Diagnosis of Exercise-Induced Bronchospasm (EIB) and Asthma in National Collegiate Athletic Association (NCAA) Division I Athletes

We plan to identify all Division I athletes, male and female, at the University of Arizona
that are currently being treated for either EIB or asthma by review of preparticipation
physical forms or identified by the medical staff. In addition, athletes that were
prescribed inhalers through Campus Health Services will be identified through review of
electronic pharmacy records. Each athlete identified will be matched with two control
athletes (ie, not currently using asthma medications) from the same sport. Subjects will be
tested for EIB using eucapnic voluntary hyperventilation, the gold standard for making this
diagnosis.

Subject Recruitment Potential subjects will be identified as described above. Subjects will
be approached by one of the co-investigators, the study explained and an opportunity to
review the consent form and ask question provided. Subjects who consent will then be
scheduled for testing.

Questionnaire Subjects, once enrolled, will be asked to complete a 27 item questionnaire
including questions about prior history and treatment of asthma, as well as history of
respiratory symptoms. In addition, subjects will be asked to complete the Asthma Control
Test (ACT).

EVH and Spirometric Testing All subjects will undergo baseline assessment of lung function
using the KoKo Legend Portable Spirometer. The subjects will then undergo eucapnic voluntary
hyperventilation testing. EVH testing will require the subject to hyperventilate dry air
containing 5% carbon dioxide at room temperature for six minutes at a target ventilation of
30 times the subject's forced expiratory volume in one second (FEV1). The EVH test will be
considered positive if a fall in FEV1 of 10% or more from baseline is recorded after a 6
minute period of hyperpnea. To overcome the problem of any post-test respiratory muscle
fatigue, the FEV1 will be recorded at least three minutes after challenge and then repeated
at three-minute intervals through 21 minutes.

Spirometry will be carried out according to American Thoracic Society standards. Both
absolute and percent-predicted spirometric values will be recorded. Predicted values will be
calculated from validated, published, race-specific regression equations. (Hankinson, et al.
Spirometric reference values values from a sample of the general US population. Am J Respir
Crit Care Med 1999; 159:179-187.) Asian-American athletes will be evaluated using norms for
whites.

To provide the optimal test circumstances, some medications will be withheld for 8 to 96
hours before the bronchial provocation test: no short-acting bronchodilators, sodium
cromoglycate, nedocromil sodium, or ipratropium bromide for 8 hours; no long-acting
bronchodilators or antihistamines for 48 hours; no leukotriene antagonists for four days.
Steroids should not be inhaled on the day of the test. No caffeine should be taken on the
morning of the test. Vigorous exercise will be avoided for at least four hours prior to the
start of the test as well as any exercise on the day of testing. Subjects will be scheduled
for testing to allow at least 6-8 hours to elapse between previous vigorous activity and
testing.

Exhaled Nitric Oxide (eNO) Measurement

Measurement of eNO will be obtained prior to measurement of pre-EVH spirometry. Exhaled NO
will be measured employing a technique modified after Silkoff et al (1997) and following
American Thoracic Society guidelines for eNO assessment (American Thoracic Society, 1999).
In brief, this technique utilizes a resistive device that provides a constant low expiratory
flow rate and ensures vellum closure. The combination of vellum closure and low flow rates,
specifically 50 ml/s, assures accurate measurement of specific pulmonary derived eNO, while
excluding potential contamination by nasal and paranasal sinuses NO (which can be a large
source of eNO). Nitric oxide concentrations will be measured using a rapid-response
chemiluminescent analyzer (NIOX™ System, Aerocrine, Sweden), which has a response time of <
700 ms for 10-90% full scale. The Food and Drug Administration has approved this device for
clinical application in asthma management. The measurement circuit will consist of a
mouthpiece-filter connected to a resistor/flow meter and collection bag. The participant
will inhale to total lung capacity (TLC), insert the mouthpiece, and then immediately exhale
slowly. During expiration, the participant will attempt to maintain a target flow of 50
ml/sec. The target period of exhalation time will be 10 seconds. However, for participants
that are not able to perform the 10 second exhalation, the time requirements may be
decreased to 6 seconds. Dietary history by recall for the 4-6 hours prior to testing will be
obtained to screen for dietary sources of NO.

Data Collection Spirometric values and quality control measures for EVH testing will be
recorded on forms specifically designed for this purpose and, for spirometry, already in use
in the Pediatric Pulmonary Function Laboratory. Data will entered into a computer
spreadsheet and double-checked by a second person to assure accuracy. It will then be
transferred to a statistical package (STATA) for subsequent analysis.

Data Analysis For this observational study summative and descriptive statistics will be
carried out. If opportunities for comparative analysis are identified, parametric and
nonparametric analysis will be carried out as appropriate.

A fall occurring early in the post-EVH period, especially in conjunction with documented
pre-exercise elevation in eNO, will be taken as being more suggestive of poorly controlled
asthma, while a fall 9-12 minutes after EVH, especially in the absence of an elevated eNO,
will be interpreted as being more indicative of true EIB.

Inclusion Criteria:

- varsity athlete

- ability and willingness to give written informed consent

Exclusion Criteria:

- inability to give written informed consent

- unwillingness to perform spirometry or eucapnic voluntary hyperventilation