The need for standardization in exercise challenge testing for exercise-induced asthma/bronchoconstriction
2010; Elsevier BV; Volume: 126; Issue: 4 Linguagem: Inglês
10.1016/j.jaci.2010.07.032
ISSN1097-6825
AutoresMichael K. Stickland, Carol H Spooner, Donna M Dryden, Brian H. Rowe,
Tópico(s)Inhalation and Respiratory Drug Delivery
ResumoTo the Editor: Objective measurement of lung function based on FEV1 before and after exercise is required for valid diagnosis of exercise-induced asthma (EIA) and exercise-induced bronchoconstriction (EIB). Airway drying caused by increased minute ventilation during exercise is considered the primary trigger for EIA/EIB,1Rundell K.W. Slee J.B. Exercise and other indirect challenges to demonstrate asthma or exercise-induced bronchoconstriction in athletes.J Allergy Clin Immunol. 2008; 122: 238-246Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar and the magnitude of airway drying varies based on the exercise protocol and environmental conditions. The American Thoracic Society (ATS) published guidelines for conducting a standardized exercise challenge test (ECT) that take into account the exercise protocol, as well as environmental conditions.2Crapo R.O. Casaburi R. Coates A.L. Enright P.L. Hankinson J.L. Irvin C.G. et al.Guidelines for methacholine and exercise challenge testing 1999.Am J Respir Crit Care Med. 2000; 161: 309-329Crossref PubMed Scopus (2250) Google Scholar Since these guidelines were released, a variety of alternate tests have been proposed to objectively diagnose EIA/EIB, including a methacholine challenge, a sport/venue-specific challenge, eucapnic voluntary hyperpnea (EVH), a free running asthma screening test, and mannitol provocation. To determine the diagnostic accuracy of these alternate tests, they are often compared with a treadmill or cycle ergometer ECT. It is imperative that the ECT protocol be in accordance with ATS guidelines. Indeed, the ATS-ECT guidelines consider the ECT a dose-response test and that delivery of the proper dose and measurement of the response must be accurate for a valid test.2Crapo R.O. Casaburi R. Coates A.L. Enright P.L. Hankinson J.L. Irvin C.G. et al.Guidelines for methacholine and exercise challenge testing 1999.Am J Respir Crit Care Med. 2000; 161: 309-329Crossref PubMed Scopus (2250) Google Scholar Failure to adhere to ECT guidelines would influence the accurate determination of sensitivity and specificity of the alternate diagnostic test. In a recent review3Dryden DM, Spooner CH, Stickland MK, Vandermeer B, Tjosvold L, Bialy L, et al. Exercise-induced bronchoconstriction and asthma. Evidence Report/Technology Assessment no. 189 (Prepared by the University of Alberta Evidence-based Practice Center under Contract No. 290-2007-10021-I) AHRQ Publication No. 10-E001. Available at: http://www.ahrq.gov/clinic/tp/eibeiatp.htm. Accessed April 10, 2010.Google Scholar we found substantial heterogeneity in sensitivity/specificity of these alternate tests in predicting EIA/EIB, suggesting other variables might be a factor. The current project evaluated the ECT protocols used in these studies (either as reported or referenced) to determine the level of adherence to the 1999 ATS-ECT guidelines.2Crapo R.O. Casaburi R. Coates A.L. Enright P.L. Hankinson J.L. Irvin C.G. et al.Guidelines for methacholine and exercise challenge testing 1999.Am J Respir Crit Care Med. 2000; 161: 309-329Crossref PubMed Scopus (2250) Google Scholar The full details of the systematic review have been published elsewhere.3Dryden DM, Spooner CH, Stickland MK, Vandermeer B, Tjosvold L, Bialy L, et al. Exercise-induced bronchoconstriction and asthma. Evidence Report/Technology Assessment no. 189 (Prepared by the University of Alberta Evidence-based Practice Center under Contract No. 290-2007-10021-I) AHRQ Publication No. 10-E001. Available at: http://www.ahrq.gov/clinic/tp/eibeiatp.htm. Accessed April 10, 2010.Google Scholar An overview of study selection, search