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Field Exercise vs Laboratory Eucapnic Voluntary Hyperventilation To Identify Airway Hyperresponsiveness in Elite Cold Weather Athletes^*

^* From Marywood University (Dr. Rundell and Mr. Spiering), Scranton, PA; United States Olympic Committee at Lake Placid (Mr. Judelson), Lake Placid, NY; and Royal Prince Alfred Hospital (Dr. Anderson), Camperdown, NSW, Australia.

Correspondence to: Kenneth W. Rundell, PhD, Professor of Health Science, Director of the Human Performance Laboratory, Marywood University, 2300 Adams Ave, Scranton, PA 18509-4742; e-mail rundell{at}marywood.edu

	Abstract

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Study objective: For the 2002 Winter Olympic Games, athletes were required to submit objective evidence of asthma or exercise-induced bronchoconstriction (EIB) for approval to inhale a ß₂-agonist. Eucapnic voluntary hyperventilation (EVH) was recommended as a laboratory challenge that would identify airway hyperresponsiveness (AHR) consistent with EIB. The objective was to compare the change in FEV₁ provoked by EVH with that provoked by exercise in cold weather athletes.

Design: Spirometry was measured before and for 15 min after challenges. The two challenges were performed in random order at least 24 h apart.

Setting: EVH was performed in the laboratory at 19°C, and exercise took place in the field in the cold (2°C, 45% relative humidity).

Participants: Thirty-eight athletes (25 female subjects; median age, 16 years).

Interventions: For the EVH, athletes inhaled dry air containing 5% carbon dioxide for 6 min at a target ventilation equivalent to 30 times baseline FEV₁. Exercise was performed by cross-country skiing, ice skating, or running for 6 to 8 min.

Measurements and results: AHR consistent with EIB was defined as 10% fall in FEV₁ from baseline after challenge. Eleven athletes were exercise positive (EX+) [FEV₁ fall, 20.5 ± 7.3%], and 17 athletes were EVH positive (FEV₁ fall, 14.5 ± 4.5%) [mean ± SD]. Of 19 subjects with AHR, 58% were identified by exercise and 89% were identified by EVH. EVH identified 9 of 11 subjects who were EX+ and a further 8 subjects with potential for EIB. The average ventilation during EVH was 28 times FEV₁.

Conclusion: Performing EVH for 6 min in the laboratory had a greater chance of identifying AHR in these athletes compared with 6 to 8 min of field exercise in the cold. The EVH test will be useful to evaluate elite summer sports athletes whose widely different forms of exercise provide an "equipment" challenge to any laboratory.

Key Words: airway hyperresponsiveness • dry air • exercise • exercise-induced bronchoconstriction • eucapnic voluntary hyperpnea

	Introduction

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Laboratory evaluation of exercise-induced bronchoconstriction (EIB) is increasingly important, as the reported prevalence of the problem has reached epidemic proportions both among elite athletes¹ and the general population.² Approximately 25% of 1998 US Winter Olympic athletes were identified as EIB positive by spirometry, with as many as 50 to 60% of the athletes in certain sport disciplines afflicted.^{3 4} Among 1996 US Summer Olympians, 15.3% reported a previous diagnosis of asthma, exercise-induced asthma, or EIB.¹

While self-reported symptoms (cough, wheeze, chest tightness, excess mucus production) are often used as the sole diagnostic tool, they have been shown to be unreliable predictors of EIB in elite winter and summer athletes.^{5 6} Objective criteria defined by postbronchial provocation change in pulmonary function are necessary to confirm the diagnosis. The bronchial provocation tests used to identify subjects with EIB include exercise (laboratory or field), eucapnic voluntary hyperventilation (EVH) of dry gas mixtures (room temperature or chilled), hypertonic saline solution inhalation,^{7 8} or mannitol powder inhalation.^{9 10} Bronchial provocation using pharmacologic agents appears less sensitive for identifying EIB in athletes⁶ or in school children^{2 11} than the physical and osmotic challenges. The reason for this discrepancy most likely relates to the use of a single agonist (usually methacholine or histamine) during a pharmacologic challenge in contrast to multiple receptor agonists (histamine, leukotrienes, prostaglandins) released in response to the physical and osmotic stimuli.

