BRONCHIAL ASTHMA

Asthma is a chronic inflammatory disorder of the airways causes recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread, but variable airflow obstruction is often reversible either spontaneously or with treatment.

ASTHMA a lung disease characterized by 1. airways obstruction is reversible (but not completely in some patients), either spontaneously or with treatment, 2. airways inflammation, and 3. increased airways responsiveness to a variety of stimuli.

 Allergens Allergic asthma is frequently seasonal. A

nonseasonal form may result from allergy to feathers, animal danders a.s. Pharmacologic Stimuli - aspirin, coloring agents such as tartrazine, beta-adrenergic antagonists. The typical aspirinsensitive respiratory syndrome a perennial vasomotor rhinitis, a hyperplastic rhinosinusitis, nasal polyps and progressive asthma. Environment And Air Pollution. Occupational Factors Occupation-related asthma can result from working with metal salts (platinum, chrome, nickel), wood and vegetable dusts (oak,grain, flour, green coffee bean), pharmaceutical agents (antibiotics, piperazine, cimetidine), industrial chemicals and plastics (persulfates, ethylenediamine), biologic enzymes (laundry detergents), and animal and insect dusts, serums, and secretions. Infections - respiratory viruses.

Etiologic factors of asthma

Indoor allergens

Pollen allergens

Pathogenesis of asthma

The pathophysiology of asthma involves the following components: (1) airway inflammation,
(2) intermittent airflow obstruction, and (3) bronchial hyperreactivity (hyperresponsiveness).

Mechanisms of inflammation in asthma

The inflammation in asthma may be acute, subacute, or chronic. Eosinophil cell and mononuclear infiltration, airway edema mucus hypersecretion, desquamation of the epithelium, smooth muscle cells hyperplasia, and airway (bronchial tree) remodeling are present. Cells identified in airway inflammation include mast cells, eosinophils, epithelial cells, macrophages, and activated T lymphocytes. T lymphocytes play role in the regulation of airway inflammation through the release of pro-inflammatory cytokines. Fibroblasts, epithelial and endothelial cells contribute to the chronicity of the disease. Adhesion molecules (eg, selectins, integrins) directs the inflammatory changes in the airway. Cell-derived mediators influence smooth muscle tone and produce structural changes and remodeling of the airway.

Mechanisms of airways obstruction in asthma

Airflow obstruction can be caused by acute bronchoconstriction, airway edema, chronic mucous plug formation, and airway remodeling. Acute bronchoconstriction is the consequence of immunoglobulin Edependent 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.

Mechanisms of bronchial constriction in asthma

1) the offending agent results in the formation of a specific IgE, and the cause seems immunologic (the immunologic reaction can be immediate, late, or dual); the substance causes a direct liberation of bronchoconstrictor substances; the substance causes direct or reflex stimulation of the airways of either latent or frank asthmatics. In the case of asthmatic symptoms caused by occupational exposures patients give a characteristic cyclic history. Exercise is one of the most common precipitants of acute episodes of asthma -exercise-induced asthma. Emotional Stress

2) 3)

4) 5)

Mechanisms of bronchial hyperreactivity (hyperresponsiveness) in asthma

The bronchial hyperreactivity (hyperresponsiveness) 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 mediatorsecreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

Pathophysiology

Airway inflammation and edema in period of asthma attack

14

Pathophysiology
Bronchial constriction ore spasm in period of asthma attack

15

PATHOLOGY
In a patient who has died of acute asthma, the most striking feature of the lungs at necropsy is their gross overdistention and failure to collapse when the pleural cavities are opened. When the lungs are cut, numerous gelatinous plugs of exudate are found in most of the bronchial branches down to the terminal bronchioles. Histologic examination shows hypertrophy of the bronchial smooth muscle, hyperplasia of mucosal and submucosal vessels, mucosal edema, denudation of the surface epithelium.

History of Asthma
Symptoms may include: cough, wheezing, shortness of breath, chest tightness, sputum production. Symptom patterns can vary as follows: - Perennial versus seasonal; - Continual versus episodic; - Duration, severity, and frequency; - Diurnal variations (nocturnal and early-morning awakenings). Precipitating or aggravating factors may include: allergens, occupation, medications, exercise. Disease development variables include: age at onset, history of injury early in life due to infection or passive smoke exposure, progress of disease, current response to management, comorbid conditions, the profile of exacerbation. Family history may reveal the following conditions: asthma, allergy, sinusitis, rhinitis. Social history may reveal the following conditions: home characteristics, smoking, workplace or school characteristics, educational level, employment, social support.

