Updates in pathophysiology ,phenotypes,PFTs and radiology of COPD

2. Updates in Diagnosis of COPD
Gamal Rabie Agmy, MD,FCCP
Professor of Chest Diseases, Assiut university

3. LUNG INFLAMMATION
COPD PATHOLOGY
Oxidative
stress Proteinases
Repair
mechanisms
Anti-proteinasesAnti-oxidants
Host factors
Amplifying mechanisms
Cigarette smoke
Biomass particles
Particulates
Source: Peter J. Barnes,
MD
Pathogenesis of COPD

4. *Influx of inflammatory cells into
the lung (leading to chronic
inflammation of the airways) .
Respir Res. 2006 Mar 30;7:53.

5. Role of apoptosis in the pathogenesis of COPD
and pulmonary emphysema.
Respir Res. 2006 Mar 30;7:53.
•Recently, an increasing number of data suggest a fourth
important mechanism involved in the development of
COPD: apoptosis of structural cells in the lung might
possibly be an important upstream event in the
pathogenesis of COPD. There is an increase in apoptotic
alveolar epithelial and endothelial cells in the lungs of
COPD patients. Since this is not counterbalanced by an
increase in proliferation of these structural cells, the net
result is destruction of lung tissue and the development
of emphysema.

6. Role of apoptosis in the pathogenesis of COPD
and pulmonary emphysema.
Respir Res. 2006 Mar 30;7:53.
•Data from animal models suggest a role for
Vascular Endothelial Growth Factor (VEGF)
in the induction of apoptosis of structural
cells in the lung. Other mediators of
apoptosis, such as caspase-3 and ceramide,
could be interesting targets to prevent
apoptosis and the development of
emphysema.

7. Hypothesis: Does COPD have an autoimmune
component?
A Agustí1, W MacNee2, K Donaldson2 and M Cosio3
A new hypothesis that considers the role of
the immune system in the pathogenesis of
COPD is explored which, if true, will
generate new therapeutic opportunities in
this condition. [Thorax, 2003]

9. Vascular theory

10. 1010
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

11. Dr.Sarma@works
11
CLINICAL FEATURES

12. Dr.Sarma@works
12
CHRONIC BRONCHITISEMPHYSEMA
1. Mild dyspnea
2. Cough before dyspnea starts
3. Copious, purulent sputum
4. More frequent infections
5. Repeated resp. insufficiency
6. PaCO2 50-60 mmHg
7. PaO2 45-60 mmHg
8. Hematocrit 50-60%
9. DLCO is not that much ↓
10. Cor pulmonale common
1. Severe dyspnea
2. Cough after dyspnea
3. Scant sputum
4. Less frequent infections
5. Terminal RF
6. PaCO2 35-40 mmHg
7. PaO2 65-75 mmHg
8. Hematocrit 35-45%
9. DLCO is decreased
10. Cor pulmonale rare.

13. Dr.Sarma@works
13
CHRONIC BRONCHITISEMPHYSEMA
BLUE BLOTTERPINK PUFFER

14. ALPHA1 ANTITRYPSIN ↓EMPHYSEMA
Specific circumstances of Alpha 1- AT↓include.
• Emphysema in a young individual (< 35)
• Without obvious risk factors (smoking etc)
• Necrotizing panniculitis, Systemic vasculitis
• Anti-neutrophil cytoplasmic antibody (ANCA)
• Cirrhosis of liver, Hepatocellular carcinoma
• Bronchiectasis of undetermined etiology
• Otherwise unexplained liver disease, or a
• Family history of any one of these conditions
• Especially siblings of PI*ZZ individuals.
• Only 2% of COPD is alpha 1- AT ↓

15. Characterization of patients with COPD: GesEPOC
Miravitlles M, et al.
Arch Bronconeumol 2012
Phenotype
Infrequent
exacerbator
ACOS
Exacerbator with
emphysema
Exacerbator with
chronic bronchitis
Treatment strategy* Bronchodilators
Bronchodilators
+ ICS
Bronchodilators
(in some cases + ICS)
Bronchodilators
+ ICS
*Choice of treatment should be based on clinical phenotype and the
intensity determined by severity
ACOS = asthma‒COPD overlap syndrome; GesEPOC = Guía Española de la EPOC
[Spanish Guidelines for COPD]; ICS = inhaled corticosteroid
No Yes
ACOS? ACOS?
No Yes NoYes
Chronic cough?
YesNo
Diagnosis of COPD and ≥2 exacerbations per year?

