Peak Expiratory Flow Rates in Possible Occupational Asthma

Peak Expiratory Flow Rates in Possible Occupational Asthma* Gary M. Liss, M.D.;t and Susan M. Tarlo, M.B., B.S., RC.C.R*

Objective criteria for interpretation of peak expiratory Bow rate readings were assessed in 50 patients evaluated for suspected occupational asthma who had at least two weeks of PEFR readings and an objective diagnosis based on other investigations. The prevalence of OA was 36 percent. Peak Bows were interpreted by two observers blinded to other results. Criteria for a PEFR interpretation of OA were as follow: diurnal variation ~20 percent relatively more frequently or with greater variation on working days than days otT work. With the objective diagnoses as the gold standard, the sensitivity of the PEFR interpretations was 72 percent for OA; specificity for DO asthma was 53

A number of modalities have been described for

use in the diagnosis of occupational asthma including history, changes in pulmonary function (FEV.), serial peak Howrecordings, immunologic studies (specific antibodies, skin tests), nonspecific tests for airways responsiveness (with methacholine, for example), and bronchial provocation testing (specific sensitizer challenge)." No single test can be used for the diagnosis, as even specific bronchial challenge in the laboratory with workplace agents has not been well standardized and is subject to false positives and negatives. 4 There have been few attempts reported in the literature to develop explicit criteria for the interpretation of self-recorded peak expiratory How rate records for use in the detection of occupational asthma. Smith et al5 recently commented that the interpretation of peak How patterns is not well established. Burge" noted that reading these records is currently done subjectively The problems and limitations of peak How tracings have been described." These include that workplace studies could be dangerous for those with severe asthma; investigation may not be feasible for those who have already left/lost their jobs; they are effortdependent and require substantial motivation from the doctor and worker to record; records may be subject to fabrication; and the results are nonspecific with respect to the provocative agents. Burge et al? described hourly, daily; and weekly peak How patterns of OA among those exposed to *From the tHealth Studies Service, Ontario Ministry of Labour,

and the *Gage Research Institute and Toronto General Hospital, Department of Medicine, University of Toronto, Toronto, Canada. Manuscript received May 11; revision accepted November 12. Reprint requests: Dr. Tarlo, 7bronto General Hospital, 10 Eaton N216, 7bronto, Ontario, Canada M5G 2C4

percent. Excluding those with ~20 percent variation on only one day sensitivity improved to 93 percent for OA, and specificity to 77 percent. There was an acceptable level of interobserver variation (kappa 62 to 83 percent). We conclude that simple objective criteria for PEFR interpretation can be developed with acceptable interobserver variation. (Cheat 1991; 100:63-9)

=

=

NPV negative predictive value; OA occupational asthma; PEFR = peak expiratory 80w rate; PPV = positive predictive value; TLV = threshold limit value.

colophony; the authors attempted to assess the accuracy of bronchial provocation and peak flows against the gold standard of "final assessment," They noted that the final assessment was based on the history and the effects of subsequent exposure at work after bronchial provocation testing. The authors noted, however, that the PEFR records had not been analyzed when assessments were made and were interpreted without knowledge of subject symptoms or challenge tests. It is not indicated if the PEFR records were interpreted blind to the final assessment. The criteria of Burge et al7•8 also required 75 percent of the working weeks or weekends to show specific patterns. However, there was a minimum of only two weeks of records. The patterns of Burge et al7 •8 did not give the quantitative change required for diagnosis. To place a frequency on the number of times a given decrease in PEFR (eg, 20 percent) should occur, or to determine criteria for the relative frequency of falls in PEFR at work vs home, is difficult. This is due, in part, to the fact that the tracings may not always cover a sufficient period, they lack consistency from week to week, subjects may also work on weekends, or weekend tracings may be omitted by the subject. In contrast, Smith et al9 used a fall in PEFR on anyone day of 20 percent or more of a day's maximum PEFR with concurrent symptoms to define symptomatic bronchial lability, although these recordings were made over one week only Others' have arbitrarily recommended recordings every two hours for at least two weeks with at least a 20 percent fall in PEFR at work compared to a period away from work. These authors noted the need for the development of objective criteria for interpreting data obtained by monitoringofPEFR. CHEST I 100 I 1 I JUL'(, 1991

