Bronchial Asthma - Information Overview

Bronchial asthma is a chronic inflammatory disease of the respiratory tract involving cells (mast cells, eosinophils, T-lymphocytes), mediators of allergy and inflammation, accompanied in predisposed individuals by hyperreactivity and variable obstruction of the bronchi, which is manifested by an attack of suffocation, the appearance of wheezing, coughing or difficulty breathing, especially at night and/or early in the morning.

Symptoms of asthma include shortness of breath, chest tightness, and wheezing. Diagnosis is based on history, physical examination, and pulmonary function tests. Treatment of asthma involves control of triggers and drug therapy, usually inhaled beta-agonists and inhaled glucocorticoids. Prognosis is good with treatment.

This definition is consistent with the main provisions of the joint report of the National Heart, Lung, and Blood Institute (USA) and WHO “Bronchial Asthma. Global Strategy” (1993).

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Epidemiology of bronchial asthma

Since the 1970s, the prevalence of asthma has been increasing steadily, and currently affects approximately 4% to 7% of the world's population. Asthma affects approximately 12% to 17 million people in the United States; between 1982 and 1992, the prevalence of asthma increased from 34.7 to 49.4 per 1,000 people. The rate is higher among people younger than 18 years (6.1%) than among those aged 18 to 64 years (4.1%), and is higher in prepubertal males and postpubertal females. Asthma is also more common among urban residents and among blacks and some Hispanics. Mortality from asthma has also increased, with approximately 5,000 asthma deaths occurring in the United States each year. The mortality rate is five times higher among blacks than among Caucasians. Asthma is the leading cause of hospitalization in children and the most common chronic disease leading to absenteeism in elementary school. In 2002, the total cost of treating asthma was $14 billion.

There is a steady increase in the number of people suffering from bronchial asthma throughout the world, which is especially characteristic of economically developed countries.

More than 100 million people worldwide suffer from bronchial asthma. The prevalence of bronchial asthma ranges from 3 to 8%. The incidence rate is particularly high in New Zealand and Australia. In Western European countries, the prevalence of bronchial asthma is 5%.

About 30% of patients with bronchial asthma rarely resort to the use of anti-asthmatic drugs, another 30% use them regularly, 20-25% suffer from a severe form of the disease and are forced to resort to taking several anti-asthmatic drugs, 8-10% suffer from a disabling form of the disease.

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Causes of bronchial asthma

Bronchial asthma is a multifactorial disease, its development depends on interactions between multiple genetic and environmental factors.

Genetic factors responsible for the predisposition to the development of bronchial asthma include genes for T-helper cells type 2 (TH) and their cytokines (IL-4, -5, -9 and -13) and the recently discovered ADAM33 gene, which can stimulate airway smooth muscle and fibroblast proliferation or regulate cytokine production.

The importance of household factors (dust mites, cockroaches, pets) and other environmental allergens (pollen) in the development of the disease in older children and adults has been proven. Contact with bacterial endotoxin in early childhood can cause the formation of tolerance and protective mechanisms. Air pollution is not directly associated with the development of the disease, although this factor can cause exacerbations of the disease. A diet low in vitamins C and E and omega-3 fatty acids is associated with bronchial asthma, as is obesity. Asthma is also associated with perinatal factors, such as young maternal age, poor maternal nutrition, premature birth, low birth weight, and artificial feeding. The role of exposure to cigarette smoke in childhood is controversial, with some studies proving a provoking role and others a protective effect.

Indoor exposure to nitric oxide and volatile organic compounds is implicated in the development of reactive airways dysfunction syndrome (RADS), a syndrome of persistent reversible airway obstruction in people without a history of asthma. Whether RADS is a separate syndrome from asthma or a form of occupational asthma is controversial, but both conditions have many similarities (e.g., wheezing, shortness of breath, cough) and respond to glucocorticoids.

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Pathogenesis of bronchial asthma

Genetic and environmental factors may interact to determine the balance between T-helper type 1 (TH1) and 2 (TH2) cells. Experts believe that children are born with a predisposition to pro-allergic and pro-inflammatory TH immune responses, which are characterized by the growth and activation of eosinophils and the production of IgE, but exposure to bacterial and viral infections and endotoxins at an early age shifts the immune system towards TH responses, which suppresses TH cells and induces tolerance. Developed countries tend to have smaller families, fewer children per family, near-perfectly clean homes, and early vaccination and antibiotic treatment of children. All of this prevents children from being exposed to environmental factors that suppress TH immune responses and induce tolerance, which may partly explain the continuous increase in the prevalence of bronchial asthma in developed countries (the hygiene hypothesis).