Physical examination
General: respiratory distress (increased respiratory and cardiac rates, diaphoresis, and use of accessory muscles of respiration); weight loss or wasting (indicate emphysema); pulsus paradoxus (may occur during an acute asthma exacerbation), depressed sensorium (during a severe asthma exacerbation with impending respiratory failure). Chest examination: end-expiratory wheezing or a prolonged expiratory phase is found; diminished breath sounds and chest hyperinflation (during exacerbations). Upper airway: look for the presence of polyps from sinusitis, allergic rhinitis, or upper respiratory infection.
Skin: Observe for the presence of atopic dermatitis, eczema, or other manifestations of allergic skin conditions.

Causes (factors that can contribute to asthma)

Environmental allergens, pollutants, tobacco smoke Viral respiratory infections Exercise; hyperventilation Gastroesophageal reflux disease Chronic sinusitis or rhinitis Aspirin or NSAID-hypersensitivity, sulfite sensitivity Beta-blockers Occupational exposure, emotional factors Irritants (household sprays and paint fumes). Factors that contribute to EIA symptoms include: 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

Laboratory Findings
Eosinophilia (> 250 to 400 cells/L), > 4 %; Sputum: Grossly, it is tenacious, rubbery, and whitish; in the presence of infection, especially in adults, it may be yellowish. Many eosinophils, are found microscopically; large numbers of histiocytes leukocytes are also present. and polymorphonuclear

Eosinophilic granules from disrupted cells (Creola bodies) may be seen throughout the sputum smear. Elongated dipyramidal crystals (Charcot-Leyden) originating from eosinophils are commonly found.

When bacterial respiratory infection is present, and particularly when there are bronchitic elements (Coorshman spirales), polymorphonuclear leukocytes and bacteries predominate.

Lab Studies
Eosinophilia greater than 4% or 300-400/L supports the diagnosis of asthma. Eosinophil counts greater than 8% may be observed in patients with concomitant atopic dermatitis, allergic bronchopulmonary aspergillosis. Total serum immunoglobulin E levels greater than 100 IU are frequently observed in patients experiencing allergic reactions, but this finding is not specific for asthma. A normal total serum immunoglobulin E level does not exclude the diagnosis of asthma.

Imaging Studies
Chest radiography. In most patients, chest radiography findings are normal or indicate hyperinflation. Findings may help determine other pulmonary diseases such as chronic bronchitis (emphysema, pneumosclerosis, increase pulmonary roots), pneumonia.

Sinus CT scan may be useful to determine acute or chronic sinusitis as a contributing factor.

Other Tests:
Allergy skin testing is a useful adjunct in individuals with atopy. Results help guide indoor allergen mitigation or help diagnose allergic rhinitis symptoms.
In patients with reflux symptoms and asthma, 24-hour pH monitoring or FGDS can help determine if gastroesophageal reflux disease is a contributing factor.

Pulmonary function testing (spirometry)

Perform spirometry measurements before and after inhalation of a short-acting bronchodilator in all patients in whom the diagnosis of asthma is considered to determine the degree of reversibility of the airways obstruction. Spirometry measures the forced vital capacity, the maximal amount of air expired from the point of maximal inhalation, and the Force expiratory volume for the first second (FEV1). A reduced ratio of FEV1 to forced vital capacity, when compared with predicted values, demonstrates the presence of airway obstruction. Reversibility is demonstrated by an increase of 12% or 200 mL after administration of a short-acting bronchodilator.

Pulmonary function tests

Static lung volumes and capacities - total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV) are usually increased. Vital capacity (VC) may be normal or decreased. Dynamic lung volumes and capacities, an index of airways obstruction, are reduced in asthmatics and return toward normal after inhalation of an aerosolized bronchodilator. Assessment of etiologic factors Positive skin tests indicate the presence of IgE Ab to the test allergen and represent only the potential for allergic reactivity to the allergens (hypersensitivity to the allergen).

Diagnostics Determination of severity

Determination of prognosis
Monitoring of disease progression

Basic indexes of spirometry FEV1 the Force expiratory volume for the first second; FVC the Force vital capacity; FEV1/FVC (%) - the relation shown in percents

Exercise spirometry
Exercise spirometry is the evaluating patients with EIA. standard method for

Testing involves 6-10 minutes of strenuous exertion at 8590% of predicted maximal heart rate and measurement of postexercise spirometry for 15-30 minutes. The defined cutoff for a positive test result is a 15% decrease in FEV1 after exercise.

Exercise testing may be accomplished in 3 different ways, using cycle ergometry, a standard treadmill test, or free running exercise.

