Dyspnea and Wheezing in the Athlete

1
Dyspnea and Wheezing in the Athlete

• Joel Shaw MAJ, MD
• Primary Care Sports Medicine
• March, 2007

2
Objectives

• Definition
• Epidemiology
• Pathophysiology
• Presentation
• Diagnosis
• Treatment
• Differential Diagnosis

3
Mandatory Sports Medicine Cartoon
4
Definition

• Asthma- reversible airway obstruction caused by
  chronic airway inflammation and
  hyper-responsiveness.
• Exercise-induced bronchospasm (EIB)- transient
  and reversible airway narrowing precipitated by
  vigorous exercise.

5
Epidemiology

• Chronic asthma
• 1997 NIH expert panel on asthma
• 17 million adults in US
• 5 million children

6
EIB epidemiology

• EIA affects 12-15 of college athletes
• 80-90 of asthmatics report exercise as a trigger
• EIA occurs in 80 of asthmatics who dont use
  inhaled steroids and in 50 who do
• 40 of allergic rhinitis/atopic dermratitis
  patients have EIA
• 10 of normal subjects

7
Achievements by athletes

• 1984 Los Angeles Summer Olympics
• 67 of 597 US athletes had EIA (11.2)
• 41 of these athletes won medals
• 1994 Nagano Winter Olympics
• 17 of US Team had EIA
• 1996 Atlanta Summer Olympics
• 117 out of 699 US athletes had history of asthma
  and/or took medications (16.7)
• 35 of these athletes won medals

8
Olympic B-Agonist Use

• Sydney 2000 gt18 of athletes from Canada, US,
  GB, Australia, New Zealand
• Sydney 2000 sports variation triathlon 20,
  cycling 17, swimming 14.5, track and field 4.1
• Nagono 1988 14-20 in Norway, Sweden, US and
  Australia 33 in Netherlands

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EIB in Cross Country Skiers

• Winter vs. Summer Olympics
• 42 elite cross country skiers Pohjantahti Scand
  J Med Sci Sports 2005.
• 50 of competitive ski mountaineers Durand Int J
  Sports Med 2005

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Pathophysiology of EIBTheory 1

• Thermal Hypothesis (cold air)
• Airways are forced to warm large volumes of air
  during exercise
• High ventilation rates and compensatory mouth
  breathing lead to airway cooling
• Rapid airway rewarming post-exercise causes
  reactive hyperemia of the bronchial
  micro-vasculature and edema of the airway wall

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Pathophysiology of EIBTheory 2

• Osmotic Hypothesis (water loss)
• Airways are forced to humidify large volumes of
  dry air during exercise
• High ventilation rates and compensatory mouth
  breathing lead to evaporative water loss
• Airway dehydration causes increased surface
  osmolarity? mast cell degranulation
• ?Chemical mediator release
• ?Bronchial smooth muscle contraction
• ?Increased bronchial blood flow/airway edema

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Other theories for EIB

• Dog model- airway remodeling similar to asthma
  after exposure to cold, dry air. Davis MSSE 2003
• Sputum samples in EIB show increase in
  eosinophils. Kanazawa Chest 2002
• Concentration of NO in sputum higher in EIB,
  which correlates with vascular permeability
• Combination of vascular permeability, drying,
  inflammation, and airway remodeling

13
Clinical Effects of Cold Air

• Swedish cross country skiers
• 33 incidence vs. 3 age-matched controls
• Norwegian cross country skiers
• 14 compared to 5 age-matched controls
• US winter sports athletes
• 23 incidence, 50 incidence for cross-country
  skiers

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Evidence for chronic changes

• Training gt20 hours/week increased risk of asthma
  development.
• Elite vs. lower level swimmer 21 vs. 11.2
• Endobronchial biopsies cross country skiers
  increased T-lymphocyte, macrophage, eosinophil,
  basement membrane tenascin expression (marker for
  airway modeling) vs. control

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Presentation Patient Symptom Accuracy

• Poor correlation between self-reported symptoms
  and both lab and field challenge tests
• 61 of athletes who were positive on a field test
  reported symptoms
• 45 with a negative challenge reported symptoms
• (Tikkanen et al. Med Sci Sports Exerc 1999)
• Study of college athletes referred for PFTs
  based on history consistent with EIA
• Only 46 had a positive laboratory exercise
  challenge test
• (Rice et al. Ann Allergy 1985)

• Diagnosis of EIA/EIB based purely on symptoms may
  result in either over or underdiagnosis of the
  condition leading to the inappropriate use of
  medications

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Making the DiagnosisThe Medical History

• History of asthma or respiratory symptoms
• Timing of the onset of symptoms
• Duration and severity of symptoms
• Triggers
• ER visits/Hospitalizations/Intubations
• History of allergic rhinitis or atopy
• History of medication use or immunotherapy
• Smoking history
• Family history of asthma or atopy

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Making the DiagnosisThe Medical History

• Useful screening questions
• Have you ever missed school or work due to chest
  tightness, coughing, wheezing, or prolonged
  shortness of breath?
• Do you ever have chest tightness?
• When you exercise, do you often have wheezing?

