Respiratory

Current Guidelines forAsthma Treatment Ass.Prof.Dr:MUHAMMED WAHEEB AL,OBAIDYConsultant Chest Physician MEDICAL CITY

Mild Intermittent Asthma

Symptoms < 2 days/week
Symptoms < 2 nights/month
PEF or FEV1 > 80%
PEF variability < 20%
No daily medication needed
PRN beta agonists
Course of systemic steroids for exacerbations

Mild Persistent Asthma

Symptoms > 2 days/wk but < 1x/day
> 2 nights/month
PEF or FEV1 > 80%
PEF variability 20-30%
Preferred treatment low dose inhaled corticosteroids
Alternatives include cromolyn, leukotriene modifiers, necromodil, or sustained release theophylline


Moderate Persistent Asthma
Symptoms daily
> 1 night/week
PEF or FEV1 > 60% and < 80%
PEF variability > 30%
Preferred treatment is low to medium dose inhaled corticosteroid and a long acting inhaled beta 2 agonist
Alternative includes increasing ICS within moderate dose range, or low to medium dose ICS with either leukotriene modifier or theophylline

Severe Persistent Asthma

Continual symptoms
Frequent nocturnal attacks
PEF or FEV1 < 60%
PEF variability > 30%
Preferred treatment is high dose inhaled corticosteroid and long acting beta 2 agonists
If needed, can add systemic corticosteroids

Goals of Therapy

Minimal or no chronic symptoms day or night
Minimal or no exacerbations
No limitations on activities; no school/work missed
Maintain (near) normal pulmonary function
Minimal use of short-acting inhaled beta 2 agonist
Minimal or no adverse effects from medications


Stepwise Approach

Review treatment every 1 to 6 months, and gradually step down treatment

If asthma controlled not maintained, then a step up in treatment may be warranted

Reasons for Poor Asthma Control

Inhaler Technique
Compliance
Environment
Also assess for an alternative diagnosis
“All that wheezes is not asthma, and not all asthma wheezes”

Factors Affecting Compliance

Education
Route of drug administration (inhaled vs. oral)
Complexity of drug regimens
Side effects of medications
Cost

Beta 2 Agonists

Beta 2 Agonists
Most potent and rapidly acting bronchodilators currently available for clinical use
Given in different forms:
short acting = isoproterenol
intermediate acting = albuterol, levalbuterol ,pirbuterol,metaproterenol, terbutaline, fenoterol
long acting = salmeterol, formoterol

Mechanism of Action

Beta 2 agonists interact with beta 2 receptors on the surface of a variety of cells that may play a role in asthma pathogenesis
Beta agonists have the potential to relax bronchial smooth muscle,

Also B2 agonist :

Decrease mast cell mediator release
Inhibit neutrophil, eosinophil, and lymphocyte functional responses
Increase mucociliary transport
Affect vascular tone and edema formation

MDI with Spacer vs. Nebulizer

Equivalent bronchodilation can be achieved by giving beta 2 agonist with a spacer/holding chamber or by nebulizer therapy
Continuous administration with a nebulizer may be more effective in severely obstructed adults and in those who have difficulty with an MDI plus spacer


Chronic Use of Beta Agonists
Arguments against chronic use:
Mortality may be increased
Control of asthma may worsen
Equal or superior efficacy can be achieved with inhaled corticosteroids

Increased Mortality with Chronic Use?

A case-control study using linked health insurance databases found:
Increased risk of death or near-death from asthma was associated with the regular use of inhaled beta agonists, especially fenoterol
Did not appear to be confounded by asthma severity, and there was no relation to non–asthma mortality

Increased Mortality with Chronic Use?

However, increased odds ratios were also noted for theophylline and oral corticosteroids

Increased Mortality with Chronic Use?

A subsequent analysis demonstrated a relationship between CV death and use of beta agonists taken orally or by nebulizer but not when taken by MDI
Risk of CV death was also greater in patients who used theophylline
Most of CV deaths in patients with underlying CV disease, including acute coronary insufficiency and congestive cardiomyopathy*

Long Acting Beta Agonist Monotherapy

Prolonged treatment with long-acting beta agonists and without inhaled corticosteroids has been associated with increased mortality
28-week placebo-controlled trial assessing the safety of the long-acting beta agonist salmeterol enrolled over 25,000 patients, but was stopped early when interim analysis revealed a significantly increased risk of death in those not taking concomitant inhaled corticosteroids .
*"The Pink Sheet" FDC Reports. Chevy Chase, MD. 2003; 65(4):10


Tolerance to Beta Agonists
More frequent in chronic use
Induced more with oral rather than inhaled preparations
Tolerance to long acting beta agonists may or may not occur (conflicting data)

Corticosteroids

Glucocorticoids
Most potent antiinflammatory agents available for the treatment of asthma
More effective than beta agonists, theophylline, and cromolyn sodium in reducing airway hyperresponsiveness during maintenance therapy

Glucocorticoid Mechanisms

Alleviating airway inflammation
Reducing collagen and tenascin deposition, two features associated with airway remodeling
Inhibit the synthesis of almost all known cytokines
Alteration of the number and availability of circulating leukocytes
Reduction in vascular permeability
Inhibition of mediator synthesis and release

Steroids and Long Acting Beta Agonists

Results in greater improvements in lung function and symptom control than monotherapy with escalating doses of inhaled glucocorticoid
Act synergistically to activate transcription factors, decrease smooth muscle proliferation, and impair eosinophil adhesion


Potency of Inhaled Corticosteroids

COMBINATION INHALERS

There is no difference in effi cacy in giving inhaled steroid and long-acting β2 agonist in combination or in separate inhalers.
Once a patient is on stable therapy, combination inhalers have the advantage of guaranteeing that the long-acting β2 agonist is not taken without inhaled steroid.

In adult patients at step 3 who are poorly controlled, the use of budesonide/formoterol in a single inhaler as rescue medication instead of a short-acting β2 agonist, in addition to its regular use as a controller treatment, has been shown to be an effective treatment option.
This management technique has not been investigated with other combination inhalers

Can ICS Cause Osteoporosis?

Three year prospective study looked at dose of inhaled triamcinolone and rate of bone loss in premenopausal women with asthma
There was a dose-related decline in bone density in the total hip and trochanter
No dose-related decline in the femoral neck or spine