Management of the patients with broncho-obstructive syndrome. Management of the patients with acute and chronic respiratory failure

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

Clinically significant, irreversible, generalized airways obstruction associated with varying degrees of chronic bronchitis, abnormalities in small airways, and emphy­sema. The designation was introduced because chronic bronchitis, small airways abnormalities, and emphysema often coexist and it may be difficult in an individ­ual case to decide which is the major factor producing the airways obstruction.

When it is clear that the patient’s entire disease can be explained by emphysematous changes in the lung, the diagnosis “chronic obstructive emphysema” is pre­ferred to the more general designation COPD. Similarly, the diagnosis “chronic obstructive bronchitis” should be used when the obstructive abnormality is a di­rect result of an inflammatory process in the airways.

To avoid the semantic confusion often encountered in discussions of these dis­orders, the following definitions are provided. Chronic bronchitis, when unquali­fied, is defined as a condition associated with prolonged exposure to nonspecific bronchial irritants and accompanied by mucus hypersecretion and certain structural alterations in the bronchi. Clinically, it is characterized by chronic productive cough and is usually associated with cigarette smoking. Pulmonary emphysema is defined as enlargement of the air spaces distal to the terminal nonrespiratory bronchioles, accompanied by destructive changes of the alveolar walls. Airways obstruction is defined as increased resistance to air flow during forced expiration. It may result from narrowing or obliteration of the airways secondary to intrinsic bronchial disease or from excessive collapse of airways during forced expiration secondary to pulmonary emphysema.

The interrelationships between chronic bronchitis, pulmonary emphysema, and COPD are depicted in fig. 34-1. Some degree of emphysematous change is ex­tremely common in the general population, but not all patients with emphysema have sufficient airways obstructive problems to be considered as having COPD. Similarly, many cigarette smokers have evidence of chronic bronchitis, but only a minority have clinically significant airways obstruction, usually associated with marked changes in the small airways of the lung. As noted in fig. 34-1, most patients with clinically significant irreversible airways obstruction (COPD) have some combination of chronic bronchitis and emphysema. It is uncertain, however, whether this overlap results from a common causal factor or whether emphysema and chronic bronchitis predispose to one another.

Picture 1 Smoking and COPD

Etiology

The development of chronic bronchitis, emphysema, and chronic airways ob­struction appears to be determined by a balance between individual susceptibility and exposure to provocative agents.

The basic lesion of emphysema apparently results from the effect of proteolytic enzymes on the alveolar wall. Such enzymes can be released from leukocytes participating in an inflammatory process. Thus, any factor leading to a chronic inflammatory reaction at the alveolar level encourages development of emphysematous lesions. Smoking presumably plays a role due to its adverse effects on lung defense mechanisms (particularly by impairing the function of the alveolar macrophage) permitting low-grade inflammatory reactions to develop with conse­quent recurrent or chronic release of leukocytic proteolytic enzymes (see Ch. 48). Fortunately, most people caeutralize such enzymes as a result of antiproteolytic activity of the «i-globulin fraction of their sera. In a rare condition known as homozygotic antitrypsin deficiency, however, the serum antiproteolytic activity is markedly diminished. In such patients, emphysema may develop by middle age even in the absence of exposure to substances that interfere with lung defense mechanisms. In the absence of severe deficiency of ai-globulin in the serum, how­ever, the factors which make some cigarette smokers more susceptible to develop­ment of emphysema than others remain uncertain. It is also uncertain why persons with similar degrees of emphysema may have considerably varying de­grees of severity of airways obstruction.

With sufficient exposure to bronchial irritants, particularly cigarette smoke, most persons develop some degree of chronic bronchitis. The lesion essential to development of severe airways obstruction is apparently located in the small air­ways and may be basically different from the ordinary large airways abnormality which leads to hypersecretion of mucus in most smokers. The reason why small airways abnormalities develop in some patients with chronic bronchitis is uncer­tain, but viral or bacterial pulmonary infections in childhood, an unidentified immunologic mechanism, a mildly impaired ability to inactivate proteolytic en­zymes (as in heterozygotic antitrypsin deficiency), or unidentified genetic char­acteristics could be predisposing factors. While typical allergic bronchial asthma is not a common precursor of COPD, the exact interrelationships of these disor­ders are not known.

Prevalence

COPD is a major cause of disability and death. In the USA, it is second to heart disease as a cause of disability in Social Security statistics, and reported mortality rates have been doubling about every 5 yr. Its true mortality probably exceeds that from lung cancer. Some of this increase reflects the longer survival of patients who previously would have died of bacterial pneumonia before their COPD became known. Overall, it has been estimated that COPD affects as many as 15% of older men. Symptomatic COPD affects men 8 to 10 times more often than women, presumably as a result of the more frequent, prolonged, and heavier smoking in men; however, the incidence in women is now increasing.

Pathology

In patients with severe emphysema, the lungs are large and pale and often fail to collapse when the thorax is opened. Microscopic examination reveals “departitioning” of the lung due to loss of alveolar walls. Large bullae may be present in advanced disease. Changes may be most marked in the center of the secondary lobule (centrilobular emphysema) or more diffusely scattered throughout the lobule (panacinar emphysema). In all forms, the normal architecture is destroyed; rupture of septa results in air sacs of various sizes. The number of capillaries in the remaining alveolar walls is reduced, and the pulmonary arterial vessels may show sclerotic changes. These abnormalities lead not only to a reduction in the area of alveolar membrane available for gas exchange, but also to the perfusion of non-ventilated areas and to the ventilation of nonperfused parts of the lung; i.e., ventilation/perfusion abnormalities. They also lead to poor support of the airways of the lung, accounting for excessive collapse of airways on expiration.

In chronic bronchitis, the bronchial walls are thickened, there is mucus in the lumen, and the number of goblet cells and mucous glands is increased. There may be purulent secretions and inflammatory changes in bronchial walls and sur­rounding lung parenchyma if infection is present. Such large airways changes do not account for severe airways obstruction, however, and in patients dying of COPD, narrowing or obliteration, or both, of small airways may be observed.

Right ventricular hypertrophy (cor pulmonale) is common in patients with ad­vanced respiratory insufficiency.

Symptoms, Signs, and X-ray Findings (picture 2)

COPD is thought to begin early in life, though significant symptoms and dis­ability usually do not occur until middle age. Mild ventilatory abnormalities may be discernible long before the onset of significant clinical symptoms. A mild “smoker’s cough” is often present many years before onset of exertional dyspnea.

Gradually progressive exertional dyspnea is the most common presenting com­plaint. Patients may date the onset of dyspnea to an acute respiratory illness, but the acute infection may only unmask a preexisting subclinical chronic respiratory disorder. Cough, wheezing, recurrent respiratory infections, or, occasionally, weakness, weight loss, or lack of libido may also be initial manifestations. Rarely, initial complaints are related to congestive heart failure secondary to cor pulmo­nale, patients with such complaints apparently ignoring their cough and dyspnea prior to the onset of dependent edema and severe cyanosis.

Cough and sputum production are extremely variable. The patient may admit only to “clearing his chest” on awakening in the morning or after smoking the first cigarette of the day. Other patients may have severe disabling cough. Sputum varies from a few ml of clear viscid mucus to large bronchiectasis-like quantities of purulent material.

Wheezing also varies in character and intensity. Asthma-like episodes may oc­cur with acute infections. A mild chronic wheeze that is most obvious on reclining may be noted. Many patients deny having any wheeze.

The physical findings in COPD are notoriously variable, especially in early cases. A consistent abnormality is obstruction to expiratory air flow manifested by a slowing of forced expiration. To demonstrate this, the patient is asked to take a deep breath and then empty his lungs as quickly and completely as possible. Forced expiration is normally virtually complete in < 4 seconds. This test, which should be part of every routine physical examination, may be abnormal even though the patient does not complain of dyspnea.

