Tracheobronchomalacia and Excessive Dynamic Airway Collapse · bronchus (LMB), and even total collapse in the bronchus intermedius.12 A different study showed that the mean % collapse

Tracheobronchomalacia andExcessive Dynamic AirwayCollapse
Septimiu Murgu, MDa,*, Henri Colt, MDb
KEYWORDS

� Tracheobronchomalacia � Excessive dynamic airway collapse � Airway stents � Tracheoplasty� Noninvasive positive pressure ventilation � Airflow dynamics � Choke points� Functional bronchoscopy

KEY POINTS

� Tracheobronchomalacia is characterized as weakened or destroyed cartilage in the central airwaysresulting in expiratory flow limitation.

� Excessive dynamic airway collapse is characterized by excessive bulging of the posterior mem-brane inside the central airway lumen.

� A careful physiologic assessment of the impact of expiratory central airway collapse on airflow andfunctional status is warranted before treatment.

� Identification of the flow-limiting airway segments can be obtained by performing functional bron-choscopy before invasive interventions.

� Even when the central airway collapse is identified as responsible for symptoms, we suggest a con-servative approach with medical treatment and noninvasive positive pressure ventilation beforecommitting patients to potentially harmful effects resulting from airway stents or open surgicalprocedures.

DEFINITIONS AND CLASSIFICATIONS

Unambiguous definitions and clinically useful clas-sifications provide a common language for healthcare providers managing expiratory central airwaycollapse (ECAC). By applying accepted terminol-ogy in their practices, clinicians and scientists canstratify patients according to predefined objectivecriteria and analyze data. Consensual frameworksoffered by classification systems allow comparisonof data within populations over time and betweenpopulations at the same point in time, thus facili-tating meaningful research.1,2

Disclosure: The authors have no relationship with any coin the subject matter or materials discussed in this articlea Department of Medicine, University of Chicago PritzkeChicago, IL 60637, USA; b Department of Medicine, Univ400 City Tower, Orange, CA 92868, USA* Corresponding author.E-mail address: [email protected]

Clin Chest Med 34 (2013) 527–555http://dx.doi.org/10.1016/j.ccm.2013.05.0030272-5231/13/$ – see front matter � 2013 Elsevier Inc. All

In this regard, the collapse of the intrathoracictrachea and mainstem bronchi in adult patientshas been described using a variety of terms, in-cluding tracheobronchomalacia (TBM), tracheo-bronchial collapse, expiratory tracheobronchialcollapse, expiratory tracheobronchial stenosis,tracheobronchial dyskinesia, dynamic airway col-lapse (AC), and ECAC.3 However, these terms donot distinguish between collapse of the pars mem-branosa and collapse of the cartilaginous wall.ECAC is an accepted term to describe the narrow-ing of the central airways during expiration; it is a

mmercial company that has a direct financial interestor with any company making a competing product.r School of Medicine, 5841 South Maryland Avenue,ersity of California Irvine, 101 The City Drive South,

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Murgu & Colt528

syndrome comprising 2 different pathophysiologicentities: TBM, characterized by weakness of thetracheobronchial cartilaginous structures, and ex-cessive dynamic AC (EDAC), defined as excessivebulging of the posterior membrane into the air-way lumen during expiration without cartilagecollapse.2–6

A major controversy in the published literatureand among experts managing these patients isrepresented by the amount of collapse labeledas excessive. The frontier between normal andabnormal narrowing of the central airways duringexhalation has not been clarified, and investigatorspropose various cutoff values.6–12 There is vari-ability among studies in regards to anatomic loca-tion and respiratory maneuver used to measurenarrowing of the expiratory airway (Table 1).10–15

These facts may be the main source of inconsis-tency in reported prevalence of these disorders.The anatomic site used for measuring the collapseneeds to be standardized, because physiologicairway narrowing is more pronounced in the bron-chus intermedius and main carina than at theaortic arch or cricoid level.12

Results of dynamic computed tomography (CT)studies show that 70% to 80% of normal individ-uals meet the 50% criteria used for abnormalcollapse.6,12,16 Healthy volunteers with normallung function have shown mean levels of expira-tory collapse of 54% in the trachea, 67% in theright main bronchus (RMB), 61% in the left mainbronchus (LMB), and even total collapse in thebronchus intermedius.12 A different study showedthat the mean % collapse of normal volunteerswas 66.9% in the RMB and 61.4% in the LMB,with 73% of participants exceeding the currentlyaccepted cutoff value of 50% threshold fordefining bronchomalacia.17 Even in a disease pro-cess such as chronic obstructive pulmonary dis-ease (COPD), in which the central AC is morepronounced, the degree of narrowing may be in-dependent of disease severity and does not corre-late significantly with physiologic parameters.6,11

Excessive expiratory tracheal collapse defined asmore than 80% expiratory reduction in trachealluminal cross-sectional during dynamic CT wasshown to not significantly correlate with the pul-monary function tests (PFTs) or quality-of-life(QOL) measures.6,11

To reduce false-positive diagnoses and avoidunwarranted treatments, EDAC may be definedonly if clinically relevant excessive collapse isnoted during tidal breathing (Fig. 1). The degreeof pathologic expiratory collapse has not yetbeen established on physiologic basis becausework of breathing and symptoms depend notonly on the degree of airway narrowing but also

on its geometry and flow velocity.18 Therefore,the accurate assessment of the reduction in airwaylumen cross-sectional area becomes relevant forthe purpose of having a common language whenevaluating patients and communicating aboutTBM and EDAC, and not necessarily only todecide on need for therapeutic interventions.The degree of narrowing is only 1 factor involved

in flow limitation; it is only 1 criterion included inclassifications for this syndrome. Most systemsare limited by inconsistent definitions or by criteriaaddressing only the extent, severity, or cause butnot the 2 separate morphologic types of TBMand EDAC or the patient’s functional impairment(Table 2).10,13–15,19 A classification based onobjective quantifiable criteria has been developedand can be applied before and after therapeutic in-terventions to objectively document not only thechanges in the extent and severity of AC but alsothe impact of these changes on functional class(Table 3).2 The criteria of this system can begrouped in 2 sets: the descriptive factors includingmorphology and etiology, and stratification factorsthat can be scored objectively. The morphologycriterion describes the shape of the airway lumen,which is reduced during expiration as assessed bybronchoscopy or radiologic studies. ECAC has 5morphologic types (Fig. 2). Origin (etiology) de-scribes the underlying mechanism responsiblefor the abnormality: idiopathic or secondary toother disorders (Table 4). To describe functionalclass, this system used the World Health Organi-zation functional impairment scale, because of itseasy clinical applicability and because it does notaddress just dyspnea but the overall impact ofsymptoms on patient’s functional status. Theextent criterion describes the location and distri-bution of the abnormal airway segment as as-sessed by bronchoscopy or radiographic studies.The severity criterion describes the degree of theAC during expiration as assessed by bronchos-copy or radiographic studies. Since its introduc-tion in 2005, the terminology proposed in thissystem has been applied in clinical research ofthese disorders.5,6,20–24 This classification allowsmonitoring of the progression or improvement ofthe disease process and the outcome and dura-bility of different treatment strategies on airwaylumen patency and patient symptoms. Five do-mains are addressed: functional class (F), extent(E), morphology (M), origin (O), and severity ofAC (S). The F, E, and S parts of the system havean ordinal scale of 1 to 4 (see Table 3). Outcomesare documented as subscripts, for example F2 E2

S4, and should not be combined to form a singlenumber. This information can be tabulated orplotted to provide a visual temporal treatment

Table 1Studies using different cutoff values to define excessive central AC

ReferenceCutoff Value to Define Abnormal,Excessive AC During Expiration Comments

Aquino et al,7 2001 >28% expiratory reduction insagittal diameter

>18% expiratory reduction inCSA in the upper trachea

>28% expiratory reduction inCSA in the middle trachea

Only for tracheal collapseUsed paired inspiratory–staticend-expiratory CT

Stern et al,8 1993 35% expiratory reduction inCSA in normal individuals

Only for tracheal collapseUsed paired inspiratory–dynamic-expiratory CT

Nuutinen,9 1977 >50% expiratory reductionin sagittal diameter

For tracheal and bronchial collapseUsed bronchoscopic estimations

Zhang et al,75 2003 >50% expiratory reductionin CSA

Only for tracheal collapseLow-dose CT (40–80 mA) was justas accurate as the standard dose(240–280 mA)

Used paired inspiratory–dynamic-expiratory CT

Gilkeson et al,130 2001 >50% expiratory reduction in CSA For tracheal and bronchial collapsePaired inspiratory–dynamic-expiratory CT

Hein et al,66 2000 >50% expiratory reduction in CSA Only for tracheal collapseUsed paired inspiratory–dynamic-expiratory electron beamtomography

Boiselle et al,12 2009 >50% expiratory reduction in CSA Only for tracheal collapse inhealthy volunteers

Used low-dose pairedinspiratory–dynamic-expiratory CT

80% of healthy study participantsmet the criteria for abnormalcollapse

Litmanovich et al,17

2010>50% expiratory reduction in CSA Only for bronchial collapse


73% of healthy participantsexceeded the diagnostic thresholdlevel for abnormal bronchialcollapse

Masaoka et al,10 1996 >80% expiratory narrowing For tracheal and bronchial collapseUsed bronchoscopic estimations andfrontal and lateral radiographfilms to estimate the narrowing

Narrowing is not clearly defined asreduction of CSA or reduction indiameter

Boiselle et al,6 2012 >80% expiratory reduction in CSA Only for tracheal collapse inpatients with COPD


Abbreviations: COPD, chronic obstructive pulmonary disease; CSA, cross-sectional area; CT, computed tomography.

Tracheobronchomalacia 529

Fig. 1. Impact of respiratory maneuver and effort on degree of airway narrowing. Images A–D are obtained fromthe same patient undergoing flexible bronchoscopy for an unrelated reason (ie, right lower lobe atelectasis). Thetracheal cartilaginous wall is intact during all respiratory maneuvers. Normal tracheal lumen during inspiration(A). Physiologic, dynamic airway compression during tidal expiration (B). EDAC during forced expiration (C)and coughing (D).

Murgu & Colt530

map, charting patient progress through treatment.In this article, a description is given of how thissystem can be used in 2 clinical scenarios: TBMand EDAC.

