Exercise-associated Excessive Dynamic Airway Collapse in Military Personnel

Transcription

1 Exercise-associated Excessive Dynamic Airway Collapse in Military Personnel Daniel J. Weinstein 1, James E. Hull 2, Brittany L. Ritchie 3, Jackie A. Hayes 2, and Michael J. Morris 2 1 Internal Medicine Residency, Department of Medicine, 2 Pulmonary and Critical Care Service, Department of Medicine, and 3 CT Imaging, Department of Radiology, San Antonio Military Medical Center, Joint Base San Antonio Fort Sam Houston, Texas Abstract Rationale: Evaluation of military personnel for exertional dyspnea can present a diagnostic challenge, given multiple unique factors that include wide variation in military deployment. Initial consideration is given to common disorders such as asthma, exercise-induced bronchospasm, and inducible laryngeal obstruction. Excessive dynamic airway collapse has not been reported previously as a cause of dyspnea in these individuals. Objectives: To describe the clinical and imaging characteristics of military personnel with exertional dyspnea who were found to have excessive dynamic collapse of large airways during exercise. Methods: After deployment to Afghanistan or Iraq, 240 active U.S. military personnel underwent a standardized evaluation to determine the etiology of persistent dyspnea on exertion. Study procedures included full pulmonary function testing, impulse oscillometry, exhaled nitric oxide measurement, methacholine challenge testing, exercise laryngoscopy, cardiopulmonary exercise testing, and fiberoptic bronchoscopy. Imaging included highresolution computed tomography with inspiratory and expiratory views. Selected individuals underwent further imaging with dynamic computed tomography. Measurements and Main Results: A total of five men and one woman were identified as having exercise-associated excessive dynamic airway collapse on the basis of the following criteria: (1) exertional dyspnea without resting symptoms, (2) focal expiratory wheezing during exercise, (3) functional collapse of the large airways during bronchoscopy, (4) expiratory computed tomographic imaging showing narrowing of a large airway, and (5) absence of underlying apparent pathology in small airways or pulmonary parenchyma. Identification of focal expiratory wheezing correlated with bronchoscopic and imaging findings. Conclusions: Among 240 military personnel evaluated after presenting with postdeployment exertional dyspnea, a combination of symptoms, auscultatory findings, imaging, and visualization of the airways by bronchoscopy identified six individuals with excessive dynamic central airway collapse as the sole apparent cause of dyspnea. Exercise-associated excessive dynamic airway collapse should be considered in the differential diagnosis of exertional dyspnea. Keywords: exercise; dyspnea; airway collapse; wheezing (Received in original form December 1, 2015; accepted in final form April 18, 2016 ) The opinions in this manuscript do not constitute endorsement by San Antonio Military Medical Center, the US Army Medical Department, the US Army Office of the Surgeon General, the Department of the Army, Department of Defense, Veterans Affairs, or the US Government of the information contained therein. Author Contributions: D.J.W.: patient evaluation, data collection, and primary manuscript author; J.E.H.: patient evaluation, data analysis, and manuscript author; B.L.R.: computed tomographic scan interpretation and manuscript author; J.A.H.: data analysis and manuscript author; and M.J.M.: study design, patient evaluation, data analysis, and manuscript author. Correspondence and requests for reprints should be addressed to Michael J. Morris, M.D., Pulmonary Disease Service (MCHE-MDP), San Antonio Military Medical Center, 3551 Roger Brooke Drive, Fort Sam Houston, TX michael.j.morris34.civ@mail.mil Ann Am Thorac Soc Vol 13, No 9, pp , Sep 2016 Copyright 2016 by the American Thoracic Society DOI: /AnnalsATS OC Internet address: Evaluation of military personnel for exertional dyspnea can be a diagnostic challenge, given multiple unique factors concerning this patient population. They are generally more fit than their civilian counterparts and are required to pass a timed running event on a semiannual basis. The ability to maintain cardiovascular fitness and pass a physical fitness test is essential to maintaining career progression and avoiding separation from military service. In a 2002 study of 106 active duty military personnel with exertional dyspnea, researchers identified nearly 50% with airway hyperreactivity (asthma- or exerciseinduced bronchospasm), 10% with vocal cord dysfunction, and 25% with a negative 1476 AnnalsATS Volume 13 Number 9 September 2016

