Presentation on theme: "Melissa Wei MS4/MPH student Diagnostic Radiology July 2, 2009"— Presentation transcript:
1Melissa Wei MS4/MPH student Diagnostic Radiology July 2, 2009 Tracheomalacia and Tracheobronchomalacia Challenging the diagnostic gold standard and refining the definitionMelissa WeiMS4/MPH studentDiagnostic RadiologyJuly 2, 2009
2I 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.
3The 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?
4Presentation outline Part I: Background Definition, Epidemiology, Classification,Pathophysiology, Clinical presentationPart II: Diagnostic optionsHistorical perspective, bronchscopy as the currentgold standard, CT, alternatives to CT, spirometryPart III: Redefining TBMChallenges, suggestionsPart IV: Treatment (briefly)
5Part I: What is Tracheomalacia? Malacia: softening of the tissuesTracheomalacia (TM): weakness of tracheal wall and/or supporting tracheal cartilage, resulting in excessive expiratory collapseTracheobronchomalacia (TBM): mainstem bronchi also involvedSeverity defined by extent of lumenal obstruction duringexpirationMild: 50% lumen obstructedModerate: 75% lumen obstructedSevere: posterior wall reaches anterior wallClinical significance:Flaccidity of tracheal cartilage increases risk of airway collapse especially with increased airflow demand5
6Mild tracheomalacia45 year old asymptomatic man with normal pulmonary function51% decreased cross-sectional area of tracheal lumen during expiration on axial dynamic CTNormal oval-shaped tracheal lumenLee 2009
7Severe tracheomalacia Young child with compressed trachea from mediastinal vascular anomalyMild tracheal compression from right-sided aortic arch (R)Near collapse of tracheaLee 2009
8Epidemiology 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 adults10-15% 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
9ClassificationSecondary (acquired) TMPost-traumaticIntubationTracheostomyExternal chest traumas/p lung transplantationChronic inflammation/irritantsEmphysemaChronic infection/bronchitisChronic external compression of the tracheaTumors (benign or malignant)CystsAbscessesAortic aneurysmVascular rings, undiagnosed in childhoodPrimary (congenital) TM <<Genetic eg polychondritisIdiopathic “giant trachea” or“Mounier-Kuhn” syndromeIn kids, TM = #1 congenital tracheal anomaly; associated with transesophageal fistula
10Pathophysiology Normal intrathoracic trachea Trachea dilates with inspiration, narrows with expirationReflects difference between intrthoracic and intraluminal pressuresTracheomalacia = exaggerated physiologic process Accentuated changes in tracheal diameterIntrathoracic problem (most common): excessive narrowing whenIntrathoracic pressure > Intraluminal pressureEx) Forced expiration, Cough, Valsalva maneuverExtrathoracic problem: negative intrapleural pressures transmitted to extrathoracic trachea due to pleural reflections upper airway collapses during inspirationAtrophy of longitudinal elastic fibers of pars membranacea or impaired cartilage integrity airway soft, susceptible to collapse10
11Most common causes #1 Weakening of tracheal wall Intubation: recurrent, prolonged pressure necrosis, impaired blood flow, recurrent infections, mucosal inflammationHigh-dose steroids#1 Inflammation/irritation of tracheal wallSmokingRecurrent infections: chronic bronchitis, pneumonia3. Compression of tracheaMalignancy, abscess, cysts, goiter4. Direct damage to tracheal wallExternal trauma or surgery5. Vascular malformationsDouble aortic arch, R aortic arch with aberrant L subclavian a, ligamentum arteriosum11
12Clinical presentation 1. Symptoms are nonspecific (Jokinen 1977, Carden 2005)Dyspnea (63-75%)Chronic cough (50%)- sputum production- “seal like” or barking coughHemoptysis (33%)Episodic choking; syncope with forced exhalation and cough2. Concurrent respiratory disease common (Carden 2005)Chronic bronchitisEmphysemaBronchial cancerRecurrent respiratory infectionAsthma3. Pts may be Asymptomatic …… until stressed by infection (bronchitis, pneumonia)Intubated patients: masked by PPV maintaining airway12
14Differential diagnosis LaryngomalaciaSubglottic stenosisVocal cord paralysisTBM is commonly misdiagnosed as:COPDAsthmaAmong 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 200914
15Part II: What are the diagnostic options? Imaging modalitiesPlain radiographs – not diagnosticHistorical modalitiesFlexible bronchoscopy – current gold standardStandard spiral CTDynamic expiratory multi-detector CT (MDCT)MRIVirtual bronchoscopyPulmonary function testsResearch ongoing, not diagnostic15