details, and inclusion/exclusion criteria, can be found in Appendix E1, Fig E1, and Table E1, Table E2 in this article's Online Repository at www.jacionline.org. Using the ATS guidelines, we examined 12 criteria that were deemed most important for ECT quality: (1) diagnostic criteria of EIA/EIB (≥10% to 15% decrease in FEV1); (2) pulmonary medications withdrawn as outlined by guidelines; (3) no vigorous exercise 4 hours before the ECT; (4) 4 hours separating exercise challenges; (5) treadmill testing with target intensity reached within 2 to 4 minutes (cycle = work rate set at 60% of target ventilation in the first minute and then increased to target heart rate [HR] by the fourth minute); (6) HR or minute ventilation of 80% to 90% or 40% to 60%, respectively, of predicted maximum; (7) target HR or minute ventilation maintained for 4 to 6 minutes; (8) relative humidity (RH) of less than 50%; (9) air temperature of 20°C to 25°C; (10) use of nose clip to force mouth breathing; (11) measurement of spirometry up to 15 to 20 minutes after ECT provided values are returning to baseline; and (12) use of the higher of at least 2 acceptable FEV1 values. Two authors (M. K. S. and C. H. S.) independently reviewed the extracted data and agreed on 106 (98%) of 108 data points. Of note, the ATS-ECT guidelines acknowledge that there remains controversy regarding a cutoff of 10% or 15% in FEV1, and therefore a reduction of 15% was also considered consistent with ATS guidelines. When required, the percentage of age-predicted maximum HR was calculated from reported HR and age by using a standard age-predicted maximal HR formula (220 − age). Room air was assumed to be less than 25°C, but RH was not assumed to be less than 50% in air-conditioned environments. Nine studies were reviewed and are summarized in Table E3, Table E4 (available in this article's Online Repository at www.jacionline.org).4Kersten E.T. Driessen J.M. van der Berg J.D. Thio B.J. Mannitol and exercise challenge tests in asthmatic children.Pediatr Pulmonol. 2009; 44: 655-661Crossref PubMed Scopus (37) Google Scholar, 5Rundell K.W. Spiering B.A. Baumann J.M. Evans T.M. Effects of montelukast on airway narrowing from eucapnic voluntary hyperventilation and cold air exercise.Br J Sports Med. 2005; 39: 232-236Crossref PubMed Scopus (52) Google Scholar, 6Souza A.C.T.G. Pereira C.A.C. Bronchial provocation tests using methacholine, cycle ergometer exercise and free running in children with intermittent asthma.J Pediatr (Rio J). 2005; 81: 65-72Crossref PubMed Google Scholar, 7Anderson S.D. Charlton B. Weiler J.M. Nichols S. Spector S.L. Pearlman D.S. et al.Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthma.Respir Res. 2009; 10: 4Crossref PubMed Scopus (140) Google Scholar, 8Dickinson J.W. Whyte G.P. McConnell A.K. Harries M.G. Screening elite winter athletes for exercise induced asthma: a comparison of three challenge methods.Br J Sports Med. 2006; 40: 179-182Crossref PubMed Scopus (65) Google Scholar, 9Castricum A. Holzer K. Brukner P. Irving L. The role of the bronchial provocation challenge tests in the diagnosis of exercise induced bronchoconstriction in elite swimmers.Br J Sports Med. 2010; 44: 736-740Crossref PubMed Scopus (26) Google Scholar, 10Henriksen A.H. Tveit K.H. Holmen T.L. Sue-Chu M. Bjermer L. A study of the association between exercise-induced wheeze and exercise versus methacholine-induced bronchoconstriction in adolescents.Pediatr Allergy Immunol. 2002; 13: 203-208Crossref PubMed Scopus (21) Google Scholar, 11Verges S. Devouassoux G. Flore P. Rossini E. Fior-Gozlan M. Levy P. et al.Bronchial hyperresponsiveness, airway inflammation, and airflow limitation in endurance athletes.Chest. 2005; 127: 1935-1941Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar, 12Pedersen L. Winther S. Backer V. Anderson S.D. Larsen K.R. Airway responses to eucapnic hyperpnea, exercise, and methacholine in elite swimmers.Med Sci Sports Exerc. 