2 evaluation (1). Since 2003, military personnel deployed to conflicts in Southwest Asia have been exposed to various airborne inhalational hazards that may predispose them to chronic respiratory disease. Several Department of Defense studies are addressing the types and severity of disease related to deployment (2, 3). In many of these patients, identification of the underlying etiology for symptoms is challenging. Excessive dynamic airway collapse (EDAC) is a diagnostic term applied to individuals identified with focal functional collapse of the trachea or main bronchi. EDAC is defined specifically as excessive bulging of the posterior tracheal membrane into the airway lumen during expiration without associated collapse of the cartilaginous rings. The definition distinguishes this disorder from tracheobronchomalacia, which is characterized by loss of structural integrity of the cartilaginous rings (4). EDAC is commonly associated with underlying airway disorders such as chronic obstructive pulmonary disease (COPD), asthma, and bronchiectasis (5). Indeed, prior studies have not identified this disorder in the absence of underlying lung disease (5 7). EDAC is thought to result from interactions between pleural pressures, elastic recoil, airway compliance, and peripheral airway resistance. Since partial expiratory collapse (up to 50% reduction in airway cross-sectional area) may be identified in 70 80% of healthy individuals during dynamic computed tomography (CT), further stratification is required (8). Current guidelines suggest that functional status (exertion, daily activities, or rest), length of the tracheobronchial wall affected, and degree of obliteration of the airway lumen are important to define (5). Patients with moderate to severe EDAC typically present with cough, wheezing, dyspnea, or recurrent respiratory infections related to exacerbations of their lung disease or after mild to moderate exertion. We are reporting the evaluation of six military personnel with no underlying lung disease identified with symptomatic EDAC only during high levels of exertion. The diagnosis was based on the following findings: exertional dyspnea, focal expiratory wheezing during exercise, airway narrowing on expiratory CT, and direct observation of focal excessive bulging of the posterior tracheal membrane during bronchoscopy. Methods Subjects This study was reviewed and approved by the Brooke Army Medical Center Institutional Review Board. The subjects described were active duty military personnel referred for evaluation of exertional dyspnea after deployment to Iraq or Afghanistan. Beginning in July 2010, these patients provided consent for participation in several postdeployment dyspnea studies (363715, ) (2, 3). In association with these protocols, patients underwent a standard battery of testing procedures to evaluate exertional dyspnea. To date, 240 patients have completed study procedures. During preliminary evaluation of dyspnea symptoms, all six patients reported the presence of audible breathing noises during physical training. Diagnostic Studies Radiographic imaging included a standard posteroanterior and lateral chest radiograph as well as chest high-resolution computed tomography (HRCT) (1-mm and 3-mm intervals) with both expiratory prone and inspiratory supine views per standard protocol. In selected cases after identification of airway collapse as the potential etiology for dyspnea, three patients underwent further imaging with dynamic chest CT after normal HRCT. The first two patients were referred from outlying military hospitals and were unable to return for dynamic CT. Dynamic chest CT consisted of helically acquired 3-mm axial computed tomographic images through the tracheobronchial tree with the patient positioned supine while in inspiration and during forceful expiration. Acquiring images during forceful expiration allowed for dynamic imaging of the trachea to capture the anatomic changes during physiologic expiration. Images were sent to a three-dimensional workstation for postprocessing and volumetric reformatting. Luminal area was measured in both inspiration and forceful expiration to determine the degree of collapse (9, 10). All patients performed a spirometric examination using a Vmax spirometer (CareFusion, Yorba Linda, CA). They performed a standard forced expiratory maneuver from maximal inhalation to maximal exhalation so that FEV 1 and FVC could be recorded in accordance with American Thoracic Society standards for spirometry. Reference values were taken from the Third National Health and Nutrition Examination Survey (11). All patients were given four puffs of albuterol to measure FEV 1 post-bronchodilator improvement. Lung volumes were determined using Vmax body plethysmography (CareFusion) to determine total lung capacity and residual volume values. The diffusing capacity of the lung for carbon monoxide was determined using the single-breath technique with a Vmax spirometer (CareFusion). Two impulse oscillometry replicate measurements were obtained using system software (MasterScreen PFT System; Jaeger