Other findings, including bronchi, diminished vesicular breath sounds, tachy­cardia, distant heart tones, and decreased diaphragmatic motion, are not consis­tently present. The typical findings of gross pulmonary hyperinflation, prolonged expiration during quiet breathing, depressed diaphragm, pursed-lip breathing, stooped posture, calloused elbows from repeated assumption of the “tripod posi­tion,” and marked use of accessory muscles of respiration are seen only in later stages of COPD. A barrel-chested appearance is an unreliable finding since it is ofteoted in elderly patients without significant respiratory problems. Late in the disease, there may be frank cyanosis from hypoxemia, a plethoric appearance associated with secondary erythrocytosis, and, in patients with severe cor pulmo­nale, signs of congestive heart failure. Mild, chronic, dependent edema is quite common and does not necessarily indicate heart failure. It may result from pro­longed sitting, elevated intrathoracic pressures, and renal retention of salt second­ary to blood gas abnormalities even in the absence of cor pulmonale. X-ray findings are also variable. In early stages of the disease, the x-ray is often normal. Changes indicative of hyperinflation (e.g , depressed diaphragm, general­ized radiolucency of the lung fields, increased retrosternal air space, and tenting of the diaphragm at the insertions to the ribs) are common and suggestive of emphysematous disease, but are not diagnostic. They may also be found in pa dents with asthma and occasionally m healthy persons Localized radioluceno with attenuation of vascular markings is a more reliable indicator of emphysema

 

 

Picture 2 These radiographs of a patient with chronic obstructive pulmonary disease (COPD) reveal pulmonary hyperinflation. In the PA projection above the diaphragms are at the level of the eleventh posterior ribs and appear flat. The lateral radiograph below demonstrates the prominence of the anterior clear-space and of the AP diameter of the chest as well as the flat diaphragms.

 

Bullae are seen occasionally with COPD. Large bullae are generally well seen on ordinary x-rays, but small ones are more reliably detected with planograms. They may occur as part of a diffuse emphysematous process or as isolated phe­nomena and thus do not necessarily indicate a generalized lung disease.

Bronchitis itself does not have a characteristic appearance on ordinary chest x-ray, but bronchograms may reveal cylindrical dilation of bronchi on inspiration bronchial collapse on forced expiration, and enlarged mucous ducts Prank: saccular bronchiectasis is unusual and generally occurs only in patients who have had a previous severe respiratory infection.

In patients with recurrent chest infections, a variety of nondescript postinflammatory abnormalities may be noted, such as localized fibrotic changes, hone^ combing, or contraction atelectasis of a segment or lobe.

Isotopic lung scans generally demonstrate uneven ventilation and perfusion Diagnosis COPD should be suspected in any patient with chronic productive cough or exertional dyspnea of uncertain etiology, or whose physical examination reveals evidence of slowing of forced expiration. Definite diagnosis depends on (1) demonstration of physiologic evidence of airways obstruction which persists despite intensive and maximum medical management, and (2) exclusion of any specific disease (e.g., silicosis, tuberculosis, or upper airway neoplasm) as a cause of this physiologic abnormality.

Spirometric testing reveals characteristic obstruction to expiratory air flow with slowing of forced expiration as manifested by a reduced 1-second forced expiratory volume (FEV₁) and a low maximum mid-expiratory flow. Slowing of forced expiration is also evident on flow-volume curves. The vital capacity (VC) and forced vital capacity (FVC) are somewhat impaired in patients with severe disease but are better maintained than the measures of the speed of expiration. For this reason, the FEV₁/VC and FEV₁/FVC ratios are regularly reduced to < 60% with clinically significant COPD. This degree of abnormality should persist despite prolonged, maximal therapy before a diagnosis of COPD is considered confirmed

Maldistribution of ventilation and perfusion occurs in COPD and is manifested m several ways. An excessive physiologic dead space ventilation indicates that there are areas of the lung in which ventilation is high relative to blood flow (a high ventilation/perfusion ratio), resulting in “wasted” ventilation. Physiologic shunting indicates the presence of alveoli with reduced ventilation in relation to blood flow (a low ventilation/perfusion ratio) which allows some of the pulmonary blood flow to reach the left heart without becoming fully oxygenated, resulting in hypoxemia. In late stages of the disease, overall alveolar underventilation with hypercapnia occurs, aggravating any hypoxemia present due to physiologic shunting. Chronic hypercapnia is usually well compensated, and pH levels are close to normal.

The pattern of physiologic abnormality in an individual case depends to some extent on the relative severity of intrinsic bronchial disease and anatomic emphy­sema. Diffusing capacity is regularly reduced in patients with severe anatomic emphysema, but is more variable in patients with airways obstruction associated with predominant intrinsic bronchial disease. In patients with severe emphysema. resting hypoxemia is usually mild and hypercapnia does not occur until terminal stages of the illness. In these patients, cardiac output may be quite low, but frank pulmonary hypertension and cor pulmonale are usually late developments. In patients with airways obstruction associated primarily with an intrinsic bronchial disorder, severe hypoxemia and hypercapnia may be noted relatively early. Such patients usually have a well-maintained cardiac output and tend to develop severe pulmonary hypertension with chronic cor pulmonale. The residual volume (RV) and total lung capacity (TLC) are markedly elevated in emphysematous patients, while pulmonary hyperinflation may be relatively slight in bronchitic COPD, but the ratio of RV to TLC tends to be elevated in both types of disease.

Detailed lung function measurements help to determine the severity of emphy­sema and intrinsic bronchial disease in an individual case, but are rarely needed for ordinary clinical evaluation. With severe emphysema, pressure-volume curves show a characteristic loss of recoil and increased compliance. Airways resistance measurements made in the body plethysmograph tend to reflect the severity of intrinsic bronchial narrowing.

In a few cases with severe emphysema but little bronchitis or with severe ob­structive bronchitis but little, if any, emphysema, it is possible to distinguish emphysematous type (Type A) disease from bronchial type (Type B) disease on the basis of clinical and physiologic findings (see table 1). Unfortunately, most patients appear to have a “mixed” syndrome.

Specific parenchymal lung diseases which may lead to airways obstruction can usually be excluded by chest x-ray. Upper airway lesions (generally associated with stridor) and localized bronchial obstructions (often associated with a local­ized wheeze) must also be excluded. It is particularly important to exclude pri­mary cardiac disease with congestive failure as a cause of the patient’s respiratory insufficiency. A normal or small cardiac silhouette on chest x-ray is characteristic of COPD prior to development of frank cor pulmonale, but is most unusual in patients who are dyspneic as a result of a cardiac disorder.

table 1  CLINICAL TYPES OF CHRONIC OBSTRUCTIVE PULMONARY DISEASES

 

Homozygotic antitrypsin deficiency should be suspected when there is a family history of obstructive airways disease, or when emphysema occurs in a woman, a relatively young man, or a nonsmoker. The diagnosis may be confirmed by mea­suring serum antitrypsin levels or by specific phenotyping.

Course and Prognosis

Some reversal of airways obstruction and considerable symptomatic improve­ment can often be obtained initially, but the long-term prognosis is less favorable in patients with persistent obstructive abnormality. After initial improvement, the FEV₁ generally falls 50 to 75 ml/yr, which is 2 to 3 times the rate of decline expected from aging alone. There is a concomitant slow progression of exertional dyspnea and disability. The course is punctuated by acute symptomatic exacerba­tions, generally related to superimposed bronchial infections.

Prognosis is closely related to the severity of expiratory slowing. When the FEV₁ exceeds 1.25 L, the 10-yr survival rate is about 50%; when the FEV, is 1 L, the average patient survives about 5 yr; when there is very severe expiratory slowing (FEV₁ about 0.5 L), survival for > 2 yr is unusual, particularly if the patient also has chronic hypercapnia or demonstrable cor pulmonale.

Treatment

Therapy does not result in cure, but provides symptomatic relief and controls potentially fatal exacerbations. It may also slow progression of the disorder, though this is unproved. Treatment is directed at alleviating conditions which cause symptoms and excessive disability (e.g., infection, bronchospasm, bronchial hypersecretion, hypoxemia, and unnecessary limitation of physical activity).

