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.[28] 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 (PD20).
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.
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[30] ; 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.
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.
National Heart, Lung, and Blood Institute. Global Initiative for Asthma. National Institute for Health Publication. 1995;95-3659.
Global strategy for asthma management and prevention. Global initiative for asthma (GINA) 2006. Available at http://ginasthma.org.
Akinbami LJ, Moorman JE, Garbe PL, Sondik EJ. Status of childhood asthma in the United States, 1980-2007. Pediatrics. Mar 2009;123 Suppl 3:S131-45. [Medline].
National Health Interview Survey, National Center for Health Statistics. CDC. Available at http://www.cdc.gov/nchs/products/pubs/pubd/hestats/ashtma03-05/asthma03-05.htm.
Anderson WJ, Watson L. Asthma and the hygiene hypothesis. N Engl J Med. May 24 2001;344(21):1643-4. [Medline].
Goksör E, Alm B, Thengilsdottir H, Pettersson R, Aberg N, Wennergren G. Preschool wheeze - impact of early fish introduction and neonatal antibiotics. Acta Paediatr. Dec 2011;100(12):1561-6. [Medline].
Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med. May 2000;161(5):1720-45. [Medline].
Ege MJ, Mayer M, Normand AC, Genuneit J,et al. Exposure to environmental microorganisms and childhood asthma. N Engl J Med. Feb 24 2011;364(8):701-9. [Medline].
Zucker, M. Asthma phenotype, genotype may guide future therapies. http://www.pulmonaryreviews.com [serial online]. June 2003;8:Available at http://www.pulmonaryreviews.com/jun03/pr_jun03_phenotype.html.
Drazen JM, Yandava CN, Dubé L, Szczerback N, Hippensteel R, Pillari A, et al. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat Genet. Jun 1999;22(2):168-70. [Medline].
Thompson EE, Pan L, Ostrovnaya I, Weiss LA, Gern JE, Lemanske RF Jr, et al. Integrin beta 3 genotype influences asthma and allergy phenotypes in the first 6 years of life. J Allergy Clin Immunol. Jun 2007;119(6):1423-9. [Medline].
Wechsler ME, Lehman E, Lazarus SC, Lemanske RF Jr, Boushey HA, Deykin A, et al. beta-Adrenergic receptor polymorphisms and response to salmeterol. Am J Respir Crit Care Med. Mar 1 2006;173(5):519-26. [Medline]. [Full Text].
Moore WC, Meyers DA, Wenzel SE, Teague WG, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med. Feb 15 2010;181(4):315-23. [Medline]. [Full Text].
Torgerson DG, Ampleford EJ, Chiu GY, et al. Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat Genet. Jul 31 2011;43(9):887-92. [Medline].
Ferreira MA, Matheson MC, Duffy DL, et al. Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet. Sep 10 2011;378(9795):1006-14. [Medline].
Lemanske RF Jr, Jackson DJ, Gangnon RE, Evans MD, Li Z, Shult PA, et al. Rhinovirus illnesses during infancy predict subsequent childhood wheezing. J Allergy Clin Immunol. Sep 2005;116(3):571-7. [Medline].
[Best Evidence] Guilbert TW, Morgan WJ, Zeiger RS, Mauger DT, Boehmer SJ, Szefler SJ, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. May 11 2006;354(19):1985-97. [Medline].
Vesper S, McKinstry C, Haugland R, et al. Development of an Environmental Relative Moldiness index for US homes. J Occup Environ Med. Aug 2007;49(8):829-33. [Medline].
Reponen T, Vesper S, Levin L, et al. High environmental relative moldiness index during infancy as a predictor of asthma at 7 years of age. Ann Allergy Asthma Immunol. Aug 2011;107(2):120-6. [Medline].
Farah CS, Kermode JA, Downie SR, et al. Obesity is a determinant of asthma control independent of inflammation and lung mechanics. Chest. Sep 2011;140(3):659-66. [Medline].
Quinto KB, Zuraw BL, Poon KY, Chen W, Schatz M, Christiansen SC. The association of obesity and asthma severity and control in children. J Allergy Clin Immunol. Nov 2011;128(5):964-9. [Medline].
Goleva E, Searing DA, Jackson LP, Richers BN, Leung DY. Steroid requirements and immune associations with vitamin D are stronger in children than adults with asthma. J Allergy Clin Immunol. Feb 11 2012;[Medline].
Asthma prevalence and control characteristics by race/ethnicity--United States, 2002. MMWR Morb Mortal Wkly Rep. Feb 27 2004;53(7):145-8. [Medline].
