The Phadiatop In Vitro Test for Allergy in General Practice: Is it Useful?

Transcription

1 Family Practice Oxford University Press 1990 Vol. 7, No. 2 Printed in Great Britain The Phadiatop In Vitro Test for Allergy in General Practice: Is it Useful? F W DEKKER, J D MULDER DZN, J A KRAMPS*, A A KAPTEIN, J P VANDENBROUCKE" AND J H DUKMAN* DekkerFW, Mulder DznJ D, Kramps J A, Kaptein A A, Vandenbroucke J Pand Dijkman J H. The Phadiatop in vitro test for allergy in general practice: is it useful? Family Practice 1990: 7: A study was performed in order to assess the value of the Phadiatop, a new in vitro allergy test, in general practice. A total of 248 patients were screened for bronchial allergy with PRIST, RAST and the Phadiatop. Information about the patient's history and the results of the PRIST, Phadiatop and RAST tests were presented consecutively to the general practitioner and his diagnoses based on and evolving from these were evaluated and compared with the diagnosis of a specialist. The general practitioner's diagnosis based on the results of the Phadiatop was the closest of all the tests to the specialist diagnosis. It is concluded that Phadiatop is of great use in diagnosing bronchial allergy in general practice. Recognition of allergic factors in bronchial obstruction has important consequences for the care of asthmatic patients. To date, a number of diagnostic tests are available for the assessment of allergy. Traditionally, patient history and in vivo diagnostic tests, such as skin and provocation tests, play an important role. About 20 years ago, in vitro tests became available. The total amount of IgE in serum can be assessed with the paper radio immunosorbent test (PRIST). 1 For specific IgE antibodies in serum the radio allergosorbent test (RAST) is most frequently used. 2 Recently, the Council on Scientific Affairs of the American Medical Association delivered a report on the use and value of in vivo as well as in vitro tests for allergy. 3 It concluded that the information provided by RAST correlates well with information obtained from the allergy history or from various tests with specific allergen extract, including skin test and bronchial provocation. Bronchial provocation is only to be used in a research setting, for example when investigating new allergens occurring in occupational asthma, but not in a general practitioner's setting dealing with allergy to common airborne allergens. To recognize Department of General Practice, University of Leiden, The Netherlands; 'Department of Pulmonology, University Hospital, Leiden, The Netherlands; * * Department of Clinical Epidemiology, University of Leiden, The Netherlands. Correspondence to: F W Dekker, Department of General Practice, PO Box 2088,2301 CB Leiden, The Netherlands. 144 atopic allergy in general practice, skin tests may be used but are liable to a number of problems when performed by general practitioners (choice and storage of allergens, technique of intracutaneous injection, individual interpretation). RAST has the advantage of convenience for the patient, the lack of patient risk and the possibility of testing for allergy in those patients unable to stop medication that can potentially influence the results of skin tests. Depending on the type of inhalation allergens, RAST is said to be less sensitive than skin tests, although a much high specificity of RAST is claimed by other authors. However, one major disadvantage of the RAST is its price, especially when used as a screening method. An alternative is the PRIST, but its sensitivity as well as its specificity are far from perfect. In a recent review Holgate and Kay concluded that the measurement of total serum IgE concentrations are of little use in the management of asthma, though in children they may be helpful in identifying an atopic status. 6 Recently, a new in vitro diagnostic allergy test has been developed Phadiatop (Pharmacia Diagnostics AB, Uppsala, Sweden). This two-step sandwich radioimmunoassay employs a paper disc multi-allergosorbent to which a mixture of common airborne allergens are attached. The composition of this mixture is withheld by the firm. Results are classified into 'positive' or 'negative' for the mixture as a whole. Until now, only a few studies have been published on the value of the Phadiatop test. Herold and colleagues retrospectively