16. Spanish COPD Phenotypes
 ACOS
 Non frequent exacerbator chronic bronchitis
 Non frequent exacerbator emphysema
 Frequent exacerbator chronic bronchitis
 Frequent exacerbator emphysema

17. © 2014 Global Initiative for Chronic Obstructive Lung Disease
Global Strategy for Diagnosis, Management and Prevention of COPD
Diagnosis of COPD
EXPOSURE TO RISK
FACTORS
tobacco
occupation
indoor/outdoor pollution
SYMPTOMS
shortness of breath
chronic cough
sputum
è
SPIROMETRY: Required to establish diagnosis

18. © 2014 Global Initiative for Chronic Obstructive Lung Disease
Global Strategy for Diagnosis, Management and Prevention of COPD
Diagnosis and Assessment: Key Points
 Spirometry should be performed after the
administration of an adequate dose of a short-
acting inhaled bronchodilator to minimize
variability.
 A post-bronchodilator FEV1/FVC < 0.70 confirms
the presence of airflow limitation.
 Where possible, values should be compared to
age-related normal values to avoid overdiagnosis
of COPD in the elderly.

19. Acceptability
At least three (3) acceptable maneuvers:
• Good start to the test.
• No hesitation or coughing for the 1st second.
• FVC lasts at least 6 seconds with a plateau
of at least 1 second.
• No valsalva maneuver or obstruction of the
mouthpiece.
• FIVC shows apparent maximal effort.

20. Repeatability
Repeatability criteria act as guideline to
determine need for additional efforts.
– Largest and 2nd largest FVC must be within 150
mL.
– Largest and 2nd largest FEV 1 must be 150 mL.
– PEF values may be variable (within 15%).
If three acceptable reproducible maneuvers
are not recorded, up to 8 attempts may be
recorded.

21. Spirometry Value
• Spirometry is typically reported in both
absolute values and as a predicted
percentage of normal.
• Normal values vary and are dependent on:
– Gender,
– Race,
– Age,
– Weight and
– Height.

22. Reporting Standards
• Largest FVC obtained from all acceptable
efforts should be reported.
• Largest FEV1 obtained from all acceptable
trials should be reported.
• May or may not come from largest FVC
effort.
• All other flows, should come from the effort
with the largest sum of FEV 1 & FVC.
• PEF should be the largest value obtained
from at least 3 acceptable maneuvers.

23. Results Reporting Example

24. Pre & Post Bronchodilator Studies: Withholding
Medications

25. Reversibility
Reversibility of airways obstruction can be
assessed with the use of bronchodilators.
• > 12% increase in the FEV1 and 200
ml improvement in FEV1
OR
• > 12% increase in the FVC and 200
ml improvement in FVC.

26. Changes in Lung Volumes in
Various Disease States
Ruppel GL. Manual of Pulmonary Function Testing, 8th ed., Mosby 2003

27. Patterns of Abnormality
Restriction low FEV1 & FVC, high FEV1%FVC
Recorded Predicted SR %Pred
FEV 1 1.49 2.52 -2.0 59
FVC 1.97 3.32 -2.2 59
FEV 1 %FVC 76 74 0.3 103
PEF 8.42 7.19 1.0 117
Obstructive low FEV1 relative to FVC, low PEF, low FEV1%FVC
Recorded Predicted SR %Pred
FEV 1 0.56 3.25 -5.3 17
FVC 1.65 4.04 -3.9 41
FEV 1 %FVC 34 78 -6.1 44
PEF 2.5 8.28 -4.8 30
high PEF early ILD
low PEF late ILD

