Use of the Refractory Period in the Treatment of Exercise- Induced Bronchoconstictions in a

Collegiate Football Player: A Case Study

Brian G Pietrosimone, M.Ed, ATCJohn MacKnight, MD

Ethan Saliba, PhD, PT,ATC,SCSJay Hertel, PhD, ATC

Asthma• Exercise triggers asthma in 50 -90% of known

Asthmatics (Parsons et al., Freed et al.)

• 10 % of non – asthmatics report symptoms of asthma during exercise (Parsons et al.)

• Wheezing• Coughing • Tightness in chest• Inability to catch one’s breath• Increased mucus production

Pathogenesis of EIB• The pathogenesis behind exercise

induced bronchospasm is not fully understood (Tan et al. & Chang- Yeung)

• Different Theories – Dehydration of mucosal lining – Bronchial mucosal hyperemia

Dehydration of Mucosal Lining• Cold, dry air causes dehydration of the

mucus membrane• Water loss causes an increase in osmotic

pressure• Mast Cell degranulation leads to

inflammatory mediator release (Parsons & Mastronarde, Tan, Maler)

Hyperemia• Re- warming in the lungs causes distal

airways to increase blood flow• Increased hydrostatic pressure in

bronchial vasculature• Increased airway edema (Parsons & Mastronarde, Tan, Maler)

History• Setting

• ACC, NCAA Division 1 Football Program• Climate Zone 3

• Athlete Demographics– 18 year old – Male– Single– Caucasian– Height: 6’ 2’’– Weight: 258 pounds– Position: Defensive Line– Hometown in Climate Zone 3

Past Asthma History• Health history form – Indicated past history of

asthma• Exercise was a stimulus• No other health problems, or family problems

• Prescribed prior to enrolling at the University– Albuterol MDI prn- short-acting bronchodilator– Salmeterol (Serevent) MDI - long-acting

bronchodilator– Fluticasone propionate (Flovent) MDI- inhaled

corticosteroid

Encounter Physical Examination Treatment

September2001

wheezing, coughing, mucus production, difficulty breathing, and tightness in chest

Transition to Fluticasone-Salmeterol (Advair diskus) bid Albuterol prn

December Same symptoms continue, * subject not compliant with previous treatment

Continue previous prescribed treatmentReturn if symptoms worsen

January No change in intensity, duration or frequency of EIA bouts

ADDED Montelukast (Singulair) 10 mg

February No relief with Montelukast

Advair was increased ADDED Cromolyn Sodium (mast cell stabilizer) was taken qid

September 2002

The athlete would not be able to finish the first quarter

Team Physician orders echocardiogram & spirometry post exercise treadmill test

Differential Diagnosis• Exercise Induced Bronchospasm • Extrinsic Asthma• Chronic Bronchitis• Cardiomyopathy

FEV1

• Spirometry measurements reported a decrease of 19% in FEV1 - confirming the diagnosis of EIB (Tan and Spector)

• FEV1 = (Pretest FEV1 - Post test FEV1) x100

Pretest FEV1

• No significant findings on Echocardiogram

Pattern• Team Physician noticed pattern

1st2nd

3rd4th

Unable to participate

Able to participate

6- 10 m 20-25 m2 h

3h4 h

Refractory Period

Real Time

Game Time

Refractory Period• The refractory period is the time in which

the athlete remained asymptomatic after the first bout of symptoms

• Refractory period occurs in 40% to 50% of asthmatics (Milgrom & Taussig )

Refractory Period• Theory suggests that a depletion in

inflammatory mediators occurs with an initial bronchospasm

(Freed & Chang- Yeung et al.)

• Subsequent exercise results in no additional mediator release

• The refractory period last for 2 to 4 hours after the first bout of EIA (Ben- Dov et al. & Wilson et al.)

Treatment• 75 minutes prior to game time under the

supervision of the Team Physician – 4 x 50 yard sprints at a moderate intensity – Series of 5, 10 and 20 yard shuttle runs

• 30 second rest was taken between each shuttle run in order to determine if the athlete had provoked sufficient bronchospasm to allow for a refractory period.

