Patients with chronic obstructive pulmonary disease and chronically colonized with Haemophilus influenzae during stable disease phase have increased airway inflammation

Abstract

Background: Some patients with chronic obstructive pulmonary disease (COPD) show increased airway inflammation and bacterial colonization during stable phase. The aim of this study was to follow COPD patients and investigate chronic colonization with pathogenic bacteria during stable disease phase, and relate these findings to clinical parameters, inflammatory pattern, lung function, and exacerbations.

Methods: Forty-three patients with COPD were included while in a stable state and followed up monthly until exacerbation or for a maximum of 6 months. The patients completed the Clinical COPD Questionnaire and Medical Research Council dyspnea scale questionnaires, and exhaled breath condensate was collected, followed by spirometry, impulse oscillometry, and sputum induction.

Results: Ten patients were chronically colonized (ie, colonized at all visits) with Haemophilus influenzae during stable phase. These patients had higher sputum levels of leukotriene B4 (P<0.001), 8-isoprostane (P=0.002), myeloperoxidase activity (P=0.028), and interleukin-8 (P=0.02) during stable phase when compared with other patients. In addition, they had lower forced vital capacity (P=0.035) and reactance at 5 Hz (P=0.034), but there was no difference in forced expiratory volume in 1 second (FEV1), FEV1 % predicted, forced vital capacity % predicted, exhaled breath condensate biomarkers, C-reactive protein, or Clinical COPD Questionnaire and Medical Research Council dyspnea scale results. Three patients had intermittent colonization (colonized at only some visits) of H. influenzae during stable phase, and had lower levels of inflammatory biomarkers in sputum when compared with the chronically colonized patients. The difference in airway inflammation seen during stable phase in patients chronically colonized with H. influenzae was not observed during exacerbations.

Conclusion: Some COPD patients who were chronically colonized with H. influenzae during stable phase showed increased airway inflammation and reduced lung volumes when compared with non-chronically colonized patients.

Keywords: biomarker; chronic obstructive pulmonary disease; colonization; inflammation; spirometry; sputum.

Figure 1

Concentrations of sputum biomarkers (LTB₄, 8-isoprostane, MPO activity, IL-8) and purulence scores for patients chronically colonized with Haemophilus influenzae (yes) and in patients not chronically colonized with H. influenzae (no). Notes: The graphs show levels of these parameters at stable phase (using the mean of each parameter at all stable visits). The data are presented as the median (interquartile range) and *P≤0.05, **P≤0.01, ***P≤0.001 for comparisons between colonized and non-colonized patients. Abbreviations: H. influenzae, Haemophilus influenzae; LTB₄, leukotriene B₄; MPO, myeloperoxidase; IL, interleukin.

Figure 2

Lung function parameters in patients chronically colonized with H. influenzae (yes) and in patients not chronically colonized with H. influenzae (no) as measured by (A) spirometry and (B) impulse oscillometry. Notes: The graphs show levels of these parameters at stable phase (using the mean of each parameter at all stable visits). The data are presented as the median (interquartile range) and *P≤0.05 for comparison between colonized and non-colonized patients. Abbreviations: H. influenzae, Haemophilus influenzae; %p, percent predicted; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity.

Figure 3

Concentrations of EBC biomarkers (A) and clinical parameters (B) in patients chronically colonized with H. influenzae (yes) and in patients not chronically colonized with H. influenzae (no). Notes: The graphs show levels of these parameters at stable phase (using the mean of each parameter at all stable visits). The data are presented as the median (interquartile range). Abbreviations: H. influenzae, Haemophilus influenzae; LTB₄, leukotriene B₄; MRC, Medical Research Council dyspnea scale; CRP, C-reactive protein; CCQ, Clinical COPD Questionnaire; EBC, exhaled breath condensate.

Figure 4

Kaplan–Meier curve of the proportion of patients who exacerbated during the 6-month study period.

Figure 5

Sputum biomarkers, ie, LTB₄ (A), 8-isoprostane (B), MPO activity (C), IL-8 concentration (D), and purulence score (E) in patients chronically colonized with H. influenzae (chronic), in patients with intermittent colonization with H. influenzae (intermittent) and in patients not colonized by pathogenic bacteria (no growth). The graphs show levels of these parameters at stable phase (using the mean of each parameter at all stable visits). The data are shown as the median (interquartile range) and *P≤0.05 and **P≤0.01 for comparison between marked patient groups. Abbreviations: LTB₄, leukotriene B₄; MPO, myeloperoxidase; IL, interleukin.