83

'The purpose of this paper was to determine the following in a group of patients referred for possible OA: (1) whether simple practical criteria with quantitative diurnal variation could be developed for interpretation of peak flows; (2) the interobserver variation in interpretation when two investigators applied the criteria; and (3) the relationship of peak flow determination to an objective diagnosis based on other modalities (methacholine sensitivity change, specific work substance challenge, skin test} blinded to peak flo\~ In other words, does the PEFR record predict those having or not having OA (or nonoccupational asthma); does it add additional information? MATERIALS AND METHOUS

Patients were selected from the files of consecutive workers referred for assessment of possible occupational asthma. They were all seen in the occupational asthma clinics of the Gage Research Institute and the Toronto General Hospital between 197~ and 1988 by one of us (S. M .'L) using the same diagnostic approach throughout, as previously described. to A full history of all subjects included occupational exposure, information Oil any known spills or unusually high exposures, respiratory symptoms, date of onset, and temporal relationship to the workplace. Smoking history, upper respiratory symptoms, history of respiratory symptoms, and family history of allergy were also included, and a full physical examination was performed. Skin testing was done by the prick method llsing a group of 16 common allergenic extracts (Bencard) and diluent in all patients. Additional skin tests were performed with known allergens or potential allergens present in the individual's workplace. A positive skin test was taken as a weal 2 nun or more larger in diameter than that of the control response, with a surrounding Hare. Baseline pulmonary tests were performed in all patients at the initial visit, consisting of spirometry, pulmonary volumes, and diffusing capacity. Challenge testing with methacholine inhalation was done usin~ the method described by Juniper and colleagues. II A methacholine PC;2l1 of 8 mg/ml or less was taken to indicate bronchial hyperresponsiveness. Where possible, methacholine challenges were repeated within 48 hours after a day at work and after 10 to 14 days ofl' work. If the baseline FEV I was SO percent of predicted or less, or 1 L or less, or if the FEV I VC ratio was 50 percent or less, the methacholine challenge was not done, hut spirometry was repeated 15 minutes after administration ofp2-adrenergie inhaler (albutcrol [salbutamol]: 400 JJ.W. Au increase of 15 percent or more in FEV I from baseline was taken to indicate reversible airflow limitation. A bronchodilator response to alhutcrol was also performed in those patients unable or unwilling to discontinue their bronchodilator medications long enough f{,ra methacholine challenge to be performed (raIlgin~ from 8 hours prior to challenge for inhaled ~;!-adrener~ic agents to 48 hours for slow-release theophylline preparations). In patients who were still at work continuing exposure to similar amounts of the suspected causative agent as reported in the history, and in those who had left but could return to the fOrIHer work environment. studies of peak 00\\' at horne and at work were performed over a four-week period when possible (at least two working weeks, and if possible, two weeks otl· work). using a peak Howmeter (either a Wright or mini- Wright peak Huwmeter [Armstrong Medical Industries], an Assess [Health Scan] peak Howmeter, or a Spira peak Howmeter [Trudell Medicalj). The type of peak flowmeter used was determined by availability in the hospital clinics over the ten-year period but was constant f.)r an individual patient. Patients were instructed by the same physician (S.M.l:) in the

