Respiratory physiopathology I ASTHMA EXERCISEINDUCED ASTHMA PY

Respiratory physiopathology I ASTHMA & EXERCISEINDUCED ASTHMA PY 3002 Dr P. KIPPELEN School of Medical Sciences University of Aberdeen

LECTURE OUTLINE n What is asthma? n Why does exercise trigger-off asthma attacks? n Prevalence of asthma in u the general population

DESCRIPTION n n Chronic pulmonary disorder Obstructive disease n With recurrent attacks of u u u Wheezing Shortness of breath Cough

DEFINITION of ASTHMA n n Inflammatory disorders of the airways Paroxysmal or persistent symptoms u u Dyspnea Chest tightness Wheezing u Sputum production u Cough u n Variable airflow limitation n Variable degree of airway hyperresponsiveness (AHR) to Endogenous stimuli u Exogenous stimuli u Canadian Asthma Consensus Guidelines 1999 AHR = abnormally large response of the airways to the inhalation of minor irritants such as cold air

CAUSES Hypersensitivity reaction in air passage Over-activity and spasm Swelling of the passages and thickening of lung secretions diameter or total closure of the airways

MAIN STIMULI n Allergens u u n Air irritants u u u n Pollen Dust Smoke Pollutants Chlorine Aspirin n Lung infections u n Bronchitis EXERCISE

EXERCISE-INDUCED ASTHMA (EIA) n n Transient narrowing of the airways that follows vigorous exercise In people with a clinical diagnosis of asthma EXERCISE-INDUCED BRONCHOCONSTRICTION (EIB) n Transient airway narrowing in those who do not have a clinical diagnosis of asthma

AIRWAY NARROWING FEV 1 in Litres 5 4 < 10% Normal < 25% Mild 3 > 25% Moderate 2 > 50% Severe Exercise 1 0 8 14 Time in Minutes 20

FACTORS DETERMINING EIA / EIB n Temperature & water content of inspired air n Level of ventilation reached and sustained during exercise u u u At rest: VE = 5 -10 L/min Maximal exercise in untrained subject = 100140 L/min Elite endurance athlete = 160 -200 L/min

THERMAL THEORY Mc. Fadden et al. 1986, 1990, 1999 n Increased ventilation Exercise Mucosal cooling Vasoconstriction n End of exercise Rapid rewarming Vascular engorgement and oedema ! No mediators Airway narrowing

POSTEXERTIONAL AIRWAY REWARMING Mc. Fadden et al. , 1986 n Pattern of airway response in 8 asthmatic subjects Exercise: 4 min to exhaustion Recovery: 5 min Temperature of inhaled air EXO RECOVERY 1: cold + cold 2: cold + room 3: cold + body 4: body + room FEV 1 (%) -30 -20 -10 0 1 2 3 4

OSMOTIC THEORY Anderson et al. , 1982, 1984 n Exercise Increased ventilation Dehydration of airways surface liquid ASL [Na+], [Cl-], [Ca 2+], [K+] Cough Increased osmolarity of ASL Mucus Water moves from cells to restore ASL Cell shrink Mediators released (histamine, PG, LT) Smooth muscle contraction ± oedema Airway narrowing

INSPIRED WATER CONTENT

INSPIRED WATER CONTENT 50 % Fall FEV 1 40 30 20 10 0 0 10 20 30 40 50 INSPIRED WATER mg/L Anderson et al. , 1982 Eur J Respir Dis 63; 459 -71

A UNIFYING THEORY Anderson et al. , 1999, 2000 Vigorous exercise If cold air inhaled ventilation heat loss Respiratory water loss +++ Recruitment of smaller airways (10 to 12 th generation) Hyperaemia Oedema Mucosal dehydration +++ Airway narrowing

Scotland: 18. 4% England: 15. 3% USA: 10. 9% France: 6. 8% China: 2. 1% GINA, 2004

CONCLUSION n Asthma = chronic inflammation of the airways associated with variable airflow limitation & symptoms n Exercise = major stimulus because of water loss induced by hyperventilation n 300 million people of all ages, and all ethnic backgrounds suffer from asthma u u Prevalence increasing worldwide Prevalence +++ in English-speaking countries

Respiratory physiopathology II ATHMA IN ATHLETES PY 3002 Dr P. KIPPELEN School of Medical Sciences University of Aberdeen

LECTURE OUTLINE n Prevalence of asthma and exercise-induced asthma (EIA) in different sports u u u n Amateur versus elite Winter versus summer Endurance versus resistance Environmental factors triggering EIA u u u Cold dry air Allergens Pollutants

