1. COPD Chronic Obstructive Pulmonary Disease
Dr.dr.Tahan P.H., SpP., DTCE., MARS
Penyakit Dalam FK-UWKS

2. Introduction
Chronic 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

3. Worldwide Prevalence of COPD
Male/1000
Female/1000 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
Speaker Notes
In the Global Burden of Disease Study, conducted under the auspices of the WHO and the World Bank, the worldwide prevalence of COPD in 1990 was 9.34/1,000 men and 7.33/1,000 women. However, these estimates include all ages and underestimate the true prevalence of COPD in older adults.
The prevalence of COPD is highest in countries where cigarette smoking has been, or still is, very common. The prevalence is lowest in countries where smoking is less common, or total tobacco consumption is low.
Until recently, virtually all population-based studies in developed countries showed a markedly greater prevalence of COPD in men compared with women. Gender-related differences in exposure to risk factors, mostly cigarette smoking, probably explain this pattern. Recent results from the US indicate that death from COPD in women now exceeds that in men.
This study represents the most recent global overview of the prevalence of COPD, and has paved the way for country-specific and global updates.
Reference
From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2005.
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.

4. COPD Misdiagnosis Is Common in Women
Shows the misdiagnosis of COPD symptoms as asthma is increasingly common in women.
COPD Misdiagnosis Is Common in Women
Hypothetical Male Patient With
COPD Symptoms
Diagnosed as COPD by
65% of physicians
65%
Speaker Notes
Misdiagnosis of COPD symptoms as asthma is increasingly common in women.
A recent survey of primary care physicians confirmed the frequent misdiagnosis of COPD in women.
The survey analysed the diagnostic approach of physicians to a hypothetical ex-smoker suffering from breathlessness and uncomfortable breathing upon exertion. The sex of the hypothetical patient varied.
When the patient was male, almost two thirds (64.6%) of physicians considered COPD to be the most likely diagnosis. When the patient was female, fewer than half (49.0%) considered COPD to be the most likely diagnosis. COPD symptoms in women were most commonly misdiagnosed as asthma.
Reference
Chapman KR, Tashkin DP, Pye DJ. Gender bias in the diagnosis of COPD. Chest. 2001;119:
49%
Hypothetical Female Patient With COPD Symptoms
Diagnosed as COPD by
49% of physicians
Diagnosis, Misdiagnosis, Prevalence, Sex
COPD symptoms in women were most commonly misdiagnosed as asthma
Chapman KR, et al. Chest. 2001;119:

5. COPD Is an Increasingly Common Cause of Death Worldwide
Includes projections of the global burden of disease which indicate that COPD was the number 5 cause of death in 2002 and that it will rise to number 4 by 2030.
COPD Is an Increasingly Common Cause of Death Worldwide
Cause of Death
Rank in 2002
Rank in 2030
Ischaemic heart disease 1
Cerebrovascular disease 2
Lower respiratory infections 3 5
HIV/AIDS 4
COPD
Perinatal conditions 6 9
Diarrhoeal diseases 7 16
Tuberculosis 8 23
Trachea, bronchus, lung cancers
Road traffic accidents 10
Speaker Notes
Projections of the global burden of disease indicate that COPD was the number 5 cause of death in 2002 and that it will rise to number 4 by 2030.
It is estimated that COPD will result in 7.8% of all deaths by 2030.
Reference
Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to PLoS Med. 2006;3:
Mortality, Worldwide
Mathers CD, et al. PLoS Med. 2006;3:

6. 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

7. COPD is caused by inhalation of noxious substances

8. Mucociliary Apparatus

9. COPD has pulmonary and systemic components
Inhaled substances +
Genetic susceptibility
Airway limitation
Systemic
inflammation
Speaker notes
GOLD states that COPD has pulmonary and extra-pulmonary, or systemic, components, which arise from a mixture of inhalation of noxious substances and genetic susceptibility.1
In the lungs, exposure to noxious substances causes inflammation of the airways, mucociliary dysfunction (overproduction of mucus and reduced ability to clear mucus from the lungs) and structural changes (such as degradation of elastin). These factors result in airway limitation.
COPD has a variable natural history that affects all patients differently, and a patient may exhibit symptoms of bronchitis, emphysema or both.1
The type of damage to the lungs determines the symptoms of COPD. COPD caused primarily by obstructive bronchiolitis can be associated with chronic coughing and/or sputum production, while lung damage caused primarily by emphysema is characterised by hyperinflation of the lungs and wheezing.
Systemic inflammation in COPD is associated with development of many co-morbidities, such as cardiovascular disease, diabetes and osteoporosis. A recent study reported that among approximately 70,000 patients hospitalised for COPD exacerbations in 2007, over half had hypertension, one-third had diabetes or ischaemic heart disease and one-quarter had congestive heart failure.2
References
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of COPD
Silver H, Blanchette CM, Roberts M, et al. Prevalence of comorbidities in patients hospitalised for COPD exacerbations and impact on inpatient mortality and hospital expenditures. Am J Respir Crit Care Med 2010;181:A5943.
Airway inflammation
Mucociliary dysfunction
Structural changes
Breathlessness
Bronchitis: coughing, sputum production
Emphysema: hyperinflation, wheezing
Weight changes
Co-morbidities (e.g. diabetes, cardiovascular disease)
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10. What is the role of inflammation in COPD?

