Download Tracheobronchomalacia

Tracheobronchomalacia
The ugly, but treatable step-cousin of
the COPD family
Colin McKnight, MSIII, 2007
Presentation Outline
• Brief review of “COPD” definition, epidemiology
and economic costs
• Tracheobronchomalacia
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Definition
Pathophysiology
Known epidemiology and natural history
Evolving methods of diagnosis
New treatment strategies and outcomes
Significance
Proposed study design
COPD: An unpopular disease from
the start
An Interesting perspective from
1976:
• “Chonic bronchitis with it
accompanying emphysema is a
disease on which a good deal of
wholly unmerited sympathy is
frequently wasted. It is a disease
of the gluttonous, bibulous,
otiose, and obese and represents
a well-deserved nemesis for
these unlovely indulgences . . .
The majority of cases are
undoubtedly due to surfeit and
self-indulgence”
Fletcher C, Peto R., Tinker C, Speizer FE. The natural history of chronic bronchitis and
emphysema. New York: Oxford University Press, 1976.
Risk Factors for “COPD”
• “Well established”:
– Tobacco smoke
– α1-Antitrypsin
deficiency
– Environmental
exposures
• “Good evidence”:
– Air pollution
– Low birth weight
– Childhood respiratory
infection
– Atopy
– Low socioeconomic
status
– Alcohol intake
*Viegi
How Far Have We Really Come
Since 1976?
• Research of ‘tobacco induced’ cancers such as
lung cancer, receive only 10-15% of that for
breast or prostate cancer when dollars spent per
death are examined*
• Perhaps our willingness to blame the health of
our patients on smoking has presented us from
a more sophisticated understanding of
obstructive pulmonary physiology.
*Dennis
Which Diseases Lead to Obstructive
Pulmonary Physiology?
• A conglomeration of various pathophysiological
processes, of which the treatment varies
substantially:
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Emphysema
Chronic Bronchitis
Asthma
Bronchiectasis
Bronchiolitis obliterans
Tracheobronchomalacia
Assumptions
• Unfortunately, patients
with obstructive
pulmonary physiology
are often assumed to
have emphysema
• This is particularly true
for those who smoke
cigarettes
Picture
GOLD criteria for COPD diagnosis
• GOLD* criteria:
– airflow limitation
– not fully reversible.
– usually both
progressive
– Usually associated
with an abnormal
lung inflammatory
response to noxious
particles or gases
*GOLD:
Global initiative for
Chronic Lung Disease
Current
GOLD definition of
airflow limitation is FEV1:FVC
ratio <70%
Stage I:
Stage IIA:
FEV1 > 80%
FEV1 50-80%
Stage IIB:
FEV1 30-50%
Stage III:
FEV1 < 30%
“COPD”
• Emphysema
• Sx:
– Severe, constant dyspnea,
mild cough
• PE:
– Pink Puffers:
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Tachypneic
Non-cyanotic
Thin
Diminished Breath sounds
• Chronic Bronchitis
• Sx:
– Intermittent dyspnea
– Copious sputum
• PE:
– Blue Bloaters:
• Cyanotic
• Obese
• Edematous
• Rhonchi and Wheezes
COPD “diagnosis”
• Individuals with irreversible obstructive
pulmonary physiology and the following
non-specific findings are unfortunately
often lumped together under one
“diagnosis”:
– Dyspnea
– Cough
– Sputum
COPD Epidemiology
• 2000 estimate was >10 million
diagnosed in U.S.
• Millions more are undiagnosed.