16Imaging: Plain radiographs Limited use of plain radiographs to diagnose TBMTBM is a dynamic process accentuated by forced expirationCannot visualize on anterioposterior or lateral chest radiographsExceptionTBM secondary to compression from other structures (e.g. mediastinal goiter, tumor) may be visualized
17Historic modalities: We’ve come a long way Cinetracheograms to visualize tracheal flutterFluroscopy to estimate tracheal diameterTracheograms and bronchograms Replaced by bronchoscopy, which is more sensitive for diagnosing TBM
18Bronchoscopy is the current gold standard for diagnosing TBM Visualize dynamic tracheal or bronchial collapseTrachea may also be widenedFlexible bronchoscope over rigidPatient can breathe spontaneously and perform additional maneuvers to elicit collapse of the airwaysExpiratory effort to achieve airway wall collapse through maneuvers (deep breathing, forced expiration, straining, coughing, others) has not been standardized
20However, bronchoscopy has limitations Invasive, requires general anesthesia (rigid bronchoscopy) or local anesthesia (flexible bronchoscopy), and more than half of patients sedatedContraindications: ongoing arrhythmias or refractory hypoxemiaComplications:1.3% of 4,000 flexible bronchoscopies (Pue 1995)25% of complications due to premedications or anesthetic drugs (Credle 1974)Bleeding, infection
21CT can also be used to diagnose TBM and has several advantages over bronchoscopyNoninvasiveFast, entire central airway imaged in a few secondsHigh spatial resolution, great anatomic coverageOpportunity for multiplanar reformation and 2D, 3D reconstruction imagesCan observe additional imaging features characteristic of TBM
23An important advantage of CT over bronchoscopy: Additional radiographic abnormalities can be identified to characterize TBM.A few observations include …
24“Frown sign” in 50% TBM patients Dynamic expiratory CT64 year old man with chronic coughTrachea is collapsed with crescentaric, frown-like configuration of the airway lumenLee 2009
25“Lunate configuration” Dynamic expiratory CT71 year old woman with dyspnea, chronic coughCoronal diameter is widened compared with sagittal diameterLee 2009
26Air trapping has also been observed in TBM patients 52 year old man with idiopathic TM and persistent cough after mainstem bronchi stentFocal collapse of proximal right upper lobe bronchus. Right upper lobe is hyperlucent, consistent with air-trappingGilkeson 2001
27What 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 2004Retrospective case-control study10 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 testof the median group value for cases vs. controls
28Controls: 6/10 air trapping, median score 2 (range 0-3) Cases: 10/10 air trappingmedian 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
29Is 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 controlsLimitations of Zhang 2004:Small sample sizeWilcoxon is a parametric test of the median difference between the groups. It is highly influenced by outliers.29
30Air 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 0-3After 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.
31Given the advantages of CT… What is the quality of CT studies, and how well do CT findingscorrelate with the gold standard, bronchoscopic diagnosis of TBM?
32CT vs. bronchoscopy landmark studies Single-detector spiral CT scan: compare cross-sectional area of the trachea during inspiratory and end-expiratory CT scanAquino (2001), case-control studyMulti-detector helical CT scan: captures continuous expiratory phase of respirationGilkeson (2001), case series
33Expiratory CT vs. bronchoscopy Aquino (2001), case-control studyN=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 curveCross-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
34Percent change in tracheal area not always >50% among Aquino study of bronchospically confirmed TBM casesAquino 2001
35Percent 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
36Aquino strengths & limitations Bronchospically confirmed TM casesAutomated measurement of tracheal lumen and cross sectional areaLimitations:Selection bias: Appropriate exclusion of 2 bronchospically confirmed TM cases (2/12)? Inclusion would decrease reported positive and negative predictive valuesSmall sample size … but use of student’s t-test assumes normalityPotential investigator bias: radiologists not blindedSimilarity between cases and (younger) controls?