2 assessed the Phadiatop test in 50 patients with positive skin prick tests and positive RAST results, and in 50 patients with negative skin prick tests and negative RAST results. 7 The same authors also assessed Phadiatop, skin prick tests and PRIST prospectively in 100 patients with a suspicion of allergy. 8 They concluded that the Phadiatop has a distinctly higher efficacy compared with PRIST. MerTett and Merrett studied Phadiatop restrospectively in 187 patients with different RAST scores, levels of total IgE and history of allergy.' They also concluded that Phadiatop is a test that is simple to perform and produces reliable results. In studies on the value of Phadiatop in children similar conclusions have been drawn. 10 " The study reported here was performed in order to assess the value of the Phadiatop for diagnosing bronchial allergy in general practice and to find out to what extent the test can be used as a scteening measure for atopy compared with PRIST or RAST. METHOD In nine adjacent general practices all patients between 12 and 64 years old were selected according to whether any antiasthma drug (bronchodilators, CTomoglycate or inhaled corticosteroids) had been prescribed in the year before the start of the study. Patients could be traced easily with the aid of the computer at the dispensary. Only patients who had not contacted a specialist in the two years before the start of the study were selected. Patients were asked by their general practitioner to come to the surgery, fill in a short case history form and give a sample of blood. The following evaluations were performed: a structured history based on current respiratory symptoms and provoking factors; RAST on grasses, weeds, trees, moulds, mite, cat and dog; PRIST; and Phadiatop (all provided by Pharmacia Diagnostics AB). The RAST was considered to be positive if at least one allergen scored class two or higher. 5 The PRIST was considered to be positive at levels above 100 ku" In order to assess the relevance of the Phadiatop test in general practice compared with PRIST and RAST, test results were provided to the general practitioner in a structured manner as described in a flow chart (Figure 1). An interactive computer programme running on a personal computer was developed using a database with history and test results. For each patient, the computer first asked the general practitioner whether he or she considered the patient to be allergic or not. This 'diagnosis' was the known diagnosis from usual care. After the general practitioner had given his answer, results of the structured patient history were presented by the computer, after which the general practitioner was asked again to give his or her opinion whether he considered the patient to be allergic or not. Results of PRIST and Phadiatop were presented in a similar way, each followed by the same question about THE PHADIATOP IN VITRO TEST FOR ALLERGY 145 this patient being allergic or not. Finally, the general practitioner was asked whether he would like to request any RAST evaluation and, if so, which out of the seven mentioned earlier. After this, the whole sequence was repeated for the next patient. In order to exclude any learning bias by the general practitioner, it was not until the general practitioner had finished all his patients that the results of the requested RAST analyses were presented. Hisfinaldiagnosis after evaluating any requested RAST was also stored in the memory of the computer. In order to construct the best possible 'gold standard' of diagnosis in this setting, a senior chest physician (JHD) evaluated all available test results including RAST results as well as the patient history and gave his opinion about each patient having specific allergic complaints or not. This was done by considering the weight of RAST results and history based information about specific sensitization against data on non-specific bronchial responsiveness. The question to the general practitioner as well as to the specialist about the patient being allergic or not, was posed with five answer categories, ranging from 'certainly', 'likely', 'don't know' to 'likely not' and 'certainly not'. In general practice, 'likely allergic' often means that the patient is treated as being allergic until it becomes clear that the patient does not get any benefit from the therapy. Thus, from a therapeutic point of view we have aggregated the categories 'certainly' and 'likely' into 'allergic' and the categories 'likely not' and 'certainly not' into 'not allergic'. RESULTS Based on the registration of the dispensary computer 301 out of in total registered patients were Known diagnosis from usual care: Structured history PRIST Phadiatop GP diagnosis I GP diagnosis II GP diagnosis III GP diagnosis IV Requesting of RAST All information + requested RAST results > GP diagnosis V FIGURE 1 Flow chart

3 146 FAMILY PRACTICE AN INTERNATIONAL JOURNAL TABLE 1 Number of general practitioner diagnoses at each stage with the percentage of these patients accurately diagnosed according to the specialist Number of patients diagnosed by GP at each stage (% diagnosed by specialist) I II III IV V Allergic Don't know Not allergic 135 (75.6) 27(0) 86(66.3) 141 (75.9) 19(0) 88 (70.6) 144 (79.2) 20(0) 84 (79.8) 144(88.9) 16(0) 88 (95.5) 143 (93.0) 4(0) 101(94.1) I = known from usual care; II = after structured history; III = after results from PRIST; IV = after results from Phadiatop; V : after results from requested RAST selected, of whom 249 (82.7%) agreed to participate. In one patient a blood sample could not be obtained, so the results are based on 248 patients, 113 male and 135 female, age range 12 to 64 years (median 31 years). Almost 30% suffered from respiratory problems daily through the year, about 70% complained of intermittent respiratory symptoms and only 1.6% never complained. A total of 148 patients (59.7%) were RAST-positive (score 2+ or higher on any of the seven tested allergens). In only three out of 248 patients did the Phadiatop and RAST show discordant results. 13 Specialist diagnosis was positive in 141 out of 248 patients. All of these patients had a positive RAST. The specialist considered another seven patients with a positive RAST not to have specific allergic complaints, mainly because of a history lacking clear allergic symptoms against prominent complaints of non-specific bronchial hyperresponsiveness. Comparing specialist diagnosis with consecutive general practitioner diagnoses, the primary general practitioner diagnosis (the known diagnosis from usual care) appeared to be quite accurate: a positive primary diagnosis had a predictive value of 75.6%, a negative primary diagnosis had a predictive value of 66.3% (Table 1). In patients with a positive general practitioner diagnosis, the positive predictive value was calculated as the proportion of these patients receiving a positive specialist diagnosis. In patients with a negative general practitioner diagnosis, the negative predictive value was calculated as the proportion of these patients receiving a negative specialist diagnosis. The predictive values continuously increased as more diagnostic measures became available (Figure 2). Figure 2 also shows a marked increase in predictive values when the general practitioner diagnosis based on Phadiatop was compared with the general practitioner diagnosis based on PRIST. Finally, it can be seen that the predictive value of a negative general practitioner diagnosis decreased slightly as the results of requested RAST became available to the general practitioner: in this case the information from the requested RAST appeared to confuse rather than help the general practitioner. Comparing consecutive general practitioner diagnoses, the number of patients receiving a more accurate diagnosis was calculated, as was the number of patients receiving a less accurate general practitioner diagnosis (Table 2). A change in the right direction was judged to be more accurate and a change into the wrong direction was judged to be less accurate. McNemar's chi square test showed a highly statistically significant change between the general practitioner diagnosis based on PRIST compared with the general practitioner diagnosis based on Phadiatop (X 2 = 36.54; P< ). PRIST and RAST, separately also contributed significantly to a more correct general practitioner diagnosis, though they contributed far less than Phadiatop did. FIGURE 2 Predictive values of general practitioner diagnoses, based on specialist diagnosis. I = known from usual care; II = after structured history; III = after results from PRIST; IV = after results from Phadiatop; V = after results from requested RAST

