This document provides an overview of COPD (chronic obstructive pulmonary disease). It defines COPD and discusses its burden, risk factors, pathology, and history. It notes that COPD is characterized by airflow limitation caused by an inflammatory response in the lungs to noxious particles. The document outlines the learning objectives which are to understand COPD definition, burden, risk factors, and pathogenesis. It also discusses the prevalence of COPD internationally, underdiagnosis in the US, and the economic and social burden of the disease.
Chronic Obstructive Pulmonary Disease BY
Dr Akram Yousuf
Resident Internal Medicine
Liaquat University of Medical Health and Sciences Jamshoro Pakistan
Chronic Obstructive Pulmonary Disease BY
Dr Akram Yousuf
Resident Internal Medicine
Liaquat University of Medical Health and Sciences Jamshoro Pakistan
New technology called Electromagnetic Navigation Bronchoscopy® (ENB) that uses virtual bronchoscopy and real time 3-dimensional CT images that enable me to localize these peripheral lung nodules for diagnosis and treatment. This outpatient procedure is minimally invasive and therefore has a small risk of pneumothorax (2-3%) and its published diagnostic yield rates range from 67% - 86%
Lecture slides about bronchiectasis with contents including definition, causes, pathogenesis and pathology, and how to make diagnosis. Treatment for bronchiectasis is presented separately.
Dynamic Central Airway Obstruction: Tracheomalacia, Tracheobronchomalacia, An...Bassel Ericsoussi, MD
Dynamic Central Airway Obstruction: Tracheomalacia, Tracheobronchomalacia, And Excessive Dynamic Airway Collapse: Classification, Diagnosis, and Treatment
Practical approach to interstitial lung diseases Hamdi Turkey
These lecture notes were prepared by Dr. Hamdi Turkey- Pulmonologist- Department of internal medicine - Taiz university
Do Not Forget To Visit Our Pages On Facebook on the following Links:
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An approach to Interstitial Lung Disease / Diffuse Parenchymal Lung DiseaseThomas Kurian
YouTube link: https://youtu.be/gPr31qrivUc
An approach to Diffuse Parenchymal Lung disease / Interstitial Lung disease with emphasis on the idiopathic causes.
Tiêu chuẩn chẩn đoán và điều trị copd của ats 1995
CTMT Quốc gia phòng chống bệnh phổi tắc nghẽn mạn tính và hen phế quản http://benhphoitacnghen.com.vn/
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New technology called Electromagnetic Navigation Bronchoscopy® (ENB) that uses virtual bronchoscopy and real time 3-dimensional CT images that enable me to localize these peripheral lung nodules for diagnosis and treatment. This outpatient procedure is minimally invasive and therefore has a small risk of pneumothorax (2-3%) and its published diagnostic yield rates range from 67% - 86%
Lecture slides about bronchiectasis with contents including definition, causes, pathogenesis and pathology, and how to make diagnosis. Treatment for bronchiectasis is presented separately.
Dynamic Central Airway Obstruction: Tracheomalacia, Tracheobronchomalacia, An...Bassel Ericsoussi, MD
Dynamic Central Airway Obstruction: Tracheomalacia, Tracheobronchomalacia, And Excessive Dynamic Airway Collapse: Classification, Diagnosis, and Treatment
Practical approach to interstitial lung diseases Hamdi Turkey
These lecture notes were prepared by Dr. Hamdi Turkey- Pulmonologist- Department of internal medicine - Taiz university
Do Not Forget To Visit Our Pages On Facebook on the following Links:
https://www.facebook.com/groups/569435236444761/
AND
https://www.facebook.com/groups/690331650977113/
An approach to Interstitial Lung Disease / Diffuse Parenchymal Lung DiseaseThomas Kurian
YouTube link: https://youtu.be/gPr31qrivUc
An approach to Diffuse Parenchymal Lung disease / Interstitial Lung disease with emphasis on the idiopathic causes.