2008; 40: 1567-1572Crossref PubMed Scopus (46) Google Scholar Combined, only 1 (11%) article followed all ATS-ECT guidelines.4Kersten E.T. Driessen J.M. van der Berg J.D. Thio B.J. Mannitol and exercise challenge tests in asthmatic children.Pediatr Pulmonol. 2009; 44: 655-661Crossref PubMed Scopus (37) Google Scholar Three studies were rated as “unclear” because they failed to detail exercise intensity5Rundell K.W. Spiering B.A. Baumann J.M. Evans T.M. Effects of montelukast on airway narrowing from eucapnic voluntary hyperventilation and cold air exercise.Br J Sports Med. 2005; 39: 232-236Crossref PubMed Scopus (52) Google Scholar or no vigorous exercise was conducted before the ECT.6Souza A.C.T.G. Pereira C.A.C. Bronchial provocation tests using methacholine, cycle ergometer exercise and free running in children with intermittent asthma.J Pediatr (Rio J). 2005; 81: 65-72Crossref PubMed Google Scholar, 7Anderson S.D. Charlton B. Weiler J.M. Nichols S. Spector S.L. Pearlman D.S. et al.Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthma.Respir Res. 2009; 10: 4Crossref PubMed Scopus (140) Google Scholar Based on the published methodology, we determined that the remaining 5 (56%) studies did not follow ATS-ECT guidelines: room temperature13Avital A. Godfrey S. Springer C. Exercise, methacholine, and adenosine 5'-monophosphate challenges in children with asthma: relation to severity of the disease.Pediatr Pulmonol. 2000; 30: 207-214Crossref PubMed Scopus (58) Google Scholar or RH8Dickinson J.W. Whyte G.P. McConnell A.K. Harries M.G. Screening elite winter athletes for exercise induced asthma: a comparison of three challenge methods.Br J Sports Med. 2006; 40: 179-182Crossref PubMed Scopus (65) Google Scholar, 9Castricum A. Holzer K. Brukner P. Irving L. The role of the bronchial provocation challenge tests in the diagnosis of exercise induced bronchoconstriction in elite swimmers.Br J Sports Med. 2010; 44: 736-740Crossref PubMed Scopus (26) Google Scholar, 13Avital A. Godfrey S. Springer C. Exercise, methacholine, and adenosine 5'-monophosphate challenges in children with asthma: relation to severity of the disease.Pediatr Pulmonol. 2000; 30: 207-214Crossref PubMed Scopus (58) Google Scholar, 14Rundell K.W. Wilber R.L. Szmedra L. Jenkinson D.M. Mayers L.B. Im J. Exercise-induced asthma screening of elite athletes: field versus laboratory exercise challenge.Med Sci Sports Exerc. 2000; 32: 309-316Crossref PubMed Scopus (173) Google Scholar was too high, a nose clip was not used,10Henriksen A.H. Tveit K.H. Holmen T.L. Sue-Chu M. Bjermer L. A study of the association between exercise-induced wheeze and exercise versus methacholine-induced bronchoconstriction in adolescents.Pediatr Allergy Immunol. 2002; 13: 203-208Crossref PubMed Scopus (21) Google Scholar the ECT duration was too long,11Verges S. Devouassoux G. Flore P. Rossini E. Fior-Gozlan M. Levy P. et al.Bronchial hyperresponsiveness, airway inflammation, and airflow limitation in endurance athletes.Chest. 2005; 127: 1935-1941Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar or graded exercise was used.12Pedersen L. Winther S. Backer V. Anderson S.D. Larsen K.R. Airway responses to eucapnic hyperpnea, exercise, and methacholine in elite swimmers.Med Sci Sports Exerc. 2008; 40: 1567-1572Crossref PubMed Scopus (46) Google Scholar That the majority of studies failed to follow ATS-ECT guidelines is a significant concern when interpreting results of comparisons between an ECT and alternate diagnostic airway challenges. Because airway drying caused by increased minute ventilation is considered the primary trigger for EIA/EIB,1Rundell K.W. Slee J.B. Exercise and other indirect challenges to demonstrate asthma or exercise-induced bronchoconstriction in athletes.J Allergy Clin Immunol. 