Exercise Induced Bronchoconstriction

Exercise induced bronchoconstriction is transient narrowing of the lower airways that begins during or, more typically, 5 to 15 minutes after the end of vigorous exercise, and peaks at 5 to 20 minutes, with spontaneous recovery in 30 to 60 minutes. It occurs in people with asthma (called exercise induced bronchoconstriction with asthma, in 40 to 90% of asthmatics) and in people without asthma (called exercise induced bronchoconstriction without asthma).

• Prevalence is about 5 to 20% of the general population, 30 to 70% of elite athletes in cold air sports (swimming, cross country skiing, ice hockey, figure skating, long distance running), and more than 10% of school children.
• Mechanism: during exercise, high ventilation of cool, dry air dries the airway surface liquid, raising its osmolality, which triggers mast cell and eosinophil release of histamine, leukotrienes (cysteinyl leukotrienes) and prostaglandins, causing smooth muscle contraction, oedema and mucus. Rewarming of the airways after exercise adds vascular engorgement.
• Triggers and risk factors: cold, dry air, low humidity, air pollution, chlorine in indoor pools, ozone, high intensity or sustained exercise (6 to 8 minutes at 80 to 90% of the maximum heart rate), allergens and respiratory infection. Poorly controlled asthma, atopy, obesity and a family history raise the risk. Elite athletes may develop it from repeated airway injury.
• Mimics to exclude: poor fitness, obesity, vocal cord dysfunction (inducible laryngeal obstruction), dysfunctional breathing, cardiac disease, and anaemia.

• Cough, wheeze, chest tightness, shortness of breath and chest pain, beginning during or after strenuous exercise (peak 5 to 15 minutes after stopping). Cough is the commonest symptom and may be the only one, with a prolonged post-exercise cough. Symptoms last 30 to 60 minutes, and a refractory period of 1 to 3 hours follows during which a repeat exercise bout causes less bronchoconstriction.
• Symptoms are worse in cold, dry or polluted air and in the pollen season, and improve with a warm up and after a repeat effort within an hour. Some patients have a "second wind" with improvement of symptoms during exercise.
• Reduced exercise tolerance, avoidance of sport, fatigue, a gastro oesophageal reflux symptom (chest burning), throat tightness or noisy breathing with inspiration (suggesting vocal cord dysfunction), and sleep disturbance in poorly controlled asthma.
• Examination is often normal at rest, and may show wheeze after exercise.
• Differential diagnosis: poorly controlled asthma, vocal cord dysfunction or inducible laryngeal obstruction (inspiratory stridor, tight throat, voice change), exercise induced hyperventilation or dysfunctional breathing, deconditioning, obesity, cardiac conditions (arrhythmia, cardiomyopathy, congenital disease, anomalous coronary arteries), anaemia, gastro oesophageal reflux, pulmonary hypertension, and exercise induced anaphylaxis.
• Red flags: chest pain on exertion, syncope or near syncope, palpitations, a family history of sudden cardiac death, breathlessness out of proportion to effort, and no response to bronchodilator therapy (needs cardiac assessment before further exercise).
• Complications: severe attacks (rare, but fatal events occur in athletes with poorly controlled asthma), long term exercise avoidance, obesity, and reduced quality of life.

• A clinical diagnosis may be made on a typical history, but objective confirmation is recommended, because symptoms alone are unreliable in 30 to 50% of cases.
• Baseline spirometry (forced expiratory volume in 1 second, forced vital capacity) at rest, and with bronchodilator reversibility testing for asthma (an increase of 12% and 200 mL or more).
• Exercise challenge test: free running or treadmill (or cycle ergometer), 6 to 8 minutes at 80 to 90% of the predicted maximum heart rate (220 minus age), with dry air (relative humidity below 50%, room temperature 20 to 25 C). Measure the forced expiratory volume in 1 second before, and at 5, 10, 15, 20 and 30 minutes afterwards. A fall of 10% or more from baseline on at least 2 consecutive time points is positive (a fall of 10 to 25% is mild, 25 to 50% moderate, above 50% severe).
• Eucapnic voluntary hyperpnoea test: breathing dry air with 5% carbon dioxide at 85% of the maximum voluntary ventilation (30 times the baseline forced expiratory volume in 1 second) for 6 minutes, with a positive test a fall of 10% or more. It is the usual test for athletes.
• Mannitol challenge: inhaled dry powder, 0 mg then 5, 10, 20, 40, 80, 160, 160, 160 mg, with a positive test being a 15% fall at a cumulative dose of 635 mg or less, or a 10% fall between consecutive doses. It is simple, and does not need exercise.
• Methacholine challenge identifies airway hyperresponsiveness but is less specific for exercise induced bronchoconstriction.
• Field exercise testing (the usual sport, in the usual environment), with peak flow or hand held spirometry before and after, is practical for children and when laboratory testing is not available.
• For vocal cord dysfunction and other mimics: flow volume loops (truncated inspiratory limb), continuous laryngoscopy during exercise, and cardiopulmonary exercise testing, if the pattern is unusual.
• Cardiac assessment (ECG, echocardiogram, and exercise ECG) for chest pain, syncope, palpitations, or a family history of sudden death.
• Measure fractional exhaled nitric oxide (above 40 ppb favours eosinophilic inflammation), blood eosinophils and total IgE when atopy is suspected.

