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ASTHMA UPDATE

ASTHMA UPDATE. NEW DIRECTIONS IN 2009 CHANGES IN NIH GUIDELINES CONTROL VS. SEVERITY HETEROGENEITY REGARDING ETIOLOGY DIFFERENT PHENOTYPES DIFFERENTIAL DIAGNOSIS- MASQUERADERS BETTER MONITORING ASTHMA EDUCATION BETTER SELF MONITORING MEDICAL MONITORING:SPIROMETRY NEW THERAPIES

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ASTHMA UPDATE

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  1. ASTHMA UPDATE • NEW DIRECTIONS IN 2009 • CHANGES IN NIH GUIDELINES • CONTROL VS. SEVERITY • HETEROGENEITY REGARDING ETIOLOGY • DIFFERENT PHENOTYPES • DIFFERENTIAL DIAGNOSIS- MASQUERADERS • BETTER MONITORING • ASTHMA EDUCATION • BETTER SELF MONITORING • MEDICAL MONITORING:SPIROMETRY • NEW THERAPIES • INHALED STEROIDS WITH NO OR MINIMAL BIOVAILABILITY • OTHER NEW MOLECULES • IMPROVED IMMUNOTHERAPIES • IMPROVED EMPHASIS ON SELF-IMPROVEMENT: NUTRITION; PERSONAL HABITS; HOME ENVIRONMENT

  2. ASTHMA UPDATE • PREVALENCE & IMPACT: • 22 million in U.S. (9 million children) • Hospitalizations-stable except for children under 4 years. • 500,000 hospitalizations annually • Increase incidence noted throughout the world • Cost: estimated 16 billion dollars annually • Estimated days missed (school-14 million school days; work-24 million work days)

  3. ASTHMA UPDATE • EARLY IDENTIFICATION OF HIGH RISK PATIENTS: • IMMEDIATE CONCERNS: • Improve quality of life • Reduce risk for hospitalizations and death. • LONG TERM CONCERNS: • Prevent irreversible changes in airway structure i.e. remodeling with sub-basement fibrosis, mucus hypersecretion, s.m hypertrophy, & injury of lining (epithelium).

  4. ASTHMA UPDATE WHICH PATIENTS ARE AT RISK: CHILDREN: • Children with early onset under 3 yrs have more out of control asthma after 6 yrs. age & lung deficits later on in life. • More then 3 episodes of wheezing a year • Eczema or parental hx of asthma • 2/3 phenotypes (eosinophilia; wheezing without URI; allergic rhinitis

  5. ASTHMA UPDATE • USEFUL PREDICTIVE INDEX FOR CHILDREN -VERY IMPORTANT! • 76% of children with asthma after age 6 yr had positive predictive index; • 97% of children without asthma had negative predictive index.

  6. ASTHMA UPDATE WHICH PATIENTS ARE AT RISK: CHILDREN: • Children with early onset under 3 yrs have more out of control asthma after 6 yrs. age & lung deficits later on in life. • More then 3 episodes of wheezing a year • Eczema or parental hx of asthma • 2/3 phenotypes (eosinophilia; wheezing without URI; allergic rhinitis

  7. ASTHMA UPDATE ADULTS at RISK: • ATS (1 or 2 major; 2 minor). • Major • Rx with steroids >50% year • High dose inhaled steroid • Minor • Need for additional controller Rx. • Daily use of beta 2 agonist • Persistent airway obst (Fev1<80%; PEF variability >20%

  8. ASTHMA UPDATE ADULTS: Minor (CONTINUED): • One or more emergency visits per yr. • 3 or more steroid burst per yr. • Deterioration following <25% reduction of steroid • Near fatal asthma (intubation in past).

  9. ASTHMA UPDATE • DEFINITION OF ASTHMA: • Chronic inflammatory disease with >12 % (>250ml ) FEV1 reversibility: • Airflow limitation • Airway hyper-responsiveness

  10. ASTHMA UPDATE • AIRFLOW LIMITATION • Bronchoconstriction occurs secondary to release of multi-mediators (histamine, leukotrienes, prostaglandins, PAF etc. • Aeroallergen sensitivity • Aspirin ( Non-IgE) • Multi-factorial (exercise and cold air-osmotic; airborne irritants, laughing, GERD & sinusitis via neurogenic reflex; infections)

  11. ASTHMA UPDATE • OTHER FACTORS LIMITING AIRFLOW • Airway edema secondary to eosinophilic inflammation • Mucus hypersecretion • Structural changes i.e. hypertrophy and hyperplasia of smooth muscular tissue; tissue fibrosis as part of remodeling.