11. COPD Is a Disease Characterised by Inflammation
Cigarette smoke
This slide illustrates that COPD is a complex disease with many inflammatory pathways that initiate and potentiate the disease process.
Epithelial cells
Speaker Notes
This slide illustrates that COPD is a complex disease with many inflammatory pathways that initiate and potentiate the disease process.
Neutrophils, macrophages and CD8+ T-lymphocytes are the key inflammatory cell types involved in COPD.
Airway inflammation in COPD is characterised by a neutrophilic inflammation with increased numbers of macrophages and CD8+ T-lymphocytes. These cells release the reactive oxygen species (ROS), chemokines (e.g. interleukin [IL]-8), cytokines (e.g. tumor necrosis factor [TNF]-) and proteases (e.g. neutrophil elastase and matrix metalloproteinase) that are instrumental in producing a chronic inflammatory state.
The ongoing inflammatory process leads to enlargement of the alveolar spaces, fibrosis, destruction of the lung parenchyma, loss of elasticity and small airways obstruction (obstructive bronchiolitis). Mucus hypersecretion is a prominent feature of COPD. In contrast to asthma, airway hyper-responsiveness is not a routinely present feature of COPD.
References
Barnes PJ. Mechanisms in COPD. Differences from asthma. Chest. 2000;117;(Suppl 2): 10S-14S.
Barnes PJ. COPD: is there light at the end of the tunnel? Curr Opin Pharmacol. 2004;4:
Barnes PJ, Hansel TT. Prospects for new drugs for chronic obstructive pulmonary disease. Lancet. 2004;364:
Monocyte
Macrophage/Dendritic cell
Neutrophil
Proteases
Fibroblast
CD8+, Cigarette, Emphysema, Epithelial, Macrophage, Monocyte, Mucus, Neutrophil
CD8+ Tc cell
Fibrosis
Obstructive bronchiolitis
Mucus hypersecretion
Emphysema

12. Chronic Inflammation plays a central role in COPD
Smoke
Pollutants
Neutrophils
CD8+ T-lymphocytes
Macrophages
Key inflammatory cells
Inflammation
Speaker notes
Chronic inflammation of the airways, lung tissue and pulmonary blood vessels results from exposure to inhaled irritants such as tobacco smoke and other pollutants.
Inflammation of the airways is present from the onset of COPD1 and increases with disease severity.1,2
Inflammatory cells accumulate in the lung tissue and trigger an inflammatory cascade that results in airflow limitation and systemic inflammation outside the lung.
In COPD, these cells include neutrophils, CD8+ T-lymphocytes, and macrophages.1,3 They release inflammatory mediators such as tumour necrosis factor-α (TNFα), matrix-metalloproteinases (MMP-9), and interleukins (IL-1, IL-6, IL-8).3,4
An acute COPD exacerbation represents a further amplification of the inflammation that is present in the stable state 5,6
References
Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:
Saetta M. Airway inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160:S17-S20.
Barnes PJ, Hansel TT. Prospects for new drugs for Chronic Obstructive Pulmonary Disease. Lancet 2004;364:
Barnes PJ. Chemokines in COPD. In: Stockley RA, Rennard SI, Rabe K, Celli B, editors. Chronic Obstructive Pulmonary Disease. Oxford, England: Blackwell Publishing; 2007:860.
Papi A, Bellettato CM, Braccioni F, et al. Infections and Airway Inflammation in Chronic Obstructive Pulmonary Disease Severe Exacerbations. Am J Respir Crit Care Med 2006;173:1114–1121
Perera W, Hurst JR, Wilkinson TM, et al. Inflammatory changes, recovery and recurrence at COPD exacerbation. Eur Respir J 2007;29:
Chronic inflammation
Structural changes
Systemic inflammation
Bronchoconstriction,
oedema, mucus,
emphysema
Acute exacerbation
Airflow limitation
Adapted from Barnes PJ, in Stockley, et al (editors), Chronic Obstructive Pulmonary Disease. Oxford, England: Blackwell Publishing; 2007:860.
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13. COPD inflammation is different from asthma inflammation
Neutrophils
CD8+ T-lymphocytes
Macrophages
Noxious agent
Not fully reversible
Asthma
Eosinophils
CD4+ T-lymphocytes
Mast cells
Reversible
Sensitising agent
Onset
Inflammatory cells
Speaker notes
Although COPD and asthma are both respiratory diseases characterised by underlying inflammation, the nature of the inflammatory cascade is different in each disease.
COPD-specific inflammation is characterised by increased activity of neutrophils, CD8+ T-lymphocytes and macrophages. The airflow limitation is not fully reversible.
In asthma, airflow limitation is often reversible, either spontaneously or with treatment, and is characterised by a different profile of inflammatory cells that includes eosinophils and CD4+ T-lymphocytes.
Structurally, both the airways and lung parenchyma are affected by COPD and airflow limitation is progressive. In asthma, only the airways are affected.
Patients with COPD are typically 40 years or older and have a history of smoking. Asthma typically begins during childhood and is not associated with smoking.
Establishing the correct diagnosis of COPD ensures that patients can be given appropriate anti-smoking and lifestyle advice, treatments and prognosis.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of COPD
Airflow limitation
From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Available from:
NYC/DAXAS/10/012

