Chronic obstructive bronchitis and
emphysema
chronic obstructive airway disease
(COAD, COLD)
( chronic obstructive pulmonary disease )
COPD
COPD
emphysema
„pink puffer”
bronchitis
„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., 1965-1998
Proportion of 1965 Rate
3.0
3.0
2.5
2.5
Coronary
Heart
Disease
Stroke
Other CVD
COPD
All Other
Causes
–59%
–64%
–35%
+163%
–7%
2.0
2.0
1.5
1.5
1.0
1.0
0.5
0.5
0.0 0
1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998
„Global burden of disease”
(Science 1996; 274:740-743.)
Epidemiology
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
COPD morbidity in Hungary
OKTPI, 2015
Prevalence
180 983
Incidence
15 362
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
Chronic
bronchitis
Emphysema
COPD
Airflow
obstruction
Asthma
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
?
CD8+
lymphocyta
Alveolar macrophage
neutrophil chemotactic factors
cytokines ( IL-8 )
mediators ( LTB4 )
neutrophil
alfa1-antitrypsin
SLPI
protease
inhibitors
-
alveolar destruction
( emphysema)
proteázok
proteases
neurophil elastase
cathepsines
matrix metalloproteinases
increased mucus productio
( chronic bronchitis )
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 COPD
Barnes, NEJM,2004
Loss of alveolar attachments
in smokers
Normal
Smoker
Saetta et al. ARRD 1985
Airway muscle thickness
Increase 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
Driving pressure (parenchyma)
Resistance (small airways)
Airflow
=
limitation
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)
Inflammation and lung function
In asthma and COPD
Overlap ~ 10 - 40%
Barnes, 2009
asthma
COPD
neutrophils
mild AHR*
no(poor) bronchodilation
no corticosteroid
effect
eosinophils
AHR*
10 –
40 %
good bronchodilator
effect
good corticosteroid
effect
“ Wheezy bronchitis ”
reversibility threshold: 12 –15% (>200ml) FEV1increase
*AHR= airway hyperreactivity
Characteristics of phenotypes
bronchitis
Dynamic lung volumes
decreased
emphysema
decreased
( FEV1 , FEV1/FVC)
Static lung volumes
TLC
RV
Diffusion capacity
Blood gas
exercise
Cor pulmonale
normal or mild increase
moderate increase
increased
increasd
normal or mild
decrease
decreased
hypoxaemia, hypercapnia
hypoxaemia: no change, improves
or deteriorates
frequently
hypoxaemia in
end-stage
hypoxaemia
deteriorates
seldom
Diagnosis: postbronchodilator (4 puff salbutamol) FEV1/FVC<70%
Classification
FEV1 (ref %)
symptoms
cough, sputum
mild
moderate
severe
very severe
 80 %
morning sputum,
minimal breathing dyscomfort
50 - 80 %
dyspnea on moderate exertion
with or without wheezing,
discolored sputum,
acute worsening with infection, with
significant erosion of QoL
30 – 50 %
< 30%
n
cough, wheezing,
breathlessness on minimal exertion
signs of RHF,
significantly impaired QoL
Pharm.spir.
Beta-2 agonist
Parasympatholytics
Xantin derivate
Systemic consequences/comorbidities
in COPD
COPD
COPD
Exacerbation
Expiratory flow limitation
Air trapping
Hyperinflation
Dyspnea
Reduced exercise
tolerance
Quality of life
Inactivity
Deconditioning
Systemic consequences
e.g. Muscle atropgy/wasting, atherosclerosis, depression,
osteoporosis, anaemia, diabetes
Airway inflammation and systemic
consequences in COPD (theory)
Tüdő
Muscle
wasting/atrophy
TNFa
Inzulin resistance,
II. type diabetes
IL-6
?
Local
inflammation
Cardiovascular
events
CRP
Liver
Osteoporosis
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
Effects of smoking intervention and the use of an
inhaled anticholinergic bronchodilator on the rate
of decline of FEFV1
Anthonisen 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, vareniclin)
Smoking: early and late quit
Doll, BMJ 2004
34 439 Brittish male physicians, 1951-2001
Treatment of COPD
ipratropium bromid, (SAMA) MDI, 4 x
3-6 ( 60-120 µg ) puff
+ β2 agonist (SABA) MDI
4 x 2-4 puff ( 200-400 µg )
+ LAMA (tiotropium) DPI, 1x1
LABA (salmeterol, formoterol) 2x1
or
(indacaterol, olodaterol) 1x1
ICS/LABA
+ retard theophyllin tabl.
300-900 mg ( Se- level 8-12 µg/ml )
antibiotics(5-10 days) + corticosteroid
exacerbation
(32 mg methylprednisolon, 10-14
days)
fluticason/salmet
erol
or
budesonid/formot
erol
Treatment of COPD
Surgical treatment ?
(GOLD 2006)
longterm oxigen treatment
(chronic respiratoryy failure)
inhalative corticosteroids
(  3 exacerbation in the previous 3 years)
One or more long acting bronchodilators,
rehabilitation
Short acting anticholinergic and/or 2-agonist as needed
Avoidance of risk factors, influenza
FEV1  80%
without
50%  FEV1 < 80%
or
vaccination
30%  FEV1 < 50%
with symptoms
FEV1 < 30%
or
chronic respiratory or
right heart failure
airway obstruction (FEV1/FVC < 70%)
I. mild
II. moderate
III. severe
IV. very severe
Longterm oxygen in COPD
NOTT: Ann Intern Med, 1980
BMC: Lancet, 1981
the only treatment which
prolongs life in hypoxic COPD
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
Respiratory insufficiency in COPD
acute exacerbation
pink puffer
partial
(hypoxaemic/transfer failure)
blue bloater
global
(pump-, ventilatory failure)
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
1./ acute tracheobronchitis
atipical agent
2./ Chronic bronchitis
without comorbidity
treatment
?
H. influenzae
M. catarrhalis
res. S. pneumoniae ?
( FEV1 > 50% )
3./ Chronic bronchitis with
comorbidity ( FEV1 < 50% )
„
res. Pneumococcus !
4./ Chronic bronchial infection
„
Gram-neg enterobact.
macrolide ?
aminopenicillin/cv
cefalo. II, III
makrolide II.
„
respiratory kinolon
respiratory kinolon
Ps. eruginosa
= ciprofloxacin
Non-invasive mechanical ventilation in
respiratory insufficiency