• COPD is the fourth leading cause of
chronic morbidity and mortality in the
US and within a decade will surpass
stroke to become the third leading
cause of death
Current COPD treatments
– Corticosteroids
– Oxygen
– Prevention
• Smoking cessation
• vaccination
– Dilators
• Anticholinergics
• B2-agonists
• Theophyllline
– Rehabilitation
• Current goals of
treatment:
– Slow further
progression
– Reduce
exacerbation
hospitalizations
– Maximize activity
Only
Oxygen has
been shown to
improve mortality
A Tremendous Burden
• The economic impact of
COPD in the US:
– 1993: $23.9 Billion*
• Direct costs $14.7 billion
• Indirect costs $9.2 billion
• 2002: $32.1 billion*
*Sullivan
*National Heart and Lung Institute
• Annual mean individual cost is $5,646*
– $2,000 for mild cases
– $16,000 for severe cases
• This Probably underestimates true burden
because COPD often not:
– “primary reason for hospital visit”
– “cause of death”
*Wouters
*Halpan
My Frustrations
• COPD expenditures represent a
tremendous cost to a health care
system that is already on the verge
of collapse and does not provide
basic services to a large proportion
of the population.
• Treatments offer very little hope of
improvement.
• Despite expensive new medications,
relative gains are little.
Tracheomalacia and
Tracheobronchial malacia
• Definition: Malacia = Weakness
• Tracheomalacia (TM)  weakness of the
trachea
• Tracheobronchomalacia (TBM)  weakness of
the trachea and main stem bronchi
*This presentatin will focus on adult, acquired tracheobronchomalacia rather than the congenital
form of the disease
Postulated Pathophysiology
• Flaccid posterior membranous wall of the
trachea bows anteriorly during dynamic
expiration in response to elevated intrathoracic,
extratracheal pressure.
• This is a dynamic process that is accentuated by
forced expiration, thus routine AP and Lateral
chest radiographs often show no abnormality.
Trachea cross section
Inspiration:
Decreased extratracheal
pressure
During inspiration, the trachea
dilates and lengthens.
Normal trachea
Tracheomalacia
Expiration:
Increased extratracheal
pressure
A weakened posterior tracheal wall
leads to an exaggeration of the
normal narrowing during expiration.
Etiology
• Excessive bowing is
• Presumed causes of
thought to be due to
acquired TM/TBM
reduction/atrophy of
– Treacheostomy
the longitudinal elastic
– Intubation
fibers of the pars
– Tobacco smoke
membranacea or
– Radiation/previus
impaired cartilage
surgery
integrity.
– Recurrent infections
(with or without
cigarette smoking)
Symptoms of TM and TBM
• Dyspnea
• Cough
• Sputum Production
• May have:
– Inspiratory wheezing/stridor
– “Barking seal cough”
– Multiple admissions for
“asthma exacerbations”
with only modest treatment
results
• These are non-specific,
and very often attributed
to:
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Emphysema
Chronic Bronchitis
Cigarette Smoking
Asthma
• This is an obscure, insignificant disease…
Right???
NO!!!
Population studies indicate very significant
prevalence within certain populations:
-Jolinen et al reported
-Palombini revealed that
finding TM in 50 of
TBM may be present
214 patients (23%)
in 10-15% of patients
with chronic bronchitis
who see a
who were examined
pulmonologist for
bronchoscopically
chronic cough
Malacia epidemiology continued…
• The most recent epidemiological data comes
from a Japanese study that demonstrated TBM
was present 542 of 4,283 patients (12.7%) with
pulmonary disease who underwent
bronchoscopy. (72% of this study were between
50-80years old).
• It is generally accepted that TBM is seldom
found in individuals without some evidence of
obstructive lung disease
* Ikeda
A Progressive disease
• TM and TBM have been shown in various
studies to be progressive diseases. In one
longitudinal study, of 94 patients with TM and
TBM with an average follow-up period 5.2 years
progression had occurred in 6 of 9 patients.
Zero patients showed improvement of their
malacia.
• It has been postulated that TM causes a defect
in secretion clearing, allowing for pathology to
spread down the bronchial tree.
A relatively good candidate for
“COPD” intervention
• Thus, TM represents a progressive
pathophysiologic process where it may be
possible to avoid further progression.
