Effects of Physical Activity on Exercise Capacity in Twins With α-1 Antitrypsin Deficiency

Abstract

Key Words: antitrypsin deficiency, chronic obstructive pulmonary disease (Clin J Sport Med 2005;15:183-185) A lpha-1 antitrypsin deficiency (a1-ATD) was first identified in the 1960s and was subsequently linked to chronic lung disease. a1-ATD is a genetically transmitted disorder resulting from mutations in the a1-AT gene, 1 and it is associated with a high risk for the development of early-onset pulmonary emphysema. It is estimated that a1-ATD is implicated in 2% to 3% of chronic obstructive pulmonary disease (COPD) cases. 2,3 Therapeutic modalities for a1-ATD are limited. Exercise as a therapeutic intervention is commonly viewed as an integral component of disease management for a variety of chronic conditions. Significant debilitation, impaired exercise tolerance, dyspnea during exercise, and a reduced quality of life are often present in COPD. 4 Exercise training has overwhelmingly been shown to elicit favorable responses in patients with COPD, 5 but little is known about the interactions among physical activity, a1-ATD, and disease management. In the case of a1-ATD, the phenotype is known, and the disease pathology well documented; however, treatment is limited, and the role of physical activity as a management strategy is not well described. This case reports on monozygotic twins as a natural experiment to understand the relationship between physical activity and the a1-ATD genetic disorder. CASE REPORTParticipants were male monozygotic twins (57 y; twin A, twin B) who were diagnosed with a1-ATD (PiZ phenotype) 16 years ago. All procedures were approved by the University of British Columbia, and written informed consent was obtained. Neither twin had a history of asthma, cardiac, vascular, or neuromuscular conditions. Neither used supplemental O 2 at rest or during exercise. Both were clinically stable for over 1-year prior to any testing. Both were exsmokers, had stopped smoking more than 15 years ago, and had similar smoking histories. Each received the same regular infusion of human a1-AT (25-30 g once/2 wk), and each took similar standard medications (Table 1). Neither participated in a structured pulmonary rehabilitation program. Twin A was habitually sedentary, and twin B regularly played golf (2-3 times/wk) and walked the golf course (18 holes). Although we were unable to perform a retrospective quantification of physical activity, it was clear from 10 to 15 years of physician-patient interviews that twin A was habitually sedentary and twin B was regularly physically active. The twins had vocationally similar physical activity patterns.Standard pulmonary function analyses were performed. Lean body mass was determined using dual-energy x-ray absorptiometry (4500 DXA; Hologic, Waltham, MA). Eccentric quadriceps strength was assessed using an isokinetic dynamometer (Chattanooga Group, Hixson, TN). Participants performed a graded cycle exercise test (GXT) to exhaustion. Expired gases, minute ventilation ( _ VE), and derived respiratory variables were recorded (2900; Sensor Medics, Yorba Linda, CA), an...