Chronic obstructive bronchitis and emphysema

chronic obstructive airway disease(COAD, COLD)

( chronic obstructive pulmonary disease )

COPD

COPD

emphysema bronchitis „pink puffer” „blue bloater”

1. COPD, a common preventable and treatable disease, is characterized by persistent airflow limitation.

2. The airway obstruction is usually progessive and associated with an

enhanced chronic ionflammatory response in the airways and the

parenchyma to noxius particles and gases.

3. Exacerbations and comorbidities contribute to the overall severity in

an individual patient.

GOLD 2011

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

„Global burden of disease”

(Science 1996; 274:740-743.)

4-7% of adult population, 9-10 % for those over 40

Prevalence expected to rise 3x in 10 years.

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

death

Epidemiology

COPD morbidityin Hungary

OKTPI, 2014

0

100

200

300

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

%00

0

0500100015002000

%00

0

Ú j be tegek

Ös s zesreg is ztrá lt

Prevalence: 175 000

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+lymphocyta

alfa1-antitrypsinSLPI

-

Pathology

1. chronic bronchitis – increased mucus production, chronic cough

2. obstructiv bronchiolitis – small airway obstruction with inflammation and fibrosis of bronchioles

3. Emphysema – alveolar destruction, hiperinflation, loss of elastic recoil, gázcserezavar, bronchiális obstrukció

Small airways in COPDBarnes, NEJM,2004

Loss of alveolar attachmentsin smokers

Saetta et al. ARRD 1985

Normal Smoker

Airway muscle thicknessIncrease in COPD

Non-smoker COPD

Saetta. 1998

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)

Pathology and gas exchange in COPD

Stockley, Rennard, Rabe, Celli, 2007

Differencial diagnostics

• Asthma

• CHF

• Bronchiectasis• Bronchiolitis obliterans (young, non-smoker, RA, smoke

exposition, HRCT:hypodens area)

• Diffuse panbronchiolitis (non-smoker malei, sinusitis, HRCT:centrilobular foci and hyperinflation)

Overlap ~ 10 - 40%

Inflammation and lung functionIn asthma and COPD Barnes, 2009

COPD asthma neutrophils

mild AHR*

no(poor) 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 FEV1 (ref %) symptoms

cough, sputum mild 80 % morning sputum,

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

Diagnosis: postbronchodilator (4 puff salbutamol) FEV1/FVC<70%

Pharm.spir.

Beta-2 agonist

Parasympatho-lytics

Xantin derivate

Systemic consequences/comorbiditiesin COPD

Systemic consequences

Quality of life

e.g. Muscle atropgy/wasting, atherosclerosis, depression, osteoporosis, anaemia, diabetes

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 whichmay retard the steep loss in lung function inCOPD

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

Smoking: early and late quit

34 439 Brittish male physicians, 1951-2001

Doll, BMJ 2004

ipratropium bromid, (SAMA) MDI, 4 x 3-6 ( 60-120 µg ) puff

+ β2 agonist (SABA) MDI

4 x 2-4 puff ( 200-400 µg )

+ retard theophyllin tabl.

300-900 mg ( Se- level 8-12 µg/ml )

antibiotics(5-10 days) + corticosteroid

(32 mg methylprednisolon, 10-14 days)

Treatment of COPD

exacerbation

+ LAMA (tiotropium) DPI, 1x1 or LABA (salmeterol, formoterol) 2x1

(indacaterol) 1x1 ICS/LABAfluticason/salmeterol

or

budesonid/formoterol

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 2006)

Longterm oxygen in COPD

NOTT: Ann Intern Med, 1980BMC: Lancet, 1981

Indication: resting• PaO2 < 55 mmHg or SAT < 88%• 55 Hgmm < PaO2 < 60 mmHg, and pulmonary hypertension, polyglobulia or heart failure

Target: PaO2 ≈ 60 mmHg or SAT ≈ 90 % Pa CO2 increase < 15-20 mmHg

Dose: > 15 h/day, 1-2 L/min through nasal prong

the only treatment which prolongs life in hypoxic COPD

Respiratory insufficiency in COPD

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

acute exacerbation

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)

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

Non-invasive mechanical ventilation in respiratory insufficiency