Asthma

Asthma Asthma is a common disease, affecting approximately 5% of the population Men and women appear to be equally affected

Definition • Asthma is characterized by chronic airway inflammation and increased airway hyper-responsiveness leading to symptoms of wheeze, cough, chest tightness and dyspnea • Functionally characterized by presence of airflow obstruction reversible with treatment

• Episodic or chronic symptoms of airflow obstruction: breathlessness, cough, wheezing, and chest tightness • Symptoms frequently worse at night or in the early morning • Prolonged expiration and diffuse wheezes on physical examination • Limitation of airflow on pulmonary function testing or positive broncho-provocation challenge • Complete or partial reversibility of airflow obstruction, either spontaneously or following bronchodilator therapy

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Factors contributing to asthma Environmental allergens (House dust mites, animal allergens [especially cat and dog], cockroach allergens, and fungi are most commonly reported)

• Viral respiratory infections • Exercise; hyperventilation • Gastroesophageal reflux disease (GERD) • Chronic sinusitis or rhinitis • Aspirin or nonsteroidal anti-inflammatory drug hypersensitivity, sulfite sensitivity • Use of beta-adrenergic receptor blockers (including ophthalmic preparations)

• Obesity • Environmental pollutants, tobacco smoke • Irritants such as household sprays and paint fumes • Occupational exposure : insects, plants, latex, gums, diisocyanates, anhydrides, wood dust, and fluxes. • Emotional factors or stress • Perinatal factors (Prematurity and increased maternal age increase; maternal smoking and prenatal exposure to tobacco smoke also increase the risk of developing asthma) • "Cardiac asthma" is wheezing precipitated by

Exercise Induced Asthma • Exposure to cold or dry air • Environmental pollutants (eg, sulfur, ozone) • Level of bronchial hyperreactivity • Chronicity of asthma and symptomatic control • Duration and intensity of exercise • Allergen exposure in atopic individuals • Coexisting respiratory infection

Pathophysiology The pathophysiology of asthma is complex and involves the following components:

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(1) airway inflammation

(2) intermittent airflow obstruction

(3) bronchial hyper-responsiveness

Airway inflammation • The mechanism of inflammation in asthma may be acute, subacute, or chronic • Mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present. • Some of the principal cells identified in airway inflammation include mast cells, eosinophils, epithelial cells, macrophages, and activated T lymphocytes. • T lymphocytes play an important role in the regulation of airway inflammation through the release of numerous cytokines • Other constituent airway cells, such as fibroblasts, endothelial cells, and epithelial cells, contribute to the chronicity of the disease • Finally, cell-derived mediators influence smooth muscle tone and produce structural changes and remodeling of the airway

Airflow obstruction Airflow obstruction can be caused by a variety of changes: • Acute bronchoconstriction is the consequence of immunoglobulin E–dependent mediator release upon exposure to aeroallergens and is the primary component of the early asthmatic response • Airway edema occurs 6-24 hours following an allergen challenge and is referred to as the late asthmatic response • Chronic mucous plug formation consists of an exudate of serum proteins and cell debris that may take weeks to resolve • Airway remodeling is associated with structural changes due to long-standing inflammation and may profoundly affect the extent of reversibility of airway obstruction

Airway hyperresponsiveness • The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli

• The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or non-myelinated sensory neurons • The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma

Pathogenesis of Exercise Induced Asthma

• Controversial

• The disease may be mediated by water loss from the airway, heat loss from the airway, or a combination of both • The upper airway is designed to keep inspired air at 100% humidity and body temperature at 37°C (98.6°F). The nose is unable to condition the increased amount of air required for exercise, particularly in athletes who breathe through their mouths • The abnormal heat and water fluxes in the bronchial tree result in bronchoconstriction, occurring within minutes of completing exercise • Results have not demonstrated an increase in inflammatory mediators

Histopathology • Denudation of airway epithelium • Collagen deposition beneath the basement membrane • Airway edema • Mast cell activation • Inflammatory cell infiltration with neutrophils, eosinophils, and lymphocytes (especially T lymphocytes) • Hypertrophy of bronchial smooth muscle and hypertrophy of mucous glands with plugging of small airways with thick mucus can occur • This airway inflammation underlies disease chronicity and contributes to airway hyperresponsiveness, airflow limitation, and respiratory symptoms (including recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly during the nighttime and early morning hours).

