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Airway Eosinophilia in Children with Severe Asthma

Predictive Values of Noninvasive Tests

Departments of Pediatric Respiratory Medicine and Histopathology, and Cell Biology and Clinical Studies Units, Imperial College of Science, Technology, and Medicine at the Royal Brompton Hospital and National Heart and Lung Institute, London, United Kingdom; and Department of Paediatric Cardiology and Pulmonology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany

Correspondence and requests for reprints should be addressed to Prof. Andrew Bush, M.D., Department of Pediatric Respiratory Medicine, Imperial College of Science, Technology, and Medicine at the Royal Brompton Hospital and National Heart and Lung Institute, Sydney Street, London SW3 6NP, UK. E-mail: a.bush{at}rbht.nhs.uk

Rationale: Children with severe asthma experience persistent symptoms despite maximal conventional treatment. Fraction of exhaled nitric oxide (FE_NO) and sputum eosinophils are used as markers of airway inflammation to guide treatment with steroids, but no data are available on how reliable they are in predicting airway eosinophilia assessed bronchoscopically in these children.

Objectives: To determine how FE_NO and sputum eosinophils predict airway eosinophilia measured in both bronchoalveolar lavage (BAL) and endobronchial biopsy.

Methods: Twenty-seven children with moderate to severe persistent asthma attempted measurement of FE_NO and sputum eosinophils, followed by bronchoscopy, BAL, and endobronchial biopsy within 24 h.

Main Results: Significant correlations were found between eosinophils in sputum and both BAL eosinophils (n = 20, r = 0.45, p = 0.045) and FE_NO (n = 23, r = 0.42, p = 0.049). The relationship between FE_NO and BAL eosinophils was also significant with a stronger correlation (n = 24, r = 0.54, p = 0.006). The positive predictive value (PPV) for increased sputum eosinophil percentage (> 2.5%) to detect elevated eosinophils in BAL (> 1.19%) was 75%; the negative predictive value (NPV) was 63%. All patients with both increased sputum eosinophils and an elevated FE_NO value (> 23 ppb) had elevated eosinophils in BAL (PPV, 100%); the NPV of these two markers was 65%. Eight of nine patients without any sputum eosinophils had normal subepithelial eosinophil numbers (< 1.2%; NPV, 89%). However, the PPV of any sputum eosinophils for increased subepithelial eosinophilia was only 36.4%.

Conclusions: There was moderate agreement between both FE_NO and sputum eosinophils and BAL eosinophils. There was good NPV, but only poor PPV for these markers for mucosal eosinophilia.

Key Words: airway inflammation • bronchoalveolar lavage • endobronchial biopsy • exhaled nitric oxide • sputum induction

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Asthma is characterized by eosinophilia in sputum, in bronchoalveolar lavage, and in the bronchial wall, but the relationship between the three compartments is not known. What This Study Adds to the Field We show that, whereas bronchoalveolar lavage and sputum eosinophil counts are very similar, they do not relate to airway wall eosinophilia; it is unclear which is clinically important.

 

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