Exercise induced asthma (EIA) occurs in approximately 90% of chronic asthmatics¹ and has previously been reported to occur in 7–50% of athletic individuals.^2–6 Asthmatic elite athletes currently require evidence of asthma to obtain a therapeutic use exemption certificate which enables them to use therapeutic doses of inhaled β₂ agonists in and out of competition.⁷ EIA has previously been diagnosed by a number of challenge methods including exercise,^8,9 eucapnic voluntary hyperventilation (EVH),^10,11 methacholine,^12,13 histamine,¹⁴ saline,¹⁵ and mannitol.^16,17 The International Olympic Committee’s Medical Commission (IOC-MC) considers positive tests from exercise, EVH, saline, histamine, and methacholine challenges as evidence of EIA. Methacholine and histamine, however, have been shown to be less specific than exercise for EIA diagnosis.^16,18,19 Exercise and EVH challenges are regarded as the most specific methods of diagnosing EIA in elite athletes.¹¹

In all EIA tests recognised by the IOC-MC, forced expiratory volume in 1 second (FEV₁) is the parameter by which changes in maximal expiratory function are assessed, but no “gold standard” methodology exists for athletes or non-athletes.²⁰ Previous studies that have used FEV₁ to diagnose EIA have suggested using falls in FEV₁ ranging from 7% to 20% as cut off criteria.^21–23 The work carried out by Helenius et al²³ suggests that a fall of 10% in FEV₁ following an exercise test is not sensitive enough to diagnose EIA in elite athletes. Despite the absence of a “gold standard” methodology for diagnosing EIA in athletes, the IOC-MC has ruled that an exercise or EVH challenge is positive for EIA when the FEV₁ falls ⩾10% from the baseline measurement.

It is possible that the addition of other measurements of expiratory lung function may provide greater sensitivity in the diagnosis of EIA. For example, forced expiratory flow between 25–75% of vital capacity (FEF_25–75) has been used in conjunction with FEV₁ to aid the diagnosis of EIA in children^24,25 and athletes.^8,26 Implicitly, FEV₁ measures expiratory flow at high and mid lung volumes, whereas FEF_25–75 and forced expiratory flow at 50% of vital capacity (FEF₅₀) are markers of expiratory flow through middle lung volumes. It has been suggested that FEF_25–75 and FEF₅₀ are more sensitive to airway obstruction in the small airways than FEV₁.^27,28 Custovic et al²⁴ noted that cut off points for EIA in children (defined as the normal group mean value −2 SD) occurred with a fall in FEV₁ of >10% and a fall in FEF_25–75 of >26%. In this study, the combined application of FEV₁ and FEF_25–75 criteria enabled detection of all subjects with EIA. Furthermore, using both FEV₁ and FEF_25–75 criteria, none of the subjects with allergic rhinitis or dermatitis presented with EIA. The fall in FEV₁ after exercise in children with allergic rhinitis was within the normal range (⩽2SD), but with a significantly lower mean value than control subjects. The study by Custovic et al²⁴ therefore provides promising evidence to support the addition of mid expiratory flow rates to FEV₁ in the diagnosis of EIA in children that might also be applied to elite athletes. FEF₅₀ and FEF_25–50 measurements are highly correlated and the ratio of the two is reasonably constant. Based on this finding, Bar-Yishay et al²⁹ suggested that reporting both measurements is unnecessary, and they suggested that FEF₅₀ should be the preferred measure. This preference was based on the argument that FEF₅₀ is easily and directly determined while FEF_25–50 is a calculated parameter that is affected by the spirometer manufacturer’s choice of algorithm.

The purpose of the present study was to examine the role of FEF₅₀ as an adjunct to FEV₁ in the diagnosis of EIA in elite athletes following a bronchoprovocation challenge.

