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Expiratory Air Trapping on Thoracic CT: A Diagnostic Subclassification

Wallace T. Miller, Jr. MD Corresponding author: Associate Professor of Radiology University of Pennsylvania Medical Center Department of Radiology 3400 Spruce St. Philadelphia, PA 1104 [email protected] 215-615-3720 fax: 215-614-0033 Jonathan Chatzkel, MD University of Pennsylvania Medical Center 3400 Spruce St. Philadelphia, PA 1104 [email protected] Michael G. Hewitt, DO University of Pennsylvania Medical Center Department of Radiology 3400 Spruce St. Philadelphia, PA 1104 [email protected]

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1 The authors have no conflicts of interest and no disclosures. The study is unfunded. Descriptor number: 9.30 Running Head: Air Trapping on Expiratory CT Word Count: 2,606

Wallace T. Miller, Jr. MD:

Takes responsibility for the study as a whole Contributions: study design, data collection, data analysis, statistical analysis, manuscript preparation

Jonathan Chatzkel, MD:

Contributions: data collection, data analysis, manuscript preparation

Michael D. Hewitt, DO:

Contributions: data collection, manuscript preparation

Key Words: Air trapping; asthma; chronic bronchitis; bronchiolitis obliterans; obstructive lung disease; computed tomography (CT)

Abbreviations: CT – computed tomography

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2 Abstract Rationale: Multiple causes for air trapping as identified by expiratory CT have been reported but a unified evaluation schema has never been proposed. Objectives: It was our purpose to identify imaging features that would help distinguish etiologies of mosaic air trapping. Methods: Cases with the term “air trapping” in the radiology report in 2010 were identified by searching the Radiology Information System of an academic tertiary care center and associated community hospital. Medical records and CT examinations were reviewed for the causes of air trapping. Results: Causes for moderate to severe air trapping could be identified in 201/230 (87.4%) of cases and could be subdivided into those associated with bronchiectasis (76/201, 38%), those associated with interstitial lung disease (62/201, 31%), those associated with tree-in-bud opacities (5/201, 2%) and those with air trapping alone (58/201, 29%). When found with bronchiectasis, nontuberculous mycobacteria, cystic fibrosis, idiopathic bronchiectasis and transplant related bronchiolitis obliterans were the most common causes of air trapping. When found with interstitial lung disease, sarcoidosis, hypersensitivity pneumonitis or unspecified interstitial lung disease were the most common cause of air trapping. When found in isolation, chronic bronchitis, asthma, bronchiolitis obliterans and unspecified small airways disease were the most common causes of air trapping. Unusual conditions causing isolated air trapping included vasculitis and diffuse idiopathic neuroendocrine cell hyperplasia. Conclusion: A variety of conditions can cause air trapping. Associated imaging findings can narrow the differential diagnosis.

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3 Introduction: The term air trapping indicates retention of inspired air during expiration. This term is applicable to a variety of obstructive lung diseases. In 1993, Webb et al reported their experience with a new type of CT called “expiratory” CT. A standard thoracic CT examination is performed with the patient holding his or her breath at deep inspiration while scanning the lung. Expiratory CT is performed with the patient holding his or her breath at end expiration while scanning the lung. Webb et al showed that normal young men can retain air within individual or groups of secondary pulmonary lobules, a finding that they termed “air trapping” [1]. These lobular areas of decreased attenuation represented hyperinflated lobules caused by obstruction of the supplying bronchioles and are specific for small airways diseases. This radiographic finding is compared with the more general meaning of “air trapping” as measured by pulmonary function tests, which includes a variety of obstructive lung diseases other than small airways disease. In fact, pulmonary function tests can be insensitive to the detection of small airways disease, with the FEF 25-75 reported as the most sensitive pulmonary function test measure of small airways disease [2]. As a consequence, expiratory CT is among the more important tests to identify individuals with small airways disease. Reported causes of CT air trapping include chronic bronchitis [3-10], asthma [3-5, 11-14], bronchiolitis obliterans (obliterative bronchiolitis, constrictive bronchiolitis)[3, 15-22], bronchiectasis [3-5, 23-29], sarcoidosis [5, 30-33], subacute and chronic hypersensitivity pneumonitis [5, 34, 35] and a variety of less common conditions [36-45].

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4 Prior reports are mostly composed of pictorial essays, review articles or reports of preselected disease states. There are three studies of small cohorts of 40-49 patients with consecutive cases of air trapping [3-5]. A large, comprehensive, unselected study of the relative frequency of causes of CT air trapping has not been published previously.