  12. ASTHMA UPDATE • AIRWAY HYPER-RESPONSIVENESS (TWITCHY LUNGS) • Exaggerated bronchoconstrictor response to stimuli- triggers such as exercise, cold air, laughing, stress. • Defined by methacholine/adenosine/mannitol responsiveness • Rx directed towards reducing inflammation can reduce airway hyper-responsiveness.

  13. ASTHMA UPDATE HETEROGENOUS PHENOTYPES OF ASTHMA: Different patterns of inflammation-targets for eventual treatment Many patients have overlapping phenotypes. • Intermittent; Persistent • Atopic (extrinsic) vs. Intrinsic • Exercise induced • Aspirin sensitive • Late Onset • Infection induced (RSV; parainfluenza; adenovirus, rhinovirus) • Cough variant asthma • Steroid resistant

  14. ASTHMA UPDATE • ESTABLISH DIAGNOSIS OF ASTHMA: • History, physical and PFT to establish there are symptoms of airflow obstruction and/or airway hyperresponsiveness; • At least evidence for reversibility • Value of history • What are the triggers in the home? • Outdoor triggers?-pollens, time of year • What else triggers asthma- aspirin, NSAIDs, URI’s cold air exercise, forest fires, smoking; positioning, foods, • Family history

  15. Differential diagnosis:co-morbidities GERD; vocal cord dysfunction; foreign body; anatomical abn; hypersensitivity bronchopulmonary aspergillosis; Chronic sinusitis Churg’s syndrome; Samter’s syndrome; Cystic Fibrosis bronchiectasis; sleep apnea with aspiration; occupation and hobbies (birds); wheezing” with COPD ASTHMA UPDATE

  16. ASTHMA UPDATE PHYSICAL EXAM: • Nasal exam- polyps • Level of wheezing (high, low) • High level over trachea: consider vocal cord dysfunction • Hyperexpansion of chest • Signs of chronicity i.e.(clubbing); consider bronchiectasis, COPD, C.F. • Signs of hypoxemia (cyanotic nail beds) • Lymphadenopathy or lack of with history of recurring respiratory infections (consider ID workup) • Keep in mind undiagnosed adult CF (sweat test is not useful in adults)

  17. ASTHMA UPDATE LABORATORY EVALUATION: • r/o Atopy: skin tests properly applied and interpreted; RAST cap IgE • Properly performed PFT pre and post BD • PEF > FEV1; Expiration plateau for at least 6 seconds • Reproducibility with BD- at least 2 measurements with FEV1 within 0.15 L. • Reversibility in adults: >250 ml; FEV1> 12% or > 10% increase of pred FEV1% for adults. Later may separate COPD from asthma. May need oral steroids for reversibility. • FEV1/FVC% should be included for children .

  18. ASTHMA UPDATE Laboratory evaluation: • Other PFT: • Inspiratory loop for VCD • Methacholine challenge • Nasal exam/endoscopy- polyps; sinusitis;VCD • Chest Xray/ CT of chest on rare occasion • Sinus CT • Trial with protonics as a diagnostic tool (pH studies) • Consider bronchoscopy and lung biopsy for difficult to diagnose and/or treat.

  19. ASTHMA UPDATE NIH Guidelines: asthma classification • Initially severity assessment: • Based on medication usage; history of recent exacerbations, PFT; night time awakenings; persistent or intermittent. • Initial Rx based on classification of severity • Manage based on control of symptoms i.e. more functional emphasis: • Use of rescue meds • Night time awakenings • Exacerbation rate • Objective parameters –PFT; NO measurements

  20. ASTHMA UPDATE • Goals of Therapy • Reduce impairment (current) • Prevent troublesome symptoms (cough, breathlessness with exertion and at night) • Reduce frequent use of SABA to < 2 days a week • Maintain near normal PFT • Maintain normal activity • Reduce risk (future) • Exacerbations • Prevent ER visits and hospitalizations • Prevent loss of lung function; children-prevent reduced lung growth