Clinical Application: TBM

A patient with a history of extensive mediastinallymph node calcifications and bilateral upperlobe fibrosis was unable to clear secretions, hadprogressive dyspnea on exertion, and coughlimiting normal physical activities. The patientwas treated for asthma with inhaled and systemicsteroids for more than a year before a bronchos-copy, which revealed collapse of the anterior wallof the lower trachea. During tidal expiration, thiscollapse reached a 100% closure of the lumen(Fig. 3). This morphology was characteristic of

crescent-type malacia and was considered to becaused by secondary tracheobronchomegaly(caused by bilateral upper lobe fibrosis). Becauseof the patient’s lack of discomfort at rest, but pres-ence of increased symptoms with normal physicalactivity, his functional class was labeled as F2. Theprocess was limited to the lower trachea, thereforethe extent was labeled E2, and because the 2 wallsof the trachea were touching each other duringexpiration (100% closure), severity of airway nar-rowing was labeled as S4. Rigid bronchoscopywas performed and a straight silicone stent in-serted in to the lower trachea. After intervention,the patient was tapered off the steroids for his pre-sumed asthma and symptoms improved to normal(F1). Bronchoscopy showed no residual malacia(E1) and normal expiratory airway lumen (S1) (seeFig. 3).


Clinical Application: EDAC

A patient with COPD and obesity presented withworsening dyspnea. She had a history of severeoxygen and corticosteroid-dependent COPDlimiting her daily activities. The main finding onbronchoscopy was bulging of the posterior mem-brane in the lower trachea during tidal breathing,with narrowing of the airway lumen by 100% atthe level of main carina. This finding was con-sistent with EDAC morphology. The findingsextended in the lower tracheal and mainstembronchi, and the extent was labeled E4; theseverity was S4 (100% closure during exhalation),and given her symptoms with minimal activity,functional class was F3. The patient underwent aY silicone stent insertion, and after this procedure,she was classified as F2 E1 S1 (see Fig. 3). Thelack of complete symptomatic response to stentinsertion was explained by confounding disorders(COPD and obesity) and by the choke pointmigration seen just distal to the stent (see Fig. 3).

Definitions and classifications: key points

1. TBM is characterized by weakness or destruc-tion of the airway cartilaginous wall.

2. EDAC is characterized by bulging of the parsmembranosa inside the airway lumen.

3. The 50% reduction in airway cross-sectionalarea (CSA) during forced expiration is inade-quate to define abnormal collapse.

4. Multidimensional classification systems forECAC include an assessment of the patient’sfunctional status, craniocaudal extent,morphology of the airway during expiration,cause, and degree of AC.

PATHOPHYSIOLOGY

TBM and EDAC have different morphology on im-aging studies and bronchoscopy. The 2 processesare also distinct in terms of impact on flow dy-namics. Physiologic studies addressing the col-lapse of the central airways suggest that EDAC islikely a consequence of peripheral airway obstruc-tion from emphysema, chronic bronchitis, orasthma or resulting from the restrictive physiologyand positive pleural pressures in morbid obe-sity.25–29 TBM, on the other hand, is a true centralairway cartilaginous disease resulting in AC andflow limitation. Theories and mathematical modelshave been proposed and tested to explain expira-tory flow limitation in health and obstructive venti-latory disorders and are relevant to understandingflow limitation in EDAC and TBM.30,31

Flow-Limitation Theories

Equal pressure point theory: dynamiccompression and determinants of maximalexpiratory flowThere is a region within the intrathoracic airwaywhere intraluminal and extraluminal pressuresbecome equal once expiratory flow becomeslimited at a given lung volume.30 The point withinthe airway at which this situation occurs is calledthe equal pressure point (EPP) (Fig. 4). Thisconcept is based on the following facts: alveolarpressure is the driving pressure that causesgas to flow through airways during expiration.This pressure (Palv) is determined by the recoilpressure of the lungs (Pst) and the pleural pressure(Ppl):

Palv 5 Ppl 1 Pst (1)

A pressure decrease is required to accelerate airas it moves from an upstream (toward the alveoli)region of low velocity to a downstream (towardthe mouth) region of high velocity. Because ofthis pressure decrease, the intraluminal pressure(PL) eventually becomes equal to pleural pressure(Ppl). The point in the airway at which this processoccurs, the EPP, divides the airways into upstreamsegments (alveolarward from the EPP), at whichtransmural pressure (PL–Ppl) is positive, anddownstream segments (mouthward from theEPP), at which the transmural pressure is positivewithin the extrathoracic airways and negativewithin the intrathoracic airways. For a given lungvolume, driving pressure upstream from the EPPwould be equal to lung elastic recoil (driving pres-sure5 Palv–PL, but at EPP, PL5 Ppl and based onEquation 1, driving pressure 5 Pst and becomeseffort independent); downstream from the EPP,airways are compressed during expiration (seeFig. 4). This region of airway compression isreferred to as a flow-limiting segment (FLS). Thiscompressed airway segment develops close tothe EPP where Ppl exceeds PL and where thereis absence or inadequate cartilaginous supportor traction provided by neighboring alveoli. Thissituation explains collapse of the trachea andmainstem bronchi at the weakest point in theairway wall, namely the pars membranosa, whichis not supported by airway cartilage.

As lung volume decreases during expiration,elastic and alveolar pressures are reduced withrespect to pleural pressure, and EPP moves to-ward the alveoli. This situation results in a length-ening of the increasingly narrow downstreamsegment. This lengthening can be seen on bron-choscopy or dynamic CT as EDAC (see Fig. 4).Thus, the FLS have tracheal location at high lung

Table 2Classification systems used for ECAC

Reference Criteria Included in the System Comments

Rayl,13 1965 Extent: proximal (type I), mediastinal(type II), and intrapulmonary(type III) airways

Tracheobronchial collapse wasassessed during cough on cine-bronchography

Johnson et al,14 1973 Severity: 4� of airway narrowing TM: >50% collapse during coughingon fluoroscopy

Feist et al,15 1975 Cause: congenital and acquired TM: >50% collapse during coughingon fluoroscopy

Jokinen et al,19 1977 Severity: mild (<50%), moderate(50%–75%), severe (100%)

Extent: TM, TBM, BM

TBM: expiratory reduction of 50% ormore in the anteroposteriordiameter of the airways

First classification based onbronchoscopic findings

Mair et al,131 1992 Cause: congenital (type 1), extrinsiccompression (type 2), acquired(type 3)

Severity: mild (<70%), moderate(70%–90%), severe (>90%)collapse

Described for pediatric TBMEmpirical severity score

Masaoka et al,10 1996 Cause and extent criteriaPediatric, adult, and secondary

TBM: >80% collapse duringexpiration

Based on bronchoscopic estimationsand frontal and lateral radiographfilms to estimate the narrowing

Abbreviations: BM, bronchomalacia; TM, tracheomalacia.

Table 3Stratification factors from FEMOS classification system for ECAC

Definition

Criterion Grade

1 2 3 4

Functional statusRefers to degree

of functionalimpairment asdefined byWorld HealthOrganization

Asymptomatic Symptomatic onexertion

Symptomatic withdaily activity

Symptomaticat rest

ExtentDefines the

length of thetracheobronchialwall affected andthe location of theabnormal airwaysegment

No abnormal AC 1 main, lobar,or segmentalbronchus or 1tracheal region(upper, mid, orlower)

In 2 contiguous or�2 noncontiguousregions

In >2 contiguousregions

SeverityDescribes the degree

of the AC duringexpiration asdocumented bybronchoscopic orradiologic studies

Expiratory ACof 0%–50%

Expiratory AC of50%–75%

Expiratory AC of75%–100%

Expiratory AC of100%; theairway wallsmake contact

532 Murgu & Colt

Fig. 2. Morphologic types of ECAC based on the shape of the airway lumen during expiration. (A) Normal dy-namic airway compression during exhalation with the posterior membrane slightly bulging within the airwaylumen (arrow). This compression usually narrows the airway lumen by less than 50%. (B) In EDAC, the posteriormembrane bulges in (arrow) and excessively narrows the airway lumen by 50% or more. This process occurswithout cartilaginous wall weakness. (C) In crescent-type TBM, the anterior cartilaginous wall is weakened andcollapses inside the lumen (large arrow). (D) In saber-sheath TBM, the lateral walls are collapsing inside the lumen(arrows). (E) In circumferential-type TBM, typically seen in relapsing polychondritis, the anterior and lateral carti-laginous walls are collapsing inside the lumen (large arrows) and there is diffuse airway edema and hyperemia.The small arrows denote normal expected physiologic dynamic compression, whereas the large arrows denoteabnormal airway wall collapse.


volumes (ie, total lung capacity [TLC]), but as lungvolume decreases during exhalation, FLS moveperipherally but still stay in the central airways (inthe lobar, segmental, and at the mostsubsegmental bronchi), as shown in previous ex-perimental and human studies. Even at residualvolume (RV), the FLS were found in the central air-ways, fixed and in parallel in the right middle lobe,left upper lobe, and left lower lobe bronchi. Theselobar and segmental locations of FLS were shownin normal individuals and individuals with obstruc-tive ventilatory impairment over considerableranges of lung volume.32–34 Based on the EPP the-ory, if the FLS are located in the lobar or segmentalairways, then the downstream resistance shouldnot affect flow. Intraluminal pressure monitoringwith airway catheters shows the lack of decreasein pressure in airways between the mouth andthe FLS.34 Therefore, tracheal and mainstem bron-chial collapsibility observed on dynamic bron-choscopy or dynamic CT in the form of EDACshould not impede flow.35

The EPP theory explains how lung complianceand airway resistance affect airflow limitation andhow changes in these 2 factors result in increasedcompression of the airway downstream from theFLS responsible for the bronchoscopic or radio-graphic EDAC. For instance, a decrease in elasticrecoil of the lungs (either because of low lung vol-ume as seen in morbid obesity or because ofemphysema) reduces the airway pressure relativeto pleural pressure, resulting in greater dynamiccompression. A decrease in elastic recoil of thelungs results in less traction on the adjacent air-ways and therefore greater dynamic compression.As for airway resistance, the greater the pressuredecrease along the airway from the alveoli to theEPP (along the upstream segment), the soonerthe development of an EPP and the greater the dy-namic compression. The EPP theory, therefore,sustains the theory that central airway compres-sion downstream from EPP (bronchoscopic/radio-graphic EDAC) is not pathologic from a flowdynamic standpoint.