2008; 122: 238-246Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar any protocol in which exercise intensity is not appropriate would affect minute ventilation and corresponding stimulus for EIA/EIB. The guidelines state that both graded exercise tests and prolonged ECT protocols could cause refraction. Similarly, when challenges are conducted in a warm/humid environment, the amount of airway drying and stimulus for EIA/EIB would be diminished. Of note, although this report only includes studies published after the guidelines, we found that studies published before 2000 were similarly inconsistent with documentation of ECT protocols (data not shown). Lack of adherence to ATS-ECT guidelines would alter the severity of the ECT as an airway challenge and underestimate or overestimate the prevalence of EIA/EIB. For example, the EVH test is currently the challenge recommended by the International Olympic Committee's Medical Commission,1Rundell K.W. Slee J.B. Exercise and other indirect challenges to demonstrate asthma or exercise-induced bronchoconstriction in athletes.J Allergy Clin Immunol. 2008; 122: 238-246Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar, 15Anderson S.D. Brusasco V. Haahtela T. et al.Criteria for diagnosis of asthma, EIB and AHR for athletes: lessons from the Olympic games.in: Carlsen K.-H. Delgado L. Del Giacco S. Diagnosis, prevention and treatment of exercise-related asthma, respiratory and allergic disorders in sports. European Respiratory Society Journals Ltd, Wakefield (United Kingdom)2005: 44-66Crossref Google Scholar and although it is considered more sensitive than the ECT,1Rundell K.W. Slee J.B. Exercise and other indirect challenges to demonstrate asthma or exercise-induced bronchoconstriction in athletes.J Allergy Clin Immunol. 2008; 122: 238-246Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar, 15Anderson S.D. Brusasco V. Haahtela T. et al.Criteria for diagnosis of asthma, EIB and AHR for athletes: lessons from the Olympic games.in: Carlsen K.-H. Delgado L. Del Giacco S. Diagnosis, prevention and treatment of exercise-related asthma, respiratory and allergic disorders in sports. European Respiratory Society Journals Ltd, Wakefield (United Kingdom)2005: 44-66Crossref Google Scholar of the 4 studies comparing EVH with ECT, it cannot be confirmed that any of the ECT protocols adhered to ATS criteria. In this set of studies, graded exercise testing was used12Pedersen L. Winther S. Backer V. Anderson S.D. Larsen K.R. Airway responses to eucapnic hyperpnea, exercise, and methacholine in elite swimmers.Med Sci Sports Exerc. 2008; 40: 1567-1572Crossref PubMed Scopus (46) Google Scholar or RH was too high,8Dickinson J.W. Whyte G.P. McConnell A.K. Harries M.G. Screening elite winter athletes for exercise induced asthma: a comparison of three challenge methods.Br J Sports Med. 2006; 40: 179-182Crossref PubMed Scopus (65) Google Scholar, 9Castricum A. Holzer K. Brukner P. Irving L. The role of the bronchial provocation challenge tests in the diagnosis of exercise induced bronchoconstriction in elite swimmers.Br J Sports Med. 2010; 44: 736-740Crossref PubMed Scopus (26) Google Scholar both of which would reduce the severity of the ECT challenge. In 1 study5Rundell K.W. Spiering B.A. Baumann J.M. Evans T.M. Effects of montelukast on airway narrowing from eucapnic voluntary hyperventilation and cold air exercise.Br J Sports Med. 2005; 39: 232-236Crossref PubMed Scopus (52) Google Scholar is it likely that ATS-ECT guidelines were followed because the subjects were instructed to exercise at the highest intensity sustainable; however, there is no documentation of exercise intensity. Based on these studies, the sensitivity of EVH relative to the ECT conducted per ATS guidelines to detect EIA/EIB is unclear. Diagnostic testing research requires complete and accurate reporting so that bias, generalizability, and applicability of results can be evaluated by the reader.16Bossuyt P.M. Reitsma J.B. Bruns D.E. Gatsonis C.A. Glasziou P.P. Irwig L.M. et al.The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration.Ann Intern Med. 2003; 138: W1-W12Crossref PubMed Scopus (936) Google Scholar