• Non-drug measures:
  • A warm up of 10 to 15 minutes before exercise, with intervals of high intensity effort followed by a rest period, which produces a refractory period lasting up to 2 hours in about 50% of patients.
  • Breathing through the nose and wearing a scarf or mask over the mouth in cold weather. Avoid exercise in cold, dry or polluted air and during high pollen counts.
  • Choose sports with short bursts of activity (for example swimming in warm humid air, volleyball, baseball, gymnastics) when the condition is severe, although no one should be excluded from exercise.
  • Fitness training reduces the severity of exercise induced bronchoconstriction, as do weight loss in obese patients and a low salt diet (limited evidence).
  • Avoid chlorinated pool air, indoor air with irritants, and smoking.
• Short acting beta agonist before exercise (the first line drug for occasional prevention):
  • Salbutamol 200 to 400 micrograms (2 to 4 puffs of 100 micrograms via a spacer) 10 to 15 minutes before exercise, and effective for 2 to 4 hours (child under 12 years 200 micrograms, over 12 years 200 to 400 micrograms). Repeat as needed, and carry a reliever inhaler during activity.
  • Terbutaline 500 micrograms (1 inhalation by dry powder) 5 to 15 minutes before exercise is an alternative.
  • Tolerance (loss of the protective effect) develops with frequent daily use, usually after 3 to 5 days of regular use, so avoid daily pre-exercise doses over a long period.
• Long acting beta agonist: formoterol 12 micrograms inhaled 5 to 15 minutes before exercise gives protection for up to 12 hours, but should be used with an inhaled corticosteroid in asthma, and not as monotherapy. Salmeterol 50 micrograms 30 to 60 minutes before exercise protects for 8 to 12 hours, with a lower tolerance in occasional use. Avoid regular use as monotherapy.
• Inhaled corticosteroid (the first line preventer for people with asthma or frequent symptoms): budesonide 200 to 400 micrograms twice daily, or beclometasone 100 to 200 micrograms twice daily, or fluticasone propionate 100 to 250 micrograms twice daily, for 4 to 8 weeks, which reduces the severity of exercise induced bronchoconstriction by 50% or more. For patients with asthma needing more than occasional use of reliever, use a combination inhaler of budesonide and formoterol (200/6 micrograms, 1 to 2 inhalations before exercise and as needed, maximum 12 inhalations per day).
• Montelukast 10 mg orally once daily at night (child 2 to 5 years 4 mg chewable, 6 to 14 years 5 mg chewable), or a single dose 2 hours before exercise. It protects in about 50% of patients, is not subject to tolerance, and is effective over 24 hours. Monitor for neuropsychiatric adverse effects (sleep disturbance, mood change, agitation).
• Sodium cromoglicate 10 mg (2 puffs of 5 mg) or nedocromil sodium 4 mg (2 puffs), inhaled 10 to 15 minutes before exercise, where available. Protection lasts 1 to 2 hours.
• Ipratropium bromide 40 micrograms (2 puffs) before exercise for those intolerant to beta agonists, with less effect.
• Treat associated asthma or rhinitis. Review inhaler technique and use of a spacer. Treat allergic rhinitis with intranasal corticosteroid, because upper airway disease worsens bronchoconstriction.
• Acute attack during exercise: stop, sit upright, and use salbutamol 100 micrograms, 4 to 10 puffs through a spacer, repeating every 20 minutes for the first hour. Seek medical help for no improvement, breathlessness preventing speech, or lips turning blue.
• Competitive athletes: confirm diagnosis with objective testing, check which medicines are permitted in competition with a sports medicine physician, and keep records of testing and treatment.
• Special groups:
  • Children: use salbutamol 100 to 200 micrograms via a spacer 10 to 15 minutes before exercise, encourage participation in physical education, and add budesonide 100 to 200 micrograms twice daily or montelukast for frequent symptoms. Avoid discouraging exercise.
  • Pregnancy: use salbutamol and budesonide, which are safe, and montelukast only if the benefit outweighs risks. Maintain moderate exercise.
  • Elderly: check for cardiac causes of exercise intolerance, and take care with beta agonists in arrhythmia or coronary disease.
  • Cardiac disease or arrhythmia: use beta agonists with caution, and seek cardiac review.
  • Beta blocker users: these drugs worsen bronchoconstriction, and non-selective drugs should be replaced.
  • Obesity: promote weight loss and graded activity.
• Follow up: review in 4 to 6 weeks to confirm control, check for tolerance with frequent beta agonist use, review technique and step down treatment after 3 to 6 months of stable control. Refer to a respiratory physician or sports medicine physician if there is no response to treatment, if the diagnosis is uncertain, for vocal cord dysfunction, or for athletes needing testing and documentation.