Methods: Study Design The study was approved by the center’s Institutional Review Board (IRB#7, Protocol #813882) and is HIPAA compliant. Informed consent was waived due to the purely retrospective nature of the project. For inclusion into the study, we required the following: 1) the patient had a medical record at our institution, 2) received a CT scan that imaged the entire lung 3) the CT scan had adequate expiratory images to asses the severity of air trapping and 4) had moderate or severe air trapping identified on the CT examination. The study was performed at two affiliated university-based hospitals in the northeastern United States: a 725-bed academic tertiary care center and an urban 324-bed community hospital. The patient population consisted of an unselected mixture of both inpatients and outpatients. The Radiology Information System was searched for the term “air trapping” from January 1, 2010 to December 31, 2010 identifying a total of 1295 examinations. We searched specifically for the term “air trapping” and not the less specific term “mosaic attenuation” because our radiologists have been trained to specifically identify “air trapping” when expiratory images are provided and explain the presence of a mosaic

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5 pattern. Per our inclusion criteria, incomplete or duplicate exams (N=348) were excluded including 73 abdominal, neck or airway exams that did not include the entire lungs, 227 thoracic exams without expiratory images and 48 duplicate examinations. Of the 947 exams with expiratory series 383 had a report indicating “no air trapping” and were excluded. Furthermore, 141 exams had poor quality expiratory images preventing adequate evaluation for air trapping and 3 patients had large pleural effusions or extensive lung consolidation that prevented accurate evaluation of air trapping leaving 420 examinations that met our inclusion criteria. Inadequate expiratory exams were defined as those in which a mosaic pattern was identified on inspiratory exams but the expiratory images were not performed in adequate expiration to determine whether the mosaic pattern was a result of air trapping or other causes. Inadequate expiration was identified if the trachea retained a circular crosssectional appearance and the non-air trapped portions of lung parenchyma failed to increase in attenuation with expiration.

CT Analysis In normal expiratory CT the lung attenuation increases as the proportion of air to tissue decreases with expiration of air. The Fleischner society defines air trapping as “parenchymal areas with less than normal increase in attenuation and lack of volume reduction” as seen on end-expiration CT scans.[46] These areas appear as polygonal regions of low attenuation adjacent to areas of lung that have the normal increased attenuation with expiration. Two of the authors, one with 22 years and one with 1 year of subspecialty experience in thoracic imaging independently reviewed the thoracic CT

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6 examinations, blinded to the clinical history. Expiratory images were reviewed for the presence and severity of air trapping. Inspiratory series were evaluated for ancillary findings, including the presence of bronchiectasis, tree-in-bud opacities, non-tree-in-bud centrilobular nodules, peri-bronchovascular (perilymphatic) nodules, reticulation, architectural distortion and ground-glass opacities as defined by the Fleischner Society.[46] Any differences in interpretation between the two reviewers were resolved by consensus after a second review of the CT examinations. We have defined “isolated air trapping” when air trapping was the only lung abnormality, excluding common, benign findings such as a few subcentimeter nodules or small focal scars. Air-trapping was subdivided into mild (less than 25%), moderate (25%-50%) and severe (greater than 50%) air trapping based on a subjective estimation of the total lung volume of air trapped lung. Previous reports have indicated that mild air trapping is a commonly clinically asymptomatic[1, 46, 47] and therefore, we excluded the 190 patients with mild air trapping from further analysis, leaving 230 individuals with moderate to severe air trapping.

Proof of Diagnosis The electronic medical records were reviewed for the cause of air trapping, blinded to the CT interpretation. Of the 230 patients 208 were evaluated by one of 42 board-certified pulmonologists working at our institution. We did not review the individual clinical data but assumed that ICD-9 (International Statistical Classification of Disease and Related Health Problems, version 9) pulmonary related diagnoses made by these pulmonologists met established criteria for disease. In 22 patients, the cause of air

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7 trapping was not investigated primarily because of other more pressing diseases, predominantly metastatic carcinoma. In 7 cases, the pulmonologists failed to identify a cause for air trapping. These cases were also excluded from further review leaving a total of 201 cases with a proven cause of moderate to severe air trapping.

CT protocols All patients received the same unenhanced CT protocol: Series 1: 1mm contiguous spiral, deep inspiration viewed at 1mm contiguous axial slices and 3mm coronal reconstructions in lung windows; Series 2) 1mm contiguous spiral, end expiration viewed at 1mm contiguous axial slices and 3mm coronal reconstructions in lung windows. Images were obtained on a variety of scanners including: Siemens Definition 64, Siemens Definition AS, Siemens, Siemens Sensation 64, Siemens Sensation Cardiac, Siemens Volume Zoom (Siemens Medical Systems, Forcheim, Germany). Images were reviewed on a picture archiving system (PACS, GE Centricity, Milwaukee, Wi.)