In patients with asthma, these TH cells and other cell types, especially eosinophils and mast cells but also other CD4+ cell subtypes and neutrophils, form extensive inflammatory infiltrates in the airway epithelium and bronchial smooth muscle, leading to desquamation, subepithelial fibrosis, and smooth muscle hypertrophy. Smooth muscle hypertrophy narrows the airways and increases reactivity to allergens, infections, irritants, parasympathetic stimulation (which causes the release of proinflammatory neuropeptides such as substance P, neurokinin A, and calcitonin gene-related peptide), and other triggers of bronchoconstriction. An additional contribution to increased airway reactivity is made by the loss of bronchospasm inhibitors (epithelial-derived relaxing factor, prostaglandin E) and other substances that metabolize endogenous bronchoconstrictors (endopeptidases) due to epithelial sloughing and mucosal edema. Mucus formation and peripheral blood eosinophilia are additional classic signs of asthma that may be secondary manifestations of airway inflammation.

Common triggers for asthma attacks include occupational and environmental allergens; infections (respiratory syncytial virus and parainfluenza virus in young children, acute respiratory infections and pneumonia in older children and adults); exercise, especially in cold, dry environments; inhaled irritants (air pollution); and anxiety, anger, and agitation. Aspirin is a trigger in 30% of older or more severe asthmatics, usually associated with nasal polyposis and sinus congestion. Gastroesophageal reflux disease (GERD) has recently been recognized as a common trigger of asthma, possibly due to bronchospasm caused by reflux or microaspiration of acidic gastric contents. Allergic rhinitis is frequently associated with asthma; It is unclear whether these two diseases are different manifestations of the same allergic process, or whether rhinitis is a separate trigger for bronchial asthma.

In the presence of triggers, the pathophysiological changes characteristic of asthma cause reversible airway obstruction and uneven pulmonary ventilation. Relative perfusion exceeds relative ventilation in obstructed areas, resulting in a decrease in alveolar O2 pressure and an increase in alveolar CO2 tension. Most patients can compensate for this condition by hyperventilation, thus maintaining Pa-CO2 below normal levels. However, in severe exacerbations, diffuse bronchospasm causes severe gas exchange impairment, and the respiratory muscles are unable to create respiratory effort and provide increased respiratory work. At the same time, hypoxemia and muscle tension increase, and PaCO2 increases. The result may be respiratory and metabolic acidosis, which, if untreated, may lead to cardiac and respiratory arrest.

Depending on the symptoms, bronchial asthma is classified into four categories (according to severity): mild intermittent, mild persistent, moderate persistent and severe persistent.

The inflammatory process in the bronchi leads to 4 forms of bronchial obstruction:

• acute spasm of the smooth muscles of the bronchi;
• subacute edema of the bronchial mucosa;
• chronic formation of viscous bronchial secretions;
• irreversible sclerotic process in the bronchi.

At the IV National Russian Congress on Respiratory Diseases (Moscow, 1994), the following definition of bronchial asthma was adopted.

Bronchial asthma is an independent disease based on chronic inflammation of the respiratory tract, accompanied by changes in the sensitivity and reactivity of the bronchi and manifested by an attack of suffocation, asthmatic status or, in the absence of such, symptoms of respiratory discomfort (paroxysmal cough, distant wheezing and shortness of breath), reversible bronchial obstruction against the background of a hereditary predisposition to allergic diseases outside the lungs signs of allergy, blood eosinophilia and/or sputum eosinophilia.

Symptoms of bronchial asthma

Between exacerbations, patients with mild intermittent or mild persistent asthma are usually asymptomatic. Patients with more severe asthma or exacerbations experience shortness of breath, chest tightness, audible wheezing, and cough; cough may be the only symptom in some patients (cough-variant asthma). Symptoms may have a circadian rhythm and worsen during sleep, often around 4 a.m. Many patients with more severe asthma awaken at night (nocturnal asthma).

Symptoms of asthma include wheezing, pulsus paradoxus (a drop in systolic blood pressure > 10 mm Hg during inspiration), tachypnea, tachycardia, and visible inspiratory effort (use of cervical and suprasternal [accessory] muscles, upright sitting position, retracted lips, inability to speak). The expiratory phase of breathing is prolonged, with an inspiratory/expiratory ratio of at least 1:3. Stridor may be present in both phases or only on expiration. A patient with severe bronchospasm may not have any audible wheezing because of markedly restricted airflow.

A patient with severe exacerbation and impending respiratory failure usually has some combination of altered consciousness, cyanosis, pulsus paradoxus greater than 15 mmHg, O2 saturation (O2 sat.) less than 90%, PaCO2 > 45 mmHg (at sea level), and pulmonary hyperinflation. Chest radiography may rarely reveal pneumothorax or pneumomediastinum.

Asthma symptoms disappear between acute asthma attacks, although a soft stridor may be heard during forced expiration, after exercise, and at rest in some asymptomatic patients. Increased lung airiness may alter the chest wall in patients with long-standing uncontrolled asthma, causing a barrel chest.

