Basics
Description
- Characterized by 3 components:
- Reversible airway obstruction
- Airway inflammation
- Airway hyperresponsiveness to a variety of stimuli
- Diagnosis (the 3 "R"�s)
- Recurrence: Symptoms are recurrent.
- Reactivity: Symptoms are brought on by a specific occurrence or exposure (trigger).
- Responsive: Symptoms diminish in response to bronchodilator or anti-inflammatory agent.
Alert
Pitfalls �
- Not recognizing that asthma can manifest as chronic cough; wheezing may not be evident.
- Reluctance to "label"� child with having asthma (using terms such as reactive airway disease or bronchitis)
- Frequent antibiotic or cough medicine use to treat asthma symptoms
- "Recurrent pneumonias"� often are actually asthma exacerbations; subsegmental atelectasis on chest radiograph misdiagnosed as an infiltrate
- Underreporting of asthma symptoms; beware of the child who "doesn't like to play sports"�; he/she may have learned that exercise causes dyspnea.
- Poor adherence with therapy when symptoms are controlled
- Failure to use inhaled medications properly: Inhaled medication use must be taught and reviewed at each visit. A fixed-volume holding chamber should always be used with a pressurized metered-dose inhaler (pMDI), regardless of patient age. pMDIs should be refilled based on the number of doses used, not by estimating contents by shaking or spraying. pMDIs with a built-in dose counter are preferred.
Epidemiology
Incidence
- Most common chronic illness in children
- About 20% of children are diagnosed with asthma at some point before age 20 years.
- Death from asthma in children more than tripled from 1979 to 1996 but has been decreasing since then, perhaps owing to better recognition and increased use of anti-inflammatory medications. The incidence of death from asthma does not seem to correlate with severity.
Prevalence
- Wheezing in children is extremely common in the industrialized world (cumulative prevalence, 30-60%).
- In younger children, most episodes occur following viral infections.
- >50% of children who wheeze in early childhood stop wheezing by age 6 years.
- 14% of all young children (40% of those who wheeze during infancy) continue to wheeze.
Risk Factors
Genetics
- Children of asthmatics have higher incidence of asthma.
- 6-7% risk if neither parent has asthma
- 20% risk if 1 parent has asthma
- 60% risk if both parents have asthma
- Several genes are known to be associated with the development of atopy and bronchial muscle responsiveness.
General Prevention
- Patient and caregiver education is mandatory to establish provider/caregiver partnership and ensure adherence with treatment plan.
- Every patient/caregiver should be taught that asthma is a chronic, inflammatory condition that can be controlled with proper therapy.
- All medications should be explained and potential risks (side effects) and benefits reviewed.
- A written asthma management plan should be provided, outlining daily therapy and an "action plan"� for managing exacerbations of asthma.
- Environmental counseling:
- Avoid airborne irritants (tobacco smoke, wood stoves, noxious fumes).
- Minimize dust-mite exposure.
- Minimize stuffed animals, quilts, books, and clutter.
- Use dust mite-proof coverings on mattresses, pillows, and box springs.
- Wash pillows, blankets, and sheets in hot water.
- Avoid molds by decreasing relative humidity to 50%.
- Remove pets from child's bedroom and from house if patient is allergic to the animal.
Pathophysiology
- Immune and inflammatory responses in the airways are triggered by an array of environmental antigens, irritants, or infectious organisms.
- Atopy and asthma are related.
- Eosinophilia and the ability to make excess IgE in response to antigen are associated with increased airway reactivity.
- Asthma is more common in children who have allergic rhinitis and eczema.
- Viral infections, particularly respiratory syncytial virus (RSV) during infancy, may play a role in the development of asthma or may modify the severity of asthma.
- Exposure to cigarette smoke and other airway irritants influences the development and severity of asthma.
- Airway is stimulated and primary inflammatory mediators released.
- Airway is invaded by inflammatory cells (mast cells, basophils, eosinophils, macrophages, neutrophils, B and T lymphocytes).
- Inflammatory cells respond to and produce various mediators (cytokines, leukotrienes, lymphokines), augmenting the inflammatory response.
- Airway epithelium is inflamed and becomes disrupted, and basal membrane is thickened.
- Airway smooth muscle is hyperresponsive, and bronchoconstriction ensues.
- Airway smooth muscle hypertrophy and airway epithelial hyperplasia are characteristic chronic changes resulting from poorly controlled asthma.
