Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU
Asthma is the most common chronic respiratory disease, affecting up to 10% of adults and 30% of children (JACI, 2011).
Dust mites play a major role in asthma pathogenesis.
Bronchial provocation with particles: dust mite fecal particles are 30 µm in diameter (same size as pollen grain). They do not stay airborne and do not cause allergic comjunctivitis. Pollen grains are airborne, have spicules and cause 90% of allergic conjunctivitis cases.
10% of inhaled pollen grains and mite fecal particles enter lungs. Dust mite fecal particles and pollen grains are 1000 times larger than penicillin spores. A single mite fecal particle will produce a small focus of inflammation in lung.
Not all wheezing is asthma
Wheezing occurrences in children:
- single episode in 30% to 50% of children before 5 yr of age
- 40% who wheeze before 3 yr of age continue at 6 yr (“persistent wheezers”)
- 50% of infants who wheeze once will wheeze again within several months
Wheezing in Children - Phenotypes (click to enlarge the image).
Childhood asthma phenotypes:
- transient early wheezers - wheeze sometime during first year of life; risk factors include prematurity, history of parental smoking during pregnancy, and passive exposure to tobacco smoke; such patients do not respond to inhaled bronchodilators or inhaled corticosteroids (ICS); wheezing tends to remit as child’s airway gets larger (between ages 2-3 yr)
- nonatopic wheezers - 0 to 6 yr of age; wheeze associated exclusively with viral infection; usually no eczema or family history; wheezing tends to remit by 6 yr of age
- atopic wheezers - past 5 yr of age, allergic - have positive blood and skin testing to inhalant allergens; tend to present within 2 to 3 yr of age, and continue to wheeze; wheezing not related to URTI
Childhood asthma phenotypes (click to enlarge the image).
A 2012 study described 2 "new" phenotypes for young children with wheezing: "boys atopic multiple-trigger" and "girls nonatopic uncontrolled wheeze". JACI, 2012.
Toward a definition of asthma phenotypes in childhood: early viral wheezers, multitrigger wheezers (MTWs), and nonatopic uncontrolled wheezers (NAUWs). Some children have “allergic bronchitis” rather than “asthma”. JACI, 2012.
Modified Asthma Predictive Index (API):
Children under the age of 3 with ALL of the following:
- 4 wheezing exacerbations in past year
- with one physician-confirmed episode
- plus one major criteria OR 2 minor criteria
Major criteria - 1 of the following:
- parental history (mother who had childhood asthma only, father with exercise-induced asthma)
- physician-diagnosed atopic eczema
-allergic sensitization to one aeroallergen
Minor criteria - 2 of the following:
- allergic sensitization to milk, eggs, or peanuts (positive skin or blood test sufficient)
- wheezing unrelated to respiratory illness (ie, cold)
- blood eosinophilia 4% of total white blood cell (WBC) count
Positive API = 10 times more likely to have persistent asthma.
Modified Asthma Predictive Index (mAPI) (click to enlarge the image). A positive mAPI greatly increased future asthma probability (eg, 30% pretest probability to 90% posttest probability) http://buff.ly/ZJfMgQ
mAPI relies heavily on wheezing. However, asthma can occur in children without wheezing.
Chronic, persistent cough - without wheezing - may be the only manifestation of asthma. More than 60% bronchial obstruction is needed to produce wheezing - asthma can occur without wheezing - spirometry is required for diagnosis.
Cough-variant asthma presents as dry cough at night. It worsens with exercise (EIA) and nonspecific triggers (cold air).
Cough-variant asthma responds to asthma therapy with ICS.
Cough-variant asthma is diagnosed with pulmonary function testing (PFTs) with response to bronchodilator.
The most common cause of chronic cough in children is cough-variant asthma.
National Heart, Lung, and Blood Institute (NHLBI) guidelines for diagnosis and management of asthma (2007) are only available online. Key concepts:
- severity dictates therapy
- distinction between intermittent and persistent asthma - "rule of 2s”
- 4 levels of asthma severity - intermittent; 3 sublevels of persistent
- inhaled corticosteroids (ICS) preferred for all levels of persistent asthma
- use of asthma action plans
- spirometry recommended
Rule of 2s - if symptoms are present for more than 2 days per week or for more than 2 nights per month, asthma categorized as persistent. Within this category, disease must be classified as mild, moderate, or severe. However, as severity of asthma not constant, must monitor patients for changes; as severity changes, therapy should change too.
The category of “mild intermittent” asthma was eliminated in the 2007 guidelines - now it is just called “intermittent” asthma.
The concepts of “impairment”, “risk”, and “control” were introduced in the 2007 guidelines:
- impairment - refers to symptoms
- risk - refers to likelihood that the patient will eventually have exacerbation of asthma and present to emergency department (ED) or hospital, or need course of oral corticosteroids
- control - refers to the level of patient’s asthma control
ICS therapy probably does not make difference in prevention of airway remodeling.
Classification of asthma severity:
- impairment domain - daytime and nighttime symptoms (rule of 2's), use of short-acting beta-agonist (SABA), interference with normal activities
- risk domain - number of exacerbations per year (if more than 2, daily controller medication is needed). Increased risk is conferred by parental history of asthma or history of eczema.
