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Journal of Sports Sciences, 2001, 19, 865± 873

Dietary salt alters pulmonary function during exercise in exercise-induced asthmatics TIMOTHY D. MICKLEBOROUGH,1* ROBERT W. GOTSHALL,2 LOREN CORDAIN2 and MARTIN LINDLEY1 1

School of Sport Science, Physical Education and Recreation, University of Wales Institute, Cardiþ , Cyncoed Road, Cardiþ CF23 6XD, UK and 2Department of Exercise and Health Science, Colorado State University, Fort Collins, CO 80523± 1582, USA

Accepted 2 June 2001

Epidemiological and experimental studies have suggested that dietary salt may play a role in airway responsiveness. We have previously shown that a low salt diet improves and a high salt diet exacerbates post-exercise pulmonary function in individuals with exercise-induced asthma. The aim of this study was to determine the in¯ uence of both elevated and restricted salt diets on pulmonary function during exercise in individuals with exercise-induced asthma. Nine men and six women participated in this double-blind, crossover study. The participants entered the study on their normal salt diet and were placed on either a low or high salt diet for 2 weeks. Each diet was randomized, with a 1 week washout period between diets before crossing over to the alternative diet for 2 weeks. The participants underwent treadmill testing at 85% of their age-predicted heart rate on the normal salt diet and at the end of each treatment period. Pulmonary function was assessed during exercise by arterial saturation (ear oximetry) and indirect calorimetry. Twenty-four hour urine collections con® rmed compliance with the diets. Arterial saturation was reduced on the high and improved on the low salt diet at higher exercise intensities. Tidal volume and frequency selection during exercise varied with the diets, with a higher tidal volume and lower frequency on the high salt diet, but a lower tidal volume and higher frequency on the low salt diet. This suggested greater airway resistance during the high salt diet. In conclusion, the low salt diet improved and the high salt diet exacerbated pulmonary function during exercise in individuals with exercise-induced asthma. The mechanism of action remains unclear. Keywords: arterial oxygen saturation, dietary sodium, exercise-induced bronchoconstriction.

Introduction Exercise-induced asthma and exercise-induced bronchoconstriction are used synonymously to describe a reversible airway disease and to refer to the post-exercise decrement in airway function characterized by airway narrowing and increased airway resistance. Hyperpnoea of exercise is generally considered the main initiator of exercise-induced asthma. Two hypotheses have been put forward to explain how hyperpnoea causes the airways to narrow. The ® rst suggests airway cooling and rewarming (McFadden, 1990; Gilbert and McFadden, 1992) and the second mucosal dehydration and an increase in osmolarity (Anderson et al., 1982; Anderson, 1984). Exercise-induced asthma occurs in 80± 90% of * Author to whom all correspondence should be addressed. e-mail: [email protected]

all asthmatics and 35± 40% of those with allergic rhinitis (Jones et al., 1962; Kawabori et al., 1976; Anderson, 1985; Mahler, 1993). It has been shown that approximately 11% of the 1984 US summer Olympic team (Voy, 1986) and 20% of the 1996 US summer Olympic team had exercise-induced asthma (Weiler et al., 1998), which is similar to its prevalence in the general population (Rupp et al., 1992; Rupp, 1996). Exercise-induced asthma is typically diagnosed using a standard exercise protocol to 85± 90% of predicted maximum heart rate for 6± 8 min with pulmonary function being measured 5 min after exercise (Virant, 1992). After exercise, a fall in forced expiratory volume in 1 s (FEV1) of more than 10% of the pre-exercise value is indicative of exerciseinduced asthma (Eggleston et al., 1979). Epidemiological studies have suggested that increasing dietary salt within a population increases the prevalence and severity of asthma (Burney, 1987a,b;

Journal of Sports Sciences ISSN 0264-0414 print/ISSN 1466-447X online Ó http://www.tandf.co.uk/journals