Diagnosis
History
- Inquire about these symptoms: coughing, wheezing, shortness of breath, chest tightness:
- Frequency of symptoms defines severity.
- Precipitating factor (trigger)
- Response to bronchodilator or anti-inflammatory medication
- Family history of asthma or atopy
- Pattern of symptoms:
- Perennial versus seasonal
- Continuous versus acute
- Duration and frequency of episodes
- Diurnal variation/nocturnal symptoms
- Do any of the following set off the breathing difficulty?
- Infections (upper respiratory, sinusitis)
- Exposure to dust (mites), animal dander, pollen, mold
- Cold air or weather changes
- Exercise or play
- Environmental stimulants (e.g., cigarette smoke, strong odors, pollutants)
- Emotional factors (e.g., laughing, crying, fear)
- Drug intake (aspirin, nonsteroidal anti-inflammatory drugs, β-blockers)
- Food additives
- Endocrine factors (e.g., menses, pregnancy, thyroid dysfunction)
- Review of systems:
- Symptoms of complicating factors (gastroesophageal reflux, sinusitis, allergies)
- Dyspepsia, sour taste (gastroesophageal reflux); throat clearing, purulent nasal discharge, halitosis, cephalalgia, or facial pain (sinusitis); nasal itching ("allergic salute"�), eye rubbing, sneezing, watery nasal discharge (allergies)
- Impact of asthma:
- Number of hospitalizations/intensive care unit admissions
- Number of emergency room visits/doctor's office visits
- Asthma attack frequency
- Number of missed school days/parent workdays
- Limitation on activity (may be subtle)
- Number of courses of systemic steroids needed
- Environmental history:
- Type of home
- Location of home (urban, suburban, rural)
- Heating system/air conditioning
- Use of humidifier
- Presence of molds, cockroaches, rodents
- Fireplace/wood burning stove
- Carpeting
- Stuffed animals
- Pets
- Exposure to cigarette smoke
Physical Exam
- Pulmonary exam may be normal when asymptomatic.
- Assess work of breathing:
- Level of distress
- Intercostal/supraclavicular muscle retractions
- Chest shape (i.e., normal vs. barrel-shaped)
- Lung auscultation:
- Wheezing
- End-expiratory involuntary cough
- Prolonged expiratory phase
- Crackles or coarse breath sounds
- Stridor (indicates extrathoracic airway obstruction)
- Head, eyes, ears, nose, and throat exam: signs of allergies or sinusitis:
- Watery or itchy eyes
- Allergic shiners
- Dennie lines
- Nasal congestion
- Boggy nasal turbinates
- Nasal polyps
- Postnasal drip
- General exam (vital signs):
- Blood pressure (pulsus paradoxus)
- Respiratory rate (tachypnea)
- Skin: evidence of eczema
- Extremities: digital clubbing (very rare in asthma; suggests alternative diagnosis)
- Physical exam pearl: forced-exhalation maneuver to observe for wheezes or for precipitating coughing
Diagnostic Tests & Interpretation
Lab
- Pulmonary function tests
- Very sensitive; may show airway obstruction even when the physical exam is normal
- Essential for the assessment and ongoing care of children with asthma
- Spirometer measures the degree of airway obstruction and the response to bronchodilators.
- Values obtained can measure absolute degree of airway obstruction.
- Serial values can follow progress of disease and response to treatment.
- Children as young as 4-5 years old can usually perform spirometry with practice.
- Provocational testing
- Exercise challenge: determines effect of exercise on triggering airway obstruction
- Cold-air challenge: indirect test of airway hyperresponsiveness
- Methacholine challenge: A positive test supports the diagnosis of asthma (useful in cases for which history is equivocal and pulmonary function test is normal), measures the degree of airway hyperreactivity.
- Allergy evaluation:
- Blood tests (eosinophil count, IgE level)
- Skin testing (best test for assessing allergen sensitivity)
- RAST testing (not as accurate as skin testing)
- Sputum/nasal examination for presence of eosinophilia
- Exhaled nitric oxide
- Identifies Th2-mediated airway inflammation
- May identify/exclude steroid responsive airway inflammation
- Other studies:
- Gastroesophageal reflux evaluation
- pH probe
- Milk scan
- Barium swallow (confirms normal anatomy)
- Peak flow meter (home testing)
- Measures peak flow rate (PEFR)
- Effort-dependent
- Assesses central, not peripheral, airway obstruction
- Used with patients who have poor symptom recognition or labile asthma
- Dips in peak flow rate precede onset of clinical asthmatic symptoms.