FAMOUS ATHLETES WITH ASTHMA

PREVALENCE OF EIA IN ATHLETES n Amateur athletes u u n 5. 3% South of France (Kippelen et al. , 2003) versus 6. 8% in the general population Elite athletes u US track & field Championships: 15% (Schoene et al. , 1997) u US Winter Olympic Team, 1998: 23% (Wilber et al. , 2000) ! versus 10. 9% in the US population

SUMMER versus WINTER SPORTS n Asthma in US Team (Weiler et al. , 1998, 2000) u 1996 Summer Games (n=699): t t u 15. 3% with a previous diagnosis of asthma 10. 4% current use of asthma medication 1998 Winter Games (n=196): t t 21. 9% with a previous diagnosis of asthma 17. 4% current use of asthma medication Prevalence higher in winter activities

COLD DRY AIR n Larsson et al. , BMJ, 307: 1326 -9, 1993 u n 80% of cross country skiers with asthma or AHR, or both Sue-Chu et al. , Respir Med, 90: 99 -105, 1996 u u cross country skiers from Norway & Sweden (colder drier winters) t t In Norway, 14% of the skiers present AHR compared to 43% in Sweden clinically diagnosed asthma 12% in Norway and 42% in Sweden Inhalation of cold dry air during exercise triggers of asthma & AHR (“ski asthma”)

INHALED BETA 2 -AGONISTS USE IN SUMMER OLYMPICS SYDNEY 2000 (notified) ATHENS 2004 (approved) IBAs PERCENT 11 65 62 50 11 4 11. 3% 13. 7% 23. 3% 9. 1% 4. 1% 6. 6% n NOC IBAs n NZL AUS UK USA CAN FIN 31 128 62 112 55 10 n n n PERCENT 21. 1% 20. 7% 19. 9% 18. 6% 14. 3% Uneven geographic distribution

INHALED BETA 2 -AGONISTS USE IN WINTER OLYMPICS NOC TORINO 2006 SLC 2002 NAGANO 1998 NOR NED GBR AUS SUI USA 31. 9% 27. 3% 20. 5% 17. 5% 15. 7% 12. 1% 9. 9%# 22. 6% 4. 0% 19. 2% 18. 8% 12. 9% 14. 5% 33. 3% 4. 8% 20. 0% 4. 2% 16. 9% # IF ALL NOR APPLICATIONS HAD BEEN APPROVED = 21. 0%

BETA 2 -AGONISTS USE BY SPORTS SYDNEY (2000) n n n Triathlon Cycling Mod Pent Swimming Rowing Canoeing Athletics ATHENS (2004) 20. 0% 17. 3% 14. 6% 14. 5% 8. 8% 7. 0% 4. 1% Prevalence higher in endurance sport 12. 1% 13. 4% 12. 5% 10. 3% 6. 3% 4. 9% 4. 4%

BETA 2 -AGONISTS USE BY SPORTS TORINO SLC NAGANO (2006) (2002) (1998) 16. 9% 13. 6% 14. 9% 9. 3% 10. 4% 14. 8% 10. 6% 10. 4% 8. 2% 4. 4% 17. 9% 12. 2% 17. 4% 3. 9% 10. 7% n Cross country Nordic Comb Speed skating Biathlon Short track Ø Prevalence higher in endurance sport n n

COLD DRY AIR & EIA Anderson et al. , 1999, 2000 Vigorous exercise If cold air inhaled If dry air is inhaled ventilation heat loss +++ Respiratory water loss +++ Recruitment of smaller airways (10 to 12 th generation) Hyperaemia Oedema +++ Mucosal dehydration +++ Airway narrowing

HYPERVENTILATION & EPITHELIAL SHEDDING n In endurance-trained athletes high ventilatory flow rates severe dehydration of the airways +/- mechanical stress epithelial disruptions AHR u Normal epithelium Damaged epithelium

ENDURANCE versus SPEED & POWER SPORTS n Helenius et al. , Thorax, 52: 157– 160, 1997 u u u ASTHMA PREVALENCE Controls 3% Long distance runners 17% Speed and power athletes 8% t t t Sprinters Jumpers, decathletes Throwers 7% 6% 15% Hypothesis: prolonged hyperventilation + increased exposure to allergens & irritants

ALLERGY & ASTHMA n Helenius et al. , J Allergy Clin Immunol; 101: 646 -52, 1998 u Odd ratio for the occurrence of total asthma: 7. 54 in atopic versus non-atopic athletes Asthma strongly associated with atopy

ALLERGY & EIA Exercise ALLERGENS / POLLUANTS High ventilatory flow rates n Allergic reaction u Epithelial lesions Production of Ig. E antibodies Mast cells activation Inflammatory mediators release (e. g. , histamine) permeability Stimulation vagal terminaisons BRONCHONSTRICTION INFLAMMATION