Toennies/CareFusion, Höchberg, Germany). Participants were asked to breathe quietly for seconds using a rigid oval mouthpiece while supporting both cheeks. Measurements of resistance at 5 Hz (total respiratory resistance), resistance at 20 Hz (proximal resistance), reactance at 5 Hz (distal capacitive reactance), and reactance area were recorded. Post-bronchodilator values were also recorded after administration of inhaled albuterol (12). All patients underwent methacholine challenge testing after discontinuing any scheduled pulmonary medications for 1 week. Increasing doses of methacholine were administered in normal saline at the concentrations of mg/ml, 0.25 mg/ml, 1.0 mg/ml, 4 mg/ml, 8 mg/ml, and 16 mg/ml in accordance with American Thoracic Society guidelines. The bronchoprovocation test was considered positive at a 20% decrease in FEV 1 with a dose of 4 mg/ml or less (13). Each participant underwent laryngoscopy performed with an Olympus ENF-VQ flexible laryngoscope (Olympus America, Center Valley, PA) after application of local anesthesia with 2% lidocaine to the nares. Evaluation of the larynx was performed both pre- and postexercise for evidence of anatomical and functional glottic disorders. After undergoing a baseline examination by laryngoscopy with various vocal maneuvers, each patient exercised on a treadmill at a comfortable pace until reproducible symptoms of dyspnea, exhaustion, or maintaining 85% of target heart rate for more than 5 minutes. Auscultation over the trachea followed by repeat laryngoscopic Weinstein, Hull, Ritchie, et al.: Exercise-associated EDAC 1477

3 Table 1. Pulmonary function testing and impulse oscillometry Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Pulmonary function testing FEV 1 (% predicted) 3.12 (100%) 2.89 (84%) 4.59 (106%) 3.40 (80%) 3.75 (80%) 4.34 (106%) FVC (% predicted) 3.80 (94%) 3.47 (86%) 6.43 (120%) 4.67 (87%) 4.11 (71%) 5.37 (102%) FEV 1 /FVC FEV 1 post-bd (% predicted) 3.42 (110%) 2.78 (81%) 4.53 (105%) 3.56 (84%) 3.73 (80%) 4.26 (104%) FVL Normal Normal Normal Normal Normal Normal TLC (% predicted) 6.26 (108%) 5.34 (101%) 7.91 (114%) 6.67 (93%) 5.18 (69%) 7.18 (100%) RV (% predicted) 2.18 (123%) 1.86 (126%) 1.67 (94%) 1.93 (98%) 1.07 (57%) 1.74 (83%) DL CO (% predicted) 31.6 (130%) N/A 43.0 (133%) 25.0 (75%) 24.2 (66%) 33.7 (94%) DL CO /VA 5.94 (103%) N/A 5.46 (116%) 4.01 (85%) 5.25 (109%) 7.16 (103%) Impulse oscillometry R (148%) 4.71 (139%) 4.04 (147%) 2.54 (92%) 3.53 (131%) 3.88 (135%) R5 post-bd 4.42 (149%) N/A 2.22 (81%) 2.50 (90%) 3.56 (132%) 3.59 (125%) R (131%) 4.24 (152%) 3.29 (141%) 2.31 (98%) 3.15 (137%) 2.86 (116%) R20 post-bd 3.55 (138%) N/A 2.03 (97%) 2.36 (100%) 3.11 (136%) 2.66 (107%) X5 pre-/post-bd 21.75/21.52 N/A 20.85/ / / /21.41 AX Methacholine FEV 1 decrease at 16 mg/ml 13% 218% 215% 22% 21% 210% Definition of abbreviations: AX = area of reactance; BD = bronchodilator; DL CO = diffusing capacity of the lung for carbon monoxide; DL CO /VA = diffusing capacity of the lung for carbon monoxide adjusted for alveolar volume; FVL = flow volume loop; N/A = not available; R5 = resistance at 5 Hz (total airway resistance); R20 = resistance at 20 Hz (large airway resistance); RV = residual volume; TLC = total lung capacity; X5 = reactance at 5 Hz. evaluation was performed for evidence of paradoxical inspiratory closure of the vocal cords consistent with exercise-induced inducible laryngeal obstruction. These patients likewise performed a maximal graded exercise test using a Bruce incremental protocol on the series 2000 treadmill (GE Marquette Electronics, Milwaukee, WI) with continuous pulse oximetry and 12-lead electrocardiographic monitoring. Expired gas analysis was performed using the 2900 series metabolic cart (SensorMedics) to directly measure _VO 2,VCO 2,VT, respiratory rate, and _VE. As part of the standard research protocol, all patients underwent flexible fiberoptic bronchoscopy (Olympus 160; Olympus America) with light sedation to examine the airways. After standard airway preparation with topical and nebulized lidocaine, patients were given conscious sedation with intravenous midazolam and fentanyl. Careful observation was made of the trachea and bronchi to identify areas of excessive bulging of the posterior membrane during tidal and deep breathing maneuvers (14). Two patients (patients 1 and 6) were also given an oral lidocaine preparation for an exercise bronchoscopy. The airway was initially inspected at rest, and then the patients began exercising on a bicycle ergometer in an upright position to the point of symptoms and audible wheezing. The patients continued cycling while the bronchoscope was inserted into the central trachea to identify the location of airway collapse. After the location of functional collapse was visually determined, the patients stopped exercising until the airway visibly became more patent and audible wheezing ceased (see video file in the online supplement). Results The group of patients identified with EDAC consisted of five men and one woman with a mean age of 39.5 years (range, yr). Theirmeanbodymassindexwas28.6kg/m 2 (range, kg/m 2 ). All were lifelong nonsmokers. Pulmonary symptoms ranged Table 2. Summary of airway findings Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Chest HRCT Bilateral LL air trapping (expiratory) Normal Expiratory tracheal narrowing (see Figure 1) Normal Normal Expiratory collapse of bronchi (see Figure 2) Dynamic chest CT N/A N/A N/A Normal Expiratory collapse of bronchi (see Figure 3) Expiratory collapse of bronchi Exercise laryngoscopy Normal Normal Normal Prominent arytenoids, Normal Normal no ILO Bronchoscopy location of collapse Distal trachea/right Distal trachea/left Distal trachea/right Distal trachea/bilateral Distal trachea Expiratory wheezing Audible Audible Audible Auscultation Auscultation Audible Wheeze localization Midtrachea Midtrachea Midtrachea Right upper chest Right upper chest Right midchest Right /bronchus intermedius Definition of abbreviations: CT = computed tomography; HRCT = high-resolution computed tomography; ILO = inducible laryngeal obstruction; LL = lower lobe; N/A = not available AnnalsATS Volume 13 Number 9 September 2016

4 from 1 to 11 years since onset. None of the patients had preexisting symptoms or diagnosis of lung disease prior to military deployment to Southwest Asia. All reported exposures to geologic dust and proximity to burn pits, but denied any specific acute pulmonary exposure during deployment. Several had been tried on daily inhaled corticosteroid/long-acting b-agonist combinations without improvement in exertional symptoms. Findings related to pulmonary function testing are shown in Table 1. Only patient 5 had a mild restrictive pattern (with no parenchymal changes on CT), and none of the cohort had evidence of airway obstruction or reduction in diffusing capacity. Impulse oscillometry values for resistance at 5 Hz and resistance at 20 Hz were not significantly elevated to be diagnostic for increased central airways resistance. Post-bronchodilator values for spirometry or impulse oscillometry did not meet criteria for significant airway hyperreactivity. Methacholine challenge testing was negative in all patients at a maximum dose of 16 mg/ml. None of the resting flow volume loops were indicative of variable intrathoracic or extrathoracic obstruction. Results related to confirmation of the EDAC diagnosis, including imaging, auscultation, and airway inspection, are shown in Table 2. All patients had a normal chest radiograph. HRCT with inspiratory and expiratory views was significant in two patients, with identifiable collapse observed on expiratory images (see Figures 1 and 2). Dynamic CT was performed on three patients and was notable for airway collapse in patients 5 and 6 (see Figure 3). None of the patients were reported to be symptomatic during imaging procedures. Using flexible bronchoscopy, we were able to localize the site of obstruction (.75% obstruction of the affected airway), including patients 1 and 6, who underwent awake bronchoscopy during exercise (see video file in the online supplement). Four of the six patients had audible expiratory wheezing that developed during exercise (not present at rest) with localization by chest auscultation. The two remaining patients had expiratory wheezing identified and localized only by auscultation. In general, the wheezing was described as high pitched, monophonic, and present throughout the expiratory cycle. Figure 1. Axial high-resolution computed tomographic images through the chest in (A) inspiration and (B) expiration at a similar level of the trachea. Inspiration image demonstrates a normal tracheal morphology and luminal area. On expiration, the middle and distal trachea was significantly narrowed, with a greater than 75% decrease in luminal area and posterior bowing of the tracheal membrane. Cardiopulmonary exercise testing values are shown in Table 3. Despite symptomatic airway collapse during exercise, the patients had excellent exercise tolerance, with a mean _VO 2 max percent predicted of 119% (range, %) and a mean ventilatory anaerobic threshold of 76% (range, %). Review of exercise tidal flow volume loops were not suggestive of central airways obstruction. Mean values for other respiratory variables at peak exercise also were not suggestive of ventilatory limitation to exercise. Discussion The term excessive dynamic airway collapse refers to a functional collapse of airway lumen by greater than 75% with structurally intact airway cartilage. We found EDAC in six physically fit and otherwise apparently healthy individuals who reported dyspnea on exertion. All of these patients had the following features: (1) exertional dyspnea without resting symptoms, (2) expiratory wheezing during exercise (in some cases