Sergio Bonini. Professor of Internal Medicine, Second University of Naples INMM-CNR, Rome, Italy.

Transcription

1 Assessment of EIA in the community and in athletes: the role of standardized questionnaires Sergio Bonini Professor of Internal Medicine, Second University of Naples INMM-CNR, Rome, Italy

2 EIA Case 1 30-year old white woman with an office administrative position Lifelong history of asthma which became quiescent in the late teens 5 year ago shortness of breath when recovering from exercise No symptoms after 320 µ/daily beclomethasone with salbutamol as an as-needed rescuse medication N Engl J Med 2007; 356: 296

3 EIA Case 2 7-year old girl referring chest tightness after running No family or personal history of atopy, asthma or wheezing Skin-tets negative Wheeze after a 5-min open-air run (associated with a 15% drop of PEF values) Serafini U, Bonini S. Int J Tissue Reac 1979; 1: Serafini U, Bonini S. Clin Exp Allergy 1981; 10:

4 EIA Case 3 22-year old italian olympic swimmer with negative history soy(episodic coughafter training) No personal and family history of asthma Skin-tets positive to grass and house dust mites Normal pulmonary function tests Positive exercise-challenge (treadmill) and EVH test Lapucci G et al. J Allergy Clin Immunol 2003; 111: S142

5 Working definitions of Exercise-Induced dasthma (EIA) and Exercise-Induced Brochospasm (EIB) EIA: the condition in which exercise induces symptoms of asthma in patients who have asthma EIB: the airways obstruction that occurs in association with exercise without regard to the presence of chronic asthma Weiler JM, Bonini S, Coifman R, et al. J Allergy Clin Immunol 2007; 119:

6 Phenotypes of EIA 1. Exercise induces symptoms in an asthmatic patient EIA 2. Exercise-induced symptoms in a healthy child EIB 3. Positive exercise challenge in an (allergic) athlete EIB

7 Assessment of feia EIA is a sign of poor asthma control Assessment of EIA implies the diagnosis of asthma, to be made according to GINA guidelines Bronchial hyperreactivity y can be documented both by direct (histamine, methacholine) and indirect (exercise, EVH, mannitol) bronchial challenge

8 Assessment of EIB In the general population In athletes

9 Assessment of EIB in the general population 5-15% of subjects More frequent in children Associated with respiratory diseases (wheezing, rhinitis, URTI, cistic fibrosis)

10 Factors which h influence EIB Type of physical exercise > running, cycling < swimming Duration of physical activity (recovery after a short exercise: 3-6 minutes) Environmental conditions (cold, allergens, pollutants)

11 For many yy years, it was generally assumed that this was because the severity of exercise was also different. EFFECT OF EXERCISE TYPE Frequency and Severity Free-range running ( 47% PEF ) of feia Running on a treadmill Cycling ( 25%) ( 33% ) Swimming,kayaking,walking ( 15%) Anderson, Br J Dis Chest 1975 ; Fitch, JAMA 1976

12 The Ferrari-Maserati Study Ferrari, Maranello N of cases Mean age (range) M/F (4-14) 1.17 Usl H (11-15) 0.96 Rome Methods: Questionnaires (ISAAC; Style of Life) Allergy and Pulmonary Function Tests Body Mass Index (BMI)

13 EIB prevalence in school children % in Rome 13.7 in Maranello EIB Chest Cough Dyspnoea yp Tightness

14 Distribution of the population pp samples on the basis of BMI Rome Maranello Male Male Female 60 Female Normal weight Overweight Obese Normal weight Overweight Obese Overweight: BMI Obese: BMI > 30.00

15 Lifestyle in the populations studied Rome 22.8 TV PC Open Air Indoor SPORTS SPORTS >2h/day >2h/week Maranello TV PC Open Air Indoor SPORTS SPORTS >2h/day >2h/week

16 Assessment of EIB in the general population PEF monitoring after free-range 3-6 min running in children Pulmonary function tests and bronchial provocation tests in adults But is EIB a phenotype of asthma? Or a risk-factor for asthma?