64

correct use of the peak 8owoleter, using maximum exhalation from total lung capacity, without jerking the meter or obstructing any of the outflow holes. Patients were asked to record the highest of three readings at home and at work four times per day every four hours, as well as prior to the use of any inhalers, and additionally, if awakened from sleep by symptoms, The subjects also recorded inhaler use and any changes in medication and indicated their location at the time of the readings. Occupational inhalation challenges were performed in selected patients using the method of Pepys and Hutchcrcft" in trying to reproduce the workplace exposure in the laboratory. These were performed in patients who could not return to their former workplace, in whom the history was atypical for occupational asthma, the history was suggestive, but no objective evidence for asthma was available, or the suspected agent was not recognized to cause occupational asthma. Challenges were not performed in patients with irritant-induced asthma, as the implicated levels of chemicals were thought to be above the threshold limit value. Safety data sheets on the workplace chemicals, and where possible, representative sampling of workplace levels, were provided by the Ontario Ministry of Labour and the Ontario Workers' Compensation Board. Since 110 single investigative test is absolutely diagnostic of OA, 4 for the purpose of this study, the following objective criteria were used for diagnoses, determined blinded to the peak flow recordings: 1. OA: A history consistent with asthma, starting while at work, worsening on working days and improving away from work, on weekends or holidays, with a methacholine PC m decreased two or more dilutions (four fold) at work vs home; or methacholine PC m less than or equal to 8 mg/ml and positive skin test to work allergen or positive challenge with workplace substances. 2. Asthma nonoccupational: A history consistent with asthma, with methacholine PC:2Jlt less than or equal to 8 mg/ml but no workplace change or negative workplace substance challenge or negative skin test with work allergen. 3. Normal: Methacholine PC 21,>8 mg/ml at work or work substance challenge negative. 4. ? OA: A history consistent with asthma, worsening at work, with methacholine changes at work vs horne greater than twodilutions but not into asthmatic range. After interpreting a pilot batch of peak How records to get used to the process and revise initial guideline attempts, we then independently interpreted the 78 available tracings coded only with identification number {no name or occupation listed) using the criteria described below. The number of weeks with recorded values varied from at least two weeks to several months. Of these 78, we excluded those with less than two weeks of data, those without a period both at horne and work, and those for whom objective diagnostic criteria were not available for comparison. A total of 50 (64 percent) of the 78 patients who had performed peak Row readings were suitable for analysis in this study. The interpretations were performed from 1988 to 1989 blinded to the results of any other proc-edures, since identifying information was removed from the recordings by all independent assistant prior to interpretation at this time.

Criteria for Interpretation of Peak Flows

1. Nonoccupational asthma: Presence of ~20 percent diurnal variation, defined as the differen<.-e between minimum and maximum PEFR on at least one day exceeding 20 percent of the day's maximum, This was diBerentiated from a pattern of occupational asthma in that there was 110 difJeren<.:e in the relative frequency of positive days between horne and work days (Fig Ib), 2. Occupational asthma (OA): ~20 percent diurnal variation occuring either Inure frequently at work taking into account the relative frequency of positive days at work compared to that at horne, whether the lowest PEFR occurred on days at work, or PEFR in Possible Occupational Asthma (Uss, Terlo)

Asthma - Occupational

Table l-Characteriatica ojSubjectB Aaeued by

Peak Flow Studiea

630 600 570

540 510 480 450 ff:420 ~390 360 330 300 270 240 210 180 150 L....J-....\-.L--£.-...........................--£.-..L..-.I.................. .............. L......L.......L.......I.......I..-.............................--'-..L..-.I............................... ....L.......I............, 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 Days of the month

*

Number Gender, M/F Mean age, yr Mean duration of work-attributed symptoms, yr Mean duration of workplace exposure, yr Skin atopic response, one or more positive aeroallergens Work exposure agents, Isocyanates Flour

Others" Objective diagnoses,

Occupational asthma ? Occupational asthma Asthma Normal

--'-~

Asthma - Non-Occupational

fE

630 600 570 540 510 480 450 420

360

330 300 270 240 210 180 150 L-"---l""-"ll-"'----'---""- --'---'---'---'--.-\.-....I.-..&.-..L..-..A..--..L...-..L-L-..-..J""-"II---"-' 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Daysof the month

540

Indeterminate

*Work

510

480 450 fE420 w390 Q. 360

28 22 5 23

(56%) (44%) (10%) (46%)

18 (36%) 3

(6%)

10 (20%) 19 (38%)

3. Indeterminate readings: (a) OA Category 2: if a ~20 percent change occurred on only one occasion. (b) No diurnal variation exceeding 20 percent with ~20 percent change only longitudinally across days, with the lowest recordings on days at work (Fig lc). 4. No asthma: None of the above (Fig Id), For those tracings for which there was disagreement between the two observers, a consensus interpretation was reached as one of the five possible categories (no asthma, asthma, OA, indeterminate [a] and [b]). When each PEFR record was categorized in this way; a comparison was then made with the diagnosis made using the other objective criteria. Statistical Analysis

330 300 270 240 210 180 150 ~,"""",,"="~,,-:-,,,"~:-,,-::~~--,-~~~---!-~.a........a--""---'-......I..-...&.-&-....L----'---I-...J

630 600 570 540 510 480 450 fE420 ~390 360 330 300 270 240 210 180

3.5 12

*Other exposure agents in one or two patients each were: grain dust, pectin, nickel, chromates, acids, burning urethane and vinyl, molds, colophony, acrylates, phthalates, cedar dust, metabisulphite, cephalosporin powder, fiberglass, hairdressing chemicals, cigarette smoke, calcium oxide dust.