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Clinical Presentation

• Classic symptoms
• Cough
• Chest tightness
• Shortness of breath
• Burning chest pain
• Wheezing is rare
• Unrecognized symptoms
• Excessive fatigue after exercise
• Poor exercise tolerance
• Decreased athletic performance

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EIB symptoms

• Most commonly symptomatic after exercise
• 3 to 5 minutes after cessation of exercise
• Peak 10 to 20 minutes after exercise
• Late inflammatory phase
• 2 to 12 hours after exercise
• May persist for 1 or 2 days (URI?)
• 30 of patients with EIB Lacroix Phys Sportmed
  1999

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Making the DiagnosisPeak Expiratory Flow

• PEF rate commonly reduced but cannot substitute
  for full PFTs
• Effort dependent
• Less reproducible than FEV1
• Portable devices varying between manufacturers
• Ambulatory monitoring can help with the
  management of asthma
• Look for asthma triggers
• Empowers asthmatics to control their disease
• Early signal for exacerbations
• Monitor effectiveness of therapy

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Making the DiagnosisSpirometry

• Measurement of the FEV1 is the best PFT for
  diagnosing asthma and assessing severity
• Ensure consistent effort/reproducibility
• Spirometry performed looking for baseline
  obstruction (FEV1/FVC lt70)
• If obstruction perform bronchodilator response
  (BDR)
• Look for 12 and 200mL improvement

• Baseline PFTs in mild asthmatics and
• patients with EIB are usually normal

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Making the DiagnosisBronchial Provocation Testing

• After baseline PFT
• Bronchial provocation testing (BPT) is essential
  to demonstrate objective evidence of airway
  hyperresponsiveness.
• Methacholine Challenge
• Exercise Challenge
• Eucapnic Voluntary Hyperventilation

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Making the DiagnosisMethacholine Challenge Test

• More sensitive than exercise challenge
• Low specificity at higher doses.
• Other conditions can have a positive MC.
• Allergic Rhinitis (30)
• Vocal Cord Dysfunction
• Chronic Bronchitis (20)
• Smoking
• 1999 ATS Guidelines
• When pretest likelihood of asthma is 30-70.
• Negative predictive power gt90
• Positive predictive power 90-98 (at PC20 1mg/ml)
  and 70 (at PC20 4mg/ml).

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Making the DiagnosisExercise Challenge

• 8-10 minutes minimum of hard exercise without
  warm-up, following by serial spirometry post
  exercise
• Reproduces environment more accurately
• More sensitive than indoor treadmill tests
• Lack of standardization in methods and
  interpretation of results
• Positive test gt10 drop in FEV1
• Requires access to spirometry to be accurate
• PEF less reliable
• Requires available trained personnel to
  administer

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Making the DiagnosisEucapnic Voluntary
Hyperventilation

• Voluntary hyperventilation of dry air containing
  5 carbon dioxide
• Steady state protocol 85 max ventilation for 6
  minutes
• Similar airway response to exercise at the same
  ventilation
• High specificity for asthma
• 100 with 20 drop of FEV1
• Major problem is access to centers performing the
  test

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EVH compared to Exercise

• Similar level of ventilation and inhaled water
  content of the inspired air
• Airway response on most occasions is delayed to
  after the test
• Majority of subjects have maximum airway response
  within 10 minutes of cessation
• Increasing duration of challenge increases the
  response
• Respond to same drugs
• Production of refractory period

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Environmental ControlAllergen and Irritant
Avoidance

• Dander and Dust mite control
• Mattress covers
• Frequent cleaning
• Avoid carpets
• Choose pets wisely
• Avoid outside activities during peak exposures
• High pollen counts
• Smog/Ozone alerts

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Environmental ControlSport Selection for
Asthmatics

• Choose warm, humid environment over cold and dry
• Choose short burst activities over prolonged
  steady exercise
• Avoid asthma triggers especially for outside
  activities

