Tuesday, April 2, 2013

Bronchial Asthma In Children

Bronchial asthma is a disease manifested reversible (fully or partially), bronchial obstruction, which is based on pathogenetic allergic inflammation of airways and, in most cases, bronchial hyperreactivity.

It is characterized by recurring attacks of breathlessness, resulting from smooth muscle spasm, edema of mucous membrane of the bronchi and their blockage by viscid secret that leads to the BOS.

                                       Etiology and pathogenesis.

                   Asthma may be allergic origin, ie, occurs in individuals with increased sensitivity to certain chemicals or physical factors - allergens. Increased sensitivity may be a manifestation of hereditary-constitutional features of the organism, or develops as a result of prolonged contact with the allergen, while the impact on the body of a number of adverse factors (cooling, fatigue, chronic inflammatory diseases, etc.).
                  Asthma may also be infectious origin. At the outbreak of infectious bronchial asthma important role have bacteria, viruses and other microbes, which in interaction with the organism cause its allergic restruction. Most often it develops on a background of chronic respiratory diseases or paranasal sinusitis, at which in the body there is infection focus of a long time, as well as products of the microbes and substances produced during inflammation, have the properties of allergens.
              Noninfectious asthma is caused by allergens of animal and vegetable origin. Allergens of animal origin include wool, horse hair, fish scales, etc. Sensitivity is sometimes also observed in some insect - bugs, cockroaches, butterflies, etc. Among the allergens of plant pollens play a special role. Bronchial asthma caused by plant allergens occur in a certain season of the year (April - July) - the period of flowering plants. In addition, the cause of asthma may be house dust and dry food for aquarium fish, etc., certain foods (eggs, crabs, chocolate, mushrooms, strawberries, oranges, etc.), some medicines.
             In the event of attack of asthma there are importance of  individual characteristics of nervous and endocrine systems. There are known occasions that in  the patient with sensitiveness to the smell of roses, attack started at the sight of artificial roses. Negative emotions may provoke attacks also. In some patients attacks of asthma do not appear in periods of intense work, or during deep sleep.
             The development and course of bronchial asthma depend on climatic factors. Exacerbations of the disease are often observed in spring and fall moon, patients often feel worse in windy weather, with sudden changes in temperature and atmospheric pressure at high humidity. In addition, high humidity contribute to the exacerbation of chronic bronchial and lung infections, which aggravates the course of bronchial asthma.
             The modern theory of the pathogenesis of asthma is the concept of allergic inflammation, which has become an integrating, connecting the mediator (histamine), lipid membranes - receptor (β2 - adrenergic receptors), neurovegetative (vagotonia), reagine (Ig E) and other concepts. Development of suffocation is conditioned directly by three major pathophysiological mechanisms: bronchospasm, edema of bronchial mucosa and hypersecretion of bronchial glands.
The inflammatory response in asthma is illustrated in this airway section from a patient with mild asthma who died in an accident. There is a submucosal infiltration of eosinophils and a marked deposition of collagen below the basement membrane. (From Hilman BC (ed): Pediatric Respiratory Disease. Philadelphia, WB Saunders, 1993, p.625.)
                                                 Classification of bronchial asthma

               The severity of asthma is classified on the basis of complex clinical and functional signs of bronchial obstruction. The physician evaluates the frequency, severity and duration of attacks of expiratory dyspnea, patient's condition during the period between attacks, severity, variabillity, and repayment of functional bronchial obstruction, response to treatment. Evaluation of functional indicators for determining the severity of the disease is carried out in the absence of episodes expiratory dyspnea. According to this classification, the patient's condition is determined by the degrees of seriousness of bronchial asthma. So there are  intermittent (episodic) course; persistent (constant) course: mild, moderate and severe.