17 THE SPECTRUM OF ALLERGIC DISEASE HLA genes and Genetic and environmental influences causing 5q cluster- Neural and allergen exposure cytokine genes overexpression tissue factor (?) GM-CSF Il-4 IL-3 IL-5 Enhanced specific IgE response High total IgE Upregulation of inflammatory cells Increased number Eosinophilic and releasability of inflammation MC and basophils Tissue hyperreactivity I II III IV V Clinical phenotypes

18 EIB in Athletes Higher prevalence than in other populations Reported and objectively assessed in a higher number of athletes than those with clinical asthma, particularly in winter sports Peculiar mechanisms (osmotic, thermal and mechanical) linked to hyperpnea. Often associated with neutrophilic rather than eosinophilic inflammation. Autonomic deregulation? Poorly predicted by baseline pulmonary function tests More frequently associated with a positive indirect provocation test (office or field exercise, eucapnic voluntary hyperventilation, mannitol, etc.) than with direct provocation tests (methacholine, histamine) Less responsive to inhaled corticosteroids than EIA.

19 Prevalence of EIB in Athletes Swimmers Controls Zwick et al., Lung 1990; 168: % 36% Potts, Sports Med 1996; 21: % 12%

20 Bonini M. et al. Allergy 2007; 62:

21 Assessment of feib in athletes t EIB may affect perfomances According to IOC rules, only documentation of EIB may justify a TUE for using beta-2 agonists

22 Anti-Allergic Allergic drugs and WADA regulations Treatment WADA rules Notes Antihistamines Antileukotrienes Oral steroids Topical steroids Oral b2 agonists Inhaled b2 agonists salbutamol, terbutaline formoterol, salmeterol Ephedrine, methylephedrine Immunotherapy Permitted Permitted Prohibited in competition require TUE Require A-TUE Prohibited Require A-TUE Prohibited in competition Permitted Second generation molecules should be preferred to avoid side effects Topical preparations for dermatological, auricolar, nasal, buccal, ophtalmic use are not prohibited A concentration of salbutamol greater than 1000 ng/ml is considered an adverse analytical finding umless proven as due to therapeutic use A concentration in urine greater than 10 ug/ml represent an adverse analytical findings SCIT should not be performed before or after physical exercise

23 AQUA Allergy QUestionnaire for Athletes Bonini M et al. MSSE submitted

24 AQUA (Methodology) Derived from the ECRHS questionnaire On the basis of interviews with team doctors, coaches and athletes specific questions were added Preliminary administration to verify comprehensiveness and reproducibility Administration to 128 professional soccer players of 6 elite teams Validation against documented clinical allergy (Anamnesis, OE, Skin-prick-test and/or Phadiatop) Key-questions scored from 1 to 5 on the basis of their positive likelihood ratio

25 AQUA Allergy QUestionnaire for Athletes Bonini M et al. MSSE submitted

26 AQUA (Results) Sensitization to the inhalant allergens tested was present in 46.8% of athletes (60/128). % ANY ALLERGIC DISEASE RHINITIS CONJUNCTIVITIS DERMATITIS ASTHMA Nine athletes referred food allergy and four adverse reactions to drugs. A total score > 5 showed the best positive predictive value for allergy (0.93) with a specificity of 97.1% and a sensitivity of 58.3%.

27 AQUA scores Question Sensitivity % Specificity % LR+ Score Q Q Q5 Q Q Q15 Q Q. 7b ---* ---* ---* 3 Q. 7c Q. 7d Q Q Q Q12 Q Q

28 IOC criteria requested to document the presence of asthma at Beijing Olympic Games in 2008 An increase in FEV1 of 12% or more of the baseline or predicted FEV1 and exceeds 200 ml after administering an inhaled permitted beta-2 agonist by inhalation. A fall in FEV1 of 10% or more from baseline recorded during the first 30 minutes post field or laboratory exercise test or after a 6 minutes period of hyperpnoea in dry air. A fall in FEV1 of 15% or more from baseline after a dose of 22.5 ml of 4.5 gm% saline (e.g. 4.5 g NaCl/100 ml water) or a dose of 635 mg of dry powdered mannitol A fall in FEV1 of 20% or more from baseline at a dose of methacoline (PD20) less than or equal to 400 mcg/2 micromoles (cumulative dose) or 200 mcg/1 micromole (non cumulative dose), or at a concentration (PC20), less than or equal to 4 mg/ml. For applicants taking inhaled steroids for at least one month, the PD20 should be less than or equal to 1600 mcg/8.0 micromoles (cumulative dose) or 800 mcg/4.0 micromoles (non cumulative dose), or a PC20 less than or equal to16.o mg/ml.