~390

630 600 570

50 36/14 44

The sensitivity, specificity, and predictive value of the consensus PE FR interpretations were calculated in relation to the objective diagnoses, using the latter as the "gold standard:' Sensitivity (the proportion of those who have the disease who test positive), specificity (the proportion of those free of disease who test negative), positive predictive value (the proportion of patients with positive tests who have the target disorder), and negative predictive value were calculated as described by Sackett et al. 13 Interobserver variation in interpretation could be determined for the final 31 eligible tracings and was assessed by means of the kappa statistic (Sackett et al13 ) ; interpretations were collapsed into three categories as follow: asthma, OA, no asthma. Because there was concern a priori that subjects with an

Table 2-Compa,;,on o/Peak Flow, _ and DiagnoBiB MiMU by Other TeBta Peak Flow Diagnosis

*Work

150 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Days of the month

FIGURE 1. Examples of peak Howdiagnostic interpretation.

Objective diagnosis using other tests

[

OA

?;

Total whether there was more marked variation at work. A ~20 percent diurnal variation occurring on a "home" day within one day of work was generally considered as a working day change. Diurnal changes had to occur on at least two days (Fig la).

OA

A

N

13 1 1

0

1 1 10 1 13

15

6

2 1 9

Total 4

2 6

1 13

18 10 19 3 50

OA, occupational asthma; A, asthma, nonoccupational; N, normal; ?OA, methacholine changes at work vs home greater than 2-dilutions but not into asthmatic range; and I, indeterminate peak How interpretation (see test). CHEST I 100 I 1 I JUL'f, 1991

65

Table 3- Sensitivity and Specificity of Peak Flow Studies Total (%)

Parameter A. All subjects Sensitivity of interpretation of: Asthma for diagnosis of asthma: OA for diagnosis of OA: Specificity B. Excluding indeterminate interpretations Sensitivity of interpretation of: Asthma for diagnosis of asthma: OA for diagnosis of OA: Specificity C. Predictive value of peak How studies Positive Asthma PV(PPV) OA Negative No asthma PV(NPV)

6110 (60) 13118 (72) 10119 (53)

618 (75) 13114 (93) 10113 (77) 619 (67) 13115 (87) 10/13 (77)

indeterminate recording may differ from those interpreted as OA, the findings are presented both including and excluding these subgroups. RESULTS

Demographic Characteristics The demographic characteristics are summarized in Table 1; the majority of the patients were men, about one half were atopic, and isocyanates were the most frequent exposure agent. All patients had a history consistent with occupational asthma. The prevalence of OA (based on the objective diagnoses) was 18 (36 percent) among the 50 eligible patients. Consensus discussion was needed to settle initial disagreement between the observers for 12 of the 50 records. Table 2 shows the overall comparison of peak How interpretations to the diagnosis made by other tests.

Relationship of Interpretations to Objective Diagnosis Sensitivity and Specificity (Table 3): The sensitivity of consensus interpretations of OA for a diagnosis of OA was 72 percent overall (Table 3A); the incorrect interpretations (ie, those incorrectly not called OA) included normal (in one subject), indeterminate (a) (one subject) and (b) (three subjects). The sensitivity of an interpretation of asthma for a diagnosis of asthma was 60 percent overall; the incorrect interpretations included indeterminate (b) (two subjects) and normal and OA (one subject each). Among those with an objective diagnosis of "normal;' the specificity of the PEFR interpretations was only 53 percent, with incorrect interpretations of asthma (two subjects), OA (one subject), indeterminate (b) (two subjects), and (a) (four subjects). Sensitivity and Specificity Excluding lndetenninate Readings: Because we had concerns that peak How interpretations of indeterminate readings may repre66