                The National Asthma Education and Prevention Program Expert Panel Report II (EPR-2), "Guidelines for the Diagnosis and Management of Asthma," highlight the importance of correctly diagnosing asthma. To establish the diagnosis of asthma, the clinician must establish the following: (a) episodic symptoms of airflow obstruction are present, (b) airflow obstruction or symptoms are at least partially reversible, and (c) alternative diagnoses are excluded.
                  The severity of asthma is classified as mild intermittent, mild persistent, moderate persistent, or severe persistent, according to the frequency and severity of symptoms, including nocturnal symptoms, characteristics of acute episodes, and pulmonary function.
                 These categories do not always work well in children. First, lung function is difficult to assess in younger children. Second, asthma that is triggered solely by viral infections does not fit into any category. While the symptoms may be intermittent, they may be severe enough to warrant hospitalization. Therefore, a category of severe intermittent asthma has been suggested.
                           Features of the categories include the following:
                 Patients with mild intermittent disease have symptoms fewer than 2 times a week, and pulmonary function is normal between exacerbations. Exacerbations are brief, lasting from a few hours to a few days. Nighttime symptoms occur less than twice a month. The variation in peak expiratory flow (PEF) is less than 20%.
             Patients with mild persistent asthma have symptoms more than 2 times a week but less than once a day. Exacerbations may affect activity. Nighttime symptoms occur more than twice a month. Pulmonary function test results (in age-appropriate patients) demonstrate that the forced expiratory volume in 1 second (FEV1) or PEF is less than 80% of the predicted value, and the variation in PEF is 20-30%.
              Patients with moderate persistent asthma have daily symptoms and use inhaled short-acting beta2-agonists every day. Acute exacerbations in patients with moderate persistent asthma may occur more than 2 times a week and last for days. The exacerbations affect activity. Nocturnal symptoms occur more than once a week. FEV1 and PEF values are 60-80% of the predicted values, and PEF varies by more than 30%.
             Patients with severe persistent asthma have continuous or frequent symptoms, limited physical activity, and frequent nocturnal symptoms. FEV1 and PEF values are less than 60% of the predicted values, and PEF varies by more than 30%.
             Disease with any of their features is assigned to the most severe grade. The presence of one severe feature is sufficient to diagnose severe persistent asthma. The characteristics in this classification system are general and may overlap because asthma is highly variable. The classification may change over time. Patients with asthma of any level of severity may have mild, moderate, or severe exacerbations. Some patients with intermittent asthma have severe and life-threatening exacerbations separated by episodes with almost normal lung function and minimal symptoms; however, they are likely to have other evidence of increased BHR (exercise or challenge testing) due to ongoing inflammation.

            Physical examination during an acute episode may reveal different findings in mild, moderately severe, and severe episodes and in status asthmaticus with imminent respiratory arrest.
Mild episode: The respiratory rate is increased. Accessory muscles of respiration are not used. The heart rate is less than 100 beats per minute. Pulsus paradoxus is not present. Auscultation of chest reveals moderate wheezing, which is often end expiratory. Oxyhemoglobin saturation with room air is greater than 95%.
Moderately severe episode: The respiratory rate is increased. Typically, accessory muscles of respiration are used, and suprasternal retractions are present. The heart rate is 100-120 beats per minute. Loud expiratory wheezing can be heard. Pulsus paradoxus may be present (10-20 mm Hg). Oxyhemoglobin saturation with room air is 91-95%.
Severe episode: The respiratory rate is often greater than 30 breaths per minute. Accessory muscles of respiration are usually used, and suprasternal retractions are commonly present. The heart rate is more than 120 beats per minute. Loud biphasic (expiratory and inspiratory) wheezing can be heard. Pulsus paradoxus is often present (20-40 mm Hg). Oxyhemoglobin saturation with room air is less than 91%.
Status asthmaticus with imminent respiratory arrest: Paradoxical thoracoabdominal movement occurs. Wheezing may be absent (associated with most severe airway obstruction). Severe hypoxemia may manifest as bradycardia. Pulsus paradoxus noted earlier may be absent; this finding suggests respiratory muscle fatigue.

                  Asthma may be manifested in the form of whistles, wheezing when breathing, shortness of breath (dyspnea) with exertion or at rest, in the form of coughing, which may be paroxysmal.
                  The classic manifestation of bronchial asthma is the attack of asphyxia. Typically, it begins suddenly, usually at night. The patient feels a pain and lack of air. Breathing is difficult, exhaling long and is accompanied by a loud whistling wheezing (so-called, expiratory dyspnea). Cough may join soon. In order to facilitate breathing patient takes the forced position - rising or setting, leaning on the edge of the bed, chair, straining his pectoral muscle.

                   After some time, breathing becomes calmer, sputum is separating; attack stops. Attacks last from several minutes to several hours or even days. Such prolonged or frequent (occurring at short intervals during the day) the attacks are called an asthmatic state. Occasional attacks do not leave behind any changes in the lungs, but with the development of the disease and the increasing frequency of attacks may occur emphysema, impairment of the heart. It should be in mind that asphyxia may be caused not only by asthma but other diseases. In most cases, the doctor during the examination of  the patient may determine the nature and origin of suffocation, with the need to use instrumental and laboratory methods.
                 Objectively: skinis pale, cyanosis of the lips, nasolabial triangle, acrocyanosis. Thorax is blown, shoulders are raised, lung percussion sound is bandbox, auscultation reveals relaxed breathing, prolonged exhaling, a large number of dry whistling wheezing and changing moist rales. Borders of the heart are not defined, the tones are weakened, tachycardia.
                        Diagnostic criteria
Anamnesis. Symptoms: wheezing, shortness of breath, cough, fever, the formation of phlegm, and other allergic disorders. There is possible presence of contributing factors (allergens, infection, etc.), occurrence of asthma attacks at night. Attacks are curable. The outcome of previous attacks (the need for hospitalization, treatment with steroids).
Physical examination. Total: tachypnea, tachycardia, part of the auxiliary respiratory muscles, cyanosis, paradoxical pulse (the inclusion of support muscles and paradoxical pulse are correlated with the severity of obstruction). Lungs: adequate aeration, with auscultation the symmetry of breath, wheezing, long exhalation, increased volume of lungs are determined. Heart: signs of CVF. Allergic rhinitis and (or) sinusitis or dermatitis. 
                  The clinical picture varies. Symptoms may be associated with URTIs, nocturnal or exercise-induced asthmatic symptoms, and status asthmaticus. Status asthmaticus, or an acute severe asthmatic episode that is resistant to appropriate outpatient therapy, is a medical emergency that requires aggressive hospital management. This may include admission to an ICU for the treatment of hypoxia, hypercarbia, and dehydration and possibly for assisted ventilation because of respiratory failure.
                   Physical findings vary with the absence or presence of an acute episode and its severity, as follows:
                    –Physical examination in the absence of an acute episode (eg, during an outpatient visit between acute episodes)
                   –The physical findings vary with the severity of the asthma. During an outpatient visit, it is not uncommon for a patient with mild asthma to have normal findings at physical examination. Patients with more severe asthma are likely to have signs of chronic respiratory distress and chronic hyperinflation.
                  Signs of atopy or allergic rhinitis, such as conjunctival congestion and inflammation, ocular shiners, a transverse crease on the nose due to constant rubbing associated with allergic rhinitis, and pale violaceous nasal mucosa due to allergic rhinitis, may be present.
                  The anteroposterior diameter of the chest may be increased because of hyperinflation. Hyperinflation may also cause an abdominal breathing pattern.
                 Lung examination may reveal prolongation of the expiratory phase, expiratory wheezing, coarse crackles, or unequal breath sounds.
Clubbing of the fingers is not a feature of straightforward asthma and indicates a need for more extensive evaluation and work-up to exclude other conditions, such as cystic fibrosis.

