• 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.

• Symptoms of asthma may include wheezing, coughing, chest tightness, and others.

• Wheezing: 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 also is 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.

• 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 tightness in the chest 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 a softer, shorter cry and feeding difficulties.

• Symptoms during a severe episode: Patients are breathless during rest, are not interested in feeding, sit upright, talk in words (not sentences), and usually are 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.

Physical:

• The clinical picture varies. Symptoms may be associated with viral upper respiratory infections (URIs), 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 might 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 might be increased because of hyperinflation. Hyperinflation might 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 very unusual in straightforward asthma and indicates a need for more extensive evaluation.

• 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 often is 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 might be increased (10-20 mm Hg). Oxyhemoglobin saturation with room air is 91-95%.

• Severe episode: The respiratory rate often is greater than 30 breaths per minute. Accessory muscles of respiration usually are used, and suprasternal retractions commonly are present. The heart rate is greater than 120 beats per minute. Loud biphasic (expiratory and inspiratory) wheezing can be heard. Pulsus paradoxus often is 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 might be absent (associated with most severe airway obstruction). Severe hypoxemia may present as bradycardia. Pulsus paradoxus noted earlier may be absent; this finding suggests respiratory muscle fatigue.

Causes: In most cases of asthma in children, multiple triggers or precipitants exist, and the patterns of reactivity might change with age. Treatment also can change the pattern. Certain viral infections, such as respiratory syncytial virus (RSV) bronchiolitis in infancy, predispose the child to asthma.

• Respiratory infections: Most commonly, these are viral infections. In some patients, fungi (eg, allergic bronchopulmonary aspergillosis), bacteria (eg, mycoplasmata, pertussis), or parasites might be responsible. Most infants and young children who continue to have a persistent wheeze and asthma have high immunoglobulin E (IgE) production and eosinophilic immune responses (in the airways and in circulation) at the time of the first viral URI. They also have early IgE-mediated responses to local aeroallergens.

• Allergens: In patients with asthma, 2 types of bronchoconstrictor responses to allergens exist.

• Early asthmatic responses occur via IgE-induced mediator release from mast cells within minutes of exposure and last for 20-30 minutes.

• Late asthmatic responses occur 4-12 hours after antigen exposure and result in more severe symptoms that can last for hours and contribute to the duration and severity of the disease. Inflammatory cell infiltration and inflammatory mediators play a role in the late asthmatic response. Allergens can be foods, household inhalants (eg, animal allergens, molds, fungi, roach allergens, dust mites), or seasonal outdoor allergens (eg, mold spores, pollens, grass, trees).

• Irritants: Tobacco smoke, cold air, chemicals, perfumes, paint odors, hair sprays, air pollutants, and ozone can initiate BHR by inducing inflammation.

• Weather changes: Asthma attacks can be related to changes in barometric pressure and the quality of air (eg, humidity, allergen and irritant content).

• Exercise: Exercise can trigger an early asthmatic response. Mechanisms underlying exercise-induced asthmatic response remain somewhat uncertain. Heat and water loss from the airways can increase the osmolarity of the fluid lining the airways and result in mediator release. Cooling of the airways results in congestion and dilatation of bronchial vessels. During the rewarming phase after exercise, the changes are magnified because the ambient air breathed during recovery is warm rather than cool.

• Emotional factors: In some individuals, emotional upsets clearly aggravate asthma.

• Gastroesophageal reflux (GER): The presence of acid in the distal esophagus, mediated via vagal or other neural reflexes, can significantly increase airway resistance and airway reactivity.

• Allergic rhinitis, sinusitis, and chronic URI: Inflammatory conditions of the upper airways (eg, allergic rhinitis, sinusitis, or chronic and persistent infections) must be treated before asthmatic symptoms can be completely controlled.

• Nocturnal asthma: Multiple factors have been proposed to explain nocturnal asthma. Circadian variation in lung function and inflammatory mediator release in the circulation and airways (including parenchyma) have been demonstrated. Other factors, such as allergen exposure and posture-related irritation of airways (eg, GER, sinusitis), also can play a role. In some patients, abnormalities in CNS control of the respiratory drive might be present, particularly in patients with a defective hypoxic drive and obstructive sleep apnea.

• 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 might 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.

• 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 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 might help when allergic factors are suspected.

Imaging Studies:

• Chest radiograph: 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.

• Paranasal sinus radiograph or CT scan: Consider using these to rule out sinusitis.

Other Tests:

• Allergy testing: Allergy testing can be used to identify allergic factors that might 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.

• 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 in children aged 2 years and older was approved.

  • 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.

  • 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.

Consultations: 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.

Diet: When major allergies to dietary products are present, 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.

• Once the patient is admitted, further investigations (eg, PFTs, allergy testing, and investigations to rule out other associated conditions and complications) can be performed.

Further Outpatient Care:

• Regular follow-up visits (1-6-mo intervals) are essential to ensure control and appropriate therapeutic adjustments.