All symptoms of bronchial asthma are non-specific, reversible with timely treatment and usually develop when exposed to one or more triggers.

For the correct choice of treatment measures for bronchial asthma, the etiological classification of the disease and the degree of bronchial obstruction (severity of the disease) are of great importance.

The modern etiological classification of bronchial asthma provides for the identification of exogenous, endogenous and mixed forms.

Exogenous (atopic) bronchial asthma is a form of the disease caused by known exogenous (external) etiological factors (non-infectious allergens). Such factors may be:

• household allergens (house dust mites; domestic animal allergens; cockroaches; rodents - mice, rats; mold and yeast fungi);
• pollen allergens (weeds - timothy grass, fescue; trees - birch, alder, hazel, etc.; weeds - wormwood, quinoa; ragweed, etc.);
• drug allergens (antibiotics, enzymes, immunoglobulins, serums, vaccines);
• food allergens and food additives;
• professional allergens (wheat flour dust, scales of butterfly bodies and wings in the silk industry, coffee bean dust, platinum salts in the metalworking industry, epidermal allergens in animal husbandry).

The main mechanism of development of this asthma is an immediate-type immunological reaction mediated by specific IgE. This reaction develops as a result of interaction of an allergen (antigen) with specific antibodies of the IgE class; fixed mainly on submucous mast cells of the respiratory tract and basophils circulating in the blood. Interaction of the antigen with IgE on the surface of these cells leads to their degranulation with the release of biologically active mediators causing bronchospasm, edema of the bronchial mucosa, hypersecretion of mucus and inflammation (histamine, leukotrienes, proinflammatory prostaglandins, platelet-activating factor, etc.).

Identification of an etiological external factor in patients with exogenous bronchial asthma allows for successful targeted treatment: allergen elimination or specific desensitization.

Endogenous (non-atopic) bronchial asthma is a form of the disease that is not based on allergic sensitization and is not associated with the impact of a known exogenous allergen. The following may act as etiological factors of bronchial asthma:

• arachidonic acid metabolism disorders ("aspirin" asthma);
• endocrine disorders;
• neuropsychiatric disorders;
• disturbances of receptor balance and electrolyte homeostasis of the respiratory tract;
• physical activity.

Mixed bronchial asthma is a form of the disease that combines the signs of exogenous (atopic) and endogenous (non-atopic) forms.

Diagnosis of bronchial asthma

The diagnosis of asthma is based on the patient's history and physical examination and is confirmed by pulmonary function tests. It is also important to identify the underlying cause and rule out conditions that also cause wheezing.

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Pulmonary function tests

Patients suspected of having asthma should have pulmonary function tests to confirm and quantify the severity and reversibility of airflow obstruction. Pulmonary function tests are effort-dependent and require careful patient education before testing. If possible, bronchodilators should be stopped before testing: 6 hours for short-acting beta-agonists such as salbutamol; 8 hours for ipratropium bromide; 12 to 36 hours for theophylline; 24 hours for long-acting beta-agonists such as salmeterol and formoterol; and 48 hours for tiotropium.

Spirometry should be performed before and after inhalation of a short-acting bronchodilator. Manifestations of airflow obstruction before bronchodilator inhalation include a reduced forced expiratory volume in the first second (FEV ) and a reduced ratio of FEV to forced vital capacity (FEV /FVC). The FVC may also be reduced. Measurements of lung volumes may show an increase in residual volume and/or functional residual capacity due to air trapping. An increase in FEV of more than 12% or more than 0.2 L in response to a bronchodilator confirms reversible airflow obstruction, although bronchodilator treatment should not be discontinued if this effect is absent. Spirometry should be performed at least annually to monitor the disease course in patients diagnosed with asthma.

Flow-volume loops should also be examined to diagnose or exclude vocal cord dysfunction, which is a common cause of upper airway obstruction similar to asthma.

Provocative testing with inhaled methacholine chloride (or with alternative stimuli such as inhaled histamine, adenosine, bradykinin, or exercise) to induce bronchospasm is indicated when asthma is suspected with normal spirometry and flow-volume studies, cough-variant asthma is suspected, and there are no contraindications. Contraindications include FEV <1 L or <50%, recent acute myocardial infarction (AMI) or stroke, and severe hypertension (systolic BP >200 mmHg; diastolic BP >100 mmHg). A decrease in FEV >20% confirms the diagnosis of asthma. However, FEV may also decrease in response to these drugs in other diseases such as COPD.

Other tests

In some situations, other tests may be useful.

A carbon monoxide diffusing capacity (DLC0) test can help differentiate asthma from COPD. Volumes are normal or increased in asthma and usually decreased in COPD, especially with the development of emphysema.