Table 4Secondary causes of ECAC

MorphologicType of ECAC Associated Disease or Process Potential Mechanism

BM After lung transplantation Impaired blood supply and necrosis

TM History of ETT or tracheostomy tube Pressure necrosis, impaired bloodsupply, and chondritis

TM Chest trauma Cartilage fracture

TBM Relapsing polychondritis Cartilage inflammation

TBM Chronic recurrent airway infections Cartilage inflammation

TBM Chronic indwelling ETT or tracheostomytube

Chronic inflammation of the airwaywalls

TM, BM Cancer (lung, thyroid, esophageal, ormetastasis from extrathoracicmalignancies)

Direct tumor invasion of thecartilaginous wall

TM, BM Radiation therapy Cartilage necrosis

Bronchoscopic electrocautery and laser Thermal energy destruction of thecartilaginous wall

TM, BM, TBM After thyroidectomy, postpneumonectomysyndrome, severe scoliosis

Mechanical factors

TM, BM Mediastinal goiterTumors (carcinoma, teratoma, lymphoma,

neuroblastoma)Vascular anomalies (innominate artery,

aortic arch ring, pulmonary artery sling,aberrant right subclavian)

Cysts (thymic cyst, bronchogenic cyst,lymphatic malformation)

Cardiac (enlarged left atrium, enlargedpulmonary arteries or veins)

Chronic extrinsic compression andsecondary weakness of the cartilage

EDAC COPD Decreased elastic recoila

Small airway inflammationa

Atrophy of elastic fibers

EDAC Asthma, bronchiectasis, bronchiolitis Small airway inflammationa

EDAC Obesity Decreased elastic recoila

Positive pleural pressuresa

EDAC Healthy individuals during forcedexhalation and coughing

Increased pleural pressuresa

EDAC Mounier-Kuhn syndrome Congenital atrophy of elastic fibers

Abbreviations: BM, bronchomalacia; ETT, endotracheal tube; TM, tracheomalacia.a For explanations on how decreased elastic recoil, small airway inflammation, and increased pleural pressures cause

EDAC, please refer to the section on flow-limitation theories.

Murgu & Colt534

Wave speed theory: airway compliance andimpact on choke point physiologyA different approach to explain expiratory flow lim-itation is offered by the wave speed theory, whichstates that flow limitation in elastic tubes occurs atthe speed at which the fluid (eg, air) in the tube (eg,airways) propagates pressure waves.31 Thesewaves develop from the interaction of recoil forceof the elastic airway wall and the axial inertial forceof the flowing gas. The wave speed is the speed atwhich a small disturbance travels in a fluid-filled

compliant tube. Thus, expiratory flow limitation oc-curs when flow velocity equals the speed of prop-agation of pressure pulse waves at some pointwithin the tubes; this point, called the choke pointor FLS, tends to be at a region of minimum CSAand minimum intraluminal airway pressure whenmaximal flow has been reached:

_V ws 5 A ½A =ðr� CawÞ�0:5 (2)

This wave-speed flow ( _V ws) depends on theCSA (A), airway compliance (Caw 5 dA/dPtm),

Fig. 3. TBMcase (upperpanel): (A) Bronchoscopic imageduring tidal respiration: lower tracheal lumenduring inspi-ration; (B) lower tracheal lumen during expiration showing 100% closure resulting in severity grade S4; (C) pairedinspiratory–dynamic-expiratory CTshowing lower tracheal lumen during inspiration; (D) lower tracheal lumen dur-ing expiration shows that in addition to thenormal dynamic airway compression (small arrow), there is flatteningofthe anteriorwall of the lower trachea (largearrow), consistentwith focal (E2) crescent-type tracheomalacia; (E) rigidbronchoscopic image after stent insertionduring inspiration; (F) bronchoscopic image during tidal expiration showspatent airway with no residual malacia (E1) and normal airway caliber (S1). EDAC case (lower panel): (G) lowertracheal lumen during inspiration; (H) during tidal expiration, the collapse of the posterior membrane closes theairway completely, resulting in severity grading (S4); (I) paired inspiratory–dynamic-expiratory CT shows normalcartilaginous wall configuration; (J) during expiration, the excessive collapse of the posterior membrane is noted(large arrow), consistent with EDAC. The findings extended to mainstem bronchi, resulting in extent grading ofE4. (K) After stent insertion, there was maintained airway patency with no AC (S1). (L) Follow-up bronchoscopyshowsACdistal to the left and right bronchial armsof theY silicone stent, consistentwithmigration of chokepoints.


Fig. 4. Expiratory flow limitation theory and affect bronchoscopic EDAC. (Upper panel, left) The alveolar pressure(Palv) causes air to flow during expiration and is approximately equal to the recoil pressure of the lungs (Pst) plusthe pleural pressure (Ppl): Palv 5 Ppl 1 Pst. During forced expiration, the intraluminal pressure (PL) eventuallybecomes equal to pleural pressure (Ppl) at a point called the EPP. In the upstream segment (alveolarward fromthe EPP), the transmural pressure (Ptm 5 PL–Ppl) is positive, but in the downstream segment (mouthward fromthe EPP), it is negative within the intrathoracic airways. At a given lung volume, driving pressure upstreamfrom the EPP would be equal to lung elastic recoil (Pst), whereas downstream from the EPP, airways would becompressed during expiration. This region of compression of intraluminal caliber is referred to as a flow-limiting segment (FLS) or choke point In emphysema, for instance, the reduced elastic recoil and increased resis-tance of the upstream segment result in decreased transluminal pressure and consequent increased AC; in morbidobesity, the reduced elastic recoil from restriction and increased pleural pressures also results in EDAC. (Upperpanel, right) As lung volume decreases from total lung capacity (TLC) toward residual volume (RV), the elasticrecoil (Pst) decreases as well, and pleural pressure (Ppl) increases during forced expiration. (Lower panel, left)Thus, the EPP migrate upstream, resulting in a lengthening of the increasingly narrow downstream segment(note compressed trachea and right mainstem bronchus [RMB]). This situation increases airway resistance andprevents further increases in expiratory airflow, causing the EPP to become fixed when airflow becomes constant.FLS move peripherally during exhalation to the lobar/segmental and at most subsegmental bronchi (note leftlower lobe bronchus open during inspiration but nearly completely closed during exhalation in a patient flowlimited at rest).

Murgu & Colt536

which is the slope of the curve describing A as afunction of transmural pressure (Ptm 5 PL–Ppl),and the density (r) of the gas, according to Equa-tion 2.36 A functional definition for choke points isas follows: the most downstream (mouthward)points where the airway pressure does notchange with driving pressure. Intraluminal airwaycatheters can be used to localize choke pointsby measuring airway pressure during inducedflow limitation by decreasing the downstreampressure. This concept has led to the develop-ment of intraoperative location of the choke pointtechniques that might predict response to stentinsertion.37

From Equation 2, it can be seen that _V ws de-creases when A becomes smaller, and Caw andr become larger, as would be the case for a hyper-compliant intrathoracic airway during expiration asseen in TBM. Increasing central airway complianceincreases airway resistance and decreases max-imum expiratory flow, which contributes to theairflow limitation in TBM, characterized by hyper-compliant airways. Results from studies of airflowlimitation in theoretic, experimental models andclinical studies show that when the collapsing tra-chea is supported by a rigid tube, airflow improvesand the choke point could migrate from the centralairway toward the periphery.38–40 In addition, _V ws


indirectly depends on the lung elastic recoil pres-sure (Pst) and the pressure loss (Pfr) upstreamfrom the choke point, because a decreased pres-sure head (defined as Pst–Pfr) makes the dis-tending transmural pressure (Ptm) smaller and,accordingly, makes A smaller (see Fig. 4). This the-ory is in accordance with the EPP theory. Thechoke point is the equivalent of the juncture of up-stream and FLS according to EPP theory. Wavespeed theory supplements EPP theory by address-ing pressure-area relationships at the choke pointand predicting values of maximal flow.

The EPP and wave speed theories and experi-ments support the concept that upstream anddownstream segments are connected by a dis-crete airway segment, the choke point, which dis-sipates all increases in driving pressure and limitsflow. Clinical application of these concepts im-proves our understanding of the impact of struc-tural wall changes on flow dynamics in diseaseprocesses. For example, chronic inflammationand remodeling in asthma affect mechanical prop-erties of the airway wall.41 Using esophageal bal-loons to measure pleural pressure and airwaypressure probes, airway compliance can be deter-mined at multiple anatomic points. Long-lastingasthma was found to cause less compliant centralairways, suggesting that chronic inflammation andremodeling of the airway wall may result in stifferdynamic elastic properties of the asthmaticairway.

Applied Physiology

EPP theory and wave speed theory explainEDAC during forced expiration in healthyindividualsThe flow-limitation theories show that increasingpleural pressures during forced expiration resultin greater dynamic airway compression down-stream from the EPP and adjacent choke points.Clinical studies show sex and age differences inthe degree of dynamic collapse.24 Dynamic CT in-vestigations showed that regardless of age, mentend to have greater inspiratory and expiratoryforce-generating capacity. Maximum expiratorypressure is 30% to 50% greater among mencompared with women throughout adulthood.42

If the effort is maintained throughout expiration,greater compression of the downstream airwaysegment might be expected in men than inwomen. Although the mean % collapse is similarfor men (55% � 23%) and women (52% � 17%),only men (older men had both greater CSA atTLC and smaller CSA during dynamic exhalationthan younger men) showed a significant positivecorrelation between % collapse and age.