• Outpatient visits should include the following:

• Interval history of asthmatic complaints, including history of acute episodes (eg, severity, measures and treatment taken, response to therapy)

• History of nocturnal symptoms

• History of symptoms with exercise and exercise tolerance

• Review of medications, including use of rescue medications

• Review of home-monitoring data (eg, symptom diary, peak flow meter readings, daily treatments)

• Patient evaluation should include the following:

• Assessment for signs of bronchospasm and complications

• Evaluation of associated conditions (eg, allergic rhinitis)

• Pulmonary function testing (in appropriate age group)

• Address issues of treatment adherence and avoidance of environmental triggers and irritants.

• Long-term asthma care pathways that incorporate the aforementioned factors can serve as roadmaps for ambulatory asthma care and help streamline outpatient care by different providers.

• In our asthma clinic, a member of the asthma care team sits with each patient to review the written asthma care plan and to write and discuss in detail a rescue plan for acute episode, which includes instructions about identifying signs of acute episode, using rescue medications, monitoring, and contacting the asthma care team. These items are reviewed at each visit.

In/Out Patient Meds:

• Bronchodilators (short and long acting)

• Controlling medications (nonsteroidal, steroidal, newer agents such as leukotriene modifiers)

• Medications for the treatment of associated conditions (antiallergy medications, nasal steroids for allergic rhinitis)

• Rescue medications for use in acute episodes (short burst of steroids)

Transfer:

• Any patient with a high risk of asthma should be referred to a specialist. The following may suggested a high risk:

• Past history of sudden severe exacerbations

• History of prior intubation for asthma

• Admission to an ICU because of asthma

• Two or more hospitalizations for asthma in the past year

• Three or more emergency department visits for asthma in the past year

• Hospitalization or an emergency department visit for asthma within the past month

• Use of 2 or more canisters of inhaled short-acting beta2-agonists per month

• Current use of systemic corticosteroids or recent withdrawal from systemic corticosteroids

• The choice between a pediatric pulmonologist and an allergist may depend on local availability and practices. A patient with frequent ICU admissions, previous intubation, and a history of complicating factors or comorbidity (eg, cystic fibrosis) should be referred to a pediatric pulmonologist. When allergies are thought to significantly contribute to the morbidity, an allergist may be helpful.

Deterrence/Prevention:

• The goal of long-term therapy is to prevent acute exacerbations.

• The patient should avoid exposure to environmental allergens and irritants that are identified during the evaluation.

Complications:

• Pneumothorax status asthmaticus with respiratory failure

• Fixed (nonreversible) airway obstruction

• Death

Prognosis:

• Of infants who wheeze with URIs, 60% are asymptomatic by age 6 years; however, children who have asthma (recurrent symptoms continuing at age 6 y) have airway reactivity later in childhood.

• Some findings suggest a poor prognosis if asthma develops in children younger that 3 years. Unless it occurs solely in association with viral infections.

• Individuals who have asthma during childhood have significantly lower FEV₁ and airway reactivity and more persistent bronchospastic symptoms than those with infection-associated wheezing.

• Children with mild asthma who are asymptomatic between attacks are likely to improve and be symptom-free later in life.

• Children with asthma appear to have less severe symptoms as they enter adolescence, but half of these children continue to have asthma.

• Asthma has a tendency to remit during puberty, with a somewhat earlier remission in girls. However, compared with men, women have more BHR.

Patient Education:

• Patient and parent education should include instructions on how to use medications and devices (eg, spacers, nebulizers, MDIs). The patient’s MDI technique should be assessed on every visit.

• Discuss the management plan, which includes instructions about the use of medications, precautions with drug and/or device usage, monitoring symptoms and their severity (peak flow meter reading), and identifying potential adverse effects and necessary actions.

• Write and discuss in detail a rescue plan for an acute episode. This plan should include instructions for identifying signs of an acute attack, using rescue medications, monitoring, and contacting the asthma care team.

• Parents should understand that asthma is a chronic disorder with acute exacerbations; hence, continuity of management with active participation by the patient and/or parents and interaction with asthma care medical personnel is important.

• Emphasize the importance of compliance with and adherence to treatment.

• Incorporate the concept of expecting full control of symptoms, including nocturnal and exercise-induced symptoms, in the management plans and goals (for all but the most severely affected patients).

• Avoid unnecessary restrictions in the lifestyle of the child or family. Expect the child to participate in recreational activities and sports and to attend school as usual.

Medical/Legal Pitfalls:

• Failure to recognize the severity of an acute severe episode (ie, status asthmaticus) and to initiate aggressive management (eg, intubation and ventilation) can lead to fatal complications such as respiratory failure and even death.

• Failure to diagnose pneumothorax can lead to serious consequences.

• Identification of associated or complicating conditions (eg, allergic rhinitis or sinusitis) is important for comprehensive management.

• Underdiagnosis of asthma, including recurrent bronchitis, chronic bronchitis, and asthmatic bronchitis can be a problem.

Special Concerns:

• In the children, long-term use of high-dose steroids (systemic or inhaled) may lead to adverse effects, including growth failure. Recent data from the Childhood Asthma Management Program (CAMP) study and results of the long-term use of inhaled steroids (budesonide) suggest that the long-term use of inhaled steroids has no sustained adverse effect on growth in children.

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