Chest radiography may help exclude underlying causes of asthma or alternative diagnoses such as heart failure or pneumonia. Chest radiography in asthma is usually normal but may show increased airiness or segmental atelectasis, suggesting bronchial mucus obstruction. Infiltrates, particularly those that come and go and that are associated with central bronchiectasis, suggest allergic bronchopulmonary aspergillosis.

Allergy testing is indicated for all children with a history suggestive of allergic triggers (since all children are potentially responsive to immunotherapy). This testing should also be considered for adults with a history of symptom relief with allergen cessation and for those for whom anti-IgE antibody therapy is being considered. Skin testing and measurement of allergen-specific IgE by radioallergosorbent testing (PACT) can identify specific allergic triggers. Elevated blood eosinophils (>400 cells/μL) and nonspecific IgE (>150 IU) are suggestive but not diagnostic of allergic asthma because they can be elevated in a variety of conditions.

Sputum eosinophil testing is not routinely performed; the presence of large numbers of eosinophils is suggestive of asthma, but the test is neither sensitive nor specific.

Measuring peak expiratory flow rate (PEF) with inexpensive portable peak flow meters is recommended for home monitoring of disease severity and ongoing therapy.

Assessment of exacerbations

Patients with diagnosed exacerbated asthma should have pulse oximetry and either PEF or FEV measurement. All three measures quantify the severity of the exacerbation and document the response to treatment. PEF values are interpreted in light of the patient's individual best, which can vary widely among equally well-controlled patients. A 15% to 20% decrease from this baseline value indicates a significant exacerbation. When baseline values are unknown, mean predicted values may provide some indication of airflow limitation but not the degree of deterioration in the patient's condition.

Chest radiography is not required for most exacerbations, but should be performed in patients with symptoms suggestive of pneumonia or pneumothorax.

Arterial blood gases should be obtained in patients with severe respiratory distress syndrome or signs and symptoms of impending respiratory failure.

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Treatment of bronchial asthma

Treatment of asthma, both chronic and acute, includes control of triggers, pharmacotherapy appropriate to disease severity, monitoring of response to treatment and disease progression, and patient education to improve disease self-management. The goals of treatment are to prevent exacerbations and chronic symptoms, including nocturnal awakenings; minimize the need for intensive care unit admissions; maintain baseline lung function and patient activity; and prevent adverse effects of treatment.

Controlling trigger factors

Trigger factors may be controlled in some patients by using synthetic fiber pillows and impermeable mattress covers, and by frequently washing bedding and sheeting in hot water. Upholstered furniture, stuffed toys, carpets, and pets should be removed (dust mites, pet dander), and dehumidifiers should be used in basements and other poorly ventilated, damp areas (mold). Wet cleaning of homes reduces dust mite allergens. The fact that these trigger factors are difficult to control in urban environments does not diminish the importance of these measures; elimination of cockroach excrement by house cleaning and extermination is especially important. Vacuum cleaners and high-efficiency particulate air (HEPA) filters may reduce symptoms, but their effects on lung function and medication requirements are unproven. Sulfite-sensitive patients should avoid red wine. Nonallergenic triggers such as cigarette smoke, strong fragrances, irritating fumes, cold temperatures, high humidity, and exercise should also be avoided or controlled if possible. Patients with aspirin-induced asthma may use paracetamol, choline trisalicylate, or cyclooxygenase (COX-2) inhibitors instead of nonsteroidal anti-inflammatory drugs (NSAIDs). Asthma is a relative contraindication to the use of nonselective beta-blockers, including topical preparations, but cardioselective agents (eg, metoprolol, atenolol) are unlikely to have any adverse effects.

Of great importance in the treatment of bronchial asthma is the elimination of trigger factors that cause exacerbation of the disease. These include:

• long-term exposure to causative factors (allergens or occupational factors) to which the patient’s respiratory tract is already sensitized;
• physical activity;
• excessive emotional stress;
• the influence of cold air and weather changes;
• air pollution (tobacco smoke, wood smoke, aerosols, air pollutants, etc.);
• respiratory infection;
• some medicinal substances.

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Drug treatment of bronchial asthma

The major drug classes commonly used in the treatment of stable asthma and its exacerbations include bronchodilators (beta2-agonists, anticholinergics), glucocorticoids, mast cell stabilizers, leukotriene modifiers, and methylxanthines. Drugs in these classes are inhaled or taken orally; inhaled drugs come in aerosol and powder forms. Use of aerosol forms with a spacer or holding chamber facilitates delivery of drug to the airways rather than to the mouth or pharynx; patients should be instructed to wash and dry the holding chamber after each use to prevent bacterial contamination. In addition, use of aerosol forms requires coordination between inhalation and actuation of the inhaler (medication device) and inhalation; powder forms reduce the need for coordination because the drug is delivered only when the patient inhales. In addition, powder forms reduce the release of fluorocarbon propellants into the environment.