Results The inter-observer agreement for individual CT findings between reviewers is listed in Table 1. Percent agreement ranged from a low of 97.9% (411/420 examinations) to a high of 100% (420/420 examinations). Kappa statistics were considered to be “very good” to “perfect” ranging from 0.896 to 1.00. All subsequent statistics are based on the consensus review. The 947 high-resolution exams represented 6.99% (947/13,540) of thoracic CTs performed at our institution in 2010. The quality of the expiratory series was not adequate

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8 to accurately evaluate air trapping in 14.9% (141/947). Of 803 adequate exams, 383 (47.6%) had no air trapping, 190 (23.7%) had mild (50%) air trapping. Ancillary imaging findings are listed in Table 2. Patients with moderate to severe air trapping could be divided into four subgroups based on their ancillary CT findings: 1) associated with bronchiectasis, 2) associated with interstitial lung disease, 3) associated with tree-in-bud opacities and 4) isolated air trapping. These groups had differing causes for air trapping. In 89 (44%) patients, air trapping was associated with bronchiectasis. In 13 cases, the bronchiectasis was associated with interstitial lung disease and represented traction bronchiectasis (6 sarcoidosis, 4 unspecified, 2 idiopathic pulmonary fibrosis, 1 mixed connective tissue disorder). Causes of the remaining 76 (38%) patients with non-traction bronchiectasis and air trapping are listed in Table 3. Atypical mycobacteria (23/76, 30%), cystic fibrosis (18/76, 24%), idiopathic bronchiectasis (11/76, 14%) and bronchiolitis obliterans/bronchiolitis obliterans syndrome (11/76, 14%) accounted for the majority of causes. (Figure 1) In 62 (31%) patients, air trapping was associated with interstitial lung disease. Causes of air trapping in patients with interstitial lung disease are listed in Table 4 and were most commonly sarcoidosis (18/62, 29%), hypersensitivity pneumonitis (6/62, 10%) and an undiagnosed interstitial lung disease (13/62, 21%). (Figure 2) There was isolated air trapping in 58 (29%) patients, which are listed in Table 5. Chronic bronchitis (16/58, 28%), asthma (15/58, 26%) and bronchiolitis obliterans (13/58, 22%) accounted for the majority of patients with isolated air trapping. (Figure 3 and 4)

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9 The remaining patients had a mixture of unclassified obstructive diseases, interstitial diseases and other uncommon conditions. (Figure 5 and 6) Finally 5 (2%) patients had air trapping with associated tree-in-bud opacities but without bronchiectasis. Four of these cases were lung transplant recipients diagnosed with BOS. The fifth patient had a clinical diagnosis of asthma.

Discussion Obstruction of small airways is a common finding on CT examinations of the thorax. In our population, 52.4% had air trapping, a frequency similar to other studies. [47, 48] However, mild air trapping is commonly asymptomatic and only when moderate or severe is it likely to have a clinical significance [1, 47, 48]. Therefore, we limited our study to patients that semi-quantitatively had greater than 25% of the lung volume air trapped. A wide variety of diseases have been reported to cause air trapping.[3-45]. Our study indicates that the etiology of air trapping can be subdivided based on the presence or absence of two additional findings: bronchiectasis and interstitial lung disease. Bronchiectasis is a known cause of air trapping [3-5, 23-29] and accounted for 38% (76/201) of our cases. In our population, the cause of bronchiectasis was most often nontuberculous mycobacterial infection, cystic fibrosis and idiopathic bronchiectasis, but occasionally was due to a variety of other disorders, including primary ciliary dyskinesia, allergic bronchopulmonary aspergillosis, Swyer-James syndrome and chronic aspiration. (Figure 1) Other reports have also noted air trapping and bronchiectasis in patients with immunodeficiency states [24, 25]. It seems likely that bronchiectasis is a direct cause of

