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Exacerbations are heterogeneous events in terms of trigger and natural history and this has contributed to difficulty in defining a reproducible and reliable biomarker. Using an array of biomarkers, we showed that CRP was the best for detection of exacerbations though not reliable to use on its won without a change in symptoms. Plasma fibrinogen is also a potential biomarker and we showed that it increased at exacer- bations where there was an infective component, either viral or bacterial. However it is more likely that biom- arkers will be developed that respond to the infection associated with an exacerbation and we showed that serum IP-10 was a marker of respiratory viral (rhinovi- ral) infection while others have suggested that PCT may reflect bacterial infection and guide antibiotic therapy at exacerbation. COPD exacerbations also have heterogeneous recovery periods and we have also suggested that CRP measured during recovery may predict whether exacerbations cluster and if the patient suffers an early recurrence. It is well recognised that respiratory viral infection may predispose to myocardial infarction and recently we reported an association between exacerbation and myocardial infarction. In addition patients with fre- quent exacerbations were more prone to develop ischaemic heart disease. Thus exacerbations increase cardiovascular risk and this emphasises the impor- tance of exacerbation detection, management and prevention. Epidemiological aspects of systemic inflammation in COPDPeter Lange Department of Cardiology and Respiratory Medicine, Hvidovre Hospital, University of Copenhagen, Denmark [email protected] The notion that low-grade systemic inflammation is present in COPD, has lead to numerous clinical studies of different inflammatory markers in blood including CRP, fibrinogen, IL-6, TNF, leucocytes and others. In general, most of the studies have showed elevated levels of these biomarkers in the blood of COPD patients compared to healthy smokers and non-smokers. A number of smaller studies have also suggested a dose response relationship, as the biomarker levels were highest in subgroups of patients with most impaired spirometry, lowest quality of life and highest risk of exacerbations and respiratory failure. In the epidemio- logical setting, measurements of different markers of inflammation have been performed in many large cohorts comprising several thousands individuals. Also in this setting, individuals with COPD have higher blood levels of markers like CRP and fibrinogen. Inter- estingly, these higher levels are associated with poor prognosis including COPD-exacerbations, death from COPD and all causes and with an increased risk of developing ischaemic heart disease (IHD). Especially the latter association has promoted the theory that systemic inflammation may be the mechanism respon- sible for the high prevalence of IHD in COPD. In addi- tion, reports that both inhaled corticosteroids and statins may reduce the levels of inflammatory markers in the blood have lead to speculations that these drugs could be effective in the treatment of both COPD and IHD, a notion, which is supported by some pharmaco- epidemiological studies. In this lecture, the above mentioned findings will be discussed and an attempt will be made to answer the question if we can use biomarkers like high sensitivity CRP in the management of our COPD patients. Non-bronchodilatory effects of anticholinergicsMichael Pieper Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany [email protected] Anticholinergics are a proven and effective basal therapy for the treatment of obstructive airway diseases, like COPD, and are part of international treatment guidelines (e.g. www.goldcopd.org). Anti- cholinergics are used as bronchodilators which inhibit bronchoconstrictive effects of acetylcholine.Acetylcho- line mediates its bronchoconstrictive effects by activa- tion of muscarinic receptors on airway smooth muscle cells. An increased cholinergic tone is considered a major driving force in obstructive airway diseases like COPD resulting in an increased bronchomotor tone, mucus hypersecretion, and probably other patho- Abstracts – state of the art Abstracts – state of the art 3 The Clinical Respiratory Journal 2011; 5 (Suppl. 1): 1–10 © 2011 Blackwell Publishing Ltd

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Page 1: Epidemiological aspects of systemic inflammation in COPD

Exacerbations are heterogeneous events in terms oftrigger and natural history and this has contributedto difficulty in defining a reproducible and reliablebiomarker. Using an array of biomarkers, we showedthat CRP was the best for detection of exacerbationsthough not reliable to use on its won without a changein symptoms. Plasma fibrinogen is also a potentialbiomarker and we showed that it increased at exacer-bations where there was an infective component, eitherviral or bacterial. However it is more likely that biom-arkers will be developed that respond to the infectionassociated with an exacerbation and we showed thatserum IP-10 was a marker of respiratory viral (rhinovi-ral) infection while others have suggested that PCTmay reflect bacterial infection and guide antibiotic

therapy at exacerbation. COPD exacerbations alsohave heterogeneous recovery periods and we have alsosuggested that CRP measured during recovery maypredict whether exacerbations cluster and if the patientsuffers an early recurrence.

It is well recognised that respiratory viral infectionmay predispose to myocardial infarction and recentlywe reported an association between exacerbation andmyocardial infarction. In addition patients with fre-quent exacerbations were more prone to developischaemic heart disease. Thus exacerbations increasecardiovascular risk and this emphasises the impor-tance of exacerbation detection, management andprevention.

Epidemiological aspects of systemic inflammation in COPDcrj_265 3..12

Peter Lange

Department of Cardiology and Respiratory Medicine, Hvidovre Hospital, University of Copenhagen, [email protected]

The notion that low-grade systemic inflammation ispresent in COPD, has lead to numerous clinical studiesof different inflammatory markers in blood includingCRP, fibrinogen, IL-6, TNF, leucocytes and others. Ingeneral, most of the studies have showed elevated levelsof these biomarkers in the blood of COPD patientscompared to healthy smokers and non-smokers. Anumber of smaller studies have also suggested a doseresponse relationship, as the biomarker levels werehighest in subgroups of patients with most impairedspirometry, lowest quality of life and highest risk ofexacerbations and respiratory failure. In the epidemio-logical setting, measurements of different markers ofinflammation have been performed in many largecohorts comprising several thousands individuals. Alsoin this setting, individuals with COPD have higherblood levels of markers like CRP and fibrinogen. Inter-

estingly, these higher levels are associated with poorprognosis including COPD-exacerbations, death fromCOPD and all causes and with an increased risk ofdeveloping ischaemic heart disease (IHD). Especiallythe latter association has promoted the theory thatsystemic inflammation may be the mechanism respon-sible for the high prevalence of IHD in COPD. In addi-tion, reports that both inhaled corticosteroids andstatins may reduce the levels of inflammatory markersin the blood have lead to speculations that these drugscould be effective in the treatment of both COPD andIHD, a notion, which is supported by some pharmaco-epidemiological studies.

In this lecture, the above mentioned findings will bediscussed and an attempt will be made to answer thequestion if we can use biomarkers like high sensitivityCRP in the management of our COPD patients.

Non-bronchodilatory effects of anticholinergicscrj_265 3..12

Michael Pieper

Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, [email protected]

Anticholinergics are a proven and effective basaltherapy for the treatment of obstructive airwaydiseases, like COPD, and are part of internationaltreatment guidelines (e.g. www.goldcopd.org). Anti-cholinergics are used as bronchodilators which inhibitbronchoconstrictive effects of acetylcholine.Acetylcho-

line mediates its bronchoconstrictive effects by activa-tion of muscarinic receptors on airway smooth musclecells. An increased cholinergic tone is considered amajor driving force in obstructive airway diseases likeCOPD resulting in an increased bronchomotor tone,mucus hypersecretion, and probably other patho-

Abstracts – state of the art Abstracts – state of the art

3The Clinical Respiratory Journal 2011; 5 (Suppl. 1): 1–10© 2011 Blackwell Publishing Ltd

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