2001 Taylor & Francis Ltd

866 Burney et al., 1987). Additionally, some (Burney et al., 1986, 1989; Javaid et al., 1988) but not all (Lieberman and Heimer, 1992; Britton et al., 1994; Devereux et al., 1995) intervention studies have indicated that increased salt exacerbates bronchiolar smooth muscle reactivity in asthmatics at rest. Individuals with exercise-induced asthma often complain of wheezing and breathlessness during and after exercise. Researchers cannot agree whether airway obstruction occurs during exercise or only after exercise (Sly, 1986; Mahler, 1993). It has been demonstrated that airway obstruction may only develop during exercise of 20 min duration or more (Freeman et al., 1990; Beck et al., 1994; Suman et al., 1995, 1999), but not during exercise of shorter duration or isocapnic hyperventilation less than 12 min in duration (Stirling et al., 1983; Gilbert et al., 1988; Blackie et al., 1990). We have previously demonstrated that a high salt diet exacerbates and a low salt diet improves airway function after exercise in individuals with exercise-induced asthma (Gotshall et al., 2000; Mickleborough et al., 2000). Thus, it is rational to hypothesize that changing dietary salt intake will in¯ uence airway function during exercise in exercise-induced asthmatics. The experimental hypothesis tested in the current study was that dietary salt restriction would improve and dietary salt enhancement would exacerbate pulmonary function during exercise in individuals with exercise-induced asthma.

Methods Participants Fifteen individuals with clinically diagnosed exerciseinduced asthma (6 females, 9 males; age 18± 36 years), recruited from a university population, volunteered for the study (Table 1). All participants had a history of post-exercise shortness of breath and intermittent wheezing, relieved by bronchodilator therapy; they were otherwise free of atopic asthma as diagnosed by their physician. All participants had been taking physicianprescribed medication for exercise-induced asthma before the study. Medications included inhaled corticosteroids (`maintenance medication’ ) and short-acting b2 agonists (`rescue medication’ ) (Table 1). Each participant completed a health questionnaire and provided written informed consent before enrolment in the study, which was approved by the Colorado State University Institution Review Board. Most participants discontinued using their medications 12 h before the exercise test; the one individual on corticosteroids maintained a stable dose throughout the entire study. During a preliminary screening test, all participants

Mickleborough et al. demonstrated exercise-induced asthma as indicated by a reduction in post-exercise FEV1 of more than 10% (Eggleston, 1979). Study design The study had a randomized double-blind crossover design and was conducted over 5 consecutive weeks. All 15 participants entered the study on their normal salt diet, which varied among participants, and were assigned at random to either a high (n = 8) or a low (n = 7) salt diet for 2 weeks. Then, after a washout period of 1 week on their normal salt diet, they followed the alternative diet for 2 weeks. All participants were required to consume a base diet of 1500 mg of sodium each day, whether on the low or high salt diet, which was provided by a menu plan. The base diet was supplemented during the high salt diet with ten 1 g salt capsules per day (4 g of sodium per day). For the low salt diet, the base diet was supplemented in the same way but with placebo (sucrose) tablets. To monitor dietary compliance, 24 h urine collections were made at the beginning and after each phase of the study for the determination of 24 h sodium excretion. Protocol and measurements The participants were instructed to avoid any strenuous physical activity and to refrain from using `rescue medications’ in the 24 h before the exercise test. During a screening test to diagnose exercise-induced asthma and at the end of each phase of the study, the participants underwent a standardized exercise challenge with pulmonary function being measured before and after exercise (Eggleston et al., 1979). Pre- and post-exercise pulmonary function tests were conducted using a SensorMedics Vmax 22 computerized spirometer, which required the participants to perform three acceptable spirograms according to the American Thoracic Society (1995). The exercise test, which lasted approximately 10 min, required each participant to run on a treadmill (Quinton Instrument Co., Seattle, WA) at 85± 90% of predicted maximum heart rate for at least 5 min using a standard graded protocol of incrementally increasing workloads (Eggleston, 1984). A constant-load protocol was applied once the participant achieved the target heart rate for a further 5 min. Each participant performed the same workload over the same period of time, with both speed and elevation being matched. The exercise protocol was tailored to each participant to achieve heart rate criteria. Heart rate was monitored continuously using electrocardiography (Quinton 4500 Stress Test Monitor, Quinton Instruments, Seattle, WA). Environmental conditions were 23°C and 50%

