Is Asthma Really a

Risk Factor for COPD?

Jennifer Ann Mendoza-Wi, MD,
FCCP
Philippine College of Chest
Physicians
RESPINA 2004

Asthma and COPDDefinitions

Asthma:
BHR, airway inflammation, airflow obstruction, which
may be relieved spontaneously or with medication.
Most frequently diagnosed during childhood
Associated with atopy and eosinophilic inflammation

COPD:
a chronic and usually progressive disease
characterized by airflow limitation that is not fully
reversible
Most frequently diagnosed during the middle or late life
Associated with neutrophilic inflammation

Similarities and Differences

in Asthma & COPD:
The Dutch Hypothesis

In 1995, the ATS stated it may be

impossible to differentiate patients
with asthma whose airflow obstruction
does not remit completely from
persons with chronic bronchitis and
emphysema with partially reversible
airflow obstruction and bronchial
hyperresponsiveness (BHR).

Similarities and Differences

in Asthma & COPD:
The Dutch Hypothesis

Numerous studies have

documented the presence of partial
reversibility after short-term and
long-term bronchodilator
administration in patients with
COPD.
This partial reversibility contrasts
with asthma which has variable and
reversible airflow obstruction

Similarities and Differences

in Asthma & COPD:
The Dutch Hypothesis
there is increasing scientific
and clinical evidence that
asthma and COPD share many
common origins (ie,
epidemiologic characteristics
and clinical manifestations)
Orie and coworkers, 1961
Bleecker ER, CHEST 2004; 126 (2), 93S-95S
Postma DS et al, CHEST 2004; 126 (2) 96S104S

Characteristics of asthma and COPD

Bleecker, E. R. Chest 2004;126:93S-95S

Similarities and Differences

in Asthma & COPD:
The Dutch Hypothesis
COPD and asthma are not
distinct entities in selected
individuals, and that similar
pathogenetic mechanisms may
be involved in the pathogenesis
of asthma and COPD in some
individuals.
Orie and coworkers, 1961

Bleecker ER, CHEST 2004; 126 (2), 93S-95S

Postma DS et al, CHEST 2004; 126 (2) 96S104S

Similarities and Differences

in Asthma & COPD:
The Dutch Hypothesis
The three components of the hypothesis:

Overlapping clinical features

(symptoms, allergy, BHR) of OLD may
define the specific clinical phenotype

One form of OLD (asthma) may evolve

into another (COPD)

OLD is based on allergy (ie.

inflammation) and BHR, and
endogenous (host) factors determined
by heredity (genes), but is modulated
by exogenous (ie environmental) factors
(eg. allergens, infections, smoking,
pollution, age, and airway geometry)

Potential interactions between asthma and COPD

Bleecker, E. R. Chest 2004;126:93S-95S

Similarities and Differences

in Asthma & COPD:
The British Hypothesis
proposes that asthma
and COPD are distinct
clinical entities that are
generated by distinct
mechanisms.

Elias,J: CHEST 2002; 126(2), 111S-115S

The Relationship Between

Asthma & COPD
COPD/Emphysema

Asthma

Tissue injury- proteolysis/apoptosis/remodeling

Alveoli

Destroyed
normal
Complianc Abnormal
e
normal

normal
abnormal

Proposed relationship between asthma and emphysema

Elias,J: CHEST 2002; 126(2), 111S-115S

The Relationship Between

Asthma and COPD

Structural alterations are prominent in asthmatic airways (airway

remodelling)
Mucous responses in patients with chronic bronchitis and asthma

The Relationship Between

Asthma & COPD

Asthma

COPD

Eosinophilic and
mononuclear cell
infiltration

Neutrophilic
inflammation

Mucous metaplasia,
increase in goblet cells
and submucous glands
and intermittent
mucous plugging

