Can AQUA (c) questionnaire and FeNO predict atopy in early-career athletes?

Abstract

Allergic sensitization and allergic diseases have been reported to have a high prevalence in athletes. 1,2 Moreover, atopy has been significantly associated with bronchial hyperreactivity and exercise-induced bronchoconstriction in elite athletes. 3,4 Sensitization to allergens is generally determined by a skin prick test (SPT) and/ or allergen-specific serum IgE analysis. 5 Recently, the Allergy Questionnaire for Athletes (AQUA©), 6 a screening tool to predict atopy in elite adult athletes, was validated for screening of atopy in young elite athletes. 7 This screening tool may help with the early identification of atopy, which may burden the physical performances , and is especially helpful in young elite athletes. 5 Increased fractional exhaled NO (FeNO) levels are, considered to be an effective , noninvasive tool to assess the presence of eosinophilic airway inflammation and as tool to diagnose childhood asthma. 8-10 This has also been correlated with allergic sensitization. 11 Therefore, we hypothesize that measuring FeNO levels may also be a useful noninva-sive method to predict atopy in this population. The aim of this study was to investigate the diagnostic accuracy of AQUA© and FeNO in predicting atopy in a young elite athlete population. Therefore, we recruited 90 elite early-career athletes (12-18 years, mean age 15 ± 1.4 years, 57% male) in different sport disciplines attending "Flemish Elite Sports' Schools": basketball (n = 24), soccer (n = 38), volleyball (n = 14) and swimming (n = 14). The study was approved by the institutional review board of UZ/KU Leuven (s59778). Subject characteristics are summarized in Table 1. To objectively assess their atopic state, SPT for nine common aeroaller-gens: grass pollen, weed pollen, birch pollen, mixed tree pollen (hazel, birch, and alder), house dust mite (HDM, Dermatophagoides pteronys-sinus), cat, dog, Alternaria alternata, and Aspergillus fumigatus, together with a histamine control (10 mg/mL) and a negative control were performed (HAL Allergy). A subject was considered atopic if at least one SPT for an allergen was positive by SPT (wheal ≥3 mm and larger than the negative control). The total AQUA© score was determined by scoring the questions related to allergy (Q4 to Q13 as well as Q15), as reported by Jonckheere et al. 7 In addition, FeNO levels were measured with Niox Vero (Accuramed) recorded in parts per billion (ppb). Thirty-three of 90 young athletes (37%) were atopic, of which 25 (76%) were poly-sensitized (Table 1). The most common positive SPT was observed for grass pollen (n = 24), followed by HDM (n = 22; Online repository Table E1). AQUA© scores were significantly elevated in atopic athletes (median: 10, P25-P75: 3.5-17.5) compared with nonatopic athletes (median: 4, P25-P75: 2-11; p = .0084, Figure 1A). Moreover, AQUA© scores were able to predict atopic state with AUC of 0.665 (p < .0001, Figure 1C). As previously reported in young athletes, 7 a cutoff value of six had the highest sensitivity (73%) and specificity (53%; p = .03, Table 2). Using the traditional cutoff value of five yielded a similar sensitivity of 73%, with a slightly lower specificity (51%; p < .05, Table 2). Interestingly, FeNO levels were significantly elevated in atopic athletes (median: 22 ppb, P25-P75: 13-44 ppb) compared with nonatopic athletes (median: 12 ppb, P25-P75: 9-18 ppb; p < .0001, Figure 1A). The AUC for FeNO to predict atopy was 0.765 (p < .0001, Figure 1C). Athletes with FeNO levels higher than 15 ppb had a significantly higher risk to be atopic, with a sensitivity of 70% and specificity of 65% (p = .002, Table 2). Using a cutoff value of 20 ppb reduced sensitivity (58%), but increased the specificity to 77% (p < .001, Table 2). Moreover, AQUA© scores and FeNO levels both significantly correlated positively with the number of positive SPT (Spearman, r = .31 p = .0028; r = .47, p < .0001, respectively). This gradient was clearly observed for FeNO levels, since FeNO levels of atopic athletes with two or more positive reactions were significantly increased compared with nonatopic athletes (Figure 1B). The AUC of FeNO increased from 0.765 (p < .0001) to 0.814 (p < .0001) if we considered multiple sensitizations (participants with ≥2 positive SPTs; Figure 1C), suggesting that FeNO levels might be a useful indicator for multiple sensitizations within atopic athletes. Accordingly, the sensitivity of FeNO ≥15 ppb increased to 80% with same specificity (65%) to detect multiple sensitizations within athletes (Table 2). For FeNO ≥20 ppb, sensitivity decreases to 68%, with specificity of 79%, respectively. Finally, combining FeNO levels (≥15 ppb) and AQUA© scores (≥6), slightly decreased sensitivity (52%), but increased specificity to 82% (p = .002, Table 2) to detect atopy. In this study, we found a presence of atopy of 37%, which is slightly higher than reported for the general Belgian population (19%), 12 but in line with other authors studying atopy in early-career elite athletes. 7,13 A previous study in Taiwanese children already showed that FeNO levels can discriminate children with and without allergic sensitizations with an optimal cutoff of 15.4 ppb. 14 Similarly, we now confirmed in early-career elite athletes the cutoff value of 15 ppb. We are aware of the limitation that we had a limited cohort consisting of 90 athletes only. However, Belgium (Flanders) only has a limited number of young athletes performing