28. Patterns of Abnormality
Upper Airway Obstruction low PEF relative to FEV1
Recorded Predicted SR %Pred
FEV 1 2.17 2.27 -0.3 96
FVC 2.68 2.70 0.0 99
FEV 1 %FVC 81 76 0.7 106
PEF 2.95 5.99 -3.4 49
FEV 1 /PEF 12.3
Discordant PEF and FEV1
High PEF versus FEV1 = early interstitial lung disease (ILD)
Low PEF versus FEV1 = upper airway obstruction
Concordant PEF and FEV1
Both low in airflow obstruction, myopathy, late ILD

29. Common FVL Shapes
Volume
Flow
Normal Young or quitter Poor effort
Hesitation Knee Coughing

30. Upper Airway Obstruction
0 1 2 3 4 5 6
-6
-4
-2
0
2
4
6 Age 40 yrs
FVC 3.52 L 0.84 SR
FEV1
3.0 L 0.74 SR
PEF 4.57 L/s -2.18 SR
FEV/PEF = 10.9
Inspiratory
Expiratory
FlowinL/s
Volume in Litres
FEV1 in mls
PEF in L/min
> 8

31. Diffusing Capacity
 Diffusing capacity of lungs for CO
 Measures ability of lungs to transport inhaled gas
from alveoli to pulmonary capillaries
 Depends on:
- alveolar—capillary membrane
- hemoglobin concentration
- cardiac output

32. Diffusing Capacity
 Decreased DLCO
(<80% predicted)
 Obstructive lung disease
 Parenchymal disease
 Pulmonary vascular
disease
 Anemia
 Increased DLCO
(>120-140% predicted)
 Asthma (or normal)
 Pulmonary hemorrhage
 Polycythemia
 Left to right shunt

33. DLCO — Indications
 Differentiate asthma from emphysema
 Evaluation and severity of restrictive lung
disease
 Early stages of pulmonary hypertension

35. Emphysema
histopathological definition
…..permanent abnormal enlargement of
airspaces distal to the bronchioles terminales
and
…...destruction of the walls of the involved
airspaces
And
Fibrosis is not integral part

39. Centrilobular Emphysema

40. Panlobular Emphysema

41. Fibrosis and Emphysema

42. CT findings:
• Relatively well-defined, low attenuation areas
with very thin (invisible) walls, surrounded by
normal lung parenchyma.
• As disease progresses:
– Amount of intervening normal lung decreases.
– Number and size of the pulmonary vessels
decrease.
– +/- Abnormal vessel branching angles (>90o), with
vessel bowing around the bullae.

43. Emphysema
•Curved arrow: area of low attenuation.
•Solid arrow: zones of vascular disruption.
•Open arrow: area of lung destruction.

44. Emphysematous Bullae
www.ctsnet.org/doc/6761

47. Where is the pathology ???????
in the areas with increased density
meaning there is ground glass
in the areas with decreased density
meaning there is air trapping

48. Pathology in black areas
Airtrapping: Airway Disease
Bronchiolitis obliterans (constrictive bronchiolitis)
idiopathic, connective tissue diseases, drug reaction,
after transplantation, after infection
Hypersensitivity pneumonitis
granulomatous inflammation of bronchiolar wall
Sarcoidosis
granulomatous inflammation of bronchiolar wall
COPD/Asthma / Bronchiectasis / Airway diseases

49. Airway Disease
what you see……
In inspiration
sharply demarcated areas of seemingly increased
density (normal) and decreased density
demarcation by interlobular septa
In expiration
‗black‘ areas remain in volume and density
‗white‘ areas decrease in volume and increase in density
INCREASE IN CONTRAST DIFFERENCES
AIRTRAPPING

51. Pathology in white Areas
Alveolitis / Pneumonitis
Ground glass
desquamative intertitial pneumoinia (DIP)
nonspecific interstitial pneumonia (NSIP)
organizing pneumonia
In expiration
both areas (white and black) decrease in
volume and increase in density
DECREASE IN CONTRAST
DIFFERENCES

52. Mosaic Perfusion
Chronic pulmonary embolism
LOOK FOR
Pulmonary hypertension
idiopathic, cardiac disease, pulmonary
disease

53. CTEPH =
Chronic thrombembolic
pulmonary hypertension

54. Quantitative CT Assessment of
Chronic Obstructive Pulmonary
Disease

55. 1-Describe the differences between emphysema-
predominant, airway-predominant, and mixed COPD.
2-Discuss CT-based methods for quantifying the
pathologic and morphologic changes in COPD.
3-Differentiate COPD phenotypes by using a combination
of CT-based methods.