4 THE PHADIATOP IN VITRO TEST FOR ALLERGY 147 TABLE 2 Comparison of consecutive general practitioner diagnoses related to specialist diagnosis (n=248 patients) GP diagnoses II (+ history) versus I III (+ PRIST) versus II IV (+ Phadiatop) versus III V (+ RAST) versus IV (McNemar's x 2, two-tailed) More accurate Less accurate x Significance NS P<0.05 P< P<0.0l DISCUSSION In this study a considerable number of patients in general practice were tested for bronchial allergy with several diagnostic tests. As in every clinical epidemiological study the selection of patients is of great concern. Our patients were selected on the basis that pulmonary medication was prescribed. Certainly most of them could be considered to have asthma or had chronic obstructive pulmonary disease. However, as these diseases are underdiagnosed and undertreated a great deal in general practice, it is likely that we missed at least some patients with airflow obstruction out of the nine general practices studied. 14 On the other hand some patients could have been included who received a bronchodilator only because of a common cold. By and large, our population showed a broad spectrum of allergic and non-allergic patients with airflow obstruction. Also, it was a typical general practice population. This is important because general practice is likely to become a major field of use for the Phadiatop test. Our population was carefully screened for bronchial allergy by means of PRIST, Phadiatop and specific IgE evaluation (RAST) on most common airborne allergens. However, patient history remains the cornerstone of diagnosing allergy. In our study a structured, self-administered history form was used. A more detailed history from direct real patient contact could have revealed more information, especially where late bronchial allergic reactions are concerned. Besides, bronchial responsiveness to histamine was not assessed, but estimates were based on the patient history of complaints following exercise, cold and misty air, smoky environment and so on. A definite judgement about the patients being allergic or not could therefore not always be given. In the literature the Phadiatop is reported to produce very reliable results compared with the RAST and skin tests. 7 "" Even more important, however, is the fact that general practitioners can work with the Phadiatop very well. Our study demonstrates that based on the results of the Phadiatop, general practitioners may indeed come to a very accurate diagnosis whether bronchial allergy plays an important role or not. Compared with specialist diagnosis, the predictive value of a positive general practitioner diagnosis after the Phadiatop is 88.9% while the predictive value of a negative diagnosis is 95.5%. We conclude that Phadiatop is of great use in diagnosing bronchial allergy in general practice. It produces clear information, which is easy to interpret and which general practitioners can work with. Finally, as a screening test it saves money because one test can be performed instead of a whole panel of allergens tests in the RAST. It is to be expected that use of the Phadiatop in general practice will lead to an increased detection rate of allergic patients, more rational referrals to a chest physician and a higher quality of care for patients with obstructive lung diseases. ACKNOWLEDGEMENTS We gratefully acknowledge H Richardson for her advice in designing theflow chart, P J Schuurmans and J Wever-Hess for all help and advice, A C van der Linden for performing laboratory tests and P J Thys for developing the database and programming the flow-chart. REFERENCES 1 Gleich G J, Jones R T. Measurement of IgE antibodies by the radioallergosorbent test. I. Technical considerations in the performance of the test. J Allergy Clin Immunol 1975; 55: Wide L, Bennich H, Johansson S G O. Diagnosis of allergy by an in-vitro test for allergen antibodies. Lancet 1976; 2: Council on Scientific Affairs. In vitro testing for allergy. Report II of the allergy panel. JAMA 1987; 258: Position statement from the American Academy of Allergy and Immunology. Skin testing and radioallergosorbent testing (RAST) for diagnosis of specific allergens responsible for IgE-mediated diseases. J Allergy Clin Immunol 1983; 72: Vooren P H, Kramps J A, Franken C, Dijkman J H. Diagnostic relevance of the modified RAST using De2 specific anti-ige antibodies. Eur J Respir Dis 1983; 64: Holgate S T, Kay A B. Mast cells, mediators and asthma. Clin Allergy 1985; 15: Herold D A, Duyan I, Kunkel G. Phadiatop versus gesamt- IgE. Eine vergleichende Untersuchung uber die Effizienz zweier ScTeening-Methoden in der Allergiediagnostiek. Teil I. Allergologie 1987; 10: Herold D A, Duyan I, Kunkel G. Phadiatop versus gesamt- IgE. Eine vergleichende Untersuchung uber die Effizienz zweier screening-methoden in der Allergiediagnostiek. Teil II. Allergologie 1987; 10:

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