Tiêu chuẩn chẩn đoán và điều trị copd của ats 1995
CTMT Quốc gia phòng chống bệnh phổi tắc nghẽn mạn tính và hen phế quản http://benhphoitacnghen.com.vn/
Chuyên trang bệnh hô hấp mãn tính: http://benhkhotho.vn/
the scenario given at the start of ppt z nt interstitial lung diseases... its a similar diseases to it.... diagnose it urself to differniate it and hv better command over diffferntial diagnosis.
Oxygen Therapy is not Beneficial in COPD Patients with Moderate HypoxaemiaGamal Agmy
A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation
The Long-Term Oxygen Treatment Trial Research Group*
N Engl J Med. 2016 October 27; 375(17): 1617–1627
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
2. COPD
Gamal Rabie Agmy, MD,FCCP Professor of Chest Diseases, Assiut university
3.
4. Goal of this learning modules
•To Provide a framework to make informed decisions regarding the diagnosis and treatment of Chronic obstructive pulmonary disease
5. Learning objectives
After completing this module you should know:
•know the definition of COPD
•Understand the burden of COPD
•know the risk factors of COPD occurrence
•Learn about the pathology, pathogenesis and Pathophysiology of COPD.
6. History of COPD
•A British medical textbook (1860s )→ C/P of chronic bronchitis as an advanced disease with repeated bronchial infections that ended in right-sided heart failure.
•20th century, Ciba symposium of 1958 proposed definitions of chronic bronchitis and emphysema → concept of airflow obstruction.
•Chronic bronchitis: chronic productive cough for 3 months during each of 2 consecutive years (other causes of cough being excluded).
•Emphysema: an abnormal, permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis
7. Definition & Overview Common preventable & treatable disease Characterized by persistent airflow limitation that is usually progressive Associated with an enhanced chronic inflammatory response in the airways & the lung to noxious particles or gases Exacerbations & comorbidities contribute to the overall severity in individual patients
8. COPD is a progressive disease The Downward Spiral in COPD
9. Burden of COPD COPD is a leading cause of morbidity & mortality worldwide The burden will increase in coming decades due to continued exposure to risk factors & the aging of the world’s population COPD is associated with significant economic burden
10. Prevalence Buist AS, McBurnie MA, Vollmer WM, et al. International variation in the prevalence of COPD (the BOLD Study): a population- based prevalence study. Lancet. 2007;370:741-750. 11.8% 8.5% 10.1% overall
11. COPD Misdiagnosis Is Common in Women
Chapman KR, Tashkin DP, Pye DJ. Gender bias in the diagnosis of COPD. Chest. 2001;119:1691-1695
12. Under diagnosis of COPD in the United States
• Over 12 million people in the United
States have been diagnosed with
COPD; another 12 million are
estimated to be undiagnosed1
• Data from NHANES III indicate that
approximately 24 million US adults
have evidence of impaired lung
function indicative of COPD2,3
• Most (70%) of patients with
undiagnosed COPD are <65 years
70%
<Age 65
30%
≥Age
65
Percent With Undiagnosed COPD
1. NHLBI; available at http://www.nhlbi.nih.gov/health/public/lung/copd/index.html. 3. Mannino DM, et al. Proc Am Thorac Soc. 2007;4:502-306
2. Mannino DM, et al. MMWR Surveill Summ. 2002;51:1-16.
13. Mortality :
Global burden of Disease study: COPD rank Murray and Lopez Lancet 1997
15. Mortality :
Global burden of Disease study
•Almost 90% of COPD deaths occur in low- and middle-income countries.
16. Economic and social burden
Economic
•USA: Direct costs $ 29.5 billion & Indirect costs $ 20.4 billion
•Europe: 38.6 billion Euros
•In developing countries:
–Workplace & home productivity loss > Medical costs loss
Social
•Disability-Adjusted Life year (DALY)
–1990→ 12th leading cause of DALYs
–2030 → 7th leading cause of DALYs
17. Risk factors for COPD Influence disease development & progression
18. Genes
•Gene-environmental interaction are the key for development of COPD.