56. Figure 1 Axial CT image obtained in a 66- year-old man with COPD and severe airflow obstruction
Axial CT image obtained
in a 66- year-old man with
COPD and severe airflow
obstruction (percentage of
predicted FEV1, 40.8%)
shows mild emphysema
(relative low-attenuation
area with attenuation of
−950 HU or lower, 5.8%).
Low-attenuation areas
representing
emphysematous change
(―holes‖) are indicated by
arrowheads.

57. Figure 2 Axial CT image obtained in an asymptomatic 69-year-old smoker with normal pulmonary
Axial CT image obtained in an
asymptomatic 69-year-old smoker with
normal pulmonary function (percentage
of predicted FEV1, 87.8%) shows
moderate to severe emphysema
(arrowheads) (relative low-attenuation
area with attenuation of −950 HU or
lower, 25.8%).

58. Figure 4 Coronal CT image obtained in a 62-year-old man with COPD shows upper-lung–predominant
Coronal CT image obtained in a 62-
year-old man with COPD shows
upper-lung–predominant
emphysema. The relative low-
attenuation area with attenuation of
−950 HU or lower (red) is 46.8%,
and the percentage of predicted
FEV1 is 56.8%.

59. Figure 5 Coronal CT image obtained in a 72-year-old man shows lower-lung–predominant
Coronal CT image obtained in a 72-
year-old man shows lower-lung–
predominant emphysema. The
relative low-attenuation area with
attenuation of −950 HU or lower (red)
is 45.8%, and the percentage of
predicted FEV1 is 45.6%. The extent
of lower-lung–predominant
emphysema is more closely
correlated with the result of
pulmonary function testing than the
extent of upper-lung–predominant
emphysema. (In both figures, black
indicates areas with attenuation of
−500 to −949 HU and gray indicates
vascular and other nonparenchymal
structures.)

60. CT densitovolumetry

62. Figure 8a Volumetric CT-based measurement of airway dimensions. (a) Schema obtained
Volumetric CT-based measurement of
airway dimensions. (a) Schema obtained
with the region-growing method shows
airway segmentation and selection of a
bronchial pathway (black line) for
measurement. A curved multiplanar
reformatted image is reconstructed along
the selected pathway, and a short-axis
image is reconstructed in a plane exactly
perpendicular to the long axis of the
airway. The red dot indicates the location of
the short-axis image in b. (b) Short-axis
image with overlaid diagram shows the
radii (red and green lines) used to delimit
the inner lumen and calculate its area.
From the point of their intersection, the
centroid point, rays (blue lines) are drawn
over a 360° radius through the airway wall
to allow calculation of the airway wall
thickness by using the full width at half
maximum principle.

63. Vascular Alterations
Pulmonary vascular alteration is a characteristic feature
of COPD. Narrowing and numeric reduction of small
pulmonary arteries can be observed in patients with
severe COPD .
Typically, passive vascular compression due to
emphysema and hypoxic vasoconstriction has been
considered the major manifestation of vascular
alteration in COPD.
However, pulmonary vascular alterations are not
exclusive to advanced-stage COPD but also have been
found in mild COPD and in smokers with normal
pulmonary function

64. Recent studies suggest that both
pulmonary and extrapulmonary vascular
alterations in patients with COPD are
closely related to endothelial dysfunction .
In addition, several researchers
demonstrated a close relationship between
endothelial dysfunction and emphysema .
Endothelial dysfunction results from
changes in the expression and release of
vasoactive mediators. In particular,
vascular endothelial growth factor (VEGF)
plays an important role in the pathogenesis
of both vascular alteration and emphysema

65. VEGF level in induced sputum from
patients with emphysema is decreased
in comparison with that from patients
with chronic bronchitis.
Vascular alterations also may be
relevant to the diagnosis and
characterization of COPD. Some
researchers have evaluated pulmonary
perfusion and its relationship to airflow
obstruction by using dynamic magnetic
resonance imaging

66. Quantitative CT Characteristics of
COPD according to Phenotype