Infection: An attempt should be made to clear purulent sputum with a broad-spectrum antibiotic (e.g., tetracycline 250 mg q.i.d. for 10 days), the course re­peated promptly at the first sign of recurrent bronchial infection or sputum purulence. Ampicillin or cephalothin may be used to treat severe exacerbations Regular courses of a broad-spectrum antibiotic are indicated in patients with frequent infectious exacerbations.

Bronchospasm: The degree of reversibility of airways obstruction can be as­sessed only by a vigorous and prolonged therapeutic trial of bronchodilators.

Corticosteroids have a very limited role in treating COPD, but a trial of these agents may be required to prove conclusively that the airways obstruction is not a result of potentially reversible bronchospasm. This is especially true when there is a past history suggesting asthma, eosinophilia, fluctuations in the severity of air­ways obstruction, or a good immediate response to inhalation of a bronchodilator. If a corticosteroid trial (e.g., prednisone 30 to 40 mg every morning for 3 wk) is undertaken, its usefulness should be documented by objective improvement w spirometric tests before long-term corticosteroid therapy is recommended, al which time the lowest maintenance dose which sustains improvement is used. In some patients, alternate-day therapy can be used for maintenance.

Bronchial secretions: Adequate systemic hydration is essential to prevent 10-spissation of secretions. In some patients bronchial hygiene may also be improved by inhalation of mist, postural drainage, and chest physical therapy, particularly following bronchodilator inhalation. Saturated solution of potassium iodide 10 drops in H20 t.i.d. is used by some physicians in an attempt to thin bronchial secretions. Despite their wide use, IPPB machines have not been shown to im­prove the patient’s ability to raise secretions or to affect favorably the overall condition of ambulatory patients with COPD.

Hypoxemia: Severe chronic hypoxemia, often associated with hypercapnia, accentuates pulmonary hypertension and leads to development of cor pulmonale in patients with COPD. Recurrent cardiac failure may develop and necessitate long-term 02 therapy. Low flow (1 to 2 L/min) 02 therapy via nasal prongs for 15 h or more/day (including sleeping hours) may be effective in reversing pulmonary hy­pertension and improving cardiac status. Around-the-clock 02 supplementation has been shown to be preferable for patients with severe chronic hypoxemia (arte­rial O2 tensions consistently < 55 mm Hg at rest) and appears to prolong survival. When instituting long-term O2 therapy, it is important to monitor the blood gas responses. No more O2 should be given than is needed to raise the arterial 02 tension to 55 mm Hg. One should also be sure that chronic 02 therapy does not lead to a progressive rise in C02 tension as a consequence of removing hypoxic ventilatory drive; in fact, this has rarely proved to be an important problem.

Even in patients without severe cor pulmonale, O2 may be needed to correct severe exertional hypoxemia when the patient is started on a graded exercise program. Use of 02 for symptomatic relief of dyspnea without verification of severe hypoxemia, however, is unjustified and potentially dangerous.

Hypercapnia: Patients with rapidly developing or worsening hypercapnia re­quire immediate hospitalization and intensive therapy, but chronic well-compen­sated hypercapnia is generally well tolerated and requires no specific therapy.

Heart failure: The most important measure for controlling heart failure second­ary to cor pulmonale is correction of excessive hypoxemia. Diuretic therapy and controlled sodium intake are important adjuncts. Digitalis must be used cau­tiously, if at all, since digitalis intoxication readily occurs in patients with COPD, probably as a result of fluctuating blood gas and electrolyte abnormalities.

Exercise tolerance: Prolonged inactivity leads to excessive disability in patients with COPD. As long as there is no severe cardiac disease, it is important to maintain a regular exercise program. This can usually be prescribed directly by the physician. If the patient is severely disabled, however, the program may be more effective if supervised by a trained physical therapist. The exercise program should have a specific meaningful goal (e.g., walking to the store, golfing) and should train those muscles needed for this specific activity. Breathing “exercises” (breathing training) may have a place in treating anxious patients who develop an excessively rapid ventilatory rate during exertion, but such exercises have not been shown to improve ventilatory capacity.

Depression: Periods of severe depression or marked anxiety are frequent in patients with COPD. A vigorous therapeutic program and an enthusiastic physi­cian are most helpful. A nihilistic attitude toward management of this disease is inexcusable. The patient must understand the nature of the disease and the goals and expectations of therapy.

Exacerbations: Treat promptly; e.g., if sputum becomes purulent, prescribe a course of broad-spectrum antibiotics and a more intensive program of bronchodilation and bronchial hygiene (see above). Patients with increasing hypoxemia or hypercapnia should be hospitalized promptly for intensive therapy. Sedatives and hypnotics should always be avoided in patients with COPD, particularly during exacerbations, since they increase the risk of acute ventilatory failure.

Picture 3  Terapy of Each  Stage of COPD

Web resourse deals with guidelines how to manage COPD are located here.

http://www.gp-training.net/protocol/respiratory/copd/COPD_niceguideline.pdf

 

Bronchial Asthma

 

Essentials of Diagnosis:

• Recurrent acute attacks of dyspnea, cough, and mucoid sputum, usually accompanied by wheezing.

• Prolonged expiration with generalized wheezing and musical rales.

• Bronchial obstruction reversible by drugs

 

General Considerations:

Asthma is a bronchial hypersensitivity disorder characterized by reversible airway obstruction, produced by a combination of mucosal edema, constriction of the bronchial musculature, and excessivesecretion of viscid mucus, causing mucous plugs.

Atopic, or “extrinsic,” asthma has been thought to result from sensitization of the bronchial mucosa by tissue-specific antibodies. The antibodies produced are specific immunoglobulins of the IgE (type I) class, and the total serum IgE concentration is usually elevated. Exposure to the appropriate allergens by inhala-tion results in an antigen-antibody reaction, that releases vasoactive bronchoconstrictive chemical mediators, causing the characteristic tissue changes (pictures 1-3). More recent work suggests that immunoglobulin G (IgG) may play a role similar to that of IgE in some cases.

 

 

 

 

Pictures 1-3. Bronchial obstruction in case of asthma.

 

Approximately 50% of asthmatics are of the nonatopic (“intrinsic”) type in which the bronchial reaction occurs in response to nonimmunologic stimuli such as infection, irritating inhalants, cold air, exercise, and emotional upset. These patients do not demonstrate elevated IgE antibodies in their serum, and the history does not suggest hypersensitivity to specific allergens, although there may be other immunologic mechanisms that have not yet been demon strated.  Agrowing list of agents encountered in the work place have been shown to cause asthma. Some organic materials such as wood dust act through an immunologic mechanism, whereas certain chemicals and metal dusts apparently cause direct irritation or protein denaturation in low concentrations. Susceptible individuals may be affected by concentrations well below those allowed by US government standards. Occupational asthma should be suspected when symptoms occur repeatedly at work or within several hours there after and improve away from work. Improvement may require several days Beta-adrenergic blocking agents such as propranolol cause intense bronchial constriction in patients with asthma, apparently due to parasympathetic nerve stimulation. Aspirin and nonsteroidal antiinflammatory agents may cause severe asthma in some patients.

 

 

Clinical Findings

Symptoms and Signs:

 Asthma is characterized by recurrent attacks of dyspnea, cough, and expectoration of tenacious mucoid sputum, and usually wheezing. Symptoms may be mild and may occur only in association with respiratory infection, or they may occur in various degrees of severity to the point of being life-threatening.

Classic allergic (atopic) asthma usually begins in childhood and becomes progressively more severe throughout life, although spontaneous remissions may occur in adulthood. Hay fever often accompanies atopic asthma.

The acute attack is characterized by dyspnea usually associated with expiratory wheezing that may be heard without a stethoscope. Cough may be present but is usually not the predominant symptom. There is a small group of patients with asthma in whom paroxysmal cough may be the predominant symptom.

