Melissa Wei MS4/MPH student Diagnostic Radiology July 2, 2009

Melissa Wei MS4/MPH student Diagnostic Radiology July 2, 2009
Tracheomalacia and Tracheobronchomalacia Challenging the diagnostic gold standard and refining the definition Melissa Wei MS4/MPH student Diagnostic Radiology July 2, 2009

I have taken a few epidemiology courses.
Caveats: I am not a radiologist, and I do not regularly peruse radiology literature. I have taken a few epidemiology courses. As an epidemiologist in training, I enjoy counting, critiquing study methodology, and attempting at recommendations to hopefully advance research and ultimately patient care.

The focus of this presentation is on diagnosing and defining TBM:
What are the diagnostic possibilities? What are the advantages and limitations of newer modalities (e.g. CT) over the gold standard, bronchoscopy, in diagnosing TBM? How well do these modalities correlate with bronchoscopy and with each other in diagnosing TBM? If the gold standard is replaced, how should the definition of TBM be revised so that it has a positive predictive value for symptomatic individuals and negative predictive value for healthy, asymptomatic individuals?

Presentation outline Part I: Background
Definition, Epidemiology, Classification, Pathophysiology, Clinical presentation Part II: Diagnostic options Historical perspective, bronchscopy as the current gold standard, CT, alternatives to CT, spirometry Part III: Redefining TBM Challenges, suggestions Part IV: Treatment (briefly)

Part I: What is Tracheomalacia?
Malacia: softening of the tissues Tracheomalacia (TM): weakness of tracheal wall and/or supporting tracheal cartilage, resulting in excessive expiratory collapse Tracheobronchomalacia (TBM): mainstem bronchi also involved Severity defined by extent of lumenal obstruction during expiration Mild: 50% lumen obstructed Moderate: 75% lumen obstructed Severe: posterior wall reaches anterior wall Clinical significance: Flaccidity of tracheal cartilage increases risk of airway collapse especially with increased airflow demand 5

Mild tracheomalacia 45 year old asymptomatic man with normal pulmonary function 51% decreased cross-sectional area of tracheal lumen during expiration on axial dynamic CT Normal oval-shaped tracheal lumen Lee 2009

Severe tracheomalacia
Young child with compressed trachea from mediastinal vascular anomaly Mild tracheal compression from right-sided aortic arch (R) Near collapse of trachea Lee 2009

Epidemiology TBM in general adult population
Prevalence highest in men > 40 years (Jokinen 1977) Incidence increases with age (Jokinen 1977) 73% of TBM patients are between years of age (Ikeda 1992) TBM in symptomatic adults 10-15% of patients referred to pulmonologist for evaluation of chronic cough (Palombini 1999) 4.5% of 2150 patients who underwent bronchoscopy (Jokinen 1977) 1% with respiratory symptoms and bronchoscopy (Herzog 1958) 23% with history of chronic bronchitis and bronchoscopy (Jokinen 1976) 8

Classification Secondary (acquired) TM Post-traumatic Intubation Tracheostomy External chest trauma s/p lung transplantation Chronic inflammation/irritants Emphysema Chronic infection/bronchitis Chronic external compression of the trachea Tumors (benign or malignant) Cysts Abscesses Aortic aneurysm Vascular rings, undiagnosed in childhood Primary (congenital) TM << Genetic eg polychondritis Idiopathic “giant trachea” or “Mounier-Kuhn” syndrome In kids, TM = #1 congenital tracheal anomaly; associated with transesophageal fistula

Pathophysiology Normal intrathoracic trachea
Trachea dilates with inspiration, narrows with expiration Reflects difference between intrthoracic and intraluminal pressures Tracheomalacia = exaggerated physiologic process  Accentuated changes in tracheal diameter Intrathoracic problem (most common): excessive narrowing when Intrathoracic pressure > Intraluminal pressure Ex) Forced expiration, Cough, Valsalva maneuver Extrathoracic problem: negative intrapleural pressures transmitted to extrathoracic trachea due to pleural reflections  upper airway collapses during inspiration Atrophy of longitudinal elastic fibers of pars membranacea or impaired cartilage integrity  airway soft, susceptible to collapse 10