Childhood Asthma Control Test (ACT) is validated down to age 4 yr. Adult ACT questionnaire should be used for teenagers (cutoff age is 11 years).
- step 1 - SABA as needed
- step 2 - low-dose ICS monotherapy vs. leukotriene receptor antagonist (LTRA)
- step 3 - low-to-medium dose ICS plus long-acting beta-agonist (LABA)
- step 4 - high-dose ICS therapy plus LABA and (if needed) systemic corticosteroids. Omalizumab (Xolair; anti-IgE antibody) is prescribed before placing patient on daily oral corticosteroids.
"Rule of 2s” is used to determine level of control. If any of these are positive, consider a daily controller medication:
- daytime symptoms more than 2 days/wk
- rescue β2 -agonist use more than 2 times per week
- nighttime symptoms more than 2 nights/mo
- more than 2 asthma exacerbations per year
- more than 2 rescue β2-agonist canisters/yr
When to step down therapy?
If patient is well-controlled for 3 months, consider stepping down therapy.
When to step up therapy?
If the patient is not well-controlled, step up therapy and re-evaluate in 2 to 6 weeks. If the patient is very poorly controlled, step up therapy 2 steps, consider short course of steroids, and reassess in 2 weeks.
There was an increase in the use of preventive asthma medication from 18% in 1988–1994 to 35% in 2005–2008 among children with asthma (Pediatrics, 2012).
Which ICS to choose?
- delivery system best for patient’s developmental stage
- optimal lung deposition
Particle size may play a role in lung deposition of ICS - ciclesonide (Alvesco) has smaller particle size that results in good lung deposition.
When to consider long-term ICS treatment:
- positive API and more than 3 wheezing episodes in previous 12 mo lasting more than 1 day and affecting sleep
- consistent requirement for SABA treatment (more than 2 times/wk, on average, over 1-2 mo); 2 exacerbations in 6 mo requiring oral corticosteroids
As severity increases, increase ICS dose:
Children younger than 5
- budesonide inhalation suspension (Pulmicort Respules)
- fluticasone propionate (Flovent)
- mometasone tripattern inhaler (Asmanex Twisthaler)
Children 5 to 11 yr of age
- low-dose ICS (budesonide dry powder inhaler (DPI) or inhalation suspension (Pulmicort Respules)
- beclomethasone hydrofluoroalkane (HFA)
- add long-acting β agonist (LABA) or leukotriene receptor antagonists (LTRA)
ICS treatment options for pediatric asthma (click to enlarge the image).
Asthma Inhalers (click to enlarge the image).
Inhaled corticosteroid (ICS)
Relative binding affinity for glucocorticoid receptor (GR): mometasone > fluticasone > budesonide > triamcinolone.
Relative anti-inflammatory potency: mometasone = fluticasone > budesonide = beclomethasone > triamcinolone.
Severe asthma - differential diagnosis and management (click to enlarge the image).
Algorithm for the diagnosis and management of early childhood asthma, JACI, 2012:
New NHLBI guidelines for asthma: is anything really new? Michael J. Welch, MD. Audio-Digest Pediatrics, Volume 56, Issue 01, January 7, 2010.
Advances in pediatric asthma in 2010: Addressing the major issues. Szefler SJ. J Allergy Clin Immunol. 2011 Jan;127(1):102-15.
Immunopathogenesis of Asthma in Childhood. Thomas A.E. Platts-Mills. Audio-Digest Pediatrics, Volume 55, Issue 02, January 21, 2009.
Asthma management update. Hary T. Katz, MD. Audio-Digest Pediatrics, Volume 55, Issue 02, January 21, 2009.
The Asthma Predictive Index: A very useful tool for predicting asthma in young children. Jose A. Castro-Rodriguez. JACI, 2010.
Predicting the long-term prognosis of children with symptoms suggestive of asthma at preschool age. J Allergy Clin Immunol. 2009.
The Asthma Predictive Index: Not a useful tool in clinical practice. J Allergy Clin Immunol. 2010.
A clinical index to define risk of asthma in young children with recurrent wheezing. Castro-Rodriguez JA, Holberg CJ, Wright AL, Martinez FD. Am J Respir Crit Care Med. 2000;162:1403–1406.
Patterns of fetal and infant growth are related to atopy and wheezing disorders at age 3 years - Thorax http://goo.gl/UGB8a
Inhaled steroids can suppress growth of children who are 2 years of age weighing less than 15 kg (high dose per kg). AAAAI, 2011.
Compared with low doses, moderate doses of ICS may not have benefits in asthmatic children. Pediatrics, 2010. Doubtful conclusion.
Asthma Predictive Index not better than simple prediction based only on preschool wheeze? (performance was low for both). JACI, 2011.
Achieving control of asthma in preschoolers. CMAJ, March 9, 2010; 182 (4).
House dust mite sensitization in toddlers predicts wheeze at age 12 years (JACI, 2011).
Timeline of Major Advances in Treatment of Asthma from 1812 through 2012 - NEJM, 2012.