Allergic shiners. (From Marks M: Physical Signs of Allergy of the Respiratory Tract in Children. New York, American College of Allergy, Asthma and Immunology, 1990.)

Nose wrinkling of an allergic child. (From Marks M: Physical Signs of Allergy of the Respiratory Tract in Children. New York, American College of Allergy, Asthma and Immunology, 1990.)

Allergic salute. (From Marks M: Physical Signs of Allergy of the Respiratory Tract in Children. New York, American College of Allergy, Asthma and Immunology, 1990.)

Transverse nasal crease in an allergic child. (From Marks M: Physical Signs of Allergy of the Respiratory Tract in Children. New York, American College of Allergy, Asthma and Immunology, 1990.)

"Rabbit nose" of allergic rhinitis. (From Marks M: Physical Signs of Allergy of the Respiratory Tract in Children. New York, American College of Allergy, Asthma and Immunology, 1990.)

Dark circles beneath the eyes of a child with allergic rhinitis. (From Marks M: Physical Signs of Allergy of the Respiratory Tract in Children. New York, American College of Allergy, Asthma and Immunology, 1990.)

Ocular allergy. (From Marks M: Physical Signs of Allergy of the Respiratory Tract in Children. New York, American College of Allergy, Asthma and Immunology, 1990.)

 Polymorphis erythema (Courtesy of Robert A. Silverman, M.D.)

Urticaria. (Courtesy of LM Pachter, M.D.)

                  Symptoms of asthma may include wheezing, coughing, and chest tightness, among others.
                     A musical, high-pitched, whistling sound produced by airflow turbulence is one of the most common symptoms. In the mildest form, wheezing is only end expiratory. As severity increases, the wheeze lasts throughout expiration. In a more severe asthmatic episode, wheezing is also present during inspiration. During a most severe episode, wheezing may be absent because of the severe limitation of airflow associated with airway narrowing and respiratory muscle fatigue.
                Asthma can occur without wheezing when obstruction involves predominantly the small airways. Thus, wheezing is not necessary for the diagnosis of asthma. Furthermore, wheezing can be associated with other causes of airway obstruction, such as cystic fibrosis and heart failure.
                Patients with vocal cord dysfunction have a predominantly inspiratory monophonic wheeze (different from the polyphonic wheeze in asthma), which is heard best over the laryngeal area in the neck. Patients with bronchomalacia and tracheomalacia also have a monophonic wheeze.
                In exercise-induced or nocturnal asthma, wheezing may be present after exercise or during the night, respectively.
Coughing: Cough may be the only symptom of asthma, especially in cases of exercise-induced or nocturnal asthma. Usually, the cough is nonproductive and nonparoxysmal. Also, coughing may be present with wheezing. Children with nocturnal asthma tend to cough after midnight, during the early hours of morning.
Chest tightness: A history of tightness or pain in the chest may be present with or without other symptoms of asthma, especially in exercise-induced or nocturnal asthma.
Other nonspecific symptoms: Infants or young children may have history of recurrent bronchitis, bronchiolitis, or pneumonia; a persistent cough with colds; and/or recurrent croup or chest rattling. Most children with chronic or recurrent bronchitis have asthma. Asthma is the most common underlying diagnosis in children with recurrent pneumonia. Older children may have a history of chest tightness and/or recurrent chest congestion.
                 During an acute episode, symptoms vary according to the severity.
Symptoms during a mild episode: Patients may be breathless after physical activity such as walking. They can talk in sentences and lie down, and they may be agitated.
Symptoms during a moderate severe episode: Patients are breathless while talking. Infants have feeding difficulties and a softer, shorter cry.
Symptoms during a severe episode: Patients are breathless during rest, are not interested in feeding, sit upright, talk in words (not sentences), and are usually agitated.
Symptoms with imminent respiratory arrest (in addition to the aforementioned symptoms): The child is drowsy and confused. However, adolescents may not have these symptoms until they are in frank respiratory failure.
Additional data. Despite the fact that lung function tests are not decisive in the diagnosis, they help assess the severity of airway obstruction and subsequent response to therapy in chronic and acute situations. VC, FVC,, FEV, the maximum air velocity in the middle of expiration, the maximum expiratory flow rate (test Tiffno), FEV / VC decrease, residual volume (RV) and total lung capacity (TLC) increase  during episodes of obstruction. Reduced FVC <25% of the proper or <0,75 after the appointment of bronchodilator indicates the severity of the disease.
 Pulmonary function test (PFT) results are not reliable in patients younger than 5 years. In young children (3-6 y) and older children who can't perform the conventional spirometry maneuver, newer techniques, such as measurement of airway resistance using impulse oscillometry system, are being tried. Measurement of airway resistance before and after a dose of inhaled bronchodilator may help to diagnose bronchodilator responsive airway obstruction.
Spirometry: In a typical case, an obstructive defect is present in the form of normal forced vital capacity (FVC), reduced FEV1, and reduced forced expiratory flow over 25-75% of the FVC (FEF 25-75). The flow-volume loop can be concave. Documentation of reversibility of airway obstruction after bronchodilator therapy is central to the definition of asthma. FEF 25-75 is a sensitive indicator of obstruction and may be the only abnormality in a child with mild disease. In an outpatient or office setting, measurement of the peak flow rate by using a peak flow meter can provide useful information about obstruction in the large airways. Take care to ensure maximum patient effort. However, a normal peak flow rate does not necessarily mean a lack of airway obstruction.

