COPD 2

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12/14/2012 Amr Badreldlin Hamdy MD FCCP 1

COPD:

COPD Introduction 12/14/2012 amr badreldin hamdy MD FCCP 2

Prof Pulmonary Medicine:

Prof Pulmonary Medicine Amr Badreldin Hamdy MD FCCP 12/14/2012 amr badreldin hamdy MD FCCP 3

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Banha Faculty of Medicine Egypt 12/14/2012 amr badreldin hamdy MD FCCP 4

Pulmonary Consultant:

Pulmonary Consultant Ibn Nafees Medical Centre Abu Dhabi 12/14/2012 amr badreldin hamdy MD FCCP 5

Objectives:

Objectives Definition Prevalence. Pathophysiology . Economic burden . 12/14/2012 amr badreldin hamdy MD FCCP 6

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“Make everything as simple as possible, but not one bit simpler” Einstein

COPD also known as::

COPD also known as: Chronic airflow limitation Chronic obstructive lung disease. Chronic airflow limitation. 12/14/2012 amr badreldin hamdy MD FCCP 8

Definition:

Definition 12/14/2012 amr badreldin hamdy MD FCCP 9

Definition of COPD:

Definition of COPD

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Definition of a disease is the description of the clinical features that distinguish individuals who have the disease from those who do not . 12/14/2012 amr badreldin hamdy MD FCCP 11

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Diagnostic criteria are clinical features of a disease that have been proven to distinguish the disease from other diseases that manifest similarly. 12/14/2012 amr badreldin hamdy MD FCCP 12

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COPD , which represents a mixture of pathologic processes, should not be defined based on symptoms because it is non specific, nor should it be based on a pathologic definition because this is impractical in clinical practice. 12/14/2012 amr badreldin hamdy MD FCCP 13

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It is a preventable and treatable disease with some significant extra-pulmonary effects that may contribute to the severity in individual patients. 12/14/2012 amr badreldin hamdy MD FCCP 15

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Its pulmonary component is characterized by airflow limitation that is not fully reversible. 12/14/2012 amr badreldin hamdy MD FCCP 16

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COPD is not fully reversible : the obstruction noted does not revert either in response to bronchodilators, anti-inflammatory treatment, or spontaneously. 12/14/2012 amr badreldin hamdy MD FCCP 17

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The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. 12/14/2012 amr badreldin hamdy MD FCCP 18

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The airflow limitation or obstruction that happens in COPD is caused by a mixture of small airway, parenchyma destruction (emphysema), and in many cases, increased airways responsiveness (asthma). 12/14/2012 amr badreldin hamdy MD FCCP 19

Mechanisms of Airflow Limitation in COPD (Peripheral Airways):

Mechanisms of Airflow Limitation in COPD ( Peripheral Airways ) Adapted from: Barnes P. NEJM 2000; 343; 269

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The extra-pulmonary effects are seen frequently and some of these other diseases are probably related to the respiratory disorder. 12/14/2012 amr badreldin hamdy MD FCCP 22

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These include muscle wasting , cardiovascular disease, depression , reduced fat free mass, osteopenia , and chronic infections . 12/14/2012 amr badreldin hamdy MD FCCP 23

COPD is a Preventable Disease:

COPD is a P reventable Disease Primary, secondary, and tertiary prevention strategies exist for COPD. 12/14/2012 amr badreldin hamdy MD FCCP 24

Primary Prevention:

Primary Prevention Increasing smoking cessation . Adequate treatment of asthma . 12/14/2012 amr badreldin hamdy MD FCCP 25

Secondary Prevention:

Secondary Prevention Early detection of disease. Subsequent modification of risk factor exposure. 12/14/2012 amr badreldin hamdy MD FCCP 26

Tertiary Prevention:

Tertiary Prevention Prevention of complications in patients with established disease. 12/14/2012 amr badreldin hamdy MD FCCP 27

Types of COPD:

Types of COPD 12/14/2012 amr badreldin hamdy MD FCCP 28

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Chronic bronchitis. Emphysema. Asthma 12/14/2012 amr badreldin hamdy MD FCCP 29