Classification of severity and treatment options

Step 1 Intermittent bronchial asthma Intermittent symptoms occurring less than once a week Brief exacerbations Nocturnal symptoms occurring less than twice a month Asymptomatic with normal lung function between exacerbations FEV1 or PEF rate greater than 80%, with less than 20% variability Step 2 - Mild persistent bronchial asthma Symptoms occurring more than once a week but less than once a day Exacerbations affect activity and sleep Nocturnal symptoms occurring more than twice a month FEV1 or PEF rate greater than 80% predicted, with variability of 20-30%

Step 3 - Moderate persistent bronchial asthma Daily symptoms Exacerbations affect activity and sleep Nocturnal symptoms occurring more than once a week FEV1 rate 60-80% of predicted, with variability greater than 30% Step 4 - Severe persistent bronchial asthma Continuous symptoms Frequent exacerbations Frequent nocturnal asthma symptoms Physical activities limited by asthma symptoms FEV1 rate less then 60-80% of predicted

Treatment of Asthma (1)

Agent Albuterol (Ventolin, Proventil) Dose and Route Selective beta2 -agonists 100 mcg, 1-2 puffs q4-6h; not to exceed 12 puffs/d; may use 2-4 puffs q20min for 3 doses to treat an acute exacerbation. Nebulizer: Dilute 0.5 mL (2.5 mg) 0.5% inhalation solution in 1-2.5 mL of NS; administer 2.5-5 mg q4-6h, diluted in 25 mL sterile saline or water Selective beta2 agonist; beta1 (cardiac) effects at higher doses (inhalation preferred route) Comment

Salmeterol

2 puffs (50 mcg) bid. Discuss: 1 puff (50 mcg) bid

2 puffs (4,5-9-12 mcg) bid

Selective beta2 agonist; long-acting agent for maintenance therapy

Quick & long-acting agent

Formoterol

Treatment of Asthma (2)

Agent Theophylline (Theo-Dur, Uniphyl) Aminophylline Dose and Route Methylxanthlnes 150 300 mg td PO , Nervousness, nausea, IV twice per day or vomiting, anorexia, and once daily 0.5 mg/kg headache. 5 10 ml 2,5 % IV 1 Side-effects common. 2 d, 5-6 mg/kg toad Therapeutic level 10-20mug/ml 0.3-0.6 mg/kg maint. infusion Anticholinergic Ipatropium bromide (Atrovent) Nebulizer: 1-dose vial 60 to 90 min may be required (20-40-80 mcg) q2h before peak bronchodilation is for acute achieved. exacerbations MDI: 2 puffs qid; not to exceed 12 puffs/d Comment

Treatment of Asthma (3)

Agent Dose and Route
Topical corticosteroids Fluticasone (Flovent) 50 mcg MDI: 2 puffs bid for mild persistent asthma 125-250 mcg MDI: 2 puffs bid for moderate-to-severe persistent asthma 2 puffs tid/qid or 4 puffs bid; not to exceed 4 puffs qid for mild persistent or easily controlled moderately severe asthma 125-250 mcg 2 puffs 3 to 4 times daily for adults Severe asthma: 250-500 mcg 2 puffs bid; adjust dose downward to response; not to exceed 2000 mcg/d Onset of action 2 hours Onset of action 6 hours thrush (Orophar yngeal candidias is) and dysphoni a

Comme nt

Triamcinolone (Azmacort)

Beclomethasone dipropionate (Beclofort, Becloson, Beclovent)

Treatment of Asthma (4)

Dose and Route Comment Systemic corticosteroids Methyl-prednisolone IV 1-2 mg/kg q6- Onset of action 6 hours (Solu-Medrol) 12h Prednisolone PO 30-40 mg/d Onset of action 6 hours IV 30-60mg, IV infusion 90120 mg/d Hydrocortisone IV infusion 4 mg/kg q6h Dexamethasone IV 4-8 mg, thrush (Oropharyngeal IV infusion 12-16 candidiasis) and mg/d dysphonia Triamcinolone PO 24-40 mg/d -------acetonide Agent

Treatment of Asthma (5)

Mast cell-stabilizing agents Cromolyn sodium (Intal) 20 mg 2 puffs 4 for maintenance therapy times daily for 4 to 6 only and has no place in weeks treatment of the acute attack 2 mg 2 puffs qid (14 mg/d) ---------

Nedocromil sodium (Tilade)

Antibiotics for treatment infective-dependent exasorbation

Levofloxacin (Loxof)
Spiramicin (Rovamycin) Cefuroxime

PO, IV infusion 400 mg d

PO 3000000 IU q12h IV, IM 750 mg q8h

Used only with clinical evidence of bacterial infection.