Plethysmography: Patients with chronic persistent asthma may have hyperinflation, as evidenced by an increased total lung capacity (TLC) at plethysmography. Increased residual volume (RV) and functional residual capacity (FRC) with normal TLC suggests air trapping. Airway resistance is increased when significant obstruction is present.
Air Displacement Plethysmography (ADP)
Bronchial provocation tests: Bronchial provocation tests may be performed to diagnose BHR. These tests are performed in specialized laboratories by specially trained personnel to document airway hyperresponsiveness to substances (eg, methacholine, histamine). Increasing doses of provocation agents are given, and FEV1 is measured. The endpoint is a 20% decrease in FEV1 (PD20).
Exercise challenge: In a patient with a history of exercise-induced symptoms (eg, cough, wheeze, chest tightness or pain), the diagnosis of asthma can be confirmed with the exercise challenge. In a patient of appropriate age (usually >6 y), the procedure involves baseline spirometry followed by exercise on a treadmill or bicycle to a heart rate greater than 60% of the predicted maximum, with monitoring of the electrocardiogram and oxyhemoglobin saturation. The patient should be breathing cold, dry air during the exercise to increase the yield of the study. Spirographic findings and the PEF rate (PEFR) are determined immediately after the exercise period and at 3, 5, 10, 15, and 20 minutes after the first measurement. The maximal decrease in lung function is calculated by using the lowest postexercise and highest preexercise values. The reversibility of airway obstruction can be assessed by administering aerosolized bronchodilators.

Blood testing: Eosinophil counts and IgE levels may help when allergic factors are suspected.
Recent evidence suggests the usefulness of measuring the fraction of exhaled nitric oxide (FeNO) as a noninvasive marker of airway inflammation, in order to adjust the dose of inhaled corticosteroids treatment. Currently FeNO measurement, due to high cost of equipment, is used primarily as a research tool.
Histologic Findings.
Asthma is an inflammatory disease characterized by the recruitment of inflammatory cells, vascular congestion, increased vascular permeability, increased tissue volume, and the presence of an exudate. Eosinophilic infiltration, a universal finding, is considered a major marker of the inflammatory activity of the disease. Histologic evaluations of the airways in a typical patient reveal infiltration with inflammatory cells, narrowing of airway lumina, bronchial and bronchiolar epithelial denudation, and mucus plugs. Additionally, a patient with severe asthma may have a markedly thickened basement membrane and airway remodeling in the form of subepithelial fibrosis and smooth muscle hypertrophy or hyperplasia.
            Peakflowmetria allows, though tentatively, to control state of the respiratory system and helps to some extent monitor of the effectiveness of treatment.


Portable spirometer MicroLoop

(Micro Medical Ltd., UK)

with color sensor screen.                      


Imaging Studies
Chest radiography: Include chest radiography in the initial workup if the asthma does not respond to therapy as expected. In addition to typical findings of hyperinflation and increased bronchial markings, a chest radiograph may reveal evidence of parenchymal disease, atelectasis, pneumonia, congenital anomaly, or a foreign body. In a patient with an acute asthmatic episode that responds poorly to therapy, a chest radiograph helps in the diagnosis of complications such as pneumothorax or pneumomediastinum. Chest x-ray is not always necessary. It can document the increase of pulmonary volume, infiltrates areas due to atelectasis of distal obturated airway, this feature is important in suspecting of their infection.