Prevalence & Mortality:

Prevalence & Mortality 12/14/2012 amr badreldin hamdy MD FCCP 30

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The conflicts among published COPD prevalence rates may be due to many factors, including true differences in disease occurrence , differences in defining COPD , cultural biases, and whether spirometry was used to confirm the diagnosis. 12/14/2012 amr badreldin hamdy MD FCCP 31

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The method by which prevalence is estimated (i.e. expert opinion, patient-reported diagnosis, symptom based, or spirometry based) seems to influence reported prevalence. 12/14/2012 amr badreldin hamdy MD FCCP 32

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Lack of agreement on the definition of COPD is another source of variation in prevalence estimates. 12/14/2012 amr badreldin hamdy MD FCCP 33

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After decades of a relative lack of interest in the disease, there is increased realization that we are in the midst of an epidemic , with a major impact on the health care resources. 12/14/2012 amr badreldin hamdy MD FCCP 34

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It is widely under-diagnosed in the primary care setting. Under-diagnosis is one of the major barriers to more effective treatment of COPD . 12/14/2012 amr badreldin hamdy MD FCCP 35

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( 36 of 44) 54–86% Undiagnosed/misdiagnosed Diagnosed COPD 2.4 – 7 million Estimated total COPD 15.3 – 17.1 million Only A Small Proportion Of COPD Cases Are Diagnosed in the US Stang P et al. Chest 2000; 117: 354S –9S

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The most likely cause of under diagnosis is that disabling COPD symptoms do not appear until the disease is well advanced and pulmonary function significantly impaired. 12/14/2012 amr badreldin hamdy MD FCCP 37

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It is estimated that 210 million have COPD world wide. Mortality from COPD is currently the fourth leading cause of mortality world wide, accounting for more than three million deaths per year. 12/14/2012 amr badreldin hamdy MD FCCP 38

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COPD Prevalence Relative To Other Diseases COPD is : The 4th leading cause of morbidity and mortality 1 The 2nd leading cause of disability 2 The 6th in prevalence of major chronic conditions: 12.6 million 1,3 1 Rabe KF, et al. Am J Respir Crit Care Med 2007;176:532 – 55; 2 Agency for Healthcare Research and Quality ( US HHS). Improving health care for Americans with disabilities. AHRQ Pub. No.02-M016. March 2002; 3 Lethbridge-Çejku M, et al. NHIS 2004 Vital Health Stat. 10(228), 2006. ( 39 of 44)

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COPD is the only leading cause of death that is increasing in prevalence worldwide. 12/14/2012 amr badreldin hamdy MD FCCP 40

World Wide Mortality 1990-2030:

World Wide Mortality 1990-2030 12/14/2012 amr badreldin hamdy MD FCCP 41

COPD is the only one of the major causes of death that has increased significantly in recent years:

COPD is the only one of the major causes of death that has increased significantly in recent years 3.0 Percentage change in age-adjusted death rates in USA, from 1965 to 1998 1.0 2.0 0 Proportion of 1965 rate 2.5 1.5 0.5 Coronary heart disease Stroke Other CVD COPD All other causes –59% –64% –35% +163% –7% CVD = cerebrovascular disease www.copdgold.com

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By 2030 , COPD is predicted to become the third leading cause of death world wide. 12/14/2012 amr badreldin hamdy MD FCCP 43

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COPD mortality is expected to more than double over the next 20 years, so that by 2030, it will be responsible for 10% of the world’s total mortality ( currently 7% ), accounting for 7 million deaths annually. 12/14/2012 amr badreldin hamdy MD FCCP 44

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The World Health Organization (WHO) projected that in 2005 chronic respiratory disease would be the third leading cause of deaths from chronic disease, worldwide Adapted from: World Health Organization. Preventing c hronic diseases: a vital investment. (2005) Available at: http://www.who.int/chp/chronic_disease_report/contents/en/index.html ; Accessed June 2009. ( 45 of 44) Chronic Respiratory Disease Is A Leading Cause Of Chronic Disease Deaths, Worldwide