For the first time, athletes at the 2002 Winter Olympics at Salt Lake City were required to provide evidence of asthma, EIA, or EIB when notifying the International Olympic Committee of ß₂-agonist use prior to competition.¹² One of the tests recommended to identify EIB in the laboratory was EVH.¹³ EVH involves inhaling dry air containing 5% carbon dioxide at exercising ventilation rates. The advantages proposed for using EVH instead of exercise in the laboratory relate to the ease with which high levels of ventilation can be reached and maintained and the control of inspired gas that can be altered to simulate the conditions of exercise.¹⁴ EVH has the potential to permit laboratory evaluation of both summer and winter sports athletes, and its use eliminates the need for expensive ergometers.

Exercise in the field has been shown to be more potent than exercise performed under laboratory conditions for detection of EIB.¹⁵ However, there are limitations in performing exercise field tests. These include lack of control over environmental variables and challenge intensity and logistical difficulties when large numbers of athletes are required to perform different types of exercise. The aim of this study was to compare the airway responses to EVH in the laboratory using a standardized protocol (6 min ventilating at 30 times FEV₁)¹³ with the airway response to a field-based exercise challenge of 6 to 8 min in cold/dry ambient conditions in elite athletes. If EVH identifies subjects who are positive for EIB in the field, it would be a suitable alternative to field- or laboratory-based exercise tests. This has important implications for future Olympic games in Athens if the International Olympic Committee Medical Commission continues to require objective evidence for EIB in order to permit inhaled ß₂-agonist use.

	Materials and Methods

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Subjects
Thirty-eight subjects volunteered to participate in this study after receiving a verbal explanation of the procedures and possible risks. The protocol was approved by the Institutional Review Board of the United States Olympic Committee, and subjects signed informed consent. The subjects participated in synchronized figure skating (n = 20), Nordic combined (n = 1) canoe/kayak (n = 7), cross-country skiing (n = 2), and biathlon (n = 1). These athletes ranged in accomplishment from Developmental to Senior National Team levels. Seven other subjects were athletes who were competitive at the state level and trained approximately 10 h/wk. Eight subjects had a previous diagnosis of asthma and/or EIB; five subjects reported using a ß₂-agonist before competition and high-intensity training sessions. Two athletes were receiving the inhaled corticosteroid fluticasone, one athlete was receiving fluticasone in combination with salmeterol, and one athlete was receiving montelukast (Table 1 ).

The field-based exercise challenge consisted of 6 to 8 min of cross-country skiing (n = 15), ice skating (n = 20), or running (n = 3). Subjects were instructed to exercise at the highest intensity sustainable for the duration of the test. An allotment of subjects wore wireless heart rate monitors to verify exercise intensity (Polar Vantage XL; Polar Electro; Oy, Finland). Environmental conditions were 2 ± 5.6°C, 45 ± 21.3% relative humidity, and 717 ± 21.3 mm Hg during field tests (mean ± SD) [VWR Digital Hygrometer/Thermometer; VWR International; West Chester, PA]. The low temperature and water content of the ambient air in the field made conditions suitable for provocation of EIB.²

The EVH protocol required subjects to breathe a compressed dry gas mixture (21% O₂, 5% CO₂, balance N₂) at a predetermined rate (30 times FEV₁) for 6 min.^{13 14} Gas flowed from a cylinder through a calibrated rotameter (1110 Series Flowmeter; Brooks Instruments; Hatfield, PA) to three 300-g reservoir bags via high-pressure tubing. From the reservoir bags, the gas was directed to the subject via a 35-mm breathing tube, two-way breathing valve, and mouthpiece (Hans Rudolf; Kansas City, MO). Expired gas passed through a flow sensor, and the ventilation rate was recorded (2900 Metabolic Measurement Cart; SensorMedics; Yorba Linda, CA). Inhaled gas during EVH was at laboratory temperature but completely dry. Ambient conditions in the laboratory were 19.4 ± 0.61°C, 16.1 ± 3.22% relative humidity, and 722 ± 7.8 mm Hg.