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10 air trapping and any potential cause of bronchiectasis can also lead to air trapping. Thus, the differential diagnosis of air trapping, when associated with bronchiectasis should be based on the usual differential diagnosis of bronchiectasis. Thirty-one percent (62/210) of our cases were associated with interstitial lung disease, most commonly sarcoidosis and hypersensitivity pneumonitis, which are the interstitial diseases most frequently associated with air trapping in the literature [30-35]. (Figure 2) Chronic beryllium disease accounted for 6% (4/62) of interstitial diseases causing air trapping in our population because our institution has one of the few labs that specializes in testing for beryllium hypersensitivity. Beryllium exposure can cause an interstitial lung disease that is pathologically identical to sarcoidosis and therefore, it is not surprising that it might cause air trapping on expiratory CT. In 21% of cases with interstitial lung disease, the cause was unspecified. These patients had common imaging features: peribronchovascular or peripheral reticulation often with architectural distortion, findings typical of chronic hypersensitivity pneumonitis [35]. It is our belief that many of these cases represent undiagnosed hypersensitivity pneumonitis. Seven patients had interstitial diseases that are not typically associated with air trapping, including idiopathic pulmonary fibrosis, connective tissue diseases, and idiopathic NSIP. We suspect that these individuals had undiagnosed small airways disease in addition to their interstitial lung disease. Furthermore, ten patients with small airways diagnoses had interstitial abnormalities on their CT scans. We suspect that these patients had undiagnosed interstitial disorders in addition to their small airways disease.

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11 Isolated air trapping was most often due to chronic bronchitis, asthma or bronchiolitis obliterans. (Figure 3 and 4) Asthma and chronic bronchitis are the two most common causes of small airways disease in general practice and so it was not surprising that they would be two of the most common causes of isolated air trapping, However, the relatively rare condition, bronchiolitis obliterans, had a similar frequency to asthma and chronic bronchitis in our population. This large number of cases of bronchiolitis obliterans/bronchiolitis obliterans syndrome is primarily due to lung and bone marrow patients that accounted for 26/32, 81% of cases in our series. If we excluded transplant related cases from the total, then chronic bronchitis would have accounted for 34% (16/47), asthma for 32% (15/47), unspecified small airways disease for 15% (7/47) and bronchiolitis obliterans for 4% (2/47) of patients with isolated air trapping. It is interesting to note that 15% (7/47) of patients with isolated air trapping had an otherwise imaging occult interstitial lung disease or other rare causes of air trapping. The interstitial diseases were sarcoidosis, hypersensitivity pneumonitis and unspecified interstitial lung disease. The other unusual diseases causing air trapping were: 1) Churg Strauss vasculitis, 2) granulomatosis with polyangiitis and 3) diffuse idiopathic neuroendocrine cell hyperplasia. (Figure 5 and 6)) Other reports have also identified some unusual causes of air trapping including: Silicosis [36], Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia [37], Betathalassemia [38], HIV infection [40], tracheobronchomalacia [41,42], toxic inhalation [43], pulmonary embolism [44] and relapsing polychondritis [45]. Therefore, in symptomatic patients with isolated air trapping that do not appear to meet standard criteria for chronic bronchitis or asthma and do not have the appropriate clinical

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12 presentation for bronchiolitis obliterans, a variety of unusual etiologies should be considered. The primary limitation to this study is the retrospective nature of the research. We did not review the data establishing the clinical diagnoses but relied on the evaluations of subspecialty pulmonologists to establish the causes of air trapping. It is possible that some individuals were misdiagnosed or had multiple superimposed causes for imaging findings leading to a misclassification or information bias. As with any single institution study, the relative frequencies of causes reflect the patient composition of our institution and those patients more likely to receive CT scans. Patients with asthma and chronic bronchitis are frequently managed without CT scans and are likely under represented in our study population. As we have previously noted, our large lung and bone marrow transplantation population and our cystic fibrosis clinic likely increased the representation of bronchiolitis obliterans and cystic fibrosis as causes of air trapping in our study. We also have an active interstitial lung disease clinic, including a specialized beryllium exposed population and therefore, the proportion of cases of air trapping due to interstitial lung disease may have been inflated. Due to these limitations, our results can only be considered preliminary. The relative frequencies of causes of air trapping in other settings will be dependent on the patient population being evaluated. It is likely that the rank order of causes of air trapping in this study is close to the rank order of causes of air trapping in the general population. However, the specific relative frequencies is likely biased by the particular population served at our institution. In conclusion, air trapping is a common finding on thoracic CT and the etiology is influenced by associated imaging findings. When seen with bronchiectasis, usual causes

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13 of bronchiectasis should be considered such as atypical mycobacterial infection, cystic fibrosis, idiopathic bronchiectasis and transplant related bronchiolitis obliterans. Air trapping seen with interstitial lung disease, is most often secondary to sarcoidosis or hypersensitivity pneumonitis. Air trapping seen in isolation, is most often due to chronic bronchitis, asthma and bronchiolitis obliterans. Isolated air trapping in patients without chronic bronchitis, asthma or bronchiolitis obliterans can be due to a wide variety of unusual conditions including vasculitis, diffuse idiopathic neuroendocrine cell hyperplasia, relapsing polychondritis and tracheobronchomalacia.