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These figures probably underestimate the global impact of COPD on overall mortality, because COPD contributes significantly to other major causes of mortality, such as IHD , stroke , and lung cancer. 12/14/2012 amr badreldin hamdy MD FCCP 46

Natural History of COPD:

Natural History of COPD 12/14/2012 amr badreldin hamdy MD FCCP 47

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COPD has a variable natural history, and individuals with this disease may not follow the same disease course. 12/14/2012 amr badreldin hamdy MD FCCP 48

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12/14/2012 amr badreldin hamdy MD FCCP 49

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It is generally a slowly progressive disease, particularly if there is continued exposure to noxious agents (e.g. tobacco, indoor/ outdoor pollution). 12/14/2012 amr badreldin hamdy MD FCCP 50

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There is a long asymptomatic period during which individuals can lose up to 50% of their lung function prior to presenting with clinical symptoms. 12/14/2012 amr badreldin hamdy MD FCCP 51

Natural History of Chronic Bronchitis:

Natural History of Chronic Bronchitis Smokers cough . Chronic cough + exacerbations of sputum production. Progressive SOB with more frequent exacerbations. 12/14/2012 amr badreldin hamdy MD FCCP 52

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Chronic respiratory failure; hypoxemia, hypercarbia , polycythemia , cyanosis, cor pulmonale . Acute on chronic respiratory failure. 12/14/2012 amr badreldin hamdy MD FCCP 53

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Early diagnosis of COPD is important because appropriate management can prevent and decrease symptoms (especially dyspnea), reduce the frequency and severity of exacerbations, improve health status, improve exercise capacity, and prolong survival. 12/14/2012 amr badreldin hamdy MD FCCP 54

Pathogenesis:

Pathogenesis 12/14/2012 amr badreldin hamdy MD FCCP 55

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The pathobiology of COPD encompasses multiple injurious processes including : 12/14/2012 amr badreldin hamdy MD FCCP 56

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Inflammation ( excessive or inappropriate innate or adaptive immunity). Cellular apoptosis . Altered cellular and molecular alveolar maintenance program. 12/14/2012 amr badreldin hamdy MD FCCP 57

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Abnormal cell repair . Extracellular matrix destruction (protease and anti-protease imbalance) Oxidative stress (oxidant and antioxidant imbalance). 12/14/2012 amr badreldin hamdy MD FCCP 58

Pathophysiological features of COPD:

Pathophysiological features of COPD Mucus hypersecretion Reduced mucociliary transport Mucosal damage Increased numbers of inflammatory cells/activation Elevated inflammatory mediators: IL-8, TNF- a , LTB-4 and oxidants Protease/anti-protease imbalance Goblet cell hyperplasia/ metaplasia Mucous gland hypertrophy Increased smooth muscle mass Airway fibrosis Alveolar destruction Poor nutritional status Reduced BMI Impaired skeletal muscle weakness wasting Loss of alveolar attachments Loss of elastic recoil Increased smooth muscle contraction IL = interleukin LTB-4 = leukotriene B4 TNF- α = tumour necrosis factor- α

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12/14/2012 amr badreldin hamdy MD FCCP 61

Burden of COPD:

Burden of COPD 12/14/2012 amr badreldin hamdy MD FCCP 62

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COPD is rapidly becoming a global public health crises, with around 3 million people predicted to die from the disease in 2006. 12/14/2012 amr badreldin hamdy MD FCCP 63

The burden of disability from COPD is projected to increase Change in the rank order of DALYs:

Lower respiratory infection Diarrhoeal diseases Unipolar depressive disorders Ischaemic heart disease HIV/AIDS Cerebrovascular disease Prematurity/low birth weight Birth asphyxia/trauma Road traffic accidents Neonatal infections and other 13th The burden of disability from COPD is projected to increase Change in the rank order of DALYs 12/14/2012 Amr Badreldlin Hamdy MD FCCP 64 Hearing loss, adult onset Refractive errors Diabetes mellitus 5th 2004 2030 DALYs = Disability Adjusted Life Years WHO 2008 COPD