Statistical Analysis
Baseline pulmonary function measurements were compared to accepted norms for calculation of percentage-of-predicted values.¹⁶ The maximum percentage change in FEV₁ in response to exercise or EVH was calculated by taking the lowest value recorded in the 15 min after challenge and expressing it as a percentage of the baseline value measured immediately before challenge. A fall in FEV₁ 10% from baseline was considered positive for EIB. Within-subject comparisons between exercise and EVH were made using paired t tests. Differences between EIB-positive and EIB-negative subjects were examined using independent t tests. Sensitivity, specificity, positive and negative predictive values, and odds ratio were calculated for EVH to identify EIB. Limits of agreement for EVH and exercise were determined by graphing the difference between postexercise falls in FEV₁ for exercise and EVH to the average fall in FEV₁ by exercise and EVH. A p value < 0.05 was considered statistically significant for all analyses; all values are presented as mean ± SD.

	Results

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Baseline lung function values and the fall in FEV₁ in response to exercise and EVH for the 38 subjects are given in Table 1 . Values for pulmonary function variables at baseline exceeded the normative predicted values for age, height, and gender, and were in accord with resting values of elite athletes.⁵ No differences in values expressed as percentage of predicted were found between those who were positive or negative (p = not significant [NS]). Based on a 10% fall in FEV₁ from baseline, there were 11 subjects positive to exercise (EX+) and 17 subjects positive to EVH (EVH+).

Among the 11 EX+ subjects, the percentage fall in FEV₁ was 20.5 ± 7.3%; for those 27 subjects who were negative to exercise (EX-), the fall was 4.5 ± 2.5% (p < 0.05). The 17 EVH+ subjects demonstrated a percentage fall in FEV₁ of 14.5 ± 4.5%; for the 21 subjects who were negative to EVH (EVH-), the fall was 4.7 ± 3.2% (p < 0.05). Of the 17 EVH+ subjects, 9 subjects were EX+. Twenty-eight subjects had concordant findings, that is, they were positive to both or negative to both exercise and EVH (odds ratio, 10.7; Table 2 ). The effectiveness of the EVH test in identifying those EIB positive during exercise is presented in Table 3 .

View larger version (21K): [in this window] [in a new window] [Download PPT slide]   Figure 1. The maximum fall in FEV1, expressed as a percentage of the baseline value, documented in the 15 min after 6 min of EVH of dry air (containing 5% carbon dioxide) at a target ventilation rate equivalent to 30 times FEV1, in relation to the fall in FEV1 after exercising for 6 to 8 min at 2 ± 5.6°C, with relative humidity of 45 ± 21.3%, 717 ± 21.3 mm Hg. The subjects were elite athletes who performed exercise by cross-country skiing, ice skating, or running. The lines represent the 10% cutoff point commonly used to define AHR to exercise and EVH. Note that two subjects were EVH- but EX+ and eight subjects were EVH+ and EX-.

View larger version (21K): [in this window] [in a new window] [Download PPT slide]   Figure 2. The difference in percentage fall in FEV1 between exercise (Exer) and EVH plotted against the mean value of exercise and EVH percentage fall in FEV1 for each subject. Values for all but two subjects fell within 2 SD of the mean.

View larger version (23K): [in this window] [in a new window] [Download PPT slide]   Figure 3. The maximum fall in FEV1, expressed as a percentage of the baseline value, documented in the 15 min after 6 min of EVH of dry air (containing 5% carbon dioxide) at a target ventilation rate equivalent to 30 times FEV1, in relation to the fall in FEV1 after exercising in cold air (2 ± 5.6°C) for 6 min.

