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Exhaled Nitric Oxide and Induced Sputum Analysis as Markers of Airway Inflammation in Subjects With COPD^*

^* From the National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, CO.

Correspondence to: Philip E. Silkoff, MD, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, 1400 Jackson St, Denver, CO 80206

	Introduction

TOP Introduction

 
Abbreviations: FENO = exhaled nitric oxide; IL = interleukin; IS = induced sputum; LTB₄ = leukotriene B₄

Background: Airway inflammation is an important mechanism underlying deterioration in COPD and can be noninvasively assessed by exhaled nitric oxide (FENO) and induced sputum (IS). We wished to examine the short-term reproducibility of FENO and IS in a cohort of subjects with COPD.

Methods: We recruited 11 subjects (9 men; age, 46 to 69 years) with COPD (American Thoracic Society criteria) and FEV₁ 45 to 70% predicted. FENO and spirometry were assessed at baseline, 2, 4, and 6 weeks, and IS for differential cell count, leukotriene B₄ (LTB₄) and interleukin (IL)-8 at baseline, 4, and 6 weeks.

Results: There was a significant decline in FEV₁ (p = 0.029) and FEV₁/FVC ratio (p = 0.001) over the study period. This was accompanied by a significant increase (geometric mean with 95% confidence limits) from 15.2 (10.9 to 21.2) to 23.6 (17.1 to 32.4) parts per billion (p = 0.037) and LTB₄ from 1.79 (1.03 to 3.11) to 3.57 (1.95 to 6.53) pg/mL (p = 0.018). There was no significant change in total or differential cell counts or IL-8 for the group as a whole; however, the change in both FENO and IL-8 correlated with the change in percent neutrophil count (r = 0.648, p = 0.028) and (r = 0.60, p = 0.05). Additionally, IL-8 and percent neutrophil count showed a borderline correlation (r = 0.34, p = 0.056). Finally, FEV₁ showed a strong negative correlation with percent neutrophil count (r = 0.55, p = 0.001). The induction of sputum was well tolerated by all subjects, although FEV₁ fell significantly from 1.83 ± 0.44 to 1.46 ± 0.44 L.

Conclusion: The worsening lung function over the study period, perhaps related to seasonal/climatic change, was accompanied by a significant increase in FENO and LTB₄. FENO may be related to neutrophil inflammation, which is driven by the chemoattractant IL-8. FENO and IS promise to be useful markers of airway inflammation in COPD but IS causes a significant fall in FEV₁ requiring careful monitoring and appropriate caution.

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