•Susceptibility to COPD is not dichotomous variable and a range of susceptibility exits.
–Some smokers develop the disease earlier than others.
–Progression in COPD is very heterogeneous
19. Genes
•In patients with COPD
–emphysema represents accelerated ageing of the lung
–studies showed telomere shortening & dysfunction
•Telomerase null mice with short telomeres
–increased emphysema
–double-strand DNA breaks
•after exposure to chronic cigarette smoke
•with evidence of reduced epithelial repair
•Family with a telomerase mutation
–have early-onset emphysema
21. Airway Responsiveness-Dutch Hypothesis
•Increased airways responsiveness and allergy are clinical phenotypes that predict increased susceptibility to cigarette smoke.
•Methacholine and histamine responsiveness precedes and predicts accelerated decline in lung function, thus a risk factor for COPD.*
•Increased airways responsiveness noted among 1st degree relatives of patients with early onset COPD.^
*Silva, GE et al. Asthma as a risk factor for COPD in a longitudinal study. Chest 2004; 126:59.
^Celedon JC et al. Bronchodilator responsiveness and serum total IgE levels in families of probands with severe early-onset COPD. Eur Respir J 1999; 14:1009.
23. These data are communicated for scientific purpose only. Confidential slide set
23
Apoptotic Pathways in COPD
Demedts IK, et al. Respir Res. 2006;7:53. Reproduced with permission from Biomed Central.
Survival factor
Granzyme B
Perforin
TNF-α
sFasL
cytoplasm
nucleus
ER Stress
Apoptosome
Apaf 1
Procasp-9
Procasp-9
Casp-9
Casp-8
CAD
CAD
ICAD
Casp-8
Procasp-8
Procasp-8
FADD
Bid
tBid
Bax
Bak
Cyt C
ER stress
DNA fragmentation
1
2
4
3
5
?
Fas
COPD Pathogenesis
24. These data are communicated for scientific purpose only. Confidential slide set
25. These data are communicated for scientific purpose only. Confidential slide set
25
Angiogenesis in COPD
Reprinted from International Journal of COPD, 2, Siafakas NM, et al., Role of angiogenesis and vascular remodeling in chronic obstructive pulmonary disease, 453-462, Copyright 2007, with permission from Dove Medical Press Ltd.
extravasated plasma proteins
Inflammatory cells (Mac, Neu, Epith, Lymph)
Release of angiogenic mediators
Fibrinogen products
Inflammation
Tissue hypoxia
Airway fibrosis
Mechanical Injury
Increased blood flow
Vessel growth Angiogenesis Vascular remodeling
Up-regulation of Angiogenic factors
Shear stress on the endothelium
COPD Pathogenesis
26. These data are communicated for scientific purpose only. Confidential slide set
Angiogenic and Angiostatic Factors in COPD
•Angiogenic CXC Chemokines, CC Chemokines, and Growth Factors:
–CXCL1
–CXCL5
–CXCL8
–CCL2
–VEGF
–bFGF
–Angiopoietin-1
–HGF
–EGF
• Angiostatic CXC Chemokines, CC Chemokines, and Growth Factors:
–CXCL10
Siafakas NM, et al. Int J Chron Obstruct Pulmon Dis. 2007;2:453-462.
COPD Pathogenesis
28. These data are communicated for scientific purpose only. Confidential slide set
Inflammatory Cells in Stable COPD
Gamal Agmy 2-5-2014
Inflammation in COPD
29. These data are communicated for scientific purpose only. Confidential slide set
29
Neutrophils in COPD
Mucous hypersecretion
Serine proteases
Neutrophil Elastase
Cathepsin G
Proteinase-3
O2-
MPO
LTB4, IL-8, GRO-
LTB4, IL-8
Adapted from Barnes PJ. N Engl J Med. 2000; 343: 269-280
Adapted from Barnes PJ, et al. Eur Respir J. 2003; 22: 672-688
Emphysema
Severe emphysema
Images courtesy R Buhl.