There was no order effect in response to the two tests. Twenty-three subjects performed EVH 24 to 30 h after the exercise challenge. No evidence of refractoriness was apparent. Mean falls in FEV₁ for exercise and EVH were 10.1 ± 9.3% and 11.6 ± 5.7%, respectively (p = NS). The falls in FEV₁ for the 15 subjects who were EX+ and/or EVH+ in this group were not different (13.1 ± 10.3% vs 14.3 ± 4.8%, p = NS). Only one subject in this group was EX+/EVH- (14.5 vs 7.8 respective falls in FEV₁). Challenges for the other 15 subjects were separated by 2 days; mean falls in FEV₁ were not different (p = NS). Likewise, no differences were found in FEV₁ postchallenge falls for exercise or EVH among hyperreactive subjects in these 15 subjects or among the 23 subjects who performed EVH within 30 h of exercise (p = NS).

	Discussion

TOP Abstract Introduction Materials and Methods Results Discussion References

 
The results of this study clearly demonstrate that EVH for 6 min breathing dry air at a ventilation rate equivalent to 28 times FEV₁ is an adequate provocative stimulus to identify athletes with demonstrable EIB during field testing in cold dry air conditions. Nine of the 11 subjects with EIB in the field were identified with EVH. This sensitivity to identify those with EIB is significantly greater than found previously when comparing the responses to exercise performed in the laboratory with those in the field.¹⁵ In that study, only 5 of the 23 subjects who responded to exercise in the field were responsive to treadmill running in a laboratory. Moreover, with EVH testing we identified a further eight subjects with airway hyperresponsiveness (AHR) and probable EIB. Thus, of the total of 19 subjects who demonstrated AHR, 17 subjects (89.5%) were identified with EVH and only 11 subjects (58%) with exercise. In a study of figure skaters, on the basis of a 10% fall in FEV₁, 8 of 29 subjects were EVH+, 8 of 29 subjects were EX+, and 4 EX+ subjects were EVH-.¹⁷ However, the time of EVH in that study was 5 min and the target ventilation rate was 21 times FEV₁ rather that the recommended 6 min at 30 times FEV₁. The exercise consisted of 3 min of warm-up followed by 5 min of figure skating routines.

We used changes in FEV₁ as an indirect measure of changes in airway caliber as it represents approximately 90% of the entire flow volume curve and is the most widely used index of AHR.^{18 19} It was also the index identified by the International Olympic Committee independent panel to evaluate EIB.¹² Some investigators have used additional indexes as well as FEV₁ to define an abnormal response (eg, change in FEF_25–75 and peak expiratory flow).^{17 20} However, these indexes are more variable than FEV₁, and changes in FEF_25–75 are only valid when measured over the same volume or when the vital capacity is unaltered. Such measurements are often difficult to interpret. A value of 10% as the cut-off point to define EIB with exercise is within the range normally recommended and used by the investigators.^{15 18 19 21} It was the value used in the analysis of the data submitted for approval for use of ß₂-agonist prior to an event for the Winter Games at Salt Lake City.¹² The cutoff value to define abnormality is usually based on the mean plus two or three SDs of the response in healthy subjects. A value of 7.9% has been suggested to define abnormality to exercise in elite cold weather athletes,¹⁵ whereas a value of 13.2% has been suggested for exercising children.²² A value of 10% has also been recommended for EVH.^{18 23 24} However, this cutoff value may be too strict when used as exclusion criteria for the military or scuba diving exclusion.

AHR in people with asthma is often, though not always, associated with abnormalities in baseline lung function. In this group of athletes, lung function was at the higher end of the range generally considered to be normal for these tests (80 to 120% predicted). It was not possible to identify from baseline lung function who would be more likely to test positive to an exercise or EVH challenge, and no significant difference was observed for any index of resting lung function including the FEF_25–75 between those who were positive or negative (p = NS).

