Astmafenotyper. Symposium Om Idrott Och Astma Moderator Søren Wille Sponsor GSK Läkemedel. Astma Fenotyper Klinisk Fysiologisk /Svårighetsgrad

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1 Symposium Om Idrott Och Astma Moderator Søren Wille Sponsor GSK Läkemedel Professor Kjell Larsson Enheten för Lung & Allergiforskning Karolinska Institutet Stockholm Idrotts-Astma patologi och prevalens Dr. Kerstin Romberg Näsets Läkargrupp, Höllviken. Utredning och omhändertagande av ungdomar med idrotts astma Kaffe + Utställningsbesök Dr. Sverker Nilsson Neptunuskliniken Varberg och Förbundsläkare Friidrottsförbundet Stockholm Doping Idrott och Astma. Vilka läkemedel är tillåtna Hur skriva läkare intyg Vilka krav ställs på diagnos Minisymposium Idrott och Hjärta Råd och Risker Doc Göran Wetrell Barncardiologen USIL Idrott och hjärtdöd Hur vanligt Hur farligt Vad skall utredas och hur Astmafenotyper Klinisk/fysiologisk Svårighetsgrad Inflammation/Patologi Läkemedelsrespons Utlösande faktorer Anpassat efter Sally Wenzel AAAAI Miami 26 Astma Fenotyper Klinisk Fysiologisk /Svårighetsgrad Astma fenotyper Patologi Mild intermittent Debutålder Mild persisterande Svårighetsgrad Moderat intermittent Labil/Stabil Moderat Kronisk lungfunktionssänkning persisterande Svår intermittent Svår persisterande Fatal FETMA Smala luftrör Neutrofil inflammation Eosinofil Inflammation Bronkiel Hypereaktivitet Pauci Granulocyt Fenotyper Behandlings respons Cromon Teofyllin Anti IgE Teofyllin Anticholinergica Antibiotika GERD Astma Fenotyper Triggers Idrott Menstruations astma Steroid Känsliga LTA känsliga Host astma Ansträngning Infektion Svår astma NSAID astma KOL Allergisk astma Beta 2 agonist känsliga Sensorisk Hyper reaktivitet VCD 1

2 Idrott och astma Kjell Larsson Enh för Lung och Allergiforskning IMM Karolinska Institutet Helsingborg The two questions of asthma and exercise Does exercise induce bronchoconstricti on in asthmatic subjects? Does exercise cause asthma in healthy subjects? Exercise-induced bronchoconstricti on Exercise induced = Hyperventilation induced = Cold air induced Airway response to exercise Influencing factors Airflow Air water content Air temperature? Bronchial responsiveness Stimulus Dry air Cold air High ventilation Response Bronchial responsiveness Activation of inflammatory mechanisms 2

3 3 Exercise-induced Ansträngningsutlöst bronkobstruktion vid olika typer av arbete FEV1 (%) 1 9 Exercise Minutes 6 8 min exercise Post-exercise Type of exercise is of importance FEV1-sänkning efter arbete Exercise at different temperatures Asthmatic vs healthy subjects Bronchial responsiveness to histamine in asthmatic subjects Asthma FEV1 decrease (%) Warm air + saline Cold air + saline Warm air + histamine Cold air + histamine Exercise in ambient temperature Exercise in cold-air conditions Oseid et al Scand J Med Sci Sports 1995;5:88 Number of inhalations n=7 Dosman et al ARRD 1992;144:45 Exercise-induced The vascular hypothesis Vasoconstriction Vasodilation and vascular engorgement Airway cooling during exercise Rewarming after exercise McFadden et al Water content of the air at different temperatures Water content (g/m 3 ) Temperature ( C) Temperature ( C) H 2 O-content (g/m 3 ),9 2,2 9,4 17,3 3,4 5,

4 Cold air = Dry air Hyperventilation - air temperature sraw (l x cm H 2 O/l/s) 15 8 Hot Cold Ventilation (L/min) FromEschenbacher & Sheppard ARRD 1985;131:894 Increasing ventilation of hot (38.4 C) and cold (-23. C) dry air in one patient with asthma Retrotracheal temperature is lower during inhalation of cold air. The osmolarity hypothesis Relationship between airway responsiveness to eucapnic hyperpnea and exercise in 38 athletes Airway epithelium Airway lining fluid Dry air Airway lumen Water Increased osmolarity Mediator release Anderson et al Rundell et al Chest 24;125:99 Relationship between response to dry air and mannitol Hyperventilation Water loss Heat loss Increased osmolarity Airway cooling Inflammatory responses Airway rewarming Holzer AJRCCM 23;167:534 Airway obstruction Airway vascular engorgement 4