When asthma becomes prolonged, with severe intractable wheezing, it is known as status asthmaticus.

Presence of any of these signs and symptoms should increase the suspicion of asthma:

§  Wheezing high-pitched whistling sounds when breathing out — especially in children (a normal chest examination does not exclude asthma).

§  History of any of the following:

·        Cough, worse particularly at night

·        Recurrent wheeze

·        Recurrent difficult breathing

·        Recurrent chest tightness

§  Symptoms occur or worsen at night, awakening the patient.

§  Symptoms occur or worsen in a seasonal pattern.

§  The patient also has eczema, hay fever, or a family history of asthma or atopic diseases.

§  Symptoms occur or worsen in the presence of:

·        Animals with fur

·        Aerosol chemicals

·        Changes in temperature

·        Domestic dust mites

·        Drugs (aspirin, beta blockers)

·        Exercise

·        Pollen

·        Respiratory (viral) infections

·        Smoke

·        Strong emotional expression

§  Symptoms respond to anti-asthma therapy

§  Patients colds “go to the chest” or take more than 10 days to clear up

 

Evaluation of asthma severity

There is no agreement about how best to assess overall asthma severity. Assessment of asthma severity before or without treatment usually takes into account 3 factors, including 2 considered in the diagnosis:  symptoms, physiologic indicators of airway disease and asthma morbidity. Thus, some algorithm based on frequency and severity of symptoms (including the need for inhaled β2- agonist rescue therapy), degree of airflow obstruction and indices of morbidity (admissions to hospital, need for intubation, emergency room visits, time away from work or school, etc.) can be used to classify asthma severity (Table 1). Because asthma is controllable, the factors that define its severity before treatment become markers of its control in

the treated patient. The amount of anti-inflammatory medication required to control symptoms is often added to the severity algorithm. However, a case has been made that the primary measure of asthma severity in the treated patient should be the minimum anti-inflammatory medication required  to achieve ideal control

 

Classification of Asthma Severity by Clinical Features Before Treatment

 

Classification of severety of chronic stable asthma

 

Adapted from National Asthma Education and Prevention Program. Guidelines for the diagnosis and management of asthma, 2007.

 

 

 

Classification of severety of asthma exacerbations

Adapted from National Asthma Education and Prevention Program. Guidelines for the diagnosis and management of asthma, 2007.

 

Laboratory Findings: The sputum is characteristically tenacious and mucoid, containing “plugs” and “spirals.” Eosinophils are seen microscopically. The differential blood count may show eosinophilia. In severe, acute bronchospasm, arterial hypoxemia may be present as a result of disturbed perfusion /ventilation relationships, alveolar hypoventilation, or functional right-to-left shunts.

X-Ray Findings: Chest films usually show no abnormalities. Reversible hyperexpansion may occur in severe paroxysms, or hyperexpansion may persist in long-standing cases. Transient, migratory pulmonary infiltrations may be present. Severe attacks are sometimes complicated by pneumothorax.

Acute hyperinflation of lungs complicated by limited pneumothorax in patient with asthma

 

Spirometry should be done before and after inhalation of a short-acting bronchodilator. Signs of airflow limitation before bronchodilator inhalation include reduced FEV1 and a reduced FEV1/FVC ratio. An improvement in FEV1 of  > 12% or an increase  ≥ 10% of predicted FEV1 in response to bronchodilator treatment confirms reversible airway obstruction. Spirometry should be repeated at least every 1 to 2 yr in patients with asthma to monitor disease progression.

Flow-volume loops should also be reviewed to diagnose vocal cord dysfunction, a common cause of upper airway obstruction that mimics asthma.

Provocative testing, in which inhaled methacholine is used to provoke bronchoconstriction, is indicated for patients suspected of having asthma who have normal findings on spirometry and flow-volume testing, and for patients suspected of having cough-variant asthma, provided there are no contraindications. A decline in FEV1 of > 20% on provocative testing supports the diagnosis of asthma.

Other tests:  Other tests may be helpful in some circumstances: Diffusing capacity for carbon monoxide (DLco), chest x-ray, allergy testing.

DLco testing can help distinguish asthma from COPD. Values are normal or elevated in asthma and usually reduced in COPD, particularly in patients with emphysema.

 

Allergy testing should be considered for adults whose history indicates relief of symptoms with allergen avoidance and for those in whom a trial of therapeutic anti-IgE antibody therapy is being considered. Skin testing and measurement of allergen-specific IgE via radioallergosorbent testing can identify specific allergic triggers.

 

Diagnostic challenges

§  Cough-variant asthma. Some patients with asthma have chronic cough (frequently occurring at night) as their principal, if not only, symptom. For these patients, documentation of lung function variability and airway hyperresponsiveness are particularly important.

§  Exercise-induced bronchoconstriction. Physical activity is an important cause of asthma symptoms for most asthma patients, and for some (including many children) it is the only cause. Exercise testing with an 8-minute running protocol can establish a firm diagnosis of asthma.

§  Children 5 Years and younger. Not all young children who wheeze have asthma. In this age group, the diagnosis of asthma must be based largely on clinical judgment, and should be periodically reviewed as the child grows.

§  Asthma in the elderly. Diagnosis and treatment of asthma in the elderly are complicated by several factors, including poor perception of symptoms, acceptance of dyspnea as being “normal” for old age, and reduced expectations of mobility and activity. Distinguishing asthma from COPD is particularly difficult, and may require a trial of treatment.

§  Occupational asthma. Asthma acquired in the workplace is a diagnosis that is frequently missed. The diagnosis requires a defined history of occupational exposure to sensitizing agents; an absence of asthma symptoms before beginning employment; and a documented relation ¬ ship between symptoms and the workplace (improvement in symptoms away from work and worsening of symptoms upon returning to work).

Evaluation of exacerbations: Patients with asthma with an acute exacerbation should have certain tests: pulse oximetry, PEF or FEV1 measurement. These tests help to establish the severity of an exacerbation and document treatment response. PEF values are interpreted in light of the patient’s personal best, which may vary widely among patients who are equally well controlled. A 15 to 20% reduction from this baseline indicates a significant exacerbation.

Chest x-ray is not necessary for most exacerbations but should be done in patients with symptoms suggestive of pneumonia or pneumothorax.

ABG measurements should be taken in patients with marked respiratory distress or symptoms and signs of impending respiratory failure.

 

Differential diagnosis of bronchial asthma

·        COPD

·        Bronchial tumor

·        Angioedema

·        Bronchiectasis

·        Vocal cord paralysis

·        Hysteria

·        Foreign body aspiration

Treatment

Medications used to treat asthma are generally divided  into 2 main categories: relievers and controllers. Relievers are best represented by the inhaled short-acting β2-agonists. These quick-acting bronchodilators are used to relieve acute intercurrent asthma symptoms, only on demand and at the minimum required dose and frequency.

Inhaled ipratropium bromide is less effective, but is occasionally used as a reliever medication in patients intolerant of short-acting β2-agonists. Controllers (or preventers) include anti-inflammatory medications, such as inhaled (and oral) glucocorticosteroids, leukotriene-receptor antagonists, and anti-allergic or inhaled nonsteroidal agents, such as cromoglycate and nedocromil. These agents are  generally taken regularly to control asthma and prevent exacerbations. Inhaled

glucocorticosteroids are the most effective agents in this category.

The controller group also includes some bronchodilators that are taken regularly in addition to inhaled glucocorticosteroids to help achieve and maintain asthma control.

These include the long-acting inhaled β2-agonists salmeterol and formoterol, which are the first choice in this category, as well as theophylline and ipratropium. The β2-agonists and ipratropium are considered of no significant benefit in reducing airway inflammation.