We did not contact authors for clarification when ECT protocols were not fully detailed, and therefore it is possible that in these cases the authors did indeed follow ATS guidelines; however, researchers are encouraged to adhere to ATS-ECT guidelines and clearly document this adherence within published articles. Furthermore, editors must accept the ATS-ECT guidelines as a minimum standard for all EIA/EIB articles. When studies fail to follow ATS-ECT guidelines, care should be taken when developing clinical practice guidelines for appropriate methods to diagnose EIA/EIB. We searched MEDLINE, EMBASE, EBM Reviews–Cochrane Central Register of Controlled Trials, AMED, PsycINFO, PASCAL, CINAHL, SPORTDiscus with Full Text, Academic Search Elite, Web of Science, BIOSIS Previews, PubMed, Scopus, the Medion Database of Diagnostic Reviews–University of Maastricht, and Proquest Dissertations and Theses (see Table E1 for the Medline search strategy). Two reviewers independently screened the search results (titles and abstracts) to determine whether a study met broad inclusion criteria. The full text of potentially relevant articles was retrieved, and 2 reviewers independently assessed each study by using a standard inclusion/exclusion form (see attached). Disagreements were resolved by discussion or through third-party adjudication, as needed. Relevant data extracted from included studies were extracted onto a paper form and checked by a second person (see Table E2). Tabled 1Diagnosis of EIB/EIA review: search strategy for Medline (OVID)Search date: November 20, 2008Number of results: 2,321MEDLINE, 1950 to November week 2, 20081. exp “Exercise Induced Asthma”/or exp Asthma, Exercise-Induced/2. (“induced bronchoconstriction” or “induced asthma” or “induced bronchospasm”).kw,ie,id,sh. and (exercise∗ or (train∗ and (military or army)) or fitness or “physical activity” or exertion or athlet∗ or sport∗).mp.3. (bronchoconstrict∗ or asthma∗ or antiasthma∗ or wheez∗ or (respiratory adj sound?) or (bronchial adj5 (spasm∗ or constrict∗)) or bronchospas∗ or “bronchial hyperreactivity” or “respiratory hypersensitivity”).mp.4. ((bronchial∗ or respiratory or airway∗ or lung∗) adj5 (hypersensitiv∗ or hyperreactiv∗ or allerg∗ or insufficiency)).mp.5. or/3-46. (EIB or EIA).ti,ab.7. ((exercise adj5 induced) or “exercised-induced” or (exercise adj5 challenge) or “exercise tolerance” or “physical exercise” or (train∗ and (military or army)) or fitness or “physical activity” or exertion or athlet∗ or sport∗).mp,jn. or exp Sports/or Exercise/8. or/6-79. and/5,810. or/1-2,911. (sensitiv∗ or diagnos∗ or predictive value∗ or probability).mp.12. (accurac∗ or specificity).tw.13. ((pre-test or post-test) adj probability).mp.14. likelihood ratio∗.mp.15. di.fs.16. ∗Diagnostic Accuracy/17. (mannitol or methacholine or MCT or EVH or eucapnic or hyperpnea∗ or FRAST or provocation or marker∗ or screen∗ or test∗).mp.18. or/11-1719. 18 and 1020. limit 19 to English language21. limit 20 to humanFRAST, Free running asthma screening test. Open table in a new tab FRAST, Free running asthma screening test. Tabled 1Inclusion criteria worksheet: diagnosis of EIB/EIA reviewReviewer ID:Date://2009Record ID:CriteriaYesNoUnclear1. ENGLISH LANGUAGE□□2. PUBLICATION TYPE a. Report of primary research□□□3. Study objective a. Must be to diagnose or confirm diagnosis of EIB□□□4. Study design a. Comparative study or…□□□ b. Single arm study (but results are compared to a previous standardized test (i.e. cannot just be a prevalence study)□□□5. Population a. >80% patients ≥6 years who are otherwise healthy (i.e., do not have bronchitis, COPD, cystic fibrosis, bronchiectasis, etc)□□□NOTE: participants may have asthma or suspected EIA/EIB6. index test (circle the test) a. One of the following diagnostic tests:□□□ i. Self-reported history ii. Self-reported symptoms diary iii. Methacholine challenge iv. Sport or venue specific exercise challenges v. Eucapnic (or normocapnic) voluntary hyperpnea vi. Free running asthma screening test (FRAST) vii. MannitolNOTE: if another testing method not listed above is used please flag as an “other” below and keep separate from excluded pile7. reference standard a. Standardized exercise challenge test (treadmill or cycle ergometry) that resulted in a drop in FEV1 ≥ 10% from baseline□□□8. outcome a. Numeric data sufficient to create a 2 × 2 table and/or calculation of sensitivity, specificity, positive and negative likelihood ratios.