COPD Chronic Obstructive Pulmonary Disease Dr.dr.Tahan P.H., SpP., DTCE., MARS Penyakit Dalam FK-UWKS 15-06-12
Dec 21, 2015
COPD Chronic Obstructive Pulmonary
Disease
Dr.dr.Tahan P.H., SpP., DTCE., MARSPenyakit Dalam FK-UWKS
15-06-12
IntroductionChronic Obstructive Pulmonary Disease (COPD) is one of the top five causes of global mortality
COPD affects 210 million people worldwide and causes 3 million deaths annually (5% of all deaths worldwide)1
It is predicted to become the third leading cause of global mortality by 20302
The economic burden of COPD is high, with costs increasing as the disease progresses
- Costs associated with severe COPD are up to 17 times higher than those associated with mild COPD3
- High costs are associated with treatment of exacerbations, such as hospitalisation3
- Indirect costs include loss of productivity in the workplace owing to symptoms3
Worldwide Prevalence of COPD
Adapted from the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2005.
Male/1000
Female/1000
0 2 4 6 8 10 12
Former Socialist economies
Established market economies
India
Sub-Saharan Africa
Latin America and Caribbean
Middle Eastern Crescent
Other Asia and islands
Chapman KR, et al. Chest. 2001;119:1691-1695.
Hypothetical Male Patient With COPD Symptoms
Hypothetical Female Patient With COPD Symptoms
Diagnosed as COPD by 65% of physicians
Diagnosed as COPD by 49% of physicians
65%
49%
COPD symptoms in women were most commonly misdiagnosed as asthma
COPD Misdiagnosis Is Common in Women
Mathers CD, et al. PLoS Med. 2006;3:2011-2030.
COPD Is an Increasingly Common Cause of Death Worldwide
Cause of Death Rank in 2002 Rank in 2030
Ischaemic heart disease 1 1
Cerebrovascular disease 2 2
Lower respiratory infections 3 5
HIV/AIDS 4 3
COPD 5 4
Perinatal conditions 6 9
Diarrhoeal diseases 7 16
Tuberculosis 8 23
Trachea, bronchus, lung cancers 9 6
Road traffic accidents 10 8
What is COPD?Global Initiative for Chronic Obstructive Lung
Disease (GOLD) defines COPD as (2009):“a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with abnormal inflammatory response of the lung to noxious particles or gases”
Key points:- COPD is preventable and treatable- Airway limitation is not fully reversible and is usually
progressive- Extrapulmonary (systemic) effects play a significant
role- Associated with chronic inflammation in response to
inhaled noxious irritants
COPD IS CAUSED BY INHALATION OF NOXIOUS SUBSTANCES
Mucociliary Apparatus
Airway limitation
COPD has pulmonary and systemic components
Airwayinflammation
Structuralchanges
Mucociliarydysfunction
Systemicinflammation
BreathlessnessBronchitis: coughing, sputum production
Emphysema: hyperinflation, wheezing
Weight changesCo-morbidities
(e.g. diabetes, cardiovascular disease)
Inhaled substances +Genetic susceptibility
NYC/DAXAS/10/012
WHAT IS THE ROLE OF INFLAMMATION IN COPD?
COPD Is a Disease Characterised by Inflammation
Cigarette smoke
Epithelial cells
CD8+ Tc cell
Emphysema
Proteases
Mucus hypersecretion
Macrophage/Dendritic cell
NeutrophilMonocyte
Fibroblast
Obstructive bronchiolitis
Fibrosis
Chronic Inflammation plays a central role in COPD
Adapted from Barnes PJ, in Stockley, et al (editors), Chronic Obstructive Pulmonary Disease. Oxford, England: Blackwell Publishing; 2007:860.
Smoke Pollutants
Inflammation
Chronic inflammationStructural changes
Neutrophils
CD8+ T-lymphocytes
Macrophages
Key inflammatory cells
Systemic inflammation
Airflow limitation
Bronchoconstriction, oedema, mucus,
emphysema
Acute exacerbation
NYC/DAXAS/10/012
COPD inflammation is different from asthma inflammation
From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2009. Available from: http://www.goldcopd.org.
AsthmaAsthma
EosinophilsCD4+ T-
lymphocytesMast cells
Reversible
Sensitising agent
Inflammatory cells
COPDCOPD
NeutrophilsCD8+ T-
lymphocytesMacrophages
Noxious agent
Not fully reversible Airflow limitation
Onset
NYC/DAXAS/10/012
Airway Inflammation occurs from COPD onset and increases with disease severity
0
20
40
60
80
100GOLD Stage I
GOLD Stages II and III
GOLD Stage IV
Adapted from Hogg JC et al, 2004.
Airw
ays
with
mea
sura
ble
cells
(%)
Neutrophils Macrophages CD8+ cells
NYC/DAXAS/10/012
GOLD stage I GOLD stage IVGOLD stage II dan III
How is COPD diagnosed and managed?