There is some evidence that theophylline may have immunomodulatory effects, but the clinical significance of this remains to be demonstrated. Asthma drugs are  preferably inhaled, because this route minimizes systemic absorption and, thus, improves the ratio of the therapeutic benefit to the potential side-effects. The patient must have repeated instruction on how to use the inhaled medication. The recently developed oral leukotriene-receptor antagonists have good safety and tolerance

profiles and are taken orally, which may help certain patients comply with treatment.

Asthma medications should be used at the minimum dose and frequency required to maintain acceptable asthma control; they should not be used as a substitute

for proper control of the environment. Asthma medications are considered to be safe over many years when used appropriately. The participants in the asthma consensus conference have reviewed the role of each category of medication. In the following sections they describe briefly the mode of action, pharmacologic and clinical profile, mode of administration and potential side-effects of these drugs. The treatment may be divided into 2 phases: treatment of the acute attack and  interim therapy, which is aimed at preventing further attacks.

 

Drug Category: Bronchodilators

Provide symptomatic relief of bronchospasm due to acute asthma exacerbation (short-acting agents) or long-term control of symptoms (long-acting agents). Also used as the primary medication for prophylaxis of EIA. A metered-dose inhaler (MDI) can be used for administration.

 

 

 

 

 

 

Nebulizer used for inhalation therapy of asthma

 

 

Drug Category: Leukotriene receptor antagonists

Direct antagonist of mediators responsible for airway inflammation in asthma. Used for prophylaxis of EIA and long-term treatment of asthma as alternative to low doses of inhaled corticosteroids.

 

Drug Category: Corticosteroids

Highly potent agents that are the primary DOC for treatment of chronic asthma and prevention of acute asthma exacerbations. Numerous inhaled corticosteroids are used for asthma and include beclomethasone (Beclovent, Vanceril), budesonide (Pulmicort Turbuhaler), flunisolide (AeroBid), fluticasone (Flovent), and triamcinolone (Azmacort).

 

 

 

 

Drug Category: Mast cell stabilizers

Prevent the release of mediators from mast cells that cause airway inflammation and bronchospasm. Indicated for maintenance therapy of mild-to-moderate asthma or prophylaxis for EIA.

Drug Category: Combination beta-agonist/corticosteroid

Advair is a unique inhaled combination medication used frequently in the treatment of asthma. It consists of a long-acting beta-agonist (salmeterol) and inhaled corticosteroid (fluticasone).

Drug Category: 5-Lipoxygenase inhibitors

Inhibit the formation of leukotrienes. Leukotrienes activate receptors that may be responsible for events leading to the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with inflammatory reactions.

 

 

Further Inpatient Care

• The initial assessment of acute asthma exacerbations should focus on several key areas.

·          

• Perform a functional assessment of airway obstruction with a measurement of the FEV₁ or PEF initially to assess the patient’s response to treatment.
• Assess the adequacy of arterial oxygen saturation in patients with severe distress.
• Obtain a brief history to include symptoms, onset of exacerbation, medications, prior emergency department visits, and hospitalizations (including endotracheal intubations).
• Perform a physical examination to assess the severity of the exacerbation, the overall patient status, the presence of other diseases or complications, and to rule out upper airway obstruction.
• Laboratory studies should be considered based on the status of the patient. These and other studies may include arterial blood gas measurement, complete blood cell count, serum theophylline level (if indicated), chest radiograph to assess for complications, and electrocardiograms in patients older than 50 years.
• Once the initial assessment is completed, begin treatment based on the severity of the asthma exacerbation.

·          

• Supplemental oxygen should be used in most patients to maintain oxygen saturations greater than 90%.
• Inhaled short-acting beta-agonists are the initial treatment.

o     

• Repetitive or continuous administration by nebulizer
• In the emergency department, 3 treatments every 20-30 minutes as initial therapy
• High-dose (6-12 puffs) beta-agonist by MDI or nebulizer therapy (Nebulizer is most effective with more severe exacerbations.)
• Consider inhaled ipratropium bromide in patients with severe exacerbations.
• Administer systemic corticosteroids early in the course of disease in patients with an incomplete response to beta-agonists. Oral administration is equivalent in efficacy to intravenous administration. Corticosteroids speed the resolution of airway obstruction and prevent a late-phase response.
• Methylxanthines (theophylline) can be considered in patients with severe exacerbations, but their use is controversial.
• Antibiotics should be reserved for patients with fever and purulent sputum or other evidence of pneumonia or sinusitis.
• Aggressive hydration is not recommended for adults.
• Chest physiotherapy, mucolytics, and sedation are not recommended.
• Indications for hospitalization are based on findings from the repeat assessment of a patient after the patient receives 3 doses of an inhaled bronchodilator. Determine the decision to admit on (1) the duration and severity of symptoms, (2) the severity of airflow obstruction, (3) the course and severity of prior exacerbations, (4) medication use and access to medications, (5) the adequacy of support and home conditions, and (6) the presence of psychiatric illness.
• In certain situations, admit the patient to the ICU for close observation and monitoring.

·          

• Rapidly worsening asthma or a lack of response to the initial therapy in the emergency department is an indication for ICU admission.
• If patients have confusion, drowsiness, signs of impeding respiratory arrest, or loss of consciousness, they should be admitted to the ICU.
• Impending respiratory arrest, as indicated by hypoxemia (PO₂ <60 mm Hg) despite supplemental oxygen and/or hypercarbia with PCO₂ greater than 45 mm Hg, should prompt ICU admission.
• If intubation is required because of the continued deterioration of the patient’s condition despite optimal treatment, admit the patient to the ICU.

 

  Epinephrine and intravenous aminophylline are the drugs of choice for the emergency management of acute asthma. However, for status asthmaticus or for acute attacks in epinephrine-resistant patients, the adrenal corticosteroids are usually necessary. Intravenous hydrocortisone and methylprednisolone are the preparations of choice.

  Note: Epinephrine should not be used in patients with hypertension or angina or in elderly patients.

 A. Acute Attack: Maintain adequate rest and relieve apprehension by reassurance and sedatives. Treat respiratory infections vigorously with antibiotics Give fluids orally or parenterally as necessary to prevent dehydration and liquefy secretions.

1.     Drugs:

a. Epinephrine (1:1000), 0.2-0.5 mL subcutaneously, is the initial drug of choice. It may be repeated every 1-2 hours. (Note the precautions mentioned above.)

 b. Aminophylline, 250 mg in 10-20 mL saline slowly intravenously, can be used ifepinephrine is not effective and if the patient is not already receiving a theophylline preparation. Both can be given initially in moderately severe attacks.

c. Nebulized drugs – most useful in mild attacks

(1) Isoproterenol, 1:200, 1-2 inhalations from a hand nebulizer every 30-60 minutes, or 0.5 mL in 2.5-3 mL saline by compressed air nebulizer or inter- mittent positive pressure breathing every 4 hours.

(2) Isoetharine with phenylephrine (Bronkosol) may be used in the same dose as isoproterenol, 1:200.

(3) Epinephrine (1:100) (for inhalation only), 1-2 inhalations from hand nebulizer. Do not use for prolonged nebulization.

d. Corticosteroid drugs:

Most effective in severe attacks that do not respond satisfactorily to the above bronchodilators

Give prednisone, 40—60 mg/d orally in divided doses, and gradually reduce to nil over 7-10 days. In moderate to severe attacks, hydrocortisone sodium succinate (Solu-Cortef), 100-250 mg intravenously, may be given simultaneously with the first dose of oral corticosteroid.

e. Other drugs-

(1) The various bronchodilator agents given orally are of limited value in stopping an acute attack (see below).

(2) Sedation should be avoided in severe asthma.

 In mild to moderate symptoms, hydroxyzine, 25 mg, or diazepam, 5 mg 3-4 times daily, may be helpful in counteracting the central nervous system stimulant effects of sympathomimetic bronchodilator drugs

f. Fluids-Patients with persistent symptoms who require hospitalization generally need supplement intravenous fluids to help liquefy secretions.  

g. Oxygen by nasal prongs or mask is indicated in the presence of moderate to severe symptoms.