Beta-agonists (beta-adrenergic agents) relax bronchial smooth muscles, inhibit mast cell degranulation and histamine release, reduce capillary permeability and enhance the cleansing ability of the ciliated epithelium; beta-agonists are short-acting and long-acting. Short-acting beta-agonists (eg, salbutamol) are inhaled 2-8 times as needed and are the drug of choice for relieving acute bronchospasm and preventing exercise-induced bronchospasm. Their effect occurs within minutes and lasts up to 6-8 hours, depending on the specific drug. Long-acting drugs, which are inhaled before bedtime or 2 times a day and whose activity lasts 12 hours, are used for moderate to severe asthma, as well as for mild asthma that causes night awakenings. Long-acting beta-agonists also act synergistically with inhaled glucocorticoids and allow lower doses of glucocorticoids to be used. Oral beta-agonists have more systemic side effects and should generally be avoided. Tachycardia and tremor are the most common acute adverse effects of inhaled beta-agonists and are dose-related. Hypokalemia is rare and only mild. The safety of regular long-term use of beta-agonists is controversial; chronic, possibly excessive, use has been associated with increased mortality, but it is unclear whether this is an adverse effect of the drugs or whether regular use reflects inadequate disease control with other drugs. Taking one or more packs per month suggests inadequate disease control and the need to initiate or intensify other therapy.

Anticholinergics relax bronchial smooth muscle through competitive inhibition of muscarinic (M3) cholinergic receptors. Ipratropium bromide has minimal effect when used alone in asthma, but may have additive effects when used with short-acting beta-agonists. Adverse effects include pupil dilation, visual disturbances, and xerostomia. Tiotropium is a 24-hour inhaled medication that has not been well studied in asthma.

Glucocorticoids inhibit airway inflammation, reverse beta-receptor suppression, block leukotriene synthesis, and inhibit cytokine production and protein adhesin activation. They block the late response (but not the early response) to inhaled allergens. Glucocorticoids are administered orally, intravenously, and by inhalation. In acute asthma, early use of systemic glucocorticoids often aborts the exacerbation, reduces the need for hospitalization, prevents relapses, and accelerates recovery. Oral and intravenous routes are equally effective. Inhaled glucocorticoids have no role in acute exacerbations but are indicated for long-term suppression, control, and suppression of inflammation and symptoms. They significantly reduce the need for oral glucocorticoids and are considered disease-modifying agents because they slow or stop the decline in lung function. Undesirable local effects of inhaled glucocorticoids include dysphonia and oral candidiasis, which can be prevented or minimized by the patient using a spacer and/or rinsing with water after inhalation of the glucocorticoid. All systemic effects are dose-dependent, can occur with oral or inhaled forms, and occur mainly at inhaled doses greater than 800 mcg/day. Undesirable effects of glucocorticoids include suppression of the pituitary-adrenal axis, osteoporosis, cataracts, skin atrophy, hyperphagia, and mild weight gain. It is not known for certain whether inhaled glucocorticoids suppress growth in children: most children achieve predicted adult height. Asymptomatic tuberculosis (TB) may be reactivated by systemic use of glucocorticoids.

Mast cell stabilizers inhibit histamine release by mast cells, reduce airway hyperreactivity, and block early and late reactions to allergens. They are given as prophylactic inhalations to patients with allergic asthma and exercise-induced asthma; however, they are ineffective once symptoms develop. Mast cell stabilizers are the safest of all antiasthmatic drugs, but the least effective.

Leukotriene modifiers are taken orally and can be used for long-term control and prevention of symptoms in patients with mild to severe persistent asthma. The main adverse effect is an increase in liver enzymes; very rarely, patients develop a clinical syndrome resembling Churg-Strauss syndrome.

Methylxanthines relax bronchial smooth muscle (probably by nonselective phosphodiesterase inhibition) and may improve myocardial and diaphragmatic contractility through unknown mechanisms. Methylxanthines probably inhibit intracellular Ca2+ release, reduce capillary permeability in the airway mucosa, and inhibit the late response to allergens. They reduce eosinophil infiltration of the bronchial mucosa and T-lymphocyte infiltration of the epithelium. Methylxanthines are used for long-term control as an adjunct to beta-agonists; sustained-release theophylline is helpful in the treatment of nocturnal asthma. The drugs are falling out of use because of a higher incidence of adverse effects and interactions compared with other drugs. Adverse effects include headache, vomiting, cardiac arrhythmias, and seizures. Methylxanthines have a narrow therapeutic index; Many drugs (any drug metabolized via the cytochrome P450 pathway, eg, macrolide antibiotics) and conditions (eg, fever, liver disease, heart failure) alter methylxanthine metabolism and elimination. Serum theophylline levels should be monitored periodically and maintained between 5 and 15 μg/mL (28 and 83 μmol/L).

