Jukka Koskela

Differences in plasma and sputum biomarkers between COPD and COPD-asthma overlap

The pathophysiological features of chronic obstructive pulmonary disease (COPD)–asthma overlap are poorly understood and there has been no study of plasma or sputum biomarkers in overlap patients. In order to clarify the similarity and differences between overlap and COPD or asthma, we have investigated four potential biomarkers of COPD: surfactant protein A (SP-A), soluble receptor for advanced glycation end-products (sRAGE), myeloperoxidase (MPO) and neutrophil gelatinase-associated lipocalin (NGAL). SP-A and sRAGE are pneumocyte-derived markers. MPO and NGAL are neutrophil-derived molecules, but NGAL can also be expressed by respiratory epithelial cells. Plasma levels of SP-A and sRAGE and induced sputum levels of MPO and NGAL were measured by enzyme immunoassay/ELISA in 134 subjects: nonsmokers (n=26), smokers (n=23), asthma (n=32), COPD (n=39) and COPD–asthma overlap patients (n=14). In patients with COPD–asthma overlap, sputum MPO and plasma SP-A were significantly elevated whereas plasma sRAGE levels were reduced compared with asthma patients. Only sputum NGAL was significantly elevated in COPD–asthma overlap compared with COPD (p=0.00016) and could be used to differentiate patients with overlap from those with COPD. Increased induced sputum levels of NGAL might be a characteristic feature of overlap, suggesting enhanced neutrophilic airway inflammation and/or airway epithelial injury in COPD–asthma overlap. Increased sputum levels of neutrophil gelatinase-associated lipocalin in COPD–asthma overlap versus COPD/asthma patients http://ow.ly/qxC8X

Characterization of sputum biomarkers for asthma–COPD overlap syndrome

Asthma–COPD overlap syndrome (ACOS) is a commonly encountered chronic airway disease. However, ACOS is still a consensus-based clinical phenotype and the underlying inflammatory mechanisms are inadequately characterized. To clarify the inflammatory mediatypical for ACOS, five biomarkers, namely interleukin (IL)-13, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), chitinase-like protein (YKL-40), and IL-6, were selected. This study hypothesized that sputum biomarkers relevant for airway inflammation in asthma (IL-13), COPD (MPO, NGAL), or in both asthma and COPD (YKL-40, IL-6) could be used to differentiate ACOS from COPD and asthma. The aim of this study was to characterize the inflammatory profile and improve the recognition of ACOS. Induced sputum levels of IL-13, MPO, NGAL, YKL-40, and IL-6 were measured by enzyme-linked immunosorbent assay/Luminex assay in a Finnish discovery cohort (n=90) of nonsmokers, smokers, and patients with asthma, COPD, and ACOS and validated in a Japanese cohort (n=135). The classification accuracy of potential biomarkers was compared with area under the receiver operating characteristic curves. Only sputum NGAL levels could differentiate ACOS from asthma (P<0.001 and P<0.001) and COPD (P<0.05 and P=0.002) in the discovery and replication cohorts, respectively. Sputum NGAL levels were independently correlated with the percentage of pre-bronchodilator forced expiratory volume in 1 second predicted in multivariate analysis in the discovery and replication cohorts (P=0.001 and P=0.002, respectively). In conclusion, sputum biomarkers reflecting both airway inflammation and remodeling of the tissue show potential in differentiation between asthma, COPD, and ACOS.