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Dietary salt and asthma Table 1. Characteristics of the participants and their medications Participant

Sex

Age (years)

Height (m)

Mass (kg)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

M M M M M M M M M F F F F F F

18 23 26 31 36 24 21 22 25 19 23 22 22 22 24

1.75 1.77 1.73 1.79 1.82 1.78 1.83 1.77 1.74 1.52 1.61 1.53 1.54 1.47 1.49

61.3 65.6 64.6 69.2 72.3 70.7 74.2 69.4 70.2 49.5 56.6 52.7 53.2 53.8 48.7

Medications Terbutaline (Bricanyl) Terbutaline (Bricanyl) Corticosteriod (Budesonide) Albuterol (Ventolin) Albuterol (Ventolin) Albuterol (Ventolin) Terbutaline (Bricanyl) Albuterol (Ventolin) Terbutaline (Bricanyl) Albuterol (Ventolin) Albuterol (Ventolin) Terbutaline (Bricanyl) Terbutaline (Bricanyl) Albuterol (Ventolin) Albuterol (Ventolin)

Note: Terbutaline and Ventolin are short-acting b2 agonists (rescue medications).

relative humidity. All participants were tested in the same laboratory, which was located 1524 m above sea level. During exercise, breath-by-breath analysis of expired gases was accomplished by open circuit spirometry (SensorMedics 2900 Metabolic Cart, SensorMedics Corporation, Yorba Linda, CA). As is required with such pulmonary measurements, the participants breathed through a mouthpiece with their nose clipped. This prevented nasal breathing and forced mouth breathing. Thus, the pre-warming and pre-humidifying of air through the nasal mucosal was bypassed. Breathing by mouth in individuals with exercise-induced asthma results in dryer, cooler air being presented to the airways, possibly contributing to the induction of their asthma with exercise. The following ventilatory variables were measured or calculated: total ventilation (VÇ E), respiratory rate, tidal volume and the ventilatory equivalents for oxygen (VÇE / VÇ O2 ) and carbon dioxide (VÇ E/VÇ CO2). Arterial oxygen saturation was measured during exercise by ear oximetry (Ohmeda Biox II, Bioximetry Technology, Inc., Boulder, CO). At 5 min post-exercise, pulmonary function tests were conducted in the same manner as before exercise. The participants were allowed the use of their bronchodilators after all pulmonary function tests had been completed. Urine samples were analysed for sodium and potassium concentrations using a Beckman Astra analyser (Beckman Instruments, Inc., LaBrea, CA) and ionspeci® c electrodes. Urinary creatinine concentration was determined by a modi® ed Jaþ e rate reaction, using the same instrument, to verify completeness of the 24 h urine samples.

Statistical analysis The data were analysed using the SAS statistical package (SAS Institute, Cary, NC). The metabolic and ventilatory data were computed as the mean of 40 s periods at rest, 50%, 75% and 90% of predicted maximum heart rate. A repeated-measures analysis of variance was performed on the data, with treatment as a `within-individual’ eþ ect. Where a signi® cant F-ratio was found (P < 0.05), a Fisher’ s protected leastsigni® cant-diþ erence post-hoc test was applied to identify diþ erences in group means (P < 0.05). The data were analysed for crossover eþ ects between treatments, but none were detected.