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Costs increase with severity. 12/14/2012 amr badreldin hamdy MD FCCP 65

COPD Economic Burden:

COPD Economic Burden 12/14/2012 Amr Badreldlin Hamdy MD FCCP 66

Direct and Indirect Annual Costs* for a Patient Aged >40 Years with COPD:

Direct and Indirect Annual Costs * for a Patient Aged >40 Years with COPD * Direct costs: hospitalisations, healthcare use, medication; Indirect costs: lost productivity. Source: Wouters EFM. Respir Med 2003;97(suppl C): s3–s14. Canada CAD 3,195 ($ 3,020) (€ 2,044) USA $ 5,646 (€ 3,798) UK £ 1,639 ($ 2,729) (€ 1,826) Spain € 3,538 ($ 5,296) The Netherlands € 1,608 ($ 2,407) France € 1,608 ($ 2,407) Italy € 1,308 ($ 1,958)

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The increasing global burden of COPD is not only in terms of mortality, but also its prevalence , morbidity and economic cost. 12/14/2012 amr badreldin hamdy MD FCCP 68

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COPD causes physical impairment, debility , reduced quality of life, and death . 12/14/2012 amr badreldin hamdy MD FCCP 69

COPD: Impact on Quality of Life:

Quality of Life Exacerbations Dyspnea, Cough Airflow Limitation Loss of Independence Decreased Exercise Capacity Burden of Medical Care Social Isolation, Depression, Anxiety Insomnia, Fatigue COPD: Impact on Quality of Life

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It causes high resource utilization, which includes frequent clinical office visits, frequent hospitalizations due to acute exacerbations , and chronic therapy. 12/14/2012 amr badreldin hamdy MD FCCP 71

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Patients with COPD typically have co-morbid diseases, such as muscle wasting, cardiovascular disease, depression, reduced fat-free mass, osteopenia , and chronic infections. 12/14/2012 amr badreldin hamdy MD FCCP 72

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These disorders contribute to a high disease burden and early mortality in patients with COPD . 12/14/2012 amr badreldin hamdy MD FCCP 74

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Deaths in individuals with COPD are frequently attributed to a cause other than COPD . 12/14/2012 amr badreldin hamdy MD FCCP 75

Risk Factors for COPD:

Risk Factors for COPD 12/14/2012 amr badreldin hamdy MD FCCP 76

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Risk for COPD is related to an interaction between genetic factors and many different environmental exposures. 12/14/2012 amr badreldin hamdy MD FCCP 77

Tobacco Smoke:

Tobacco Smoke Smoking is recognized as the most important causative factor for COPD , with an individual’s susceptibility being a continuous, rather than a categorical characteristic that can interact synergistically with other risk factors. 12/14/2012 amr badreldin hamdy MD FCCP 78

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The WHO estimates that in high-income countries, 73% of COPD mortality is related to smoking. In low and middle income nations, it is 40%. 12/14/2012 amr badreldin hamdy MD FCCP 79

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Lately a much higher proportion of smokers – perhaps as much as 50% - have been noted to develop COPD . If smokers continue to smoke lifelong, they have at least a one in two chance to develop COPD . 12/14/2012 amr badreldin hamdy MD FCCP 80

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Cigarette smoking accounts for about 80% to 90% of COPD cases. 12/14/2012 amr badreldin hamdy MD FCCP 81

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The prevalence of prior prenatal ETS exposure was higher among adults with COPD than in those without the disease. 12/14/2012 amr badreldin hamdy MD FCCP 82

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The prevalence of any subsequent lifetime home or workplace ETS exposure is higher among those with COPD than among those without COPD . 12/14/2012 amr badreldin hamdy MD FCCP 83

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On the other hand, the risk of developing COPD falls by about half with smoking cessation. 12/14/2012 amr badreldin hamdy MD FCCP 84

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Genetic influence may enhance an individual’s susceptibility to the detrimental effects of cigarette smoke . 12/14/2012 amr badreldin hamdy MD FCCP 85

How does cigarette smoke work?:

