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.
a lung disease characterized by
airways obstruction is reversible (but not completely in some patients), either spontaneously or with treatment,
airways inflammation, and
increased airways responsiveness to a variety of stimuli.
Etiologic factors of asthma
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 aspirin-sensitive 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.
Pathogenesis of asthma
The pathophysiology of asthma
involves the following components:
intermittent airflow obstruction, and
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 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.
Mechanisms of bronchial constriction in asthma
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 .
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 mediator-secreting 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
B ronchial constriction ore spasm in period of asthma attack
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: a ge at onset , history of injury early in life due to infection or passive smoke exposure, p rogress of disease , c urrent response to management , c omorbid conditions , the profile of exacerbation.
Family history may reveal the following conditions: a sthma , a llergy , s inusitis , r hinitis .
Social history may reveal the following conditions: h ome characteristics , s moking , w orkplace or school characteristics , e ducational level , e mployment , s ocial support .
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.
Aspirin or NSAID-hypersensitivity, sulfite sensitivity
Occupational exposure , e motional 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/μL), > 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 and polymorphonuclear leukocytes are also present. 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/ μ 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 ( FEV 1 ).
A reduced ratio of FEV 1 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 FEV 1 – the Force expiratory volume for the first second; FVC – the Force vital capacity; FEV 1 /FVC (%) - the relation shown in percents
Exercise spirometry is the standard method for evaluating patients with EIA.
Testing involves 6-10 minutes of strenuous exertion at 85-90% 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 FEV 1 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
Nocturnal symptoms occurring less than twice a month
Asymptomatic with normal lung function between exacerbations
FEV 1 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
FEV 1 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 FEV 1 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 FEV 1 rate less then 60-80% of predicted
Treatment of A sthma (1) Selective beta 2 agonist; long-acting agent for maintenance therapy 2 puffs (50 mcg) bid. Discuss: 1 puff (50 mcg) bid Salmeterol Comment Dose and Route Agent Selective beta 2 -agonists Quick & long-acting agent 2 puffs (4,5-9-12 mcg) bid Formoterol Selective beta 2 agonist; beta 1 (cardiac) effects at higher doses (inhalation preferred route) 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 2-5 mL sterile saline or water Albuterol (Ventolin, Proventil)
Treatment of A sthma (2) 60 to 90 min may be required before peak bronchodilation is achieved. Nebulizer: 1-dose vial (20-40-80 mcg) q2h for acute exacerbations MDI: 2 puffs qid; not to exceed 12 puffs/d Ipatropium bromide (Atrovent) Anticholinergic Side-effects common. Therapeutic level 10-20mug/ml 5 – 10 ml 2,5 % IV 1 – 2 d, 5-6 mg/kg toad 0.3-0.6 mg/kg maint. infusion Aminophylline Nervousness, nausea, vomiting, anorexia, and headache. 150 – 300 mg td PO , IV twice per day or once daily 0.5 mg/kg Theophylline (Theo-Dur, Uniphyl) Methylxanthlnes Comment Dose and Route Agent
Treatment of A sthma (3) thrush ( Oropharyngeal candidiasis ) and dysphonia 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 Beclomethasone dipropionate (Beclofort, Becloson, Beclovent) Onset of action 6 hours 2 puffs tid/qid or 4 puffs bid; not to exceed 4 puffs qid for mild persistent or easily controlled moderately severe asthma Triamcinolone (Azmacort) Onset of action 2 hours 50 mcg MDI: 2 puffs bid for mild persistent asthma 125-250 mcg MDI: 2 puffs bid for moderate-to-severe persistent asthma Fluticasone (Flovent) Topical corticosteroids Comment Dose and Route Agent
Treatment of A sthma (4) thrush ( Oropharyngeal candidiasis ) and dysphonia IV 4-8 mg, IV infusion 12-16 mg/d Dexa methasone -------- PO 24-4 0 mg/d T riamcinolone acetonide IV infusion 4 mg/kg q6h Hydrocortisone Onset of action 6 hours PO 30-4 0 mg/d IV 30-60mg, IV infusion 90-120 mg/d Prednisolone Onset of action 6 hours IV 1-2 mg/kg q6-12h Methyl-prednisolone (Solu-Medrol) Systemic corticosteroids Comment Dose and Route Agent
Treatment of A sthma (5) IV, IM 750 mg q8h Cefuroxime ------------ PO 3000000 IU q12h Spiramicin (Rovamycin) Used only with clinical evidence of bacterial infection. PO, IV infusion 400 mg d Levofloxacin (Loxof) Antibiotics for treatment infective-dependent exasorbation --------- 2 mg 2 puffs qid (14 mg/d) Nedocromil sodium (Tilade) for maintenance therapy only and has no place in treatment of the acute attack 20 mg 2 puffs 4 times daily for 4 to 6 weeks Cromolyn sodium (Intal) Mast cell-stabilizing agents
Treatment options of bronchial asthma Step 1 – Intermittent bronchial asthma No daily medication needed . Occasional use of inhaled short acting beta 2 -adrenoceptor agonist bronchodilators (ventolin, salbutamol). Step 2 - Mild persistent bronchial asthma Regular inhaled anti-inflammatory agents. Inhaled short acting beta 2 -adrenoceptor agonists as required plus a low dose inhaled steroid (beclomethasone 200-500 mcg/d or fluticasone 1 00-250 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 beta 2 -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 beta 2 -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 beta 2 -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 beta 2 -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
onset or worsening of sleep disturbance by asthma
persistence of morning symptoms until midday
progressively diminishing response to an inhaled
symptoms severe enough to require treatment with
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 ↓↓↓ ↑↑ ↓↓ 10% N Severe respiratory distress, lethargy, confusion, prominent pulsus paradoxus 30-50 mm Hg, use of accessory muscles IV (respi-ratory failure) ↓↓ N or ↑ ↓ 25% N Marked respiratory distress, cyanosis, use of accessory muscles, marked wheezes or absent breath sounds; check for pulsus paradoxus 20-30 mm Hg III (severe) ↑ ↓ N or ↑ 50% N Respiratory distress at rest. hyperpnea, use of accessory muscles. marked wheezes, air exchange N or ↓ II (moderate) N or ↓ N or ↑ N or ↑ 50-80% of N Mild dyspnea, diffuse wheezes, adequate air exchange I (mild) PaO 2 (Room air) PaCO 2 pH FEV 1 or FVC Symptoms and Signs Stage
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
Unable to speak in sentences
Peak flow < 50% of expected
Exhaustion, confusion, reduced conscious level
Unrecordable peak flow
Arterial blood gases in life-threatening asthma
A normal (5-6 kPa) or high CO 2 tension
Severe hypoxaemia (< 8 kPa) especially if being treated
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 methyl-prednisolone 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
Exhaustion, confusion, drowsiness
Deterioration of arterial blood gas tensions despite optimal therapy:
PaO 2 < 8 kPa and falling
PaCO 2 >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).
O 2 therapy is always indicated. O 2 may be given effectively with nasal prongs or, if tolerated, a Venturi mask with low Flo 2 (2 to 4 L/min). It should always be humidified.
A drenocortical steroid s: methylprednisolone (or prednisolon) 1 to 2 mg/kg (9 0 - 12 0mg) IV q 4 to 6 h or hydrocortisone 4 mg/kg (125-250 mg ) IV q 2 to 4 h.
Beta 2 - adrenergic agonist s: 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).