Results The participants were shown to have complied with the low and high salt diets by the 24 h urinary excretions of sodium (Table 2). Neither potassium excretion nor creatinine excretion was altered by the diets (Table 2). The eþ ect of diet on pre- and post-exercise pulmonary function is presented in Table 3 and has been discussed elsewhere (Mickleborough et al., 2000). However, compared with pre-exercise, forced expiratory volume in 1 s decreased post-exercise during the normal salt diet, was exacerbated by the high salt diet and improved on the low salt diet (Table 3). In addition, by performing a regression analysis, we showed that no relationship exists between minute ventilation and the change in pre- to post-exercise pulmonary function (Mickleborough et al., 2000). This suggests that the

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Mickleborough et al.

changes in pulmonary function that occur after exercise are the result of diet and not varying ventilatory stimuli. Arterial oxygen saturation at rest and at 50% and 75% of predicted maximum heart rate did not diþ er between diets (Fig. 1). However, it was signi® cantly reduced by higher exercise intensities (90% predicted maximum heart rate) on the high salt compared with the normal and low salt diets. As shown in Fig. 2, total ventilation increased throughout exercise for all diets. However, it was higher for the high and lower for the low salt diet for each exercise intensity. Tidal volume also increased with increasing exercise intensity for all diets, but was higher for the high and lower for the low salt diet at all exercise intensities (Fig. 3). Similarly, respiratory rate increased with increasing exercise intensity for all diets (Fig. 4). However, in contrast to tidal volume, respiratory rate was higher for the low and lower for the high salt diet for all intensities of exercise. The ventilatory equivalents for oxygen and carbon dioxide are shown in Figs 5 and 6 respectively. Both diþ ered signi® cantly between diets at all intensities of exercise, being higher on the high and lowest on the low salt diet. Respiratory exchange ratios (RER) were unchanged at rest between diets. However, RER

increased with exercise duration on all diets, being signi® cantly higher on the high and lowest on the low salt diet (Fig. 7).

Discussion The principal ® nding of this study was that exercise arterial oxygen saturation was improved by reducing dietary salt and was exacerbated by increasing dietary salt in individuals with documented exercise-induced asthma. The pattern of exercise ventilation diþ ered with diet, with the high salt diet resulting in a higher tidal volume and lower respiratory rate; the low salt diet saw the reverse of this pattern, with a lower tidal volume and

Table 2. Twenty-four hour urine analysis (mg ´day-1; mean ± sxÅ) Diet

Sodium Potassium Creatinine

Low salt

Normal

High salt

958 ± 17a 3708 ± 247 1395 ± 93

3630 ± 63b 2500 ± 167 1629 ± 109

8133 ± 140c 4911 ± 327 1747 ± 117

Note: Diþ ering superscript letters represent signi® cance among values (P < 0.05). There were no signi® cant diþ erences among potassium or creatinine values.

Fig. 1. Eþ ect of dietary salt on oxygen saturation of arterial blood (SaO2) during exercise in individuals with exerciseinduced asthma (mean ± sxÅ). Letters denote signi® cance for comparison of diets at P < 0.05; letters that diþ er are signi® cantly diþ erent from one another. d , low salt diet; s , normal salt diet; . , high salt diet; PMHR, predicted maximum heart rate.

Table 3. Results of pulmonary function tests before and after exercise (mean ± sxÅ) Low salt diet

FVC (l) FEV1 (l) FEV1/FVC (%) FEF25± 75% (l ´s-1) PEFR (l ´s-1)

Normal diet

High salt diet

Before

After

Before

After

Before

After

5.12 ± 0.28 3.96 ± 0.17 77.3 ± 1.86 3.63 ± 0.19 8.51 ± 0.51

6.07 ± 0.29*a 4.36 ± 0.20*a 71.8 ± 1.52*a 4.46 ± 0.16*a 8.40 ± 0.42a

4.94 ± 0.29 3.86 ± 0.19 78.1 ± 1.57 3.66 ± 0.23 7.83 ± 0.15

4.87 ± 0.24b 3.55 ± 0.22*b 72.9 ± 1.86*a 3.33 ± 0.24*b 7.42 ± 0.36*b

4.97 ± 0.29 3.85 ± 0.18 77.5 ± 1.70 3.54 ± 0.16 8.60 ± 0.45

4.75 ± 0.22*b,c 3.48 ± 0.24*b 73.3 ± 1.76*a 2.99 ± 0.21*c 7.59 ± 0.40*b

Abbreviations: FVC, forced vital capacity; FEV1, forced expiratory volume in 1 s; FEF25± 7 5%, forced expiratory ¯ ow at 25± 75% of forced vital capacity; PEFR, peak expiratory ¯ ow rate. Note: There were no signi® cant diþ erences for any pre-exercise variable among diets. * P < 0.05 with respective pre-exercise value. Superscript letters refer to comparisons by diet post-exercise within a speci® c variable; diþ erent letters designate signi® cant diþ erence.