audible), (3) functional collapse of the large airways with preservation of tracheal ring integrity during bronchoscopy, (4) expiratory CT with narrowing of the airways in 50% of the cases, and (5) absence of other apparent pulmonary pathology. This finding has not been reported previously in patients with no apparent underlying lung disorder. Exercise-associated EDAC has not been reported previously in the medical literature. While all six of these patients were active duty military personnel, they shared limited common features with respect to their deployment history and military service. They all had limited if any specific environmental inhalational exposures to suggest causality related to onset. In all Figure 2. Axial high-resolution computed tomographic images through the level of the carina in (A) inspiration and (B) expiration. In this examination, the expiration image was obtained with the patient positioned prone. There is distal tracheal narrowing extending into the bronchi and bronchus intermedius during expiration. A normal luminal area of the bronchi is seen on the inspiratory image. Weinstein, Hull, Ritchie, et al.: Exercise-associated EDAC 1479

5 Figure 3. Axial dynamic chest computed tomographic images through the trachea. (A C) These images obtained at end inspiration show a normal morphology and luminal area of the trachea. (D F) These images were obtained during forceful exhalation and correspond to the level shown in A C. There is marked tracheal narrowing throughout the trachea and extending into the bronchi. (G) Volumetric three-dimensional endoluminal reconstruction of the midtrachea oriented toward the bronchi illustrates significant tracheal narrowing and protrusion of the tracheal membrane into the tracheal lumen. cases, symptom onset was insidious and did not appear to be progressive in nature. The subjects were relatively young, typical of the military population, with a mean age of nearly 40 years, but their age range widely, from 24 to 53 years. There was also a wide range of military service, suggesting the process is not specifically related to overall strenuous activity. Our patients had no clinical, physiological, or imaging features consistent with COPD, asthma, bronchiectasis, or any other pulmonary or fixed airway dysfunction. Resting pulmonary function studies were specifically unremarkable, although a reduction in airway diameter during expiratory maneuvers was identified in three patients (15). In a previous study of EDAC in 18 patients with COPD, researchers identified no correlation between the degree of airway obstruction and pulmonary function test results (16). Most important, during significant levels of exertion, our patients developed significant dyspnea and expiratory wheezing. Auscultation during exercise testing was important during exercise because conventional cardiopulmonary exercise testing with exercise flow volume loops did not detect airway collapse. Similar findings can be identified with inducible laryngeal obstruction, but it is primarily inspiratory, can be heard loudest over the larynx, and should have corresponding paradoxical vocal cord adduction (17). Another key finding is that all patients had normal pre- and postexercise laryngoscopic findings. The pathogenesis of EDAC has been described as being a result of two primary circumstances. One factor is weakening of the smooth muscle tone of the posterior membrane. The other factor is a decrease in luminal pressures in regions of tapering airways (Bernoulli s principle) in a setting of reduced elastic recoil, thus creating even greater stenosis and leading to a greater transmural pressure gradient (18). The diagnosis of EDAC has been described only in patients with underlying lung disorders such as COPD or asthma, especially in those patients with identifiable tracheobronchomalacia. The underlying lung pathology likely contributes to the chronic atrophy and strain of longitudinal smooth muscle, given the excessive airway pressure gradients typically seen in these 1480 AnnalsATS Volume 13 Number 9 September 2016

6 Table 3. Cardiopulmonary exercise testing Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Mean _VO 2 max, L/min (% predicted) 3.48 (146%) 2.95 (133%) 3.65 (109%) 3.05 (124%) 3.25 (88%) 3.10 (112%) 119% VAT, L/min (% predicted) 2.39 (100%) 1.95 (88%) 2.42 (72%) 1.70 (69%) 1.87 (51%) 2.25 (73%) 76% HR response, beats/min _VO 2 max/hr (O 2 pulse) 21.2 (156%) 15.5 (134%) 19.2 (106%) 15.9 (119%) 16.2 (83%) 19.9 (114%) 119% Respiratory rate, breaths/min VEmax/MVV VT/IC Sa O2 at maximal exercise 94% 98% 97% 98% 95% 96% 96% FEF/FIF at maximal exercise N/A N/A End-tidal CO 2 at maximal exercise Definition of abbreviations: FEF = forced expiratory flow; FIF = forced inspiratory flow; HR = heart rate; IC = inspiratory capacity; MVV = maximal voluntary ventilation; N/A = not available; VAT = ventilatory anaerobic threshold; VE = minute ventilation; VO 2 = oxygen consumption; VT = tidal volume. disease processes (19). Nonetheless, the severity of airway collapse has been demonstrated to be independent of disease severity, which may suggest that other factors may play a role (20, 21). There is considerable overlap between EDAC and tracheobronchomalacia as described in the current literature. EDAC has been described mostly in patients with COPD who also have some degree of tracheobronchomalacia. While some authors have defined EDAC as a form of large airway collapse involving excessive bulging of the posterior tracheal membrane during expiration, others include this form of tracheal collapse as a subset of tracheobronchomalacia. There may be significant overlap between the two processes, and it can be difficult to tell if an individual s dyspnea is related to EDACtracheobronchomalacia or other underlying disease (5). Part of the difficulty in determining the clinical significance of EDAC is that functional airway collapse has previously been documented in apparently healthy individuals (8). Boiselle and colleagues identified a wide variation in bronchial collapse with forced expiration on multidetector CT in healthy volunteers with normal pulmonary function test results and no significant smoke exposure. Posterior membrane collapse in the tracheobronchial tree has also been described to be partly physiological as well as an isolated finding associated with forced expiration or cough. This physiology is not implausible, given impressive pressure variations seen with coughing and forced expiration, especially when enacted upon the relatively pliable tracheobronchial membrane. While normal physiology can account for transient collapse in healthy individuals, it did not account for reproducible symptoms and auscultatory findings exhibited with exercise in our patients. Airway collapse, when demonstrated on expiratory CT, was greater than 75% and nearly occluded the distal trachea and bronchi, a finding not identified in any other military patients with exertional dyspnea (1). It may be postulated, in the absence of underlying lung disease, that these patients had large airway collapse as a result of multiple contributors during high levels of exertion. Increased luminal airflow velocity during exercise leading to decreased luminal pressures, especially in tapering airways, creates a stress on luminal integrity with subsequent smooth muscle fatigue or strain. This muscle lassitude in the setting of continued pressure differential is a likely explanation for why this is not seen in nonexertional pulmonary testing (22). Primary treatment modalities for tracheobronchomalacia and EDAC include treatment of the underlying pulmonary disorder (i.e., COPD control) and noninvasive positive pressure ventilation. Airway stenting and possible tracheobronchoplasty are reserved for selected individuals. As described in several studies of patients with severe tracheobronchomalacia, improvement of respiratory symptoms, quality of life, and functional status all resulted after airway stenting and/or surgical intervention in selected candidates (23 26). Given the unique findings in our patient population related primarily to exercise, we did not offer or recommend any therapeutic strategies such as positive pressure ventilation, given the lack of consensus on treatment for functional airway collapse in patients without baseline pulmonary dysfunction. Limitation of exercise below symptomatic levels was typically recommended, and, to our knowledge, these patients were able to continue military service. We suggest further study with intermittent breathing techniques such as pursed-lip breathing or positive pressure ventilation to reduce the extent of functional collapse seen with exertion. However, there are no longitudinal data available in our patients to determine if reduction in exercise provides any longterm benefits. Conclusions While not previously described, the findings in our six patients clearly demonstrate functional large airway collapse during exercise by multiple modalities. In each case, the combination of symptoms, auscultatory findings, CT, and visualization of the airways with bronchoscopy leads to the conclusion for exercise-associated EDAC. Whether this represents underlying pathophysiology related to underlying tracheobronchomalacia or simply an exaggeration of airway response to increased flows is undetermined. This syndrome should be considered in the differential diagnosis of exertional dyspnea when other possibilities, such as asthma, COPD, and inducible laryngeal obstruction, have been excluded. n Author disclosures are available with the text of this article at Acknowledgment: The authors thank George Eapen, M.D., for his review of the manuscript. Weinstein, Hull, Ritchie, et al.: Exercise-associated EDAC 1481

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