NYC/DAXAS/10/012
SYMPTOMSCough
Sputum productionShortness of breath
RISK FACTORSTobacco
Occupational hazardsIndoor/outdoor pollution
+
Spirometry
COPD is diagnosed based on symptoms, risk factors and spirometry
From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2009. Available from: http://www.goldcopd.org.NYC/DAXAS/10/012
Classification of cough
• Cough is classified into acute and chronic and• Clinically subdivided into productive and
dry cough.
Productive coughis present at an expectoration
rate of 30 ml/24 hours,
Classification of cough
• Acute cough is defined as one lasting less than three weeks
• Chronic cough is defined as one lasting
greater than eight weeks
Acute Cough ... < 3 weeks
• URTI : Sinusitis viral / bacterial• URTI triggering exacerbations of Chronic
Lung Disease eg Asthma; COPD• Pneumonia • Left Ventricular Heart Failure• Foreign Body Aspiration
Differential Diagnosis
INITIAL ASSESSMENT OF SEVERITY OF ACUTE ASTHMA IN ADULTS
SYMPTOMSMILD MODERATE
SEVERE AND LIFE-THREATENING
Physical Exhaustion No No Yes, may have paradoxical chest wall movement
Pulse rate < 100 / min 100 – 120 / min > 120 / min
Central cyanosis absent May be present Likely to be present
Wheeze intensity variable Moderate Often quiet
Peak expiratory flow(% predicted)
. 75% 50 – 75% < 50 %
Arterial Blood Gas Test not necessary If initial response is poor
Yes
–Relieve symptoms–Improve exercise tolerance–Improve health status
–Prevent and treat exacerbations–Prevent disease progression–Prevent and treat complications–Reduce mortality
Adapted from the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2009. Available from: http://www.goldcopd.org.
GOALS OF COPD MANAGEMENT
Improve current control
Reduce future risks
NYC/DAXAS/10/012
Continued smoking leads to rapid decline of FEV1
Adapted from Fletcher C and Peto R , 1977.
100
Smoked regularly and susceptible to
its effects
Never smoked or not
susceptible to smoke
Stopped at 45
Stopped at 65
Disability
Death
FEV 1 (%
of v
alue
at a
ge 2
5)
25
50
75
0
Age (years)25 50 75
Disability
NYC/DAXAS/10/012
What are exacerbations ?
NYC/DAXAS/10/012
“an event in the natural course of the disease characterized by a change in the patient’s baseline dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset and may warrant a change in regular medication”1
– May be mild, moderate or severe in nature. More severe exacerbations can require hospitalisation and are associated with a prolonged recovery period2
– Commonly caused by bacterial/viral infections of the lungs and airways1
– Associated with increases in markers of inflammation3,4
– Distressing for patients and their loved ones
What are exacerbations?
Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines an exacerbation as:
frequent exacerbations drive disease progression
Patients with frequent exacerbations
Increased risk of recurrent exacerbations
Increased inflammation
Lower quality of life Increased mortality rate
Increased likelihood of hospitalisation
Adapted from Wedzicha JA et al, 2007; Donaldson GC et al, 2006.
Faster disease progression
NYC/DAXAS/10/012
Cough and sputum production indicate an increased risk of exacerbations
– Number of exacerbations
Adapted from Burgel PR et al, 2009.
Frequent exacerbations
Chronic cough and sputum
Chronic inflammation
Num
ber o
f exa
c er b
ation
s pe
r p a
tien t
per
ye a
r
0
1
2
3
Patients WITH chronic cough and
sputum
Patients WITHOUT chronic cough and
sputum
p<0.0001
NYC/DAXAS/10/012
Definitions of Exacerbations
COPD exacerbations were classified in clinical studies as follows:
– ‘Severe’ COPD exacerbation
–Requiring hospitalisation and/or leading to death
– ‘Moderate’ COPD exacerbation
–Initiation of oral or parenteral glucocorticosteroid therapy is required
Calverley PMA et al, 2009. Fabbri L,et al, 2009.NYC/DAXAS/10/012
Pulmonary and Systemic Inflammation in Exacerbations
Systemicinflammation
Bronchoconstrictionoedema, mucus
Expiratory flowlimitation
Cardiovascularcomorbidity
Exacerbationsymptoms
Dynamichyperinflation
InflamedCOPD airways
Greater airwayinflammation
Viruses
BacteriaPollutants
EFFECTS
TRIGGERS
28Reprinted from The Lancet, 370, Wedzicha JA, Seemungal TA, COPD exacerbations: defining their cause and prevention, 786-796, Copyright 2007, with permission from Elsevier.
FACTORS PRECIPITATING ACUTE FAILURE
•Sputum retention•Bronchospasm•Infection•Pneumothorax•Large bullae•Uncontrolled O2 - administration•Pulmonary embolism•Left-ventricular failure•End-stage disease
PATHO- PHYSIOLOGY….
FACTORS AFFECTING AIR-FLOW
• Mucosal edema• Hypertrophy of mucosa• Increased secretions• Increased bronchospasm • incr. Airway tortuosity• More airway turbulance• Loss of lung recoil
PATHO-PHYSIOLOGY….contd
AIR-FLOW OBSTRUCTION
PROLONGED EXPIRATION
PULMONARY HYPERINFLATIONDUE TO AIR-TRAPPING
INCREASED WORK OF BREATHING
DYSPNOEA
PATH-PHYSIO…..CONTD
ALVEOLAR DISTORTIONAND DESTRUCTION
LOSS OF HYPOXIA CAUSING
CAPILLARY BED PULMONARY
VASOCONSTRICTION
PULMONARY HYPERTENSION
SECONDARY VASCULAR CHANGES
COR-PULMONALE
Pharmacological treatments should be added stepwise as copd progresses
From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2009. Available from: http://www.goldcopd.org.