Refractoriness has also been reported to develop during challenge with EVH,^{25 26 27} particularly with cold air.²⁸ Refractoriness is defined as the occurrence of reduced bronchoconstriction from exercise within 2 h of an initial bronchoconstricting exercise bout. In some cases, refractoriness occurs during exercise so that a longer duration provokes a lesser response.²⁹ Even though Rundell et al³⁰ found little evidence of refractoriness in elite athletes with EIB, we allowed 24 h between tests. While the response to an initial challenge test may have influenced the subsequent challenge in some individuals, we found no consistent effect in the airway response due to time between tests or order of tests, even with the marked difference in inspired air temperature. Of the 23 subjects who had the exercise challenge first and EVH within 24 to 30 h after exercise, only 1 subject was EX+ and EVH-. Six minutes of EVH with dry air was appeared to be more potent than 6 min of exercise in this particular group of subjects. The reason for this may relate to the square-wave increase in ventilation at the beginning of EVH, whereas with exercise ventilation increases progressively over time.²³ Values for ventilation measured during EVH were 104 ± 26 L/min, equivalent to 82.6% of measured MVV. The effort dependence involved in the MVV maneuver however has raised concerns of its accuracy and reliability.³¹

The mechanism whereby hyperpnea is thought to cause the airways to narrow relates to the thermal and osmotic consequences of respiratory water loss from humidifying the inspired air.^{32 33} As the field exercise challenge was performed under cold dry conditions, it might have been expected that airway cooling would be greater than during EVH in the laboratory. Reports of responses in asthmatic subjects have shown that 8 min of EVH with warm air decreases FEV₁ to the same extent as 4 min of EVH with cold air.³⁴ To find only two subjects with a positive response to exercise in the cold for 6.5 to 8 min and a negative response with 6 min of EVH breathing gas at room air temperature demonstrates the efficacy of EVH as a bronchoprovocation challenge. Further support to the potency of EVH can be found in the eight EVH+/EX- subjects. For this study, the exercise tests were performed in the field, and measurements both before and after exercise occurred under the same environmental conditions. It is possible that for EX-/EVH+ subjects, the airways were not sufficiently rapidly rewarmed after exercise to initiate the bronchoconstrictor response.³²

From a practical viewpoint, with EVH as the test of choice, only two subjects who were EX+ were missed by EVH, rather than eight EVH+ subjects who were missed by exercise, as would have been the case if exercise had been the test of choice. The reasons for this discrepancy are unclear; however, the difficulty in controlling exercise ventilation rate during a field challenge may have influenced our results.

Recruitment of the smaller airways into the conditioning process has been suggested as an important determinant of the severity of the bronchoconstrictor response to exercise.^{33 35} For the same level of ventilation and duration of exercise, the recruitment of small airways is more likely to occur at a lower inspired air temperature.³⁶ Measurement of ventilation was made during exercise in eight subjects and found to be 84.6% of the measured MVV, and close to that measured on EVH.

It is possible that EVH may overdiagnose EIB because the ventilation produced is higher than most people would achieve in the normal course of exercise. However in elite athletes, ventilation rates during exercise do reach values closer to those achieved during MVV.³¹ Therefore, testing to a target ventilation of 30 times FEV₁ would seem appropriate for this group of subjects. In this study, the athletes achieved 87.6 ± 23% of the target ventilation rate.

In summary, the EVH test at a ventilation equivalent to 28 times the FEV₁ identified 82% of subjects who demonstrated EIB with an exercise challenge under cold dry conditions in the field. Importantly EVH identified a further eight subjects hyperresponsive to dry air and thus with the potential to have EIB in the field. This finding is in keeping with other surrogate tests used to identify EIB.¹⁰ We conclude that an initial test with 6 min of EVH breathing dry air under controlled laboratory conditions has a greater chance of identifying EIB than 6 to 8 min of exercise in cool air in athletes performing cold weather sports. These findings suggest that EVH will also be a useful test to evaluate elite summer sport athletes whose widely different forms of exercise (cycling, running, swimming) provide an "equipment challenge" to any testing laboratory.

	Acknowledgements

 
The authors thank Meredith H. Wilson for technical assistance and data management.

	Footnotes

 
Abbreviations: AHR = airway hyperresponsiveness; EIB = exercise-induced bronchoconstriction; EVH = eucapnic voluntary hyperpnea; EVH+ = positive to eucapnic voluntary hyperpnea; EVH- = negative to eucapnic voluntary hyperpnea; EX+ = positive to exercise; EX- = negative to exercise; FEF_25–75 = forced expiratory flow through the mid-portion of the vital capacity; MVV = maximum voluntary ventilation; NS = not significant

Received for publication March 31, 2003. Accepted for publication September 8, 2003.