Moorman JE, Rudd RA, Johnson CA, King M, Minor P, Bailey C, et al. National surveillance for asthma--United States, 1980-2004. MMWR Surveill Summ. Oct 19 2007;56(8):1-54. [Medline].
Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. Jan 19 1995;332(3):133-8. [Medline].
Castro-Rodríguez JA, Holberg CJ, Wright AL, Martinez FD. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med. Oct 2000;162(4 Pt 1):1403-6. [Medline].
[Best Evidence] Coffman JM, Cabana MD, Yelin EH. Do school-based asthma education programs improve self-management and health outcomes?. Pediatrics. Aug 2009;124(2):729-42. [Medline]. [Full Text].
[Guideline] Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol. Nov 2007;120(5 Suppl):S94-138. [Medline].
Wu AC, Tantisira K, Li L, Schuemann B, Weiss ST, Fuhlbrigge AL. Predictors of Symptoms are Different from Predictors of Severe Exacerbations from Asthma in Children. Chest. Feb 3 2011;[Medline].
Stern G, de Jongste J, van der Valk R, Baraldi E, Carraro S, Thamrin C, et al. Fluctuation phenotyping based on daily fraction of exhaled nitric oxide values in asthmatic children. J Allergy Clin Immunol. Aug 2011;128(2):293-300. [Medline].
Holbrook JT, Wise RA, Gold BD, et al. Lansoprazole for children with poorly controlled asthma: a randomized controlled trial. JAMA. Jan 25 2012;307(4):373-81. [Medline].
[Best Evidence] Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. Jan 2006;129(1):15-26. [Medline].
[Best Evidence] Salpeter SR, Wall AJ, Buckley NS. Long-acting beta-agonists with and without inhaled corticosteroids and catastrophic asthma events. Am J Med. Apr 2010;123(4):322-8.e2. [Medline].
US Food and Drug Administration. FDA Drug Safety Communication: New safety requirements for long-acting inhaled asthma medications called Long-Acting Beta-Agonists (LABA). Human Department of Health and Human services. Feb 18, 2010;1-4. [Full Text].
Lemanske RF, Mauger DT, Sorkness CA, et al. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med. March 30, 2010;362:975-85.
[Best Evidence] Rachelefsky G. Inhaled corticosteroids and asthma control in children: assessing impairment and risk. Pediatrics. Jan 2009;123(1):353-66. [Medline].
Martinez FD, Chinchilli VM, Morgan WJ, Boehmer SJ, Lemanske RF Jr, Mauger DT, et al. Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial. Lancet. Feb 19 2011;377(9766):650-7. [Medline].
Quon BS, Fitzgerald JM, Lemière C, Shahidi N, Ducharme FM. Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children. Cochrane Database Syst Rev. Dec 8 2010;CD007524. [Medline].
Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med. Oct 12 2000;343(15):1064-9. [Medline].
Long-term effects of budesonide or nedocromil in children with asthma. The Childhood Asthma Management Program Research Group. N Engl J Med. Oct 12 2000;343(15):1054-63. [Medline].
Rodrigo GJ, Neffen H, Castro-Rodriguez JA. Efficacy and safety of subcutaneous omalizumab vs placebo as add-on therapy to corticosteroids for children and adults with asthma: a systematic review. Chest. Jan 2011;139(1):28-35. [Medline].
Busse WW, Morgan WJ, Gergen PJ, Mitchell HE, Gern JE, Liu AH, et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med. Mar 17 2011;364(11):1005-15. [Medline].
[Best Evidence] Cates CJ, Bestall J, Adams N. Holding chambers versus nebulisers for inhaled steroids in chronic asthma. Cochrane Database Syst Rev. Jan 25 2006;CD001491. [Medline].
[Best Evidence] Vuillermin PJ, Robertson CF, Carlin JB, Brennan SL, Biscan MI, South M. Parent initiated prednisolone for acute asthma in children of school age: randomised controlled crossover trial. BMJ. Mar 1 2010;340:c843. [Medline]. [Full Text].
Halterman JS, Szilagyi PG, Fisher SG, Fagnano M, Tremblay P, Conn KM, et al. Randomized controlled trial to improve care for urban children with asthma: results of the school-based asthma therapy trial. Arch Pediatr Adolesc Med. Mar 2011;165(3):262-8. [Medline].
Postma DS, O'Byrne PM, Pedersen S. Comparison of the effect of low-dose ciclesonide and fixed-dose fluticasone propionate and salmeterol combination on long-term asthma control. Chest. Feb 2011;139(2):311-8. [Medline].
| 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 | ||||