However, both sexes showed % collapse ofmore than 50% in healthy individuals.24 These re-sults suggest that sex and age differences shouldbe considered when assessing patients for sus-pected pathologic collapse and support the factthat the 50% cutoff for defining abnormality resultsin false-positive findings without consequence onflow.12,17,24

EPP theory and wave speed theory explainEDAC in COPDTwo abnormalities in COPD contribute to early ACduring expiration: decreased elastic recoil at alllung volumes (emphysema) and inflammatory nar-rowing of the airways (bronchitis). These pro-cesses determine the major site of increasedresistance to be in the small airways (ie, airwaysof <2 mm diameter).43 In the presence of smallairway obstruction, EPP and the choke pointswere shown to be further upstream (toward the al-veoli) than in normal individuals.44 The destructionof lung tissue decreases the number and elasticityof the radial attachments from the parenchyma tothe airway, and thus decreases airway stability.Experimental studies applying wave speed theoryin canine models of emphysema show that themain reduction in maximum flow is explained bythe decrease in elastic recoil; the other contrib-uting factors are increases in frictional resistancefrom alveoli to sublobar bronchi and changesin airway compliance.45 A decrease in airwaystability in emphysema decreases the maximumflow by decreasing CSA for a given transmuralairway pressure, and by relatively increasingairway compliance. Alternatively, altered bron-chial pressure-area behavior could result from arelative increase in peribronchial interstitial pres-sure. Thus, for a given intraluminal pressure PL,airway CSA in emphysema would be smallerthan in healthy lungs, because the transmuralpressure (PL–peribronchial pressure) would beless (see Fig. 4). This reduction in CSA in COPDhas not been proved to be caused by cartilageabnormalities and thus cannot be consideredtrue malacia. Physiologic and morphologicstudies of determinants of maximal expiratoryflow in COPD show that airway collapsibility didnot correlate with the amount of airway cartilage,inflammation, or airway wall thickness.46 De-creased cartilage volume in COPD has been de-scribed by several investigators47–49 but was notfound by others.50 Because the mechanicalproperties of airway cartilage have not beeninvestigated, it cannot be excluded that theseproperties would relate in airway collapsibility.Some investigators51 reported that the proteolyticenzyme, papain, could weaken airway cartilage

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but not destroy it, because its histologic appear-ance remained unchanged.A clinical study52 addressed the question

whether expiratory flow limitation is caused pri-marily by narrowing of the central airways or bythe more peripheral airways in patients who haveCOPD and concurrent abnormal degrees of cen-tral AC. The investigators analyzed the degree ofcentral airway collapsibility by using a semiquanti-tative analysis of bronchoscopic images andrelated it to expiratory flow limitation in patientswith what the investigators named TBM. However,all patients had invagination of the posterior mem-branous portion, which caused tracheal narrow-ing; the tracheal collapse was not caused bysoftening of the cartilaginous rings, thus makingthe entity studied consistent with a diagnosis ofEDAC. Simultaneous pressure measurements inthe trachea and esophagus were performed toidentify expiratory flow limitation during quietbreathing and to determine the critical transmuralpressure required for maximum expiratory flow.The investigators found that 15% of patients withEDAC were not flow limited during quiet breathing,53% were flow limited throughout exhalation, and30% were flow limited only during the latter part ofthe exhalation. Patients with flow limitation at resthad more tracheal narrowing (EDAC) than thosewithout, but the severity of expiratory flow limita-tion was not closely related to tracheal collaps-ibility. AC during quiet breathing was unrelated toFEV1 (forced expiratory volume in first second ofexpiration). Twenty-three patients (28%) wereflow limited during quiet exhalation at transmuralpressures that did not cause central AC. In thesepatients, the tracheal collapse was less than50% during quiet exhalation and increased tomore than 50% only during forced exhalation,when the pleural pressures increased, suggestingthat tracheal collapse to more than 50% narrowingduring forced exhalation is not responsible forlimiting maximum expiratory flow. The importantfinding of this study was that EDAC was mostlyseen in patients with tidal expiratory flow limitation.These data are relevant when considering inter-ventions addressing EDAC, especially if symp-tomatic central airway narrowing exists withoutsignificant documented airflow obstruction. Itcould be argued that even in patients with EDACduring tidal exhalation, given the expiratory flowlimitation at rest, EDAC represents the airwaydownstream (mouthward) from the choke pointsand is not responsible for pressure decrease andflow limitation. The way to show whether EDACis flow limiting is to measure the degree of pres-sure decrease along the collapsing segment.37

However, the success of stent insertion or trache-oplasty is assessed not just by improvement inairflow but also by relief of symptoms such ascough and dyspnea and reduced frequency ofinfection. This finding is especially relevant forthose patients with central AC in which collapseof the posterior membrane is noted and there isconcurrent collapse of the cartilaginous wall,namely those patients with crescent-type malaciaor a combination of malacia and EDAC. For thispurpose, the use of intraluminal airway pressurecatheter measurements distal and proximal tothe narrowed airway during tidal breathing allowsintraoperative estimation of the physiologic bene-fits of a particular interventional procedure.37

The evidence that the degree of central AC inCOPD is independent of disease severity anddoes not correlate significantly with physiologicparameters is reproducible.6,11 Dynamic CTstudies suggest that the incidental identificationof excessive expiratory tracheal collapse (mea-sured at 1 cm above the aortic arch [midtrachea]and 1 cm above the carina [lower trachea]) inCOPD is not clinically significant. One study evalu-ated 100 adults meeting GOLD (Global Initiative forChronic Obstructive Lung Disease) criteria forCOPD who underwent PFT, 6-minute walk test(6MWT), Saint George’s Respiratory Questionnaire(SGRQ), and spirometry gated low-dose CT at TLCand during dynamic exhalation with spirometricmonitoring (CT was performed during a forcedexpiratory maneuver: participants took a deepbreath and then blew out hard and fast [similar toa forced vital capacity [FVC] maneuver in the PFTlaboratory]). The mean FEV1 was 64% predicted,and percentage expiratory collapse was 59% �19% for tracheal measurement and 61 � 18% forlower tracheal measurements. Twenty percent ofthe study participants met study criteria for exces-sive expiratory collapse, which was defined as areduction of more than 80% in the tracheal lumenduring forced expiration. Consistent with the bron-choscopic study described earlier,52 there was nosignificant correlation between percentage expira-tory tracheal collapse and pulmonary functionmeasures, total SGRQ score, or 6MWT distance.The SGRQ symptom subscale was only weaklycorrelated with percentage collapse of the midtra-chea (R 5 0.215, P 5 .03).6

Bronchoscopic and dynamic CT studies high-light the fact that clinically significant EDAC thatinterferes with flow or symptoms should not bedefined by forced expiratory maneuvers. Thelack of association between the severity oftracheal collapse and GOLD stage of COPD wasalso described by other investigators, who

Pathophysiology: key points

1. Healthy volunteers performing forced expi-ratory maneuvers and patients with morbidobesity, COPD, and other obstructive ventila-tory disorders have EDAC as a result of inter-actions between pleural pressures, elasticrecoil, airway compliance, and peripheralairway resistance.

2. EDAC documented on bronchoscopy ordynamic CT may not interfere with flow,regardless of the degree of AC.

3. EDAC may not correlate with severity ofventilatory impairment or QOL measures.


studied 71 patients with COPD,11 but these latterinvestigators reported a higher prevalence ofexcessive expiratory tracheal collapse (53%),likely because they used a lower threshold fordiagnosis (>50%). Thus, the incidental detectionof excessive expiratory tracheal collapse in apopulation with COPD of different degrees ofairflow obstruction may not be clinically relevant,especially in the absence of other comorbidities.The resistance of the upstream segment basedon EPP theory affects flow and determines thelocation of the choke points and the downstreamcompressed airway segment. From a clinicalstandpoint, severity of bronchial wall thickness,responsible for increased Resistance of the up-stream segment (Rus), was significantly higher inpatients with EDAC and correlated with the de-gree of maximal AC.11 Based on the mechanismsof flow limitation outlined earlier, central AC is aconsequence of:

1. Increased pleural pressures, as seen duringforceful expiratory maneuver or cough

2. Hypercompliant central airway during expira-tion, with relatively low pleural pressures, asseen with weakened or destroyed cartilage(TBM) or decreased drive pressure in thesetting of peripheral airway obstruction (EDACin COPD)

3. Increased resistance in the segment upstreamfrom the choke point, as seen in chronic bron-chitis, asthma, and bronchiectasis, which leadsto EDAC

4. Decreased elastic recoil and early formation ofchoke points at high lung volumes during exha-lation responsible for EDAC in emphysema

Such central AC could occur in patients with orwithout COPD, may not be flow limiting, andpossibly not associated with impaired functionalstatus. From a flow dynamic perspective, detec-tion of expiratory tracheal or mainstem bronchialcollapse at the level of the posterior membraneshould trigger a search for causes of airflowobstruction within the lung (COPD, bronchiolitis,asthma), not the central airways.35

EPP theory and wave speed theory explainEDAC in obesityObesity can cause low lung volumes and restric-tive ventilatory impairment. Individuals with abody mass index (BMI, calculated as weight inkilograms divided by the square of height in me-ters) greater than 40 kg/m2 have reduced TLC,functional residual capacity (FRC), and vital ca-pacity. In otherwise healthy obese individualswith BMI greater than 40 kg/m2, expiratory flowlimitation is common in the supine position.27

Pleural pressure in obese individuals at relaxa-tion volume is greater than normal, often be-coming positive. This finding was shown inobese supine and paralyzed individuals undergo-ing general anesthesia28 and also in consciousobese individuals.29 Based on the EPP theory,the increased pleural pressure throughout thechest in these individuals explains the EDACthat is often encountered during bronchoscopyor dynamic CT, because transmural pressure(PL–Ppl) is decreased, and during exhalation theairway collapses at the posterior membraneportion, causing EDAC (see Fig. 4).

FUNCTIONAL EVALUATIONPulmonary Function Testing

Spirometry in patients with central AC may revealobstructive ventilatory impairment but does notcorrelate with severity of the airway narrowing.52

Spirometry measurements are not necessarilyrepresentative of the degree of symptomaticimprovement after interventions such as stentinsertion or tracheoplasty,53,54 suggesting that in-terventions either improve other factors (cough,secretion management) or do improve pulmonarymechanics but not airflow as measured byFEV1% predicted. However, the flow-volumecurve contour in COPD correlates with pulmonarymechanics,55 and 2 different types of flow-volumeloops are identified: AC and scooped-out patterns(Fig. 5). AC pattern is characterized by a decreasein flow rate from the peak flow to an inflection pointless than 50% of peak flow rate. The inflectionpoint occurs within the first 25% of expired vitalcapacity. The inspiratory limb of the curve showingno evidence of obstruction can be seen in almost40% of patients with COPD,25 and it correlateswith the bronchoscopic finding of EDAC.26 Thegroups of patients with the 2 distinct flow-volume

Fig. 5. Flow-volume loop patterns in COPD. (A) The AC pattern shows a sudden decrease in peak expiratory flow,defined as a 50% decrease within 25% of FVC. (B) The scooped-out pattern is without an initial spike and is char-acterized by a more curvilinear reduction in flow rate over the vital capacity.

