collapse in patients with tracheobronchomalacia,

J. Zhang 1,2 I. Hasegawa 1,3 H. Hatabu 1,3 D. Feller-Kopman 1,3 P. M. Boiselle 1,3 Received June 5, 2003; accepted after revision July 23, 2003. 1 Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline ve., Boston, M 02215. ddress correspondence to P. M. Boiselle. 2 Present address: Department of Radiology, New York University Medical Center and Harvard Medical School, New York, NY. 3 Division of Pulmonary Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, M. JR 2004;182:81 85 0361 803X/04/1821 81 merican Roentgen Ray Society Frequency and Severity of ir Trapping at Dynamic Expiratory CT in Patients with Tracheobronchomalacia OBJECTIVE. The purpose of this study was to compare the frequency and severity of air trapping in patients with and without tracheobronchomalacia using dynamic expiratory volumetric CT. MTERILS ND METHODS. The study group consisted of 20 subjects, including 10 patients with bronchoscopically proven tracheobronchomalacia and 10 control subjects of similar ages without tracheobronchomalacia. ll 20 subjects underwent MDCT performed at the end of deep inspiration and during dynamic expiration. The images were analyzed at three lung levels, and the extent of air trapping was assessed visually using a 5-point scale. For each subject, a total air-trapping score was derived by summing the values for the three lung levels (possible range, 0 12). Statistical analysis was performed using the Mann-Whitney U test. RESULTS. In the tracheobronchomalacia group, 10 (100%) of 10 patients showed air trapping, with a median score of 5 (range, 2 12). In the control group, six (60%) of 10 subjects showed air trapping, with a median score of 2 (range, 0 3). The median total air-trapping score was significantly higher (p < 0.001) for the tracheobronchomalacia group compared with the control group. Excessive central airway collapse (expiratory reduction in cross-sectional area of > 50%) was seen on CT scans in all tracheobronchomalacia patients but in none of the control subjects. CONCLUSION. ir trapping was observed with a higher frequency and greater severity in patients with tracheobronchomalacia than in a control group of patients of similar ages without tracheobronchomalacia. ir trapping is caused by excessive retention of gas in the lung during expiration. On CT scans, a normally ventilated lung shows a homogeneous increase in attenuation during expiration because the amount of air in the lung is reduced [1]. On expiratory imaging, regions of the lung with air trapping increase in attenuation to a lesser degree than in a normally ventilated lung [1, 2] and therefore appear more radiolucent compared with the healthy lung. Expiratory high-resolution CT is accepted as a reliable test for the assessment of air trapping [1 4]. Gotway et al. [5] reported that dynamic expiratory thin-section CT is a more sensitive method than end-expiratory CT for detecting air trapping. Tracheobronchomalacia is a condition characterized by excessive central airway collapsibility due to weakness of the airway walls and supporting cartilage [6 8]. In the clinical practice of interpreting dynamic expiratory CT scans obtained for the evaluation of central airway collapse in patients with tracheobronchomalacia, we have often observed the presence of air trapping in the lungs. The purpose of this study was to compare the frequency and severity of air trapping in patients with and without tracheobronchomalacia using dynamic expiratory CT. Materials and Methods Subjects This retrospective study was designed to compare the degree of air trapping among patients with and without tracheobronchomalacia who underwent a combined inspiratory and dynamic expiratory CT protocol at our institution. We used our hospital record system to identify 10 consecutive patients with bronchoscopically proven tracheobronchomalacia who underwent paired inspiratory and dynamic expiratory CT at our institution between November 1999 and May 2002. We also randomly identified 10 control patients of similar ages without tracheobron- JR:182, January 2004 81