37Dynamic MDCT vs. bronchoscopy Gilkeson (2001), case series13 patients with “suspected” TBM (7 men, 6 women, aged y, 3 asthma)Multidetector inspiratory—dynamic expiratory CT and spirometry performed on all patientsFiberoptic bronchoscopy performed on 6/13 patientsStatistical analysis: Not provided!Results: All patients had airway collapse on inspiratory—dynamic expiratory CT that was highly correlated with degree of collapse on bronchoscopyConclusion: supports more conservative diagnostic threshold of >50-70% narrowing on forced expiration to diagnose TBM
38Bronchos-copy results for 6/13 patients Note:Bronchos-copy results for 6/13 patientsExact value of collapse not given for CT and bronchos-copy, only ranges e.g ,Gilkeson 2001
39Limitations of Gilkeson’s dynamic MDCT vs Limitations of Gilkeson’s dynamic MDCT vs. bronchoscopy case series studySelection 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-blindedSmall sample size: N=6 with both bronchoscopy & CTCase series, no control group, cannot evaluate statistical significance of resultsNebulous statistical methodologyCT and bronchoscopy values given as 25 percentage point ranges (e.g , ), not exact valuesCorrelation coefficients not provided Questionable internal & external validity generalization
40To illustrate how selection bias could impact results in a case series study: BronchoscopyTBM Case Control+ TBM- TBMDynamicMDCTabcdOdds ratio, OR = a * d = a * d = ORb * c b * cIncreased 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)
41There 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)
42Dynamic CT vs. end-expiratory CT Baroni (2005), case seriesN = 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, bronchusStatistical analysis: paired two-tailed t testDynamic 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
43Bronschospic results available for N =10 From bronchoscopy:7/14 with TBM3/14 without TBM4/14 data unavailableBaroni 2005
44TBM No TBM Bronchoscopy 3 2 Dynamic Expiration 1 End Expiration > Baroni 200544
45TBM No TBM Bronchoscopy 5 2 Dynamic Expiration 4 1 End Expiration > Baroni 2005
46TBM No TBM Bronchoscopy 4 2 Dynamic Expiration End Expiration 1 > End Expiration1Baroni 2005
47Baroni cont. Dynamic vs. end expiratory imaging: Airway collapse was consistently greater in dynamic expiration compared with end expirationDynamic: More often diagnosed TBM correctly… but also over-diagnosed TBM in non-casesEnd expiration: More likely to miss TBM… but never diagnosed TBM in non-casesWhen 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 intermediusLimitations: selection bias, small sample size with 20/34 excluded, non-blinded, lumens hand-tracedBut also diagnosed TBM when it didn’t exist =But fewer instances calling TBM when it didn’t exist
48Dynamic CT vs. end-expiratory CT Ferretti (2008), prospective study70 patients with suspected TBMCentral airway collapse measured from the percentage change in area and diameter between end inspiration, and two expiratory techniques at:Trachea at three levelsRight and left main bronchi, sagittal diameterAirway 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
49What are the limitations in using CT imaging to diagnose TBM? Healthy, asymptomatic individuals may demonstrate expiratory collapse that exceeds the criterion for TBMRecommendationsUse a more conservative threshold of 70% in dynamic CT as indicative of TBMCorrelate MDCT results with respiratory symptoms and functional impairmentFurther research that stratifies by age, sex, race/ethnicity, coexistent pulmonary disease, and other risk factors for TBMLee 2009
50CT limitations Limitation 2: Potential “double dose” radiation exposure in paired inspiratory-expiratory CTRecommendationsLow-dose technique possible without compromising image qualityHigh contrast between air-filled trachea and soft tissue structures already presentNo difference observed between standard ( mA) and low-dose (40-80mA) radiation for assessing tracheal lumen during dynamic expiration (Zhang 2003)Lee 2009
51Should 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 warranted2. Should MDCT be the new gold standard? Consider both strengths and limitations of CT3. How/When is there consensus to replace the gold standard? Historically not always data-driven, may be influenced by subspecialty groups4. If CT replaces bronchoscopy, how should the definition and diagnostic criteria of TBM be revised?
52Beyond CT, what alternative diagnostic imaging modalities have been studied?