Asthma. A. The typical X-ray data 9-year-old child.
 The inflation and increased lung pattern. B. 7-year-old child with a more pronounced changes. C. Side projection showing swelling with flattening of the diaphragm and increased anteroposterior diameter at the top.
(From Edwards D III: The child who wheezes. <IT+>In:<IT-> von Waldenburg Hilton S, Edwards DIII (eds): Practical Pediatric Radiology, 2nd ed. Philadelphia, WB Saunders, 1994, p 106.)

Paranasal sinus radiography or CT scanning: Consider using these to rule out sinusitis.

                             Computor tomography. Emphysema.
     Chronic Sinusitis

Other Tests
Allergy testing: Allergy testing can be used to identify allergic factors that may significantly contribute to the asthma. Once identified, environmental factors (eg, dust mites, cockroaches, molds, animal dander) and outdoor factors (eg, pollen, grass, trees, molds) may be controlled or avoided to reduce asthmatic symptoms. Allergens for skin testing are selected on the basis of suspected or known allergens identified from a detailed environmental history. Antihistamines can suppress the skin test results and should be discontinued for an appropriate period (according to the duration of action) before allergy testing. Topical or systemic corticosteroids do not affect the skin reaction.
                  In the period of remission allergic skin tests are conducted, positive analysis of which gives the possibility to exclude contact with the causative allergen, that is the key of the recovery.
                                Allergic prick text. (Courtesy of MR Sly, M.D.)
The analysis of sputum: eosinophilia, Kurshman spiral (cylinders of the bronchioles), crystals Charcot - Leiden; neutrophilia proves the existence of bronchial infection.


B– Charcot - Leiden crystals
C– Kurshman spiral
Arterial blood gases: typical symptoms of hypoxemia during attacks and is usually expressed in hypocapnia and respiratory alkalosis, a normal or increased partial pressure pCO2 showes a significant fatigue of respiratory muscles and airway obstruction.

                      Differential diagnosis
"Any wheezing" - is not bronchial asthma. Differentiated with CNS diseases, chronic bronchitis and (or) emphysema, obstruction URT caused by foreign body, tumor, edema of the larynx, carcinoid tumors (usually followed by a crowing, but not wheezing), repeated emphysema, eosinophilic pneumonia, dysfunction of the vocal folds, systemic vasculitis with lesions of the lungs.
Clinically the most important is differential diagnosis with bronchiolitis and laryngotracheal stenosis due to similar clinical picture.

Differential diagnostics
 attack of bronchial asthma that laryngotracheal stenosis

Bronchial asthma
Laryngotracheal stenosis
Background of process

Period of precursors

ARVI (parainfluenza)


Dry, with transition in moist one

Dry, barking




Change of voice


Hoarse of voice

Shortness of breath



Forsed position


Non characteristically


The loosened breathing, the prolonged inspiration, dry whistling and moist wheezes

