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Clinical Investigations: PULMONARY FUNCTION TESTING |

Sensitivity of Exercise Testing for Asthma in Adolescents Is Halved in the Summer* FREE TO VIEW

Shmuel Goldberg, MD; Shepard Schwartz, MD; Gabriel Izbicki, MD; Ronit Belisha Hamami, BSc; Elie Picard, MD
Author and Funding Information

*From the Departments of Pediatric Pulmonology (Drs. Goldberg and Picard, and Ms. Hamani) and Pediatrics (Dr. Schwartz), Institute of Pulmonology (Dr. Izbicki), Shaare Zedek Medical Center, Jerusalem.

Correspondence to: Shmuel Goldberg, MD, Pediatric Respiratory Medicine, Shaare Zedek Medical Center, PO Box 3235, Jerusalem 91301, Israel; e-mail: pedpul@szmc.org.il



Chest. 2005;128(4):2408-2411. doi:10.1378/chest.128.4.2408
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Study objectives: The exercise test is one of the most widely used challenge tests for asthma. It is not clear if the sensitivity of this test is lower when patients with asthma are not symptomatic. Since asthma activity is season dependent, with lower activity in the summer, we sought to determine if the percentage of positive exercise test results for asthma is lower in the summer as well.

Design: In this retrospective study, the proportion of positive exercise test results for asthma during each of the four seasons of the year, over a 5-year period, was compared.

Setting: The study was conducted at the pediatric respiratory clinic and pulmonary function laboratory of Shaare Zedek Medical Center.

Participants: The study group consisted of 532 consecutive patients, all 17 years of age, who were referred for exercise testing for evaluation of suspected asthma. All had normal baseline FEV1 levels, and none received maintenance asthma treatment.

Measurements and results: Spirometry was performed before and after a standard exercise regimen. A decrease of ≥ 10% in FEV1 after exercise was considered positive; 141 patients (26%) had a positive test result. The percentage of positive results in the summer (July to September quartile) was 12.9%, less than half the percentage of positive results during any of the other three quartiles (January to March, 28.9%, p < 0.05; April to June, 30.6%, p < 0.05; October to December, 29.1%, p < 0.05).

Conclusions: This study shows that the percentage of positive exercise challenge test results in the summer is half that of any other season. It is likely that the lower percentage of positive results for asthma in the summer reflects the lower sensitivity of the test during this season due to decreased asthma activity. We suggest performing exercise challenge testing only when patients are symptomatic. Physicians caring for patients with symptoms suggestive of exercise-induced asthma whose exercise test results are negative while asymptomatic should consider repeat exercise testing when their patients are symptomatic.

Figures in this Article

The diagnosis of asthma is based on clinical signs and symptoms as well as the presence of reversible airway obstruction demonstrated by pulmonary function testing. In questionable cases, a challenge test, which detects airway hyperresponsiveness to various stimuli, may assist in establishing the diagnosis. The two most widely used challenge tests are the exercise test and the methacholine challenge test.1

Asthma morbidity varies with the season and is relatively low during the summer.23 The degree of airway hyperresponsiveness in asthmatic patients correlates well with the severity of clinical symptoms.45 Hence, we hypothesized that results of challenge testing may be season dependent, with lower sensitivity in the summer. If this is the case, a negative challenge test result in the summer might not reliably exclude the diagnosis of exercise-induced asthma. The aim of this study was to assess seasonal variability in the sensitivity of exercise testing in a large group of 17-year-old patients.

Patients

We retrospectively studied a group of 17-year-old patients who underwent exercise testing during a 6-year period (1998 to 2003). All patients were referred by army physicians for evaluation of suspected asthma prior to military recruitment. Only patients with a normal baseline FEV1 (≥ 80%) and who did not receive maintenance asthma treatment were tested. Patients were instructed not to take inhaled β2-agonist or anticholinergic agents for 24 h prior to being tested. Patients who had a recent viral infection were rescheduled for testing at least 1 month after convalescence.

Exercise Testing

Room temperature was set to 22 to 24°C throughout the year, with relative humidity of 40 to 50%. All exercise tests were performed by the same technician. Exercise testing was performed for 6 to 8 min on a treadmill at a speed of 3.4 to 7.3 miles per hour and at a slope of 10 to 15°, with maintenance of the heart rate at 80 to 90% of the predicted maximum for a minimum of 4 min. Spirometry was done before exercise and at 1, 3, 6, 10, and 15 min after completion of the exercise. The exercise test result was considered positive if FEV1 dropped ≥ 10% from baseline on any one of the postexercise spirometry evaluation.