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Environmental ControlSport Selection for
Asthmatics

• Avoid highly asthmogenic activities
• High minute ventilation
• Distance running
• Cycling
• Soccer
• Basketball
• Rugby
• Cool dry climate
• Ice hockey/ skating, Cross-country skiing

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Environmental ControlSport Selection for
Asthmatics

• Good Choices
• Swimming/Diving
• Gymnastics
• Sprints/Field Events
• Volleyball
• Baseball
• Tennis
• Golf
• Goal Keeper

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Behavioral ControlSport Performance for
Asthmatics

• Use of a mask
• Capture heat and water on expiration
• Found successful in reducing severity of EIA
• Would you wear one??
• Nose breathing
• Promotes inhalation of humidified air
• Achieves similar effect as mask
• Natural switch to mouth breathing at 35 L/min

• Buteyko Breathing Technique
• Developed in 1960sto avoid hyperventilation and
  restore CO2 levels to normal
• Involves controlled shallow breathing with
  intermittent breath holding
• Popular in Australia and New Zealand
• Warm-up/Refractory Period
• 30 second sprints vs. continuous low-intensity
  warm-up
• Shown to induce 1-2 hour refractory period
• May be due to improved bronchial blood flow and
  H2O delivery to surface
• Only effective in approximately 50 of asthmatics
• Inhibited by NSAIDs

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Asthma exacerbation treatment

• Baseline Peak Expiratory Flow (PEF)
• Albuterol- 2 puffs now
• Oxygen if available and needed
• Ambulance vs. watch.

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Return to play

• Peak expiratory flow
• Green- gt80
• May compete with observation
• Yellow- 50-80
• Treat and watch
• Red- lt50
• Transfer

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Medical Treatment For AsthmaBeta2-Agonists

• The most effective drugs for acute symptom relief
• Mechanism
• Relax bronchial smooth muscle?bronchodilation
• Prevent mediator release from mast cells
• Modify contractile effect of mediators on smooth
  muscle
• Short-acting agents used as first line agents for
  pre-treatment prior to exercise in recreational
  athletes and those performing intermittent
  exercise

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Medical Treatment For AsthmaBeta2-Agonists

• Short-acting agents2 puffs 15-30 minutes prior
  to activity lasts 2-4 hours
• Albuterol (Proventil)
• Terbutaline (Brethaire)
• Pirbuterol (Maxair)
• Bitolterol (Tornalate)
• Long-acting agents2 puffs 30-60 minutes prior to
  activity lasts 8-12 hours
• Salmeterol (Serevent)
• Formoterolimmediate and long acting

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Medical Treatment For AsthmaBeta2-Agonists
Problems

• Tolerance develops with prolonged, regular use of
  Beta-Agonists
• Poor asthma control
• Increased bronchial hyperresponsiveness
• May result in reduction in baseline lung function
  if underlying inflammation not controlled in
  chronic asthmatic
• Not recommended for prevention of EIA in regular
  exercisers with frequent symptoms or elite
  athletes

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Medical Treatment For AsthmaMast Cell Stabilizers

• Stabilize mast cell basement membrane preventing
  degranulation
• Effective in early and late phase reaction
• No bronchodilator effect
• Sodium cromoglycate (Intal)
• 2 puffs 30 minutes prior to exercise
• Lasts 2 hours
• Nedocromil sodium (Tilade)
• 2 puffs 30 minutes prior to exercise
• Lasts up to 4 hours

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Medical Treatment For AsthmaAcetylcholine
Receptor Antagonist

• Ipratropium (Atrovent)
• Short-acting bronchodilator with duration of 3-5
  hours
• 2 puffs 15 minutes prior to exercise
• Individual response varies
• Useful as alternate to or in combination with
  albuterol or mast cell stabilizer
• Consider for
• Beta-agonist intolerance
• Incomplete relief with beta-agonist or mast cell
  stabilizer

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Medical Treatment For AsthmaLeukotriene Receptor
Inhibitors

• Daily treatment is effective in preventing
  EIA/EIB
• Studies show an immediate decreased inflammatory
  and bronchoconstrictor response when given prior
  to exercise Rundell Br J Sports Med 2005
• Long term they are more effective than salmeterol
• No tolerance is observed

• Leukotrienes are potent inflammatory mediators
• Bronchoconstrictors
• Increase mucus production
• Increase vascular permeability leading to airway
  edema
• LTIs block action of leukotrienes at the CysLT1
  receptor
• Montelukast (Singulair) 10mg once daily
• Zafirlukast (Accolate) 20mg twice daily

