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EXERCISE-INDUCED ASTHMA: FRESH INSIGHTS AND AN OVERVIEW

R Khajotia MD (Bombay), MD (Vienna), FAMA (Vienna), FAMS (Vienna), International Medical University, Seremban, Malaysia

Address for correspondence: Dr Rumi Khajotia, Associate Professor in Internal Medicine and Pulmonology, International Medical University, Clinical School, 70300 Seremban, Malaysia. Tel: 606-767 7798 ext 190. Email: rumikhajotia@yahoo.com, rumi_khajotia@imu.edu.my

INTRODUCTION

Bronchial asthma is defined as a chronic inflammatory disorder of the air passages in which many cellular elements play a role, namely, mast cells, eosinophils, neutrophils, epithelial cells, T lymphocytes and macrophages. In susceptible individuals this inflammation results in increased responsiveness of the tracheobronchial tree to a multiplicity of stimuli.

This is manifested physiologically by a widespread narrowing of the air passages which may be relieved spontaneously or as a result of therapy and is clinically characterised by paroxysms of dyspnoea, cough and wheeze. It is an episodic disease, acute exacerbations being interspersed with symptom–free periods.

Exercise-induced asthma (EIA) is an asthma variant which may be defined as a condition in which exercise or vigorous physical stress triggers acute bronchospasm in people with increased airway reactivity. It is primarily seen in people who are asthmatic but can also be found in patients who have atopy or allergic rhinitis and even in healthy individuals.

Exercise-induced asthma is even more important to the chest specialist because it is a neglected diagnosis and the underlying asthma could be silent in as many as 50% of patients,¹ becoming apparent only during exercise.

EPIDEMIOLOGY 

EIA affects 12-15% of the population. Ninety percent of asthmatic individuals and 35-45% of patients with allergic rhinitis experience EIA, but even when this group of patients is excluded, a 3-10% incidence of EIA is seen in the general population.²

EIA seems to be more prevalent in some winter and cold–weather sports.³ Some studies have demonstrated rates as high as 35% or even 50% in competitive-caliber figure skaters, ice hockey players, and cross–country skiers.^4,5

FUNCTIONAL ANATOMY AND PATHOPHYSIOLOGY

The problem in EIA occurs distal to the glottis, in the lower respiratory tract. Bronchoconstriction is involuntary and is distinguishable from laryngospasm which can occur in other exercise-related conditions.

EIA usually affects individuals who participate in sports that include an aerobic component. This condition can be seen in any sport, but EIA is much less common in predominantly anaerobic activities. This is possibly due to the role of consistent and repetitive air movement through the air passages which is mainly seen in aerobic sports thereby affecting airway humidity and temperature. As a result an unknown biochemical and neurochemical pathway is triggered resulting in bronchospasm.

The classical presentation of EIA lends some insight into the possible causative mechanisms. In people prone to EIA the first 3-5 minutes of physical activity usually have no adverse effects. When the physical activity is stopped, the lung functions decrease.

The PEFR and the FEV1 levels fall within 5-10 minutes after the activity stops. On resuming the physical activity symptoms begin to manifest within the first 5-10 minutes of resumption of the activity. The decrease in lung functions accompanied by symptoms usually persists for 15-40 minutes followed by normalisation of lung functions and resolution of symptoms. During this time the PEFR and FEV1 fall by 20-50%. This early-phase response is the classic manifestation of EIA.

A refractory period ranging from 40 minutes to 2 hours follows the episode of EIA and during this refractory period it is difficult to replicate the symptoms.

In some individuals a late-phase response also occurs which is related more to inflammatory changes. This normally occurs within 3-10 hours after the physical exertion stops and the degree of fall in lung function is greater and more prolonged than in the early-phase response.

