Klaus F. Rabe MD, PhD Christian Albrecht University Kiel & LungenClinic Grosshansdorf ( MEMBERS OF THE GERMAN CENTER FOR LUNG RESEARCH )

Klaus F. Rabe MD, PhDChristian Albrecht University Kiel & LungenClinic Grosshansdorf

((MEMBERS OF THE GERMAN CENTER FOR LUNG RESEARCHMEMBERS OF THE GERMAN CENTER FOR LUNG RESEARCH))

www.lungenclinic.de

Wohin geht die COPD Forschung: Neue Ansätze für zukünftige Therapien...?

WAS IST COPD ?

Hansel TT, Lancet 2009

Anteil der Patienten mit COPD die nie selber geraucht haben....

The Lancet 347:733-43; 2009

25-30%

Hansel TT, Lancet 2009

Bronchitis Bronchiolitis


EFFECT OF ROFLUMILASTEFFECT OF ROFLUMILAST ON EXACERBATIONS IN ON EXACERBATIONS IN PATIENTS WITH CHRONIC COUGH AND SPUTUMPATIENTS WITH CHRONIC COUGH AND SPUTUM

Martinez FJ, Calverley PMA, Goehring UM, et al. COPD7 2010;

WAS IST EINE SCHWERE COPD ?

Richens JL et al., Resp Res 2009;10:29-46

Activity of COPD...

Johnston AK et al., Thorax 2008;63:599-605

0.3

0.2

0.1

00 2 4 6 8 10 12 14

Ris

k of

car

diov

ascu

lar

even

t

Years of follow-up

GOLD 3 or 4

Restricted

GOLD 2

GOLD 0

GOLD 1

Normal


A slowly progessive cardiovascular disease which is masked through pulmonary effects...?

Rutten and Hoes. Eur J Heart Fail 2012: 14:348-50


http://pats.atsjournals.org/content/vol2/issue1/images/large/200410-050SFf2.jpeg

BRAUCHEN WIR INHALIERBARE CORTICOSTEROIDE

IN DER COPD?

Hogg, J. C. et al. N Engl J Med 2004;350:2645-2653

15241533

14641487

13991426

12931339

Numberalive

02468

1012141618

0 12 24 36 48 60 72 84 96 108 120 132 144 156Time to death (weeks)

Probability of death (%)

SFC 12.6%Placebo 15.2%

HR 0.825, p=0.05217.5% risk reduction

2.6% absolute reduction

TORCH: All-cause Mortality at 3 Years

Calverley et al NEJM 2007

RATE OF MODERATE AND SEVERE EXACERBATIONSRATE OF MODERATE AND SEVERE EXACERBATIONS

*p < 0.001 vs placebo; †p = 0.002 vs SALM; ‡p = 0.024 vs FP

Mean number of exacerbations/year

1.13

0.97*0.93*

0.85*†‡

25% reduction

0

0.2

0.4

0.6

0.8

1

1.2

Placebo SALM FP SFC

Treatment

Calverley et al. NEJM 2007

1. Price D, et al. Prim Care Respir J. 2013; 22:92-100.2. Drummond MD, et al. JAMA. 2008;300: 2407-2416.

3. Lapi F, et al. Eur Respir J. doi:10.1183/09031936. 00080912.4. Williamson PA, et al. Eur Respir J. Eur Respir J. 2011; 37:206-209.


PHÄNOTYPEN DER COPD

COPD PHÄNOTYPENCOPD PHÄNOTYPEN

• Chronische BronchitisChronische Bronchitis• EmphysemEmphysem• Reversibilität...Reversibilität...• Exacerbation frequency phenotypesExacerbation frequency phenotypes• Lower airway bacterial colonisationLower airway bacterial colonisation• Fast Decliners in FEV1Fast Decliners in FEV1• Early symptomsEarly symptoms• Co-MorbiditätenCo-Morbiditäten• Alpha-1 Antitrypsin Mangel– genetische PhänotypenAlpha-1 Antitrypsin Mangel– genetische Phänotypen• Bronchiektasen...Bronchiektasen...

DAUERTHERAPIE MIT ANTIBIOTIKA ?

MACROLIDE (AZITHROMYCIN) STUDYPROPORTION OF PARTICIPANTS FREE OF ACUTE EXACERBATIONS OF COPD

Albert RK et al. N Engl J Med 2011;365:689-698.

COMORBIDITÄTEN DER COPD

The New Drugs for COPD…

Statins…ACE inhibitors ?Beta-blockers ?+ “COPD drugs”


Statin Therapy and Mortality: Peripheral Arterial Disease With Associated

COPD

Van Gestel YRBM et al., Am J Cardiol 2008;102:192-196

50

75

100

25

00 2 4 6 8 10

No COPD / Statins

No COPD / no Statins

COPD / Statins

COPD / no Statins

Su

rviv

al (

%)

Follow-up (years)Number at riskNo COPDMild COPDModerate COPDSevere COPD

1545476961327

1223348667208

1018224505107

82415434560

61010622939

4335514518

Troosters T, et al. Respir Med. 2010; 104(7): 1005–1011.


Prediction of Mortality in COPD: Measurements Beyond Lung Function

Waschki et al Chest 2011

Atherogenic DyslipidemiaTriglycerides

HDL cholesterolCholesterol/HDL cholesterol ratio

"Normal" LDL cholesterol but apo B Small, dense LDL and HDL

Postprandial hyperlipidemia

Atherogenic DyslipidemiaTriglycerides

HDL cholesterolCholesterol/HDL cholesterol ratio

"Normal" LDL cholesterol but apo B Small, dense LDL and HDL

Postprandial hyperlipidemia

Insulin ResistanceInsulin resistanceHyperinsulinemia

HyperglycemiaType 2 diabetes

Insulin ResistanceInsulin resistanceHyperinsulinemia

HyperglycemiaType 2 diabetes

Thrombotic State PAI-1

Fibrinogen

Thrombotic State PAI-1

Fibrinogen

Inflammatory State LeptinCRP

Cytokines

Inflammatory State LeptinCRP

CytokinesAbdominalObesity Metabolic Risk Factors

Inflammation

Thin fibrous cap

Lipid Core

Coronary AtherosclerosisUnstable Plaque

Adapted from Després JP, et al. Progress in Obesity Research: 9; 2003:29-35.

Risk of Acute Coronary Syndrome


Wouters et al, Endocrinology 2012


Wouters et al, Endocrinology 2012


Kelly. Science 2012 Based on data from Boström et al. Nature 2012


n=40

0.00

0, fo

llow

up

= 7

yrs

n=40

0.00

0, fo

llow

up

= 7

yrs

Wen et al. Lancet 2011; 378:1244-1253


Ouchi et al, Nat Rev Immunol 2011



Handschin and Spiegelman. Nature 2008

Transcriptional (PPARɣ) Co-activator



Klaus F. Rabe MD, PhDChristian Albrecht University Kiel & LungenClinic Grosshansdorf

((MEMBERS OF THE GERMAN CENTER FOR LUNG RESEARCHMEMBERS OF THE GERMAN CENTER FOR LUNG RESEARCH))

www.lungenclinic.de


Documents

Klaus F. Rabe MD, PhD Christian Albrecht University Kiel & LungenClinic Grosshansdorf ( MEMBERS OF THE GERMAN CENTER FOR LUNG RESEARCH )