2.     Status asthmaticus.

When severe wheezing persists after use of the measures listed above, hospitalization is required  for hospitalization.

The principal drugs for the treatment of the hospitalized patient are the following:

a. Aminophylline 6 mg/kg intravenously in 100 mL 5% dextrose in water over 20 minutes. Reduce or eliminate the loading dose (see below) for patients who have been taking theophylline preparations. (In overweight patients, calculation of the dose should be based on ideal rather than actual body weight, because theophylline does not penetrate into fatty tissue.) The intravenous infusion should be continued according to the dosage schedule recommended by the PDA, which is lower than previously recommended by various authors: children and young adult smokers, 1 mg/kg/h for 12 hours, then reduce to 0.8 mg/kg/h;

healthy nonsmoking adults, 0 7 mg/kg/h, reduced to 0.5 mg/kg/h after 12 hours; older patients and those with cor pulmonale, 0.6 mg/kg/h, reduced to 0.3 mg/kg/h after 12 hours, patients with congestive heart failure and liver failure, 0 5 mg/kg/h, reduced to 0.1- 0.2 mg/kg/h after 12 hours. The subsequent dosage schedule should be determined by the serum concentration; 10-20 Ju.g/ml is the recognized therapeutic range

For patients who have been taking theophylline drugs, determine (if possible) the amount and time of the last medication (1.2 mg aminophylline is equivalent to 1 mg theophylline) and reduce the loading dose accordingly. When this information is not available, give a reduced loading dose of aminophylline of 2.9 mg/kg, then continue with the maintenance schedule outlined above

 b. Corticosteroids:

The drugs of choice are either hydrocortisone sodium succinate (Solu-Cortef),

4 mg/kg, or methylprednisolone sodium succinate (Solu-Medrol), 2 mg/kg given intravenously every 4 hours until improvement is established In patients who have not had steroids, there is no evidence that more than 300 mg of Solu-Cortef per day is beneficial. Prednisone, 20 mg, or methylprednisolone (Medrol), 16 mg orally 4 times daily, can be started at the same time and continued in decreasing doses after the intravenous steroids are no longer needed.

B. Other Measures: Oxygen by nasal prongs or mask should be given in sufficient concentration to relieve hypoxemia. Dehydration is frequently present and must be corrected by intravenous replacement. Use up to 4 liters of 5% dextrose in water in 24 hours for an average-sized adult. Electrolytes should be monitored during continued intravenous replacement.

Nebulized isoproterenol or isoetharine with phenylephrine (Bronkosol), 0.5 ml in 3 ml of 0.5 N saline, may be added every 3-4 hours. The use of intermittent positive pressure breathing has no clear advantage over a simple nebulizer driven by compressed air or oxygen. The addition of chest percussion and postural drainage every 2-4 hours will usually aid in clearing tenacious secretions  Arterial blood gases should be monitored every 30-60 minutes initially. Unrelieved hypoxemia or a rising Pacoz  blood gas measurements are not available, clinical deterioration of the patient is an indication for intubation and assisted or controlled respiration. After intubation, sedation with small doses of diazepam or morphine intravenously may be necessary to permit ventilatory control by the respirator. When control of wheezing or removal of secretions cannot be accomplished with the above measures, general anesthesia with halothane (Fluothane) together with bronchoscopy for aspiration and saline lavage of secretions may be lifesaving.

A.                    Interim Therapy:

 Attempt to identify the of  fending allergens and protect the patient from further contact.  Desensitization may be indicated occasionally. Emotional disturbances should be eliminated if possible. Patients with “intrinsic” asthma (usually associated with bronchitis) may be helped by antibiotic therapy

Oral aminophylline (85% theophylline) in doses sufficient to produce therapeutic blood levels, usually 100-400 mg 4 times daily, is the bronchodilator of choice. Various combinations of ephednne with aminophylline and a barbiturate or hydroxyzine have been used for many years with benefit in mild asthma. Side effects (tachycardia and central nervous system stimulation) are frequent and limit their usefulness. The newer beta-adrenergic stimulators have a relatively greater degree of beta-2 specificity and longer action;

accordingly, they are somewhat more effective and have fewer side effects. Terbutaline (Brethme, Bncanyl) may be given orally (2.5-5 mg 3 times daily) or subcutaneously (0.25 mg). Albuterol (Proventil, Ventolm) may be given orally (2-4 mg 3 or 4 times daily) or as a metered dose aerosol (1-2 inhalations every 4—6 hours) These agents cause an initial adrenergic response of anxiety and tremor, but this tends to decrease over a few days even while drug intake continues Patients should be advised against excessiveuse The older nebulized drugs, epinephnne, isoproterenol, metaproterenol (Alupent, Metaprel), and isoethanne (Bronkosol) are useful in relieving or preventing mild wheezing when used in a hand bulb or pressurized nebulizer.

 Patients who are not helped by other measures may be treated on a long-term basis with a corticosteroid The dosage employed should be sufficient to keep the patient comfortable and relatively free of symptoms Begin with 10 mg 3-4 times daily and reduce gradually to the lowest effective maintenance dose, preferably on an alternate-day schedule An aerosolized corticosteroid, beclomethasone dipropionate (Beclovent, Vanceni), has been found to be effective in many asthmatic patients who require corticosteroids It is virtually unabsorbable and thus has no systemic side effects Its action occurs in the bronchial mucosa It is not effective during an acute attack, since its action depends on deposition deep in the bronchial tree It is best introduced after wheezing has been controlled by a systemic corticosteroid, which can then be reduced or eliminated  In patients who have been receiving long-term treatment with a systemic corticosteroid, joint pains and other symptoms may appear as that drug is reduced . Some patients will continue to require systemic corticosteroid drugs in smaller dosage Some receive no benefit from the aerosolized form In a recent report, no adverse effects were found in mothers or infants when inhaled beclomethasone was used dur ing pregnancy in the recommended dosage

Beclomethasone may be used after administration of a rapidly acting nebulized bronchodilator such as isoproterenol or isoethanne to achieve deeper deposition in the bronchial tree The initial dose is 2 mhalations 4 times daily, with subsequent adjustment to the lowest effective dose.  Doses as frequent as 8 times daily are acceptable if significant improvement results Some patients are well maintained on twice daily treatments (picture 8).

 

Picture 8. Inhalation of medication

 

European Respiratory Society Recommendations for nebulizer use is here:    http://www.ersnet.org/ers/lr/browse/viewPDF.aspx?id_attach=7580

 

 Even patients who are well controlled with the nebulized drug may have occasional increased wheezing during colds or intense exposure to allergens.  Short courses of prednisone may be required Cromolyn sodium (Intal) is useful mainly in atopic asthma to specifically inhibit the liberation of mediators initiated by the antigen antibody reaction .  It is effective only during remissions to prevent recurrent attacks and to reduce the requirement for corticosteroids . It is administered as a micronized powder by inhalation. Occasional pharyngeal and tracheal imitation has beeoted, but no systemic side effects have been reported

Asthma management essentials are presented on picture 9.

Picture 9. Continuum of asthma management. Severity of asthma is ideally assessed by medication required to maintain asthma control. Environmental control and education should be instituted for all asthma patients. Very mild asthma is treated with short-acting β2-agonists, taken as needed. If β2-agonists are needed more than 3 times/week (excluding 1 dose/day before exercise), then inhaled lucocorticosteroids should be added at the minimum daily dose required to control the asthma. If asthma is not adequately controlled by moderate doses (500–1000 μg/d of beclomethasone

or equivalent), additional therapy (including long-acting β2-agonists, leukotriene antagonists or, less often, other medications) should be considered. Severe asthma may require additional treatment with prednisone.

 

Stepwise approach for treatment of asthma

 

Adapted from National Asthma Education and Prevention Program. Guidelines for the diagnosis and management of asthma, 2007.

 

Long-term control medications for asthma

Adapted from National Asthma Education and Prevention Program. Guidelines for the diagnosis and management of asthma, 2007.