- Peak flow rate should be performed at least once a day.
- Peak flow rate values are divided into 3 zones:
- Green: ≥80% of baseline
- Yellow: 50-80% of baseline
- Red: 50% of baseline
- Specific peak flow rate guidelines should be individualized for each patient based on the best measurement obtained during a 14-day period when the child is well.
Imaging
- Chest radiograph
- Can be obtained if the diagnosis is uncertain or there is not the expected response to treatment, to rule out congenital lung malformations or obvious vascular malformations
- Findings can be normal.
- Common findings are peribronchial thickening, subsegmental atelectasis, and hyperinflation.
- Sinus CT is useful if symptoms suggest sinusitis.
- Chest CT should be performed if bronchiectasis or anatomic abnormality is suspected.
Diagnostic Procedures/Other
Bronchoscopy can rule out anatomic malformations, foreign bodies, mucous plugging, vocal cord dysfunction, and aspiration (lipid-laden macrophages). �
Differential Diagnosis
- Infectious
- Pneumonia
- Bronchiolitis
- Chlamydia infection
- Laryngotracheobronchitis
- Sinusitis
- Immune deficiency
- Mechanical
- Extrinsic airway compression
- Vascular ring
- Foreign body
- Vocal cord dysfunction
- Tracheobronchomalacia
- Miscellaneous:
- Cystic fibrosis
- Bronchopulmonary dysplasia
- Pulmonary edema
- Gastroesophageal reflux
- Recurrent aspiration
- Bronchiolitis obliterans
Treatment
Medication
- Corticosteroids (anti-inflammatory agents)
- Most effective anti-inflammatory agents
- Inhaled: reduce airway inflammation and hyperresponsiveness more than any other inhaled agents; inhibit production and release of cytokines and arachidonic acid-associated metabolites; enhance β-adrenoreceptor responsiveness
- Side effects include oral thrush; may minimally affect growth velocity at moderate or high doses
- Dosage individualized to each patient (see Figure 5 in Appendix for Stepwise Approach for Managing Asthma Long Term). Agents vary in topical potency and systemic bioavailability; available as pMDIs, dry-powder inhalers (DPIs), or nebulized. Fluticasone (Flovent) 44, 110, 220 mcg/puff pMDI and 50, 100, 250 mcg DPI; budesonide (Pulmicort) 90, 180 mcg/puff DPI and 250, 500, and 1,000-mcg vials for nebulizer; beclomethasone (Qvar) 40, 80 mcg/puff; flunisolide (AeroBid) 80 mcg/puff; ciclesonide (Alvesco) 80, 160 mcg/puff; mometasone (Asmanex) 100 mcg/puff pMDI and 110, 220 mcg DPI (see Table 14 in Appendix for Comparative doses)
- Oral: used for asthma exacerbations or for severe asthma that cannot be otherwise controlled.
- Exacerbations: prednisone or prednisolone 1-2 mg/kg/24 hr for 3-7 days or longer; usually tapered if >7 days of therapy required or if systemic steroids are used frequently. Shorter 2-day courses of oral dexamethasone have also been described in clinical trials.
- Ongoing therapy: 0.5-1 mg/kg/24 hr daily or every other day for patients with severe asthma
- Undesirable side-effect profile. When used daily, assess bone density and for cataract formation at least yearly.
- IV: Methylprednisolone (Solu-Medrol) 1-2 mg/kg/24 hr IV divided q6-12h until improved and able to take oral medication
- Leukotriene modifiers (anti-inflammatory agents)
- Block the synthesis and/or action of leukotrienes
- 5-lipoxygenase inhibitors, zileuton: may cause hepatic dysfunction
- Leukotriene receptor antagonists: zafirlukast (10 mg; Accolate) and montelukast (4, 5, and 10 mg; Singulair)
- Indicated as monotherapy for mild or exercise-induced asthma and in combination with an inhaled corticosteroid for more effective symptom control or using a lower dose of inhaled corticosteroid
- Mast-cell stabilizers
- Weak anti-inflammatory agents
- Preparations: cromolyn sodium; nedocromil sodium (Tilade, available in Canada)
- Decrease bronchial hyperresponsiveness
- Can be used prior to exercise for exercise-induced symptoms
- No significant side effects
- Inhaled: nebulizer; MDI
- β2-Agonists (bronchodilators)
- Indication is for relief of acute bronchoconstriction (quick-relief medicine); used as needed in people with asthma who have breakthrough symptoms; used prior to exercise in exercise-induced bronchospasm
- Regular use or overuse associated with worsened control of asthma
- Routes include metered-dose inhaler or nebulizer
- Short-acting (4-6 hours) preparations include albuterol (Ventolin, Proventil, ProAir), terbutaline (Brethaire, Brethine), and metaproterenol (Alupent); a single-isomer preparation of albuterol (Xopenex) may have a slightly longer duration of action and perhaps fewer side effects.