• Unlike emphysema, chronic bronchitis, and
bronchiolitis obliterans, the defect is discrete and
localized.
• Thus, this disease offers a rare target for
mechanical intervention of “COPD”.
3 Further Questions
• Can this TBM be diagnosed in reliable,
non-invasive manner?
• Are there effective interventions available?
• Are these interventions cost effective?
Diagnosis
• Bronchoscopy is the
established gold
standard
• Generally accepted
that 50% loss of
tracheal lumen
during expiration is
diagnostic of TM
A
B
A: Cross section in a healthy control subject during
inhalation (left), exhalation (middle) and forced
exhalation. SIs change from .95 to 0.93 to .87.
B: Tracings of a TBM patient showing bowing of the
posterior membrane. SIs change from .95 to .65 to .14.
*Loring
A Non-Invasive Method of
Diagnosis
• Gilkeson showed in 2000 that the degree
of TBM defined by bronchoscopy
correlates very well with dynamic CT
findings.
Image A: axial CT showing
trachea of normal caliber
Image B: dynamic CT showing
crescentric bowing of posterior
membranous trachea
A
B
Evolution of Diagnosis
• In 2003 Zhang et al
showed that Dynamic
CT was highly
sensitive at detecting
TBM.
• N=20. 10/10 TBM
patients were
identified by CT. 0/10
control subjects were
falsely labeled with
malacia.
• Additionally, Zhang
showed that a low dose
dynamic CT was
statistically equal at
detecting TBM, thus
indicating that high
dose CT is not
necessary for TBM
diagnosis.
Demonstration of Air Trapping
Left: End inspiratory CT
Right: Dynamic expiratory CT at a similar
level on the same patient. White arrows
indicate areas of air trapping in this TBM
patient.
Zhang et al demonstrated that patients with TBM defined by dynamic expiratory
CT have statistically more severe air trapping. This air trapping has been
postulated to be worsened in TBM patients from difficulties clearing secretions.
Secretions are though to accumulate, thus inducing chronic inflammation of
small airways, leading to air trapping.
*Zhang, 2003
Use of PFTs in Diagnosis?
-The degree of obstruction indicated
by FEV1 does not correlate well with
presence of TBM.
-In TBM patients there is often a rapid
decline in the maximal expiratory flow
after a sharp peak associated with the
collapse of central airways due to
negative transmural pressure.
PFTs therefore can be useful in raising
suspicion of TBM, but they are not
diagnostic.
Flow volume loop in
TM patient.
*Carden
Stenting
• Metal stents can be placed by bronchoscopy. They can
expand dynamically and preserve mucociliary function,
though breakage has caused severe complications,
including death.
• Silicone stents can be easily repositioned and removed.
• Trials including stented patients have shown that stents
lead to subjective and objective improvement in
respiratory symptoms.
• Further larger trials are needed.
Tracheoplasty
• Current methods call for surgical
reinforcement of the posterior
membranous wall with tracheoplasty
enhancing the rigidity of the structure
making it less susceptible to bowing during
expiration.
Benefits of Tracheoplasty
Wright et al, 2005
Baroni RH, 2004
• n=14
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N=5
• Significantly increased
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All showed a normal shaped trachea
during inspiration following treatment
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4/5 showed normal shape on
expiration
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All patients reported subjective
improvement in symptoms
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0/5 experience significant
complications
– mean forced expiratory
volume (p=.009)
– peak flow rate (p=.00001)
• All patients had decreased
– Dyspnea
– Cough
– secretion retention and
• All reported increased
activity
Dynamic CT Demonstration of
Improvement Following Tracheoplasty
A: Preoperative end inspiratory
B: Preoperative dynamic
expiratory
A
B
C: Postoperative end-inspiratory
D: Postoperative dynamic
expiratory
C
D
*Baroni
PFT Change Following Tracheoplasty
Preoperative
2 Months Postoperative
Flow volume curves in a 57-year-old man with 7 years of
progressive dyspnea, wheezing, cough, and respiratory
infections.