  21. UPDATE ON ASTHMA Therapeutic Strategies to Improve Control: • Education: preferably by experienced or certified asthma educator: • Peak flows- setting parameters of when to call. • Awareness of questions to ask: nocturnal awakenings, use of rescue meds. • Asthma treatment plan: what to do when sx develop. • How to use medications and when- very important • Compliance checks

  22. ASTHMA UPDATE Environmental & Personal Health Strategies • Eliminate tobacco smoke ( in utero and passive) • Associated with severity and dec. response to steroid Rx. • Air pollution- forest fires • Wood burning stoves • Use of air purifier (HEPA) especially near open windows during pollen seasons

  23. UPDATE ON ASTHMA Environmental & Personal Health Strategies • Encourage breast feeding up to 6 months to minimize food allergy induction • Home environmental control • Individualize recommendations for aerobics in cold weather and during peak pollen counts. • Speculative HYGIENE THEORY but worth noting: • early exposure to daycare; rural environment; early exposure to animals- Favor immune responses away from allergy development; • antibiotic use; Western lifestyle- Favor immune responses towards allergy responses.

  24. UPDATE ON ASTHMA Environmental & Personal Health Strategies • Control co-morbidities that can increase asthma: • Allergic rhinitis/sinusitis –studies demonstrate that regular use of nasal steroids and/or AH reduce asthma flares and ER visits • GERD- use of protonics decreases asthma. • Obesity-dieting is important • Leptin increases in obesity: inc. IgE sensitization • Adiponectin decreases in obesity: enhancing remodeling and increased inflammation. • CPAP for sleep apnea can help control obesity, aspiration • New concerns: overuse of vitamins, folic acid in pregnancy may be increase incidence of asthma: based on mice studies.

  25. ASTHMA UPDATE • MONITORING ASTHMA TO ASSESS CONTROL: • Symptom retrieval- ACT • Spirometrics- frequency • Other Monitoring Parameters • Peak flow measurements • Sputum Eosinophils • Nitric Oxide and pH Measurements on Exhaled Air

  26. ASTHMA UPDATE • Sputum eosinophils : correlates with inflammatory response but impractical • NO produced by epithelial and alveoli cells. Correlates with eosinophil bronchial lavage studies • Many convincing studies that suggest NO can be used to reflect status of eosinophilic inflammation in asthma. • May be best used as a compliance check with inhaled steroids.

  27. ASTHMA UPDATE Medications: • Rescue medications and long term beta agonists: • Controversy re’ LABA. New data supports use with ICS. • Xopenex® vs. albuterol • Inhaled corticosteroids- reduced decline in lung function (FEV1) • Mometasone and ciclesonide –both have minimal or no bioavailability (absorption) • Dynamic dosing- use of ICS as a burst to treat exacerbations in well controlled asthma patients and normal lung function

  28. ASTHMA UPDATE • TARGETED THERAPY: • IgE- anti-IgE (Xolair) • Leukotrienes (anti-leukotrienes – Singulair; Zyflo • Trials with Anti-IL-5- reduce eosinophils • Anti- IL-4 trials-reduce IgE

  29. ASTHMA UPDATE • Monoclonal anti-IgE (Xolair) • Must be used for difficult to manage severe and persistent asthmatics • Resistant to high dose inhaled steroids • Require oral steroids • Must have IgE levels in a certain range • Expensive • Does it work –in some cases, noticeable reduction in exacerbations • Side effects-anaphylaxis-very rare but requires close observation for 2 hours after dose. • Leukotriene modifiers: • Montelukast ( prevents exercise induction up to 24 hrs- single dose) • Zyflo ( aspirin sensitive asthmatics)

  30. ASTHMA UPDATE Approaches Based on Hygiene Theory • Shifting Th2 to Th1 to modify asthma. The shift to Th1 induces IL-2 and IFN critical in defense against infection • Alter balance between Th1 and Th2- towards Th1 by immunotherapies • SLIT vs. SCIT • Factors favoring Th1: • Older siblings; early exposure to daycare; rural environment; certain infections (TB, measles, hep A); early exposure to animals; • Factors favoring Th2: • Antibiotic use; Western lifestyle; urban environment; diet; house dust mite and cockroach sensitization; RSV

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