All technically accepted exercise tests were included in the study. Determination regarding the adequacy of the studies was made by the same physician (S.G.), who was blind to the study date.

Statistical Analysis

Differences in the proportion of positive exercise test results between quartiles were assessed by χ2 test.

Of the 802 tests performed during the study period, 532 tests (66.3%, 517 male patients) were deemed adequate. Mean ± SD baseline FVC was 94.4 ± 10.8% of predicted, mean FEV1 was 93.5 ± 10.5% of predicted, and mean FEV1/FVC was 85.1 ± 8.0. After exercise, a reduction in FEV1 compared to baseline was seen in 466 patients (88%). Among 141 of those studied (26%), the FEV1 dropped by at least 10%.

Individual drops in FEV1 are plotted in Figure 1 according to the day each occurred during the calendar year. The number of exercise tests performed each month and the proportion of positive test results are presented in Table 1 . Relatively fewer tests were performed in August because the vacations of the technician were during this month. Figure 2 displays the percentage of positive test results during the different quartiles. The percentage of positive results in the summer (July to September quartile) was 12.9%, less than half the percentage of positive results during any of the other three quartiles. (January to March, 28.9%, p < 0.05; April to June, 30.6%, p < 0.05; October to December, 29.1%, p < 0.05; Table 2 ).

This study shows that the proportion of positive exercise test results for asthma in the summer is less than half that of any other season. This work was done in adolescents, most of whom were male, with a normal FEV1.

It appears that the seasonal variability in the sensitivity of exercise testing correlates well with the seasonal variability in asthma activity. It is well known that asthma morbidity is season dependent. The highest number of emergency department visits for asthma occur in the fall1 or winter,3,6 and the fewest are in the summer.2,6Seasonal variability in asthma activity is likely related to seasonal changes in the prevalence of asthma triggers. Major triggers of asthma activity include exposure to allergens,7 air pollutants,3,8 low temperature,3 and viral infections.9 None of these triggers peak in Israel during the summer. Airborne pollens peak in Israel during the spring.6,10 The concentration of major air pollutants such as nitrogen oxides and sulfur dioxide are indeed lower in Israel during the summer compared to any other season.6 The highest temperatures in Israel are recorded during the summer months.6 Infection rates from respiratory viruses such as respiratory syncytial virus and influenza are lowest in summer.9 Thus, the relative absence of asthma triggers during the summer produces less asthma activity during this season and, consequently, lower sensitivity of exercise testing.

Previous studies have also detected a correlation between season and results of exercise testing. In Finland, 10 nonallergic asthmatic men sustained a 50% greater decrease in FEV1 after outdoor exercise in the winter compared to the spring.11In another study12 from Finland performed on elite runners, 9 of 41 runners (22%) who underwent challenge in subzero temperatures in the winter had a positive exercise test results only during the winter.

In a study13conducted in Ghana of 1,095 students, 1.55% of the students (17 children) had a positive response to 6 min of outdoor free running during the wet season, compared to 3.1% in the dry season. In a Korean study,14 69 subjects with perennial asthma performed outdoor free running tests. The percentage of positive test results in the winter (84%) was significantly higher than that in the summer (50%).

In all of these studies, the exercise test was performed outdoors. It is possible that the cold ambient temperature, and possibly other immediately acting environmental factors, accounted for the higher proportion of positive exercise test results during the winter. In contrast, in the present study all exercise tests were done under constant temperature and humidity inside a pulmonary function test laboratory, eliminating a synergistic effect of cold ambient temperature or other environmental factors on test results.

Exercise testing is one of several indirect challenge tests in which the challenge induces release of inflammatory mediators from different cells in the airways, which in turn induce smooth-muscle contraction. Other indirect tests include challenge with adenosine monophosphate, mannitol, distilled water, or hypertonic saline solution.15 A positive response to an indirect test is consistent with active airway inflammation, and treatment decreases the response to these tests.1516 Therefore, it can be anticipated that the exercise test result might become negative when asthma is not active.