Other drugs are used rarely in certain circumstances. Immunotherapy may be indicated when symptoms are caused by allergy, as suggested by the history and confirmed by allergy testing. Immunotherapy is more effective in children than in adults. If symptoms are not significantly relieved within 24 months, therapy is stopped. If symptoms are relieved, therapy should be continued for 3 or more years, although the optimal duration is unknown. Dose-limiting glucocorticoid agents are sometimes used to reduce dependence on high-dose oral glucocorticoids. All have significant toxicity. Low-dose methotrexate (5 to 15 mg weekly) can produce a small increase in FEV1 and a modest decrease (3.3 mg/day) in the daily oral glucocorticoid dose. Gold and cyclosporine are also moderately effective, but toxicity and the need for monitoring limit their use. Omalizumab is an anti-IgE antibody designed for use in patients with severe allergic asthma with elevated IgE levels. It reduces the need for oral glucocorticoids and improves symptoms. The dose is determined by body weight and IgE levels according to a specific schedule; the drug is administered subcutaneously every 2 weeks. Other drugs for the control of chronic asthma include inhaled lidocaine, inhaled heparin, colchicine, and high-dose intravenous immunoglobulin. The use of these drugs is supported by limited data, and their efficacy has not been proven; therefore, none of them can yet be recommended for clinical use.

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Monitoring the response to treatment of bronchial asthma

Peak expiratory flow (PEF), a measurement of airflow and airflow obstruction, helps to define the severity of asthma exacerbations by documenting the response to treatment and monitoring trends in disease severity in real-life settings through patient diaries. Home PEF monitoring is particularly useful for monitoring disease progression and treatment responses in patients with moderate to severe persistent asthma. When asthma is asymptomatic, a single PEF measurement in the morning is sufficient. If the patient's PEF falls below 80% of their personal best, twice-daily monitoring is performed to assess circadian changes. Circadian changes greater than 20% indicate airway instability and the need for a change in therapeutic regimen.

Patient education

The importance of patient education cannot be overstated. Patients do better if they know more about asthma - what triggers an attack, which medications to use and when, proper inhalation technique, how to use a spacer with a MDI, and the importance of early use of glucocorticoids during exacerbations. Each patient should have a written action plan for daily treatment, especially for acute attacks, based on the patient's personal best PEF rather than average levels. Such a plan results in the best possible asthma control, greatly increasing adherence to therapy. Exacerbation management. The goal of asthma exacerbation management is to reduce symptoms and restore the patient to his or her personal best PEF. Patients should be taught to self-administer inhaled salbutamol or similar short-acting beta-agonist during an exacerbation and to measure PEF if necessary. Patients who feel better after 2-4 puffs from the IDI should use the inhaler up to 3 times every 20 minutes in divided puffs, and those who are found to have a PEF greater than 80% predicted can treat the exacerbation at home. Patients who do not respond to the drug, have severe symptoms, or have a PEF < 80% should follow the treatment algorithm determined by the physician or go to the emergency department for aggressive treatment.

Inhaled bronchodilators (beta-agonists and anticholinergics) are the mainstay of emergency department asthma treatment. In adults and older children, salbutamol given by MDI with spacer is as effective as that given by nebuliser. Nebuliser therapy is preferred in younger children because of difficulties in coordinating the MDI and spacer; recent studies suggest that the response to bronchodilators is improved when the nebuliser is supplied with helium-oxygen (heliox) rather than oxygen alone. Subcutaneous epinephrine 1:1000 or terbutaline is an alternative in children. Terbutaline may be preferred to epinephrine because of its less pronounced cardiovascular effects and longer duration of action, but it is no longer produced in large quantities and is expensive.

Subcutaneous administration of beta-agonists is theoretically problematic in adults because of unwanted cardiac stimulatory effects. However, clinically apparent adverse effects are few, and subcutaneous administration may be useful in patients who are refractory to maximal inhalation therapy or who are unable to respond effectively to nebulised therapy (eg, with severe cough, poor ventilation, or inability to communicate). Nebulised ipratropium bromide may be used with inhaled salbutamol in patients who do not respond optimally to salbutamol alone; some studies support the use of high-dose beta-agonist and ipratropium bromide together as first-line treatment, but there are no data on the superiority of continuous over intermittent inhaled beta-agonist. The role of theophylline in treatment is minor.

Systemic glucocorticoids (prednisolone, methylprednisolone) should be given in all but mild exacerbations, as they are not needed in patients whose PEF normalizes after 1 or 2 doses of a bronchodilator. Intravenous and oral routes are equally effective. Intravenous methylprednisolone can be given if an intravenous catheter is available, and the patient can then be switched to oral therapy as needed or when convenient. Dose reduction usually begins after 7 to 10 days and should be continued for 2 to 3 weeks.