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Medical Treatment For AsthmaOther Agents

• Non-sedating anti-histamines
• Consider in patients with allergic rhinitis or
  allergic triggers
• Immunotherapy
• For atopic patients not otherwise controlled or
  intolerant of meds
• Base on skin test results
• Caffeine
• Bronchodilator and reduces respiratory muscle
  fatigue

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Medical Treatment For AsthmaInhaled Steroids

• Inhaled Corticosteroids
• Triamcinolone (Azmacort)
• Flunisolide (AeroBid)
• Fluticasone (Flovent)
• Advair

• First line therapy for chronic asthma
• Also consider in elite athletes who train nearly
  daily and require consistent prophylaxis
• Alleviate post-exercise cough
• Frequent late phase symptoms

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New research

• 2 grams Vitamin C 1 hour before exercise- 9/20
  patients responded Cohen in Arch Ped Adol Med
• Once daily treatment with Singulair at bedtime
  blocked 47 fall in FEV1 NEJM July 98
• Omega 3 Polyunsaturated fatty acids (fish oil
  supplementation) blocked 80 of fall in FEV1
  Mickleborough Am J Resp Crit Care Med 2003
• Inhaled heparin blocked 78 of drop when used 1
  hour before exercise

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Medical Treatment For AsthmaStepwise Approach

• Mild Intermittent
• Beta2 agonist or mast cell stabilizer as needed
• Mild Persistent
• Inhaled low-potency corticosteroid
• Short-acting Beta-agonist as needed
• /- long acting Beta agonist or leukotriene
  inhibitor

• Moderate Persistent
• Inhaled medium-potency corticosteroid
• Long-acting beta agonist
• Leukotriene inhibitor
• Short-acting Beta-agonist as needed
• Severe Persistent
• As above but increase to high-potency steroid

Consider immunotherapy if atopic
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EIB Treatment Algorithm
Continue treatment Reassess regularly
Pre-Exercise Treatment
Assess Response
Adequate
Control
Inadequate Control
Adequate Control
Add daily medications step-wise
Inadequate Control
Maximize medications Evaluate for other
conditions Bronchoprovocation testing
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Concerns Unique to the Athlete

• Most studies indicate increase in muscle strength
  and endurance in non-asthmatics who use
  Beta-Agonists
• Salbutamol increased strength in 16 of 16 and
  endurance in 10 of 16 non-asthmatic men tested
  Van Baak MSSE 2000
• Athletes believe it is ergogenic
• IOC ban suggests experts believe the same

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Concerns Unique to the AthleteControlled
Medications and Anti-Doping

• USOC Permitted
• Theophylline
• Cromolyn
• Ipratropium
• USOC Prohibited
• Bitolterol
• Metaproterenol
• Orciprenaline
• Oral, rectal, IM or IV corticosteroids
• Oral or injected Beta-agonists

• USOC notification required and by inhalation only
• Albuterol/Ipratropium
• Albuterol
• Salmeterol
• Formoterol
• Terbutaline
• Beclomethasone
• Budesonide
• Dexamethasone
• Flunisolide
• Fluticasone
• Triamcinolone

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Concerns Unique to the AthleteControlled
Medications and Anti-Doping

• September 2001 IOC Anti-Doping Code Update
• Written notification by a respiratory or team
  physician to the relevant medical authority 1
  week prior to competition including
• Detailed report of symptoms
• Hospital/Clinic medical records
• Evidence of positive bronchodilator test,
  positive exercise challenge test or a positive
  methacholine challenge test
• At the Olympics, athletes who request use of
  inhaled Beta-Agonists will be accessed by an
  independent medical panel
• Questionable cases will be retested prior to Games

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EIB Testing in the 2002 Winter Olympics

• 135 of 147 EIB challenge tests were approved
• FEV1 response to bronchodilators averaged 16.2
• ECT led to 15.9 average drop in FEV1

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Controlled Medications and Anti-Doping

• Medication information and documentation
  requirements
• World Anti-Doping Agency (WADA)
• www.wada-ama.org
• United States Anti Doping Agency (USADA)
• www.usantidoping.org

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Differential Diagnosis

• All that wheezes is not asthma.
• Asthma doesnt always wheeze.