The relationship between asthma activity and challenge test results might be different with direct provocation tests. With these tests, a pharmacologic agent such as methacholine acts directly on the smooth muscle, causing it to contract. A positive response to these tests is not specific for asthma, and may also occur in adults who had asthma in childhood but are currently asymptomatic.15 Studies4,7,1720 investigating the effect of asthma activity on methacholine challenge test have led to conflicting results. Benckhuijsen et al7 found that patients with asthma and house dust mite allergy who lived for 1 month in a hypoallergenic area experienced a decreased response to exercise and adenosine monophosphate challenge, with no change in bronchial hyperactivity in response to methacholine. However, several other studies4,1720 did show a decreased response to methacholine in patients with allergic asthma during low allergic load periods.

What is the proper management of a patient with symptoms suggesting exercise-induced asthma with a negative challenge test result while asymptomatic? One option is to perform other direct or indirect challenge tests with methacholine or adenosine monophosphate for example, both of which are substantially more sensitive for asthma than exercise testing (98% and 95.5% vs 65%, respectively21). These test results might still be positive even when asthma is not active. If other challenge tests too are negative, repeating the tests while asthma is clinically active should be considered. With certain patients, such as military recruits, athletes, and police or firefighters who may perform exertional activity as part of their work, the detection of exercise-induced asthma specifically is more imperative. In such cases, when a patient with symptoms suggesting exercise-induced asthma has a negative test result while asymptomatic, repeating the test while symptomatic might be the only way to establish the diagnosis.

There are several limitations to this study. It is a retrospective study, there is a lack of clinical data concerning patient symptoms, no group was tested both in the summer and winter months to determine intraindividual differences, and the study sample included mostly 17-year-old men who were identified by an active screening process. Hence, extrapolation of our finding to the general population with suspected asthma should be done with caution.

In summary, we have demonstrated that the sensitivity of an exercise test in the summer is half compared to any other season. The probable reason for this phenomenon, although not proved in the current study, is the relative lack of asthma activity in the summer, and hence may as well occur in asthmatic patients whenever their asthma is not active, not necessarily in the summer. Thus, performing challenge testing while asthma is clinically inactive increases the chance of a false-negative result. In the “real world,” the time lapse between the beginning of symptoms to the first appointment with the pulmonologist, and subsequently between that appointment to the challenge test, might be several months. In a patient with intermittent symptoms, asthma activity may subside by then, and the challenge test may yield false-negative results.

We therefore suggest performing asthma challenge testing only when patients are symptomatic. Physicians caring for patients with symptoms suggestive of exercise-induced with negative exercise test results while asymptomatic should consider a repeat exercise test when symptoms are present.

All work was done in Shaare Zedek Medical Center.

Figure Jump LinkFigure 1. Individual drops in FEV1 according to the day each occurred during the calendar year.Grahic Jump Location
Table Graphic Jump Location
Table 1. Number of Exercise Tests in Each Month and the Proportion of Positive Results
Figure Jump LinkFigure 2. Percentage of positive test results during the different quartiles. The percentage of positive test results in the summer (July to September quartile) was 12.9%, less than half the percentage of positive results during any of the other three quartiles (p < 0.05).Grahic Jump Location
Table Graphic Jump Location
Table 2. Number of Exercise Tests in Each Quartile and the Proportion of Positive Test Results
. American Thoracic Society. (2000) Guidelines for methacholine and exercise challenge testing-1999.Am J Respir Crit Care Med161,309-329. [PubMed]
 
Silverman, RA, Stevenson, L, Hastings, HM Age-related seasonal patterns of emergency department visits for acute asthma in an urban environment.Ann Emerg Med2003;42,577-586. [CrossRef] [PubMed]
 
Rossi, OV, Kinnula, VL, Tienari, J, et al Association of severe asthma attacks with weather, pollen, and air pollutants.Thorax1993;48,244-248. [CrossRef] [PubMed]
 
Boulet, LP, Cartier, A, Thomson, NC, et al Asthma and increases in nonallergic bronchial responsiveness from seasonal pollen exposure.J Allergy Clin Immunol1983;71,399-406. [CrossRef] [PubMed]
 
Platts-Mills, TA, Tovey, ER, Mitchell, EB, et al Reduction of bronchial hyperactivity during prolonged allergen avoidance.Lancet1982;25,675-678
 
Garty, BZ, Kosman, E, Ganor, E, et al Emergency room visits of asthmatic children, relation to air pollution, weather, and airborne allergens.Ann Allergy Asthma Immunol1998;81,563-570. [CrossRef] [PubMed]
 