Most common causes #1 Weakening of tracheal wall
Intubation: recurrent, prolonged  pressure necrosis, impaired blood flow, recurrent infections, mucosal inflammation High-dose steroids #1 Inflammation/irritation of tracheal wall Smoking Recurrent infections: chronic bronchitis, pneumonia 3. Compression of trachea Malignancy, abscess, cysts, goiter 4. Direct damage to tracheal wall External trauma or surgery 5. Vascular malformations Double aortic arch, R aortic arch with aberrant L subclavian a, ligamentum arteriosum 11

Clinical presentation
1. Symptoms are nonspecific (Jokinen 1977, Carden 2005) Dyspnea (63-75%) Chronic cough (50%) - sputum production - “seal like” or barking cough Hemoptysis (33%) Episodic choking; syncope with forced exhalation and cough 2. Concurrent respiratory disease common (Carden 2005) Chronic bronchitis Emphysema Bronchial cancer Recurrent respiratory infection Asthma 3. Pts may be Asymptomatic … … until stressed by infection (bronchitis, pneumonia) Intubated patients: masked by PPV maintaining airway 12

Clinical presentation
4. Physical exam findings Respiratory distress Inspiratory wheezing Stridor Barking cough Deep breathing, cough, and Valsalva manuever elicit airway collapse 13

Differential diagnosis
Laryngomalacia Subglottic stenosis Vocal cord paralysis TBM is commonly misdiagnosed as: COPD Asthma Among 80 patients with suspected or diagnosed TBM, 40% had COPD and 24% had asthma (Loring 2007) “Although TBM and COPD coexist, the implications of this coexistence are not fully understood.” -Kandaswamy 2009 14

Part II: What are the diagnostic options?
Imaging modalities Plain radiographs – not diagnostic Historical modalities Flexible bronchoscopy – current gold standard Standard spiral CT Dynamic expiratory multi-detector CT (MDCT) MRI Virtual bronchoscopy Pulmonary function tests Research ongoing, not diagnostic 15

Imaging: Plain radiographs
Limited use of plain radiographs to diagnose TBM TBM is a dynamic process accentuated by forced expiration Cannot visualize on anterioposterior or lateral chest radiographs Exception TBM secondary to compression from other structures (e.g. mediastinal goiter, tumor) may be visualized

Historic modalities: We’ve come a long way
Cinetracheograms to visualize tracheal flutter Fluroscopy to estimate tracheal diameter Tracheograms and bronchograms  Replaced by bronchoscopy, which is more sensitive for diagnosing TBM

Bronchoscopy is the current gold standard for diagnosing TBM
Visualize dynamic tracheal or bronchial collapse Trachea may also be widened Flexible bronchoscope over rigid Patient can breathe spontaneously and perform additional maneuvers to elicit collapse of the airways Expiratory effort to achieve airway wall collapse through maneuvers (deep breathing, forced expiration, straining, coughing, others) has not been standardized

Bronchoscopy Carden 2005

However, bronchoscopy has limitations
Invasive, requires general anesthesia (rigid bronchoscopy) or local anesthesia (flexible bronchoscopy), and more than half of patients sedated Contraindications: ongoing arrhythmias or refractory hypoxemia Complications: 1.3% of 4,000 flexible bronchoscopies (Pue 1995) 25% of complications due to premedications or anesthetic drugs (Credle 1974) Bleeding, infection

CT can also be used to diagnose TBM and has several advantages
over bronchoscopy Noninvasive Fast, entire central airway imaged in a few seconds High spatial resolution, great anatomic coverage Opportunity for multiplanar reformation and 2D, 3D reconstruction images Can observe additional imaging features characteristic of TBM

2D CT reconstruction Inhalation Exhalation Segmental tracheal collapse
Carden 2005 2D CT reconstruction Inhalation Exhalation Segmental tracheal collapse

An important advantage of CT over bronchoscopy:
Additional radiographic abnormalities can be identified to characterize TBM. A few observations include …

