2.  70 years old male with a history of dyspnea
for 10 years
 Presenting with dyspnea with white
productive sputum, no fever or URI
symptoms
 Skin test +ve for house dust mites, pollens,
and cockroaches
 Nonsmoker
 Prescribed drugs from clinic as follow
 seretide (50/250) evohaler 1x2, Berodual
MDI 1x4, Prednisolone (5) 1x2, Neulin 1x2
 Refer for definite diagnosis:
 Dyspnea R/O COPD or Asthma

3. Tinkelman et alวRespiration 2006;73:296–305

4. n = 417
Tinkelman et alวRespiration 2006;73:296–305

5. Tinkelman et alวRespiration 2006;73:296–305

6.  1961, Orie and colleagues from
Groningen, the Netherlands,
 “All airway diseases, including asthma,
emphysema, and chronic bronchitis,
should be considered a single disease
with common genetic origins”

7. “chronic nonspecific lung disease”

8. P G Gibson; Thorax 2009

9. P G Gibson; Thorax 2009

10. P G Gibson; Thorax 2009

11. P G Gibson; Thorax 2009

12. Asthma as a Risk Factor for
COPD in a Longitudinal Study
 Study objective: To evaluate the association between
physician-diagnosed asthma and the subsequent
development of COPD in a cohort of 3,099 adult subjects
from Tucson, AZ
 Design and methods: A prospective observational study.
Participants completed up to 12 standard respiratory
questionnaires and 11 spirometry lung function
measurements over a period of 20 years. Survival
curves (with time to development of COPD as the
dependent variable) were compared between subjects
with asthma and subjects without asthma at the initial
survey
Graciela E. Silva;Chest 2004

13. P G Gibson; Thorax 2009

14. maximal
expiratory
flows at
function
residual
capacity
(VmaxFRC)
123 unselected subjects assessed at a mean age of 2 months
by use of the chest compression technique, F/U 11, 16 and 22 yr
Infants in the lowest quartile for
VmaxFRC had the lowest mean
FEV1/FVC ratios at all ages
Stern DA; Lancet 2007;370:758–764

17. 10 %
COPD
have more
reversibility
5% severe
Asthma
usually episodic in
nature, does not
progress, usually
begins in early
childhood, and shows
a good response to
bronchodilators and
corticosteroids
Peter J. Barnes; Am J Res and Crit Med: 2006
very slowly
progressive onset
and most patients
are diagnosed in
their 60s, there is
little variability in
symptoms, and
patients show a
poor response to
bronchodilators and
corticosteroids
airflow limitation

20. Nobuyuki Hizawa; Allergology International. 2009

21.  Classical genetic predisposition is α1-
antitrypsin deficiency, but this affects
less than 1% of patients with COPD
 Some novel asthma genes, including
ADAM33, CCL5, and IL17F, have been
associated with COPD
Peter J. Barnes; Am J Res and Crit Med: 2006

22. ADAM33
 A disintegrin and metalloproteinase 33
(ADAM33) is the first positionally cloned
asthma gene
 ADAM33 were shown to be significantly
associated with the development of
COPD and annual lung function decline
in a general population
Nobuyuki Hizawa; Allergology International. 2009

23. CCL5
 CC chemokine ligand 5 gene (CCL5)
was associated with susceptibility to
late-onset asthma in patients who
developed asthma at age >40 years
 CCL5 has a genetic impact on the
variable expression of emphysema in
patients with COPD
Nobuyuki Hizawa; Allergology International. 2009

24. IL17F
 Genetic analyses of the association of
asthma with the common variants of
IL17F
 IL-17F has provided evidence for its role
in pulmonary neutrophilia through the
induction of CXC chemokines
 Increased infiltration of the airway with
neutrophils characterizes lung
inflammation in COPD and severe
asthma
Nobuyuki Hizawa; Allergology International. 2009

27. Peter J. Barnes; Am J Res and Crit Med: 2006
Infiltration of EO
into the airway
wall, with
increased
numbers of Th2
lymphocytes, and
activated mast
cells
Predominant
infiltrating
inflammatory cells
are PMN,
macrophages, and
cytotoxic T cells of
the Tc1 subtype
Histamine, cysteiny
leukotrienes, and
PGD2, IL5, IL13
PMN chemotactic mediators,
LTB4 and IL-8

