The Use of Exercise Challenge Testing and Fractional Exhaled Nitric Oxide in Diagnosis of Chest Tightness Variant Asthma in Children

Abstract

<b><i>Background:</i></b> Chest tightness variant asthma (CTVA) in children presents with chest tightness as the sole manifestation. Diagnostic tests are needed given the lack of typical asthma symptoms. The present study aimed to investigate the diagnostic value of exercise challenge testing (ECT) and fractional exhaled nitric oxide (FeNO) in pediatric CTVA. <b><i>Methods:</i></b> We included 98 children aged 6–13 years with chest tightness as the sole symptom for >4 weeks. All subjects underwent FeNO measurement, spirometry and ECT, and received 4-week budesonide/formoterol treatment. According to treatment responses, children were categorized into CTVA (<i>n</i> = 12) and non-CTVA (<i>n</i> = 86) groups. Differences in clinical characteristics and FeNO, spirometry, and ECT results were compared between the two groups. The FeNO and ECT diagnostic performances were determined using receiver operating characteristic (ROC) curve analysis. <b><i>Results:</i></b> Children with CTVA exhibited significantly higher <i>Mycoplasma pneumoniae</i> IgG, total IgE, and FeNO values; greater post-ECT forced expiratory volume in 1 s (FEV<sub>1</sub>) fall; and more frequent sensitization to mites and pets than those without CTVA. Further logistic regression revealed that higher FEV<sub>1</sub> fall (OR, 1.39; 95% CI: 1.11–1.74; <i>p =</i> 0.004) and higher FeNO values (OR, 1.04; 95% CI: 1.01–1.08; <i>p</i> = 0.014) were risk factors associated with CTVA. FEV<sub>1</sub> fall and FeNO had similar areas under the ROC curve (AUCs) (0.79 vs. 0.78; <i>p</i> = 0.924), and their optimal CTVA-prediction cutoff values were 9.9% and 15.0 ppb, respectively. The AUC of FEV<sub>1</sub> fall and FeNO combination was higher at 0.86 (95% CI: 0.78–0.93); however, no difference was observed using the single test (<i>p</i> > 0.05). Their combination exhibited a relatively higher sensitivity than that of FEV<sub>1</sub> fall alone (0.75 vs. 0.67) and higher positive predictive value than that of FeNO alone (0.60 vs. 0.29). <b><i>Conclusion:</i></b> CTVA is a cause of unexplained recurrent chest tightness in children. FeNO ≥15.0 ppb and post-ECT FEV<sub>1</sub> fall ≥9.9% are diagnostically valuable for CTVA in children, with their combination potentially contributing to greater diagnostic accuracy.

Research progress on the pathogenesis of chest tightness variant asthma characterized by chest tightness

“…胸闷是一种主观感受，往往伴有不愉快的体验。临床上很多主诉为“胸闷”的患者由于胸闷症状长期得不到诊断和治疗，最终出现明确的精神心理问题 ［ 1 - 2 ］ 。小样本研究发现有22.4%的成人胸闷患者（呼吸科就诊）及61.7%的儿童胸闷患者最终会被诊断为CTVA，并且从抗哮喘治疗中获益 ［ 3 - 4 ］ 。这种以胸闷为特点的不典型哮喘于2013年在国际上首次提出并正式命名后，引起学术界的高度重视 ［ 5 - 12 ］ 。本文从胸闷这一症状的识别及产生机制出发（包括神经传导及感知机制），进一步探讨CTVA的气道炎症、通气功能障碍、气道高反应性、精神心理因素特点及导致胸闷的机制，以期为临床诊疗提供一定的依据。…”