Benckhuijsen, J, van den Bos, JW, van Velzen, E, et al Differences in the effect of allergen avoidance on bronchial hyperresponsiveness as measured by methacholine, adenosine 5′-monophosphate, and exercise in asthmatic children.Pediatr Pulmonol1996;22,147-153. [CrossRef] [PubMed]
 
Perry, GB, Chai, H, Dickey, DW, et al Effects of particulate air pollution on asthmatics.Am J Public Health1983;73,50-56. [CrossRef] [PubMed]
 
O’Brien, MA, Uyeki, TM, Shay, DK, et al Incidence of outpatient visits and hospitalizations related to influenza in infants and young children.Pediatrics2004;113,585-593. [CrossRef] [PubMed]
 
Keynan, N, Waisel, Y, Shomer-Ilan, A, et al Annual variations of air-born pollen in the coastal plain of Israel.Grana1991;30,477-480. [CrossRef]
 
Karjalainen, J, Lindqvist, A, Laitinen, LA Seasonal variability of exercise-induced asthma especially outdoors: effect of birch pollen allergy.Clin Exp Allergy1989;19,273-278. [CrossRef] [PubMed]
 
Helenius, IJ, Tikkanen, HO, Haahtela, T Occurrence of exercise induced bronchospasm in elite runners: dependence on atopy and exposure to cold air and pollen.Br J Sports Med1998;32,125-129. [CrossRef] [PubMed]
 
Addo-Yobo, EO, Custovic, A, Taggart, SC, et al Seasonal variability in exercise test responses in Ghana.Pediatr Allergy Immunol2002;13,303-306. [CrossRef] [PubMed]
 
Koh, YI, Choi, IS Seasonal difference in the occurrence of exercise-induced bronchospasm in asthmatics: dependence on humidity.Respiration2002;69,38-45. [CrossRef] [PubMed]
 
Anderson, SD, Brannan, JD, Chan, HK Use of aerosols for bronchial provocation testing in the laboratory: where we have been and where we are going.J Aerosol Med2002;15,313-324. [CrossRef] [PubMed]
 
Jonasson, G, Carlsen, KH, Hultquist, C Low-dose budesonide improves exercise-induced bronchospasm in schoolchildren.Pediatr Allergy Immunol2000;11,120-125. [CrossRef] [PubMed]
 
Riccioni, G, Di Stefano, F, De Benedictis, M, et al Seasonal variability of non-specific bronchial responsiveness in asthmatic patients with allergy to house dust mites.Allergy Asthma Proc2001;22,5-9. [CrossRef] [PubMed]
 
Platts-Mills, TA, Tovey, ER, Mitchell, EB, et al Reduction of bronchial hyperreactivity during prolonged allergen avoidance.Lancet1982;25,675-678
 
Martin-Munoz, F, Moreno-Ancillo, A, Pestana, JA, et al Atopy and bronchial hyperresponsiveness in pure extrinsic childhood asthma.J Investig Allergol Clin Immunol1997;7,229-233. [PubMed]
 
Prieto, L, Berto, JM, Lopez, M, et al Modifications of PC20and maximal degree of airway narrowing to methacholine after pollen season in pollen sensitive asthmatic patients.Clin Exp Allergy1993;23,172-178. [CrossRef] [PubMed]
 
Avital, A, Godfrey, S, Springer, C Exercise, methacholine, and adenosine 5′-monophosphate challenges in children with asthma: relation to severity of the disease.Pediatr Pulmonol2000;30,207-214. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Individual drops in FEV1 according to the day each occurred during the calendar year.Grahic Jump Location
Figure Jump LinkFigure 2. Percentage of positive test results during the different quartiles. The percentage of positive test results in the summer (July to September quartile) was 12.9%, less than half the percentage of positive results during any of the other three quartiles (p < 0.05).Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Number of Exercise Tests in Each Month and the Proportion of Positive Results
Table Graphic Jump Location
Table 2. Number of Exercise Tests in Each Quartile and the Proportion of Positive Test Results

References

. American Thoracic Society. (2000) Guidelines for methacholine and exercise challenge testing-1999.Am J Respir Crit Care Med161,309-329. [PubMed]
 
Silverman, RA, Stevenson, L, Hastings, HM Age-related seasonal patterns of emergency department visits for acute asthma in an urban environment.Ann Emerg Med2003;42,577-586. [CrossRef] [PubMed]
 
