The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers.

Long-term tobacco smokers with chronic obstructive pulmonary disease (COPD) or chronic bronchitis display an excessive accumulation of neutrophils in the airways; an inflammation that responds poorly to established therapy. Thus, there is a need to identify new molecular targets for the development of effective therapy. Here, we hypothesized that the neutrophil-mobilizing cytokine interleukin (IL)-26 (IL-26) is involved in airway inflammation amongst long-term tobacco smokers with or without COPD, chronic bronchitis or colonization by pathogenic bacteria. By analyzing bronchoalveolar lavage (BAL), bronchail wash (BW) and induced sputum (IS) samples, we found increased extracellular IL-26 protein in the airways of long-term smokers in vivo without further increase amongst those with clinically stable COPD. In human alveolar macrophages (AM) in vitro, the exposure to water-soluble tobacco smoke components (WTC) enhanced IL-26 gene and protein. In this cell model, the same exposure increased gene expression of the IL-26 receptor complex (IL10R2 and IL20R1) and nuclear factor κ B (NF-κB); a proven regulator of IL-26 production. In the same cell model, recombinant human IL-26 in vitro caused a concentration-dependent increase in the gene expression of NF-κB and several pro-inflammatory cytokines. In the long-term smokers, we also observed that extracellular IL-26 protein in BAL samples correlates with measures of lung function, tobacco load, and several markers of neutrophil accumulation. Extracellular IL-26 was further increased in long-term smokers with exacerbations of COPD (IS samples), with chronic bronchitis (BAL samples ) or with colonization by pathogenic bacteria (IS and BW samples). Thus, IL-26 in the airways emerges as a promising target for improving the understanding of the pathogenic mechanisms behind several pulmonary morbidities in long-term tobacco smokers.

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.

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.

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

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.

Inflammatory biomarkers in sputum predict COPD exacerbations.

INTRODUCTION: Exacerbations in chronic obstructive pulmonary disease (COPD) reduce quality of life and are associated with a more rapid deterioration of the disease. It is desirable to predict an oncoming exacerbation before it occurs. The aim of the present study was to identify biomarkers that may predict a forthcoming exacerbation. MATERIALS AND METHODS: Forty-three patients with COPD in their stable state were included and followed up monthly until exacerbation, or for a maximum of 6 months. The patients come for an extra visit (prior to a scheduled visit) when exacerbated. The patients completed the questionnaires CCQ and MRC. Exhaled breath condensate (EBC) was collected followed by spirometry, impulse oscillometry, and sputum induction. RESULTS: Twenty-five patients had an exacerbation within the 6-month period. Leukotriene B4 in sputum was the only biomarker that was increased at the visit prior to exacerbation compared to at the stable phase (p = 0.05). There also was a tendency for a similar but not significant increase in the sputum levels of 8-isoprostane, myeloperoxidase activity, and interleukin-8, as well as additional increases during exacerbation. Sputum purulence was not increased until exacerbation (p = 0.02). In contrast, none of the inflammatory biomarkers in EBC, the quality-of-life questionnaire score, CRP, spirometric parameters, or impulse oscillometry parameters were increased at the visit prior to exacerbation compared to the values at the stable phase. CONCLUSION: Sputum biomarkers, especially leukotriene B4, could be used as predictors of a forthcoming exacerbation and worsening of COPD. This would be of great value for the patient, who may be a subject for early treatment and thereby avoid a progression of the disease.

Ventilation/perfusion SPECT in chronic obstructive pulmonary disease: an evaluation by reference to symptoms, spirometric lung function and emphysema, as assessed with HRCT.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation which is not fully reversible. Despite the heterogeneity of COPD, its diagnosis and staging is currently based solely on forced expiratory volume in 1 s (FEV(1)). FEV(1) does not explain the underlying pathophysiology of airflow limitation. The relationship between FEV(1), symptoms and emphysema extent is weak. Better diagnostic tools are needed to define COPD. Tomographic lung scintigraphy [ventilation/perfusion single photon emission tomography (V/P SPECT)] visualizes regional V and P. In COPD, relations between V/P SPECT, spirometry, high-resolution computed tomography (HRCT) and symptoms have been insufficiently studied. The aim of this study was to investigate how lung function imaging and obstructive disease grading undertaken using V/P SPECT correlate with symptoms, spirometric lung function and degree of emphysema assessed with HRCT in patients with COPD. METHODS: Thirty patients with stable COPD were evaluated with the Medical Research Council dyspnoea questionnaire (MRC) and the clinical COPD questionnaire (CCQ). Spirometry was performed. The extent of emphysema was assessed using HRCT. V/P SPECT was used to assess V/P patterns, total reduction in lung function and degree of obstructive disease. RESULTS: The total reduction in lung function and degree of obstructive disease, assessed with V/P SPECT, significantly correlated with emphysema extent (r = 0.66-0.69, p < 0.0001) and spirometric lung function (r = 0.62-0.74, p < 0.0005). The correlation between emphysema extent and spirometric lung function was weaker. No correlation between MRC, CCQ and objective measurements was found. CONCLUSION: V/P SPECT is sensitive to early changes in COPD. V/P SPECT also has the possibility to identify comorbid disease. V/P SPECT findings show a significant correlation with emphysema extent and spirometric lung function. We therefore recommend that scintigraphic signs of COPD, whenever found, should be reported. V/P SPECT can also be used to categorize the severity of functional changes in COPD as mild, moderate or severe.

Ventilation-perfusion SPECT with 99mTc-DTPA versus Technegas: a head-to-head study in obstructive and nonobstructive disease.

UNLABELLED: Lung scintigraphy is primarily used to diagnose pulmonary embolism. Ventilation imaging is often performed using (99m)Tc-DTPA or Technegas, an ultrafine dispersion of (99m)Tc-labeled carbon. Despite the common use of these radioaerosols, they have not been compared in an intraindividual study, and not with ventilation-perfusion (V/P) SPECT. The aim of the present head-to-head study was to systematically investigate differences in ventilation studies performed with (99m)Tc-diethylenetriaminepentaacetate (DTPA) and Technegas. METHODS: Sixty-three patients, 28 without and 35 with obstructive lung disease, were examined with V/P SPECT using both (99m)Tc-DTPA and Technegas. V/P SPECT images were randomized and assessed independently by 2 masked physicians according to a predefined scoring system. A paired comparison was performed using the Wilcoxon signed-rank test. RESULTS: In both obstructive and nonobstructive disease, the overall unevenness of radiotracer deposition and the degree of central deposition were more pronounced in (99m)Tc-DTPA than Technegas studies. Because of better peripheral penetration, the extent of reverse mismatch was less when Technegas was used. Additionally, in obstructive disease, the degree of focal deposition in distal airways was more pronounced with (99m)Tc-DTPA. Mismatched perfusion defects were more frequently found with Technegas in obstructive disease. CONCLUSION: This intraindividual comparative study shows that Technegas is the preferred radioaerosol, particularly in obstructive disease.