	References

TOP Abstract Introduction Materials and Methods Results Discussion References

 

1. Weiler, J, Layton, T, Hunt, M (1998) Asthma in United States Olympic athletes who participated in the 1996 summer games. J Allergy Clin Immunol 102,722-726[CrossRef][ISI][Medline]
2. Haby, MM, Peat, JK, Mellis, CM, et al An exercise challenge for epidemiological studies of childhood asthma: validity and repeatability. Eur Respir J 1995;8,729-736[Abstract]
3. Weiler, JM, Ryan, EJ, III Asthma in United States Olympic athletes who participated in the 1998 Olympic Winter Games. J Allergy Clin Immunol 2000;106,267-271[CrossRef][ISI][Medline]
4. Wilber, RL, Rundell, L, Szmedra, L, et al Incidence of exercise-induced bronchospasm in Olympic winter sport athletes. Med Sci Sports Exerc 2000;32,732-737[ISI][Medline]
5. Rundell, KW, Im, J, Mayers, LB, et al Self-reported symptoms and exercise-induced asthma in the elite athlete. Med Sci Sports Exerc 2001;33,208-213[CrossRef][ISI][Medline]
6. Holzer, K, Anderson, SD, Douglass, J Exercise in elite summer athletes: challenges for diagnosis. J Allergy Clin Immunol 2002;110,374-380[CrossRef][ISI][Medline]
7. Smith, CM, Anderson, SD Inhalational challenge using hypertonic saline in asthmatic subjects: a comparison with responses to hyperpnoea, methacholine and water. Eur Respir J 1990;3,144-151[Abstract]
8. Riedler, J, Reade, T, Dalton, M, et al Hypertonic saline challenge in an epidemiological survey of asthma in children. Am J Respir Crit Care Med 1994;150,1632-1639[Abstract]
9. Brannan, JD, Koskela, H, Anderson, SD, et al Responsiveness to mannitol in asthmatic subjects with exercise- and hyperventilation-induced asthma. Am J Respir Crit Care Med 1998;158,1120-1126[Abstract/Free Full Text]
10. Holzer, K, Anderson, SD, Chan, H-K, et al Mannitol as a challenge test to identify exercise-induced bronchoconstriction in elite athletes. Am J Respir Crit Care Med 2003;167,534-547[Abstract/Free Full Text]
11. Backer, V, Dirksen, A, Bach-Mortensen, N, et al The distribution of bronchial responsiveness to histamine and exercise in 527 children and adolescents. J Allergy Clin Immunol 1991;88,68-76[CrossRef][ISI][Medline]
12. Anderson, SD, Fitch, K, Perry, CP, et al Responses to bronchial challenge submitted for approval to use inhaled ß₂ agonists prior to an event at the 2002 Winter Olympics. J Allergy Clin Immunol 2003;111,44-49
13. Argyros, GJ, Roach, JM, Hurwitz, KM, et al Eucapnic voluntary hyperventilation as a bronchoprovocation technique: development of a standardized dosing schedule in asthmatics. Chest 1996;109,1520-1524[Abstract/Free Full Text]
14. Anderson, SD, Argyros, GJ, Magnussen, H, et al Provocation by eucapnic voluntary hyperpnoea to identify exercise induced bronchoconstriction. Br J Sports Med 2001;35,344-347[Abstract/Free Full Text]
15. Rundell, KW, Wilber, RL, Szmedra, L, et al Exercise-induced asthma screening of elite athletes: field vs laboratory exercise challenge. Med Sci Sports Exerc 2000;32,309-316[ISI][Medline]
16. Quanjer, PH, Tammeling, GJ, Cotes, JE, et al Lung volumes and forced ventilatory flows. Eur Respir J 1993;6,5-40[Medline]
17. Mannix, ET, Manfredi, F, Farber, MO A comparison of two challenge tests for identifying exercise-induced bronchospasm in figure skaters. Chest 1999;115,649-653[Abstract/Free Full Text]