sent different conditions than those with definitive interpretations, these validity parameters were also calculated exluding subjects with these interpretations (Table 3B). Sensitivity increased to 93 percent for OA, and to 75 percent for asthma. Among those with objective criteria of "normal;' the specificity increased to 77 percent. Predictive Value (Table 3C): For the peak How consensus interpretation of asthma, the positive predictive value of the interpretation of asthma was 67 percent; the objective diagnoses based on other tests for those misinterpreted included normal (two subjects) and ? OA (one subject). For interpretation ofOA, the PPV of the interpretation of OA was 87 percent; the objective diagnoses among those incorrectly interpreted included asthma and normal (one subject each). Among those with a peak flow interpretation of "no asthma," the negative predictive value was 77 percent; the objective diagnoses among those misinterpreted included OA, ? OA, and asthma (one subject each). Among the six subjects with a consensus interpretation of indeterminate (b), the objective diagnoses were? OA (one subject), normal (two), and OA (three). Among the seven subjects with the consensus interpretation of indeterminate (a), the objective diagnoses were normal (four), OA (one), and asthma (two). Comparison with Other Objective Tests for Occupational Asthma: The interpretation of peak How Table 4-Compamon of Other TeatB with Peale Flow lJiagnoBiB of OccupationalAatlama and no OccupationalAatlama Paired methacholine tests after a workday and holiday vs PEFRs PEFRs OA Not OA Total

~~

Paired methacholine Changes of OA

~

( Not : ?OA 2 3 Total 8 12 Specific laboratory occupational challenges vs PEFRs PEFRs OA NotOA Laboratory challenge

2 1

1 1

3

3

o

1

7 8 5 20

Total

3 2 1 6

Positive single methacholine test + positive specific skin test vs PEFRs PEFRs OA NotOA Total Positive methacholine + skin test 5 0 5 Negative methacholine test within 24 hours of work vs PEFRs PEFRs OA Not OA Total Normal methacholine response within 24 hrs of work

o

9

9

PEFR in PossibleOccupational Asthma (Uss, T8r1o)

recordings as occupational asthma vs no occupational asthma (ie, normal or nonoccupational asthma) was compared with the other methods of objective diagnosis (Table 4). There was a close relationship between the presence or absence of work-related changes in methacholine reactivity and peak flow interpretation (14 of 15 concordant) (Table 4A). However, the relationship in the few patients who had specific challenges was less clear (Table 48), perhaps due in part to the fact that specific challenges were only done when the diagnosis was uncertain. The other objective criteria: a positive methacholine challenge with a positive skin test for a diagnosis ofOA, and a negative methacholine challenge within 24 hours of work exposure to exclude OA, both showed complete agreement with peak How interpretations (Tables 4C and D).

InterobserverVariation For the purposes of examining interobserver variation, the consensus interpretations are presented both for all subjects with interpretations of OA and the ':indeterminate OA (a) and (b) readings collapsed together (Table 5A), and with the indeterminate categories exluded (Table 58). The kappa values were 61.7 percent overall, and 82.7 percent after the exclusions, respectively

\1

DISCUSSION

This study has demonstrated that explicit criteria for the interpretation of peak flow tracings can be developed with acceptable interobserver variation, as demonstrated by the moderately high kappa values.

Validity The peak flow tracings appear reasonably sensitive for both asthma and OA, especially when the indeterminate interpretations were excluded. The overall specificity of peak flow interpretations approached useful levels when the indeterminate categories just mentioned were excluded. In comparison, among workers exposed to oolophony, Burge et al? reported a sensitivity of 77 percent comparable to that in our study but a specificity of 100 percent. Among workers exposed to isocyanates,8 both sensitivity and specificity were reported to be an impressive 100 percent. As noted, in these studies, workers were asked to record PEFR every hour from waking to sleeping. Also, it is not clear if interpretations of peak flow were carried out blinded to the final assessments. Cote et al,14 using the results of plicatic acid challenge test as the gold standard, recently found PEFR recordings to have sensitivity and specificity of 86 and 89 percent, respectively among 23 patients with suspected cedar asthma, values which are intermediate between ours and those of Burge et al.? Cote et al l4 "visually" analyzed the PEFR readings and