Dietary salt and asthma

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Fig. 2. Eþ ect of dietary salt on ventilation (VÇE) during exercise in individuals with exercise-induced asthma. d , low salt diet; s , normal salt diet; . , high salt diet; PMHR, predicted maximum heart rate.

Fig. 4. Eþ ect of dietary salt on respiratory rate ( fb) during exercise in individuals with exercise-induced asthma. d , low salt diet; s , normal salt diet; . , high salt diet; PMHR, predicted maximum heart rate.

Fig. 3. Eþ ect of dietary salt on tidal volume (VT) during exercise in individuals with exercise-induced asthma. d , low salt diet; s , normal salt diet; . , high salt diet; PMHR, predicted maximum heart rate.

Fig. 5. Eþ ect of dietary salt on the ventilatory equivalent for oxygen (VÇE /VÇO2) during exercise in individuals with exerciseinduced asthma. d , low salt diet; s , normal salt diet; . , high salt diet; PMHR, predicted maximum heart rate.

higher respiratory rate. This implies increased airways resistance with the high salt diet and lowered airways resistance with the low salt diet. Dietary goals were achieved as sodium excretions fell while on the low salt diet and rose while on the high salt diet. Thus a graded dose of dietary sodium was accomplished in this study, from 958 to 8133 mg ´day-1. This occurred without a change in potassium excretion or glomerular ® ltration rate (creatinine excretion). The exercise protocol adopted in this study is typically used to induce and diagnose exercise-induced asthma (Virant, 1992). The protocol lasted approximately 10 min with the last 5 min being performed at

~90% of predicted maximum heart rate. Therefore, the exercise was of reasonably short duration, but did reach a high intensity. The results of the study can only be interpreted within the context of this exercise protocol. However, it is remarkable that arterial oxygen saturation changed signi® cantly between the low and high salt diets during the higher exercise intensities in these individuals with exercise-induced asthma. It should be noted that testing took place at an altitude of 1524 m and, in our experience, it is not unusual for signi® cant haemoglobin desaturation to occur even in normal individuals at or near maximal exercise at this altitude. However, it has been shown that hypoxaemia, which

870

Fig. 6. Eþ ect of dietary salt on the ventilatory equivalent for Ç E/VÇCO2) during exercise in individuals with carbon dioxide (V exercise-induced asthma. d , low salt diet; s , normal salt diet; . , high salt diet; PMHR, predicted maximum heart rate.

Fig. 7. Eþ ect of dietary salt on the respiratory exchange ratio (RER) during exercise in individuals with exercise-induced asthma. d , low salt diet; s , normal salt diet; . , high salt diet; PMHR, predicted maximum heart rate.

often occurs during severe exercise at moderate altitude, rarely falls below 87% (Mengelkoch et al., 1994). Therefore, the altitude may have magni® ed the changes in arterial oxygen saturation recorded in this study; a diþ erent change in arterial oxygen saturation might be seen at sea level. The mechanism by which arterial oxygen saturation was altered in the present study is unclear. A reduction in arterial oxygen saturation on the high salt diet was accompanied by elevations in the ventilatory equivalents for oxygen and carbon dioxide. Such elevations in these ventilatory equivalents imply the presence of alveolar ventilation± perfusion ratio inequalities (Wasserman