14. Airway Inflammation occurs from COPD onset and increases with disease severity
Airways with measurable cells (%)
Neutrophils
Macrophages
CD8+ cells
Speaker notes
Chronic inflammation is present from the onset of COPD1 and increases with disease severity.1,2
Inflammation may persist long after the patient stops smoking.1,3
References
Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:
Saetta M. Airway inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160:S17-S20.
Gamble E, Grootendorst DC, Hattotuwa K, et al. Airway mucosal inflammation in COPD is similar in smokers and ex-smokers: a pooled analysis. Eur Respir J 2007;30:
GOLD stage I
GOLD stage II dan III
GOLD stage IV
Adapted from Hogg JC et al, 2004.
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15. How is COPD diagnosed and managed?
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16. COPD is diagnosed based on symptoms, risk factors and spirometry
Cough
Sputum production
Shortness of breath
RISK FACTORS
Tobacco
Occupational hazards
Indoor/outdoor pollution +
Speaker notes
Spirometry is recommended at the time of diagnosis to assess the presence and severity of airflow limitation.1,2
A diagnosis of COPD should be considered in any patient who has cough, sputum production, or dyspnoea and/or a history of exposure to risk factors.1
References
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of COPD
Celli BR, MacNee W, ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004;23:
Spirometry
From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Available from:
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17. Classification of cough
Cough is classified into acute and chronic
and
Clinically subdivided into productive and dry cough.
Productive cough
is present at an expectoration rate of
30 ml/24 hours,

18. 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

19. Acute Cough ... < 3 weeks URTI : Sinusitis viral / bacterial
Differential Diagnosis
URTI : Sinusitis viral / bacterial
URTI triggering exacerbations of Chronic Lung Disease eg Asthma; COPD
Pneumonia
Left Ventricular Heart Failure
Foreign Body Aspiration

20. INITIAL ASSESSMENT OF SEVERITY OF ACUTE ASTHMA IN ADULTS
SYMPTOMS
MILD
MODERATE
SEVERE AND LIFE-THREATENING
Physical Exhaustion 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

21. Goals of COPD management
Relieve symptoms
Improve exercise tolerance
Improve health status
Prevent and treat exacerbations
Prevent disease progression
Prevent and treat complications
Reduce mortality
Improve current control
Speaker notes
GOLD’s Global strategy for the diagnosis, management, and prevention of COPD proposes four major components of COPD management:
Assess and monitor disease
Reduce risk factors
Manage stable COPD
Manage exacerbations
These components encompass the seven goals of COPD management.
Patients should be diagnosed as early in the course of disease wherever possible.
GOLD recommends a range of non-pharmacological and pharmacological treatments to help achieve these goals. Progressive introduction of new treatments is recommended to prevent further deterioration of lung function.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of COPD
Reduce future risks
Adapted from the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Available from:
NYC/DAXAS/10/012

