{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:56:15Z","timestamp":1774616175909,"version":"3.50.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2001,8,1]],"date-time":"2001-08-01T00:00:00Z","timestamp":996624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Exercise intolerance is a common complaint, the cause of which often remains elusive after a comprehensive evaluation. In this report, we describe 28 patients with unexplained dyspnea or exertional limitation secondary to biopsy-proven mitochondrial myopathies. Patients were prospectively identified from a multidisciplinary dyspnea clinic at a tertiary referral center. All patients were without underlying pulmonary, cardiac, or other neuromuscular disorders. Patients underwent history, physical examination, complete pulmonary function testing, respiratory muscle testing, cardiopulmonary exercise testing, and muscle biopsy. Results were compared with a group of normal control subjects. The estimated period prevalence was 8.5% (28 of 331). Spirometry, lung volumes, and gas exchange were normal in patients and control subjects. Compared with control subjects, the patient group demonstrated decreased exercise capacity (maximum achieved V\u02d9o2 67 versus 104% predicted; p &amp;lt; 0.0001) and respiratory muscle weakness (Pimax 77 versus 115% predicted; p = 0.001). These patients have a characteristic exercise response that was hyperventilatory (peak Ve\/V\u02d9co2; 55 versus 42) and hypercirculatory (maximum heart rate \u2212 baseline heart rate\/V\u02d9o2max \u2212 baseline V\u02d9o2max; 91 versus 41) compared to control subjects. Patients stopping exercise due to dyspnea (n = 16) (as compared with muscle fatigue, n = 11) displayed weaker respiratory muscles (Pdimax 61 versus 115 cm H2O; p = 0.01) and were more likely to reach mechanical ventilatory limitation (V\u02d9emax\/ MVV 0.81 versus 0.58; p = 0.02). The sensation of dyspnea was related to indices of respiratory muscle function including respiratory rate and inspiratory flow. We conclude that mitochondrial myopathies are more prevalent than previously reported. The characteristic physiological profile may be useful in the diagnostic evaluation of mitochondrial myopathy.<\/jats:p>","DOI":"10.1164\/ajrccm.164.3.2005110","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T14:49:24Z","timestamp":1365086964000},"page":"425-432","source":"Crossref","is-referenced-by-count":80,"title":["Unexplained Exertional Limitation"],"prefix":"10.1093","volume":"164","author":[{"given":"KEVIN R.","family":"FLAHERTY","sequence":"first","affiliation":[{"name":"Dyspnea and Pulmonary Hypertension Clinics, Division of Pulmonary and Critical Care Medicine, and the Departments of Neurology and Pathology, Division of Cardiology, and the School of Public Health, University of Michigan Health System, Ann Arbor, Michigan; Department of Clinical Investigation, Human Performance Laboratory, William Beaumont Army Medical Center, El Paso, Texas; and Department of Anesthesiology, Texas Tech University Health Sciences Center, El Paso, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JOHN","family":"WALD","sequence":"additional","affiliation":[{"name":"Dyspnea and Pulmonary Hypertension Clinics, Division of Pulmonary and Critical Care Medicine, and the Departments of Neurology and Pathology, Division of Cardiology, and the School of Public Health, University of Michigan Health System, Ann Arbor, Michigan; Department of Clinical Investigation, Human Performance Laboratory, William Beaumont Army Medical Center, El Paso, Texas; and Department of Anesthesiology, Texas Tech University Health Sciences Center, El Paso, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"IDELLE M.","family":"WEISMAN","sequence":"additional","affiliation":[{"name":"Dyspnea and Pulmonary Hypertension Clinics, Division of Pulmonary and Critical Care Medicine, and the Departments of Neurology and Pathology, Division of Cardiology, and the School of Public Health, University of Michigan Health System, Ann Arbor, Michigan; Department of Clinical Investigation, Human Performance Laboratory, William Beaumont Army Medical Center, El Paso, Texas; and Department of Anesthesiology, Texas Tech University Health Sciences Center, El Paso, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. JORGE","family":"ZEBALLOS","sequence":"additional","affiliation":[{"name":"Dyspnea and Pulmonary Hypertension Clinics, Division of Pulmonary and Critical Care Medicine, and the Departments of Neurology and Pathology, Division of Cardiology, and the School of Public Health, University of Michigan Health System, Ann Arbor, Michigan; Department of Clinical Investigation, Human Performance Laboratory, William Beaumont Army Medical Center, El Paso, Texas; and Department of Anesthesiology, Texas Tech University Health Sciences Center, El Paso, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. ANTHONY","family":"SCHORK","sequence":"additional","affiliation":[{"name":"Dyspnea and Pulmonary Hypertension Clinics, Division of Pulmonary and Critical Care Medicine, and the Departments of Neurology and Pathology, Division of Cardiology, and the School of Public Health, University of Michigan Health System, Ann Arbor, Michigan; Department of Clinical Investigation, Human Performance Laboratory, William Beaumont Army Medical Center, El Paso, Texas; and Department of Anesthesiology, Texas Tech University Health Sciences Center, El Paso, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MILA","family":"BLAIVAS","sequence":"additional","affiliation":[{"name":"Dyspnea and Pulmonary Hypertension Clinics, Division of Pulmonary and Critical Care Medicine, and the Departments of Neurology and Pathology, Division of Cardiology, and the School of Public Health, University of Michigan Health System, Ann Arbor, Michigan; Department of Clinical Investigation, Human Performance Laboratory, William Beaumont Army Medical Center, El Paso, Texas; and Department of Anesthesiology, Texas Tech University Health Sciences Center, El Paso, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MELVYN","family":"RUBENFIRE","sequence":"additional","affiliation":[{"name":"Dyspnea and Pulmonary Hypertension Clinics, Division of Pulmonary and Critical Care Medicine, and the Departments of Neurology and Pathology, Division of Cardiology, and the School of Public Health, University of Michigan Health System, Ann Arbor, Michigan; Department of Clinical Investigation, Human Performance Laboratory, William Beaumont Army Medical Center, El Paso, Texas; and Department of Anesthesiology, Texas Tech University Health Sciences Center, El Paso, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"FERNANDO J.","family":"MARTINEZ","sequence":"additional","affiliation":[{"name":"Dyspnea and Pulmonary Hypertension Clinics, Division of Pulmonary and Critical Care Medicine, and the Departments of Neurology and Pathology, Division of Cardiology, and the School of Public Health, University of Michigan Health System, Ann Arbor, Michigan; Department of Clinical Investigation, Human Performance Laboratory, William Beaumont Army Medical Center, El Paso, Texas; and Department of Anesthesiology, Texas Tech University Health Sciences Center, El Paso, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,8,1]]},"reference":[{"key":"2026032708035719500_B1","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1378\/chest.100.5.1293","article-title":"Chronic dyspnea unexplained by history, physical examination, chest roentgenogram, and spirometry: analysis of a seven year 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