Multiple factors appear to affect the frequency and severity of the change in pulmonary function and symptoms:

1. The greater the person’s baseline level of bronchial hyperreactivity as measured by histamine or methacholine challenge, the greater the likelihood of EIA developing or worsening.
2. The greater the minute ventilation (with other factors controlled), the greater the intensity and duration of EIA up to a  maximum of two thirds of the individual’s maximum working capacity.6
3. The less humid the inspired air, the greater the trigger for EIA.7-9
4. The cooler the air, the greater the trigger for EIA.7-9
5. Exposure to airborne allergens worsens EIA.
6. Certain air pollutants (e.g. ozone) may worsen EIA.

The currently preferred hypothesis also known as the water–loss hypothesis is that exercise causes decreased airway humidity through more rapid ventilation and thus increases mucosal osmolarity. As a result, osmoreceptors trigger increased bronchial blood flow, which causes oedema. Simultaneously, the increased osmolarity induces release of mediators that induce contraction of smooth muscle and further obstruction of the airway. Slower production of inhibitory prostaglandins results in bronchodilatation that ultimately reverses the smooth muscle contraction and manifests as the refractory period. Evidence against this hypothesis is that it does not explain why the most major constriction of the airways occurs after cessation of hyperpnoea.

Another hypothesis known as the post-exertional airway–rewarming hypothesis states that the initial airway heat loss associated with hyperpnoea causes a vascular dilatation and oedema that physically narrows the airways. This hypothesis is supported by the fact that some vasodilatation in systemic vasculature occurs after cold exposure and also that alpha-adrenergic agonists limit hyperventilation-induced asthma. The cellular mechanism of this process has yet to be explained. Sensory neurons have been implicated in animal models as possible pathways but have not been identified in humans.

Though the above two hypotheses attempt to explain the pathophysiology behind exercise-induced asthma there is still no plausible explanation for the mechanism behind the refractory period when on persistent exertion the person fails to get a further attack. Could it be a complete degranulation of the mast cells and their inability to degranulate further which is responsible for this refractoriness or the slow production of inhibitory prostaglandins causing bronchodilatation? Also, what is the mechanism behind the late-phase response in some patients where hours after the physical exertion stops, the fall in lung function is more pronounced than in the early-phase. Is it mast cell reactivation and mediator release attracting inflammatory cells to the airways which causes this response? I believe, in the years to come the pathophysiology of this oft neglected diagnosis will be revisited time and again.

CLINICAL MANAIFESTATIONS

The pathophysiologic mechanisms of asthma result in a multiplicity of physiologic changes occurring within the pulmonary tree during or following exercise.2,10 These include: cough, shortness of breath, wheezing, tightness of chest or chest discomfort, fatigue, below par performance on the field of play, gastrointestinal discomfort, prolonged recovery time,

Contributing factors include: cool temperatures, low-humidity environment, poor air quality, high content of pollen, concomitant respiratory infection

Exercise factors include the following: Aerobic exercise predisposes more to EIA than anaerobic exercise. Duration of aerobic exercise exceeding 10 minutes rapidly provokes an attack in a susceptible individual. High–intensity aerobic exercise predisposes to EIA.

Refractory phase in EIA

This phase starts less than 1 hour after the initial aerobic exercise and lasts up to roughly 3 hours. The refractory phase results in as little as one half the degree of bronchospasm as in the first episode. In sports this fact can be used to advantage by utilizing the warm–up period in such a way that the actual competition occurs during the refractory phase. Though the exact mechanism of this phase is unknown, it is believed to involve the possible depletion of mast cell mediators, release of endogenous catecholamines and the release of endogenous protective prostaglandins.

Sports requiring continuous activity, played in cold weather and most likely to trigger an attack of EIA in a susceptible individual, e.g. cross–country skiing, ice hockey, basketball, soccer, long-distance running

Sports less likely to trigger an attack of EIA are those that require short bursts of activity and are interspersed with breaks. These include: swimming, walking, hiking, golfing, baseball or softball, football, volleyball, gymnastics, wrestling, downhill skiing.