Strict breathing
Dry  wheezes


Box sound
Pulmonary sound
Mute” lights


Not characteristically


  Treatment of the patients
Medical Care
The goals of asthma therapy are to prevent chronic and troublesome symptoms, maintain normal or near-normal pulmonary function, maintain normal physical activity levels (including exercise), prevent recurrent exacerbations of asthma, and minimize the need for emergency department visits or hospitalizations, provide optimal pharmacotherapy with minimal or no adverse effects, and meet the family's expectations for asthma care.
Medical care includes treatment of acute asthmatic episodes and control of chronic symptoms, including nocturnal and exercise-induced asthmatic symptoms. Pharmacologic management includes the use of control agents such as inhaled corticosteroids, inhaled cromolyn or nedocromil, long-acting bronchodilators, theophylline, leukotriene modifiers, and recently introduced strategies such as the use of anti-IgE antibodies. Relief medications include short-acting bronchodilators, systemic corticosteroids, and ipratropium. Nonpharmacologic management includes measures to improve patient compliance and adherence. For all but the most severely affected patients, the ultimate goal is to prevent symptoms, minimize morbidity from acute episodes, and prevent functional and psychological morbidity to provide a healthy (or near healthy) lifestyle appropriate to the age of child.
A step-down approach based on the asthma severity classification system emphasizes the initiation of high-level therapy to establish prompt control and then decreasing therapy (National Asthma Education and Prevention Program Expert Panel Report II, 1997). Treatment should be reviewed every 1-6 months; a gradual stepwise reduction in treatment may be possible. If control is not maintained despite adequate medication and adherence and the exclusion of contributing environmental factors, increased therapy should be considered. Long- and short-term therapy is based on the severity of asthma, as follows:
ü     Mild intermittent asthma 
ü     Long-term control: Usually, no daily medication is needed.
ü     Quick relief: Short-acting bronchodilators in the form of inhaled beta2-agonists should be used as needed for symptom control.
The use of short-acting inhaled beta2-agonists more than 2 times a week may indicate the need to initiate long-term control therapy.
Mild persistent asthma 
Long-term control: Anti-inflammatory treatment in the form of low-dose inhaled corticosteroids or nonsteroidal agents (eg, cromolyn, nedocromil) is preferred. Some evidence suggests that leukotriene antagonists may be useful as first-line therapy in children. Recently, the use of montelukast was approved for children aged 2 years and older.
Quick relief: Short-acting bronchodilators in the form of inhaled beta2-agonists should be used as needed for symptom control. Use of short-acting inhaled beta2-agonists on a daily basis or increasing use indicates the need for additional long-term therapy.
Moderate persistent asthma
Long-term control: Daily anti-inflammatory treatment in the form of inhaled corticosteroids (medium dose) is preferred. Otherwise, low- or medium-dose inhaled corticosteroids combined with a long-acting bronchodilator or leukotriene antagonist can be used, especially for the control of nocturnal or exercise-induced asthmatic symptoms.
Quick relief: Short-acting bronchodilators in the form of inhaled beta2-agonists should be used as needed for symptom control. The use of short-acting inhaled beta2-agonists on a daily basis or increasing use indicates the need for additional long-term therapy.
Severe persistent asthma 
Long-term control 
Daily anti-inflammatory treatment in the form of inhaled corticosteroids (high dose) is preferred. Other medications, such as a long-acting bronchodilator leukotriene antagonist or theophylline, can be added.
Patients with moderate-to-severe asthma who react to perennial allergens despite inhaled corticosteroids may benefit from omalizumab treatment. Two 52-week pivotal Phase III clinical trials were designed to study asthma exacerbation reduction in 1071 patients with asthma (aged 12-76 y). The coprimary endpoint of each study was the number of asthma exacerbations per patient during the stable-steroid phase and the steroid-reduction phase. Patients were randomized to receive subcutaneous omalizumab or placebo every 2-4 weeks. Inhaled corticosteroid doses were kept stable over the initial 16 weeks of treatment (stable-steroid phase) and tapered during a further 12-week treatment period (steroid-reduction phase).
In both pivotal clinical trials, when used as an add-on therapy to inhaled corticosteroids, omalizumab reduced mean asthma exacerbations (ie, asthma attacks) per patient by 33%-75% during the stable-steroid phase and 33%-50% during the steroid-reduction phase. Reduction in asthma exacerbations was confirmed by improvements in other measurements of asthma control, including symptom scores (eg, nocturnal awakenings, daytime asthma symptoms).
Quick relief: Short-acting bronchodilators in the form of inhaled beta2-agonists should be used as needed for symptom control. The use of short-acting inhaled beta2-agonists on a daily basis or increasing use indicates the need for additional long-term therapy.
Acute severe asthmatic episode (status asthmaticus) 
Treatment goals are the following: 
Correction of significant hypoxemia with supplemental oxygen: In severe cases, alveolar hypoventilation requires mechanically assisted ventilation.
Rapid reversal of airflow obstruction by using repeated or continuous administration of an inhaled beta2-agonist: Early administration of systemic corticosteroids (eg, oral prednisone or intravenous methylprednisolone) is suggested in children with asthma that fails to respond promptly and completely to inhaled beta2-agonists.
Reduction in the likelihood of recurrence of severe airflow obstruction by intensifying therapy: Often, a short course of systemic corticosteroids is helpful.
Achieving these goals requires close monitoring by means of serial clinical assessment and measurement of lung function (in patients of appropriate ages) to quantify the severity of airflow obstruction and its response to treatment. Improvement in FEV1 after 30 minutes of treatment is significantly correlated with a broad range of indices of the severity of asthmatic exacerbations, and repeated measurement of airflow in the emergency department can help reduce unnecessary admissions. Use of the peak flow rate or FEV1 values, along with the patient's history, current symptoms, physical findings, to guide treatment decisions is helpful in achieving the aforementioned goals. In using the PEF expressed as a percentage of the patient's best value, the effect of irreversible airflow obstruction should be considered. For example, in a patient whose best peak flow rate is 160 L/min, a decrease of 40% represents severe and potentially life-threatening obstruction.

Consider consultation with an allergist; ear, nose, and throat (ENT) specialist; or gastroenterologist. An allergist may help with further evaluation and management when the history and physical examination findings suggest significant allergies (especially systemic involvement and allergies to dietary products). An ENT specialist may help in managing chronic sinusitis. A gastroenterologist may help in excluding gastroesophageal reflux.

When a patient has major allergies to dietary products, avoidance of particular foods may help. In the absence of specific food allergies, dietary changes are not necessary. Unless compelling evidence for a specific allergy exists, milk products do not have to be avoided.

One of the goals of therapy is to adequately control exercise-induced asthmatic symptoms so that physical activity is not restricted.

Current treatment of asthma includes the use of relievers, such as beta-adrenergic agonists, systemic corticosteroids, and ipratropium, and controllers, such as cromolyn, nedocromil, inhaled corticosteroids, long-acting beta-agonists, theophylline, and leukotriene modifiers.