METHODS

Following ethical approval from Harrow local research ethics committee, 66 male elite summer and winter athletes of mean (SD) age 25.1 (4.9) years, height 180.7 (7.8) cm, body mass 77.3 (12.5) kg and 50 female elite athletes of mean (SD) age 24.3 (5.4) years, height 168.2 (7.9) cm, and body mass 62.6 (9.9) kg who held either a Gold or Silver British Olympic Association passport (indicating current or potential Olympic competitive standard) provided written informed consent and volunteered for the study. Of the athletes who participated in this study, 83 had a previous diagnosis of EIA and where using asthma medication. The other 33 athletes had reported symptoms of EIA to a sports physician who had referred them to be tested for EIA. The testing took place at the Olympic Medical Institute, Harrow between June 2003 and June 2004. Athletes were tested at least 2 weeks after a respiratory infection and at least 12 hours following a training session.

Each athlete completed either an exercise or EVH challenge. Exercise challenges involved exercising at an intensity of >85% of maximal heart rate for 6–10 minutes in a sport-specific environment.³⁰ EVH challenges consisted of hyperventilating for 6 minutes at a rate of 85% maximal voluntary ventilation (30 × baseline FEV₁). The gas inspired during the EVH challenge was a medical gas containing 21% O₂, 5% CO₂ and 74% N₂.³¹ For both exercise and EVH challenges, maximal flow-volume loops were measured before and at 3, 5, 10 and 15 minutes after stopping exercise or EVH using a digital spirometer (MicroLab ML3500, Micro Medical Ltd, Rochester, UK) which met ATS guidelines. The lowest values of FEV₁ and FEF₅₀ following either exercise or EVH were recorded and the change was calculated (Δ). A ΔFEV₁ of ⩾−10% and ΔFEF₅₀ of ⩾−26% were considered cut off criteria for EIA diagnosis.²⁴

RESULTS

There was a strong positive correlation between ΔFEV₁ and ΔFEF₅₀ following bronchoprovocation (r = 0.94, p = 0.000). Sixty athletes (52%) had a ΔFEV₁ fall of ⩾10% leading to the diagnosis of EIA (fig 1). Using the FEF₅₀ criteria alone led to 21 (35%) asthmatic athletes receiving a false negative diagnosis; thus, 39 athletes met both FEV₁ and FEF₅₀ criteria. The lowest fall in ΔFEF₅₀ in an athlete with a ⩾10% fall in FEV₁ was 14.3%. Reducing the FEF₅₀ criterion to a ⩾14% fall included 13 athletes whose ΔFEV₁ was not ⩾10% (mean ΔFEV₁ = 5.7, range −8.9 to −1.5). Only one athlete had a ⩾26% fall in FEF₅₀ in the absence of a ⩾10% in FEV₁ (ΔFEV₁ = 8.9%).

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Figure 1

 Delta FEV₁ versus delta FEF₅₀.

Of the 83 athletes with a previous diagnosis of EIA, 33 failed to develop EIA (ΔFEV₁ <10%) following bronchoprovocation challenge. Of the 33 athletes who had been referred for testing but had no previous diagnosis of EIA, 10 athletes presented with EIA following bronchoprovocation.

The values for FEF₅₀ and forced vital capacity (FVC) before and after bronchoprovocation challenge are shown in table 1. FEF₅₀ (p = 0.000) and FVC (p = 0.000) were significantly lower after bronchoprovocation in the asthmatic athletes. There was no significant change in FEF₅₀ or FVC before and after bronchoprovocation challenge in athletes who did not have a fall in FEV₁ of ⩾10%.

The specificity, sensitivity, predictive value of positive test and efficiency of FEF₅₀ cut off criteria of 26% and 14% are shown in tables 2, 3 and 4, respectively.

DISCUSSION

This study shows that the addition of FEF₅₀ reduces the sensitivity of EIA diagnosis following exercise or EVH challenge. Of the 60 athletes who were diagnosed with EIA using IOC-MC criteria of a ⩾10% fall in FEV₁, 21 (35%) would have received a false negative diagnosis using a combination of FEV₁ and FEF₅₀ falls. Furthermore, only one athlete exceeded the criterion for FEF₅₀ but not for FEV₁. Our study therefore suggests that FEF₅₀ does not improve the diagnosis of EIA in elite athletes using the IOC-MC criteria.

