Measurement of tumor necrosis factor-α, leukotriene B4, and interleukin 8 in the exhaled breath condensate in patients with acute exacerbations of chronic obstructive pulmonary disease

Fanny WS Ko¹, Ting-Fan Leung², Gary WK Wong², Jenny Ngai¹, Kin W To¹, Susanna Ng¹, David SC Hui¹

¹Department of Medicine and Therapeutics; ²Department of Pediatrics, The Chinese University of Hong Kong, Hong Kong

Background: Assessment of airway inflammation in the clinical course of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) may advance our understanding of the pathogenesis and treatment.

Objectives: To assess airway inflammation in patients during the course of AECOPD by serial analyses of their exhaled breath condensates (EBC).

Methods: Twenty-six patients with AECOPD (22 males, mean[SD] percentage predicted forced expiratory volume in one second (FEV₁) 44.8 [14.3]), 11 with stable COPD, and 14 age and sex-matched healthy controls were studied. Patients with AECOPD were treated with systemic steroid and antibiotic for 7 days. EBC was collected from each patient with AECOPD on Day 5, 14, 30, and 60 post-hospitalization using EcoScreen (VIASYS Healthcare, USA) during tidal breathing over 10 minutes. Concentrations of tumor necrosis factor-α (TNF-α), leukotriene B4 (LTB4), and interleukin-8 (IL-8) were measured by enzyme-linked immunosorbent assay.

Results: The median (IQR) of TNF-α level on Day 5 was 5.08 (3.80–6 .32) pg/ml, which was lower than on Day 14 (5.84 [4.91–9.14] pg/ml, p = 0.017), Day 30 (6.14 [3.82–7.67] pg/ml, p = 0.045), and Day 60 (5.60 [4.53–8.80] pg/ml, p = 0.009). On Day 60, subjects receiving inhaled corticosteroid (ICS) had a lower level of TNF-α than those who were not (4.82 [4.06–5.65] vs 7.66 [5.48–10.9] pg/ml, p = 0.02). EBC LTB4 level did not change significantly during recovery from AECOPD whereas IL-8 was mostly undetectable.

Conclusions: EBC TNF-α level was low in patients receiving systemic steroid and antibiotic therapy for AECOPD. These findings suggest a potential role for serial EBC TNF-α for noninvasive monitoring of disease activity.

Keywords: COPD, exacerbation, exhaled breath condensate, TNF-α, LTB4