“Frown sign” in 50% TBM patients
Dynamic expiratory CT 64 year old man with chronic cough Trachea is collapsed with crescentaric, frown-like configuration of the airway lumen Lee 2009

“Lunate configuration”
Dynamic expiratory CT 71 year old woman with dyspnea, chronic cough Coronal diameter is widened compared with sagittal diameter Lee 2009

Air trapping has also been observed in TBM patients
52 year old man with idiopathic TM and persistent cough after mainstem bronchi stent Focal collapse of proximal right upper lobe bronchus. Right upper lobe is hyperlucent, consistent with air-trapping Gilkeson 2001

What is the extent and distribution of air trapping in TBM?
First study to report air trapping in TBM: “Air trapping was observed with a higher frequency and greater severity in patients with TBM than in the control group.” -Zhang 2004 Retrospective case-control study 10 bronchospically diagnosed cases TBM (5 men, 5 women, aged y, 1 asthma, 3 emphysema) 10 controls (3 men, 7 women, aged y, 5 asthma, 1 emphysema) Statistical analysis: Mann-Whitney Wilcoxon U test of the median group value for cases vs. controls

Controls: 6/10 air trapping, median score 2 (range 0-3)
Cases: 10/10 air trapping median score 5 (range 2-12) Controls: 6/10 air trapping, median score 2 (range 0-3) “MEDIAN TOTAL air trapping score” was significantly higher in TBM group vs. control group (p<0.001) Zhang 2004

Is air trapping specific to TBM cases?
There was also air trapping in the control group (regardless of history of chronic airway disease), although less severe (median score 5 vs. 2) Distribution: Air-trapping in cases was mostly lobular (8/10) but not always (2/10) Lobular air trapping was also observed in 3/10 controls Limitations of Zhang 2004: Small sample size Wilcoxon is a parametric test of the median difference between the groups. It is highly influenced by outliers. 29

Air trapping score (Max 12)
To check the appropriate use of the Wilcoxon test of the median difference between cases and controls: Cases: median score 5, mean 6, range 2-12 * * * * * * * * * * Air trapping score (Max 12) * * * * * * * * * * Controls: median score 2, mean 1.6, range 0-3 After assessing for outliers (case scores 11 and 12), there was no change in the median score, although the mean decreased from 6 to 4.6. Thus, I agree with Zheng et al. that there is a statistically significant difference between the median air-trapping score in cases vs. controls after a sensitivity analysis for potential outliers.

Given the advantages of CT… What is the quality of CT studies,
and how well do CT findings correlate with the gold standard, bronchoscopic diagnosis of TBM?

CT vs. bronchoscopy landmark studies
Single-detector spiral CT scan: compare cross-sectional area of the trachea during inspiratory and end-expiratory CT scan Aquino (2001), case-control study Multi-detector helical CT scan: captures continuous expiratory phase of respiration Gilkeson (2001), case series

Expiratory CT vs. bronchoscopy
Aquino (2001), case-control study N=12 bronchoscopically diagnosed cases acquired TM; after excluding patients whose TM not seen on CT, N=10 (6 men, 4 women, aged y), 23 healthy controls (15 men, 8 women, aged y) Statistical analysis: t-test, receiver operator curve Cross-sectional area between inspiratory and expiratory CT more sensitive and specific than sagittal and coronal diameters for detecting TM >18% reduction in upper trachea and >28% reduction in midtrachea cross-sectional area had positive predictive value %, negative predictive value % Suggests end-expiratory imaging may require lower threshold criterion than ≥ 50% narrowing especially if sagittal or coronal diameters used

Percent change in tracheal area not always >50% among Aquino study of bronchospically confirmed TBM cases Aquino 2001

Percent change in upper and mid trachea cross-sectional area greater in cases than controls but not always > 50% Coronal (Table 4) and saggital diameters (Table 3 not shown) lower than cross-sectional area (Table 2) and < 50% Aquino 2001

Aquino strengths & limitations
Bronchospically confirmed TM cases Automated measurement of tracheal lumen and cross sectional area Limitations: Selection bias: Appropriate exclusion of 2 bronchospically confirmed TM cases (2/12)?  Inclusion would decrease reported positive and negative predictive values Small sample size … but use of student’s t-test assumes normality Potential investigator bias: radiologists not blinded Similarity between cases and (younger) controls?