 

Management approach based on control adults and children older than 5 years

 

Level of Control	Treatment Action
Controlled	Maintain and find lowest controlling step
Partly controlled	Consider stepping up to gain control
Uncontrolled	Step up until controlled
Exacerbation	Treat as exacerbation

 

 

 

 

 

 

                                                           Treatment Steps

 

*ICS = inhaled glucocorticosteroids

** = Receptor antagonist or synthesis inhibitors

*** = Recommended   treatment (shaded boxes) based on group mean data. Individual patient needs, preferences, and circumstances (including costs) should be considered.

2

Alternative reliever treatments include inhaled anticholinergics, short-acting oral β2-agonists, some long-acting β-agonists, and short-acting theophylline. Regular dosing with short and long-acting β2-agonists is not advised unless accompanied by regular use of an inhaled glucocorticorsteroid.

 

 

Some rehabilitation measures is described here:  www.buteykoclinic.ru/english/

European and WHO guidelines are here: European Guidelines and WHO guidelines

              

Further Outpatient Care

• For all patients with asthma, monitoring should be performed on a continual basis based on the following parameters, which helps in the overall management of the disease:

·          

• Monitoring signs and symptoms of asthma: Patients should be taught to recognize inadequate asthma control, and providers should assess control at each visit.
• Monitoring pulmonary function: Regularly perform spirometry and peak-flow monitoring.
• Monitoring quality of life and functional status: Inquire about missed work or school days, reduction in activities, sleep disturbances, or change in caregiver activities.
• Monitoring history of asthma exacerbations: Determine if patients are monitoring themselves to detect exacerbations and if these exacerbations are self-treated or treated by health care providers.
• Monitoring pharmacotherapy: Ensure compliance with medications and usage of short-acting beta-agonists.
• Monitoring patient-provider communication and patient satisfaction

In/Out Patient Meds

• The pharmacologic treatment of asthma is based on stepwise therapy. Medications should be added or deleted as the frequency and severity of the patient’s symptoms change.
• Step 1: Intermittent asthma is present.

·          

• A controller medication is not needed.
• The reliever medication is a short-acting beta-agonist as needed for symptoms.
• Step 2: Mild persistent asthma is present.

·          

• The controller medication is an inhaled corticosteroid (200-500 mcg), cromolyn, nedocromil, or a leukotriene antagonist. If needed, increase the dose of corticosteroid and add a long-acting beta-agonist or sustained-release theophylline, especially for nocturnal symptoms.
• The reliever medication is a short-acting beta-agonist as needed for symptoms.
• Step 3: Moderate persistent asthma is present.

·          

• The controller medication is an inhaled corticosteroid (800-2000 mcg) and a long-acting bronchodilator (either beta-agonist or sustained-release theophylline) A combination medication of salmeterol/fluticasone (Advair) is a preferred choice to improve compliance. Other agents may include leukotriene modifying agents or omalizumab.
• The reliever medication is a short-acting beta-agonist as needed for symptoms.
• Step 4: Severe persistent asthma is present.

·          

• The controller medication is an inhaled corticosteroid (800-2000 mcg), a long-acting bronchodilator (beta-agonist and/or theophylline), and long-term oral corticosteroid therapy.
• The reliever medication is a short-acting beta-agonist as needed for symptoms.
• In patients with EIA, the primary aim of therapy is prophylaxis to prevent acute episodes.

·          

• A warm-up period of 15 minutes is recommended prior to a scheduled exercise event and has been shown to have a duration of effect as long as 40 minutes. This approach is not helpful for unscheduled events, prolonged exercise, or elite athletes.
• One of the primary treatments is to ensure good control of the underlying asthma.
• Regularly scheduled medications are generally not indicated for persons with isolated EIA without underlying asthma. Prophylaxis in the form of inhaled medications administered 15-30 minutes prior to exercise is usually required.
• The most commonly used medications are short-acting beta-agonists such as albuterol. Sodium cromolyn and nedocromil used 30 minutes prior to exercise have also been effective. The use of long-acting beta-agonists such as salmeterol (at least 90 min before exercise) can be effective for repetitive exercise. Newer agents such as the leukotriene antagonists, inhaled heparin, and inhaled furosemide have demonstrated an ability to prevent EIB. Inhaled corticosteroids have a limited role in the treatment of EIA, except to control underlying asthma.

Deterrence/Prevention

• Another essential component in the treatment of asthma is the control of factors contributing to asthma severity.
• Exposure to irritants or allergens has been shown to increase asthma symptoms and cause exacerbations. Clinicians should evaluate patients with persistent asthma for allergen exposures and sensitivity to seasonal allergens. Skin testing results should be used to assess sensitivity to perennial indoor allergens, and any positive results should be evaluated in the context of the patient’s medical history.
• All patients with asthma should be advised to avoid exposure to allergens to which they are sensitive, especially in the setting of occupational asthma. Other factors may include the following:

·          

• Environmental tobacco smoke
• Exertion during high levels of air pollution
• Use of beta-blockers
• Avoidance of aspirin and other nonsteroidal anti-inflammatory drugs if the patient is sensitive
• Avoidance of sulfites or other food items/additives to which the patient may be sensitive
• Occupational exposures

Complications

• The most common complications of asthma include pneumonia, pneumothorax or pneumomediastinum, and respiratory failure requiring intubation in severe exacerbations.
• Risk factors for death from asthma include the following:

·          

• Past history of sudden severe exacerbations, history of prior intubation, or ICU admission
• Two or more hospitalizations or 3 or more emergency department visits in the past year; hospitalization or emergency department visit in the past month
• Use of more than 2 short-acting beta-agonist canisters per month
• Current use of systemic corticosteroids or recent taper
• Comorbidity from cardiovascular disease
• Psychosocial, psychiatric, or illicit drug use problems
• Low socioeconomic status or urban residence
• Complications associated with most medications used for asthma are relatively rare. However, in those patients requiring long-term corticosteroid use, complications may include osteoporosis, immunosuppression, cataracts, myopathy, weight gain, addisonian crisis, thinning of skin, easy bruising, avascular necrosis, diabetes, and psychiatric disorders.

Prognosis

• Approximately half the children diagnosed with asthma in childhood outgrow their disease by late adolescence or early adulthood and require no further treatment.
• Patients with poorly controlled asthma develop long-term changes over time, ie, with airway remodeling. This can lead to chronic symptoms and a significant irreversible component to their disease.
• Many patients who develop asthma at an older age also tend to have chronic symptoms.

Patient Education

• The “Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma”¹ emphasizes the need for patient education about asthma and the establishment of a partnership between patient and clinician in the management of the disease. The key points of education include the following:

·          

• Integrate patient education into every aspect of asthma care.
• All members of the health care team, including nurses, pharmacists, and respiratory therapists, provide education.
• Clinicians teach patients asthma self-management based on basic asthma facts, self-monitoring techniques, the role of medications, inhaler use, and environmental control measures.^{7, 8, 9}
• Develop treatment goals for the patient and family.
• Develop a written, individualized, daily self-management plan.
• Encourage adherence by the patient.
• For excellent patient education resources, visit eMedicine’s Asthma Center. Also, see eMedicine’s patient education articles Asthma, Asthma FAQs, Asthma in Children, and Understanding Asthma Medications.

 

Medical/Legal Pitfalls

• The most important factor in the diagnosis of asthma is to recognize exacerbating factors or other diagnoses that may affect the treatment of the disease.