22. Continued smoking leads to rapid decline of FEV1
Smoked regularly and susceptible to its effects
Never smoked or not susceptible to smoke
Stopped at 45
Stopped at 65
Disability
Death
FEV1 (% of value at age 25) 25 50 75
Age (years)
100
Speaker notes
Stopping smoking is the single most effective way of slowing the decline in lung function in patients at all stages of COPD.1
This is true for all patients who are at risk, from those with no current symptoms to those with severe disease.
Patients who continue to smoke will lose lung function at a rapid rate whereas those who stop smoking will deteriorate more slowly.
However, lost lung function cannot be regained and chronic inflammation may persist for many years after the patient stops smoking.2-4
Other non-pharmacologic treatments for COPD include pulmonary rehabilitation, oxygen therapy and, for very severe disease, lung volume reduction surgery.
References
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of COPD
Fletcher C and Peto R. The natural history of chronic airflow obstruction. BMJ 1977;
Hogg J. Why does airway inflammation persist after the smoking stops. Thorax 2006;61:96-97.
Gamble E, Grootendorst DC, Hattotuwa K, et al. Airway mucosal inflammation in COPD is similar in smokers and ex-smokers: a pooled analysis. Eur Respir J 2007;30:
Adapted from Fletcher C and Peto R , 1977. 22
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23. What are exacerbations ?
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24. What are exacerbations?
Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines an exacerbation as:
“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
Speaker notes
This definition of COPD comes from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. This document is widely accepted as the most up-to-date guidance on COPD management.1
The major symptoms of exacerbations are increased breathlessness, increased cough and/or sputum, and changes in colour and/or tenacity of sputum.2
Exacerbations may be classified based on symptoms or on the type of medication used to treat the exacerbation.3 Patients may take several weeks to recover from more severe exacerbations.4
Exacerbations are commonly associated with bacterial and/or viral infections of the airways and worsening air pollution.1
Exacerbations are associated with increased levels of inflammatory markers, such as IL-6, in the airways and systemic circulation.5-8
References
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of COPD
Donaldson GC and Wedzicha JA. COPD exacerbations: Epidemiology. Thorax 2006;61:
Pauwels R, Calverley P, Buist AS, et al. COPD exacerbations: the importance of a standard definition. Respir Med 2004;98:
Seemungal TA, Donaldson GC, Bhowmilk A, et al. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;161:
Papi A, Bellettato CM, Braccioni F, et al. Infections and airway inflammation in Chronic Obstructive Pulmonary Disease severe exacerbations. Am J Respir Crit Care Med 2006;173:1114–1121.
Hurst JR, Perera WR, Wilkinson TM, et al. Systemic and upper and lower airway inflammation at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;173:71-78.
Wedzicha JA and Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet. 2007;370:
Perera W, Hurst JR, Wilkinson TM, et al. Inflammatory changes, recovery and recurrence at COPD exacerbation. Eur Respir J 2007;29:

