Asthma Epidemiology

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Asthma Epidemiology

• LCDR Potter
• Pediatrics
• NH Jacksonville

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• Statistics
• More than 22 million people in the US have
  asthma, of these 6 million are children
• Nearly 5,000 Americans die of asthma each year.
• Asthma accounts for 2 million emergency room
  visits and 500,000 hospitalizations annually.

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Asthma Definition

• Asthma is a common chronic disorder of the
  airways that is complex and characterized by
  variable and recurring symptoms, reversible
  airflow obstruction, bronchial hyper-responsivenes
  s, and an underlying inflammation.
• airway infiltrates of mast cells, eosinophils,
  neutrophils (smokers and severe asthmatics), T
  lymphocytes, macrophages and epithelial cells.
• Susceptible individuals experience recurrent
  cough (esp. at night), wheezing, breathlessness
  and chest tightness.

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Asthma Definition

• These episodes are usually associated with
  widespread but variable airflow obstruction that
  is often reversible either spontaneously or with
  treatment.
• The inflammation also causes an associated
  increase in the existing bronchial
  hyper-responsiveness to a variety of stimuli.
• Reversibility of airflow limitation may be
  incomplete in some patients with asthma.

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Inflammation and Clinical Symptoms
Inflammation
Airway Hyper-responsiveness
Airway Obstruction
Clinical Symptoms
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Bronchoconstriction

• In acute exacerbations of asthma, bronchial
  smooth muscle contraction (bronchoconstriction)
  occurs quickly to narrow the airways in response
  to exposure to a variety of stimuli including
  allergens or irritants.
• Allergen-induced acute bronchoconstriction
• IgE-dependent release of mediators from mast
  cells histamine, tryptase, leukotrienes, and
  prostaglandins
• Aspirin and other non-steroidal anti-inflammatory
  drugs can also cause acute airflow obstruction in
  some patients
• non-IgE-dependent response
• Other stimuli exercise, cold air, and irritants
  can cause acute airflow obstruction.
• intensity of the response appears related to
  underlying airway inflammation.

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Airway Hyper-responsiveness

• Exaggerated bronchoconstrictor response to a wide
  variety of stimuliis directly affected by the
  degree of airway inflammation.
• Airway hyper-responsiveness directly correlates
  with the clinical severity of asthma.
• Demonstrated by degree of responsiveness on
  testing such as Methacholine challenge.
• The mechanisms influencing airway
  hyper-responsiveness are multiple and include
  inflammation, dysfunctional neuroregulation, and
  structural changes.
• Treatment directed toward reducing inflammation
  can reduce airway hyper-responsiveness and
  improve asthma control.

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Airway Edema

• As the inflammatory process progresses the
  airways become plugged and obstructed by
• Edema
• Mucous hypersecretion
• Inspissated mucous plugs
• PERMANENT airway remodeling begins sub-basement
  fibrosis, epithelial injury, smooth muscle
  hypertrophy, angiogenesis

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Asthma Pathogenesis

• The expression of asthma is a complex,
  interactive process that depends on the interplay
  between two major factors
• host factors (particularly genetics allergic,
  Beta receptors polymorphisms, innate immunity)
• environmental exposures (allergen sensitization
  and viruses)
• The combination of host factors and environmental
  exposures at critical times in the immune system
  development determine the expression of asthma
  symptoms.

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Asthma Pathogenesis

• Host Factors Innate Immunity
• Imbalance between Th1 and Th2 cytokine profiles.
• Evidence that allergic diseases, and possibly
  asthma, are characterized by a shift toward a Th2
  cytokine-like disease.
• Th1 cells produce IL-2 and interferon-? (IFN-?),
  which are critical in cellular defense mechanisms
  in response to infection.
• Th2, in contrast, generates a family of cytokines
  (IL-4, -5, -6, -9, and -13) that can mediate
  allergic inflammation.

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Asthma Pathogenesis

• Hygiene Hypothesis hypothesis is based on the
  assumption that the immune system of the newly
  born is skewed toward Th2 cytokine generation.
• Following birth, environmental stimuli such as
  infections will activate Th1 responses and bring
  the Th1/Th2 relationship to an appropriate
  balance.
• The incidence of asthma is reduced in association
  with certain infections (M. tuberculosis,
  measles, or hepatitis A), exposure to other
  children and less frequent use of antibiotics.
• The absence of the these lifestyle events is
  associated with the persistence of a Th2 cytokine
  pattern promote the production of IgE antibodies
  to environmental antigens (house-dust mite,
  cockroach, Alternaria, cat).

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Environmental Triggers

• Two major environmental factors have emerged as
  the most important in the development,
  persistence, and possibly severity of asthma
• airborne allergens and viral respiratory
  infections
• Allergens
• Sensitization and exposure to house-dust mite and
  Alternaria are important factors in the
  development of asthma in children.
• Cock roach sensitization in inner city dwellings
  is particularly problematic.
• Earlier concerns for exposure to dog and cats
  early in life have not been borne out in long
  term outcome studies

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Environmental Triggers

• Respiratory Infections During infancy, a number
  of respiratory viruses have been associated with
  the inception or development of asthma.
• Respiratory syncytial virus (RSV) and
  parainfluenza virus in particular, cause
  bronchiolitis and recurrent wheezing that
  parallels many features of childhood asthma.
• A number of long-term prospective studies of
  children admitted to hospital with documented RSV
  have shown that approximately 40 percent of these
  infants will continue to wheeze or have asthma in
  later childhood.
• Symptomatic rhinovirus infections in early life
  also are emerging as risk factors for recurrent
  wheezing.

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Environmental Triggers

• In utero exposure to environmental tobacco smoke
  increases the likelihood for wheezing in the
  infant, although the subsequent development of
  asthma has not been well defined.
• In adults who have asthma, cigarette smoking has
  been associated with an increase in asthma
  severity and decreased responsiveness to inhaled
  corticosteroids.

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Environmental Triggers

• One recent epidemiologic study showed that heavy
  exercise outdoors in communities with high
  concentration of ozone was associated with a
  higher risk of asthma among school-age children.
• The relationship between increased levels of
  pollution and increases in asthma exacerbations
  and emergency care visits has been well
  documented.

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Inflammatory mediators

• IgE is the antibody responsible for activation of
  allergic reactions.
• IgE attaches to cell surfaces via a specific
  high-affinity receptor.
• The mast cell has large numbers of IgE receptors
  which cause the release of mediators to initiate
  acute bronchospasm as well as cytokines to
  perpetuate underlying airway inflammation.
• Omalizumab a monoclonal antibody against IgE has
  shown that the reduction of IgE is effective in
  asthma treatment.

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Treatment Implications

• Current therapies
• prevent occurrences of exacerbations.
• reduce inflammation.
• do not prevent the progression of disease in
  affected children.
• New therapies for asthma management will be
  necessary to preserve lung function and prevent
  disease progression.