Drug Category: Bronchodilator, beta2-agonists

 These agents act as bronchodilators, used to treat bronchospasm in acute asthmatic episodes, and used to prevent bronchospasm associated with exercise-induced asthma or nocturnal asthma. Several studies have suggested that short-acting beta2-agonists such as albuterol may produce adverse outcomes (eg, decreased peak flow or increased risk of exacerbations) in patients homozygous for arginine (Arg/Arg) at the 16th amino acid position of beta-adrenergic receptor gene compared with patients homozygous for glycine (Gly-Gly). Recently, similar findings are reported for long-acting beta2-agonists (eg, salmeterol).
Albuterol sulfate (Proventil, Ventolin)   This beta2-agonist is the most commonly used bronchodilator that is available in multiple forms (eg, solution for nebulization, metered-dose inhaler (MDI), oral solution). This is most commonly used in rescue therapy for acute asthmatic symptoms. Albuterol is used as needed, and prolonged use may be associated with tachyphylaxis due to beta2-receptor downregulation and receptor hyposensitivity.
Oral inhaler: 90 mcg per inhalation, 2 inhalations q4-6h; more inhalations may be used in severe, acute episodes; more frequent dosing can be used to treat acute symptoms
 Nebulizer: 2.5 mg via nebulization of 0.5% solution in 2-3 mL of sodium chloride solution q4-6h

Pirbuterol acetate (Maxair)  Available as a breath-actuated or ordinary inhaler. The ease of administration with the breath-actuated device makes it an attractive choice in the treatment of acute symptoms in younger children who otherwise cannot use an MDI. Strength is 200 mcg per inhalation.
Oral inhalation: 1-2 inhalations q4-6h; not to exceed 12 inhalations q24h
Drug Category: Nonracemic form of the beta2-agonist albuterol
This nonracemic form of albuterol was recently introduced. One advantage is better efficacy; hence, lower doses have a therapeutic effect, and a significant reduction in the adverse effects associated with racemic albuterol (eg, muscle tremors, tachycardia, hyperglycemia, hypokalemia) is reported.
Levalbuterol (Xopenex) Nonracemic form of albuterol, levalbuterol (R isomer) is effective in smaller doses and is reported to have fewer adverse effects (eg, tachycardia, hyperglycemia, hypokalemia). The dose may be doubled in acute severe episodes when even a slight increase in the bronchodilator response may make a big difference in the management strategy (eg, in avoiding patient ventilation).
 0.63 mg by nebulizer q8h

Drug Category: Long-acting beta2-agonist
 Long-acting bronchodilators are not used for the treatment of acute bronchospasm. They are used for the preventive treatment of nocturnal asthma or exercise-induced asthmatic symptoms, for example. Currently, 2 long-acting beta2-agonists are available in the United States: salmeterol (Serevent) and formoterol (Foradil). Salmeterol is discussed below. Salmeterol is available as a combination of salmeterol and fluticasone (Advair) in the United States. Advair has an expiration date of 30 days once the protective wrapper is removed.
Salmeterol (Serevent Diskus) This long-acting preparation of a beta2-agonist is used primarily to treat nocturnal or exercise-induced symptoms. It has no anti-inflammatory action and is not indicated in the treatment of acute bronchospastic episodes. It may be used as an adjunct to inhaled corticosteroids to reduce the potential adverse effects of the steroids.
<12 years: Not established
>12 years: 1 inhalation of inhalation powder (50 mcg) q12h; data
                  in children are limited

Drug Category: Methylxanthines
These agents are used for long-term control and prevention of symptoms, especially nocturnal symptoms.
Theophylline (Theo-24, Theolair, Theo-Dur, Slo-bid) is available in short- and long-acting formulations. Because of the need to monitor the drug levels (see Precautions below), this agent is used infrequently.
Initial dose: 10 mg/kg PO sustained-release tablets and capsules; not to exceed 300 mg/d
 First dose adjustment: 13 mg/kg PO; not to exceed 450 mg/d
 Second dose adjustment: 16 mg/kg PO; not to exceed 600 mg/d
Drug Category: Mast cell stabilizers
  These agents block early and late asthmatic responses, interfere with chloride channels, stabilize the mast cell membrane, and inhibit the activation and release of mediators from eosinophils and epithelial cells. They inhibit acute responses to cold air, exercise, and sulfur dioxide.
Cromolyn sodium (Intal), nedocromil sodium (Tilade). These nonsteroidal anti-inflammatory agents are used primarily in preventive therapy.
Cromolyn: 20 mg in 2 mL nebulizer solution q6-8h
 Nedocromil: 2-4 inhalations bid/tid; 1.75 mg/actuation