*Wright
Further Benefits of TBM Diagnosis
and Treatment
• Best evidence indicates depression is present in 25-50% of COPD
patients.
• 28% of COPD patients say they are embarrassed about the disease,
and the same number say they feel defeated (particularly women
and younger patients).
• An overwhelming portion of patients believe they brought on the
disease because of a smoking habit.  guilt, stigma, reinforcement
• Patients with TBM are often labeled as smokers after being
“diagnosed” with emphysema. This can lead to insurance
companies denying claims on the grounds of “false indication of
non-smoking status.”
*Norwood
TBM Review: A bigger problem
than our medical system realizes:
• COPD: >$30 billion annually…
• TBM likely present in 10% of > 12 million COPD patients,
whose current treatment is annually greater than $5,000.
TBM is likely contributing significantly to the obstructive
physiology in many of these individuals.
• TBM is a progressive disease that can be identified noninvasively through low dose dynamic CT.
• Tracheoplasty has been shown in small trials to
substantially improve objective and subjective outcomes.
An opportunity…
• Given the extraordinary chronic costs of “COPD”
therapy, and the great potential for localized
defect correction, it is possible that tracheoplasty
represents a rare opportunity to both reduce
medical costs and improve clinical outcome.
• Further studies are needed to define who would
benefit from TBM diagnostics and therapeutic
intervention.
Study Proposal
• Involving the following investigators:
– Internists/Pulmonologists
– Radiologists
– Thoracic Surgeon
Initial Enrollment
• Internists/Pulmonologists:
– Identify TBM candidates to be selected for treatment.
– Candidates would be selected from a pool of
COPD/asthmatics with long history of modest
treatment benefit.
– Enrollment of individuals with dyspnea, great difficulty
clearing secretions and barking cough will be
emphasized.
– A functional pulmonary baseline will be established.
Radiologic Diagnosis
• Radiologists:
– Conduct low dose dynamic CT to identify
TBM patients.
– Defect will be described in terms of level,
% obstruction and presence/severity of
air trapping.
Treatment phase
• Thoracic Surgeon:
– Of population with TBM defined by dynamic
CT, ½ will undergo corrective tracheoplasty.
– ½ will have “dummy” procedure.
– Patients, internists and follow up radiologists
will be blinded to procedure status.
Data Collection
• Following procedure, blinded
patients will provide 5 years of
subjective data.
• Blinded radiologists will
perform postoperative dynamic
CT to assess objective status
of TBM 3 months after surgery.
• The patient’s respective
internists/pulmonologist will
measure objective outcomes
for 5 years.
• Strict attention will be paid to
cost of care.
• The following endpoints of the
control and treatment arms will
be compared:
– subjective activity and
wellness levels
– exacerbation
frequency/severity
– % tracheal/bronchial
obstruction, presence and
severity of air trapping
– PFT scores
– Need for oxygen
– mortality
– cost of care
• Thank You!
References:
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Gilkeson, RC, Ciancibello, LM, Hejal, RB, et al Tracheobronchomalacia: dynamic airway evaluation with multidetector
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Zhang, J, Hasegawa, I, Feller-Kopman, D, et al Dynamic expiratory volumetric CT imaging of the central airways:
comparison of standard-dose and low-dose techniques. Acad Radiol 2003;10,719-724
Boiselle, PM, Feller-Kopman, D, Ashiku, S, et al Tracheobronchomalacia: evolving role of dynamic multislice helical CT.
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Zhang, J, Hasegawa, I, Hatabu, H, et al Frequency and severity of air trapping at dynamic expiratory CT in patients
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Jokinen, K, Palva, T, Sutinen, S, et al Acquired tracheobronchomalacia. Ann Clin Res 1977;9,52-57
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