Chronic obstructive bronchitis and emphysema

chronic obstructive airway disease(COAD, COLD)

( chronic obstructive pulmonary disease )

COPD

COPD

emphysema bronchitis „pink puffer” „blue bloater”

Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998

00

0.50.5

1.01.0

1.51.5

2.02.0

2.52.5

3.03.0

Proportion of 1965 Rate Proportion of 1965 Rate

1965 - 19981965 - 1998 1965 - 19981965 - 1998 1965 - 19981965 - 1998 1965 - 19981965 - 1998 1965 - 19981965 - 1998

–59%–59% –64%–64% –35%–35% +163%+163% –7%–7%

CoronaryHeart

Disease

CoronaryHeart

Disease

StrokeStroke Other CVDOther CVD COPDCOPD All OtherCauses

All OtherCauses

Evidence-based medicine

(The Global Burden of Disease study)

(Science 1996; 274:740-743.)

4-7% of adult population ( 600 million patients

worldwide)

Prevalence expected to rise 3x in 10 years.

By 2020, it becomes the 3rd most frequent cause of

death ( 4,7 million cases of death – WHO, 1999)

Epidemiology

COPD morbidityin Hungary

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Új betegek Összes regisztrált

COPD is a preventable and treatable disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarly caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.

ATS/ERS Task Force, 2004

Definition

CIBA Guest Symposium: Terminology, definitions and classifications of chronic

pulmonary emphysema and related conditions (1959)

1./ Obstructive emphysema: abnormal permanent

enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of the alveolar walls and without obvious fibrosis.

2./ Chronic bronchitis: the presence of chronic productive cough for 3 months in each of 2 successive years in a patient in whom other causes (heart failure, tbc, bronchiectasis, tumor, lung abscess) of chronic cough have been excluded.

Differential diagnosis of airway obstruction

Chronicbronchitis

Emphysema

Asthma

Airflow obstruction

COPD

Adapted from Snider 1995

Etiology: host factors

Etiology: acquired risk

Effect of smoking on annual decline in lung

function Fletcher C, Peto R: BMJ 1977:i: 1645

Alveolar macrophage

neutrophil chemotactic factorscytokines ( IL-8 )mediators ( LTB4 )

neutrophil

proteázokproteases

neurophil elastasecathepsinesmatrix metalloproteinases

proteaseinhibitors

increased mucus production( chronic bronchitis )

alveolar destruction

( emphysema)

?CD8+lymphocyte

alfa1-antitrypsinSLPI

-

Groups CD8 CD4 CD8/CD4

Healthy nonsmoker 112.8 92.0 1.3

Stable-phase CB 170.6 13.0* 11.8*

Exacerbated CB 121.7 40.1* 4.3§

* p<0.05 with healthy nonsmokers§ p<0.05 with stable CB

T lymphocytes in COPD

Zhu J et al. AJRCCM 2001; 164: 109-16

Cells orchestrating the inflammation in COPD

Oxidativ stress

epithel, macroph.

Pathology

• Large airways: goblet cell metaplasia, increased

mucus production

• Medium and small airways ( 7-9. generation):

inflammation similar to asthma in certain patients

• Small airways ( 13 - 15. generation) : bronchial wall

inflammation, degeneration, fibrosis

• Alveoli: elastin loss and alveolar surface loss

Loss of alveolar attachmentsin smokers

Saetta et al. ARRD 1985

Normal Smoker

Airway muscle thicknessIncrease in COPD

Non-smoker COPD

Saetta. 1998

Small airways in COPDBarnes, NEJM,2004

Causes of Airflow Limitation

• Irreversible

– Fibrosis and narrowing of the airways

– Loss of elastic recoil due to alveolar destruction

– Destruction of alveolar support that maintains patency of small airways

Causes of Airflow Limitation

• Reversible

– Accumulation of inflammatory cells, mucus, and plasma exudate in bronchi

– Smooth muscle contraction in peripheral and central airways

– Dynamic hyperinflation during exercise

Airflowlimitation

=Driving pressure (parenchyma)

Resistance (small airways)

27

Low VA/Q areasHigh VA/Q areas

Alveolar attachments loss

Small airways narrowing

EMPHYSEMA

Airway wall thickening

SMALL AIRWAYS ABNORMALITIES

Barberà et al. ARRD 1990

Alveolar wall destruction

Air space enlargement

Capillary network reduction

Structure - function relationshipsin COPD

. . . .

COPD asthma neutrophils

no AHR*

no bronchodilation

no corticosteroid effect

10 – 40 %

eosinophils AHR*

good bronchodilator effect

good corticosteroid effect

“ Wheezy bronchitis ”

*AHR= airway hyperreactivity

reversibility threshold: 12 –15% (>200ml) FEV1-increase

Characteristics of phenotypes bronchitis emphysema

Dynamic lung volumes decreased decreased ( FEV1 , FEV1/FVC)

Static lung volumes

TLC normal or mild increase increased RV moderate increase increasd

Diffusion capacity normal or mild decreased decrease

Blood gas hypoxaemia, hypercapnia hypoxaemia in end-stage

exercise hypoxaemia: no change, improves hypoxaemia or deteriorates deteriorates

Cor pulmonale frequently seldom

Classification ( GOLD 2006 )

FEV1 (ref%* ) symptoms

cough, sputum mild 80 % morning sputum,

( FEV1/FVC 70% ) minimal breathing dyscomfort

moderate 50 - 80 % dyspnea on moderate exertion with or without wheezing,

discolored sputum, severe 30 – 50 % acute worsening with infection, with

significant erosion of QoL

very severe < 30% n cough, wheezing, breathlessness on minimal exertion

signs of RHF, significantly impaired QoL

Pharm.spir.