POLLUTION & ASTHMA n Mc. Connell et al. , The lancet, 359: 386 -91, 2002 u Protocol t t t u 3535 children with no history of asthma Recruited from 12 communities in southern California with variable ozone levels Followed-up for 5 yr Results t In communities with high [O 3], relative risk of developing asthma: 3. 3 in children playing 3 or more sports, compared with children playing no sport Outdoor exercise + air pollution may favour the development of asthma in children

EFFECTS OF OZONE ON HUMAN HEALTH n O 3 due to chemical interactions of different hydrocarbons and radicals and NO 2 needs sunlight peak during the summer months u n Effects u u n Nose and throat irritation Cough, wheezing and shortness of breath Inability to take deep breaths because of substernal chest pain or constriction Abnormalities of pulmonary function 50% of US population live in areas that exceed current National Ambient Air Quality Standards for O 3 (Gong et al. , 1995)

OZONE EXPOSURE IN ATHLETES n Negative effects u on the health: t u ongoing inflammation in the lung of joggers during the summer months (Kinney et al. , 1996) on exercise performance (Gong et al. , Am Rev Respir Dis, 1986; Schelegle et Adams, MSSE, 1986) t peak performance t sensation of effort

EFFECTS OF PARTICULATE MATTER ON HUMAN HEALTH n n Solid or liquid material present in the air in particles small enough to remain in suspension for some hr or days Lead and other carcinogens Peaks during smogs In ice hockey u [PM 1] in ice rinks resurfaced with fossil-fuel machines 20 -fold greater than outside air or in rinks resurfaced with electricpowered machines (Rundell, 2003)

LEVELS OF PM 1 ON PLAYGROUNDS n Rundell et al. , Inhalation Toxicology, 18: 541– 547, 2006 Elementary school

LEVELS OF PM 1 ON ATHLETIC FIELDS n Rundell et al. , Inhalation Toxicology, 18: 541– 547, 2006 Interstate highway 29% 50% University soccer field

EFFECTS OF PARTICULATE MATTER IN ICE HOCKEY PLAYERS n Rundell, Inhalation Toxicology, 16: 117– 123, 2004 Rate of lung function change over a 4 yr training period Nordic skiers control subjects Woman ice hockey players [PM 1] related to lung function decay in ice rink athletes

WHY ARE ATHLETES PARTICULARLY AT RISK ? Exercise High ventilatory flow rates quantity of pollutants inhaled Larger fraction of air inhaled through the mouth Bypass the filtration system of the nose diffusion of pollutants gases Pollutants carried deeper into the airways

THE CASE OF CHLORINE n NCL 3 = strong irritants u u for eyes and upper respiratory tract (Massin et al. , 1998) inflammation and oedema of the mucous membrane (Potts, 1996) n Accidental exposures responsible for cases of acute lung injury (Tanen et al. 1999, Agabiti et al. 2001) n Levels strictly controlled in swimming pools, but… u during a 2 hr training period, swimmers can be exposed to amounts of chorine > US recommendation for a worker with 8 hr exposure ! (Drobnik et al. , 1996) Up to 50% of elite swimmers present AHR (Helenius et al. , 1998)

HIGHLY TRAINED SWIMMERS n Helenius et al. , J Allergy Clin Immunol, 109: 962– 8, 2002 5 yr follow-up

HIGHLY TRAINED SWIMMERS n Helenius et al. , J Allergy Clin Immunol, 109: 962– 8, 2002 5 yr follow-up damages partly reversible

CONCLUSION n Elite athletes at risk for asthma u Endurance athletes t u Winter sport athletes (cross country skiers + ice hockey players) t t u Because of the high ventilatory levels reached and maintained during exercise Because of the accelerated dehydration of the airways while breathing cold dry air Air pollution in ice rinks Swimmers t Because of the irritant effects of chlorine Environment = key factor in asthma development in athletes

FURTHER READING BOOK n Allergy and respiratory disease in sports medicine. Clinical Allergy and Immunology. Edited by Weiler JM. Marcel Dekker Inc, 1997 REVIEWS n Anderson SD, Holzer K. Exercise-induced asthma: is it the right diagnosis in elite athletes? J Allergy Clin Immunol. 2000 Sep; 106(3): 419 -28. n Helenius I, Haahtela T. Allergy and asthma in elite summer sport athletes. J Allergy Clin Immunol. 2000 Sep; 106(3): 444 -52. n Rundell KW, Jenkinson DM. Exercise-induced bronchospasm in the elite athlete. Sports Med. 2002; 32(9): 583 -600.