Zhang et al. chomalacia who underwent the same imaging protocol for clinical or radiographic suspicion of central airways disease but had no evidence of tracheobronchomalacia. Exclusion criteria were the presence of significant alveolar or interstitial pulmonary abnormalities on CT scans (including evidence of infectious pneumonia, interstitial pneumonia, or pulmonary fibrosis) or significant central airways disease other than tracheobronchomalacia, such as endobronchial neoplasms or mucoid impaction. The control subjects were selected within an age range similar to that of the tracheobronchomalacia patients to avoid the possibility of differences in air trapping due to age, because air trapping has been reported to increase in frequency with advancing age [9]. review of each subject s computerized hospital information system records was performed to identify a history of asthma or emphysema. Imaging Technique ll patients underwent MDCT on either a fouror eight-detector scanner (LightSpeed, General Electric Medical Systems, Milwaukee, WI). The imaging parameters were as follows: collimation, 2.5 mm; gantry rotation time, 0.8 sec (four-detector scanner) or 0.5 sec (eight-detector scanner); pitch, high-speed mode; pitch equivalent, 1.5; and 120 kvp. CT images were reconstructed with a highspatial-resolution algorithm (bone algorithm). Before volumetric scanning, initial scout topographic images were obtained to determine the area of coverage, which included the trachea and central bronchi, corresponding to a length of approximately 10 12 cm. Scanning was performed in the craniocaudal dimension for both end-inspiratory and dynamic expiratory imaging. End-inspiratory scanning was performed first in all patients, and images were obtained during suspended full inspiration. fter end-inspiratory scanning, patients were subsequently coached with instructions for the dynamic expiratory component of scanning. The beginning of the CT acquisition was coordinated with the onset of the patient s expiratory effort. Both inspiratory and expiratory scanning were performed with the patient in the supine position. Standard lung window settings (level, 650 H; width, 1,500 H) were used for display on a PCS (picture archiving communications system) (PathSpeed, General Electric Medical Systems). Visual ssessment of ir Trapping To reach consensus, two observers retrospectively reviewed the scans for evidence of air trapping. Before assessing the study images, the two observers reviewed a series of reference images that illustrated varying grades of air trapping. Subsequently, the paired inspiratory expiratory CT scans from each of the 20 patients were reviewed randomly on a PCS monitor without knowledge of the patients histories. For each subject, dynamic expiratory images were compared with end-inspiratory images at three anatomic levels: upper lung zone, defined as the level of the superior aspect of the aortic arch; middle lung zone, defined as the level of the carina; and lower lung zone, defined as the level 2 cm below the carina. The degree of air trapping was assessed by comparing end-inspiratory and dynamic expiratory images at similar anatomic levels. ir trapping was defined as the presence of radiolucent regions of the lungs on dynamic expiratory images [9, 10]. The degree of air trapping at each of the three levels was graded on a 5-point scale: 0, no air trapping; 1, 1 25% cross-sectional area affected; 2, 26 50% crosssectional area affected; 3, 51 75% cross-sectional area affected; and 4, 76 100% cross-sectional area affected. total air-trapping score was obtained by summing the individual grades for the three levels (maximal possible score, 12). The pattern of air trapping was categorized as lobular, segmental, lobar, or diffuse. lobular pattern was defined as areas of air trapping involving less than an entire segment. This pattern included small foci corresponding to the shape of secondary pulmonary lobules and larger foci, comprising several adjacent lobules with involvement of less than an entire segment. segmental pattern was defined as involvement of an entire segment or multiple adjacent segments involving less than an entire lobe. lobar pattern referred to involvement of an entire TBLE 1 Patient No. Note. N = not applicable. a Mean age = 56 years, median = 5 years, SD = 3.2 years. b Mean age = 52 years, median = 2 years, SD = 1.4 years. lobe. diffuse pattern was defined as involvement of greater than 50% of the lungs without a characteristic distribution by lobules, segments, or lobes. It was permissible to list more than one type of pattern for a subject. When more than one pattern was present, it was considered a mixed pattern. Statistical nalysis The Mann-Whitney U test was used to compare the total air-trapping score between the tracheobrancholomacia patients and the control subjects. p value of less than 0.05 was considered statistically significant. Results The demographics of the study participants and the scores and patterns of air trapping are summarized in Table 1. The tracheobronchomalacia group consisted of five men and five women, with an age range of 42 79 years (mean age, 56 years). Four (40%) of 10 patients had a history of asthma (n = 1) or emphysema (n = 3). The control group consisted of three men and seven women, with an age range of 27 75 years (mean age, 52 years). Six Demographic Information and ir-trapping Scores and Patterns for Tracheobronchomalacia (TBM) Patients and Control Subjects ge (yr) Sex History of Chronic irway Disease ir-trapping Score Pattern of ir Trapping TBM group a 1 62 M Emphysema 11 Mixed (lobular and diffuse) 2 44 F No 5 Mixed (lobular and segmental) 3 42 F No 2 Lobular 4 79 F No 5 Mixed (lobular and segmental) 5 60 M sthma 3 Segmental 6 57 F No 12 Diffuse 7 50 M No 7 Lobular 8 58 F No 4 Lobular 9 46 M Emphysema 6 Lobular 10 62 M Emphysema 5 Lobular Control group b 11 52 F sthma 0 N 12 75 M Emphysema 3 Lobular 13 44 F No 2 Segmental 14 46 F sthma 3 Lobular 15 62 M sthma 0 N 16 45 F sthma 0 N 17 51 F No 3 Mixed (lobular and segmental) 18 47 F No 3 Lobular 19 75 M No 2 Segmental 20 27 F sthma 0 N 82 JR:182, January 2004

CT of ir Trapping in Tracheobronchomalacia (60%) of 10 patients had a history of asthma (n = 5) or emphysema (n = 1). In the tracheobronchomalacia group, 10 (100%) of 10 patients showed air trapping (Figs. 1 and 2), with a median score of 5 (range, 2 12). In the control group, six (60%) of 10 patients showed air trapping, with a median score of 2 (range, 0 3). The total air-trapping score was significantly higher (p < 0.001) in the tracheobronchomalacia group compared with the control group. Because four of 10 patients in the tracheobronchomalacia group had underlying asthma or emphysema, known risk factors for air trap- ping, we also analyzed the data separately for the subgroups of patients with and without these underlying disorders. Of the six tracheobronchomalacia patients without asthma or emphysema, all showed evidence of air trapping, with a mean air-trapping score of 6. Similarly, the four patients with tracheobronchomalacia and history of underlying asthma or emphysema all showed evidence of air trapping, with a mean air-trapping score of 6. mong the six control subjects with underlying asthma or emphysema, two (33%) showed evidence of air trapping, including one (25%) of four control subjects with a history of asthma. The mean score among control subjects with asthma or emphysema who showed air trapping was 3. Similarly, the mean score among the four control subjects without asthma or emphysema who showed air trapping was 3. The air-trapping patterns are listed in Table 1. The most common air-trapping pattern in the tracheobronchomalacia group was lobular, shown in five (50%) of 10 patients. Similarly, the most common air-trapping pattern for the control group was lobular, present in three (50%) of six control subjects with evidence of air trapping. ll 10 patients with tracheobronchomalacia showed more than 50% reduction B C D Fig. 1. 50-year-old man with tracheobronchomalacia and air trapping., End-inspiratory CT scan obtained at level of aortic arch shows normal appearance of trachea and lung parenchyma. B, Dynamic expiratory CT scan obtained at level similar to shows excessive collapse of trachea (black arrows), consistent with malacia. lso note areas of geographically marginated radiolucency (white arrows) within lungs, consistent with air trapping. C, End-inspiratory CT scan obtained at level of right upper lobe bronchus shows normal appearance of bronchi and lungs. D, Dynamic expiratory CT scan obtained at level similar to C shows excessive narrowing of bronchi (black arrows) consistent with bronchomalacia. lso note extensive areas of geographically marginated radiolucency (white arrows) within lungs, consistent with air trapping. JR:182, January 2004 83

