Am. J. Respir. Crit. Care Med., Volume 164, Number 3, August 2001, 425-432

Unexplained Exertional Limitation
Characterization of Patients with a Mitochondrial Myopathy

KEVIN R. FLAHERTY, JOHN WALD, IDELLE M. WEISMAN, R. JORGE ZEBALLOS, M. ANTHONY SCHORK, MILA BLAIVAS, MELVYN RUBENFIRE, and FERNANDO J. MARTINEZ

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

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 O₂ 67 versus 104% predicted; p < 0.0001) and respiratory muscle weakness (PI_max 77 versus 115% predicted; p = 0.001). These patients have a characteristic exercise response that was hyperventilatory (peak VE/ CO₂; 55 versus 42) and hypercirculatory (maximum heart rate  baseline heart rate/ O₂max  baseline O₂max; 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 (Pdi_max 61 versus 115 cm H₂O; p = 0.01) and were more likely to reach mechanical ventilatory limitation ( Emax/ 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.

Keywords: metabolic myopathy; dyspnea; mitochondrial myopathy

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