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14 References 1. Webb WR, Stern EJ, Kanth N, Gamsu G. Dynamic pulmonary CT: findings in healthy adult men. Radiology. 1993;186(1):117-24. 2. Pellegrino R, Viegi G, Brusasco V, et al. Interpretive strategies for lung function tests. Eur Respir J. 2005; 26:948-968. 3. Arakawa H, Webb WR. Air trapping on expiratory high-resolution CT scans in the absence of inspiratory scan abnormalities: correlation with pulmonary function tests and differential diagnosis. AJR Am J Roentgenol. 1998;170(5):1349-53. 4. Lucidarme O, Grenier PA, Cadi M, Mourey-Gerosa I, Benali K, Cluzel P. Evaluation of air trapping at CT: comparison of continuous-versus suspendedexpiration CT techniques. Radiology. 2000;216(3):768-72. 5. Nishino M, Kuroki M, Boiselle PM, Copeland JF, Raptopoulos V, Hatabu H. Coronal reformations of volumetric expiratory high-resolution CT of the lung. AJR Am J Roentgenol. 2004;182(4):979-82. 6. Chen D, Webb WR, Storto ML, Lee KN. Assessment of air trapping using postexpiratory high-resolution computed tomography. J Thorac Imaging. 1998;13(2):135-43. 7. 3. Lucidarme O, Coche E, Cluzel P, Mourey-Gerosa I, Howarth N, Grenier P. Expiratory CT scans for chronic airway disease: correlation with pulmonary function test results. AJR Am J Roentgenol. 1998;170(2):301-7. 8. Lee YK, Oh YM, Lee JH, Kim EK, Lee JH, Kim N, Seo JB, Lee SD; KOLD Study Group. Quantitative assessment of emphysema, air trapping, and airway

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15 thickening on computed tomography. Lung. 2008;186(3):157-65. 9. Matsuoka S, Kurihara Y, Yagihashi K, Hoshino M, Watanabe N, Nakajima Y. Quantitative assessment of air trapping in chronic obstructive pulmonary disease using inspiratory and expiratory volumetric MDCT. AJR Am J Roentgenol. 2008;190(3):762-9. 10. Grenier PA, Beigelman-Aubry C, Fetita CI, Brillet PY. CT imaging of chronic obstructive pulmonary disease: role in phenotyping and interventions. Expert Opin Med Diagn. 2009;3(6):689-703. 11. Newman KB, Lynch DA, Newman LS, Ellegood D, Newell JD. Quantitative computed tomography detects air trapping due to asthma. Chest 1994; 106:105109. 12. Park CS, Muller NL, Worthy SA, Kim JS, Awadh N, Fitzgerald M. Airway obstruction in asthmatic and healthy individuals: inspiratory and expiratory thinsection CT findings. Radiology 1997; 203:361-367. 13. Laurent F, Latrabe V, Raherison C, Marthan R, Tunon-de-Lara JM. Functional significance of air trapping detected in moderate asthma. Eur Radiol. 2000;10(9):1404-10. 14. Busacker A, Newell JD Jr, Keefe T, Hoffman EA, Granroth JC, Castro M, Fain S, Wenzel S. A multivariate analysis of risk factors for the air-trapping asthmatic phenotype as measured by quantitative CT analysis. Chest. 2009;135(1):48-56. 15. Garg K, Lynch DA, Newell JD, King TE Jr. Proliferative and constrictive bronchiolitis: classification and radiologic features. AJR 1994; 162:803–808. 16. Franquet T, Díaz C, Domingo P, Giménez A, Geli C. Air trapping in primary

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Page 16 of 32

Page 17 of 32

ANNALSATS Articles in Press. Published on 23-June-2014 as 10.1513/AnnalsATS.201311-390OC