Mickleborough et al. et al., 1999). However, this interpretation is clouded by the presence of hyperventilation with exercise and a high salt diet (RER > 1; Fig. 7). Conversely, with improved arterial oxygen saturation on the low salt diet, the ventilatory equivalents for both oxygen and carbon dioxide were reduced, suggesting improved alveolar ventilation± perfusion matching. Without direct measurement of arterial blood gases, however, the question of alveolar ventilation± perfusion matching cannot be addressed adequately. Anderson et al. (1972) suggested that alveolar ventilation± perfusion matching is possible when exercising in individuals with exercise-induced asthma. Additionally, alveolar ventilation± perfusion mismatching has previously been shown to occur in exercise-induced asthmatics (Young et al., 1982). In the current study, the diets had signi® cant eþ ects on arterial oxygen saturation during higher exercise intensities, with blood oxygenation decreasing on the high compared with the low salt diet. This suggests that dietary salt in¯ uenced gas exchange during exercise in these individuals with exercise-induced asthma. Shimizu et al. (1997) also studied individuals with documented exercise-induced asthma. They used treadmill running for 6 min to 80% of predicted maximum heart rate as the exercise challenge. A ® nger pulse oximeter was used to determine arterial oxygen saturation. They evaluated their participants during two bouts of exercise on separate days, once with inhaled indomethicin and once without. Arterial oxygen saturation was reduced immediately after exercise in these participants, a reduction that was decreased by prior administration of indomethicin. Indomethicin also reduced the severity of the exercise-induced asthma as determined by postexercise forced expiratory volume. Although arterial oxygen saturation during exercise was either not reported or not measured, these changes in immediate post-exercise arterial oxygen saturation support the results of the current study. In further support of the current study, Cayton et al. (1991) exercised asthmatics for 5 min at 100 W on a cycle ergometer. These participants were in the recovery phase of an acute asthmatic attack requiring hospitalization. Earlobe samples of arterialized blood were used to determine arterial oxygen tension. Peak expiratory ¯ ow rates were used to document exercise-induced asthma, which only a few of the participants exhibited. Group statistics demonstrated no eþ ect of the exercise on arterial oxygen tension. However, when the data were examined by correlating arterial oxygen tension with post-exercise peak expiratory ¯ ow rates, there was a positive relationship. Thus, these data suggest decreased exercise gas exchange in individuals with exercise-induced asthma. Few other studies have determined exercise arterial oxygen saturation in individuals with exercise-induced

Dietary salt and asthma asthma. Ingemann-Hansen et al. (1980) studied athletes with asthma and indicated that arterial oxygen saturation was unchanged during exercise in these asthmatics. However, there was no change in post-exercise forced expiratory volume compared with pre-exercise in these asthmatics, which suggests that they did not have exercise-induced asthma at the time of the study. Ienna and McKenzie (1997) exercised asthmatics with a history of exercise-induced asthma. A methacholine challenge documented hyper-reactive airways in these asthmatics; however, a before versus after exercise forced expiratory volume was not accomplished and, therefore, the presence of exercise-induced asthma was not documented. Arterial oxygen saturation was unchanged in these asthmatics during exercise (incremental cycle ergometry to 90% of maximum). Since these studies did not document the presence of exerciseinduced asthma in their participants, it is diý cult to ascertain from these results the eþ ect of exercise on gas exchange in exercise-induced asthmatics. The pattern of breathing chosen by the participants in the current study on the high salt diet suggests the presence of increased airway resistance during exercise. Typically, individuals with elevations in airway resistance will increase total ventilation and decrease respiratory rate to reduce the work of breathing. The reversal of this pattern on the low salt diet may indicate a reduction in airway resistance by the same reasoning. However, no direct measure of airway resistance was performed during exercise in this study. Others have reported a similar ventilatory pattern to that in the present study in exercise-induced asthmatics compared with individuals without exercise-induced asthma or who received successful treatment (Bevegard et al., 1976; Freeman et al., 1990). In those studies that have tried to measure air¯ ow resistance during exercise in individuals with exerciseinduced asthma, the results suggest increased resistance to air¯ ow (Beck et al., 1994; Johnson et al., 1995; Suman et al., 1995, 1999). Beck et al. (1994) reported a decline in forced expiratory volume during exercise of varying intensity in individuals with documented exercise-induced asthma compared to those without. In the study of Johnson et al. (1995), exercise-induced asthmatics demonstrated an elevation in end-expiratory lung volume and air¯ ow limitations compared with a group of controls. Thus, although there are few data on airways resistance during exercise in exercise-induced asthmatics, there is indirect evidence to support reduced ¯ ow rates secondary to greater airways resistance. Bronchodilator in¯ uences are typically dominant during exercise in normals. In individuals with exerciseinduced asthma there is oþ setting bronchoconstriction, or airway narrowing, which occurs during exercise, resulting in variable measures of airway resistance

