Published ahead of print on September 14, 2006, doi:10.1164/rccm.200603-352OC Am. J. Respir. Crit. Care Med., Volume 174, Number 12, December 2006, 1286-1291 A more recent version of this article appeared on December 15, 2006
Submitted on March 10, 2006 Airway Eosinophilia in Children with Severe Asthma: Predictive Values of Noninvasive TestsChristiane Lex1,1 Department of Pediatric Respiratory Medicine, Imperial College of Science, Technology and Medicine at the Royal Brompton Hospital and National Heart and Lung Institute, London, United Kingdom; Department of Paediatric Cardiology and Pulmonology, Heirich Heine University Duesseldorf, Duesseldorf, Germany, 2 Department of Pediatric Respiratory Medicine, Imperial College of Science, Technology and Medicine at the Royal Brompton Hospital and National Heart and Lung Institute, London, United Kingdom, 3 Department of Histopathology, Imperial College of Science, Technology and Medicine at the Royal Brompton Hospital and National Heart and Lung Institute, London, United Kingdom, 4 Cell Biology Unit, Imperial College of Science, Technology and Medicine at the Royal Brompton Hospital and National Heart and Lung Institute, London, United Kingdom, 5 Clinical Studies Unit, Imperial College of Science, Technology and Medicine at the Royal Brompton Hospital and National Heart and Lung Institute, London, United Kingdom * To whom correspondence should be addressed. E-mail: a.bush{at}rbht.nhs.uk.
Rationale: Children with severe asthma experience persistent symptoms despite maximal conventional treatment. Exhaled nitric oxide (FeNO) 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 FeNO and sputum eosinophils predict airway eosinophilia measured in both bronchoalveolar lavage and endobronchial biopsy. Methods: 27 children with moderate to severe persistent asthma attempted measurement of FeNO and sputum eosinophils, followed by bronchoscopy, BAL and endobronchial biopsy within 24 hours. Main Results: Significant correlations were found between eosinophils in sputum and both BAL eosinophils (n=20, r=0.45, p=0.045) and FeNO (n=23, r=0.42, p=0.049). The relationship between FeNO 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 eosinophils 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 FeNO value (> 23 ppb) had elevated eosinophils in BAL (PPV 100%), the NPV of these two markers was 65%. 8/9 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 FeNO and sputum eosinophils and BAL eosinophils. There was good negative, but only poor positive predictive value for these markers for mucosal eosinophilia. Key words: airway inflammation, sputum induction, bronchoalveolar lavage, exhaled nitric oxide, endobronchial biopsy
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