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loops patterns cannot be distinguished from clin-ical symptoms.55 Results of studies show higherresistance to flow in AC group at high and midlung volumes but comparable resistance to flowat lower lung volumes in both groups. The RVand FRC were higher in the AC group, indicatinga more severe hyperinflation, despite comparableloss of elastic recoil, consistent with functionalclosure of small airways caused by intrinsic airwayabnormality. The degree of hyperinflation wasfound to have no correlation with the peak flowor the flow rate at the inflection point in the ACgroup. At the peak flow, the mean pleural pressurewas similar in the 2 groups; below peak, the ACgroup had considerably higher maximal pressurecompared with the non-AC group, and this wassustained through 75% of expired vital capacity.These data suggest that AC pattern seems to bedetermined by a combination of loss of elasticrecoil and peripheral AC, findings supporting theEPP theory. Flow oscillations on the flow-volumeloop have also been described in patients withECAC. These oscillations take on a saw-toothappearance, defined as a reproducible sequenceof alternating decelerations and accelerations offlow.56

Impulse oscillometry (IOS) is an effort-independent test during which brief pressurepulses generated by a loudspeaker mounted inseries with a pneumotachygraph are applied dur-ing tidal respiration, and recordings are used to

provide an estimate of total respiratory systemimpedance. Measurements of resistance (R) andreactance (X) at different frequencies might differ-entiate between central and peripheral compo-nents of airway obstruction. Increased R at alow oscillation frequency (5 Hz) reflects an in-crease in total respiratory resistance suggestiveof airway obstruction such as that found in pa-tients with COPD, whereas an increase at a higherfrequency (20 Hz) reflects more specificallyincreased central airway resistance such as thatfound in patients with central airway obstruc-tion.57 The IOS maneuver does not cause respira-tory fatigue and may be better tolerated bypatients with irritable, inflamed airways such asthose with ECAC. However, preliminary reportssuggest that IOS data from ECAC are similar tothose from patients with COPD, resulting inincreased resistance at 5 Hz, marked frequencydependence in resistance, more negative reac-tance at 5 Hz, and increased resonant fre-quency.58 Normalization or improvement of IOSdata after treatment of ECAC confirms that theIOS pattern is caused by the central AC and notperipheral obstruction.58 Furthermore, becausein EDAC the predominant site of flow limitation isin the periphery, higher R5 and R5 to R20 valuesare expected than with TBM, for which the mainsite for flow limitation is the central airways, andthus higher R20 is expected. These findingsneed to be confirmed in future studies.


Functional Bronchoscopy

Functional bronchoscopy consists of physiologicmeasurements during bronchoscopy and perfor-mance of dynamic bronchoscopy. This latter tech-nique refers to bronchoscopy performed duringvarious respiratory maneuvers with the patienthaving received at most only anxiolytics. The pa-tient can thus follow commands and cooperateduring the procedure with respiratory maneuversand changes in body position. For instance, a pa-tient with malacia and orthopnea may not have thebronchoscopic findings of malacia unless thebronchoscopy is performed in a supine position.Similarly, a patient with a history of tracheostomyand dyspnea when bending over or during neckflexion may have posttracheostomy stomal stric-ture, with malacia revealed only when the lesionbecomes intrathoracic and increased pleural pres-sures during exhalation result in further narrowingof the airway lumen and cause flow limitation,inability to raise secretions, or trigger coughingspasms. Conversely, if the lesion is at the thoracicinlet, symptoms may occur only during inspirationif the lesion becomes extrathoracic, such as whenthe patient performs neck extension.

Intraluminal pressure, changes in pressure overthe length of a stenosis, and airflows can be super-imposed over the bronchoscopic image in realtime using a technique of endospirometry.59 Dy-namic changes can be studied during quietbreathing, forced breathing maneuvers, coughing,and neck flexion/extension, and the impact onpressure change responsible for symptoms canbe determined. Results from studies show that in-traluminal pressure monitoring allows the detec-tion of the FLS responsible for flow limitation.With the use of airway catheters in dogs60 and inhumans,34,36 the FLS could be located bymeasuring airway pressure (PL) during inducedflow limitation generated by either an increase inpleural pressure or a decrease in downstreampressure.

Because assessment of the FLS requiresforced expiratory vital capacity maneuvers, de-tecting flow limitation by measuring PL cannotbe performed during bronchoscopy if patientscannot follow instructions, such as those patientsundergoing general anesthesia. However, a sim-ple and well-tolerated bronchoscopic techniquehas been proposed and studied in this setting,using PL measurements: a double-lumen airwaycatheter capable of simultaneously measuringPL at 2 sites in the trachea can be used to assesstracheal obstruction.37 When the catheter is posi-tioned with the 2 holes located on each side of astenosis, the 2 pressures plotted against each

other show a line with a slope less than 45�

caused by resistance difference between the 2points. If the 2 holes are simultaneously locatedproximal from or distal to the narrowing, pres-sures between these sites are in phase, and ifplotted against each other, show a straight linewith a slope of 45�. By measuring airway pres-sure proximal and distal to the narrow airwaysegment and plotting the 2 pressures againsteach other during quiet tidal breathing, the siteof maximum obstruction and the degree of nar-rowing can be physiologically assessed, allowingintraoperative prediction of the proceduraloutcomes.

Bronchoscopy allows direct visualization of theairway mucosa, can be performed in critically illpatients at the bedside, is not associated withionizing radiation, and allows assessment ofresponse to noninvasive positive pressure ventila-tion (NIPPV) when this is considered a treatmentalternative.61 For this purpose, a full face maskcan be used and secured to the patient’s facewith elastic straps.62 A dual-axis swivel adapter(T-adapter) is also attached to the mask and con-nected to the ventilator. NIPPV is applied in incre-mental pressures until the AC is palliated or untilthe patient becomes uncomfortable (patientshave occasionally reported chest tightness, dys-pnea, and uncomfortable pressure sensationover the face and choking during bronchoscopiccontinuous positive airway pressure [CPAP] titra-tion for ECAC), whichever comes first. A CPAPpressure of 0 cm H2O is usually initiated andtitrated upwards. If necessary, as in the evaluationof central AC, procedures are performed in the up-right and supine positions as well as on and offCPAP to evaluate the degree of airway narrowingand response to CPAP (Fig. 6). In EDAC/TBM,CPAP pressures of 7 to 10 cm H2O usually assureairway patency but pressures can be increased by3 cm H2O incrementally until airway caliber duringtidal exhalation is considered satisfactory (eg, atleast 50% of that noted during inspiration). Intralu-minal pressure monitoring during CPAP is possible(Lutz Freitag, MD, Germany, personal communi-cation, 2012) but has not yet been systematicallystudied.

Dynamic CT

Low-dose dynamic CT reveals TBM and EDACwhen performed according to a central airwayprotocol, which includes end-inspiratory anddynamic-expiratory imaging.63 Scout images arecaptured to determine the area of coverage (tra-chea, mainstem bronchi, and bronchus interme-dius). Scanning is performed in a craniocaudal

Fig. 6. Bronchoscopy on CPAP for a patient with left main bronchomalacia. (A) A full face mask is secured to thepatient’s face with elastic straps and a dual-axis swivel adapter is attached to the mask and connected to theventilator. (B) Left main bronchial lumen during inspiration at CPAP 0 cm H2O. (C) During tidal expiration, onCPAP 0 cm H2O, there is near-complete closure of the airway. (D) On CPAP of 10 cm H2O, the inspiratory airwaylumen CSA is improved. (E) During tidal expiration, on CPAP of 10 cm H2O, the airway lumen patency ismaintained.

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direction during both end-expiratory and dynamic-expiratory phases, and the percentage of AC iscalculated by subtracting the dynamic-expiratoryCSA from the end-inspiratory CSA, divided bythe end-inspiratory CSA. Some protocols captureimages at 3 different time points during the respi-ratory cycle: at the end of inspiration, at the endof expiration, and during dynamic exhalation.63–65

The use of end-inspiratory CT images alone is notuseful for detecting TBM or EDAC, because afterclosing the vocal cords for a breath-hold, the intra-luminal airway pressure can become positive, thetransmural pressure increased and the airwayscan be distended. End-expiratory CT images atsuspended exhalation may also be misleading forsimilar reasons; the intraluminal pressure may behigher than during dynamic expiration, andbecause the expiratory effort has ceased, thepleural pressure is not maximal and the degreeof collapse may be diminished. The maximalcollapse may not be detected by paired end-inspi-ratory–end-expiratory CT scans. Therefore, dy-namic (cine) CT is used in the assessment ofTBM and EDAC as an alternative or complemen-tary test to dynamic bronchoscopy (see Fig. 3).Dynamic CT reveals the greatest degree ofcollapse and is now routinely used in radi-ology.6,12,63–65 Image acquisition performed

during dynamic exhalation accentuates ACbecause images are captured during forced expi-ratory maneuver, not tidal expiration. Theabnormal collapse detected does not reflect thepatient’s airway dynamics during tidal respiration.In addition to showing potentially a nonpathologicprocess and causing false-positive diagnosis, dy-namic CT also requires additional technologisttraining. Supervision and coaching of patients isnecessary, not always feasible in very dyspneic,uncooperative, or critically ill patients. If patientsstart coughing, the degree of AC is accentuatedeven further.66 Three-dimensional reconstructionimages are useful for obtaining a perspective onthe extent and degree of collapse, but the axial im-ages are used for accurate measurements of CSA.In general, 3 anatomic levels for each respiratorycycle time point are examined (the aortic arch,main carina, and intermediate bronchus), but thereis inconsistency among studies in regards to thenumber and location of anatomic sites chosenfor airway lumen measurements.6,7,11,12,63–67

