We enrolled adolescents in the greater Chicago area with monospot-positive acute IM, identified via school nurses, pediatric practices, including the Pediatric Practice Research Group (7
) and the Virology Laboratory of Children’s Memorial Hospital. Six months following their IM diagnosis, a telephone screening interview identified those not fully recovered and 50 recovered controls willing to come for a clinical evaluation. All aspects of the study were approved by the Institutional Review Boards of Children’s Memorial Research Center and the College of Applied Sciences of the University of Illinois at Chicago.
We used the Jason et al (8
) revision of the Fukuda (1
) criteria to diagnose CFS. When a well-recognized underlying condition, such as primary depression, could explain the subject’s symptoms, we classified him/her as having “CFS-explained.”
The 6-month clinical evaluation consisted of a complete history, physical examination and laboratory screening to rule out medical causes of CFS. Routine laboratory screening for each trial participant included urianlysis and urine toxicology, urine pregnancy testing and serum estradiol (females only), complete blood count with differential, eryhthrocyte sedimentation rate, measurements of thyroid and adrenocorticotropic hormones, serum electrolytes, liver chemistries and an HIV antibody test. Using the data from the clinical evaluation, a diagnosis of CFS, CFS-explained, or recovered was made for each subject after review by an expert panel. All CFS case patients and recovered controls were offered an exercise tolerance test; those who agreed to undergo this testing were included in our analysis. As part of the exercise tolerance test, participants’ saliva was collected 10 minutes before, immediately after, and 60 minutes later to measure (changes in) cortisol, a known stress response to exercise.
Stature was measured using a stadiometer and weight was obtained using a platform beam scale. Body mass index (BMI) was calculated as weight/height (kg·m-2). Fat free mass (FFM, a measure of nutritional status) was determined using bioelectrical impedance analysis (RJL Systems, Clinton Twp, MI) to evaluate the subjects overall nutritional status (lean body mass, percent of lean muscle) per manufacturer’s instructions.
Spirometry (SensorMedics Inc., Yorba Linda, CA) was performed according to American Thoracic Society Standards before the exercise test to measure FEV1
, with values expressed as a percent of predicted for height, weight, and age (9
All study subjects were asked to refrain from strenuous activity one day before testing at the Pulmonary Exercise Laboratory. All subjects performed a graded maximal exercise test on an electronically braked cycle ergometer (Lode Excalibur, Groningen, Netherland) per the Godfrey protocol (11
). Subjects maintained a cadence of 60 revolutions per minute throughout the test. Incremental increases in work load were made each minute based on the child’s stature: 10, 15, and 20 W for those shorter than 1.2 meters, 1.2–1.4 meters, and taller than 1.4 meters, respectively. Peak work capacity (exercise tolerance) was determined as the last work load at which the patient pedaled for a full minute. Oxygen consumption (VO2
) was determined (VMax 229,SensorMedics Inc., Yorba Linda, CA) and recorded every 30 sec. Oxyhemoglobin saturation (SaO2) was monitored continuously via pulse oximetry (Nellcor, Hayward, CA) throughout the test. A test was considered maximal if the heart rate exceeded 90% of predicted maximal values, a plateau occurred in oxygen consumption that did not rise with increasing work load, or if the oxyhemoglobin saturation dropped more than 5% from baseline (12
). Verbal encouragement was given throughout the test.
The following data were collected: Work slope (Δ VO2/ Δ Work Capacity, i.e., the change in oxygen consumption divided by work capacity), minute ventilation (liters of air moved per minute) at peak work capacity, breathing reserves (as indicated by minute ventilation / Maximal Voluntary Ventilation [MVV, the theoretical amount of O2 one can breathe in] or by MVV – minute ventilation), respiratory quotient (the ratio of CO2 produced to O2 consumed), the peak O2 pulse (oxygen consumption per heartbeat) and ventilatory equivalents (VE/VCO2 and VE/VO2; the ratio of air breathed per minute related to carbon dioxide or oxygen respectively).
Technicians administering the exercise testing and the Pulmonologist (SB) interpreting the testing were blinded as to the patients’ diagnosis (CFS vs. recovered control).
Chi square tests were used to evaluate the significance of categorical data. T-tests (two-tailed) or Kruskal Wallis tests, as appropriate, were used to evaluate continuous data.