871 (Johnson et al., 1995). In exercise-induced asthma, this airway narrowing is predominant after exercise. Suman et al. (1995) demonstrated a signi® cant increase in inspiratory and expiratory pulmonary resistance during the latter stages of exercise. In a follow-up study, Suman et al. (1999) observed that pulmonary mechanics were compromised during 20 min exercise in exercising asthmatics. In the current study, airway function during exercise was not monitored, as the use of spirometry to document changes in pulmonary function during exercise has been criticized because of the possible inability of participants to perform maximal expiratory manoeuvres during strenuous exercise (McFadden and Gilbert, 1994) Several investigators have demonstrated the possible in¯ uence of dietary salt on the severity of asthma (Burney et al., 1986, 1989; Burney, 1987a,b; Javaid et al., 1988; Tribe et al., 1994). Previous studies in our laboratory have demonstrated that dietary salt modi® es post-exercise pulmonary function in individuals with exercise-induced asthma (Gotshall et al., 2000; Mickleborough et al., 2000). However, this is the ® rst study to demonstrate the potential in¯ uence of dietary salt on pulmonary function during exercise in individuals with exercise-induced asthma. Since the mechanism by which dietary salt may in¯ uence exerciseinduced asthma is unknown and its pathogenesis has not been delineated (Virant, 1992), to suggest a possible pathophysiological mechanism for the interaction of salt with exercise-induced asthma during exercise would be speculative. Some studies on dietary salt and airway reactivity have suggested that elevated dietary sodium increases bronchial smooth muscle tone (Burney et al., 1986, 1989; Tribe et al., 1994). However, not all studies have demonstrated this relationship (Lieberman and Heimer, 1992; Britton et al., 1994; Devereux et al., 1995). Tribe et al. (1994) evaluated dietary sodium intake and airway responsiveness to methacholine in asthmatics. Their results suggested that a serum-borne factor found in asthmatics caused an increase in cell membrane permeability, thereby stimulating sodium entry into cells. Dietary sodium would augment this eþ ect. It is possible that increased transcellular ¯ ux of sodium alters intracellular calcium concentrations through inhibition of the Na + -Ca2 + exchanger, thus increasing smooth muscle contractility. An increase in intracellular calcium may also enhance the release of histamine (Praetorius et al., 1998) and eicosanoids (e.g. leukotrienes and prostaglandins) from cells in the airways, such as mast cells, eosinophils and alveolar macrophages (Garland et al., 1993). The in¯ uence of dietary salt on in¯ ammatory mediators in exercise-induced asthma remains to be determined. In addition, the potential in¯ uence

872 of dietary salt on circulating blood volume and, consequently, on pulmonary haemodynamics and pulmonary function cannot be ruled out. An elevation in dietary salt may have a profound eþ ect on the bronchial circulation by increasing vascular volume and microvascular pressure, resulting in mucosal oedema and hence a narrowing of the airway lumen (McFadden, 1990). Increases in lung water as a result of altered dietary sodium may aþ ect lung elastance and mechanics, thus contributing to changes in pulmonary function. In summary, we have shown that reductions in dietary salt improve and elevations in dietary salt exacerbate pulmonary gas exchange during exercise in individuals with documented exercise-induced asthma. Presumably, alterations in dietary salt aþ ect airway narrowing and may alter ventilation± perfusion matching during exercise in individuals with exercise-induced asthma. Although no direct measurements of pulmonary function were made during exercise, we did demonstrate that airway narrowing in exercise-induced asthmatics may occur during exercise less than 10 min in duration.

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