Zhang et al. in the cross-sectional area of the central airways during dynamic exhalation, whereas all control subjects showed less than 50% reduction. Discussion Previous studies have established that air trapping on expiratory CT can be seen in association with various airway diseases, including bronchiolitis obliterans [2, 11 17], asthma [17, 18], emphysema [19 21], bronchiectasis, and chronic bronchitis [19]. Moreover, it has been established that air trapping can be seen in association with chronic infiltrative disorders that have a component of small airways disease, such as hypersensitivity pneumonitis and sarcoidosis [22]. lthough it has previously been reported that there is an association between air trapping and cigarette smoking [9, 23 25], data in the literature on this subject are conflicting [9, 23, 24 26]. dditionally, air trapping can be seen in healthy subjects with normal results on pulmonary function tests [3, 4, 9, 26]. In this study, air trapping was observed with a significantly higher frequency and greater severity in patients with tracheobronchomalacia compared with a control group of patients of similar ages without tracheobronchomalacia, despite a higher prevalence of disorders known to be associated with air trapping in the control group. To our knowledge, air trapping has not been previously reported in association with tracheobronchomalacia. The cause of air trapping in tracheobronchomalacia patients is uncertain, but it may reflect chronic small airways disease due to abnormal respiratory mechanics related to excessive central airway collapse. Because tracheobronchomalacia is associated with an abnormal coughing mechanism and difficulty clearing secretions, it is plausible that affected patients may Fig. 2. 44-year-old woman with tracheobronchomalacia and air trapping., End-inspiratory CT scan obtained at level of right inferior pulmonary vein shows normal appearance of lungs except for small, ill-defined nodule in right middle lobe. B, Dynamic expiratory CT scan obtained at level similar to shows multiple geographically marginated radiolucent areas (arrows) within lungs, consistent with air trapping. experience chronic inflammation of the small airways on this basis. Future studies are necessary to clarify the precise pathophysiologic basis of small airways disease in tracheobronchomalacia patients and to determine whether it improves after therapy for tracheobronchomalacia with stent placement or tracheoplasty. The acquired form of tracheobronchomalacia has been increasingly recognized as an important cause of chronic respiratory symptoms in recent years [6, 7]. For example, a bronchoscopic series of patients who did not smoke and were being evaluated for chronic cough found tracheobronchomalacia as the cause in 14% of cases [7]. However, tracheobronchomalacia is often overlooked because of its nonspecific clinical symptoms and its usual lack of evidence on routine imaging studies performed at end-inspiration. Clinically, the symptoms are nonspecific and include cough, wheezing, and dyspnea [6 8]. Importantly, these symptoms overlap with those of small airways disease such as asthma. We also observed air trapping in 60% of the control subjects in our study. This finding is not surprising, considering that many of the control subjects in our study group had risk factors for air trapping such as asthma or emphysema. dditionally, air trapping has been reported in healthy subjects with normal results on pulmonary function tests. Notably, however, the severity of air trapping among the control subjects was significantly lower than that of the tracheobronchomalacia patients in our series. Because focal air trapping can be seen in healthy subjects, we emphasize that it is the extent of air trapping and