Beta-2 agonist

Parasympatho-lytics

Xantin derivate

Systemic consequences/comorbiditiesin COPD

Systemic consequences

Életminőség

e.g. Muscle atrophy/wasting, CHD depression, osteoporosis, anaemia

Air trappingExpiratory flow limitation

Dyspnea

Inactivity

Hyperinflation

Reduced exercisetolerance

COPDCOPD

Deconditioning

COPD

Exacerbation

Airway inflammation and systemic consequences in COPD (theory)

Muscle wasting/atrophy

Inzulin resistance,II. type diabetes

Osteoporosis

CRPCardiovascularevents

TNF IL-6

Liver

?

Tüdő

Localinflammation

GOLD Workshop Report

Four components of COPD Management

GOLD Workshop Report

Four components of COPD Management

1. Asses and monitor disease

2. Reduce risk factors

3. Manage stabil COPD Education PharmacologicGyógyszeres Non-pharmacologic

4. Manage exacerbations

1. Asses and monitor disease

2. Reduce risk factors

3. Manage stabil COPD Education PharmacologicGyógyszeres Non-pharmacologic

4. Manage exacerbations

Effects of smoking intervention and the use of aninhaled anticholinergic bronchodilator on the rateof decline of FEFV1Anthonisen N.R. és mtsai. JAMA 1994: 272, 1497-1505.

Smoking cessation is the only intervention which may retard the steep loss in lung function in COPD

1/3 of patients are able to do this(nicotin replacement, bupropion)

I. mild II. moderate III. severe IV. very severe

airway obstruction (FEV1/FVC < 70%)

FEV1 80% 50% FEV1 < 80% 30% FEV1 < 50% FEV1 < 30% or

without or with symptoms chronic respiratory or right heart failure

Avoidance of risk factors, influenza vaccination

Short acting anticholinergic and/or 2-agonist as needed

One or more long acting bronchodilators,

rehabilitation

inhalative corticosteroids( 3 exacerbation in the previous 3 years)

longterm oxigen treatment(chronic respiratoryy failure)

Surgical treatment ?Treatment of COPD

(GOLD 2003)

Respiratory insufficiency in COPD

pink puffer blue bloater partial global (hypoxaemic/transfer failure) (pump-, ventilatory failure)

acute exacerbation

Non-invasive mechanical ventilation in respiratory insufficiency

Main symptomps in acute exacerbation of COPD

increased dyspnea

wheezing, chest tightness, increased cough and sputum purulence

+/-

reduced exercise tolerance, fever , change in chest x-ray, leukocytosis

+/-

malice, disturbed sleep, daytime sleepiness, depression, confusion (CO2 retention)

AE COPD hospitalisation re-admission death

% of hospitalised patients

Endpoint Denmark1

(n=300)a

The Netherlands2

(n=171)a

Spain3

(n=135)a

USA4

(n=1016)

Mortality

In hospital 9 8 — 11

3 months 19 16 — —

1 year 36 23 22 43

Re-admission

3 months 14 — — —

1 year 46 55 — —

1Eriksen, Ugeskr Laeger 2003

2Groenewegen, Chest 2003

3Almagro, Chest 2002

4Connors, Am J Respir Crit Care Med 1996

Exacerbations of COPD

• Viral infections (Rhino,Infl, Parainfl,Adeno, RSV)• Bacterial infections (H.i.,S.p.,M.c.,P.a.,S.a.,

Enterobact.), atypical( M.p., C.p.)• Inhalation of environmental irritants (NO2,

SO2, PM10, ozone)• deviation from diet• Predisposing factors (smoking, severe

comorbidity, bacterial colonisation in the stable phase)

New strains of bacteria and AE COPDSethi, NEJM 2002

H.influenzae withnew antigen structure

Immune andinflammatory response AE

Role of antibiotics - „fall and rise „ hypothesisMiravitlles M, ERJ 2002

Are antibiotics needed? (Procalcitonin Guided Therapy)

Christ Crain, Lancet 2004

0

20

40

60

80

100

CAP AECOPD Bronchitis Asthma

An

tib

ioti

c p

resc

rip

tio

ns

(%)

Others

Standard group Procalcitonin group

45/45

38/42 27/31

11/29

16/31

4/28

2/3

0/10

9/9

2/15

P=0.03 P<0.0001 P=0.003 P=0.003 P<0.0001

PCT (ng/ml) - < 0,1 not recommanded - > 0,5 strongly recommanded

Antibacterial treatment of AECOPD

pathogens treatment

1./ acute tracheobronchitis atipical agent ? macrolide ?

2./ Chronic bronchitis H. influenzae aminopenicillin/cv without comorbidity M. catarrhalis cefalo. II, III ( FEV1 > 50% ) res. S. pneumoniae ? makrolide II.

3./ Chronic bronchitis with „ „ comorbidity ( FEV1 < 50% ) res. Pneumococcus ! respiratory kinolon

4./ Chronic bronchial infection „ respiratory kinolon Gram-neg enterobact. Ps. eruginosa = ciprofloxacin

COPD Exacerbation - Steroids

• COPD, no steroids

• 30 pack-years

• FEV1 < 1,5 l

• Group A: Placebo

• Group B: Methylprednisolone 4x125 mg i.v. – tappering until day 14 0,7

0,750,8

0,850,9

0,951

1,051,1

1,15

0 1 2 3 14 182

FE

V1

in l

Steroid Placebo

Niewoehner DE. N Engl J Med 1999; 340: 1941-47

Antibiotic Consumption in 26 Countries

Goossens.HA. Lancet 2005; 365:579-87

Penicillin resistent S.pneumoniaeEARSS, 2006