□□□Comments:REVIEWER'S DECISION: Include □ Exclude □ Unsure □ Other □FINAL DECISION: Include □ Exclude □ Unsure □NOTE: To exclude must have said “NO” for at least one of 1-8.COPD, Chronic obstructive pulmonary disease; MCT, methacholine challenge; FRAST, free running asthma screening test. Open table in a new tab COPD, Chronic obstructive pulmonary disease; MCT, methacholine challenge; FRAST, free running asthma screening test. Tabled 1Assessment of spirometry, medication withdrawal, and inspired air conditioning in 25 comparative ECT studies according to 1999 ATS recommendationsAuthor, y, tests compared≥10% to 15% Decrease in FEV1FEV1 up to 15-20 min2 FEV1 w/<0.2-L differenceStop medications before ECTRH <50%T <25°CMouth breathingHenricksen et al,10Henriksen A.H. Tveit K.H. Holmen T.L. Sue-Chu M. Bjermer L. A study of the association between exercise-induced wheeze and exercise versus methacholine-induced bronchoconstriction in adolescents.Pediatr Allergy Immunol. 2002; 13: 203-208Crossref PubMed Scopus (21) Google Scholar 2002, ECT vs MCHYesYesNRNRYesYesNoRundell et al,5Rundell K.W. Spiering B.A. Baumann J.M. Evans T.M. Effects of montelukast on airway narrowing from eucapnic voluntary hyperventilation and cold air exercise.Br J Sports Med. 2005; 39: 232-236Crossref PubMed Scopus (52) Google Scholar 2005,ECT vs EVHYesYesUnclear repeated only if technically unacceptableYesYesYesNRSouza and Pereira,6Souza A.C.T.G. Pereira C.A.C. Bronchial provocation tests using methacholine, cycle ergometer exercise and free running in children with intermittent asthma.J Pediatr (Rio J). 2005; 81: 65-72Crossref PubMed Google Scholar 2005, ECT vs MCH, ECT vs FRASTYesYesYesYesYesYesYesVerges et al,11Verges S. Devouassoux G. Flore P. Rossini E. Fior-Gozlan M. Levy P. et al.Bronchial hyperresponsiveness, airway inflammation, and airflow limitation in endurance athletes.Chest. 2005; 127: 1935-1941Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar 2005, ECT vs MCHYesYesNRYesYesYesYesDickinson et al,8Dickinson J.W. Whyte G.P. McConnell A.K. Harries M.G. Screening elite winter athletes for exercise induced asthma: a comparison of three challenge methods.Br J Sports Med. 2006; 40: 179-182Crossref PubMed Scopus (65) Google Scholar 2006, ECT vs sport/venue ECT vs EVHYes15 min afterNRYesNoRH 56%YesNRCastricum et al,9Castricum A. Holzer K. Brukner P. Irving L. The role of the bronchial provocation challenge tests in the diagnosis of exercise induced bronchoconstriction in elite swimmers.Br J Sports Med. 2010; 44: 736-740Crossref PubMed Scopus (26) Google Scholar 2008, ECT vs SS, ECT vs EVHYesNo10 min afterYesYesNoRH 61% ± 2%YesYesPedersen et al,12Pedersen L. Winther S. Backer V. Anderson S.D. Larsen K.R. Airway responses to eucapnic hyperpnea, exercise, and methacholine in elite swimmers.Med Sci Sports Exerc. 2008; 40: 1567-1572Crossref PubMed Scopus (46) Google Scholar 2008, ECT vs MCH, ECT vs sport/venue, ECT vs EVHYesYesYesYesNANRNRNRAnderson et al,7Anderson S.D. Charlton B. Weiler J.M. Nichols S. Spector S.L. Pearlman D.S. et al.Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthma.Respir Res. 2009; 10: 4Crossref PubMed Scopus (140) Google Scholar 2009, ECT vs MCH, ECT vs mannitolYesYesYesYesYesYesYesKersten et al,4Kersten E.T. Driessen J.M. van der Berg J.D. Thio B.J. Mannitol and exercise challenge tests in asthmatic children.Pediatr Pulmonol. 