Dynamic MDCT vs. bronchoscopy
Gilkeson (2001), case series 13 patients with “suspected” TBM (7 men, 6 women, aged y, 3 asthma) Multidetector inspiratory—dynamic expiratory CT and spirometry performed on all patients Fiberoptic bronchoscopy performed on 6/13 patients Statistical analysis: Not provided! Results: All patients had airway collapse on inspiratory—dynamic expiratory CT that was highly correlated with degree of collapse on bronchoscopy Conclusion: supports more conservative diagnostic threshold of >50-70% narrowing on forced expiration to diagnose TBM

Bronchos-copy results for 6/13 patients
Note: Bronchos-copy results for 6/13 patients Exact value of collapse not given for CT and bronchos-copy, only ranges e.g , Gilkeson 2001

Limitations of Gilkeson’s dynamic MDCT vs
Limitations of Gilkeson’s dynamic MDCT vs. bronchoscopy case series study Selection bias: “Our cohort was a highly selected patient population without healthy control subjects” Potential outcome misclassification for 7/13 patients without bronchoscopy: patients with “suspected TBM” Investigator bias: patient histories known, non-blinded Small sample size: N=6 with both bronchoscopy & CT Case series, no control group, cannot evaluate statistical significance of results Nebulous statistical methodology CT and bronchoscopy values given as 25 percentage point ranges (e.g , ), not exact values Correlation coefficients not provided  Questionable internal & external validity generalization

To illustrate how selection bias could impact results in a case series study:
Bronchoscopy TBM Case Control + TBM - TBM Dynamic MDCT a b c d Odds ratio, OR = a * d = a * d = OR b * c b * c Increased patients in box “a” (patients with TBM on bronchoscopy and dynamic CT, most likely in this study) or fewer patients in box “c” would result in an increased odds that patients have TBM by bronchoscopy (outcome) given TBM by MDCT (exposure)

There are also different types of CT studies
There are also different types of CT studies. How well do they correlate with each other for diagnosing TBM? Dynamic vs. end-expiratory CT: Baroni (2005) Ferretti (2008)

Dynamic CT vs. end-expiratory CT
Baroni (2005), case series N = 34 with CT diagnosis of TBM; after exclusions N = 14 (11 men, 3 women, aged years) Airway collapse measured by multi-detector row CT at end inspiration, dynamic expiration, and end expiration at aortic arch, carina, bronchus Statistical analysis: paired two-tailed t test Dynamic expiratory CT elicited significantly greater airway collapse than standard end-expiratory CT for all individuals at all three levels (all p < 0.005) Biologically consistent with fact that dynamic expiration produces higher level of intrathoracic-extratracheal pressure than end expiration

Bronschospic results available for N =10
From bronchoscopy: 7/14 with TBM 3/14 without TBM 4/14 data unavailable Baroni 2005

TBM No TBM Bronchoscopy 3 2 Dynamic Expiration 1 End Expiration >
Baroni 2005 44

TBM No TBM Bronchoscopy 5 2 Dynamic Expiration 4 1 End Expiration >
Baroni 2005

TBM No TBM Bronchoscopy 4 2 Dynamic Expiration End Expiration 1 >
End Expiration 1 Baroni 2005

Baroni cont. Dynamic vs. end expiratory imaging:
Airway collapse was consistently greater in dynamic expiration compared with end expiration Dynamic: More often diagnosed TBM correctly … but also over-diagnosed TBM in non-cases End expiration: More likely to miss TBM … but never diagnosed TBM in non-cases When using the criteria of >50% reduced cross-sectional area, there was disagreement in TBM diagnoses in 5/9 (56%) patients at the aortic arch, 6/10 (60%) patients at the carina, 6/7 (86%) patients at the bronchus intermedius Limitations: selection bias, small sample size with 20/34 excluded, non-blinded, lumens hand-traced But also diagnosed TBM when it didn’t exist = But fewer instances calling TBM when it didn’t exist