Antibiotics are prescribed only when history, examination, or chest X-ray suggest a bacterial infection; most infections underlying asthma exacerbations are viral in origin, but mycoplasmas and ichlamydia have been recently identified in patient populations.

Oxygen therapy is indicated when patients with asthma exacerbation have SaO2 <90% as measured by pulse oximetry or arterial blood gas testing; oxygen therapy is given via nasal cannula or mask at a flow rate or concentration sufficient to correct hypoxemia.

If the cause of exacerbation of bronchial asthma is anxiety, the main thing is to calm the patient and instill confidence in him. There are relative contraindications for the use of tranquilizers and morphine, as they are associated with increased mortality and the need for artificial ventilation of the lungs.

Hospitalization is usually required if the patient's condition has not improved within 4 hours. Criteria for hospitalization may vary, but absolute indications include lack of improvement, increasing weakness, relapse after repeated beta-agonist therapy, and a significant decrease in PaO2 (< 50 mmHg) or increase in PaCO2 (> 40 mmHg), indicating progression of respiratory failure.

Patients who continue to deteriorate despite intensive therapy are candidates for noninvasive positive pressure ventilation or, in severely ill patients and those who do not respond to this approach, endotracheal intubation and mechanical ventilation. Patients who require intubation respond well to sedation, but muscle relaxants should be avoided because of possible interactions with glucocorticoids, which can cause prolonged neuromuscular weakness.

Volume cycling ventilation in assisted control mode is usually used as it provides constant alveolar ventilation in the face of high and variable airway resistance. The ventilator should be set to a rate of 8-14 breaths/min with a high inspiratory flow rate (> 60 L/min - 80 L/min) to prolong expiration and minimise autoPEEP (positive end-expiratory pressure).

Initial tidal volumes may be set in the range of 10–12 ml/kg. High peak airway pressures may generally be ignored because they are due to high airway resistance and inspiratory flow and do not reflect the degree of lung distension produced by alveolar pressure. However, if the plateau pressure exceeds 30–35 cm H2O, tidal volumes should be reduced to 5–7 ml/kg to limit the risk of pneumothorax. An exception is when decreased chest wall (eg, obesity) or abdominal (eg, ascites) response may contribute significantly to the elevated pressure. When reduced tidal volumes are necessary, a moderate degree of hypercapnia is tolerated, but if arterial pH falls below 7.10, sodium bicarbonate is given slowly to maintain the pH between 7.20 and 7.25. Once airflow obstruction is reduced and arterial PaCO3 and pH are normalized, patients can be quickly weaned off ventilation.

Other treatments have been reported to be effective in asthma exacerbations, but they have not been well studied. Heliox is used to reduce the work of breathing and improve ventilation by reducing the turbulent flow characteristic of helium, a gas less dense than O2. Despite the theoretical effects of heliox, studies have produced conflicting results regarding its effectiveness; the lack of a ready-to-use preparation also limits its practical use.

Magnesium sulfate relaxes smooth muscle, but data on its effectiveness in controlling acute asthma in the intensive care unit are conflicting. General anesthesia in patients with status asthmaticus produces bronchodilation by an unclear mechanism, possibly through a direct muscle relaxant effect on airway smooth muscle or a decrease in cholinergic tone.

Treatment of chronic bronchial asthma

With appropriate use of medications, most patients with chronic asthma can be treated outside of emergency departments and hospitals. There are many medications available, and their choice and sequence of administration are based on the severity of the disease. "Titration" therapy - reducing the dose of the drug to the minimum required to control symptoms - is indicated for asthma of any severity.

Patients with mild intermittent asthma do not require daily medication. Short-acting beta2-agonists (eg, two rescue inhalations of salbutamol) are sufficient to relieve acute symptoms; use more than twice a week, use of more than two packs of medication per year, or diminishing response to medication may indicate the need for long-term maintenance therapy. Regardless of the severity of asthma, frequent need for a beta-agonist rescue indicates poor asthma control.

Patients with mild persistent asthma (adults and children) should receive anti-inflammatory therapy. Low-dose inhaled glucocorticoids are the treatment of choice, but some patients can control asthma with mast cell stabilizers, leukotriene modifiers, or sustained-release theophylline. Short-acting acute agonists (eg, salbutamol, 2-4 puffs) are used to terminate attacks. Patients who require daily rescue therapy should receive intermediate-dose inhaled glucocorticoids or combination therapy.