Add long-termoxygen if chronicrespiratory failureConsider surgicalprocedures
Add regular treatment with one or more long-actingbronchodilators (when needed); Add rehabilitation
Active reduction of risk factor(s); influenza vaccinationAdd short-acting bronchodilator (when needed)
Stage III:Severe
Stage IV:Very Severe
Stage II:ModerateStage I:
Mild
FEV1/FVC<0.70
FEV1 ≥80%predicted
FEV1/FVC<0.70
50% FEV1 <80%predicted
FEV1/FVC<0.70
30% FEV1 <50%predicted
FEV1/FVC<0.70
FEV1 <30%predicted orFEV1 <50%predicted pluschronic respiratoryfailure
Add inhaled glucocorticosteroids ifrepeated exacerbations
NYC/DAXAS/10/012
MANAGEMENT – NONINVASIVE
# BRONCHODILATORS
• ROUTINELY GIVEN
• HELP RESIDUAL BRONCHODILATION
AND MUCO-CILIARY CLEARANCE
[ I.V.AMINOPHYLLINE / B2-AGONIST / IPRATROPIUM ]
…CONTD
CONSERVATIVE MANAGEMENT ….contd
# ANTIBIOTICS
# STEROIDS … AVOID IN ARF DUE TO INFECTION
# OTHER
* STEAM / PHYSIOTHERAPY / ENCOURAGE COUGH
* GENERAL HYDRATION
* DIURETICS / LOW DIGOXIN IF LVF
* HEPARIN S /C FOR D V T / PULM EMBOLISM
* NUTRITION
* RESPIRATORY STIMULANTS
MANAGEMENT - NON CONSERVATIVE….
1. INVASIVE TECHNIQUES FOR SPUTUM CLEARANCE
• OROPHARYNGEAL / NASOPHARYNGEAL SUCTION
• NASO-PHARYNGEAL AIR-WAY
• THERAPEUTIC AND DIAGNOSTIC F O B
• MINI TRACHEOSTOMY/ CRICOTHYROTOMY FOR SUCTION
• ENDOTRACHEAL INTUBATION
* FOR BETTER ACCESS
* FOR VENTILATORY SUPPORT
• TRACHEOSTOMY
* IF VERY THICK SECRETIONS
* INTUBATION > SEVEN DAYS
Emphysema• The fourth leading cause of death in the US• 3‐4 million people in the US suffer from emphysema• Current treatment is limited in efficacy
Bronchoscopic Lung VolumeReduction for Emphysema
The Concept of lung Volume Reduction• Lung volume Reduction1. – Removal of the most destroyed hyperinflated poorly perfused areas of the lung can enhance
the function of the remaining “normal” lung and leads to func(onal and symptoma(c improvement2. – Applicable in heterogeneous emphysema (upper lobe predominant)• Multiple retrospective and prospective studies reported success with surgical lung volume reduction
SUMMARY
COPD is a debilitating disease that presents a huge healthcare and economic burden around
the world The major risk factor for developing COPD is tobacco smoking COPD encompasses damage to the airways,
and chronic pulmonary and systemic inflammation
The symptoms of COPD include breathlessness, chronic cough and sputum production
Chronic inflammation in the airways and systemic circulation contributes to the pathology
of COPD COPD-specific inflammation is characterised by increased neutrophils, CD8+ T-lymphocytes and
macrophages, as well as cytokines and other inflammatory mediators
Inflammatory processes activated in asthma are different from COPD-specific inflammation
Chronic inflammation is present from the onset of COPD and increases with disease progression.
Airway inflammation increases during exacerbations
Effective COPD management should include agents that target the chronic inflammation
underlying the disease
Exacerbations are attacks in which symptoms increase beyond daily variations
Patients with frequent exacerbations have a poor prognosis and increased risk of
mortality
Inflammation is increased during exacerbations
The symptoms of chronic cough and sputum production are associated with an increased
risk of exacerbations
Preventing exacerbations is a major goal of COPD management
COPD is diagnosed based on medical history, exposure to risk factors and assessment of lung
function by spirometry
GOLD guidelines recommend seven goals for COPD management, including reducing the
frequency of exacerbations
Non-pharmacological management of COPD includes smoking cessation
GOLD guidelines recommend stepwise addition of pharmacological treatments based on the
severity of COPD
The Downward Spiral in COPDCOPD
Airwayobstruction
Exacerbation
Mucoushypersecretion
Continuedsmoking
Lunginflammation
Alveolardestruction
Impairedmucous clearance
Submucousal glandhypertrophy
Exacerbation
Exacerbation
Hypoxaemia
DEATHFrom the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2008. Available from: http://www.goldcopd.org.
THANK-YOU