not simply its presence that is physiologically relevant [1]. lthough many of the subjects in our study had risk factors for air trapping, the degree of air trapping observed among patients with tracheobronchomalacia was similar in subgroups with and without asthma or emphysema. Similarly, the severity of air trapping among control subjects with and without asthma or emphysema was comparable to, but significantly lower than, that among patients in the tracheobronchomalacia group. lthough air trapping has been reported in up to 90% of patients with severe asthma, mild to moderate asthma is associated with a lower frequency and severity of air trapping [28, 29]. Because only one of five subjects with asthma in our control group showed evidence of air trapping (and this subject had only mild air trapping), we suspect that these subjects had mild asthma. Interestingly, Park et al. [29] have shown that there is no significant difference in the prevalence of mild to moderate air trapping between patients with asthma and healthy subjects. These investigators concluded that inspiratory and expiratory thin-section CT scans were of limited value in distinguishing asthmatic patients with normal to mild airflow obstruction from healthy subjects. Thus, we do not believe that this factor influenced our finding that air trapping is of greater severity among patients with tracheobronchomalacia compared with control subjects of similar ages. lobular pattern was the most common form of air trapping in both the tracheobronchomalacia and control groups. Thus, the pattern of air trapping does not distinguish patients with tracheobronchomalacia from those with other causes of air trapping. However, in our experience, tracheobronchomalacia patients can readily be distinguished from those with isolated small airways disease by the presence of coexistent excessive collapse of the central airways on expiratory imaging. B 84 JR:182, January 2004

CT of ir Trapping in Tracheobronchomalacia reduction in cross-sectional area of more than 50% between inspiration and expiration is generally considered diagnostic of this condition [27]. Two limitations of this study should be mentioned. First, we do not have detailed smoking histories of the study participants. However, the relationship between cigarette smoking and air trapping is controversial [9, 23 26]. Second, a subjective visual assessment of the air-trapping score was performed, and pulmonary function test results were not available for analysis. However, Chen et al. [3] have reported significant correlation between the air-trapping score and inspiratory expiratory lung attenuation changes and a significant correlation between the airtrapping score and pulmonary function test results. Other authors have also reported similar correlation between the degree of air trapping and pulmonary function test results [9, 17]. Future prospective studies are necessary to correlate air trapping and pulmonary function tests in patients with tracheobronchomalacia. In summary, our study shows that both the frequency and severity of air trapping are increased among patients with tracheobronchomalacia compared with subjects without this disorder. Therefore, when air trapping is seen in the lung parenchyma on expiratory CT scans, one should carefully compare the caliber of the central airways on inspiratory and expiratory images to assess for tracheobronchomalacia. cknowledgments We thank lexis Potemkin for administrative assistance and Michael Larson for assistance with photography. References 1. Stern EJ, Webb WR. Dynamic imaging of lung morphology with ultrafast high-resolution computed tomography. J Thorac Imaging 1993;8: 273 282 2. Stern EJ, Frank MS. Small-airway disease of the lungs: findings at expiratory CT. JR 1994;163: 37 41 3. Chen D, Webb WR, Storto ML, Lee K. ssessment of air trapping using postexpiratory highresolution computed tomography. J Thorac Imaging 1998;13:135 143 4. Webb WR, Stern EJ, Kanth N, Gamsu G. Dynamic pulmonary CT: findings in healthy adult men. Radiology 1993;186:117 124 5. Gotway MB, Lee ES, Reddy GP, Golden J, Webb WR. Low-dose, dynamic, expiratory thinsection CT of the lungs using a spiral