There is basement membrane thickening of bronchus and submucosal infiltrates of eosinophils with chronic inflammatory cells in Asthmatic bronchus

Clinical Findings Symptoms • Episodic wheezing • Difficulty in breathing • Chest tightness • Cough

• The frequency of asthma symptoms is highly variable • Some patients may have only a chronic dry cough and others a productive cough • Some patients have infrequent, brief attacks of asthma and others may suffer nearly continuous symptoms • Asthma symptoms may occur spontaneously or may be precipitated or exacerbated by many different triggers as discussed above • Asthma symptoms are frequently worse at night; circadian variations in bronchomotor tone and bronchial reactivity reach their nadir between 3 AM and 4 AM, increasing symptoms of bronchoconstriction

Signs

General • Evidence of respiratory distress manifests as increased respiratory rate, increased heart rate, diaphoresis, and use of accessory muscles of respiration • Marked weight loss or severe wasting may indicate severe emphysema • Pulsus paradoxus: This is an exaggerated fall in systolic blood pressure during inspiration and may occur during an acute asthma exacerbation • Depressed sensorium: This finding suggests a more severe asthma exacerbation with impending respiratory failure

Chest examination • Chest examination may be normal between exacerbations in patients with mild asthma • End-expiratory wheezing or a prolonged expiratory phase is found most commonly, although inspiratory wheezing can be heard • Diminished breath sounds and chest hyperinflation may be observed during acute exacerbations

• Wheezing during normal breathing or a prolonged forced expiratory phase correlates well with the presence of airflow obstruction. Wheezing during forced expiration does not • During severe asthma exacerbations, airflow may be too limited to produce wheezing, and the only diagnostic clue on auscultation may be globally reduced breath sounds with prolonged expiration

• Upper airway: Some physical findings increase the probability of asthma, nasal mucosal swelling, increased nasal secretions, nasal polyps are often seen in patients with allergic asthma • Skin: Eczema, atopic dermatitis, or other manifestations of allergic skin disorders may also be present

Investigations

Pulmonary Function Testing SPIROMETRY • Clinicians are able to identify airflow obstruction on examination, but they have limited ability to assess it or to predict whether it is reversible • The evaluation for asthma should therefore include spirometry (FEV1, FVC, FEV1/FVC) before and after the administration of a short-acting bronchodilator • These measurements help determine the presence and extent of airflow obstruction and whether it is immediately reversible

• Airflow obstruction is indicated by a reduced FEV1/FVC ratio (< 75%) • In severe airflow obstruction with significant air trapping, the FVC may also be reduced, resulting in a pattern that suggests a restrictive ventilatory defect • Significant reversibility of airflow obstruction is defined by an increase of 12% and 200 mL in FEV1 or 15% and 200 mL in FVC after inhaling a short-acting bronchodilator

Peak expiratory flow (PEF) • Peak expiratory flow (PEF) meters are handheld devices designed as home monitoring tools • PEF monitoring can establish peak flow variability, quantify asthma severity, and provide both the patient and the clinician with objective measurements on which to base treatment decisions • Measuring PEF is recommended as part of a comprehensive approach to asthma management

• A peak flow meter is an inexpensive, pocket-sized device that measures peak expiratory flow (PEF), or how fast a person can breathe out • To measure PEF, the person takes a deep breath and then blows into a tube on the peak flow meter as hard and as fast as possible. This can be done at home.

• PEF shows diurnal variation • It is generally lowest on first awakening and highest several hours before the midpoint of the waking day • PEF should be measured in the morning before the administration of a bronchodilator and in the afternoon after taking a bronchodilator • A 20% change in PEF values from morning to afternoon or from day to day suggests inadequately controlled asthma • PEF values less than 200 L/min indicate severe airflow obstruction • Inform the patient that a peak flow of less than 80% of the patient's personal best indicates a need for additional medication and a peak flow below 50% indicates severe exacerbation

Bronchial provocation testing • Bronchial provocation testing with histamine or methacholine—or exercise challenge testing —may be useful when asthma is suspected and spirometry is nondiagnostic • Bronchial provocation is not generally recommended if the FEV1 is less than 65% of predicted • A positive test is defined as a decrease in FEV1 of at least 20% at exposure to a dose of 16 mg/mL or less • A negative test has a negative predictive value for asthma of 95%.