·          

• Sinusitis: Of patients with asthma, 50% have concurrent sinus disease. Sinusitis is the most important exacerbating factor for asthma symptoms. Either acute infectious sinus disease or chronic inflammation may contribute to worsening airway symptoms. Treatment of nasal and sinus inflammation reduces airway reactivity. Treatment of acute sinusitis requires at least 10 days of antibiotics to improve asthma symptoms.
• Gastroesophageal reflux disease: Patients with asthma are 3 times more likely to also have GERD. Aggressive antireflux therapy may improve asthma symptoms and pulmonary function in selected patients. Treatment with proton pump inhibitors, antacids, or H2 blockers may improve asthma symptoms or unexplained chronic cough. The treatment of asthma with agents such as theophylline may lower esophageal sphincter tone and induce GERD symptoms.
• An important observation is that some people with asthma have significant GE reflux without esophageal symptoms. GE reflux was found to be a definite asthma-causing factor (defined by a favorable asthma response to medical antireflux therapy) in 64% of patients; clinically silent reflux was present in 24% of all patients.^{10, 11}
• Respiratory infections: Viral respiratory infections have not been shown to cause asthma but can aggravate chronic asthma symptoms or induce symptoms in patients with allergic rhinitis. Rhinoviruses are the principal triggers of wheezing and worsening of asthma in older children and adults, but all viral respiratory infections are associated with increased asthma symptoms.
• Aspirin-induced asthma: The triad of asthma, aspirin sensitivity, and nasal polyps affects 5-10% of patients with asthma. Most patients experience symptoms during the third to fourth decade. A single dose can provoke an acute asthma exacerbation, accompanied by rhinorrhea, conjunctival irritation, and flushing of the head and neck. It can also occur with other nonsteroidal anti-inflammatory drugs and is caused by an increase in eosinophils and cysteinyl leukotrienes after exposure. Primary treatment is avoidance of these medications, but leukotriene antagonists have shown promise in treatment, allowing these patients to take daily aspirin for cardiac or rheumatic disease.
• Vocal cord dysfunction: Paradoxical inspiratory closure of the vocal cords may mimic asthma. Patients with symptoms of inspiratory wheezing or those whose asthma is refractory to standard therapy should be evaluated for evidence of vocal cord dysfunction. Usually, the diagnosis can be made by direct laryngoscopy, but only during symptomatic periods or after exercise. The presence of flattening of the inspiratory limb of the flow-volume loops may also suggest vocal cord dysfunction but is only seen in 28% of patients at baseline. Patients with chronic symptoms suggestive of asthma, normal spirometry, poor response to asthma medications, and frequent evaluations should be evaluated for vocal cord dysfunction.
• Occupational asthma: Occupational factors are associated with 10% of adult asthma cases. More than 300 specific occupational agents have been associated with asthma. High-risk jobs include farming, painting, janitorial work, and plastics manufacturing. Two types of occupational asthma are recognized. Immune-mediated asthma has a latency of months to years after exposure. Non–immune-mediated asthma or irritant-induced asthma (reactive airway dysfunction syndrome) has no latency period and may occur within 24 hours of an accidental exposure to high concentrations of respiratory irritants. Pay careful attention to the patient’s occupational history. Those with a history of asthma who report worsening of symptoms during the week and improvement during the weekends should be evaluated for occupational exposure. Peak-flow monitoring during work for 2 weeks and a similar period away from work is one recommended method to establish the diagnosis.

Special Concerns

• Nocturnal asthma

·          

• A large percentage of patients with asthma experience nocturnal symptoms once or twice a month. Some patients only experience symptoms at night and have normal pulmonary function in the daytime. This is due, in part, to the exaggerated response to the normal circadian variation in airflow.
• Bronchoconstriction is highest between the hours of 4:00 am and 6:00 pm (the highest morbidity and mortality from asthma is observed during this time). These patients may have a more significant decrease in cortisol levels or increased vagal tone at night. Studies also show an increase in inflammation compared with controls and with patients with daytime asthma.
• Nocturnal asthma is a significant clinical problem that should be addressed aggressively. Peak flow meters should be used to allow objective evaluation of symptoms and interventions. Sleep apnea, symptomatic GE reflux, and sinusitis should be controlled when present.
• Medications should be appropriately timed and consideration should be given to the use of a long-acting inhaled or oral beta2-agonist, a leukotriene modifier, and inhaled corticosteroids. A once-daily sustained release theophylline preparation and changing the timing of oral corticosteroids to the mid afternoon can be also be used.
• Pregnancy¹²

·          

• Asthma complicates 4–8% of pregnancies. Mild and well-controlled moderate asthma can be associated with excellent maternal and perinatal pregnancy outcomes. Severe and poorly controlled asthma may be associated with increased prematurity and other perinatal complications to include maternal morbidity and mortality. Optimal management of asthma during pregnancy includes objective monitoring of lung function, avoiding or controlling asthma triggers, patient education, and individualized pharmacologic therapy. Inhaled corticosteroids are the preferred medication for all levels of persistent asthma during pregnancy. Pregnant women with asthma are safer to be treated with asthma medications than to have asthma symptoms and exacerbations. The ultimate goal of asthma therapy is maintaining adequate oxygenation of the fetus by prevention of hypoxic episodes in the mother.
• With the exception of alpha-adrenergic compounds other than pseudoephedrine and some antihistamines, most drugs used to treat asthma and allergic rhinitis have not been shown to increase any risk to the mother or fetus. The National Institute of Health stated that albuterol, cromolyn, beclomethasone, budesonide, prednisone, and theophylline, when clinically indicated, are considered appropriate for the treatment of asthma in pregnancy.
• Poorly controlled asthma can result in low birth weight, increased prematurity, and increased perinatal mortality.
• The ACOG Guidelines for Management of Asthma During Pregnancy may be a helpful resource.
• Surgery

·          

• Complications associated with surgery include acute bronchoconstriction resulting from intubation, impaired cough, hypoxemia, hypercapnia, atelectasis, respiratory infection, and exposure to latex.
• The likelihood of these complications occurring depends on the severity of the underlying asthma, the type of surgery (thoracic and upper abdominal), and the type of anesthesia.
• If evidence of airflow obstruction (<80% of baseline values) is present, a brief course of corticosteroids is recommended. Patients who have received oral corticosteroids for an asthma exacerbation in the past 6 months should receive systemic corticosteroids in the perioperative period.

 

·         Davidson’s Principles and practice of medicine (21^st revised ed.) / by Colledge N.R., Walker B.R., and Ralston S.H., eds. – Churchill Livingstone, 2010. – 1376 p.

·         Harrison’s principles of internal medicine (18^th edition) / by Longo D.L., Kasper D.L., Jameson J.L. et al. (eds.). – McGraw-Hill Professional, 2012. – 4012 p.

·         The Merck Manual of Diagnosis and Therapy (nineteenth Edition) / Robert Berkow, Andrew J. Fletcher and others. – published by Merck Research Laboratories, 2011.

·         http://emedicine.medscape.com

·         http://meded.ucsd.edu/clinicalmed/introduction.htm

·         Respiratory diseases / Ghanei M. – In Tech, 2012. – 242 p.

·         Clinical respiratory medicine / Spiro S., Silvestri G., Agustí A. – Saunders, 2012. – 1000 p. 

·        

Principles and practice of interventional pulmonology / Ernst A., Herth F. –Springer, 2012. – 757 p.

·         Chest x-rays for medical students / Clarke C.,  Dux A. – Wiley-Blackwell, 2011.  – 134 p.

·         National Asthma Education and Prevention Program. Expert Panel Report 2: Guidelines for the diagnosis and management of asthma. NIH Publication No. 97-4051. National Institutes of Health; 2007. 

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• Harding SM, Sontag SJ. Asthma and gastroesophageal reflux. Am J Gastroenterol. Aug 2010;95(8 Suppl):S23-32. 
• National Heart, Lung, and Blood Institute. Executive Summary: Management of Asthma During Pregnancy. NIH Publication No. 92-3279a. National Institutes of Health; 2012.
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• Chan-Yeung M. 2003 Christie Memorial lecture. Occupational asthma–the past 50 years. Can Respir J. Jan-Feb 2008;11(1):21-6.
• Djukanovic R, Wilson JW, Britten KM, Wilson SJ, Walls AF, Roche WR, et al. Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis. Mar 2012;145(3):669-74.
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