Mucous metaplasia,
goblet cell hyperplasia,
mucous gland
enlargement

Airway
hyperresponsiveness

Alveolar destruction
Elias,J: CHEST 2002; 126(2), 111S-115S

Physiologic Similarities and

Differences Between COPD and
Asthma

Significant overlap exists in individual

patients with respect to
airway wall thickening and low-attenuation
parenchymal regions on CT scan,
Reversibility and airway hyperresponsiveness
lung diffusion
resting and dynamic hyperinflation
lung elastic recoil
exercise response
pharmaceutical volume reduction effect
following therapy with bronchodilators
Sciurba FC, CHEST 2004;126: 117S123S

CT scans of two subjects with clinical

histories that are consistent with COPD are
shown

Sciurba, F. C. Chest 2004;126:117S-124S

The Physiologic Dogma:

Asthma vs COPD
The most common working definitions
of COPD and asthma in most clinical
and research settings consistently
incorporate the following physiologic
attributes:
Degree of Variability and Reversibility of
Spirometry
Diffusing capacity
Hyperinflation
Lung elastic recoil/lung compliance
Sciurba FC, CHEST 2004;126: 117S123S

The Physiologic Dogma:

Asthma vs COPD
More physiologic attributes:
Simple measures of Pulmonary
function in asthma and COPD ( rate
of decline in lung function which in a
significant group of asthma patients
evolves into incompletely reversible
disease)
Bronchodilator reversibility and AHR
Resting and dynamic
hyperinflation
Sciurba FC, CHEST
2004;126: 117S123S

Two patterns of responses to bronchodilator therapy

include a predominant expiratory flow response (left), and
a predominant volume response (right)

Sciurba, F. C. Chest 2004;126:117S-124S

Despite distinct clinical physiologic

features at the time of diagnosis,
epidemiologic studies of asthma
and COPD have shown that the two
diseases over time may develop
physiologic features that are quite
similar.

The progression in severity of asthma

symptoms, the overlap of symptoms
seen in some patients with asthma
and COPD have lead the group to
theorize that asthma may be a
risk factor for the subsequent
development of COPD.

A prospective observational study.

Participants completed up to 12
standard respiratory questionnaires
and 11 spirometry lung function
measurements over a 20-year period.
Survival curves ( with time to
development of COPD as the
dependent variable) were compared
between subjects with asthma and
without asthma at the initial survey.

Results:
Subjects with active asthma (n=192) had
significantly higher hazard ratios than
inactive (n=156) or nonasthmatic subjects
(n=2751) for acquiring COPD.
As compared with nonasthmatics, active
asthmatics had a 10-times-higher risk for
acquiring symptoms of chronic bronchitis,
17-times-higher risk of receiving a diagnosis
of emphysema and 12.5-times-higher risk of
fulfilling COPD criteria, even after adjusting
for smoking history and other potential
confounders

Cox survival estimates for CB (top), emphysema (middle),

and COPD (bottom) by asthma categories at initial survey
adjusted for age, sex, smoking, log IgE, and skin test

Cumulative survival is much lower for

subjects in active asthma categoy
Silva, G. E. et al. Chest 2004;126:59-65

Conclusions

Asthma and COPD share a common

background, the differentiation into
one disease or the other being
modulated by environmental
(exposure to allergens, respiratory
infections, and smoking) and host
factors (AHR, atopy and genetic
predisposition).

Conclusions

It has been suggested that airway

inflammation and airflow
obstruction seen in asthmatics with
increased AHR may lead to
subsequent lung remodelling due
to airway wall thickening and
subepithelial fibrosis
This remodelling could result in
irreversible airflow obstructionAHR is a determinant in COPD?

Remodelling and
Inflammation of Bronchi in
Asthma and COPD
COPD

Asthm
a

In general there is epithelial fragility and thickening of the reticular

basement
membrane, even in mild asthma; increased airway smooth muscle
mass, hypertrophy of mucus-secreting glands, increased vascularity,
greaqter number of fibroblasts, and increased deposition of collagen
in severe asthma and COPD; and mucous metaplasia, squamous
metaplasia and parenchymal destruction in COPD

Conclusions

Results from the study of Silva et al

show a significant association
between an active asthma
diagnosis at initial survey and the
subsequent development of signs
and symptoms consistent with
COPD.
The mechanism by which asthma
may have contributed to this
development is still unresolved.