 Intal   - cromolyn sodium
   Tilade   - nedocromil

Drug Category: Corticosteroids
Steroids are the most potent anti-inflammatory agents. Inhaled forms are topically active, poorly absorbed, and least likely to cause adverse effects. No study has shown significant toxicity with inhaled steroid use in children at doses less than the equivalent of 400 mcg of beclomethasone per day. They are used for long-term control of symptoms and for the suppression, control, and reversal of inflammation. Inhaled forms reduce the need for systemic corticosteroids. They block late asthmatic response to allergens; reduce airway hyperresponsiveness; inhibit cytokine production, adhesion protein activation, and inflammatory cell migration and activation; and reverse beta2-receptor downregulation and subsensitivity (in acute asthmatic episodes with long-term beta2-agonist use). 
Inhaled steroids include beclomethasone, triamcinolone, flunisolide, fluticasone, and budesonide.
Beclomethasone (Beclovent, Vanceril, QVAR)  Inhibits bronchoconstriction mechanisms; causes direct smooth muscle relaxation; and may decrease the number and activity of inflammatory cells, which, in turn, decreases airway hyperresponsiveness.
Low dose: 84-336 mcg/d (42 mcg/oral inhalation, 2-8 inhalations q24h)
 Medium dose: 336-672 mcg/d (42 mcg/oral inhalations, 8-16
                     inhalations q24h)
 High dose: >672 mcg/d (42 mcg/oral inhalation, >16 inhalations q24h)

Fluticasone (Flovent) has extremely potent vasoconstrictive and anti-inflammatory activity. Has a weak hypothalamic-pituitary adrenocortical axis inhibitory potency when applied topically.
Low dose: 88-176 mcg/d (44 mcg/oral inhalation, 2-4 inhalations q24h)
 Medium dose: 176-440 mcg/d (110 mcg/oral inhalation, 2-4 inhalations
 High dose: >440 mcg/d (110 mcg/oral inhalation, >4 inhalations q24h or 220
 mcg/oral inhalation, 2 inhalations q24h)

Budesonide (Pulmicort Turbuhaler or Respules)  Has extremely potent vasoconstrictive and anti-inflammatory activity. Has a weak hypothalamic-pituitary adrenocortical axis inhibitory potency when applied topically. Pulmicort is available in a powder inhaler (200 mcg per oral inhalation) or as a nebulized susp (ie, Respules).
MDI: Low dose: 100-200 mcg/d (1 inhalation q24h)
 Medium dose: 200-400 mcg/d (1-2 inhalation q24h)
 High dose: >400 mcg/d (>2 inhalations q24h)
 Nebulizer (inhalation susp): 0.25-0.5 mg bid; not to exceed 1 mg/d
Drug Category: Systemic corticosteroids
 These agents are used for short courses (3-10 d) to gain prompt control of inadequately controlled acute asthmatic episodes. They are also used for long-term prevention of symptoms in severe persistent asthma as well as for suppression, control, and reversal of inflammation. Frequent and repetitive use of beta2-agonists has been associated with beta2-receptor subsensitivity and downregulation; these processes are reversed with corticosteroids.
Higher-dose corticosteroids have no advantage in severe asthma exacerbations, and intravenous administration has no advantage over oral therapy, provided that gastrointestinal transit time or absorption is not impaired. The usual regimen is to continue frequent multiple daily dosing until the FEV1 or PEF is 50% of the predicted or personal best values; then, the dose is changed to twice daily. This usually occurs within 48 hours.
Prednisone (Deltasone, Orasone) and prednisolone (Pediapred, Prelone, Orapred) -- Immunosuppressants for the treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
1-2 mg/kg/d PO for 3-10 d; not to exceed 60-80 mg/d
Methylprednisolone (Solu-Medrol)  May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
1 mg/kg IV q6h

Drug Category: Leukotriene modifier
 Knowledge that leukotrienes cause bronchospasm, increased vascular permeability, mucosal edema, and inflammatory cell infiltration leads to the concept of modifying their action by using pharmacologic agents. These are either 5-lipoxygenase inhibitors or leukotriene-receptor antagonists.
Zafirlukast (Accolate).  It is a selective competitive inhibitor of LTD4, LTE4 receptors.
5-11 years: 10 mg PO bid
 >12 years: Administer as in adults

Montelukast (Singulair)   It is a last agent introduced in its class. The advantages are that it is chewable, it has a once-a-day dosing, and it has no significant adverse effects.
12-23 months: 1 packet of 4 mg oral granules PO hs
 2-6 years: 4 mg PO hs
 6-14 years: 5 mg PO hs
 >14 years: Administer as in adults
Drug Category: Monoclonal antibody
  These agents bind selectively to human IgE on the surface of mast cells
and basophils.
Omalizumab (Xolair)  Recombinant, DNA-derived, humanized IgG monoclonal antibody that binds selectively to human IgE on surface of mast cells and basophils. Reduces mediator release, which promotes allergic response. Indicated for moderate-to-severe persistent asthma in patients who react to perennial allergens in whom symptoms are not controlled by inhaled corticosteroids.
<12 years: Not established
>12 years: 150-375 mg SC q2-4wk; inject slowly over 5-10 s because of viscosity; not to exceed 150 mg per injection site
 Precise dose and frequency established by serum total IgE level (IU/mL)


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