In many asthmatic and some non-asthmatic children, strenuous exercise is followed by acute narrowing of the airways and consequent reduction in expiratory flow rates.¹ Abrupt changes in airway temperature and humidity during exercise are probably the initiating events. “Exercise induced bronchoconstriction” is a more accurate description, but the term “exercise induced asthma” (EIA) persists through common use.² Depending on the definitions and measurements used, exercise induced asthma is reported to affect 10–15% of the general population,³ but the prevalence is much higher among asthmatics (80–90%)⁴ and those with allergic rhinitis (30–40%).⁵

The condition is defined and quantified on the basis of changes in lung function measured before and after a standardised exercise test.⁶ Limited access to specific exercise testing facilities means that in general clinical practice, most diagnoses are based on exercise related respiratory symptoms reported by the child or parents. However, several authors have shown poor correlation between self-reported exercise symptoms and the results of specific exercise testing,^7–,⁹ with high frequencies of false positive and false negative results. Our own experience gained from a large referral paediatric clinic would also suggest that misdiagnosis (particularly over-diagnosis) of EIA is common.

In the absence of specific research, we investigated the diagnostic accuracy of EIA by prospectively studying a cohort of children referred to our clinic for investigation of poorly controlled EIA. In each case, the diagnosis of EIA made by the referring physician (and the apparent poor response to treatment) were entirely based on self-reported respiratory symptoms. Each child underwent a detailed history and clinical examination, followed by pulmonary function testing before and after a standardised treadmill exercise test.⁶ Since each case was primarily referred for a clinical opinion, we also provided, as far as possible, a diagnostic explanation for each child’s respiratory complaints based on the overall results of our assessment.

METHODS

RESULTS

Fifty two children were enrolled in the study; all completed the test protocol successfully. Exercise induced asthma had been diagnosed prior to referral in each case. All, except one child (98.1%) were taking regular respiratory medications (1.4±0.2 prescription drugs/day). Thirty seven (71.2%) had been referred to other consultants and 22 (42.3%) had had at least one investigation, but none had undergone an exercise test. None of the 52 children had abnormalities on auscultation at any time before or after exercise. The child with past hospitalisation for asthma had a positive exercise test, but even a history of oral corticosteroid use was of weak predictive value (2 of 6 had EIA). Demographic details are summarised in table 1⇑. Principal measured end-points are summarised by final diagnosis in table 2⇓.

• EIA: Despite the universal referral diagnosis of EIA, only eight children (15.4%) had a significant drop in FEV₁ (⩾10%)⁶ following standardised exercise testing. If a more rigorous cut-off of ⩾15%² had been chosen, only two children (3.8%) would have met the laboratory criteria for EIA.

• Poor physical fitness: Twelve children (23.1%) were unfit. Compared to controls, they had significantly lower endurance time (7.8±2.0 min v 10.0±0, p < 0.01) and treadmill speed (6.2±0.8 kph v 7.4±0.3, p < 0.01). Obesity was also significantly more common (6/12 v 0/8, p < 0.05). Post-exercise FEV₁ was normal.

• VCD/sigh dyspnoea: Fourteen children (26.9%) had vocal cord dysfunction; competitive athletes were overrepresented. Complaints of throat tightness and inability to take a full breath were common. Dysphonia and inspiratory stridor were reproducibly induced during exercise and pulmonary function testing. Post-exercise FEV₁ was normal, but it was sometimes difficult to obtain reproducible flow volume loops because of varying degrees of laryngeal constriction.

• Habit cough: Seven children (13.5%) had a tic-like, dry cough that varied from frequent “throat clearing” to a loud staccato bark. It was invariably present at rest but usually improved as exercise progressed. Post-exercise FEV₁ was normal in all cases.

• No diagnosis: Eleven children (21.1%) had normal exercise tests despite giving a convincing symptom history. Seven of these accepted a monitored one month trial of inhaled drugs. Five completed the course; all reported symptomatic improvement. Their repeat exercise tests were all normal and unchanged.

• Competitive athletes: The eight children who gave a history of high level competitive sport were not listed as a separate diagnostic category but they emerged as a sub-group with surprisingly similar characteristics. Taken together, they had received extensive medical attention and often had a long history of medication. They had had twice as many consultations as the children with confirmed EIA (3.1±0.6 v 1.5±0.5, p < 0.001) and took significantly more daily medications (2.3±0.5 v 1.3±0.7, p < 0.01). Despite this, they all had a normal response to exercise (+10 min FEV₁, −0.25±2.3 v −13.4±4.8, p < 0.001). Six had vocal cord dysfunction, one had a very loud habit cough, and one had no diagnosis.