16 Sjögren syndrome: correlation of expiratory CT with pulmonary function tests. J Comput Assist Tomogr. 1999;23(2):169-73. 17. Taouli B, Brauner MW, Mourey I, Lemouchi D, Grenier PA. Thin-section chest CT findings of primary Sjögren's syndrome: correlation with pulmonary function. Eur Radiol. 2002;12(6):1504-11. 18. Leung AN, Fisher K, Valentine V, Girgis RE, Berry GJ, Robbins RC, Theodore J. 19. Bronchiolitis obliterans after lung transplantation: detection using expiratory HRCT. Chest. 1998;113(2):365-70. 20. Lee ES, Gotway MB, Reddy GP, Golden JA, Keith FM, Webb WR. Early Bronchiolitis Obliterans Following Lung Transplantation: Accuracy of Expiratory Thin-Section CT for Diagnosis. Radiology. 2000;216(2):472-7. 21. Siegel MJ, Bhalla S, Gutierrez FR, Hildebolt C, Sweet S. Post-lung transplantation bronchiolitis obliterans syndrome: usefulness of expiratory thinsection CT for diagnosis. Radiology. 2001;220(2):455-62. 22. Konen E, Gutierrez C, Chaparro C, Murray CP, Chung T, Crossin J, Hutcheon MA, Paul NS, Weisbrod GL. Bronchiolitis Obliterans Syndrome in Lung Transplant Recipients: Can Thin-Section CT Findings Predict Disease before Its Clinical Appearance? Radiology 2004 231:2 467-473 23. Hartman TE, Primack SL, Lee KS, Swensen SJ, Müller NL. CT of bronchial and bronchiolar diseases. Radiographics. 1994; 14(5):991-1003. 24. Obregon RG, Lynch DA, Kaske T, Newell JD Jr, Kirkpatrick CH. Radiologic findings of adult primary immunodeficiency disorders. Contribution of CT. Chest. 1994; 106(2):490-5

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17 25. Feydy A, Sibilia J, De Kerviler E, Zagdanski AM, Chevret S, Fermand JP, Brouet JC, Frija J. Chest high resolution CT in adults with primary humoral immunodeficiency. Br J Radiol. 1996;69(828):1108-16. 26. Kubo K, Yamazaki Y, Masubuchi T, Takamizawa A, Yamamoto H, Koizumi T, Fujimoto K, Matsuzawa Y, Honda T, Hasegawa M, Sone S. Pulmonary infection with Mycobacterium avium-intracellulare leads to air trapping distal to the small airways. Am J Respir Crit Care Med. 1998; 158(3):979-84. 27. Cleveland RH, Neish AS, Zurakowski D, Nichols DP, Wohl ME, Colin AA. Cystic fibrosis: predictors of accelerated decline and distribution of disease in 230 patients. AJR Am J Roentgenol. 1998; 171(5):1311-5. 28. Dodd JD, Barry SC, Barry RB, Gallagher CG, Skehan SJ, Masterson JB. ThinSection CT in Patients with Cystic Fibrosis: Correlation with Peak Exercise Capacity and Body Mass Index. Radiology. 2006; 240:1 236-245 29. Edwards EA, Metcalfe R, Milne DG, Thompson J, Byrnes CA. Retrospective review of children presenting with non cystic fibrosis bronchiectasis: HRCT features and clinical relationships. Pediatr Pulmonol. 2003;36(2):87-93. 30. 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 Apr;16(2):69-75. 31. Bartz RR, Stern EJ. Airways obstruction in patients with sarcoidosis: expiratory CT scan findings. J Thorac Imaging. 2000;15(4):285-9. 32. Davies CW, Tasker AD, Padley SP, Davies RJ, Gleeson FV. Air trapping in

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Page 18 of 32

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ANNALSATS Articles in Press. Published on 23-June-2014 as 10.1513/AnnalsATS.201311-390OC

18 sarcoidosis on computed tomography: correlation with lung function. Clin Radiol. 2000;55(3):217-21. 33. Hansell DM, Milne DG, Wilsher ML, Wells AU. Pulmonary sarcoidosis: morphologic associations of airflow obstruction at thin-section CT. Radiology. 1998;209(3):697-704. 34. Hypersensitivity pneumonitis: correlation of individual CT patterns with functional abnormalities. Hansell DM, Wells AU, Padley SP, Müller NL. Radiology. 1996;199(1):123-8. 35. Silva CI, Müller NL, Lynch DA, Curran-Everett D, Brown KK, Lee KS, Chung MP, Churg A. Chronic hypersensitivity pneumonitis: differentiation from idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia by using thin-section CT. Radiology. 2008;246(1):288-97. 36. Silicosis: expiratory thin-section CT assessment of airway obstruction. Arakawa H, Gevenois PA, Saito Y, Shida H, De Maertelaer V, Morikubo H, Fujioka M. Radiology. 2005;236(3):1059-66. 37. Cameron CM, Roberts F, Connell J, Sproule MW. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: an unusual cause of cyclical ectopic adrenocorticotrophic syndrome. Br. J. Radiol. 2011; 84:997 e14-e17 38. Khong PL, Chan GC, Lee SL, Au WY, Fong DY, Tsang KW, Ooi GC. Betathalassemia major: thin-section CT features and correlation with pulmonary function and iron overload. Radiology. 2003;229(2):507-12. 39. Magkanas E, Detorakis E, Nikolakopoulos I, Gourtsoyianni S, Linardakis M, Sidiropoulos P, Boumpas D, Gourtsoyiannis N. Air trapping in Wegener's