Arterial blood gas measurements • Arterial blood gas measurements may be normal during a mild asthma exacerbation, but respiratory alkalosis and an increase in the alveolar-arterial oxygen difference (A–a–DO2) are common • During severe exacerbations, hypoxemia develops and the PaCO2 returns to normal • The combination of an increased PaCO2 and respiratory acidosis is a harbinger of respiratory failure and may indicate the need for mechanical ventilation.

Diagnosis of Asthma Comparable clinical history with either/ or • FEV1 ≥ 15% ( and 200ml) increase following administration of a bronchodilator/ trial of corticosteroids • > 20% diurnal variation on ≥ 3 days in a week for 2 weeks on PEF diary • FEV1≥15% decrease after 6 minutes of exercise

Additional Testing Chest radiographs: • Routine chest radiographs in patients with asthma usually show only hyperinflation • Other findings may include bronchial wall thickening and diminished peripheral lung vascular shadows • Chest radiographs are indicated when pneumonia, another disorder mimicking asthma, or a complication of asthma

Bronchial asthma

Asthmatic Lungs Thee chest is hyper-expaned and the lungs are large volume

Measurement of allergic status: • Increased Eosionophils in blood or sputum • Increased serum total IgE • Skin testing or in vitro testing to assess sensitivity to relevant environmental allergens may be useful in patients with persistent asthma

Assessment of airway Inflammation: • The diagnostic usefulness of measurements of biologic markers of inflammation such as cell counts and mediator titers in blood and sputum is being investigated Evaluations for paranasal sinus disease or gastroesophageal reflux should be considered in patients with pertinent symptoms and in those who have severe or refractory asthma

Management The goals of asthma therapy • Minimize chronic symptoms that impair normal activity (including exercise) • Prevent recurrent exacerbations • Minimize the need for emergency department visits or hospitalizations • Maintain near-normal pulmonary function

These goals should be met while providing optimal pharmacotherapy with the fewest adverse effects and while meeting patients' and families' expectations of satisfaction with asthma care

Metered Dose Inhaler( MDI)

Stepwise approach for managing Long-Term Quick Relief asthma Education Control

Step 1: Mild No daily intermitte medication nt needed

Short-acting bronchodilator: inhaled β2agonists as needed for symptoms. Intensity of treatment will depend on severity of exacerbation.

Use of short-acting inhaled β2agonists > 2 times a week may indicate the need for long-term

Teach basic facts about asthma Teach inhaler/inhalation chamber technique Discuss roles of medications Develop selfmanagement and action plans Discuss appropriate environmental control measures

Long-Term Control Quick Relief Step 2: One daily medication: Step 1 actions Mild persisten t

plus:

Antiinflammatory: either inhaled corticosteroid (low doses) or cromolyn or nedocromil Less desirable alternatives: sustained-release theophylline or leukotriene modifier

Use of shortacting inhaled β 2-agonists on a daily basis, or increasing use, indicates the need for additional longterm control therapy

Education Step 1 actions plus: Teach selfmonitoring Refer to group education if available Review and update selfmanagement plan

Long-Term Control

Step Daily medication:. Step 1 3: actions plus: Moderat Either e Anti-inflammatory: inhaled persiste corticosteroid (medium dose) nt

or Inhaled corticosteroid (lowmedium dose) and a long-acting bronchodilator (long-acting inhaled β2-agonist, sustainedrelease theophylline or longacting β 2-agonist tablets) If needed: Anti-inflammatory: inhaled corticosteroid (medium-high dose) and Long-acting bronchodilator (long-acting inhaled β2-agonist, sustained-

Quick Relief Education

As for step Step 1 2 actions plus: Teach selfmonitoring Refer to group education if available Review and update selfmanagement plan