Dynamic CT vs. end-expiratory CT
Ferretti (2008), prospective study 70 patients with suspected TBM Central airway collapse measured from the percentage change in area and diameter between end inspiration, and two expiratory techniques at: Trachea at three levels Right and left main bronchi, sagittal diameter Airway collapse significantly greater with dynamic expiratory imaging than end-expiratory imaging: Lower trachea (26% vs. 17%, p<0.009) Right main bronchus (25% vs. 14%, p<0.01) Left main bronchus (25% vs. 13%, p<0.01)  Dynamic expiratory consistently diagnoses more patients with TBM than end-expiratory imaging

What are the limitations in using CT imaging to diagnose TBM?
Healthy, asymptomatic individuals may demonstrate expiratory collapse that exceeds the criterion for TBM Recommendations Use a more conservative threshold of 70% in dynamic CT as indicative of TBM Correlate MDCT results with respiratory symptoms and functional impairment Further research that stratifies by age, sex, race/ethnicity, coexistent pulmonary disease, and other risk factors for TBM Lee 2009

CT limitations Limitation 2:
Potential “double dose” radiation exposure in paired inspiratory-expiratory CT Recommendations Low-dose technique possible without compromising image quality High contrast between air-filled trachea and soft tissue structures already present No difference observed between standard ( mA) and low-dose (40-80mA) radiation for assessing tracheal lumen during dynamic expiration (Zhang 2003) Lee 2009

Should MDCT replace bronchoscopy?
Improved ability to diagnose TBM with CT?  Sparse studies afflicted by selection bias and investigator bias report correlation between CT and bronchosocpy, but more data warranted 2. Should MDCT be the new gold standard?  Consider both strengths and limitations of CT 3. How/When is there consensus to replace the gold standard?  Historically not always data-driven, may be influenced by subspecialty groups 4. If CT replaces bronchoscopy, how should the definition and diagnostic criteria of TBM be revised?

Beyond CT, what alternative diagnostic imaging modalities have been studied?

Imaging: MRI Dynamic MRI during forced expiration and cough
Preferred method for evaluating extrinsic airway abnormalities (e.g. vascular compression syndromes) in children (Faust 2002) Advantages: Repeated assessment during multiple respiratory maneuvers without ionizing radiation exposure Disadvantages: COST!! Sensitivity and specificity compared with bronchoscopy and CT? To be demonstrated in case-control studies

MRI child with vascular compression syndrome
Narrowed trachea secondary to vascular entrapment Carden 2005

Among adults, MRI during coughing showed significantly greater collapsibility in bronchospically confirmed TBM cases (N=6) compared with healthy controls (N=13) (p<0.05) Suto1998

44 year old man with bronchospically confirmed TM
Axial MRI during coughing also resulted in significantly greater collapsibility than forced expiration and inspiration for both cases and controls (p<0.01) 44 year old man with bronchospically confirmed TM forced inspiration forced expiration coughing Suto1998

Virtual bronchoscopy 57 year old woman with suspected congenital lobar emphysema of right lung
Complete collapse of lower lobe orifice (authors state this was not appreciated on axial CT imaging) Mild narrowing but patent right middle (M) and lower (L) lobe bronchi Gilkeson 2001

Imaging summary CXR - assess baseline chronic disease or new infection
However, cannot diagnose TBM Bronchoscopy, flexible - historical gold standard Dynamic CT - new standard??? Diagnositic threshold should be higher in dynamic CT but lower for end-expiratory CT MRI Multiple maneuvers and assessments possible without radiation exposure Significantly greater cost Virtual bronchoscopy – more studies warranted 58

Do TBM patients exhibit abnormalities in pulmonary function tests?
Yes, but many findings are non-specific to TBM Decreased FEV  also seen in obstruction Low peak flow rate with a rapid decrease in flow  also seen in obstruction Flow oscillations  also seen in obstructive sleep apnea, structural or functional larynx abnormalities, neuromuscular disease Elevated airway resistance Inspiratory limb shape preserved