25. frequent exacerbations drive disease progression
Patients with frequent exacerbations
Lower quality of life
Increased mortality
rate
Speaker notes
Some patients with COPD are susceptible to frequent exacerbations.1,2 Cohort studies have reported evidence of a phenotypic exacerbator,3 and other studies have reported differences in exacerbation rate despite similar FEV1 levels.4
While exacerbation frequency is linked to disease severity, it is important to consider that not only patients with severe COPD are frequent exacerbators.2
Exacerbations are associated with increased inflammation, which persists after the attack and affects the length of recovery period.5 In addition, patients who suffer from frequent exacerbations have increased airway inflammation in the stable state.6
Frequent exacerbators display worse quality of life,1,7 faster decline in lung function,1,2,7 and higher mortality rates than patients with less frequent exacerbations.1,2,8,9
Managing exacerbations, including reducing their frequency and severity, is a major goal of COPD disease management in the GOLD Global strategy for the diagnosis, management, and prevention of COPD.10
References
Wedzicha JA and Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet. 2007;370:
Donaldson GC and Wedzicha JA. COPD exacerbations: Epidemiology. Thorax 2006;61:
Seemungal TAR, Hurst JR and Wedzicha JA. Exacerbation rate, health status and mortality in COPD – a review of potential interventions. Int J COPD 2009;4:
Kim V, Han MK, Vance GB, et al. Chronic bronchitic symptoms are associated with worse symptoms and greater exacerbation frequency in COPD. Am J Respir Crit Care Med 2010;181:A1533.
Perera W, Hurst JR, Wilkinson TM, et al. Inflammatory changes, recovery and recurrence at COPD exacerbation. Eur Respir J 2007;29:
Bhowmilk A, Seemungal TA, Sapsford RJ, et al. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations. Thorax 2000;55:
Decramer M, Celli B, Kesten S et al. Frequency of exacerbations adversely impacts the course of COPD. Am J Respir Crit Care Med 2010;181:A1526.
Soler-Cataluna JJ, Martinez-Garcia MÁ, Román Sánchez P, et al. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 2005;60:
Groenewegen KH, Schols AMWJ, Wouters EFM. Mortality and mortality-related factors after hospitalization for acute exacerbation of COPD. Chest 2003;124:
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of COPD
Increased
inflammation
Increased risk of recurrent exacerbations
Faster disease progression
Increased likelihood of hospitalisation
Adapted from Wedzicha JA et al, 2007; Donaldson GC et al, 2006.
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26. Number of exacerbations per patient per year
Cough and sputum production indicate an increased risk of exacerbations
Number of exacerbations
Chronic inflammation
Number of exacerbations per patient per year 1 2 3
Patients WITH chronic cough and sputum
Patients WITHOUT chronic cough and sputum
p<0.0001
Speaker notes
The symptoms of COPD vary between individual patients. Many patients with COPD suffer from symptoms associated with chronic bronchitis, including chronic cough and/or sputum production.
Recent studies have showed that patients with chronic cough and sputum have more than twice the number of exacerbations compared with patients without these symptoms.1,2
Among 2,500 patients in the COPDGene Study, those with symptoms of chronic bronchitis had significantly more frequent and more severe exacerbations than patients without these symptoms, even though both groups had similar FEV1 levels.2
Symptoms of chronic cough and sputum are also associated with steep lung function decline3 and increased mortality.4,5
References
Burgel PR, Nesme-Meyer P, Chanez P, et al. Cough and sputum production are associated with frequent exacerbations and hospitalizations in COPD subjects. Chest 2009;135:
Kim V, Han MK, Vance GB, et al. Chronic bronchitic symptoms are associated with worse symptoms and greater exacerbation frequency in COPD. Am J Respir Crit Care Med 2010;181:A1533.
Vestbo J, Prescott E and Lange P. Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. Am J Respir Crit Care Med 1996;153:1530–1535 .
Ekberg-Aronsson M, Pehrsson K, Nilsson J-A, et al. Mortality in GOLD stages of COPD and its dependence on symptoms of chronic bronchitis. Respir Res 2005;6:98.
Guerra S, Sherrill DL, Venker C, et al. Chronic bronchitis before age 50 years predicts incident airflow limitation and mortality risk. Thorax 2009;64:
Chronic cough and sputum
Frequent exacerbations
Adapted from Burgel PR et al, 2009.
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27. 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
Speaker notes
The rate of moderate to severe exacerbations was measured in the Daxas® phase 3 clinical studies.1,2
This ‘event-based’ classification of exacerbations defines the severity of each exacerbation according to the change in medication needed.3
This type of classification does not capture exacerbations that do not require a change in medications, but is more useful in clinical studies than alternative approaches that use patients’ symptoms to define exacerbation severity.
Reference
Calverley PMA, Rabe KF, Goehring UM, et al. Roflumilast in symptomatic chronic obstructive disease: two randomised clinical trials. Lancet 2009;374:
Fabbri LM, Calverley PMA, Izquierdo-Alonso JL, et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Lancet 2009;374:
Pauwels R, Calverley P, Buist AS, et al. COPD exacerbations: the importance of a standard definition. Respir Med 2004;98:
Calverley PMA et al, Fabbri L,et al, 2009. 27
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28. Pulmonary and Systemic Inflammation in Exacerbations
TRIGGERS
Viruses
Pollutants
Bacteria
Inflamed
COPD airways
Speaker Notes
COPD exacerbations are associated with increased upper and lower airway and systemic inflammation. The airway inflammatory responses cause oedema, bronchospasm, and increased sputum production, leading to worsening airflow limitation and development of dynamic hyperinflation, which is a main cause of dyspnoea, the most common symptom of an exacerbation.
Systemic inflammation increases at exacerbation and although the causes of this response in COPD are not clear, there is probably a spill-over of inflammatory markers from the lungs.
Reference
Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet. 2007;370:
Greater airway
inflammation
EFFECTS
Bronchoconstriction
oedema, mucus
Systemic
inflammation
Expiratory flow
limitation
Cardiovascular
comorbidity
Exacerbation
symptoms
Dynamic
hyperinflation
Reprinted from The Lancet, 370, Wedzicha JA, Seemungal TA, COPD exacerbations: defining their cause and prevention, , Copyright 2007, with permission from Elsevier. 28