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19 granulomatosis: an additional finding on expiratory chest HRCT. Radiol Med. 2011;116(6):858-67. 40. Gelman M, King MA, Neal DE, Pacht ER, Clanton TL, Diaz PT. Focal air trapping in patients with HIV infection: CT evaluation and correlation with pulmonary function test results. AJR Am J Roentgenol. 1999;172(4):1033-8. 41. Zhang J, Hasegawa I, Hatabu H, Feller-Kopman D, Boiselle PM. Frequency and severity of air trapping at dynamic expiratory CT in patients with tracheobronchomalacia. AJR Am J Roentgenol. 2004;182(1):81-5. 42. Lee EY, Tracy DA, Bastos Md, Casey AM, Zurakowski D, Boiselle PM. Expiratory volumetric MDCT evaluation of air trapping in pediatric patients with and without tracheomalacia. AJR Am J Roentgenol. 2010;194(5):1210-5. 43. Ghanei M, Akbari Moqadam F, Mohammad MM, Aslani J. Tracheobronchomalacia and Air Trapping after Mustard Gas Exposure. Am. J. Respir. Crit. Care Med. 2006 173:3 304-309 44. Arakawa H, Kurihara Y, Sasaka K, Nakajima Y, Webb WR. Air Trapping on CT of Patients with Pulmonary Embolism. AJR Am J Roentgenol. 2002;178(5):12017. 45. Relapsing polychondritis affecting the lower respiratory tract. Behar JV, Choi YW, Hartman TA, Allen NB, McAdams HP. AJR Am J Roentgenol. 2002;178(1):173-7. 46. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology. 2008 Mar;246(3):697-722

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20 47. 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(3):831-6. 48. Tanaka N, Matsumoto T, Miura G, Emoto T, Matsunaga N, Ueda K, Lynch DA. Air Trapping at CT: High Prevalence in Asymptomatic Subjects with Normal Pulmonary Function. Radiology. 2003; 227(3):776-785.

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21 Tables Table 1: Inter-observer Agreement of Individual Findings on 420 CT scans Finding Air trapping Bronchiectasis Tree-in-bud opacity Centrilobular nodules Bronchovascular nodules Ground glass opacity Reticulation Architectural distortion

Number (%)(N=420) 415 (98.6) 411 (97.9) 418 (99.5) 420 (100) 420 (100) 415 (98.6) 419 (99.8) 420 (100)

Kappa 0.977 0.949 0.982 1.00 1.00 0.896 0.980 1.00

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22 Table 2 Associated Imaging Findings in 201 Patients with Proven Cause of Moderate/Severe Air Trapping Finding Isolated air trapping ^

Frequency 53 (26)

Airways findings Bronchiectasis Tree-in-bud opacities

92 (46) 47 (23)

Interstitial findings Ground glass opacity Architectural distortion Bronchovascular nodules Centrilobular nodules~ Reticulation/honeycombing Peripheral Peribronchiolar Diffuse

24 (12) 24 (12) 8 (4) 2 (1) 25 (13) 13 (6)* 14 (7)* 1 (0.5)

* 3 patients with both peripheral and peribronchovascular reticulation/honeycombing ^ Air trapping was the only clinically significant imaging finding (excluding small nodules, non-specific linear scars). ~ Non-tree-in-bud centrilobular nodules

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23 Table 3 Causes of Moderate-Severe Air Trapping with Associated Bronchiectasis in 76 Patients with Proven Cause Cause frequency (%) Atypical mycobacteria 23 (30) Diseases predisposing to airway infection Cystic fibrosis 18 (24) Allergic bronchopulmonary aspergillosis 2 (3)* Primary ciliary dyskinesia 1 (1) Panbronchiolitis 1 (1) Idiopathic bronchiectasis 11 (14) Bronchiolitis obliterans/bronchiolitis obliterans syndrome @ 11 (14)^ Unspecified obstructive disease Asthma Other