------------

Treatment options of bronchial asthma

Step 1 Intermittent bronchial asthma

No daily medication needed.

Occasional use of inhaled short acting beta2adrenoceptor agonist bronchodilators (ventolin, salbutamol). Step 2 - Mild persistent bronchial asthma Regular inhaled anti-inflammatory agents. Inhaled short acting beta2-adrenoceptor agonists as required plus a low dose inhaled steroid (beclomethasone 200-500 mcg/d or fluticasone 100-250 mcg/d ). Alternatively sodium cromoglycate or nedocromil sodium 2-4 puffs tid/qid.

Treatment options of bronchial asthma

Step 3 - Moderate persistent bronchial asthma Middle dose inhaled steroids. Inhaled short acting beta2-adrenoceptor agonists as required plus an inhaled steroid (beclomethasone 500-1000 mcg/d or fluticasone 250-500 mcg/d). Or inhaled steroid (fluticasone 250-500 mcg/d) and long acting beta2-adrenoceptor agonist (salmeterol 50-100 mcg/d), especially for nighttime symptoms (Seretid 25/125 1-2 puffs q12h); fluticasone 250-500 mcg/d and formoterol 4,5-9 mcg/d (Foracort 9/125 1-2 puffs q12h) sustained-release theophylline.

Treatment options of bronchial asthma

Step 4 - Severe persistent bronchial asthma High dose inhaled steroids and regular bronchodilators. Inhaled short acting beta2-adrenoceptor agonists as required with an inhaled steroid (beclomethasone 800-2000 mcg/d, fluticasone 500-1000 mcg/d) plus a sequential therapeutic trial of one or more of: inhaled long acting beta2-adrenoceptor agonist (salmeterol or formoterol) - Seretid 25/250 mcg (50/250mcg) 1-2 puffs q12h; or Foracort 12/250 mcg 1-2 puffs q12h; sustained release theophylline 150-300 mg/d, inhaled ipratropium bromide 20 mg 1-2 puffs q12h. Addition of regular oral steroid therapy: regular prednisolone, dexamethasone or triamcinolone tablets in the lowest dose necessary to control symptoms in a single daily dose.

Short Course Oral Steroid Treatments

For adults 30-60 mg of prednisolone can be given initially and the same dose continued in single daily doses each morning until 2 days after control has been re-established. Indications for 'rescue courses of prednisolone include: symptoms and peak expiratory flow (PEF) progressively worsening day by day fall of PEF below 60% of the patient's best known recording onset or worsening of sleep disturbance by asthma persistence of morning symptoms until midday progressively diminishing response to an inhaled bronchodilator symptoms severe enough to require treatment with nebulised or iniected bronchodilators.

An Acute Attack of Asthma

The symptoms of asthma consist of a triad of dyspnea, cough, and wheezing. Respiration becomes audibly harsh, wheezing in both phases of respiration becomes prominent, expiration becomes prolonged, and patients frequently have tachypnea, tachycardia, and mild systolic hypertension. The patient prefers to sit upright or even leans forward, uses accessory muscles of respiration, is anxious, and may appear to struggle for air. Chest examination shows a prolonged expiratory phase with relatively high-pitched wheezes throughout inspiration and most of expiration. They have "squared off" thorax. Although coarse rhonchi may accompany the wheezes, fine crackles are not heard unless pneumonia, atelectasis, or cardiac decompensation is also present. The cough during an acute attack sounds "tight" and is generally nonproductive of mucus. Tenacious mucoid sputum is produced as the attack subsides.

Staging Of The Severity Of An Acute Asthma Attack

Stage I (mild) Symptoms and Signs Mild dyspnea, diffuse wheezes, adequate air exchange FEV1 or FVC pH PaCO2 PaO2 (Room air) N or

50-80% N N or of N or 50% N N or

II Respiratory distress at rest. (modera hyperpnea, use of accessory te) muscles. marked wheezes, air exchange N or III Marked respiratory distress, (severe) cyanosis, use of accessory muscles, marked wheezes or absent breath sounds; check for pulsus paradoxus 20-30 mm Hg IV (respiratory failure)

25% N

N or

Severe respiratory distress, 10% N lethargy, confusion, prominent pulsus paradoxus 30-50 mm Hg, use of accessory muscles

Complications During an Acute Attack of Asthma

Spontaneous pneumothorax may present as a sudden
worsening of respiratory distress, accompanied by sharp chest pains and, on physical examination, a shift of the mediastinum. X-ray examination confirms the diagnosis.