DISCUSSION

We prospectively studied 52 children who had been referred to our clinic for investigation of incompletely controlled exercise induced asthma. After careful clinical and laboratory testing, we found that only eight (15.4%) of these children met conventional diagnostic criteria for EIA. Exercise associated respiratory complaints in the majority of the remainder were either due to functional disorders such as vocal cord dysfunction or were the result of poor physical conditioning. Misdiagnosis was principally due to the unreliability of the initial self-reported respiratory symptoms. In a study of 256 adolescents, Hallstrand and colleagues⁸ published very similar results. Of the 47 children they identified with previously diagnosed EIA, who reported persistent respiratory symptoms with exercise, only eight (17%) subsequently had a positive exercise test.

The biggest obstacle to any form of asthma research is diagnosis.²⁵ Asthma is an inhomogeneous condition for which there is no absolute diagnostic test combining acceptable sensitivity with specificity.²⁶ Unquantifiable diagnostic error is the unavoidable result but, surprisingly, the topic is often overlooked.²⁷ Clinical studies of diagnostic accuracy in asthma are rare, in both the adult²⁸ and paediatric²⁹ literature. Even the relatively well defined treadmill exercise test is still far from being a gold standard. Variations in the exercise load,³⁰ exercise time,³¹ or the temperature²⁴ and humidity⁶ of inspired air will all alter the fraction of children diagnosed with EIA. Simply changing the defined drop of FEV₁ from 10% to 15% (both widely used definitions)^2,6 would significantly reduce the number of children defined as having EIA (from 15.4% to 3.8% in our study).

Despite the problems of measurement error, we believe that our broad conclusions are reliable, particularly within the subgroups of poor physical fitness, VCD, and habit cough. These diagnoses were not made unless the clinical picture was unambiguous. None of these children had responded to conventional EIA therapy and all had normal exercise tests. Exaggeration of their symptoms during the test procedure was common and also helped to confirm the non-respiratory nature of their complaints.

While it is possible that some of the “no diagnosis” group were false negatives (due to insufficient exercise stimulus or the lingering effects of inhaled corticosteroid therapy), the lack of measured response to a month of therapy in five of them would suggest that the error rate was low. Equally, several of the children in the EIA group would become false positives just by changing the defined drop in FEV₁ from 10% to 15%. These diagnostic problems are not unique to our study and emphasise the fact that attention should be paid to measurement error when interpreting the results of any asthma study.

The weakest link in the diagnostic chain was the unreliability of the presenting respiratory symptoms. In keeping with others, we found that imprecise use of medical terms such as “wheeze” was particularly common.³² It was important to ask the child clear questions about their symptoms and the relation to exercise without parental prompting.⁷ With care and patience, it was usually possible to obtain a clear history. The primary complaint that eventually emerged was sometimes neither respiratory (headache, aphonia, or fainting) nor, in a few cases, even associated with exercise. For example, deep sighing or the sensation of being unable to take a full breath,²¹ although initially attributed to EIA, were often associated with watching television. Despite these problems, it should be emphasised that, in most cases, a careful history and physical examination would have revealed the possibility of alternative diagnoses.

Early puberty is a difficult time for many children, particularly when the stress of athletic competition is added.³³ Functional respiratory complaints such as habit cough¹⁸ or sigh dyspnoea²¹ are common at this age,³⁴ both in athletic³⁵ and non-athletic children.³⁶ In addition, obesity³⁷ and poor physical fitness²³ are growing problems among children across North America. Exercise related complaints are commonly associated with all of these conditions. Failure to appreciate the broad differential diagnosis of self-reported exercise symptoms in children will lead to over-diagnosis of EIA.¹⁹ The poor correlation between self-reported exercise symptoms and exercise testing in paediatric studies^7,8 is more likely due to unreliable symptoms rather than inaccurate test results.

Over-diagnosis of EIA among competitive athletes is a concern that has been raised by others, including the International Olympic Committee.³⁸ In our study, the athletic children all had normal exercise tests despite an extensive history of investigation and medication. There appeared to be almost a “culture” of asthma and allergies amongst the athletic children and their team-mates. For example, two of the hockey players believed they were allergic to diesel fumes from the ice cleaner, the competitive gymnast felt that her symptoms were due to chalk dust used on her hands, while both competitive swimmers believed they were allergic to chlorine. All of these children had normal exercise tests. There is clearly room for more research into medical beliefs among paediatric elite athletes.

Although our results suggest that symptom based diagnosis of EIA is unreliable among Vancouver schoolchildren, we would stress that as long as care is used in the initial assessment, the majority of exercise associated respiratory complaints can be diagnosed and managed without the need for exercise testing. In addition, careful questions concerning exercise symptoms should always be included in the investigation and management of any asthmatic child. We would also suggest a need for greater appreciation of the possibility of diagnostic error when interpreting any asthma study, particularly those relying primarily on self-reported respiratory symptoms.³⁹