CT scanner. J Thorac Imaging 2000;15:168 172 6. Boiselle PM, Feller-Kopman D, shiku S, Weeks D, Ernst. Tracheobronchomalacia: evolving role of dynamic multislice helical CT. Radiol Clin North m 2003;41:627 636 7. Palombini BC, Villanova C, raujo E, et al. pathogenic triad in chronic cough: asthma, postnasal drip and gastroesophageal reflux disease. Chest 1999;116:279 284 8. Johnson TH, Mikita JJ, Wilson RJ, Feist JH. cquired tracheomalacia. Radiology 1973;109:577 580 9. Lee KW, Chung SY, Yang I, Lee Y, Ko EY, Park MJ. Correlation of aging and smoking with air trapping at thin-section CT of the lung in asymptomatic subjects. Radiology 2000;214:831 836 10. ustin JH, Muller NL, Friedman PJ, et al. Glossary of terms for CT of the lungs: recommendations of the Nomenclature Committee of the Fleischner Society. Radiology 1996;200:327 331 11. Garg K, Lynch D, Newell JD, King TE Jr. Proliferative and constrictive bronchiolitis: classification and radiologic features. JR 1994;162:803 808 12. Padley SPG, dler BD, Hansell DM, Muller NL. Bronchiolitis obliterans: high-resolution CT findings and correlation with pulmonary function tests. Clin Radiol 1993;47:236 240 13. Moore D, Godwin JD, Dietrich P, Verschakelen J, Henderson WR Jr. Swyer-James syndrome: CT findings in eight patients. JR 1992; 158:1211 1215 14. Marti-Bonmati L, Ruiz PF, Catala F, Mata JM, Calonge E. CT findings in Swyer-James syndrome. Radiology 1989;172:477 480 15. Sweatman MC, Millar B, Strickland B, Turner- Warwick M. Computed tomography in adult obliterative bronchiolitis. Clin Radiol 1990;41: 116 119 16. quino SL, Webb WR, Golden J. Bronchiolitis obliterans associated with rheumatoid arthritis: findings on HRCT and dynamic expiratory CT. J Comput ssist Tomogr 1994;18:555 558 17. rakawa H, Webb WR. ir trapping on expiratory high-resolution CT scans in the absence of inspiratory scan abnormalities: correlation with pulmonary function tests and differential diagnosis. JR 1998;170:1349 1353 18. Newman KB, Lynch D, Newman LS, Ellegood D, Newell JD Jr. Quantitative computed tomography detects air trapping due to asthma. Chest 1994;106:105 109 19. Lamers RJ, Thelissen GR, Kessels G, Wouters EF, van Engelshoven JM. Chronic obstructive pulmonary disease: evaluation with spirometrically controlled CT lung densitometry. Radiology 1994;193:109 113 20. Gevenois P, De Vuyst P, Sy M, et al. Pulmonary emphysema: quantitative CT during expiration. Radiology 1996;199:825 829 21. Knudson RJ, Standen JR, Kaltenborn WT, et al. Expiratory computed tomography for assessment of suspected pulmonary emphysema. Chest 1991;99:1357 1366 22. Chung MH, Edinburgh KJ, Webb EM, McCowin M, Webb WR. Mixed infiltrative and obstructive disease on high-resolution CT: differential diagnosis and functional correlates in a consecutive series. J Thorac Imaging 2001;16:69 75 23. Remy-Jardin M, Remy J, Boulenguez C, et al. Morphologic effects of cigarette smoking on airways and pulmonary parenchyma in healthy adult volunteers: CT evaluation and correlation with pulmonary function tests. Radiology 1993;186:107 115 24. Berger P, Laurent F, Begueret H, et al. Structure and function of small airways in smokers: relationship between air trapping at CT and airway inflammation. Radiology 2003;228:85 94 25. Verschakelen J, Scheinbaum K, Bogaert J, Demedts M, Lacquet LL, Baert L. Expiratory CT in cigarette smokers: correlation between areas of decreased lung attenuation, pulmonary function tests and smoking history. Eur Radiol 1998;8:1391 1399 26. Tanaka N, Matsumoto T, Miura G, et al. ir trapping at CT: high prevalence in asymptomatic subjects with normal pulmonary function. Radiology 2003;227:776 785 27. Jensen SP, Lynch D, Brown SE, Wenzel SE, Newell JD. High-resolution CT features of severe asthma and bronchiolitis obliterans. Clin Radiol 2002;57:1078 1085 28. Park CS, Muller NL, Worthy S, Kim JS, wadh N, Fitzgerald M. irway obstruction in asthmatic and healthy individuals: inspiratory and expiratory thin-section CT findings. Radiology 1997; 203:361 367 29. Boiselle PM, Reynolds KF, Ernst. Multiplanar and three-dimensional imaging of the central airways with multidetector CT. JR 2002;179:301 308 JR:182, January 2004 85