Mediastinal and subcutaneous emphysema due to

alveolar rupture and dissection of air along vessels is occasionally observed.

Atelectasis, usually involving the right middle lobe or even an

entire lung, is more common.

Bronchiectasis is rare. While evidence of acute cor pulmonale can occasionally be

noted on an ECG, chronic cor pulmonale secondary to asthma is rare.

Immediate Assessment Of Acute Severe Asthma

Features of severity Pulse rate >120 per mm Pulsus paradoxus Unable to speak in sentences Peak flow < 50% of expected Life-threatening features Can't speak Central cyanosis Exhaustion, confusion, reduced conscious level Bradycardia 'Silent chest' Unrecordable peak flow Arterial blood gases in life-threatening asthma A normal (5-6 kPa) or high CO2 tension Severe hypoxaemia (< 8 kPa) especially if being treated with oxygen A low pH or high [H+]

General Principles of the Drugs Use:

(1) Staging of the severity of the attack is paramount, especially if it has been prolonged (> 12 h) or if the patient is unfamiliar to the examiner. (2) Bronchodilators should be used in orderly progression, with the patient under close observation during initial therapy. (3) Although most asthmatics may benefit from inhalation of nebulized bronchodilators, some cannot inhale aerosol effectively and require parenteral drugs.

Treatment of the acute attack of asthma

Stage I or II is administration of high doses of aerosolized beta2

agonists (salbutamol 2,5 5 mg or terbutaline 5 10 mg) for nebulization or with a spacers every 20 min for three doses. Thereafter, to every 2 h until the attack has subsided. Epinephrine 0.01 mL/kg (0,5-0,9 mgkg) up to a maximum of 0.3 mL, repeated once or twice in 20 to 30 min, may be given. Aminophylline should be given IV 250 mg over 20 min after the first hour in an attempt to speed resolution. The infusion starts with an IV loading dose of aminophylline 6 mg/kg given over about 20 min; then a continuous infusion is begun (0.45 mg/kg/h). Stage III - an ABC determination should be obtained immediately and IV aminophylline started. Criteria for hospitalization vary, but definite indications are (1) failure to improve, (2) relapse after repeated adrenergic therapy and aminophylline, and (3) significant decrease in Pao2 (< 50 mm Hg) or increase in Paco2 (> 50 mm Hg), indicating progression to respiratory failure. Nust be given IV infusion of prednisolone 90 mg or dexametasone 8 mg. Stage IV any patients should immediately be given methylprednisolone 1 to 2 mg/kg IV q 4 to 6 h or hydrocortisone sodium succinate 4 mg/kg IV q 2 to 4 h. IV, prednisolone 60 mg or dexametasone 8 mg q 4 to 6 h .

Indications for Assisted Ventilation in Acute Severe Asthma

1. 2. 3. 4. Coma Respiratory arrest Exhaustion, confusion, drowsiness Deterioration of arterial blood gas tensions despite optimal therapy: PaO2 < 8 kPa and falling PaCO2 >6 kPa and rising pH < 7.3 and falling

Status asthmaticus occurs the severe attack, especially if it has been prolonged (> 12 h), or severe obstruction persisting for days or weeks. Fatigue and severe distress are evident in rapid, shallow, ineffectual respiratory movements. There may be a loss of adventitial breath sounds, and wheezing becomes very high pitched. Further, the accessory muscles become visibly active, and a paradoxical pulse often develops. Cyanosis becomes evident as the attack worsens. The end of an episode is frequently marked by a cough that produces thick, stringy mucus, which often takes the form of casts of the distal airways (Curschmann's spirals).

 O2 therapy is always indicated. O2 may be given effectively

with nasal prongs or, if tolerated, a Venturi mask with low Flo2 (2 to 4 L/min). It should always be humidified. Adrenocortical steroids: methylprednisolone (or prednisolon) 1 to 2 mg/kg (90-120mg) IV q 4 to 6 h or hydrocortisone 4 mg/kg (125-250 mg) IV q 2 to 4 h. Beta2-adrenergic agonists: salbutamol 2,5-5 mg once or twice in 20 to 30 min, Inhalation every 2-4 h Ipratropium bromide 0,5 mg should be added. Alkaline solutions (sodium bicarbonate) in the IV fluid should be limited to maintain the pH between 7.2 and 7.3. Patients who show no favorable response to aggressive bronchodilator and anti-inflammatory therapy and who evidence fatigue and progressive deterioration in ABCs and pH should be considered candidates for endotracheal intubation and respiratory assistance. Such patients should be hospitalized in an intensive care unit (ICU).

Status asthmaticus