29. FACTORS PRECIPITATING ACUTE FAILURE
Sputum retention
Bronchospasm
Infection
Pneumothorax
Large bullae
Uncontrolled O2 - administration
Pulmonary embolism
Left-ventricular failure
End-stage disease

30. 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

31. DYSPNOEA AIR-FLOW OBSTRUCTION PROLONGED EXPIRATION
PATHO-PHYSIOLOGY….contd
AIR-FLOW OBSTRUCTION
PROLONGED EXPIRATION
PULMONARY HYPERINFLATION
DUE TO AIR-TRAPPING
INCREASED WORK OF BREATHING
DYSPNOEA

32. LOSS OF HYPOXIA CAUSING CAPILLARY BED PULMONARY
PATH-PHYSIO…..CONTD
ALVEOLAR DISTORTION
AND DESTRUCTION
LOSS OF HYPOXIA CAUSING
CAPILLARY BED PULMONARY
VASOCONSTRICTION
PULMONARY HYPERTENSION
SECONDARY VASCULAR CHANGES
COR-PULMONALE

33. Pharmacological treatments should be added stepwise as copd progresses
Add long-term oxygen if chronic respiratory failure Consider surgical procedures
Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation
Active reduction of risk factor(s); influenza vaccination
Add short-acting bronchodilator (when needed)
Stage III: Severe
Stage IV: Very Severe
Stage II: Moderate
Stage I: Mild
FEV1/FVC<0.70
FEV1 ≥80% predicted
50% FEV1 <80% predicted
30% FEV1 <50% predicted
FEV1 <30% predicted or FEV1 <50% predicted plus chronic respiratory failure
Speaker notes
GOLD identifies four stages of COPD severity, each defined by the FEV1 measurement obtained using spirometry, and requiring a different approach to disease management.1 In practice, disease severity is assessed by overall symptomology, including the frequency and severity of exacerbations.
During Stage I (‘Mild’), treatment with a short-acting bronchodilator (SABA), given as needed, is sufficient for relief of persistent or worsening symptoms.
As COPD progresses, (Stage II, ‘Moderate’) the addition of regular treatment with a long-acting bronchodilator is recommended.
In the later stages of COPD (Stages III and IV, ‘Severe’ to ‘Very severe’), regular combination treatment with an long-acting bronchodilator/inhaled glucocorticosteroid combination is recommended for patients with a post-bronchodilator FEV1 <50% predicted normal and a history of repeated exacerbations.1
These recommendations were put forward by GOLD to achieve the seven goals of COPD management,1 but in reality, some of the goals remain unmet − patients with COPD continue to suffer from poor health status, exacerbations, disease progression and increased mortality despite receiving recommended treatments.
None of the pharmacological agents recommended by GOLD target the systemic inflammation underlying COPD.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of COPD
Add inhaled glucocorticosteroids if repeated exacerbations
From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Available from:
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34. MANAGEMENT – NONINVASIVE
# BRONCHODILATORS
ROUTINELY GIVEN
HELP RESIDUAL BRONCHODILATION
AND MUCO-CILIARY CLEARANCE
[ I.V.AMINOPHYLLINE / B2-AGONIST / IPRATROPIUM ]
…CONTD

35. 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

36. 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

37. 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

38. Bronchoscopic Lung Volume Reduction for Emphysema
The Concept of lung Volume Reduction
• Lung volume Reduction
– 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 improvement
2. – Applicable in heterogeneous emphysema (upper
lobe predominant)
• Multiple retrospective and prospective studies
reported success with surgical lung volume reduction

39. 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

40. 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

41. Inflammation is increased during exacerbations
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

42. Non-pharmacological management of COPD includes smoking cessation
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

43. The Downward Spiral in COPD
Lung inflammation
Mucous hypersecretion
Airway obstruction
Exacerbation
Continued smoking
Impaired mucous clearance
Speaker Notes
COPD is a progressive disease in which patients experience pulmonary inflammation, mucus hypersecretion, airway obstruction, and exacerbations. This cycle continues ultimately leading to disability and death.
Reference
From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Available from:
Exacerbation
Submucousal gland hypertrophy
Alveolar destruction
Exacerbation
Hypoxaemia
DEATH
From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Available from:

44. THANK-YOU