28. Fold increases in inflammatory cells of subjects with
atopic asthma and smokers' (chronic) bronchitis
(CB) with/without COPD versus healthy controls
Asthma CB CB and COPD
CD45 2 2.2 2.3
CD3 2 2.3 4.0
CD4 2.5 ± 2.8
CD8 2 3 8.4
CD4/CD8 ratio 3:1 1:4 1:2
Neutrophil 1.5↓ ± 2.2
Eosinophil 93 1.7 3.5
Macrophage ± 4.5 8.6
Peter Jeffery; Middleton 2008

29. P J Barnes;nature reviews immunology 2008
Epithelial cells release stem-cell factor
maintaining mucosal mast cells at the airway surface

30. P J Barnes;nature reviews immunology 2008
elastin degradation

31. P J Barnes;nature reviews immunology 2008

32. Epithelial fragility and
deposition of collagen under
the airway Epithelial
“subepithelial fibrosis”
Airway smooth muscle
hypertrophy and hyperplasia
and increased bronchial
vascularity
Central airways,
although inflammatory
changes are also seen in small
airwaysin patients with more
severe disease; parenchymal
involvement is not seen
Airway epithelium may show
squamous metaplasia
Small airways and lung
parenchyma, with fibrosis of
bronchioles and parenchymal
destruction, mucous gland
hyperplasia
Peter J. Barnes; Am J Res and Crit Med: 2006

33. Healthy
Severe
asthma
Ravi S. Aysola; Chest 2008
Lamina Reticularis
;collagen I, collagen
III, collagen V,
fibronectin, and tenascin

34. Sutherland and Martin; J ALLERGY CLIN IMMUNOL2003

35. P J Barnes;nature reviews immunology 2008

36. Contraction of airway
smooth muscle as a result of
multiple bronchoconstrictor
mediators
Structural changes of small
airways and closure of small
airways as a result of
disrupted alveolar
attachments, resulting in air
trapping and dyspnea
Peter J. Barnes; Am J Res and Crit Med: 2006
airway narrowing

37. Asthma COPD
Airflow obstruction Variable (± irreversible
component)
Progressive deterioration of lung
function (? reversible
component)
Postmortem Hyperinflation: airway plugs
(exudate and mucus); no
emphysema
Excessive mucus
(mucoid/purulent); small airway
disease; emphysema
Sputum Eosinophilia, metachromatic
cells, Creola bodies
Macrophage; neutrophil (infective
exacerbation)
Surface epithelium Fragility/loss Fragility undetermined
Bronchiolar mucous cells Mucous metaplasia (debated) Metaplasia/hyperplasia
Reticular basement membrane Homogeneously thickened and
hyaline
Variable or normal
Congestion/edema Present Variable/fibrotic
Bronchial smooth muscle Enlarged mass (large airways) Enlarged (small airways)
Bronchial glands Enlarged mass (no change in
mucin histochemistry)
Enlarged (increased acidic
glycoprotein)
Cellular infiltrate Predominantly CD3, CD4, CD25
(IL-2R) positive; marked
eosinophilia (EG2 positive,
degranulated); mast cell increase
(decrease in severe/fatal cases)
Predominantly CD3, CD8, CD68,
CD25, VLA-1, and HLA-DR
positive; mild eosinophilia (not
degranulated?); mast cell
increase
Cytokines IL-4 and IL-5 gene expression
(Th2 profile)
GM-CSF protein; ±IL-4 but not
IL-5
Peter Jeffery; Middleton 2008

41. Response to β2-agonists
Modest response to
anticholinergic drugs
Good response to
corticosteroids
Respond to anticholinergics to
a similar extent as β2-agonists
Poor response to steroid
(macrophage and reduction
histone deacetylase2)
Impressive antiinflammatory
effect of a combination
therapy with a corticosteroid
and LABA
Peter J. Barnes; Am J Res and Crit Med: 2006
greater
number
of EO
and
higher
levels of
exhaled
NO

42. Sutherland; J ALLERGY CLIN IMMUNOL2004

43. Take Home message
 COPD and asthma involve chronic
inflammation of the respiratory tract, the
pattern of inflammation is markedly
different between these two diseases
 Mild asthma is characterized by
eosinophilic inflammation driven by TH2
cells and DCs, and is associated with
mast-cell sensitization by IgE, and by the
release of multiple bronchoconstrictors

44.  COPD is characterized by neutrophilic
inflammation that can be driven by a
marked increase in the number of lung-
resident macrophages, which also
attract CD4+ and CD8+ T cells to the
lungs
 However, these distinctions between
asthma and COPD may not be as clear,
overlap syndrome