with computer chip memory that could store up to 240 times and dates stamped PEF

measurements were used.

Each subject was asked to perform readings four times per day for four weeks including working weeks and periods off work for a week if possible. Otherwise, the researcher made sure that the subject at least was not working at

weekends. The subject was asked to make a minimum of three measurements at each time. The difference between the best two readings was to be within 20 l/min and if not, more measures were to be taken. These criteria should yield a record with adequate data quantity and should identify a work effect in 78% of subjects with occupational asthma.¹²⁰

The researcher demonstrated how to operate the Mini-Wright Digital meters.

The subject then was asked to practice the manoeuvre under supervision until their technique was satisfactory. Written instruction (appendix 7) was provided together with a written diary record (appendix 8). The subject was informed that a phone call was to be made after two weeks to check performance and to encourage recording. Another phone call was to be made after four weeks to arrange for collection of the device.

The first 17 subjects were not informed about the ability of the Mini-Wright Digital meters to save the measurements. Seven (41%) of the returned devices had few readings despite the supplementary handwritten diary being largely completed. The discrepancy between the hand-recorded and electronic

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measurements was attributed to device error, misuse of the device or subjects inventing readings if they missed many of them. Therefore, for the remaining subjects, the researcher stressed the device’s capability to store readings along with the date and time. The researcher provided subjects with a new design of diary where only activities and medications were required to be reported (appendix 9). This was hoped to improve compliance since the participants would realize that what would be stored in the device was the only source of data. In addition, the researcher asked some of the earlier participants to kindly repeat the test.

Method of analyzing serial PEF

The data from the digital mini-Wright device was downloaded automatically to a computer using a USB port and cradle. A record was considered to be eligible for further analysis if:

1. It included at least three readings per day for 75% of the records, 2. There were at least three complexes (work-rest-work) or

(rest-work-rest) in the record.

Three readings per day was accepted instead of the recommended four readings because the number of PEF measurements recorded by the digital mini-Wright device was almost always lower than the number on the written records in those with paired readings. As previous acceptability criteria were based on written records,¹²⁰ it is likely that these were based on a lower number of true measurements. Although the lower number of readings is known to affect the test’s sensitivity, it is still considered adequate for diagnosing

occupational asthma.¹²⁰ Gannon et al²⁸⁰ studied the ability of 2 to 10 readings in detecting PEF variability, a feature that is assessed on working and resting days by OASYS to detect work effects. The authors considered the diurnal variation calculated using the all 10 readings as the true diurnal variation, then they compared the diurnal variations calculated using 2-9 of the available readings with that calculated using the full 10 PEF readings. It was found that four

readings were optimum to detect PEF changes compared with 10 readings /day with a mean underestimation of the true diurnal variation of 1.3 percentage points. However, when three readings were used to calculate diurnal variation, it

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could still detect PEF variability with a small possibility of under-estimation that was found to be 1.7 percentage points.

The requirement to have a minimum of three consecutive workdays in most of the working periods was not strictly adhered to as many subjects worked weekends only or in other patterns that made this impossible.

OASYS-2 was used to plot charts for subjects who returned the device. The chart included daily minimum, mean and maximum PEF, as well as number of readings each day, figure 5-2.

OASYS compares PEF in consecutive work/rest/work periods and

rest/work/rest periods and gives an overall score to two decimal places from 1 to 4 to indicate the likelihood of occupational asthma. A total score of > 2.5 was considered to be suggestive of occupational asthma as proposed by Burge and co-workers.¹¹⁸

Figure 52 OASYS graphs shows daily minimum , mean and maximum --- PEF for the analysis of working days and leisure days

121 Serial methacholine tests

Subjects were invited to repeat the methacholine challenge test when they were away from work for a minimum of 7 days. Appointments were arranged at the time of the first visit for most of them. Some could not anticipate when they would be on their next holiday and asked the researcher to contact them later to confirm dates.

Repeated methacholine tests were performed following the same procedures outlined above.

Method of analyzing serial methacholine tests

The results of the methacholine tests at and away from work for each subject were presented in a table to allow comparison.

An increase in PD20 of 1.5 doubling or more when measured away from work was considered suggestive of a work-related adverse effect.¹¹⁰ Previous studies found that smaller changes in PD20 were insignificant and most likely resulted from factors such as normal physiological variation or from variations in the procedure itself.⁶¹ The average change in PD20 was summarised by a geometric mean, and the contrast between the geometric means at and away from work was expressed as the geometric mean ratio.

Clinical interview

An open semi-structured interview was conducted with each participant after the laboratory investigations; the mean duration was 20 minutes.

The questions in the interview were divided into 4 themes: clinical history of asthma/respiratory symptoms, occupational history; cleaning-related symptoms;

temporal relationship between work and symptoms.