Rossi, OV, Kinnula, VL, Tienari, J, et al Association of severe asthma attacks with weather, pollen, and air pollutants.Thorax1993;48,244-248. [CrossRef] [PubMed]
 
Boulet, LP, Cartier, A, Thomson, NC, et al Asthma and increases in nonallergic bronchial responsiveness from seasonal pollen exposure.J Allergy Clin Immunol1983;71,399-406. [CrossRef] [PubMed]
 
Platts-Mills, TA, Tovey, ER, Mitchell, EB, et al Reduction of bronchial hyperactivity during prolonged allergen avoidance.Lancet1982;25,675-678
 
Garty, BZ, Kosman, E, Ganor, E, et al Emergency room visits of asthmatic children, relation to air pollution, weather, and airborne allergens.Ann Allergy Asthma Immunol1998;81,563-570. [CrossRef] [PubMed]
 
Benckhuijsen, J, van den Bos, JW, van Velzen, E, et al Differences in the effect of allergen avoidance on bronchial hyperresponsiveness as measured by methacholine, adenosine 5′-monophosphate, and exercise in asthmatic children.Pediatr Pulmonol1996;22,147-153. [CrossRef] [PubMed]
 
Perry, GB, Chai, H, Dickey, DW, et al Effects of particulate air pollution on asthmatics.Am J Public Health1983;73,50-56. [CrossRef] [PubMed]
 
O’Brien, MA, Uyeki, TM, Shay, DK, et al Incidence of outpatient visits and hospitalizations related to influenza in infants and young children.Pediatrics2004;113,585-593. [CrossRef] [PubMed]
 
Keynan, N, Waisel, Y, Shomer-Ilan, A, et al Annual variations of air-born pollen in the coastal plain of Israel.Grana1991;30,477-480. [CrossRef]
 
Karjalainen, J, Lindqvist, A, Laitinen, LA Seasonal variability of exercise-induced asthma especially outdoors: effect of birch pollen allergy.Clin Exp Allergy1989;19,273-278. [CrossRef] [PubMed]
 
Helenius, IJ, Tikkanen, HO, Haahtela, T Occurrence of exercise induced bronchospasm in elite runners: dependence on atopy and exposure to cold air and pollen.Br J Sports Med1998;32,125-129. [CrossRef] [PubMed]
 
Addo-Yobo, EO, Custovic, A, Taggart, SC, et al Seasonal variability in exercise test responses in Ghana.Pediatr Allergy Immunol2002;13,303-306. [CrossRef] [PubMed]
 
Koh, YI, Choi, IS Seasonal difference in the occurrence of exercise-induced bronchospasm in asthmatics: dependence on humidity.Respiration2002;69,38-45. [CrossRef] [PubMed]
 
Anderson, SD, Brannan, JD, Chan, HK Use of aerosols for bronchial provocation testing in the laboratory: where we have been and where we are going.J Aerosol Med2002;15,313-324. [CrossRef] [PubMed]
 
Jonasson, G, Carlsen, KH, Hultquist, C Low-dose budesonide improves exercise-induced bronchospasm in schoolchildren.Pediatr Allergy Immunol2000;11,120-125. [CrossRef] [PubMed]
 
Riccioni, G, Di Stefano, F, De Benedictis, M, et al Seasonal variability of non-specific bronchial responsiveness in asthmatic patients with allergy to house dust mites.Allergy Asthma Proc2001;22,5-9. [CrossRef] [PubMed]
 
Platts-Mills, TA, Tovey, ER, Mitchell, EB, et al Reduction of bronchial hyperreactivity during prolonged allergen avoidance.Lancet1982;25,675-678
 
Martin-Munoz, F, Moreno-Ancillo, A, Pestana, JA, et al Atopy and bronchial hyperresponsiveness in pure extrinsic childhood asthma.J Investig Allergol Clin Immunol1997;7,229-233. [PubMed]
 
Prieto, L, Berto, JM, Lopez, M, et al Modifications of PC20and maximal degree of airway narrowing to methacholine after pollen season in pollen sensitive asthmatic patients.Clin Exp Allergy1993;23,172-178. [CrossRef] [PubMed]
 
Avital, A, Godfrey, S, Springer, C Exercise, methacholine, and adenosine 5′-monophosphate challenges in children with asthma: relation to severity of the disease.Pediatr Pulmonol2000;30,207-214. [CrossRef] [PubMed]
 
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