Dynamic CT was shown to reveal similar degreeof AC to bronchoscopy.63,68 Given its noninvasive-ness, dynamic CT can be used as the initial testwhen TBM or EDAC is suspected. However,most investigators use dynamic CT as an adjunctnot an alternative to bronchoscopy in preoperative


planning69 or posttherapy monitoring. CT mea-surements of forced expiratory tracheal collapseare highly reproducible over time and thus can beused for monitoring after intervention and progres-sion of disease.70 Dynamic CT has been used forgeneral preoperative imaging to assess the degreeof narrowing and craniocaudal extent of AC, todefine intrinsic (eg, cartilage thickening in relapsingpolychondritis) or extrinsic (eg, compression bymediastinal masses or vascular structures) abnor-malities and to plan stent insertion by allowingmeasurement of the airway caliber.71 CT hasbeen used to follow up patients after stent place-ment to assess stent patency, detect complica-tions such as migration, formation of granulationtissue, mucus obstruction, or choke point migra-tion. CT was also used in the preoperative evalua-tions of patients being considered fortracheoplasty to confirm extent, severity, andairway shape because patients with crescent-type TBM are most likely to benefit from reinforce-ment of the posterior membrane.72,73 CT allowsexclusion of other diseases requiring different in-terventions, such as a paratracheal mass or relaps-ing polychondritis. Postoperative evaluation aftertracheoplasty can be performed using CT, whichreveals changes in the degree of expiratorycollapse and potentially detects the rare but severecomplications of this procedure, such as airwaydehiscence, mediastinal hematoma, or abscess.74

In addition to noninvasiveness, the main advan-tage over bronchoscopy is the ability to evaluatethe structures around the airways potentiallyresponsible formalacia (ie, goiter, aortic aneurysm,double aortic arch) and assess the changes of lungparenchyma that may cause or be associated withcentral AC (ie, emphysema, bronchiolitis, air trap-ping). The disadvantages include the lack of detailsabout the mucosa, the necessary patient coopera-tion with respiratory maneuvers, and exposure toionizing radiation. Lower-dose techniques allow a23% radiation dose reduction compared with thestandard technique. These techniques can beused for central airway imaging because of theinherent contrast between central airways andadjacent soft tissue without compromising diag-nostic information.68,75 Advances in CT technologyallow now faster image acquisition. The 320-de-tector row scanner covers 16 cm craniocaudal vol-ume per rotation and allows real-time dynamicimaging of trachea. This technique has alreadybeen used for diagnosis of EDAC and assessmentof response to CPAP.20

However, from a physiologic standpoint, dy-namic CT findings of excessive AC during forcedexhalation have been considered of uncertainphysiologic significance.6,12,17,24 Recent dynamic

CT studies are in agreement with the physiologicunderstanding of EDAC based on the flow-limitation theories. Although the previous definitionof abnormal collapse greater than 50% cross-sectional luminal collapse is still used by investiga-tors,11 symptomatic collapse, which may requireinterventions, is usually 95% to 100%.53,54 Ad-vances in imaging resulted in changing of our un-derstanding of the pathologic central AC. Initialradiographic definition of cross-sectional diameterreduction of 50% or greater during coughing onbronchography dating from more than 45 yearsago13 is now known to be inadequate because80% of normal healthy individuals meet this crite-rion during forced exhalation.12 The different de-grees of AC noted on imaging studies led toradiologic subtyping of the 50% or greater crite-rion according to severity.2,14 Results of studiesshow that the % expiratory decrease in CSAshould not be the only criterion, because there isoverlap in degree of expiratory collapse amonghealthy volunteers and patients with central airwaydisease12,16; furthermore, the degree of collapsegreater than 50% is not uncommon in COPD andmay not be responsible for flow limitation.6

Results of studies show the presence of thehighly collapsed central airways in COPD usingdynamic-expiratory or end-expiratory CTscans11,76–78 and the lack of significant physiologicimpairment resulting from EDAC. For instance, onestudy aimed to reveal the correlations betweentracheal volumetric measures, including collaps-ibility, and lung volume measures on inspiratoryand end-expiratory CT scans and to evaluate therelationship between tracheal collapsibility andlung function. The study included 85 smokers(normal lung function [n 5 14]; GOLD stage 1[n 5 14]; stage 2 [n 5 38]; stage 3 [n 5 11]; stage4 [n 5 8]) who underwent PFTs and chest CT atfull inspiration and end-expiration. Tracheal vol-ume and collapsibility, expressed as expiratory/inspiratory (E/I) ratios of these volumes, were foundto be related to lung volume and collapsibility. Thehighly collapsed trachea on end-expiratory CT didnot indicate more severe airflow limitation or airtrapping in smokers because only weak correlationwas found with FEV1/FVC or RV/TLC ratios,respectively.67 The tracheal collapsibility nega-tively correlated with FEV1/FVC and FEV1% pre-dicted, suggesting that the highly collapsedtrachea on end-expiratory scans indicated lesssevere airflow limitation in the individuals analyzedin this study. These findings add to the body ofevidence that the collapsed trachea on end-expiratory scans in the form of EDAC is not amorbid finding and should be distinguished fromthe abnormally collapsed trachea in TBM.

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These observations are relevant for future radio-logic and physiologic studies of tracheal collapsein COPD or TBM.67 In addition to COPD, using dy-namic CT, EDAC was also shown in 69% adult pa-tients with cystic fibrosis.79 Based on data fromdynamic CT studies, radiology literature suggeststhe need for more rigorous criteria for diagnosingclinically relevant EDAC, with potentially separatediagnostic threshold levels for the trachea andright and left bronchi.12,17 Correlation of forcedexpiratory CT findings of EDAC with symptomsand pulmonary function testing is necessary inthe decision-making process before consideringEDAC a cause of a patient’s symptoms and subse-quently proceed with interventions.The increasing use of dynamic CT for TBM and

EDAC led to recognition of several morphologictypes of central AC. Similar to bronchoscopic clas-sifications, numerous descriptive terms have beenproposed, but no 1 system has been universallyadopted. CT classification is based on mor-phology on inspiratory and expiratory images.For instance, on inspiratory images, the normaltrachea is generally oval or round. In patientswith the most common type of TBM (the crescenttype), even during inspiration, the anterior wall ofthe cartilage is flattened and the shape of the tra-chea has been described on CT scans as lunate,in which the coronal/sagittal diameter ratio isgreater than 1.80–82 A second type is the saber-sheath morphology, usually associated withCOPD.83 Some patients with this type of trachealconfiguration have malacia as well,84 but thiscan occur in the presence of normal inspiratorytracheal morphology. A biconvex, fish-mouthpattern has also been described.72 Based on expi-ratory images, the terms used in the radiology liter-ature include crescent, characterized by markedanterior bowing of posterior wall, or the so-calledfrown sign82 and circumferential, characterizedby isotropic reduction in airway cross section.

Dynamic Magnetic Resonance Imaging

The use of magnetic resonance imaging (MRI) hasbeen rarely reported in adults with TBM andEDAC,85,86 but it is used to diagnose and monitorresponse to stabilization techniques for pediatricTBM.87–89 MRI studies reveal similar results withthose from dynamic CT analyses of central AC.For instance, in 1 study, a significantly highercollapse was found in patients with COPDcompared with volunteers, with 70% of patientswith COPD showing a collapse of more than50%.85 Contrary to CT scanning, MRI has theadvantage of avoiding radiation and offering supe-rior contrast resolution and more definitively

characterizes soft tissue masses. MRI can delin-eate tracheal and main bronchial patency and theirclose anatomic relationship with the adjacentvascular structures. Modern MRI allows centralairway imaging with adequate resolution.85,90 Aswith CT, contrast agents are still used, but in thecase of MRI, intravenous gadolinium contrast-based agents are generally recommended unlesscontraindications exist. Images can be affectedby respiratory and cardiac motion artifact, whichmakes interpretation of intrathoracic MRI imagesmore difficult. Mainstem bronchi trajectories areoblique and bias the accuracy of CSA measure-ment. Increased acquisition times often requirethe patient to stay still for at least several minutesat a time, which may not be possible in dyspneic,uncooperative, or critically ill patients.91 The MRIexamination takes about 15 minutes. Three dy-namic measurements can be performed in thecoronal, oblique, and transverse orientation, re-spectively. Minimal and maximal cross-sectionalluminal diameters and tracheal lumen area canbe calculated. In 1 study, the median degree oftracheal collapse was found to be 43% in volun-teers and 64% in smokers. The maximal CSA ofthe upper tracheal lumen as well as the expiratorycollapse was larger in patients with COPD than innormal individuals.85 Similar to data from CTstudies, a significant proportion of patients withCOPD (70%) and 30% of volunteers showed acollapse of more than 50%. Overall, however, thehigh spatial (submillimeter) and temporal resolu-tion (10 frames/s) of dynamic CT cannot yet beobtained by MRI techniques.92

MRI has been used to assess focal malaciaassociated with laryngotracheal stenosis93,94 ordiffuse malacia from relapsing polychondritis.95

The dynamic (cine) MRI has been particularly use-ful to define pediatric TBM.96 MRI is established asthe standard modality for imaging the pediatricmediastinal airway.96 Ventilation and perfusionmapping and quantification are also possible andmay have a role in the future MR imaging of pa-tients with TBM and EDAC.

High-Frequency EndobronchialUltrasonography

High-frequency endobronchial ultrasonography(EBUS) using a 20-MHz radial scanning probewas shown to identify the hypoechoic and hyper-echoic layers that correlate with the laminar histo-logic structures of the central airways.97 Cartilageabnormalities (weakness, fracture, edema) wasdescribed in patients with malacia caused bytuberculosis, relapsing polychondritis, lung can-cer, and compression by vascular rings.97–99

Evaluation: key points

1. Spirometry values do not correlate with thedegree of AC.

2. Expiratory flow-volume curve may show asudden decrease in peak flow very early dur-ing a forced expiratory maneuver (alsoknown as AC pattern) or flow oscillation(also known as saw-tooth pattern).

3. Dynamic and functional bronchoscopy areperformed to distinguish and classify TBMand EDAC, to determine choke point loca-tion, and subsequently to decide on theneed for and type of treatment.

4. Low-dose paired inspiratory–dynamic-expi-ratory CT is complementary to bronchoscopyby providing information about the adjacentvasculature, mediastinal masses, or paren-chymal changes that may explain the causeof ECAC.

5. Low-dose paired inspiratory–dynamic-expi-ratory CT results in false-positive findings ofEDAC if the 50% cutoff is used to defineabnormal collapse.

