Is self‐reported history of eczema and hay fever a valid measure of atopy in those who report current asthma?

To the Editor, There is growing awareness that “asthma” is a clinical syndrome with multiple distinct pathophysiological mechanisms, or endotypes, leading to variable clinical expression of disease. Distinction of asthma as a clinical syndrome is of increasing importance since the emergence of targeted biological therapies.1 Asthma is most often phenotyped as allergic or nonallergic, based on evidence of sensitisation to specific allergens measured as skin prick tests (SPT) or in vitro immunoglobulin E (sIgE). 2 However, in large-scale epidemiological studies, measurement of sIgE or SPT is often not feasible due to cost or logistical constraints. Allergic asthma has often been classified as asthma with concurrent self-reported hay fever and/or eczema.3,4 Similarly, SPT or sIgE is uncommonly measured in primary care settings, with assessment of “atopy” in those with asthma typically based on reports of other allergic conditions. It is not clear how valid this approach is or how frequently participants are misclassified. We have examined the validity of using self-reported hay fever and/or eczema to define allergic status among asthmatics compared to SPT as a “gold standard. ” This analysis used data from two independent studies: The Melbourne Atopy Cohort Study (MACS)5 and The Tasmanian Longitudinal Health Study (TAHS). 6 MACS is a birth cohort of children, with family history of allergic diseases, born between 1990 and 1994. Parents and siblings were included in later follow-ups. TAHS is a cohort of children born in Tasmania in 1961, plus their families. Parents and siblings have been studied in later phases. Participants from MACS’ 18-year follow-up, together with TAHS probands from the 2012 and TAHS siblings from the 2007 study were included if they fulfilled these criteria: (a) current asthma, (b) valid skin prick tests and (c) complete information on hay fever and eczema ever (Figure S1). Current asthma was defined by self-reported doctor-diagnosed asthma and self-reported concurrent episodes of asthma, wheezing breathing or any asthma medication use within the last 12 months. Hay fever ever was based on self-reported episodes of ever hay fever in MACS and slightly more broadly defined in TAHS by also including nasal allergies. Eczema ever was based on participant reports of ever eczema in MACS and slightly more broadly defined in TAHS by also including any kind of skin allergy. A positive skin prick test was defined as a mean wheal diameter of at least 3mm greater than the saline control for one or more of the following allergen extracts: dust mite (D pteronyssinus), cat, Alternaria, Penicillium, mixed grasses or rye grass pollen. Results were deemed invalid if the histamine control reaction was below 3 mm and no other reaction above 3 mm, to any allergen wheals, was identified. The period prevalence (in the past 12 months) of reported asthma symptoms was assessed, when the skin prick tests were performed. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratios (DOR) were calculated with 95% confidence intervals (CI). Probands, siblings and parents were initially analysed separately, and then, probands, siblings and parents were pooled in each study. Asthma defined to be allergic or nonallergic was assessed for each individual. Clustering by family was adjusted within each study using the PROC GENMOD procedure in SAS (SAS Institute Inc, Cary, NC, USA) version 9.4. Due to high heterogeneity between MACS and TAHS, as assessed by using I2, pooled estimates are not shown. Of 937 participants with current asthma, 78% had a positive SPT and 89% ever had hay fever and/or eczema (Table 1). MACS and TAHS estimates of self-reported hay fever ever compared with SPT-defined allergic asthma showed relatively high sensitivity ≥ 0.82, but moderate specificity ≥ 0.60, and DOR > 4.13, Figure 1. The corresponding PLR was ≥ 1.57 and NLR was ≤ 0.23, see Table S1. The results varied between groups and were higher in older participants (MACS parents and TAHS participants). Using self-reported ever eczema showed lower utility (DOR ≥ 0.74) as did combining hay fever and eczema ever (requiring both) (DOR ≥ 0.19). In contrast, combining current asthma with hay fever “and/or” eczema estimates of sensitivity were at least 0.90, specificity ≥ 0.69, PLR > 2.92, NLR of < 0.14 and DOR ≥ 20.5. We found that combining self-reported hay fever and/or eczema ever, provided high sensitivity, specificity, PLR and a large DOR for defining atopic asthma, and a low NLR. Current asthma combined with hay fever ever alone showed an acceptable sensitivity, moderate specificity and less useful clinical PLR, NLR and DOR when compared with SPT-defined allergic asthma. Combining current asthma with eczema alone or hay fever and eczema showed much poorer results. This is the first study to examine the validity of combining self-reported hay fever as well as eczema to identify atopic versus nonatopic asthma in young to middle-aged adults. A previous study of Swiss school children7 examined the validity of self-reported hay fever ever compared with SPT and showed high specificity (useful in including allergy), but low sensitivity. Even though DOI: 10.1111/all.14440