Are there TBM-specific findings in pulmonary function tests?
Unique “notch” in forced expiratory spirograms in TBM “Break” or “notch” in expiratory phase of flow-volume curve thought to represent the point of major airway collapse after dead space air volume is emptied First described by Koblet and Wyss (1955) and observed in 3 subsequent studies Limitation: Moderate to severe emphysema patients display similar notch, regardless of concurrent TBM  Unreliable for diagnosing TBM

Flow-volume loops in TBM
There is a rapid decline in maximal expiratory flow following a sharp peak associated with collapsed central airways from negative transmural pressure. Normal inspiratory profile from dilation of central airways during treatment with positive transmural pressure. Carden 2005

Is there an association between obstruction findings in spirometry and severity of TBM?
Most recent studies report NO association Obstruction from spirometry is proportional to severity of TBM (Nuutinen 1977) No correlation between obstruction and TBM severity (Gilkeson 2001) No correlation between central airway collapse (80 suspected and confirmed TBM cases) and degree of obstruction via FEV1. Central airway collapse was observed regardless of expiratory flow limitation during quiet breathing. One cannot assume central airway narrowing (especially during quiet exhalation) in patients with obstructive airway disease. Likewise, symptomatic central airway narrowing may exist in patients without significant airflow obstruction (Loring 2007)

of symptomatic patients who may benefit from treatment?
Part III: How should the definition and diagnostic criteria for TBM be revised to improve sensitivity and specificity of symptomatic patients who may benefit from treatment?

Challenges in diagnosing TBM
Lack of clarity in definitions, measurement criteria and terminology Need to establish normal vs. abnormal narrowing of central airways TBM is a spectrum Patients with TBM present with a range of symptoms Coexistence of asthma, COPD among TBM patients Currently no universally agreed upon classification system  Proposed system by Murgu 2007 …. 64 64

Severity of airway disease
FEMOS classification Functional status Extent of abnormality Morphology Origin Severity of airway disease Murgu 2007

FEMOS classification system
Functional status – modified World Health Organization functional classification Class I (F1) – no limitation Class II (F2) – mild limitation of physical activity Class III (F3) – marked limitation of physical activity Class IV (F4) – unable to perform any physical activity at rest Murgu 2007

Extent of abnormality based on location and distribution of the abnormal airway segment viewed on bronchoscopy Normal (E1) – no airway abnormality Focal (E2) – abnormality present in one main or lobar bronchus or one tracheal region (upper, mid or lower) Multifocal (E3) – abnormality present in two contiguous or at least two non-contiguous regions Diffuse (E4) – abnormality present in more than two contiguous regions Murgu 2007

Origin is the etiology of the airway abnormality Idiopathic – no underlying etiology identified Secondary – result of an illness or other pathological process Murgu 2007

Severity of airway collapse based on the degree of airway lumen reduction during expiration as observed in bronchoscopy Normal (S1) – no abnormal airway collapse Mild (S2) – 50-75% expiratory airway collapse Moderate (S3) – % expiratory airway collapse Severe (S4) – 100% expiratory airway collapse and airway walls make contact Murgu 2007

Suggestions for future TBM studies
Prospective cohort studies ideal to decrease selection bias, but challenging to conduct To decrease bias in case control studies: Careful selection of control group (ideally identical to cases by all characteristics except TBM) Large sample size, test normality assumption To reduce investigator bias, blinding to subjects’ case status and history Automated measurement of tracheal lumen and cross-sectional area with exact values provided Review by at least two radiologists and report kappa statistic of inter-observer agreement

Part IV: Treatment (Briefly)
Asymptomatic  No treatment Symptomatic: Supportive care Control bronchospasm Treat primary problem eg obstructive disease Critical condition: Positive-pressure ventilation CPAP increases FVC and reduces airway collapse (Ferguson 1993) Facilitate mobilization of secretions Severe cases may benefit from surgery: Tracheostomy: bypass malacic segment or tube. May be complicated by recurrent tracheobronchitis, stenosis at stoma site Ceramic rings: Longest successful follow-up in 16/16 patients after 6.4 years (Amedee 1992) Stents (silicone > metal): patients reported immediate improvement in symptoms but PFTs declined at mean 15 months follow-up after stenting (Gotway 2002). Center and operator dependent. High complications. More research needed.

