Excessive Gas Exchange Impairment during Exercise in A Subject with A History of Bronchopulmonary Dysplasia And High Altitude Pulmonary Edema

Abstract

A 27-year-old male subject (V(O2 max)), 92% predicted) with a history of bronchopulmonary dysplasia (BPD) and a clinically documented case of high altitude pulmonary edema (HAPE) was examined at rest and during exercise. Pulmonary function testing revealed a normal forced vital capacity (FVC, 98.1% predicted) and diffusion capacity for carbon monoxide (D(L(CO)), 91.2% predicted), but significant airway obstruction at rest [forced expiratory volume in 1 sec (FEV(1)), 66.5% predicted; forced expiratory flow at 50% of vital capacity (FEF(50)), 34.3% predicted; and FEV(1) /FVC 56.5%] that was not reversible with an inhaled bronchodilator. Gas exchange worsened from rest to exercise, with the alveolar to arterial P(O2) difference (AaD(O2)) increasing from 0 at rest to 41 mmHg at maximal normoxic exercise (VO(2) = 41.4 mL/kg/min) and from 11 to 31 mmHg at maximal hypoxic exercise (VO(2) = 21.9 mL/kg/min). Arterial P(O2) decreased to 67.8 and 29.9 mmHg at maximal normoxic and hypoxic exercise, respectively. These data indicate that our subject with a history of BPD is prone to a greater degree of exercise-induced arterial hypoxemia for a given VO(2) and F(I(O2)) than healthy age-matched controls, which may increase the subject's susceptibility to high altitude illness.

Histologic Evidence of Intrapulmonary Anastomoses by Three-Dimensional Reconstruction in Severe Bronchopulmonary Dysplasia

“…The existence of IAAV that bridge pulmonary arteries and veins has been identified in the late-gestation fetus (13)(14)(15), but IAAV are believed to disappear during the late neonatal period (15), and their potential physiologic roles are controversial. Such vessels have been suggested as contributing to intrapulmonary shunt in adults during catecholamine infusion, with exercise, and in an older patient with BPD (11,12,(25)(26)(27)(28)(29). Our findings support the hypothesis that IAAV are prominent and persist in the preterm infants with severe BPD and our speculation that such vessels contribute to hypoxemia from intrapulmonary anastomoses with sustained respiratory insufficiency in severe BPD.…”

“…Studies in infants have shown decreased lung diffusion capacity for carbon monoxide (DL CO ) even in patients with relatively mild BPD (5), and decreased DL CO can persist into adulthood (5). In addition, physiological shunt studies with infusions of bubbles during echocardiography suggest the presence of prominent intrapulmonary shunting during exercise in older subjects, including survivors of BPD (11). Although precapillary arteriovenous anastomoses have been identified in the fetal lung (13)(14)(15), histologic evidence of these vessels has not been demonstrated in older infants or patients with BPD.…”

Pulmonary Gas Exchange and Exercise Capacity in Adults Born Preterm

“…Furthermore, some preterm adults have obstructive lung disease (15), and computer tomographic evidence of emphysema (16)(17)(18) suggesting that the alveolar simplification persists. Blunted vasculogenesis and alveolar simplification may lead to ventilation-toperfusion mismatch and diffusion limitations that could in part contribute to the decreased exercise capacity reported in this population (12,13,(19)(20)(21). Indeed, Lovering and colleagues reported a case of a preterm adult susceptible to high-altitude pulmonary edema (21) and who exhibited significant gas exchange inefficiency, evidenced by an excessive widening of the alveolar-to-arterial oxygen difference (A-aDO 2 ), with normoxic and hypoxic exercise.…”

“…Blunted vasculogenesis and alveolar simplification may lead to ventilation-toperfusion mismatch and diffusion limitations that could in part contribute to the decreased exercise capacity reported in this population (12,13,(19)(20)(21). Indeed, Lovering and colleagues reported a case of a preterm adult susceptible to high-altitude pulmonary edema (21) and who exhibited significant gas exchange inefficiency, evidenced by an excessive widening of the alveolar-to-arterial oxygen difference (A-aDO 2 ), with normoxic and hypoxic exercise. However, of the comprehensive studies that have examined exercise tolerance (12)(13)(14)22) and gas exchange during exercise (13,14,22), several show reduced aerobic exercise capacity in adult preterms (12,13), yet none showed differences in gas exchange.…”

Histologic Identification of Prominent Intrapulmonary Anastomotic Vessels in Severe Congenital Diaphragmatic Hernia

“…There is evidence of the presence of IPAV in the late gestation fetus and these vessels were originally thought to disappear in the neonatal period (22–24). However, there have been several reports of intrapulmonary shunt vessels in normal adults, and evidence for physiologic shunt has been elicited during catecholamine infusion, hypoxia or exercise (34–40). Our findings demonstrate prominent IPAV in infants with severe CDH but lack direct physiologic evidence of their clinical impact.…”