Table 5-Eooluation ojlnterobterf'er Variation in lraterprmng INk FlotD Tracing. All subjects· No Asthma Observer 2

No Asthma Asthma OA Total

Observer 1 Asthma OAt

Total

3

0

1

4

1

4

3

8

0 4

1 5

18 22

19 31

Observed agreement = (3 + 4 + 18)/31 =80.6% Agreement expected on the basis of chance: No asthma: 0.5; Asthma: 1.3; OA: 13.5; Total = 15.3131= 49.4% Actual agreement beyond chance = (80.6 - 49.4)% = 31.2% Potential agreement beyond chance =(100 - 49.4)% = 50.6% Kappa =31.2%150.6% =61. 7% *Indeterminate a and b combined with OA; t = Occupational asthma

Excluding Indeterminate a and b interpmations Observer 1 No Asthma Asthma OA Observer 2

No Asthma Asthma OA

3 1 0 4

0 4 1 5

Total

0 0 11 11

3 5 12 20

Observed agreement = (3 + 4 + 11)120= 90% Agreement expected on the basis of chance: No asthma: 0.6; Asthma: 1.25; OA: 6.6; Total =8.45120 = 42.25% Actual agreement beyond chance =(90 - 42.25)% = 47.75% Potential agreement beyond chance = (100 - 42.25)% = 57.75% Kappa = 47.75157.75 = 82.7%

required agreement by two of three physicians of a work-relationship in two of three weeks at work. Our findings of a relatively poor association between peak flow interpretation and specific work substance challenge results (Table 4) likely reflect the difference in our criteria for performing specific challenge tests. In patients who had undergone workplace peak flow and methacholine tests, challenge tests were only performed if the results did not clearly support or refute the diagnosis, or if the work substance was not known to cause OA. In contrast, we found a very close agreement between peak How results and (1) clearcut presence or absence of paired work-related methacholine changes; (2) a single positive methacholine challenge with positive skin test response; and (3) negative methacholine test within 24 hours of being at work (Table 4). The peak flow readings were instigated in a clinic setting, and over the years, involved the use of three different peak Howmeters in different patients. Different peak Howmeters are recognized to potentially differ in accuracy and reliability, as indicated in a study by Eichenhorn and colleagues" which included two of the three types of peak Howmeters used in our study In addition, individual patient effort and their CHEST I 100 I 1 I JUL~ 1991

87

technique may vary from one recording to another so that there is potential for significant variability in recordings, unrelated to airflow limitation. An attempt was made to reduce these factors by using a single peak flowmeter per patient and by carefully instructing the patient in the correct technique of usage. However, these factors could have accounted for some variability in recordings and might have contributed to our relatively high rate of indeterminate readings.

The Interpretation of Indeterminate Readings: An interpretation of indeterminate (b) (only ~20 percent variation on longitudinal analysis) predicted OA in three (50 percent) of six cases. However, a tracing with >20 percent diurnal variation on one occasion only (indeterminate a) predicted OA in only one of seven cases, suggesting that this is a different entity than OA; in fact, the objective diagnosis was normal in four of seven. These findings suggest that, in our data, longitudinal change was more predictive of OA than diurnal variation exceeding 20 percent on one occasion only which may reflect a single episode of reduced respiratory effect. Caution is required in interpreting these observations because the subgroups are quite small. Including indeterminate (a) in the rubric of OA makes the classification too lenient, mislabelling some normal subjects as diseased. The lenient classification is also reflected by the low specificity (too many false-positives), suggesting that stricter criteria, such as a longer study period or a requirement for a specific proportion of weeks to demonstrate the pattern as proposed by Burge et al,? may improve interpretation. Of course, improving specificity would be at the expense of sensitivity.