After tracheoplasty Carden 2005

Lessons from Dr. Gosselin
Resist algorithms & binary thinking People are like snowflakes Carden 2005

References Amedee RG, Mann WJ, Lyons GD. Tracheomalacia repair using ceramic rings. Otolarngol Head Neck Surg 1992;106:270-4. Aquino SL, Shepard JO, Ginns LC, et al. Acquired tracheomalacia: detection by expiratory CT scan. J Comput Assist Tomography 2001;25:394-9. Baroni RH, Feller-Kopamn D, Nishino M, et al. Tracheobronchomalacia: comparison between end-expiratory and dynamic expiratory CT for evaluation of central airway collapse. Radiology 2005;235: Carden KA. Tracheomalacia and tracheobronchomalacia in children and adults: an in-depth review. Chest 2005;127: Credle WF Jr, Smiddy JF, Elliott RC. Complications of fiberoptic bronchoscopy. Am Rev Respir Dis 1974;109:67-72. Ferguson GT, Benoist J. Nasal continuous positive airway pressure in the treatment of tracheobronchomalacia. Am Rev Respir Dis 1993;147: Ferretti GR, Jankowski A, Perrin MA, et al. Multi-detector CT evaluation in patients suspected of tracheobronchomalacia: comparison of end-expiratory with dynamci expiratory volumetric acquisitions. Eur J Radiol 2008;68:340-6. Gilkeson RC, Ciancibello LM, Hejal RB, et al. Tracheobronchomalacia: dynamic airway evaluation with multidetector CT. AJR 2001;176: Gotway MB, Golden JA, JaBerge JM, et al. Benign tracheobronchial stenoses: changes in short-term and long-term pulmonary function testing after expandable metallic stent placement. J Comput Assist Tomogr 2002;26: Herzog H. Expiratory stenosis of the trachea and great bronchi by loosening of the membranous portion; plastic chip repair. Thoraxchirurgie 1958;5: Ikeda S, Hanawa T, Konishi T, et al. Diagnosis, incidence, clinicopathology and surgical treatment of acquired tracheobronchomalacia. Nihon Kyobu Shikkan Gakkai Zasshi 1992;30:

References Jokinen K, Palva T, Nuutinen J. Chronic bronchitis: a bronchologic evaluation. ORL J Otorhinolarygngol Relat Spec 1976;38: Jokinen K, Palva T, Sutinen S, Nuutinen. Acquired tracheobronchomalacia. Annals of Clinical Research 1977;9:52-7. Kandasway C, Balasubramanian V. Review of adult tracheomalacia and its relationship with chronic obstructive pulmonary disease. Curr Opin Pulm Med 2009;15:113-9. Lee EY, Litmanovich D, Boiselle PM. Multidetector CT evaluation of tracheobronchomalacia. Radiol Clin N Am 2009;47:261-9. Loring SH, O’Donnell CR, Feller-Kopman DJ, Ernst A. Central airway mechanics and flow limitation in acquired tracheobronchomalacia. Chest 2007;131: Murgu SD, Cold HG. Description of a multidimensional classification system for patients with expiratory central airway collapse. Respirology 2007;12: Palombini BC, Villanova CA, Araujo E, et al. A pathologenic triad in chronic cough: asthma, post nasal drip, and gastroesophageal reflux disease. Chest 1999;116: Pue CA, Pacht ER. Complications of fiberoptic bronchoscopy at a university hospital. Chest 1995;107:430-2. Suto Y, Tanabe Y. Evaluation of tracheal collapsibility in patients with tracheomalacia during dynamic MR imaging during coughing. AJR 1998;171:393-4. Zhang J, Hasegawa I, Feller-Kopamn D, et al. Dynamic expiratory volumetric CT imaging of the central airways: comparison of standard-dose and low-dose techniques. Acad Radiol 2003;10: Zhang J, Hasegawa I, Hatabu H, et al. Frequency and severity of air trapping at dynamic expiratory CT in patients with tracheobronchomalacia. AJR 2004;182:81-5. .

Melissa Wei MS4/MPH student Diagnostic Radiology July 2, 2009

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