Approach Considerations
According to the National Asthma Education and Prevention Program guidelines, spirometry is an essential objective measure for establishing the diagnosis of asthma. Additional studies are not routinely necessary, but they may be useful when the clinician is considering alternative diagnoses. [2] Eosinophil counts and IgE levels may be useful when allergic factors are suspected.
Bronchial provocation tests may be performed to diagnose bronchial hyperresponsiveness (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 (PC 20 ).
For more information, see the Medscape Reference topic Peak Flow Rate Measurement.
Pulmonary Function Tests
Results of pulmonary function testing are not reliable in patients younger than 5 years. In young children (3-6 y) and older children who are unable to perform the conventional spirometry maneuver, newer techniques, such as measurement of airway resistance using impulse oscillometry system, are used. 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 forced expiratory volume in 1 second (FEV1), and reduced forced expiratory flow more than 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.
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 peak expiratory flow (PEF) rate (PEFR) are determined immediately after the exercise period and at 3 minutes, 5 minutes, 10 minutes, 15 minutes, and 20 minutes after the first measurement. The maximal decrease in lung function is calculated by using the lowest postexercise and highest pre-exercise values. The reversibility of airway obstruction can be assessed by administering aerosolized bronchodilators.
Methacholine challenge
The degree of airway responsiveness can be assessed by methacholine challenge testing. [43] Methacholine causes bronchoconstriction via muscarinic acetylcholine receptor M3, and the resultant decrease in FEV1 is recorded by spirometry. The test can help to confirm the diagnosis of asthma in a patient with history of asthma but normal spirometry findings.
During the test, the patient inhales increasing concentrations of methacholine aerosol via a nebulizer; spirometry is performed before and after each dose. A positive response is a 20% fall in FEV1. The corresponding concentration of methacholine (mg/mL) is called PC 20 . A PC 20 of greater than 16 mg/mL indicates normal bronchial responsiveness. PC 20 values of 4-16 mg/mL, 1-4 mg/mL, and < 1 mg/mL indicate borderline, mild, and moderate-to-severe bronchial hyperresponsiveness, respectively.
Methacholine challenge testing is more useful in excluding a diagnosis of asthma than in establishing one because its negative predictive power is greater than its positive predictive power. [43] Other agents (ie, histamine, mannitol) are also used for bronchoprovocation.
Fraction of Exhaled Nitric Oxide Testing
Measuring the fraction of exhaled nitric oxide (FeNO) has proved useful as a noninvasive marker of airway inflammation, in order to guide adjustment of the dose of inhaled corticosteroids. In one study involving home monitoring of FeNO and symptom scores, the 2 correlated. Further, in some patients, the FeNO rose before significant exacerbations of the asthma [44] ; thus, although studies of FeNO in large groups have either shown it to be helpful or not, it may be a useful method of evaluating therapy in individual patients. Due to the high cost of equipment, FeNO measurement is used primarily as a research tool at present.
Measuring the level of interleukin-5 in exhaled breath condensate is a possible way of titrating asthma progress, according to one study. In a longitudinal study of 40 asthmatic children aged 6-16 years, asthma control score and level of interleukin-5 were significant predictors of an asthma exacerbation. [45]
Radiography and CT Scan
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. Consider using sinus radiography and CT scanning to rule out sinusitis.
For more information, see the Medscape Reference topic Imaging in Asthma.
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 particular agent’s duration of action) before allergy testing. Topical or systemic corticosteroids do not affect the skin reaction.
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.
Tables
Intermittent Asthma |
Persistent Asthma: Daily Medication |
|||||
Age |
Step 1 |
Step 2 |
Step 3 |
Step 4 |
Step 5 |
Step 6 |
< 5 y |
Rapid-acting beta2-agonist prn |
Low-dose inhaled corticosteroid (ICS) |
Medium-dose ICS |
Medium-dose ICS plus either long-acting beta2-agonist (LABA) or montelukast |
High-dose ICS plus either LABA or montelukast |
High-dose ICS plus either LABA or montelukast; Oral systemic corticosteroid |
Alternate regimen: cromolyn or montelukast |
||||||
5-11 y |
Rapid-acting beta2-agonist prn |
Low-dose ICS |
Either low-dose ICS plus either LABA, LTRA, or theophylline OR Medium-dose |
Medium-dose ICS plus LABA |
High-dose ICS plus LABA |
High-dose ICS plus LABA plus oral systemic corticosteroid |
Alternate regimen: cromolyn, leukotriene receptor antagonist (LTRA), or theophylline |
Alternate regimen: medium-dose ICS plus either LTRA or theophylline |
Alternate regimen: high-dose ICS plus either LABA or theophylline |
Alternate regimen: high-dose ICS plus LRTA or theophylline plus systemic corticosteroid |
|||
12 y or older |
Rapid-acting beta2-agonist as needed |
Low-dose ICS |
Low-dose ICS plus LABA OR Medium-dose ICS |
Medium-dose ICS plus LABA |
High-dose ICS plus LABA (and consider omalizumab for patients with allergies) |
High-dose ICS plus either LABA plus oral corticosteroid (and consider omalizumab for patients with allergies) |
Alternate regimen: cromolyn, LTRA, or theophylline |
Alternate regimen: low-dose ICS plus either LTRA, theophylline, or zileuton |
Alternate regimen: medium-dose ICS plus either LTRA, theophylline, or zileuton |
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- Bronchodilators, Beta2-Agonists
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- Systemic Corticosteroids
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