Longitudinal HRQoL shows divergent trends and identifies constant decliners in asthma and COPD

BACKGROUND/AIM Monitoring of lung function alone does not adequately identify the high-risk patients among elderly asthma and COPD cohorts. The additional value of Health-Related Quality of Life (HRQoL) development in the detection of patients with a disabling disease in clinical practice is unclear. The aim of this study was to statistically examine the individual development of HRQoL measured using respiratory-specific AQ20 and generic 15D questionnaires. MATERIALS AND METHODS The HRQoL of COPD (N = 739) and asthma (N = 1329) patients was evaluated at 0, 1, 2, and 4 years after recruitment. To determine a five-year HRQoL change for each patient we used mixed-effects modelling for linear trend. RESULTS In COPD, the majority (60-80%) of the individuals showed declining trend, whereas in asthma, the majority (46-71%) showed no attenuation in HRQoL. The proportion of constant decliners was estimated higher with the 15D both in asthma (6.3%) and COPD (6.3%) than with AQ20 (3.5 and 4.5%, respectively). The first measurement of HRQoL was found to predict future development of HRQoL. In asthma, obesity-related diseases such as hypertension, diabetes and gastro-esophageal reflux disease best explained the decline, whereas in COPD, age and the level of bronchial obstruction were the main determinants. CONCLUSION Based on the five-year follow-up, the HRQoL trends significantly diverging from each other could be identified both among the asthma and COPD patients. Compared to cross-sectional HRQoL, the HRQoL trend over a clinically relevant period of time allows us to ignore, to a great extent, the random error of self-assessed HRQoL and thus, it may offer a more accurate measure to describe the disease process.

Individual FEV1 Trajectories Can Be Identified from a COPD Cohort

Abstract Objective: We aim to make use of clinical spirometry data in order to identify individual COPD-patients with divergent trajectories of lung function over time. Study Design and Setting: Hospital-based COPD cohort (N = 607) was followed on average 4.6 years. Each patient had a mean of 8.4 spirometries available. We used a Hierarchical Bayesian Model (HBM) to identify the individuals presenting constant trends in lung function. Results: At a probability level of 95%, one third of the patients (180/607) presented rapidly declining FEV1 (mean -78 ml/year, 95% CI -73 to -83 ml) compared to that in the rest of the patients (mean -26 ml/year, 95% CI -23 to -29 ml, p ≤ 2.2 × 10-16). Constant improvement of FEV1 was very rare. The rapid decliners more frequently suffered from exacerbations measured by various outcome markers. Conclusion: Clinical data of unique patients can be utilized to identify diverging trajectories of FEV1 with a high probability. Frequent exacerbations were more prevalent in FEV1-decliners than in the rest of the patients. The result confirmed previously reported association between FEV1 decline and exacerbation rate and further suggested that in clinical practice HBM could improve the identification of high-risk individuals at early stages of the disease.

Physical activity in COPD patients decreases short-acting bronchodilator use and the number of exacerbations.

BACKGROUND Physically inactive patients with chronic obstructive pulmonary disease (COPD) exhibit higher rates of exacerbations and symptoms of dyspnoea than active patients. Whether the use of COPD medication explains these differences is not known. AIM This study evaluated differences in the use of COPD medication and the number of exacerbations due to physical activity. METHODS A COPD cohort (N = 719) was followed through medical records to identify hospital admissions, and exercise activity was evaluated using mailed questionnaires. The national drug reimbursement registry identified drug purchases for one year. RESULTS The use of maintenance therapies, such as long-acting muscarinic antagonists (LAMAs), long-acting beta agonists (LABAs), inhaled corticosteroids (ICS), and theophylline, did not differ significantly between physically active (N = 346) and inactive (N = 355) COPD patients. The cumulative dose of salbutamol (85 vs. 218 mg, adjusted P = 0.01) and oral corticosteroids (OCS) (621 vs. 1068 mg, adjusted P = 0.02) were significantly higher in inactive patients, regardless of disease severity. LABAs, LAMAs, and ICS were used in reduced doses in both patient groups compared to daily defined doses (DDD). Physical activity was independently associated with the number of hospital admissions and the use of OCS and short-acting bronchodilators. CONCLUSION Physical inactivity in COPD was not associated with poorer use of maintenance therapies. In contrast, inactivity was independently associated with the number of exacerbations measured by hospital admissions and the use of OCS and short-acting symptom-relieving medications.

Characterization of sputum biomarkers for asthma–COPD overlap syndrome [Erratum]

[This corrects the article on p. 2457 in vol. 11, PMID: 27757028.].