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Differential Diagnosis

• Vocal cord dysfunction
• Gastroesophageal reflux disease
• Chronic inflammatory asthma-like condition
• Laryngopharungeal reflux

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Vocal Cord Dysfunction- Prevalence

• 10-15 of unresponsive asthma
• Correlation with psychiatric disorder
• Femalemale gt 21
• Age 20-40 yoa

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Vocal Cord Dysfunction- Pathogenesis

• Vocal cord closing
• Normal- during inspiration
• VCD- during expiration

• Triggers
• URI
• Exposure (smoke, chemicals, pollution)
• Stress
• GERD
• Cold air
• Exercise

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Vocal Cord Dysfunction- Symptoms

• Dyspnea
• Wheeze
• Cough
• Chest tightness

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Vocal Cord Dysfunction- Physical Exam

• Normal at rest
• Stridor
• During or after exercise
• Often early in exercise
• During stressful situations

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Vocal Cord Dysfunction- Diagnosis

• PFTs
• Flattening of inspiratory loop
• Only positive if performed while symptomatic
• Direct Laryngoscopy
• Gold standard
• Performed when patient is symptomatic

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Vocal Cord Dysfunction- Treatment

• Classic asthma medications
• Usually no change unless combined disorder
• Breathing exercises
• Abdominal breathing?relax upper respiratory
  musculature
• Stress management
• Medications
• Heliox (20-40 helium in O2)
• Botulinum toxin injection

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GERD

• Common in asthmatic patients
• 199 asthmatic patients 82 reflux symptoms, 72
  esophageal pH testing Harding Chest 1999
• Adults with asthma 77 heartburn, 55
  regurgitation, 24 dysphagia Field Chest 1996
• Children with asthma similar GERD rate to adults
  based on 24 hour esophageal pH testing Harding Am
  J Med 2003

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GERD as trigger for asthma

• Not proven
• Proposed meachnisms
• Aspiration/microaspiration in tracheobronchial
  tree
• Acid-induced esophago-bronchial vagal reflexes
  mediated by receptors in esophageal wall

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GERD and Asthma

• 1- Stimulation of vagal afferents
• Microaspiration
• Acid refluxed directly onto esophageal epithelium
• 2- Airway vagal efferent response
• 3- Pulmonary neuroinflammatory changes
• Airway edema
• Mucus production
• Inflammation
• Bronchial smooth muscle constriction

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Treatment of GERD for Respiratory Symptoms

• Non-pharmacologic
• Diet
• Food type
• Meal timing
• Raise head of bed
• Weight control
• Stress management
• Avoid tobacco products

• Medications
• H2-blockers
• Proton pump inhibitors

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GERD treatment

• Is GERD treatment beneficial for asthma
• May improve subjective symptoms
• May reduce medication requirements
• No evidence of improved lung function by
  spirometry

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GERD response to Albuterol

• Effects of Albuterol
• Reduction of LES tone
• Reduction of esophageal contraction amplitude

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Chronic Inflammatory Asthma-like Condition

• Cold weather athletes
• High ventilation rates under specific conditions
• Cold, dry air
• Exposure to volatized fluorocarbons (ski wax
  rooms)
• Exposure to exhaust from ice resurfacing machines

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Chronic Inflammatory Asthma-like Condition

• Airway remodeling pathologically different from
  asthma
• Similar symptoms to EIB
• May not respond to Albuterol
• EIB short-track speedskaters did not improve
  airway function with Albuterol Wilber Chest 2001
• Inflammation not addressed (inhaled steroids)
• Consider in-rink testing

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Laryngopharyngeal reflux

• Prevalence
• Unknown
• Pathogenesis
• Reflux reaches the UES causing irritation of the
  larynx and pharynx
• Small amounts of acid exposure can cause
  significant irritation

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Laryngopharyngeal Reflux- Symptoms

• Hoarseness
• Excess mucus
• Throat clearing
• Globus
• Cough
• Dysphagia
• Heartburn is RARE

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Laryngopharyngeal Reflux- Diagnosis

• Physical exam
• Typically normal
• Diagnostic tests
• 24 hour pharyngo-esophageal pH monitoring
• Nasopharyngolaryngoscopy
• Erythema
• Edema
• Ulceration

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Laryngopharyngeal Reflux- Treatment

• Classic, non-pharmacologic GERD treatments
• H2-blockers
• Proton Pump Inhibitors

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Summary

• Control of airway inflammation in chronic asthma
  is critical for prevention/treatment of EIB
• Maximize EIB control with attention to
  environment, behavior, and medications
• Remember other causes of wheezing
• Sports participation and exercise are both
  beneficial to all patients with asthma
• Asthmatics compete and win at the highest levels
  in sports

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Questions??