Predictive Value A positive consensus PEFR interpretation of OA was predictive of OA in over 85 percent of cases, while a positive consensus of asthma was somewhat less but still moderately predictive of asthma. A consensus interpretation of no asthma was moderately predictive (77 percent) of a normal objective diagnosis. Finally; it should be kept in mind that the predictive values are dependent on the prevalence of disease in the population being studied. If the prevalence of OA in the population being assessed was lower, the PPV would also be lower. There are some conclusions that can be drawn with respect to the information that is added by PEFRs to the investigation of possible OA. 1. Peak flow tracings are useful both in the investigation ofindividual cases as in this study, but probably also in field studies for epidemiologic purposes as used by Smith et al.? This modality is also inexpensive and noninvasive. A PEF interpretation of OA suggests a likely diagnosis of OA and should trigger or intensify 18

the search for a sensitizer and the use of all possible objective confirmatory modalities. Paired methacholine responses after a workday and on holidays, and a positive methacholine response with positive specific skin test to a workplace allergen relate well to a positive peak flow record. 2. Similarly a PEF interpretation of no asthma had a negative predictive value of 77 percent; ie, over three-quarters proved to have no disease on objective criteria. This is consistent with the recently reported findings of Cote et al,14 who concluded that if both PEFR and history are negative, the specific challenge test does not need to be conducted. 3. Regarding the relatively low specificity of PEFR interpretations, the recent report by Josephs et al l 6 suggested that nonspecific bronchial reactivity is not invariably present with asthma. Previous case reports have documented occupational asthma without bronchial hyperresponslveness.F:" The implications of the suggestion by Josephs and. colleagues, 16 if confirmed, include that histamine or methacholine hyperresponsiveness may not necessarily be present for the diagnosis of currently symptomatic asthma, in contrast to earlier reports. m-22 This could conceivably account for the low specificity that we observed in the present study Perhaps the objective criteria suggesting no asthma (normal methacholine responsiveness) in the face of a PEFR interpretation of asthma or OA means that some mechanism other than nonspecific hyperresponsiveness underlying the airflow obstruction was present, ie, asthma was present and the peak How interpretations were correct. We do not know if these represent true disease, as suggested by Burge's studies,7,8 poor test specificity, or are a consequence of inadequate respiratory effort or inaccurate recordkeeping by the patient, as might be anticipated in a proportion of a population who would have secondary gain from an abnormal record (although one cannot separate the latter two situations). This can only be answered by further prospective assessment of peak How readings and other tests for occupational asthma interpreted independently 4. Indeterminate recordings occurred in a significant minority of patients (26 percent in this study). These patients require other investigations to confirm or disprove a diagnosis of occupational asthma. ACKNOWLEDGMENT: The authors thank Drs. I. Broder and G. J. Stopps for their helpful comments.

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22

of pc. and peak expiratory flow rate in cedar asthma. J Allergy Clin Immunoll990; 85:592-98 Eichenhorn MS, Beauchamp RK, Harper PA, Ward JC. An assessment of three portable pealc flow meters. Chest 1982; 82:306-09 Josephs LK, Gregg I, Mullee MA, Holgate ST. Nonspecific bronchial reactivity and its relationship to the clinical expression of asthma: a longitudinal stud~ Am Rev Respir Dis 1989; 140:350-57 Hargreave FE, Ramsdale EH, Pugsley SO. Occupational asthma without bronchial hyperresponsiveness. Am Rev Respir Dis 1984; 130:513-15 Smith AD, Brooks SM, Blanchard J, Bernstein IL, Gallagher J. Absence of airway hyperreactivity to methacholine in a worker sensitized to toluene diisocyanate (TDI). J Occup Med 1980; 22:327-31 Banles DE, Barleman HW Jr, Butcher In: Hammad YY, Rando BJ, Glindmeyer H~ et ale Absence of hyperresponsiveness to methacholine in a worker with methylene diphenyl diisocyanate (MDI)-induced asthma. Chest 1986; 89:389-93 Cockroft D~ Killian DN, Mellon JJA, Hargreave FE. Bronchial reactivity to inhaled histamine: a method and clinical survey Clin Allergy 1977; 7:235-43 Boulet L-E Cartier A, Thomson NC, Roberts RS, Dolovich J, Hargreave FE. Asthma and increases in nonallergic bronchial responsiveness from seasonal pollen exposure. J Allergy Clio Immunoll983; 71:399-406 Chatham M, Bleecker EB, Smith PL, Rosenthal RR, Mason ~ Norman PS. A comparison of histamine, methacholine and exercise airway reactivity in normal and asthmatic subjects. Am Rev Respir Dis 1982; 126:235-40

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