2009; 44: 655-661Crossref PubMed Scopus (37) Google Scholar 2009, ECT vs mannitolYesYesYesYesYesYesYesFRAST, Free running asthma screening test; HR, heart rate; MCH, methacholine challenge; NA, not applicable; NR, not reported; PEF, peak expiratory flow; T, temperature. Open table in a new tab FRAST, Free running asthma screening test; HR, heart rate; MCH, methacholine challenge; NA, not applicable; NR, not reported; PEF, peak expiratory flow; T, temperature. Tabled 1Assessment of prechallenge exercise avoidance, exercise challenge duration and intensity, and adherence to 2009 ATS recommendations in 25 comparative ECT studiesAuthor, y, tests comparedNo vigorous exercise 4 h before4 h Between exercise testsTarget intensity reached <4 minTarget intensity maintained 4-6 minIntensity: HR 80% to 90% or VE 40% to 60%Meets ATS criteriaHenricksen et al,10Henriksen A.H. Tveit K.H. Holmen T.L. Sue-Chu M. Bjermer L. A study of the association between exercise-induced wheeze and exercise versus methacholine-induced bronchoconstriction in adolescents.Pediatr Allergy Immunol. 2002; 13: 203-208Crossref PubMed Scopus (21) Google Scholar 2002, ECT vs MCHNRNAYesYesYesNo, no nose clipRundell et al,5Rundell K.W. Spiering B.A. Baumann J.M. Evans T.M. Effects of montelukast on airway narrowing from eucapnic voluntary hyperventilation and cold air exercise.Br J Sports Med. 2005; 39: 232-236Crossref PubMed Scopus (52) Google Scholar 2005, ECT vs EVHNRYesUnclearYesUnclear; instructed to go at highest intensity sustainableUnclear 2 parameters NR, 3 unclearSouza and Pereira,6Souza A.C.T.G. Pereira C.A.C. Bronchial provocation tests using methacholine, cycle ergometer exercise and free running in children with intermittent asthma.J Pediatr (Rio J). 2005; 81: 65-72Crossref PubMed Google Scholar 2005, ECT vs MCH, ECT vs FRASTNRYesYesYesYesUnclear 1 parameter NRVergeset al,11Verges S. Devouassoux G. Flore P. Rossini E. Fior-Gozlan M. Levy P. et al.Bronchial hyperresponsiveness, airway inflammation, and airflow limitation in endurance athletes.Chest. 2005; 127: 1935-1941Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar 2005, ECT vs MCHNRNAYesNo12-min durationYesNo Duration too longDickinson et al,8Dickinson J.W. Whyte G.P. McConnell A.K. Harries M.G. Screening elite winter athletes for exercise induced asthma: a comparison of three challenge methods.Br J Sports Med. 2006; 40: 179-182Crossref PubMed Scopus (65) Google Scholar 2006,ECT vs sport/venue, ECT vs EVHNRNRYesYesYesNo RH too highCastricum et al,9Castricum A. Holzer K. Brukner P. Irving L. The role of the bronchial provocation challenge tests in the diagnosis of exercise induced bronchoconstriction in elite swimmers.Br J Sports Med. 2010; 44: 736-740Crossref PubMed Scopus (26) Google Scholar 2008, ECT vs sport/venue, ECT vs EVHYesYesYesYesYesNo RH too highPedersen et al,12Pedersen L. Winther S. Backer V. Anderson S.D. Larsen K.R. Airway responses to eucapnic hyperpnea, exercise, and methacholine in elite swimmers.Med Sci Sports Exerc. 2008; 40: 1567-1572Crossref PubMed Scopus (46) Google Scholar 2008, ECT vs MCH, ECT vs sport/venue, ECT vs EVHNRYesNograded exerciseNoYesNo graded exerciseAnderson et al,7Anderson S.D. Charlton B. Weiler J.M. Nichols S. Spector S.L. Pearlman D.S. et al.Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthma.Respir Res. 2009; 10: 4Crossref PubMed Scopus (140) Google Scholar 2009, ECT vs MCH, ECT vs mannitolNRNAYesYesYesUnclear 1 parameter NRKersten et al,4Kersten E.T. Driessen J.M. van der Berg J.D. Thio B.J. Mannitol and exercise challenge tests in asthmatic children.Pediatr Pulmonol. 2009; 44: 655-661Crossref PubMed Scopus (37) Google Scholar 2009, ECT vs mannitolYesNAYesYesYesYesFRAST, Free running asthma screening test; HR, heart rate; MCH, methacholine challenge; NR, not reported; NA, not applicable; VE, minute ventilation. Open table in a new tab FRAST, Free running asthma screening test; HR, heart rate; MCH, methacholine challenge; NR, not reported; NA, not applicable; VE, minute ventilation.
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