Statistical problems in assessing the true value of new in vitro diagnostic tests, with special reference to the chemiluminescent assay (CLA, MAST).

By virtue of familiarity and usage over many years, diagnostic tests may become established and be regarded as infallible "Gold Standards". In the case of allergic disease no test except perhaps allergen challenge can ever precisely reflect the clinical disease at the actual site of the allergic reaction. Thus when a new test is introduced there are no fixed values available for statistical comparison when directly comparing established tests with more recent additions. This is illustrated by many articles comparing the new multiple allergosorbent test system (CLA, MAST) which is a chemiluminescent assay, to other previously established tests. The major reports on CLA in the diagnosis of allergy are here discussed and summarized. Most trials have compared the accuracy of CLA with clinical history, with the skin prick test (SPT), the universally used in vivo method, or with RAST, the most common in vitro diagnostic method. CLA performed similarly to SPT and most CLA and RAST results matched; nevertheless in statistical analyses the problems of comparing diagnostic methods without a Gold Standard against which to judge become obvious-if two fallible methods disagree, which is correct? These statistical problems are discussed as well as other difficulties, such as the impact of the use of different allergen sources and the differing prevalence of allergies in the various test populations analysed.

Sensitivity to Parietaria pollen in the Southampton area as determined by skin-prick and RAST tests.

The pollen of Parietaria species is a well-recognized and important inhalant allergen in the Mediterranean area. Parietaria judaica (Pellitory-of-the-Wall) is native to the U.K., flowering from June to September, but is not usually considered to be of any clinical importance by U.K. allergists. We skin tested 62 patients with a clinical history of summer seasonal respiratory symptoms and a control group of 11 patients with perennial respiratory symptoms only. Each was skin tested in duplicate with extracts of grass pollen, birch pollen, Parietaria pollen, Dermatophagoides pteronyssinus, Cladosporium, Alternaria, nettle pollen and negative and positive controls, and serum samples were collected for RAST assays for Parietaria and nettle. Eight of the 62 patients in the main group showed skin reactivity to Parietaria. Five of these eight had never visited the Mediterranean area and therefore it is possible that sensitization occurred in the U.K. Thirteen of the 62 patients were skin reactive to nettle but there was no correlation between skin reactivity to Parietaria and nettle. This supports a recent report that, despite their close botanical relationship, no antigenic cross-reactivity exists between the two species. No correlation was seen between skin reactivity and serum RAST activity to Parietaria or nettle. It is not known whether exposure to Parietaria pollen contributes to the seasonal symptoms of the patients found to be skin reactive. None of the 11 patients in the control group was skin reactive to Parietaria.

A multicenter trial of immunotherapy with alginate--conjugated grass pollen extract.

Conjuvac, a new generation of allergen extracts, has been developed to meet the need for improved characterization, purification, and standardization. Conjuvac consists of a dialyzed, standardized aqueous allergen extract chemically conjugated to a sodium alginate carrier and lyophilized in single-dose vials, thus ensuring stability until reconstituted with sterile water just before each injection. A preliminary study of Conjuvac 2 Grass by Pegelow (1984) involving a small number of patients showed this extract to have potential advantages. Accordingly, a study involving more patients was undertaken: two different maintenance dose levels of Conjuvac 2 Grass were investigated and compared to a pyridine-extracted, alum-precipitated two-grass extract called Allpyral, which in previous double-blind trials has been shown to be effective. The trial, which included 125 patients with hay fever and which extended over 2 years, involved ten allergists from seven European countries. Overall, the Conjuvac high-dose regimen proved slightly superior to Allpyral without any increased incidence of side effects, and all treatments stimulated marked increases in specific IgG levels without raising IgE levels.

Human nail dust and precipitating antibodies to Trichophyton rubrum in chiropodists.

The toe-nail dust produced in chiropodial practice causes allergic hypersensitivity and Trichophyton rubrum is the most common fungal cause of nail dystrophy. Use of drills and burrs to reduce the thickness of hyperkeratotic nails generates dust and chiropodists develop precipitins to T. rubrum. A survey into the prevalence of these antibodies in 11.2% of state-registered chiropodists is described and 14% of the profession estimated to have antibodies to T. rubrum. In response to a questionnaire 49% stated that toe-nail dust troubled them; complaints of nasal and eye symptoms were 72 and 41% respectively. In 384 chiropodists ventilatory function was tested with a vitalograph. Restrictive lung disease appears to be more common in chiropodists than other sedentary workers.

Clinical and endocrine side-effects of methylprednisolone acetate as used in hay-fever.

Eight patients were treated with two 80-mg. doses of methylprednisolone acetate (Depo-Medrone), given at an interval of two weeks. Pituitary-adrenal function was assessed before, during, and after treatment.Plasma cortisol levels were depressed maximally 72 hours after each injection of methylprednisolone acetate, and then gradually returned to normal. The adrenocortical response to administered corticotrophin was similarly affected; in seven patients normal values were again recorded three weeks after the second injection of methylprednisolone acetate. One patient whose adrenal function had returned to normal still showed some degree of pituitary suppression eight weeks after his second injection. Several side-effects were noted, and clinically the patients fared less well than a larger series studied during the previous year.

Comparison of preseasonal and coseasonal Allpyral with Depo-Medrone in summer hay-fever.

Three hundred patients with grass pollen hay-fever, with or without pollen asthma, were given one of three forms of treatment: preseasonal or coseasonal alum-precipitated pyridine extracted grass pollen (Allpyral) or methylprednisolone acetate in slow-release form (Depo-Medrone). Significant improvement was obtained with preseasonal Allpyral and with Depo-Medrone, but the degree of improvement obtained with coseasonal Allpyral fell within the limits of placebo response.Nevertheless, it is considered that the definite suppression of the pituitary-adrenal function which results from the use of a long-term steroid is not justified in a benign condition such as hay-fever.