In previous studies, measurements of FEF_25–75 have been used to supplement FEV₁ in the diagnosis of EIA in children^24,25 and athletes.^8,26 The studies conducted on children have supported the addition of FEF_25–75 measurements to improve the diagnosis of EIA. It has been suggested that FEF_25–75 is a more sensitive measure of obstruction in the small airways than FEV₁.³² Thus, EIA may be a disease that consistently affects the expiratory flow through the small airways. Fonseca-Guedes et al²⁵ noted that only 60% of children with “intermittent” EIA met the criteria for both FEV₁ and FEF_25–75 compared with 94.4% of children with “severe persistent” EIA. They suggested that FEF_25–75 is more likely to fall significantly than FEV₁ in children with mild EIA. Our data do not agree with this finding and suggest that FEV₁ is more likely to fall significantly in athletes with mild asthma. Indeed, only one athlete had a significant fall in FEF₅₀ (⩾26%) in the absence of a significant fall in FEV₁, while 21 athletes had a significant fall in FEV₁ (⩾10%) in the absence of a significant fall in FEF₅₀. Only 39 athletes met both criteria for FEF₅₀ and FEV₁, which would have resulted in 21 (35%) athletes (who met FEV₁ criteria) receiving a false negative diagnosis for EIA. The reduced sensitivity found following the inclusion of the FEF₅₀ measurement suggests that, in elite athletes with mild EIA, expiratory airflow is just as likely to be restricted in the larger airways as in the smaller airways. It is therefore appropriate to assess expiratory flow using an index of function for both the larger and smaller airways of the lung—that is, FEV₁.

A number of studies have examined the diagnosis of EIA in athletes but they have not specifically used mid-expiratory flow rates as a criterion for making the diagnosis. Rundell et al⁸ suggested that a fall in FEF_25–75 of 14% is significant in the diagnosis of EIA in winter athletes. This lower limit was calculated by taking the mean post exercise change from baseline spirometry and subtracting 2 standard deviations. Lowering the FEF₅₀ cut off value in our data to ⩾14% resulted in an increase in the sensitivity but a decrease in the specificity from 98% to 77%. Using a 14% cut off value, 13 athletes would have been diagnosed with EIA who did not meet the IOC-MC criterion of a 10% fall in FEV₁ from baseline values.

A further problem associated with the use of FEF₅₀ as a criterion measurement is that its reliability is dependent upon the constancy of FVC. Our results show that the mean fall in FEF₅₀ following bronchoconstriction was accompanied by a mean fall in FVC in athletes with EIA. The fall in FEF₅₀ seen in some of athletes following a bronchoprovocation test may therefore be partially attributable to a reduction in FVC. The reduction in FVC in asthmatic athletes may be due to the prolongation and discomfort associated with exhaling to residual volume during bronchoconstriction. Despite standard controls, this may cause the athlete to stop exhaling before reaching residual volume. This shortcoming further undermines the potential value of FEF₅₀ for diagnosing EIA.

In conclusion, the addition of FEF₅₀ to FEV₁ reduces the sensitivity of a diagnosis of EIA in elite athletes. Our data suggest that a more global measure of maximal expiratory airflow (FEV₁) provides the most sensitive and specific diagnosis of EIA, especially when the severity of the disease is thought to be mild. This would suggest that EIA is a disease that is associated with expiratory flow limitation in the larger and smaller airways of elite athletes. However, methodological issues associated with assessment of FEF₅₀ (reliance upon FVC) mean that this interpretation should be viewed cautiously. The authors suggest that future studies should investigate the efficacy of the IOC-MC criterion of a 10% fall in FEV₁ to define a more statistically justified cut off point for the diagnosis of EIA in elite athletes.