How does cigarette smoke work? Decrease cilia activity. Possible loss of ciliated cells. Abnormal dilatation of the distal airway space. Alveolar wall destruction. 12/14/2012 amr badreldin hamdy MD FCCP 86

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CO decreases oxygen carry capacity and impairs psychomotor performance and judgment. 12/14/2012 amr badreldin hamdy MD FCCP 87

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Cellular hyperplasia , with production of mucus, reduction of airway diameter, and increased difficulty in clearing secretions. 12/14/2012 amr badreldin hamdy MD FCCP 88

Wayne McLaren…Former Marlboro Man:

Wayne McLaren …Former Marlboro Man Age 30…a robust young man Age 51…riding into the sunset

Genetic Factors:

Genetic Factors The best known genetic factor linked to COPD is a deficiency of the serine protease alpha-1 antitrypsin , which arises in 1-3% of patients with COPD . 12/14/2012 amr badreldin hamdy MD FCCP 91

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Several genes have been implicated in COPD , including those coding transforming growth factor beta1 , tumor necrosis factor alpha , and microsomal epoxide hydrolase 1 . 12/14/2012 amr badreldin hamdy MD FCCP 93

Occupational Dust, Vapors, Fumes:

Occupational Dust, Vapors, Fumes People who reported a diagnosis of COPD or chronic bronchitis were twice as likely to recall previous worksite exposures to gases, dusts, vapors, or fumes. 12/14/2012 amr badreldin hamdy MD FCCP 94

Indoor Air Pollutants:

Indoor Air Pollutants Globally, the most important risk factor for development of COPD might be exposure to biomass fuels such as coal, straw, animal dung crop residues. 12/14/2012 amr badreldin hamdy MD FCCP 95

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WHO estimates that, in countries of low and middle income, 35% of people with COPD develop COPD after exposure to indoor smoke from biomass fuels. 12/14/2012 amr badreldin hamdy MD FCCP 96

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The use of biomass fuel, such as wood for cooking, increases the risk of COPD by 3 to 4 times. 12/14/2012 amr badreldin hamdy MD FCCP 97

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COPD prevalence in never-smoking women may be two to three times higher in a rural area where women are exposed to biomass smoke compared with urban women without this exposure (Chinese study). 12/14/2012 amr badreldin hamdy MD FCCP 98

Outdoor Pollutants:

Outdoor Pollutants The risk attributable to outdoor pollutants in development of COPD is much smaller than that for indoor air pollutant. 12/14/2012 amr badreldin hamdy MD FCCP 99

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Air pollution is also linked to lower respiratory infections and acute cardiopulmonary events, which are important in both development and progression of COPD . 12/14/2012 amr badreldin hamdy MD FCCP 100

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WHO estimates that urban air pollution causes 1% of COPD in high-income countries and 2% in nations of low and middle income. 12/14/2012 amr badreldin hamdy MD FCCP 101

Aging:

Aging COPD prevalence, morbidity, and mortality increases with age. One reason for the increasing prevalence of COPD in recent years is the changing demographic of the world’s population. 12/14/2012 amr badreldin hamdy MD FCCP 102

Gender:

Gender COPD has been far more frequent in men than in women, related to patterns of smoking and occupational exposures. 12/14/2012 amr badreldin hamdy MD FCCP 106

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Recently COPD prevalence seems to be becoming equal in men and women from high-income countries in which smoking habits are similar between both sexes. 12/14/2012 amr badreldin hamdy MD FCCP 107

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Women are more susceptible to development of COPD than men. 12/14/2012 amr badreldin hamdy MD FCCP 108

Increased prevalence in women:

Increased prevalence in women 30 50 70 0 40 60 1980 2000 1982 1984 1986 1988 1990 1992 1994 1996 1998 Male Female 20 10 Mortality rates per 100,000 USA 1980–2000 Mannino et al. MMWR 2002 Kazerouni et al. J Women’s Health 2004

The Changing Face Of COPD In The US:

The Changing Face Of COPD In The US Younger More Women In 2004, women accounted for ~63% of all self-reported COPD cases 1 2000: First year that more women died from COPD than men 2 1 Lethbridge-Çejku M, et al. NHIS 2004. Vital Health Stat. 10(228), 2006; 2 CDC. Facts About Chronic Obstructive Pulmonary Disease. August 2003. ( 110 of 19)