5 Post exercise fall in FEV 1 Exercise induced Refractory period Warm humid air Cold dry air Redrawn from Ben-Dov et al ARRD 1982;125:53 Hyperventilation Release of cysteinyl-leukotrienes Activation of cys-lt1 receptors Bronchoconstriction Release of prostaglandins (PGE 2 ) Bronchial responsiveness to histamine in healthy subjects Exercise-induced asthma PC 15 FEV 1 (histamine) Warm humid air Cold dry air Redrawn from Amirav et al 1989 BAL in healthy subjects after light exercise in cold or normal indoor air Granulocytes (1 6 cells/l) p=.1 Lymphocytes (1 6 cells/l) Alveolar macrophages (1 6 cells/l) p=.3 Bronchial responsiveness in athletes and controls Athletes (n=1) (n=5) 2 1 p= C -22 C +23 C -22 C +23 C -22 C Larsson et al ERJ 1998,12:825 Langdeau AJRCCM 2;161:1479 5

6 Asthma in cross-country skiers Positive answers (%) Physician diagnosed asthma Asthma symptoms Asthma medication n = n = 127 Larsson L et al Scand J Med Sci Sports 1994;4: Cross-country skiers Hay fever, family history Positive answers (%) Hay fever Family history of asthma n = n = Larsson L et al Scand J Med Sci Sports 1994;4:124 Symptoms in elite cross country skiers and controls (n=29) Cough 5 Wheezing 6 Breathlessness 4 Chest tightness (n=42) Larsson K et al BMJ 1993;37:1326 p-value < Lung function in elite cross country skiers and controls % of pred * TLC RV VC FEV 1 * * Referents FEV 1 /VC Referents:.81 :.83 Larsson K et al BMJ 1993;37:1326 Larsson et al BMJ 1993 Median 25th 75 th percentiles n Referents Median 25th 75 th percentiles n p PC 2 FEV 1 (mg/ml) Winter 2,5 1, - 6,1 42 6,5 3, - 64, 29 Summe r 2,8,8-8, ,4 2,6-64, 27 Winter -9,9-21,2 to - 2,8 42-1,9-8,7 to -,9 29 Slope (%/mg) Summe r -9,1-24, to - 2,4 37-1,4-5,4 to -,4 27 Asthma in cross country skiers Sweden vs Norway Prevalence (%) Asthma symptoms p< p Bronchial hyperresponsiveness Current asthma 9 28 Norway Sweden Sue-Chu et al Respir Med 1996;9:99 6

7 Asthma in Finnish summer athletes and controls Athletes (%) n = 162 (%) n = 45 Current asthma * Total asthma # * Current asthma symptoms and increased bronchial responsiveness (BHR) # Current asthma symptoms and BHR or physician diagnosed asthma Helenius et al JACI 1998;11:646 Asthma in Finnish athletes (Physician diagnosed asthma in Finnish athletes compared with healthy controls) Odds ratio 95% confidence interval 6.7 Long distance runners Speed/power athletes Helenius et al Thorax 1997;52:157 Faktorer som påverkar astmautveckling hos elitidrottare Lifetime occurrence of asthma and allergic rhinitis in former Finnish top athletes Faktorer som är relaterade till arbetet i sig Faktorer relaterade till miljön i vilken arbetet utförs Athletes (total) (n = 1282) (n = 777) Long distance runners (n = 125) Cross country skiers (n = 8) Asthma (%) 2.4 Allergic rhinitis (%) Kujala et al Thorax 1996;51:288 Similarities and differences between skiers asthma and classical asthma = asthma Symptoms Airway lymphocytosis Cytokines (TNF) BHR to direct stimuli Airway response to exercise (?) Thickening of airway basement membrane asthma Airway eosinophils and mast cells BALT Airway response to adenosine Exhaled NO Response to inhaled steroids (?) Athletes asthma route High ventilation of cold? dry? air Acute airway neutrophilia Airway remodelling? Asthma Time 7

8 Exercise induced Conclusions Exercise hyperventilation Water loss of importance Air temperature probably of minor importance Inflammatory mechanisms seem to be involved Late reaction to exercise may occur in some patients A refractory period is often observed Exercise induced asthma Conclusions Asthma is more common in elite athletes than in the general population Exercise at low temperature increases the risk The risk seems to be greater for long distance runners than for speed and power athletes Increased prevalence of asthma among top athletes seems to be new problem 8