Treatment• Desired response was a bout of EIB large

enough to provoke a subsequent refractory period

– Athlete response» Wheezing » Coughing » Tightness in chest» Sputum production

Treatment• After team physician and athlete agreed

that desired response had been reached:• Consciously slowed breathing rate• Albuterol (2 puffs)• 15-20 minute cool down time prior to team warm

up

Treatment Effect

1st 2nd

3rd

4thPre- game

Onset of EIB

6-10 m75 min 1.5 h 2.5 h 3.25- 3.5 h

4.5 h

Able to play asthma free

EIB

Critical area: Ability for bronchospasms to return

Effectiveness of Treatment• Effectiveness was greatly reliant on the

ability of physician and athlete to adequately induce the initial bronchospasm

• During the Senior year• 72% of the games asthma free (8/11)• 2/3 bouts of EIB occurred in the second half• Rare additional Albuterol use with good effect

Uniqueness• The refractory period is a well documented

phenomenon

• It has not been documented as a treatment in the athletic population

• This treatment worked consistently well and minimized the use of medication

Limitations with this Treatment• Time frame does not allow for treatment

prior to practices

• Many trials are needed to accurately predict refractoriness

Implications for Future Research• Can the refractory period be used routinely

to effectively treat athletes?

• Mechanisms behind the refractory period

• Does the refractory period decrease EIB in athletes more effectively than medications?

What do I do with this Information?• Possible treatment strategy

– Diagnosed athlete with breakthrough EIB– Rescue therapy in place

• Provides comfort in return to play decisions for ATC and sports medicine team

Conclusion• The timing of the refractory period can be

manipulated to coincide with the competition, preventing an exercise- induced bronchospasm during play.

Questions

References• 1. Parsons J, Mastronarde J. Exercise - induced bronchoconstriction in athletes. Chest. 2005;128:33966-33974.• 2. Freed A. Models and mechanisms of exerise-induced asthma. Eur Respir J. 1995;8:1770-1785.• 3. Tan R, Spector S. Exercise - Induced Asthma. Sports Med. 1998;25(1):1-6.• 4. Arif A, Delclos G, Lee E, Tortolero S, Whitehead L. Prevalence ad risk factors of asthma and wheezing among US adults:

an analysis of the NHANES III data. Eur Respir J. 2003;21:827-833.• 5. Goodman D, Lozano P, Stukel T, Chang C, Hecht J. Has asthma medication use in children become more frequent, more

appropriate, or both? Pediatrics. 1999;104:187-194.• 6. Ben-Dov I, Bar- Yishay E, Godfrey S. Refractory period after exercise induced asthma unexplained by respiratory heat

loss. Am Rev Respir Dis. 1982;125:530- 534.• 7. Milgrom H, Taussig L. Keeping children with exercise- induced asthma active. Pediatrics. 1999;104:38-43.• 8. Chang- Yeung M, Vyas M, Grzybowski S. Exersice induced asthma. Am Rev Respir Dis. 1971(104):915 - 924.• 9. Mahler D. Exercised- induced asthma. Medicine and Science in Sports and Exercise. 1993;25:554-561.• 10. Haverkamp H, Dempsey J, Miller J. Repeat exercise normalizes the gas- exchange impairment induced by a previous

exercise bout in asthmatic subjects. J Appl Physiol. 2005;99:1843- 1852.• 11. Anderson S, Daviskas E. The mechanism of exercise- induced asthma is. Allergy Clin Immunol. 2000;106:453-459.• 12. McFadden E, Nelson J, Skowronski M, Lenner K. Thermally induced asthma and airway drying. Am J Respir Crit Care

Med. 1999;160:221-226.• 13. Wilson B, Bar-Or O, Seed L. Effects of humid air breathing during arm or treadmill exercise on exercise - induced

bronchoconstriction and refractoriness. Am Rev Respir Dis. 1990(142):349- 352.• 14. Edmunds A, Tooley M, Godfrey S. Refractory period after exercise induced asthma: Its duration and relation to the

severity of exercise. Am Rev Respir Dis. 1978;177:247- 255.• 15. Rosenthal R, Laube B, Hood D, Norman P. Analysis of refractory period after exercise and eucapnic voluntary

hyperventilation challenge. Am Rev Respir Dis. 1990;141:368- 372.• 16. Matsumoto L, Araki H, Tsuda K, et al. Effects of swimming training on aerobic capacity and exercise induced

brochoconstriction in children with bronchial asthma. Thorax. 1999;54:196-201.