6. Dynamic MRI can be used to detect ECAC


EBUS could potentially distinguish between TBMand EDAC because in the latter it seems thatthe cartilage is intact, and the posterior mem-brane is thinner than normal, likely because of at-rophy of elastic fibers.99 The instability of theposterior tracheal wall is in agreement with theknown loss of elastic fibers, which enables infla-tion and collapse during respiration. Cartilage ab-normalities in the central airways of patients withCOPD and ECAC have not been systematicallystudied with EBUS. This finding is relevantbecause based on wave speed theory and EPPtheory, the CSA at the choke point is determinedby the pleural pressures, resistance of the up-stream airways and compliance of the airway. Itis relevant for treatment to know if the airwaycompliance is increased because of the reducedstiffness from weakened cartilage. However, thepathologic hallmarks of COPD are destructionof the lung parenchyma, which characterizesemphysema; inflammation of the peripheral air-ways, which characterizes bronchiolitis, andinflammation of the central airways, which char-acterizes chronic bronchitis. In patients withchronic bronchitis, inflammation was found tobe present in the airway wall and in the mucousglands, particularly in cartilaginous bronchi largerthan 2 mm in diameter. However, there is nomention of cartilaginous destruction in biopsystudies of patients with COPD.100 More studiesare needed, but there is potential for high-frequency EBUS to be used as a surrogate of his-tology in patients with ECAC.

and has lower resolution than CT scanningbut is preferred in the pediatric populationbecause of lack of ionizing radiation.

7. High-frequency EBUS may be used as a surro-gate of histology to identify structuralairway wall changes in ECAC.

Vibration Resonance Imaging

Vibration response imaging (VRI) is a noninvasiveimaging tool using piezoacoustic sensors totransform analog signals from the chest into dy-namic grayscale images similar to the processinvolved in ultrasound imaging. VRI has been re-ported in the evaluation of patients with asthma,COPD, aspiration of foreign objects, and centralairway obstruction undergoing bronchoscopic in-terventions.101 The experience in patients withECAC is limited,58 but the disappearance offloating and fluttering dynamic imaging pattern af-ter stent insertion is consistent with previousstudies showing improvement in patients withother forms of central airway obstruction afterbronchoscopic interventions.101 Because soundsat frequencies of 100 to 250 Hz are mainly gener-ated in the central airways and frequencies of 500to 650 Hz in the terminal bronchioles, the differen-tial analysis of VRI might allow localization ofpathologic processes in different compartmentsof the lung.101 TBM and EDAC may provide

different dynamic grayscale images, because inTBM, the FLS are predominantly central, whereasthey are peripheral in EDAC, although these hy-potheses remain to be studied. Given its noninva-siveness, this modality could potentially be usedfor telemedicine monitoring of symptomaticpatients.

TREATMENT

Functional impairment attributable to ECAC war-rants evaluation for treatment. Patients with inci-dental abnormal AC on bronchoscopy or CTscanning performed for other reasons should notundergo interventions.3,102 Functional impairmentin ECAC may result from at least 3 causes: dys-pnea, cough, mucus retention.9,14,53 EDAC isalso associated with higher morbidity and poorersurvival in elderly patients who have undergonebronchial and bronchovascular sleeve resectionsfor lung cancer.21 Therefore, as for other pulmo-nary disorders, QOL and functional impairmentscales may be appropriate to measure the impactof respiratory symptoms on overall health, daily

Murgu & Colt546

life, and perceived well-being in patients sufferingfrom ECAC. This evaluation typically involvesPFTs, 6MWT, and determination of Karnofsky per-formance status, American Thoracic Society Dys-pnea Score, and respiratory-affected QOL basedon the SGRQ.Significant impairment of the patient’s functional

status and QOL is necessary before consideringpotential intervention. However, there are nocontrolled studies to support 1 therapy versusanother. Research is limited by ethical issues.For instance, a randomized trial of tracheobron-choplasty versus sham surgery is obviously notfeasible, but it is possible to design a randomizedstudy of rigid bronchoscopy and rigid bronchos-copy plus Y-stent placement for diffuse and se-vere EDAC. The disease process, before invasiveinterventions, has to be clearly defined and quan-tified in terms of morphology of ECAC, extent,severity of narrowing, and impact on functionalclass and QOL scores (Fig. 7).

Cause-Based Treatment Strategies

Treatment of the primary cause of AC may or maynot improve the degree of airway narrowing orsymptoms. The invasive nature of alternative stra-tegies (stents, tracheoplasty) justifies an initialattempt at medical treatment of the cause ofEDAC/TBM. For instance, reversibility of EDACcan occur after properly treating chronic bronchitiswith bronchodilators, steroids, and antibiotics. In1 study,55 the AC pattern on the flow-volumeloop characterizing EDAC showed completereversibility in a few (3/20) patients after 3 weeks.From a physiologic standpoint, based on EPP the-ory, this finding is relevant because the AC patterncan normalize after treating bronchitis (Ruscomponent) without a concomitant normalizationof elastic recoil. On the other hand, bronchodila-tors may increase airway wall compliance, sug-gesting that increased compressibility of thelarge airways causes the EPP to become fixed ata point nearer the thoracic outlet. The increasedlength of the upstream segment (Rus) anddecreased CSA at the EPP would thus offset theadvantage gained by increased caliber of up-stream airways with respect to maximal expiratoryflow rates.103 This finding may explain why somepatients with EDAC caused by COPD do notimprove after bronchodilators. Some patientsmay have worsened maximum expiratory flowrates.104,105

Treatment of emphysema itself could lead toimprovement in EDAC, further supporting the argu-ment that EDAC is not a primary tracheobronchialdisorder. Improvement in expiratory flows after

lung volume reduction surgery is largely causedby increases in recoil pressure (Pst). Placement ofthe endobronchial valves results in less hyperinfla-tion (improved Pst), and bronchoscopic follow-upmay show improved EDAC (Hugo Oliveira, MD,Brazil, personal communication, 2008), but thishypothesis needs to be tested in emphysema treat-ment trials. For patients with a known cause ofcartilage inflammation such as relapsing polychon-dritis, treatment with immunosuppressive therapyis offered first unless the airway is critically nar-rowed and the patient in extremis (seeFig. 7). How-ever, results of studies and clinical experiencesuggest that once malacia has developed, antiin-flammatory agents may not restore cartilage integ-rity.106 For patients with disease refractory tomedical treatment, strategies aimed at restoringairway patency are offered based on the degreeof airway narrowing, craniocaudal extent, and,most importantly, impact on symptoms, predictedresponse, and expected complications (seeFig. 7).

NIPPV

Application of positive airway pressure serves as apneumatic stent,107 because the intraluminal pres-sure is increased, thus improving the airway stiff-ness and expiratory flow based on wave speedtheory (Equation 2). Alternatively, flow may beimproved simply because lung volumes are higherduring positive pressure ventilation. The higherelastic recoil, based on the EPP theory, improvesthe maximum expiratory flow (Equation 1). Datafrom pediatric TBM confirm this concept. CPAPsignificantly increased maximal expiratory flow atFRC in healthy infants and infants with tracheoma-lacia.108 This increase in flow at FRC was second-ary to the increase in lung volume with CPAP,because maximal expiratory flows measured atthe different levels of CPAP were not differentwhen compared at the same lung volumes. Theoptimal level of CPAP in infants with severe trache-omalacia may be related to increasing the lung vol-ume to a level at which the infant is not flow limitedduring tidal breathing, without also significantlyincreasing the work of breathing through adecrease in pulmonary compliance at increasedlung volumes.From a clinical standpoint, regardless of its

mechanism of action, CPAP was shown toimprove dyspnea, cough, and secretion manage-ment in selected patients with TBM. The amountof pressure necessary to maintain airway patencycan be determined by performing bronchoscopyassisted by NIPPV.61 Adjunctive NIPPV decreasespulmonary resistance and can be used to im-prove spirometry values, sputum production,


atelectasis, and exercise tolerance, but its long-term efficiency has not been clearlyshown.23,109,110 NIPPV has been used in adultswith TBM from relapsing polychondritis and tra-cheomalacia from long-standing compression bya large goiter or thyroid cancer, wherein the carti-laginous rings of the trachea are considerablyweakened or destroyed, leading to softening andfloppiness of the trachea. NIPPVwas also effectiveand safe in the management of stridor and airwaycompromise after early extubation of patients withpostthyroidectomy tracheomalacia.111 In 1 study,6 patients developed stridor and airway compro-mise, which resolved immediately with the initia-tion of NIPPV without further respiratory supportbeing required and without complications.111

Application of noninvasive positive expiratorypressure (PEP) may improve expiratory flow andcough efficiency in patientswith ECAC. This findingwas shown in a study of 40 children with TBM.112

Patients and 21 age-matched controls performedspirometry followed by cough spirometry withPEP of 0, 5, 10, 15, and 20 cmH2O using an adjust-able PEP valve. Cough expiratory flow between75% and 25% of vital capacity (CEF25-75) foreach curve was calculated to represent the effec-tiveness of cough at midlung volume. In the TBMgroup, CEF25-75 increased by a mean of 18.8%,1.7%, and 0.5% at PEP of 5, 10, and 15 cm H2O,respectively, but decreased by 2.4% at PEP of20 cm H2O. In the control group, the CEF25-75decreased at all levels of PEP, with worse flow athigher PEP levels.112 This study112 suggests thatthe use of adjustable PEP valve increases flow dur-ing cough spirometry and may provide a usefuladjunct to chest physiotherapy. It also shows theimportance of scientifically choosing PEP levels,because higher levels (ie, 20 cm H2O) may worsenexpiratory flow.

Bronchoscopic Interventions

Some patients with EDAC improve QOL afterinsertion of a central airway stabilization by stent.However, this situation is not explained byimprovement in airflow as measured by FEV1.