Asthma:

Asthma There is a large overlap of up to 30% between people who have a clinical diagnosis of COPD and asthma. 12/14/2012 amr badreldin hamdy MD FCCP 111

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Increased bronchial responsiveness , a hallmark of asthma, leads to development of COPD . 12/14/2012 amr badreldin hamdy MD FCCP 112

Socioeconomic Factors:

Socioeconomic Factors Poor populations tend to have a higher risk of developing COPD and its complications than their wealthier counterparts. 12/14/2012 amr badreldin hamdy MD FCCP 113

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However, poverty is regarded as a surrogate measure for many factors that subsequently increase the risk of COPD , such as poor nutritional status , crowding , exposure to pollutants including high work exposures and high smoking rates, poor access to health care , and early respiratory infections . 12/14/2012 amr badreldin hamdy MD FCCP 114

Pathophysiology:

Pathophysiology 12/14/2012 amr badreldin hamdy MD FCCP 115

The Real Story:

The Real Story

Pathophysiology Simplified:

Pathophysiology Simplified Bad Genes Breathe Noxious Crap COPD

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Dr Manuel Cosio Pathology of COPD (Peripheral Lung) FEV 1 / FVC < 70% Normal COPD Alveolar wall Bronchiole Loss of attachments EMPHYSEMA Smooth muscle constriction Fibrosis Inflammation CHRONIC OBSTRUCTIVE SMALL AIRWAY DISEASE

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Cigarette smoke (and other irritants) PROTEASES Neutrophil elastase Cathepsins MMPs Alveolar wall destruction (Emphysema) Mucus hypersecretion CD8 + lymphocyte Alveolar macrophage Epithelial cells Fibrosis (Obstructive bronchiolitis) Fibroblast Monocyte Neutrophil Chemotactic factors Inflammatory Cells Involved in COPD Source : Peter J. Barnes, MD ( Chronic bronchitis )

Conclusion:

Conclusion 12/14/2012 amr badreldin hamdy MD FCCP 120

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Summary of Risk Factors for COPD Lung growth and development Oxidative stress Gender Age Respiratory infections Socioeconomic status Nutrition Comorbidities Genes Exposure to particles Tobacco smoke Occupational dusts, organic and inorganic Indoor air pollution from heating and cooking with biomass in poorly ventilated dwellings Outdoor air pollution

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What Are The Issues Concerning COPD In Primary Care? COPD places a growing burden on primary care COPD has a variable natural history – not all patients are the same Understanding the course and severity of the disease Recognising the symptoms of COPD Differentiating COPD from other respiratory disease Preserving quality of life in patients with no obvious symptoms ( 122 of 44)

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Why Should COPD Be A Major Focus For PCPs ? PCPs are usually the first to encounter a COPD patient COPD patients will become a greater clinical and financial burden in primary care 1 Earlier diagnosis and intervention has been shown to have a positive effect on patient outcomes 2 Recent treatment advances : make treatment more convenient and patient friendly can improve quality of life may impact the clinical course of the disease Accurate and earlier diagnosis in primary care is the key to optimal treatment, management and outcome 1.NHLBI. COPD Essentials for Physicians. COPD Learn More Breathe Better; 2.Coultas DB et al. Am J Respir Crit Care Med 2001;164:372-377. ( 123 of 44)

References:

References 12/14/2012 amr badreldin hamdy MD FCCP 124

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Hanania NA & Sharafkhaneh A: COPD. Human press (2011). Stockley RA et al: COPD. Blackwell (2007). Howes TQ: Clinicians Guide to COPD. Hodder Arnold (2005). Rochester CL. Clinics in Chest Medicine, 28 (2007). 12/14/2012 amr badreldin hamdy MD FCCP 125

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Currie GP: ABC of COPD. BMJ. ATS Documents. Am J Respir Crit Care Med 182:693 (2008). 12/14/2012 amr badreldin hamdy MD FCCP 126

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