Inflammation and chronic colonization of Haemophilus influenzae in sputum in COPD patients related to the degree of emphysema and bronchiectasis in high-resolution computed tomography

Abstract

The presence of bacteria in the lower airways in COPD results in inflammation, further airway structural damage, and might lead to repeated exacerbations. We have previously shown that chronic colonization of Haemophilus influenzae during stable disease is related to increased inflammation, and we now aimed to relate previous findings of bacterial colonization and inflammation to the degree of radiological findings of bronchiectasis and emphysema. Thirty-nine patients with COPD were included in their stable state, and a high-resolution computed tomography of the lung was performed. They were followed-up monthly for up to a maximum of 6 months or until exacerbation, and they answered questionnaires, performed spirometry, and induced sputum at every visit. Thirty-five patients had emphysema with an emphysema degree of median 20% (interquartile range 10-50), and five patients had bronchiectasis, of which only four could expectorate sputum. The degree of emphysema correlated with several inflammatory mediators in sputum, such as interleukin-8 concentration, myeloperoxidase activity, and Leukotriene B₄ concentration. Ten patients were chronically colonized with H. influenzae (ie, had a positive culture for H. influenzae at all visits). The four sputum patients with bronchiectasis were chronically colonized with H. influenzae and showed higher degree of H. influenzae growth compared to patients without bronchiectasis. During exacerbation, there was no longer any correlation between emphysema degree and inflammation, but patients with bronchiectasis showed higher sputum purulence score than patients without bronchiectasis. Emphysema and bronchiectasis in COPD patients show different clinical features. The presence of emphysema is more related to inflammation, while bronchiectasis is associated with bacterial colonization. We believe that both emphysema and bronchiectasis are therefore COPD phenotypes of highest impact and need evaluation to prevent further disease progression.

Keywords: COPD; bronchiectasis; chronic colonization; emphysema; inflammation; pathogenic bacteria.

Figure 1

HRCT pictures showing emphysema (A) in the upper lobes (white arrows) and severe bronchiectasis (B) with bronchial wall thickening (white arrows). Abbreviation: HRCT, high-resolution computed tomography.

Figure 2

The correlation between emphysema degree and sputum biomarkers (log IL-8 concentration [A, n=29] and log MPO activity [B, n=28]) and symptom score (CCQ [C, n=37] and MRC [D, n=37]) in COPD patients during stable phase (using the mean of each parameter at all stable visits). Note: Data are presented as individual value for each patient, and Spearman’s r and P values are shown in the respective figure. Abbreviations: CCQ, Clinical COPD Questionnaire; conc, concentration; IL, interleukin; MPO, myeloperoxidase; MRC, Medical Research Council.

Figure 3

The emphysema degree measured by HRCT in COPD patients with (n=10) or without (n=21) chronic colonization (= colonization at all visits) of Haemophilus influenzae in sputum during stable phase. Notes: Data are presented as individual dots and bars for median and IQR. P-value for statistical significance between colonized and not colonized patients is shown in the figure. Abbreviations: HRCT, high-resolution computed tomography; IQR, interquartile range.

Figure 4

The degree of Haemophilus influenzae growth in sputum during stable phase (A) and exacerbation (B) in COPD patients with (n=4 during stable phase and n=5 during exacerbation) or without (n=27 during stable phase and n=16 during exacerbation) bronchiectasis according to HRCT. H. influenzae growth is classified as none, mild, moderate, and high due to routine culture at the Clinical Microbiology Department, Lund University Hospital. Notes: Data are presented as individual dots and bars for median and IQR. P-values for statistical significance between COPD patients with or without bronchiectasis are shown in the figure. Abbreviations: HRCT, high-resolution computed tomography; IQR, interquartile range.

Figure 5

Sputum purulence scores during stable phase (A) and exacerbation (B) in COPD patients with (n=4 during stable phase, and n=5 during exacerbation) or without (n=27 during stable phase, and n=16 during exacerbation) bronchiectasis according to HRCT. Notes: Data are presented as individual dots and bars for median and IQR. P-value for statistical significance between COPD patients with or without bronchiectasis is shown in the figure. Abbreviations: HRCT, high-resolution computed tomography; IQR, interquartile range.