Inflammation in COPD
32. These data are communicated for scientific purpose only. Confidential slide set
32
Reduction in Neutrophil Apoptosis in COPD
Adapted from Brown V, et al. Respir Res. 2009;10:24.
Apoptotic neutrophils (arrows)
*P<0.05
*P<0.01
Morphology
Tunel
NS
HS
COPD
60
50
40
30
20
10
0
Apoptotic neutrophils [%]
Image courtesy of R Buhl.
NS: nonsmoking controls (n=9) HS: healthy smoking controls (n=9)
TUNEL: the terminal transferase- mediated dUTP nick end-labeling method
Inflammation in COPD
34. These data are communicated for scientific purpose only. Confidential slide set
34
Inflammatory Mediators in COPD – Summary
Cell
Neutrophils
Macrophages
T-cell
Epithelial cell
IL-8, TGF- 1, IP-10, Mig, I-TAC, LTB4, GRO- , MCP-1, MMP-9
Granzyme B, perforins, IFN-, TNF-
IL-8, IL-6, TGF-1 TGF-, IP-10, Mig, I-TAC, LTB4, GRO-, MCP-1, ROS, MMP-9
Serine proteases, TNF-, ROS, IL-8, MPO, LTB4
Selected Mediators
Barnes PJ, et al. Eur Respir J. 2003;22:672-888.
Inflammation in COPD
35. These data are communicated for scientific purpose only. Confidential slide set
35
Examples of Chemotactic Factors in COPD
Barnes PJ. Curr Opin Pharmacol. 2004;4:263-272.
Hill AT, et al. Am J Respir Crit Care Med. 1999;160: 893-898.
Montuschi P, et al. Thorax. 2003;58:585-588.
MCP-1
GRO-
Elastin fragments
LTB4
IL-8
GRO-
Elastin fragments
IP-10
Mig
I-TAC
Neutrophil
Monocyte
T-cell
Inflammation in COPD
36. These data are communicated for scientific purpose only. Confidential slide set
36
TNF- Has Pro-inflammatory Actions in COPD
Mukhopadhyay S, et al. Respir Res. 2006;7:125. Reproduced with permission from Biomed Central.
Oxidative stress
Activation of NF-B and AP-1
Activation of proinflammatory molecules e.g. VCAM-1, ICAM-1 and RAGE
Subcellular ROS production
TNF-
Antioxidants
e.g. GSH, Catalase
Scavenge free radicals,
detoxify cellular
hydrogen peroxide and
inhibit ROS generation
Proinflammation
+
+
+
+
+
+
+
-
-
Inflammation in COPD
37. These data are communicated for scientific purpose only. Confidential slide set
Modulation of Inflammation by Histone Deacetylase (HDAC)
Inflammation in COPD
Gamal Agmy 2-5-2014
39. These data are communicated for scientific purpose only. Confidential slide set
39
Pulmonary HDAC Levels Decrease With COPD Severity
Adapted from Ito K, et al. N Engl J Med. 2005;352:1967-1976.
S = COPD Stage
0
.5
1.0
1.5
2.0
Non- smoker
N=11
P<0.001
HDAC2 expression (vs. lamin A/C)
P=0.04
P<0.001
P<0.001
S4
N=6
S0
N=9
S1
N=10
S2
N=10
■
■
■
■
■
Inflammation in COPD
40. These data are communicated for scientific purpose only. Confidential slide set
Inflammation Leads to Small Airway Narrowing
•Acute and chronic inflammation suspected to contribute to COPD- related small airway narrowing
•Airway narrowing leads to airway obstruction
•Narrowing results from several factors:
–Collagen deposition and increased lymphoid follicles in outer airway wall
–Mucosal thickening of airway lumen
–Inflammatory exudate in airway lumen
Barnes PJ, et al. Eur Respir J. 2003;22: 672-688.