- Longer acting (up to 12 hours) preparations include salmeterol (Serevent) and formoterol (Foradil) available as pMDI, and DPI can be used daily in conjunction with anti-inflammatory agent for improved symptom control.
- Fixed combination products of inhaled corticosteroid and a long-acting β-agonist (Advair, Dulera, Symbicort) are available as DPIs and pMDIs.
- There may be an increased risk of asthma-related deaths in patients using long-acting β-agonists (LABAs), and it is suggested that LABAs be prescribed only for patients not adequately controlled on other asthma-controller medications or whose disease severity warrants initiation of treatment with 2 maintenance therapies.
- Theophylline (bronchodilator)
- 2nd-line agent used when more conventional therapies are unsuccessful
- Indications are chronic, poorly controlled asthma and nocturnal asthma (if no gastroesophageal reflux); adjunctive therapy with β2-drugs and steroids in hospitalized patients in selected cases; route (oral or IV); serum levels must be routinely monitored (therapeutic levels are 10-20 mg/mL).
- Side effects are seen with increased levels.
- Many factors affect theophylline levels. Increased levels are seen with erythromycin, ciprofloxacin, cimetidine, viral illnesses, fever. Decreased levels are seen with phenobarbital, phenytoin, rifampin.
- Sustained-release tablets should not be crushed.
- Anticholinergic agents (bronchodilators): Adjunctive bronchodilators may be useful in patients who only partially respond to β-agonists; preparations include ipratropium bromide MDI or ampule for nebulization (Atrovent).
- Monoclonal antibodies against IgE (Xolair) can be given as a monthly SC injection in severe asthma patients with moderately high IgE levels.
Issues for Referral
- A patient who requires hospitalization more than once a year, or who has required intensive care
- A patient who requires frequent bursts of systemic corticosteroids
- A patient whose airway obstruction is not easily reversible
- A patient who has clinical features suggesting another pulmonary process
Complementary & Alternative Therapies
- Miscellaneous drugs used in severe cases
- Steroid-sparing agents:
- Troleandomycin (TAO): Macrolide antibiotic decreases clearance of corticosteroids, thus prolonging the effects of corticosteroids on the lung; lower corticosteroid dosing required
- Methotrexate: Potent immunosuppressive drug needs further investigation in children.
- Cyclosporine: shown to have steroid-sparing effect in adult population with asthma; side effects are significant and may limit use.
- Magnesium sulfate (MgSO4): used intravenously as a smooth muscle relaxer in severe acute asthma exacerbation
- Helium
- May improve airflow in severe asthma
- Can improve ventilation and potentially oxygenation
- Immunotherapy
- Efficacy in asthma is controversial.
- Most effective if a single antigen can be identified
- Used only in select cases if medical management and environmental control measures are ineffective
Ongoing Care
Follow-up Recommendations
Long-term follow-up is essential to maintain normal activity and pulmonary function. All patients should use a valved holding chamber with pMDIs, and technique for all inhaled medications should be reviewed regularly. �
Patient Monitoring
Signs that may indicate problems: increased symptoms (cough day or night, wheeze), exercise limitations or symptoms during exercise, decrease in peak flow rate, increasing use of inhaled bronchodilators, subject not improving on enhanced home therapy. For patients requiring a daily controller medication, regularly assess level of asthma control based on a standard clinical instrument (e.g., pediatric asthma control test [P-ACT], the Asthma Therapy Assessment Questionnaire for children and adolescents [the pediatric ATAQ]). If asthma not well controlled, consider increasing level of daily controller medication. �
Diet
- Avoid foods or food additives (if truly allergic).