53Imaging: 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 exposureDisadvantages: COST!!Sensitivity and specificity compared with bronchoscopy and CT? To be demonstrated in case-control studies
54MRI child with vascular compression syndrome Narrowed trachea secondary to vascular entrapmentCarden 2005
55Among 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
5644 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 TMforced inspiration forced expiration coughingSuto1998
57Virtual 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 bronchiGilkeson 2001
58Imaging summary CXR - assess baseline chronic disease or new infection However, cannot diagnose TBMBronchoscopy, flexible - historical gold standardDynamic CT - new standard???Diagnositic threshold should be higher in dynamic CT but lower for end-expiratory CTMRIMultiple maneuvers and assessments possible without radiation exposureSignificantly greater costVirtual bronchoscopy – more studies warranted58
59Do TBM patients exhibit abnormalities in pulmonary function tests? Yes, but many findings are non-specific to TBMDecreased FEV also seen in obstructionLow peak flow rate with a rapid decrease in flow also seen in obstructionFlow oscillations also seen in obstructive sleep apnea, structural or functional larynx abnormalities, neuromuscular diseaseElevated airway resistanceInspiratory limb shape preserved
60Are 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 emptiedFirst described by Koblet and Wyss (1955) and observed in 3 subsequent studiesLimitation: Moderate to severe emphysema patients display similar notch, regardless of concurrent TBM Unreliable for diagnosing TBM
61Flow-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
62Is there an association between obstruction findings in spirometry and severity of TBM? Most recent studies report NO associationObstruction 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)
63of symptomatic patients who may benefit from treatment? Part III:How should the definition and diagnostic criteria for TBM be revised to improve sensitivity and specificityof symptomatic patients who maybenefit from treatment?
64Challenges in diagnosing TBM Lack of clarity in definitions, measurement criteria and terminologyNeed to establish normal vs. abnormal narrowing of central airwaysTBM is a spectrumPatients with TBM present with a range of symptomsCoexistence of asthma, COPD among TBM patientsCurrently no universally agreed upon classification system Proposed system by Murgu 2007 ….6464
65Severity of airway disease FEMOS classificationFunctional statusExtent of abnormalityMorphologyOriginSeverity of airway diseaseMurgu 2007
66FEMOS classification system Functional status – modified World Health Organization functional classificationClass I (F1) – no limitationClass II (F2) – mild limitation of physical activityClass III (F3) – marked limitation of physical activityClass IV (F4) – unable to perform any physical activity at restMurgu 2007
67FEMOS classification system Extent of abnormality based on location and distribution of the abnormal airway segment viewed on bronchoscopyNormal (E1) – no airway abnormalityFocal (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 regionsDiffuse (E4) – abnormality present in more than two contiguous regionsMurgu 2007
68FEMOS classification system Extent of abnormality based on location and distribution of the abnormal airway segment viewed on bronchoscopyNormal (E1) – no airway abnormalityFocal (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 regionsDiffuse (E4) – abnormality present in more than two contiguous regionsMurgu 2007
69FEMOS classification system Origin is the etiology of the airway abnormalityIdiopathic – no underlying etiology identifiedSecondary – result of an illness or other pathological processMurgu 2007
70FEMOS classification system Severity of airway collapse based on the degree of airway lumen reduction during expiration as observed in bronchoscopyNormal (S1) – no abnormal airway collapseMild (S2) – 50-75% expiratory airway collapseModerate (S3) – % expiratory airway collapseSevere (S4) – 100% expiratory airway collapse and airway walls make contactMurgu 2007
71Suggestions for future TBM studies Prospective cohort studies ideal to decrease selection bias, but challenging to conductTo 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 assumptionTo reduce investigator bias, blinding to subjects’ case status and historyAutomated measurement of tracheal lumen and cross-sectional area with exact values providedReview by at least two radiologists and report kappa statistic of inter-observer agreement
72Part IV: Treatment (Briefly) Asymptomatic No treatmentSymptomatic:Supportive careControl bronchospasmTreat primary problem eg obstructive diseaseCritical condition:Positive-pressure ventilationCPAP increases FVC and reduces airway collapse (Ferguson 1993)Facilitate mobilization of secretionsSevere cases may benefit from surgery:Tracheostomy: bypass malacic segment or tube. May be complicated by recurrent tracheobronchitis, stenosis at stoma siteCeramic 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.
74Lessons from Dr. Gosselin Resistalgorithms&binary thinkingPeoplearelikesnowflakesCarden 2005
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