Inflammation in COPD
42. These data are communicated for scientific purpose only. Confidential slide set
42
Exacerbations of Chronic Bronchitis and Inflammatory Cell Types
Saetta M, et al. Am J Respir Crit Care Med. 1994;150:1646-1652. Maestrelli P, et al. Am J Respir Crit Care Med. 1995;152:1926-1931.
Barnes PJ. N Engl J Med. 2000;343:269-280.
COPD Exacerbation
Eosinophils
Eosinophils
T-Cells
Neutrophils
Cells Predominant in:
Induced sputum
Biopsy
Neutrophils
Inflammation in COPD
43. These data are communicated for scientific purpose only. Confidential slide set
43
Clinical Impact of Inflammation in COPD
Tsoumakidou M, et al. Respir Res. 2006;7:80. Reproduced with permission from Biomed Central.
Increased Airway Inflammation
Increased mucous production
Airway wall thickening
Airway wall oedema
Bronchoconstriction
Airway narrowing
V’/Q’ Mismatching
Hyperinflation
Worsening of gas exchange
Increased work of breathing
Increased oxygen consumption –
Decreased mixed venous oxygen
Cough, sputum, dyspnoea, Respiratory failure
Inflammation in COPD
44. These data are communicated for scientific purpose only. Confidential slide set
44
Inflammation: Clinical Consequences
Systemic
•Nutritional abnormalities and weight loss
•Hypoxaemia
•Skeletal muscle dysfunction
•Cardiovascular disease
•Depression
•Osteoporosis
•Anaemia
Agusti AG, et al. Eur Respir J. 2003;21:347-360.
Agusti AG. Proc Am Thorac. 2006;3:478-483.
Barnes PJ, Cell BR. Eur Respir J. 2009;33:1165-1185.
Pulmonary
Dyspnoea
Cough
Sputum production
Exacerbations
Inflammation in COPD
47. The site of pathology in COPD
Mucus gland hyperplasiaGoblet cellhyperplasiaMucus hypersecretionNeutrophilsin sputumSquamousmetaplasiaof epithelium↑MacrophagesNo basement membrane thickeningLittle increase inairway smooth muscle↑CD8+lymphocytesChanges in Large Airways of COPD PatientsChanges Patients Source: Peter J. Barnes, MD
49. The site of pathology in COPD
Disrupted alveolar attachmentsInflammatory exudatein lumenPeribronchialfibrosisLymphoid follicleThickened wall with inflammatory cells-macrophages, CD8+ cells, fibroblastsChanges in Small Airways in COPD Patients Source: Peter J. Barnes, MD
50. The site of pathology in COPD Endothelial dysfunctionIntimalhyperplasiaSmooth muscle hyperplasia↑Inflammatory cells(macrophages, CD8+lymphocytes) Changes in Pulmonary Arteries in COPD Patients Source: Peter J. Barnes, MD
53. Emphysema
•Centriacinar
–Focal destruction limited to the respiratory bronchioles and the central portions of the acini.
–associated with cigarette smoking
–most severe in the upper lobes
•Panacinar
–involves the entire alveolus distal to the terminal bronchiole.
–most severe in the lower lung zones
–AAT deficiency
•Distal acinar or paraseptal
–least common form and involves distal airway structures, alveolar ducts, and sacs.
loss of alveolar walls and dilatation of airspaces in emphysema
54. Natural History of Emphysema
•In non-smokers, maximal lung function
–attained at age 15 - 25 years
–after a variable plateau phase, declines ~ 20 -25 mL/year
•Lung Health Study (large longitudinal study)
–smoking is associated with an accelerated decline in lung function
•Females are at higher risk of lung damage
–related to smoke exposure than males
55. Fletcher C et al. 1977
FEV1 (% of value at age 25)
100
25
50 75 Never smoked or not susceptible to smoke Age (years)
Disability
Smoked regularly and susceptible to its effects
Death
0
25 50 75 Stopped at 65
Stopped at 45 Classical View of “Disease Progression” & “Disease Modification”