- Food-induced asthma is uncommon.
Patient Education
Activity �
- Most patients with asthma can participate fully in sports, even at a high level, with close follow-up. Extra medications such as albuterol and/or cromolyn may be required before vigorous exercise. All athletes should have their quick-relief medications on hand at all times.
- Athletes with asthma may need to report their medications to the governing bodies of their sport.
Prognosis
With proper therapy and good adherence to treatment regimen: excellent �
Complications
Morbidity: frequent hospitalizations and absence from school. Psychological impact of having a chronic illness. Decline in lung function over time �
Additional Reading
- Allen �JL, Bryant-Stephens �T, Pawlowski �NA. The Children's Hospital of Philadelphia Guide to Asthma. Philadelphia: Wiley-Liss; 2004.
- Bush �A, Saglani �S. Management of severe asthma in children. Lancet. 2010;376(9743):814-825. �[View Abstract]
- Ducharme �FM, Ni Chroinin �M, Greenstone �I, et al. Addition of long-acting beta2-agonists to inhaled corticosteroids versus same dose inhaled corticosteroids for chronic asthma in adults and children. Cochrane Database Syst Rev. 2010;(5):CD005535. �[View Abstract]
- Halken �S, Lau �S, Valovirta �E. New visions in specific immunotherapy in children: an iPAC summary and future trends. Pediatr Allergy Immunol. 2008;19(Suppl 19):60-70. �[View Abstract]
- Hedlin �G, Konradsen �J, Bush �A. An update on paediatric asthma. Eur Respir Rev. 2012;21(125):175-185. �[View Abstract]
- Kercsmar �CM. Current trends in management of pediatric asthma. Respir Care. 2003;48(3):194-205; discussion 205-208. �[View Abstract]
- Liu �AH, Szefler �SJ. Advances in childhood asthma: hygiene hypothesis, natural history, and management. J Allergy Clin Immunol. 2003;111(3)(Suppl):S785-S792. �[View Abstract]
- Mahr �TA, Malka �J, Spahn �JD. Inflammometry in pediatric asthma: a review of fractional exhaled nitric oxide in clinical practice. Allergy Asthma Proc. 2013;34(3):210-219. �[View Abstract]
- National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the diagnosis and management of asthma. NIH-NHLBI publication. Washington, DC: U.S. Government Printing Office; August 2007.
- Reid �MJ. Complicating features of asthma. Pediatr Clin North Am. 1992;39(6):1327-1341. �[View Abstract]
- Salvatoni �A, Piantanida �E, Nosetti �L, et al. Inhaled corticosteroids in childhood asthma: long-term effects on growth and adrenocortical function. Paediatr Drugs. 2003;5(6):351-361. �[View Abstract]
- Silverstein �MD, Mair �JE, Katusic �SK, et al. School attendance and school performance: a population-based study of children with asthma. J Pediatr. 2001;139(2):278-283. �[View Abstract]
- Stempel �DA. The pharmacologic management of childhood asthma. Pediatr Clin North Am. 2003;50(3):609-629. �[View Abstract]
Codes
ICD09
- 493.90 Asthma,unspecified type, unspecified
- 493.92 Asthma, unspecified type, with (acute) exacerbation
- 493.81 Exercise induced bronchospasm
- 493.00 Extrinsic asthma, unspecified
ICD10
- J45.909 Unspecified asthma, uncomplicated
- J45.901 Unspecified asthma with (acute) exacerbation
- J45.990 Exercise induced bronchospasm
SNOMED
- 195967001 Asthma (disorder)
- 281239006 Exacerbation of asthma (disorder)
- 31387002 Exercise-induced asthma (disorder)
- 389145006 allergic asthma (disorder)
FAQ
- Q: Will my child outgrow his or her asthma?
- A: Family history and allergies affect the ultimate outcome. Wheezing during the 1st 3 years of life is extremely common, with 40-50% of all children wheezing at some time. Many of these children do not develop asthma and "outgrow"� their illness by school age. Some patients develop asthma again as young adults.
- Q: Can my child become dependent on asthma medications?
- A: Children do not become "dependent"� on these medications as they would with narcotic agents. Daily asthma medications are required to maintain airway patency and to control airway inflammation.
- Q: Will my child be on medications for the rest of his or her life?
- A: This depends on the severity of the asthma. The types, doses, and frequency of asthma medications will change over a patient's lifetime.