ASTHMA UPDATE

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 MONITORINGSPIROMETRY
• 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 gt50 year
• High dose inhaled steroid
• Minor
• Need for additional controller Rx.
• Daily use of beta 2 agonist
• Persistent airway obst (Fev1lt80 PEF variability
  gt20

8
ASTHMA UPDATE

• ADULTS
• Minor (CONTINUED)
• One or more emergency visits per yr.
• 3 or more steroid burst per yr.
• Deterioration following lt25 reduction of steroid
• Near fatal asthma (intubation in past).

9
ASTHMA UPDATE

• DEFINITION OF ASTHMA
• Chronic inflammatory disease with gt12 (gt250ml )
  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, URIs
  cold air exercise, forest fires, smoking
  positioning, foods,
• Family history

15
ASTHMA UPDATE

• Differential diagnosisco-morbidities
• GERD
• vocal cord dysfunction
• foreign body
• anatomical abn
• hypersensitivity bronchopulmonary aspergillosis
• Chronic sinusitis

• Churgs syndrome
• Samters syndrome
• Cystic Fibrosis
• bronchiectasis
• sleep apnea with aspiration
• occupation and hobbies (birds)
• wheezing with COPD

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 gt FEV1 Expiration plateau for at least 6
  seconds
• Reproducibility with BD- at least 2 measurements
  with FEV1 within 0.15 L.
• Reversibility in adults gt250 ml FEV1gt 12 or
• gt 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 sinusitisVCD
• 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 lt 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