Patients with moderate persistent asthma should be treated with inhaled glucocorticoids at a dose that controls asthma, in combination with long-acting inhaled beta-agonists (formetrol, 2 puffs daily). Long-acting inhaled beta-agonists alone are insufficient treatment, but in combination with inhaled glucocorticoids they allow the dose of inhaled glucocorticoids to be reduced and are more effective in night symptoms. Alternatives to this approach are monotherapy with medium-dose inhaled glucocorticoids or substitution of long-acting beta-agonists with leukotriene receptor antagonists or extended-release theophylline in combination with low or medium doses of inhaled glucocorticoids. In patients with GERD and moderate asthma, antireflux treatment may reduce the frequency and dose of medications needed to control symptoms. In patients with allergic rhinitis and moderate persistent asthma, nasal glucocorticoids may reduce the frequency of asthma exacerbations requiring hospitalization.

Patients with severe persistent asthma are a minority and require high-dose multiple drugs. Choices include high-dose inhaled glucocorticoids in combination with a long-acting beta-agonist (formeterol) or a combination of an inhaled glucocorticoid, a long-acting beta-agonist, and a leukotriene modifier. Short-acting inhaled beta-agonists are used in both settings for acute relief of symptoms during an attack. Systemic glucocorticoids are used in patients who do not respond adequately to these regimens; alternate-day dosing helps minimize the adverse effects associated with daily drug administration.

Exercise-induced asthma

Inhalation of a short-acting beta-agonist or mast cell stabilizer before exercise is usually sufficient to prevent attacks of exercise-induced asthma. If beta-agonists are ineffective or if exercise-induced asthma is severe, the patient most often has more severe asthma than is diagnosed and requires long-term therapy to control the disease.

[ 36 ], [ 37 ], [ 38 ], [ 39 ], [ 40 ]

Aspirin bronchial asthma

The main treatment for aspirin-induced asthma is to avoid NSAIDs. Cyclooxygenase 2 (COX-2) inhibitors do not appear to be triggers. Leukotriene modifiers may block the response to NSAIDs. Successful inpatient desensitization has been demonstrated in a small group of patients.

[ 41 ], [ 42 ], [ 43 ], [ 44 ], [ 45 ]

Drugs of the future

A large number of drugs are being developed that target specific links in the inflammatory cascade. The possibility of using drugs targeting IL-4 and IL-13 is being studied.

Bronchial asthma in special groups of people

[ 46 ], [ 47 ], [ 48 ], [ 49 ], [ 50 ]

Infants, children and adolescents

Asthma is difficult to diagnose in infants, and underdiagnosis and undertreatment are common. Empirical administration of inhaled bronchodilators and anti-inflammatory drugs can help achieve both goals. Drugs can be given via a nebulizer or IDU with a holding chamber, with or without a mask; infants and children under 5 years of age requiring treatment more than twice a week should be given daily anti-inflammatory therapy with inhaled glucocorticoids (preferred), leukotriene receptor antagonists, or cromoglicic acid.

Children over 5 years old and teenagers

Children over 5 years and adolescents with asthma can be treated in the same way as adults, but should strive to maintain physical activity, exercise, and sports. The appropriate values for lung function tests in adolescents are closer to pediatric standards. Adolescents and older children should be involved in the development of their personal disease control plans and the formulation of treatment goals - this significantly improves compliance. The action plan should be known to teachers and school nurses - this ensures that appropriate medical care is provided promptly. Cromoglycic acid and nedocromil are often studied in this group of patients, but they are not as effective as inhaled glucocorticoids; long-acting preparations eliminate the need to take medications to school.

[ 51 ], [ 52 ]

Pregnancy and bronchial asthma

About one-third of women with asthma experience a reduction in symptoms when they become pregnant; one-third experience a worsening of their asthma (sometimes to a severe degree); and one-third notice no change. GERD may be an important component in the development of symptoms during pregnancy. Control of asthma during pregnancy should be absolute, as poorly controlled disease in the mother may result in increased antenatal mortality, preterm delivery, and low birth weight. Anti-asthma drugs have not been shown to cause adverse effects on the fetus, but large, well-controlled studies to prove true safety for the developing fetus have not been conducted.

What is the prognosis for bronchial asthma?

Asthma resolves in most children, but about 1 in 4 children have persistent wheezing into adulthood or relapse at an older age. Female sex, smoking, younger age at onset, sensitization to house dust mites, and airway hyperresponsiveness are risk factors for persistence and relapse.

Asthma causes approximately 5000 deaths per year in the United States, most of which are preventable with adequate therapy. Thus, the prognosis is good when appropriate medications are available and treatment is adequate. Risk factors for death include increasing requirements for oral glucocorticoids before hospitalization, previous hospitalizations for exacerbations, and lower peak flows at presentation. Several studies suggest that the use of inhaled glucocorticoids reduces hospitalization rates and mortality.

Over time, the airways of some asthma patients undergo permanent structural changes (remodeling) that prevent the lung from returning to normal function. Early, aggressive use of anti-inflammatory medications can help prevent this remodeling.