1. Tracheobronchomalacia
The ugly, but treatable step-cousin of the COPD family
Colin McKnight, MSIII, 2007

2. Presentation Outline
Brief review of “COPD” definition, epidemiology and economic costs
Tracheobronchomalacia
Definition
Pathophysiology
Known epidemiology and natural history
Evolving methods of diagnosis
New treatment strategies and outcomes
Significance
Proposed study design

3. 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.

4. 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

5. 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

6. Which Diseases Lead to Obstructive Pulmonary Physiology?
A conglomeration of various pathophysiological processes, of which the treatment varies substantially:
Emphysema
Chronic Bronchitis
Asthma
Bronchiectasis
Bronchiolitis obliterans
Tracheobronchomalacia

7. Assumptions
Unfortunately, patients with obstructive pulmonary physiology are often assumed to have emphysema
This is particularly true for those who smoke cigarettes
Picture

8. GOLD criteria for COPD diagnosis
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: FEV1 > 80% Stage IIA: FEV %
Stage IIB: FEV %
Stage III: FEV1 < 30%

9. “COPD” Emphysema Chronic Bronchitis Sx: PE: Sx: PE:
Severe, constant dyspnea, mild cough
PE:
Pink Puffers:
Tachypneic
Non-cyanotic
Thin
Diminished Breath sounds
Chronic Bronchitis
Sx:
Intermittent dyspnea
Copious sputum
PE:
Blue Bloaters:
Cyanotic
Obese
Edematous
Rhonchi and Wheezes

10. 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

11. 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

12. Current COPD treatments
Corticosteroids
Oxygen
Prevention
Smoking cessation
vaccination
Dilators
Anticholinergics
B2-agonists
Theophyllline
Rehabilitation

13. Only Oxygen has been shown to improve mortality
Current goals of treatment:
Slow further progression
Reduce exacerbation hospitalizations
Maximize activity

14. 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

15. 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

16. 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.

17. 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

18. 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.

19. During inspiration, the trachea dilates and lengthens.
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.

20. Etiology
Excessive bowing is thought to be due to reduction/atrophy of the longitudinal elastic fibers of the pars membranacea or impaired cartilage integrity.
Presumed causes of acquired TM/TBM
Treacheostomy
Intubation
Tobacco smoke
Radiation/previus surgery
Recurrent infections (with or without cigarette smoking)

21. 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:
Emphysema
Chronic Bronchitis
Cigarette Smoking
Asthma

22. This is an obscure, insignificant disease…
Right???

23. NO!!!

24. Population studies indicate very significant prevalence within certain populations:
-Jolinen et al reported finding TM in 50 of 214 patients (23%) with chronic bronchitis who were examined bronchoscopically
-Palombini revealed that TBM may be present in 10-15% of patients who see a pulmonologist for chronic cough

25. 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

26. 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.

27. 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”.

28. 3 Further Questions
Can this TBM be diagnosed in reliable, non-invasive manner?
Are there effective interventions available?
Are these interventions cost effective?

29. 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

30. 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

31. Evolution of Diagnosis
In 2003 Zhang et al showed that Dynamic CT was highly sensitive at detecting TBM.
N= /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.

32. Demonstration of Air Trapping
Right: Dynamic expiratory CT at a similar level on the same patient. White arrows indicate areas of air trapping in this TBM patient.
Left: End inspiratory CT
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

33. 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

34. 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.

35. 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.

36. Benefits of Tracheoplasty
Wright et al, 2005
n=14
Significantly increased
mean forced expiratory volume (p=.009)
peak flow rate (p=.00001)
All patients had decreased
Dyspnea
Cough
secretion retention and
All reported increased activity
Baroni RH, 2004
N=5
All showed a normal shaped trachea during inspiration following treatment
4/5 showed normal shape on expiration
All patients reported subjective improvement in symptoms
0/5 experience significant complications

37. Dynamic CT Demonstration of Improvement Following Tracheoplasty
A: Preoperative end inspiratory
B: Preoperative dynamic expiratory
C: Postoperative end-inspiratory
D: Postoperative dynamic expiratory A B D C
*Baroni

38. 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

39. Further Benefits of TBM Diagnosis and Treatment
Best evidence indicates depression is present in % 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

40. 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 non-invasively through low dose dynamic CT.
Tracheoplasty has been shown in small trials to substantially improve objective and subjective outcomes.

41. 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.

42. Study Proposal Involving the following investigators:
Internists/Pulmonologists
Radiologists
Thoracic Surgeon

43. 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.

44. 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.

45. 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.

46. 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

47. Thank You!

48. References:
Gilkeson, RC, Ciancibello, LM, Hejal, RB, et al Tracheobronchomalacia: dynamic airway evaluation with multidetector CT. AJR Am J Roentgenol 2001;176,
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,
Boiselle, PM, Feller-Kopman, D, Ashiku, S, et al Tracheobronchomalacia: evolving role of dynamic multislice helical CT. Radiol Clin North Am 2003;41,
Zhang, J, Hasegawa, I, Hatabu, H, et al Frequency and severity of air trapping at dynamic expiratory CT in patients with tracheobronchomalacia. AJR Am J Roentgenol 2004;182,81-85
Jokinen, K, Palva, T, Sutinen, S, et al Acquired tracheobronchomalacia. Ann Clin Res 1977;9,52-57
Ikeda, S, Hanawa, T, Konishi, T, et al Diagnosis, incidence, clinicopathology and surgical treatment of acquired tracheobronchomalacia. Nihon Kyobu Shikkan Gakkai Zasshi 1992;30,
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