18. Sterk, PJ, Fabbri, LM, Quanjer, PH, et al Airway responsiveness: standardized challenge testing with pharmacological, physical and sensitizing stimuli in adults. Eur Respir J 1993;6,53-83[Abstract]
19. Crapo, RO, Casaburi, R, Coates, AL, et al Guidelines for methacholine and exercise challenge testing - 1999. Am J Respir Crit Care Med 2000;161,309-329[Free Full Text]
20. Custovic, A, Arifhodzic, N, Robinson, A, et al Exercise testing revisited: the response to exercise in normal and atopic children. Chest 1994;105,1127-1132[Abstract/Free Full Text]
21. Folgering, H, Palange, P, Anderson, S Clinical exercise testing with reference to lung diseases: indications and protocols. Eur Respir Mon 1997;6,51-71
22. Godfrey, S, Springer, C, Bar-Yishay, E, et al Cut-off points defining normal and asthmatic bronchial reactivity to exercise and inhalation challenges in children and young adults. Eur Respir J 1999;14,659-668[Abstract]
23. Anderson, SD, Lambert, S, Brannan, JD, et al Laboratory protocol for exercise asthma to evaluate salbutamol given by two devices. Med Sci Sports Exer 2001;33,893-900[Medline]
24. Hurwitz, KM, Argyros, GJ, Roach, JM, et al Interpretation of eucapnic voluntary hyperventilation in the diagnosis of asthma. Chest 1995;108,1240-1245[Abstract/Free Full Text]
25. Bar-Yishay, E, Ben-Dov, I, Godfrey, S Refractory period after hyperventilation-induced asthma. Am Rev Respir Dis 1983;127,572-574[Medline]
26. Rosenthal, RR, Laube, BL, Hood, DB, et al Analysis of refractory period after exercise and eucapnic voluntary hyperventilation challenge. Am Rev Respir Dis 1990;141,368-372[Medline]
27. Argyros, GJ, Roach, JM, Hurwitz, KM, et al The refractory period after eucapnic voluntary hyperventilation challenge and its effect on challenge technique. Chest 1995;108,419-424[Abstract/Free Full Text]
28. O’Byrne, PM, Ryan, G, Morris, M, et al Asthma induced by cold air and its relation to nonspecific bronchial hyperresponsiveness to methacholine. Am Rev Respir Dis 1982;125,281-285[Medline]
29. Silverman, M, Anderson, SD Standardization of exercise tests in asthmatic children. Arch Dis Child 1972;47,882-889[ISI][Medline]
30. Rundell, KW, Spiering, BA, Judelson, DA, et al Bronchoconstriction during cross-country skiing: is there really a refractory period? Med Sci Sports Exerc 2003;35,18-26[ISI][Medline]
31. Spiering, BA, Judelson, DA, Rundell, KW Standardized estimated ventilation for eucapnic voluntary hyperventilation: an evaluation [abstract]. Med Sci Sports Exer 2002;34,S52
32. McFadden, ER, Lenner, KA, Strohl, KP Postexertional airway rewarming and thermally induced asthma. J Clin Invest 1986;78,18-25[ISI][Medline]
33. Anderson, SD, Daviskas, E. The mechanism of exercise-induced asthma is.... J Allergy Clin Immunol 2000;106,453-459[CrossRef][ISI][Medline]
34. McFadden, ER, Nelson, JA, Skowronski, ME, et al Thermally induced asthma and airway drying. Am J Respir Crit Care Med 1999;160,221-226[Abstract/Free Full Text]
35. Anderson, SD, Daviskas, E Pathophysiology of exercise-induced asthma. Weiler, J eds. Allergic and respiratory disease in sports medicine 1997,87-114 Marcel Dekker. New York, NY:
36. Anderson, SD, Daviskas, E Airway drying and exercise induced asthma. McFadden, ER eds. Exercise induced asthma: lung biology in health and disease 1999,77-113 Marcel Dekker. New York, NY:

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