53

One explanation for improved symptoms is thatcentral airway stability makes the flow less turbu-lent, similar to heliox, which was shown to improveexercise capacity in patients with moderate to se-vere COPD.113 In the short-term (10–14 days),airway stabilization using silicone stents in patientswith various forms of ECAC was shown to improverespiratory symptoms, QOL, and functionalstatus.53,114 In 1 large study, 45 of 58 patients(77%) reported symptomatic improvement; QOLscores improved in 19 of 27 patients (70%);

dyspnea scores improved in 22 of 24 patients(91%); and functional status scores improved in18 of 26 patients (70%).53 Stents may also improveoutcomes for patients with Mounier-Kuhn syn-drome115 and have been used in patients with mal-acia from relapsing polychondritis, with variableresults.39,116,117 Of 8 patients with bronchoscopi-cally detected TBM in a study of patients with re-lapsing polychondritis, only 3 were treated (2 bystent insertion and 1 by tracheostomy and removalof previously placed stents).118 Metal stents havebeen used in the past with variable success in pa-tients with TBM. Advantages include placement byflexible bronchoscopy, dynamic expansion, andmaintenance of airway mucociliary function withuncovered stents. However, in some studies,metal stents had to be removed because of stentmechanical failure or because of stent-relatedcomplications. Stent fracture and fatal hemor-rhage from perforation have been reported; in theUnited States, metal stents are no longer recom-mended for use in benign central airway diseaseif other alternatives are available.119,120

To potentially detect stent-related adverse ef-fects or migrated choke points requiring further in-terventions, follow-up bronchoscopy or dynamicCT has been used in clinical studies.121 Stent-related adverse events are common and usuallyoccur within the first few weeks after stent inser-tion (median time 4 weeks).53,114 These resultsseem to justify follow-up imaging 4 to 6 weeks af-ter stent insertion (see Fig. 7). Sometimes, follow-up detects distally migrated choke points afterstent insertion.39,40 Placing a stent at the site ofmaximal collapse during exhalation might resultin migration of the choke point toward the periph-ery of the lung122 and has been addressed in pa-tients with central airway obstruction caused bylung cancer and also in patients with malaciafrom relapsing polychondritis. Additional stentsmay be required if patients are still symptomaticand the choke points are still in the central airways.In 1 series, bilevel positive airway pressure wasused after stent insertion for patients whose chokepoints had migrated to the small bronchi, as docu-mented on CT.39 Rather than inserting moreforeign material into an already inflamed airway,it may be more reasonable to use adjuvant NIPPV.If stent insertion does not improve symptoms andthere is no migration of the choke points, thenstent removal is advisable to avoid complications.Stent migration, obstruction by mucus and granu-lation tissue, infection, fracture, and airway perfo-ration are well described in the literature.3 Thedistinction between stent-related adverse eventsand symptoms related to TBM may be difficult toassess based on clinical grounds, so any new

Murgu & Colt548

onset or worsening of symptoms should promptbronchoscopy or CT scanning (see Fig. 7).Yttrium aluminum perovskite (YAP) laser treat-

ment has been anecdotally reported to improve

lung function and symptoms in EDAC causedby Mounier-Kuhn syndrome; laser was appliedwith the intention of stiffening the posterior mem-brane by devascularization and subsequent

=


retraction of tissues.123 Its wavelength is doublethat of the yttrium aluminum garnet laser, allow-ing for tissue devascularization and coagulationat low power (15–20 W) in a discontinuousmode.124 The depth of penetration using YAPlaser is estimated at 3 mm and may reach thesubmucosal tissues, triggering a fibrotic pro-cess125 that may stiffen the posterior membrane.Concerns remain about posterior membraneperforation and relapse of disease with theneed for repeated interventions.

Surgical Interventions

Cervical tracheoplasty, resection/reconstruction,or tracheostomies are usually performed for extra-thoracic tracheal malacia. Tracheal resection hasbeen proposed for focal tracheomalacia, withgood outcome and low mortality in experiencedcenters.126 However, this procedure was per-formed for posttracheostomy-related malaciaand not for extensive disease. Open surgical inter-ventions for intrathoracic disease include airwaysplinting and tracheostomy. Splinting (tracheo-plasty) has been used to consolidate and reshapethe airway wall, whereas tracheostomy is per-formed to maintain a stable airway and potentiallybypass the malacic segment. Tracheostomy pro-vides invasive ventilatory support if necessary,but it can be complicated by secondary tracheo-malacia and stenosis and should not be con-sidered a first-line treatment in elective cases.Before proposing membranous tracheoplasty, a

Fig. 7. Management algorithm for diffuse ECAC. Once ideare performed (if not performed previously) to assess if tflow or dynamic hyperinflation. A clear categorization asThe extent, degree of narrowing, and impact on functiontreatment is warranted. The cause of the process (whenIn addition to disease-specific treatment, chest physiotheravalves can be used to improve secretion management. If tha follow-up strategy with clinical examination, PFTs, and Crence. If this fails and the patient is critically ill (unable tosupport), the airway has to be stabilized and stent insethen NIPPV-assisted bronchoscopy is performed to determpatency. If the airway patency is maintained during NIPPVscribed for nighttime NIPPV and intermittent use during threspond to NIPPV, 1 strategy involves a so-called stent tritracheoplasty is offered to operable patients; if patients aris an alternative understanding if there is a high risk forbronchoscopy can be performed to localize the FLS amencheoplasty). If the FLS are in the trachea or mainstem broproceed directly with tracheoplasty has not yet been studiinsertion or tracheoplasty should not be offered, becauseplanations for patient’s symptoms should be investigatebronchoscopy or dynamic CT should be performed withinadverse events. H&P, history and physical examination; 1,cific intervention; dashed line, an alternative strategy, dep

stent trial has been used to identify those patientswho are likely to benefit from surgery in the long-term. When performed on this protocol, membra-nous tracheoplasty seemed to provide a favorableoutcome in uncontrolled studies.

This procedure reinforces the membranousportion of the trachea in severe diffuseECAC.54,127 The thoracic airways are splintedfrom the thoracic inlet to the distal left mainstembronchus and distal bronchus intermedius. Theoutcomes of membranous tracheoplasty arepromising, but complications are not insignificant;for instance, 1 study evaluated 66 patients with se-vere diffuse crescent-type TBM and EDAC (dis-ease affecting trachea and bilateral mainstembronchi).128 However, the 2 entities were groupedtogether under TBM and results were not reportedseparately. Thirty-seven patients had completesets of preoperative and postoperative measure-ments of FEV1, and no significant difference wasshown before and after the procedure. Twenty-two of 37 patients had improved FEV1, with amean increase of 234 mL, whereas 15 of 37 pa-tients showed no improvement or frank worseningof their postoperative FEV1, with a mean decreaseof 235 mL, and 1 patient also had the same FEV1

values preoperatively and postoperatively. Thisstudy confirms earlier physiologic findings thatstabilization of the collapsing tracheal and bron-chial airway may not improve airflow but mayresult in improvements in short-term (3-month)QOL measurements. The median length of stayin the hospital after this surgical intervention was

ntified on dynamic CT or dynamic bronchoscopy, PFTshere is any associated impact on maximum expiratoryTBM or EDAC is performed and cause is searched for.al status and QOL are then evaluated to determine ifknown) should be medically treated first, if possible.py, mucolytics, adjustable positive expiratory pressuree underlying cause is treated and the patient improves,T/bronchoscopy is warranted in case of symptom recur-be weaned from invasive or noninvasive ventilatory

rtion is performed. If the patient is not critically ill,ine if positive pressure application maintains airwayapplication, then those particular settings can be pre-e day as triggered by symptoms. If the patient does notal. If there is improvement (objectively documented),e not surgical candidates, a permanent stent insertionstent-related adverse effects. Alternatively, functionalable to stabilization techniques (stent insertion or tra-nchi, then a stent trial is performed (an algorithm toed). If the FLS are not in the central airways, then stentthey are unlikely to improve flow and alternative ex-d. After stent insertion or tracheoplasty, a follow-up4 to 6 weeks to assess airway patency and potentialimprovement and –, lack of improvement after a spe-ending on availability/expertise with technique.

Murgu & Colt550

8 days (range, 4–92 days), of which 3 days (range,0–91 days) were in the intensive care unit. Two pa-tients (3.2%) died postoperatively and overallcomplications were seen in 38% of patients andincluded a new respiratory infection, pulmonaryembolism, and atrial fibrillation. Six patients(10%) required reintubation and 9 (14%) receiveda postoperative tracheotomy, including 4 trache-otomies intraoperatively immediately after the tra-cheobronchoplasty in anticipation of the need forfrequent therapeutic aspiration bronchoscopyand tracheal suctioning, which was needed in 47of 66 patients. A less invasive approach usedvideo-assisted thoracoscopic surgical tracheo-bronchoplasty combined with airway stent place-ment for the treatment of 2 cases of TBM.129 Theanecdotal evidence and concurrent use of stentsraise questions about the long-term benefits ofthe combined modality.

Treatment strategies: key points

1. Asymptomatic ECAC, regardless of the de-gree of AC, should not be treated.

2. Treatment of the underlying cause must beattempted before considering more invasiveinterventions.

3. NIPPV-assisted bronchoscopy allows titrationof applied pressures that maintain airwaypatency during expiration.

4. Intraluminal airway pressures measurementslocalize the choke points and may predictresponse to interventions.

5. Focal disease can be treated by resection orreconstruction or bypassed with anindwelling tracheostomy tube.

6. Significantly impaired patients with severeand diffuse EDAC or crescent TBM maybenefit from membranous tracheoplasty.

7. Inoperable patients with refractory symp-toms may benefit from silicone stentinsertion.

8. Most patients with ECAC and indwellingairway stents require frequent broncho-scopic interventions to manage stent-related mucus obstruction, migration, andgranulation tissue.

SUMMARY

TBM is characterized as weakened or destroyedcartilage in the central airways, resulting in expi-ratory flow limitation. EDAC is characterized byexcessive bulging of the posterior membrane

inside the central airway lumen. ECAC is a syn-drome that includes both TBM and EDAC.Depending on the degree of AC, anatomic site,and respiratory maneuver used for defining it,EDAC is seen in normal individuals, those withmorbid obesity, and those with a variety ofobstructive ventilatory disorders. A careful phys-iologic assessment of the impact of ECAC onairflow and functional status is warranted beforetreatment. Identification of the flow-limitingairway segments can be obtained by performingfunctional bronchoscopy before invasive inter-ventions. Even when the central AC is identifiedas responsible for symptoms, we suggest a con-servative approach with medical treatment andNIPPV before committing patients to potentiallyharmful effects resulting from airway stents oropen surgical procedures.

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Tracheobronchomalacia and Excessive Dynamic Airway Collapse · bronchus (LMB), and even total collapse in the bronchus intermedius.12 A different study showed that the mean % collapse