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Exhaled Nitric Oxide Correlated With Induced Sputum Findings in COPD^*

^* From the Department of Medicine, National Jewish Medical and Research Center, Denver, CO.

Correspondence to: Philip E. Silkoff, MD, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206; e-mail: silkoffp{at}njc.org

Study objectives: Neutrophilic airway inflammation may underlie the pathogenesis of COPD. We examined repeated measurements of the fractional concentration of exhaled nitric oxide (FENO) and the correlation with cells and mediators in induced sputum (IS) from patients with COPD.

Participants: Eleven COPD subjects (9 men and 2 women, aged 46 to 69 years) with predicted FEV₁ of 45 to 70%.

Setting: A hospital research laboratory.

Design: Single-cohort, prospective study with four visits at two weekly intervals.

Interventions: FENO and spirometry were assessed at all visits, and IS for differential cell count, leukotriene-B₄ (LTB₄) and interleukin (IL)-8, nitrite, and nitrate at visit 1, visit 3, and visit 4.

Results: During the study, there were significant declines in mean percent predicted FEV₁, from 55.2 to 51.6% (p = 0.029), and mean FEV₁/FVC ratio, from 50.4 to 45.4% (p = 0.001), accompanied by a significant increase in FENO geometric mean (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 sputum LTB₄, from 1.79 (1.03 to 3.11) to 3.57 (1.95 to 6.53) ng/mL (p = 0.033), but no significant change in other sputum parameters. From visits 1 to 4, the change in percent neutrophils correlated with the changes in FENO and IL-8 (r = 0.648, p = 0.028; r = 0.60, p = 0.05, respectively). Hypertonic saline solution induction of sputum caused a fall in FEV₁, from 1.83 ± 0.44 to 1.46 ± 0.44 L (p = 0.049).

Conclusions: The worsening spirometry results were accompanied by significant increases in FENO and sputum LTB₄. FENO may be related to neutrophilic inflammation driven by the chemoattractant IL-8. FENO and IS may be useful markers of airway inflammation in COPD patients. Sputum induction with hypertonic saline solution causes a significant fall in FEV₁ requiring appropriate caution.

Key Words: COPD • inflammation • nitric oxide • sputum

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