Step 4:       Severe persisten t

Long-Term Control

Quick Relief

Education

Daily medication:

As for step 2

Step 2 and 3 actions plus:

Anti-inflammatory: inhaled corticosteroid (high dose) and Long-acting bronchodilator (long-acting inhaled β2-agonist, sustained release theophylline or long-acting inhaled β2-agonist tablets) and Corticosteroid tablets or syrup (1–2 mg/kg/d, generally not to

Refer to individual education, counseling

Step Down Therapy Once asthma control is established the dose of inhaled or oral corticosteroid should be titrated to the lowest dose at which effective control of asthma is maintained

Asthmatic Exacerbations Precipitated by • Infections (viral) • Moulds ( Alternaria and Cladosporium) • Pollen • Air pollution Characterized by Increased symptoms, deterioration in PEF and increase in airway inflammation

Approach to Treatment of Asthma Exacerbations • Correction of hypoxemia through the use of supplemental oxygen • Reversal of airflow obstruction by repetitive or continuous administration of an inhaled short-acting β 2-agonist and the early administration of systemic corticosteroids • Serial measurement of airflow in the emergency department • The post exacerbation care plan is an important aspect of management

Approach to Treatment of Mild Asthma Exacerbations • Mild asthma exacerbations are characterized by only minor changes in airway function (PEF > 80%) and minimal symptoms and signs of airway dysfunction • Most patients respond quickly and fully to an inhaled short-acting β2-agonist alone. However, an inhaled short-acting β2-agonist may need to be continued every 3–4 hours for 24–48 hours • For mild exacerbations in patients already taking an inhaled corticosteroid, the dose is doubled until peak flow returns to predicted or personal best • In patients not already taking an inhaled corticosteroid, initiation of this agent should be considered.

Immediate assessment of Acute severe asthma Acute severe asthma • • • •

PEF 33-50% predicted Respiratory rate ≥ 25/ min Heart rate≥110/ min Inability to complete sentence in one breath

Life threatening feature • • • • • • • • • •

PEF 33-50% predictedSPO2 < 92% or PaO2 < 60mmHg Normal PCO2 Silent Chest Cyanosis Feeble respiratory effort Bradycardia or arrhythmia Hypotension Exhaustion Confusion Coma

Near Fatal asthma • Raised PaCO2 and or requiring mechanical ventilation with raised inflation pressures

Approach to Treatment of Moderate & Severe Asthma Exacerbations

• Owing to the life-threatening nature of severe exacerbations of asthma, treatment should be started immediately once the exacerbation is recognized • A brief history pertinent to the exacerbation can be completed while treatment is given. More detailed assessments, including laboratory studies, usually add little in the early phase of evaluation and management and should be delayed until after initial therapy has been completed.

Oxygen therapy • Asphyxia is a common cause of death, and oxygen therapy is therefore very important • Supplemental oxygen should be given to maintain an SaO2 > 90% or a PaO2 > 60 mm Hg • Oxygen-induced hypoventilation is very rare, and concern for hypercapnia should never delay correction of hypoxemia.

Oxygen therapy

High-dose inhaled short-acting β2-agonist

• Frequent high-dose delivery of an inhaled short-acting β2-agonist is indicated and is usually well tolerated in the setting of severe airway obstruction • At least three MDI or nebulizer treatments should be given in the first hour of therapy • Thereafter, the frequency of administration varies according to the improvement in airflow and associated symptoms and the occurrence of side effects

Systemic corticosteroids • They reduce inflammatory response and hasten resolution of exacerbations • Administered orally, prednisolone 30-60 mg but intravenous hydrocortisone 200 mg may be used

Intravenous Fluids • Dehydration due to insensible watr loss • Hydration therapy given with potassium supplementation to compensate for salbutamol induced hypokalemia

• A small minority of patients will not respond well to treatment and will show signs of impending respiratory failure due to a combination of worsening airflow obstruction and respiratory muscle fatigue • Such patients can deteriorate rapidly and thus should be monitored in a critical care setting • Mechanical ventilation is given in selected patients