Is Asthma Really a Risk

Factor for COPD?

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

RESPINA 2004
 Asthma and COPD-
Definitions
 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) 96S-104S
 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) 96S-104S
 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 normal

Compliance Abnormal abnormal normal

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 are similar
The Relationship Between
Asthma & COPD
Asthma COPD
Eosinophilic and Neutrophilic inflammation
mononuclear cell
infiltration
Mucous metaplasia, Mucous metaplasia, goblet
increase in goblet cells cell hyperplasia, mucous
and submucous glands gland enlargement
and intermittent mucous
plugging
Airway Alveolar destruction
hyperresponsiveness 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: 117S-123S
 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: 117S-123S
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: 117S-123S
 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 obstruction- AHR is
a determinant in COPD?
 Remodelling and Inflammation
of Bronchi in Asthma and COPD

COPD Asthma

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.