3 (4) 2 (3)* 5 (7)~

@ excluding traction bronchiectasis * One patient had both asthma and allergic bronchopulmonary aspergillosis. ^ 8 lung transplants, 1 idiopathic, 1 rheumatoid arthritis ~ One each of Swyer-James syndrome, chronic aspiration, chronic bronchitis, Bronchiolitis obliterans with organizing pneumonia (BOOP), Childhood bronchopulmonary dysplasia (BPD) @ Bronchiolitis obliterans/bronchiolitis obliterans syndrome

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Table 4 Causes of Moderate-Severe Air Trapping and Interstitial Abnormalities in 62 patients with Proven Cause Cause frequency (%) Sarcoidosis 18 (29) Unspecified 13 (21) Hypersensitivity pneumonitis 6 (10) Chronic beryllium disease 4 (6) Idiopathic pulmonary fibrosis 3 (4) Connective tissue disease 2 (3)^ Nonspecific interstitial pneumonia 2 (3) Respiratory bronchiolitis interstitial lung disease 2 (3) Bronchiolitis obliterans/bronchiolitis obliterans syndrome Chronic bronchitis Asthma Unspecified obstructive disease Organizing pneumonia Bronchial atresia

4 (6)* 2 (3) 2 (3) 2 (3) 1 (2) 1 (2)

* 2 bone marrow transplant, 1 lung transplant and 1Sjogren’s syndrome ^ Mixed connective tissue disease and polymyositis

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25 Table 5 Causes of Isolated Moderate-Severe Air Trapping* in 58 Patients with a Proven Cause Cause Obstructive Disease Chronic bronchitis Asthma Bronchiolitis obliterans/bronchiolitis obliterans syndrome Rheumatoid arthritis Idiopathic Bone marrow transplant Lung transplant ~ Chronic obstruction, unclassified

frequency (%) 51 (88) 16 (27) 15 (26) 13 (22) 1 (2) 1 (2) 3 (5) 8 (14) 7 (12)

Interstitial Disease Sarcoidosis Chronic beryllium disease Unspecified

4 (7) 1 (2) 2 (3) 1 (2)

Other Vasculitis Eosinophilic granulomatosis with polyangiitis Granulomatosis with polyangiitis Diffuse idiopathic neuroendocrine cell hyperplasia ^

3 (5) 1 (2) 1 (2) 1 (2)

* Air trapping as the only diffuse pulmonary finding (allow nonspecific scar, few small nodules, pleural thickening/effusion) ^ Diffuse idiopathic neuroendocrine cell hyperplasia ~ 4 bilateral and 4 single lung transplants

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26 Figure Legends

Figure 1. Air trapping associated with bronchiectasis. This 28 year old man had an acute exacerbation of cystic fibrosis. Expiratory CT shows tramtracks and ring shadows indicating the presence of widespread bronchiectasis. There is also a mosaic pattern of attenuation (black arrows indicate lower attenuation regions) indicative of severe air trapping.

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Figure 2. Air trapping associated with interstitial lung disease. This 65 year old woman had a long history severe dyspnea due to sarcoidosis and was being evaluated for lung transplantation. Image from an expiratory CT shows air trapping (black arrows), peribronchovascular honeycombing (white arrow) and multiple calcified lymph nodes (black arrowheads) typical of advanced sarcoidosis.

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Figure 3. Isolated air trapping due to asthma. This 54 year old woman presented with dyspnea and wheezing. Image from an expiratory CT shows severe air trapping (white arrows) without other finding.

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Figure 4. Isolated air trapping due to bronchiolitis obliterans. This 62 year old woman with rheumatoid arthritis developed slowly progressive dyspnea and hypoxia. Expiratory CT image shows severe air trapping (black arrows) without other imaging findings. Biopsy was diagnostic of bronchiolitis obliterans.

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Figure 5. Isolated air trapping due to granulomatosis with polyangiitis. This 64 year old woman with a history of granulomatosis with polyangiitis had recurrent dyspnea. The examination was normal except for moderate air trapping (black arrows) identified on the expiratory CT.

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Figure 6. Isolated air trapping due to diffuse idiopathic neuroendocrine cell hyperplasia. This 59 year old woman had the subacute onset of incapacitating dyspnea. The examination was normal except for severe air trapping found on expiratory CT. Surgical lung biopsy was diagnostic of diffuse neuroendocrine cell hyperplasia.

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Expiratory air trapping on thoracic computed tomography. A diagnostic subclassification.

Multiple causes for air trapping as identified by expiratory computed tomography (CT) have been reported, but a unified evaluation schema has never be...
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