The first wheezing episode: prognostic factors?

Rodríguez-Martínez CE, et al. Factors predicting persistence of early wheezing through childhood and adolescence: a systematic review of the literature. J Asthma Allergy. 2017 Mar 27;10:83-98.

Parental asthma (especially maternal), parental allergy, eczema, allergic rhinitis, persistent wheezing, wheeze without colds, exercise-induced wheeze, severe wheezing episodes, allergic sensitization (especially polysensitization), eosinophils (blood or eosinophil cationic protein in nasal sample), and fraction of exhaled nitric oxide were risk factors predicting persistence of early wheezing through school age. All of them are included in conventional algorithms, for example, Asthma Predictive Index and its modifications, for predicting future asthma.

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EBM Review: Antidepressant use during pregnancy and asthma in the offspring.

Liu X, Olsen J, Pedersen LH, et al. Antidepressant use during pregnancy and asthma in the offspring. Pediatrics. 2015 Apr;135(4):e911-7.

BACKGROUND AND OBJECTIVES: It has been suggested that maternal depression during pregnancy is associated with asthma in the offspring, but the role of medical treatment of depression is not known. Our goal was to examine whether prenatal antidepressant use increases the risk of asthma in the offspring.

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Heliox therapy for asthma

El-Khatib MF, et al. Effect of heliox- and air-driven nebulized bronchodilator therapy on lung function in patients with asthma. Lung. 2014 Jun;192(3):377-83.

“In conclusion, for asthmatic patients with baseline FEV1 ≤50 %, albuterol nebulized with heliox (80:20) leads to more significant improvements in spirometry measurements
when compared to albuterol nebulized with air. This is likely due to the low-density gas improving albuterol deposition in the distal airways. However, heliox-driven nebulization of albuterol might not provide significant improvements in spirometry measurements and any other clinical benefits over air-driven bronchodilation in stable asthmatic patients with baseline FEV1 >150 %. Heliox-driven nebulized bronchodilator use may be considered for reversibility testing in asthmatics with baseline FEV1 <50 %.”

Rodrigo GJ, Castro-Rodriguez JA. Heliox-driven β2-agonists nebulization for children and adults with acute asthma: a systematic review with meta-analysis. Ann Allergy Asthma Immunol. 2014 Jan;112(1):29-34.

“This review suggests that heliox benefits in airflow limitation and hospital admissions could be considered clinically significant. Data support the use of heliox as a nebulizing β2-agonist driving gas in the routine care of patients with acute asthma.”

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EBM Review: Comparative efficacy of oral dexamethasone versus oral prednisone in acute pediatric asthma.

Qureshi F, Zaritsky A, Poirier MP. Comparative efficacy of oral dexamethasone versus oral prednisone in acute pediatric asthma. J Pediatr. 2001 Jul;139(1):20-6.

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OBJECTIVE: The objective was to determine whether 2 days of oral dexamethasone (DEX) is more effective than 5 days of oral prednisone/prednisolone (PRED) in improving symptoms and preventing relapse in children with acute asthma.

STUDY DESIGN: This was a prospective randomized trial of children (2 to 18 years old) who presented to the emergency department with acute asthma. PRED 2 mg/kg, maximum 60 mg (odd days) or DEX 0.6 mg/kg, maximum 16 mg (even days) was used. At discharge children in the PRED group were prescribed 4 daily doses (1 mg/kg/d, maximum 60 mg); children in the DEX group received a prepackaged dose (0.6 mg/kg, maximum 16 mg) to take the next day. The primary outcome was relapse within 10 days.

RESULTS: When DEX was compared with PRED, relapse rates (7.4% of 272 vs 6.9% of 261), hospitalization rates from the emergency department (11% vs 12%) or after relapse (20% vs 17%), and symptom persistence at 10 days (22% vs 21%) were similar. In the PRED group more children were excluded for vomiting in the emergency department (3% vs 0.3%; P =.008), more parents were noncompliant (4% vs. 0.4%; P =.004), and more children missed > or =2 days of school (19.5% vs. 13.2%; P =.05).

CONCLUSION: In children with acute asthma, 2 doses of dexamethasone provide similar efficacy with improved compliance and fewer side effects than 5 doses of prednisone.

Reviewed by Rebecca Sanders, MD and Young Shim, MD

Main Points:

  • For pediatric patients presenting with status asthmaticus (requiring at least 2 nebulized albuterol treatments) no significant difference in relapse rates were noted between 2 days of dexamethasone (0.6 mg/kg) vs 5 days of prednisone (2 mg/kg x 1 then 1 mg/kg x 4 more days) treatment groups
  • People were however more compliant in taking 2 days of dexamethasone compared to PRED (although this did not effect relapse rate)
  • Dexamethasone treatment group were less likely to miss ≥ 2 days of school compared to prednisone group
  • Children were more likely to vomit prednisone (though this analysis was from excluded group)

Practice Based Learning: In which asthmatic children should we start PEP on admission, and in which children do we not need to start PEP?

Lauren Levy, MD

Presented by Lauren Levy, MD
Resident, Department of Pediatrics
Emory University

Key Points:

  • Use of PEP in combination with nebulized bronchodilators is useful in increasing delivery and distribution (as evidenced by a study utilized scintigraphy) of the drug in an outpatient setting, and may be extrapolated to have benefits in the acute care setting as well.
  • Other types of NiPPV (such as BIPAP) have been shown to improve outcomes in acute presentations in asthmatics, likely by stenting airways and improving drug delivery, along with decreasing atelectasis and air trapping. This has been shown to decrease length of ICU stays as well as to lower the mean dose of the bronchodilator needed.
  • More studies need to be conducted to look at the use of PEP with bronchodilators specifically in the ED and inpatient setting to evaluate its potential benefits.


Alcoforado L, Brandão S, Rattes C, Brandão D, Lima V, Ferreira Lima G, Fink JB, Dornelas de Andrade A. Evaluation of lung function and deposition of aerosolized bronchodilators carried by heliox associated with positive expiratory pressure in stable asthmatics: A randomized clinical trial. Respir Med. 2013 May 8. PMID: 23664767.

Brandao DC, Lima VM, Filho VG, Silva TS, Campos TF, Dean E, de Andrade AD. Reversal of bronchial obstruction with bi-level positive airway pressure and nebulization in patients with acute asthma. J Asthma. 2009 May;46(4):356-61. PMID: 19484669.

Gupta D, Nath A, Agarwal R, Behera D. A prospective randomized controlled trial on the efficacy of noninvasive ventilation in severe acute asthma. Respir Care. 2010 May;55(5):536-43. PMID: 20420722.

Schramm CM, Carroll CL. Advances in treating acute asthma exacerbations in children. Curr Opin Pediatr. 2009 Jun;21(3):326-32. PMID: 19387346.

Slats AM, Janssen K, de Jeu RC, van der Plas DT, Schot R, van den Aardweg JG, Sterk PJ. Enhanced airway dilation by positive-pressure inflation of the lungs compared with active deep inspiration in patients with asthma. J Appl Physiol. 2008 Dec;105(6):1725-32. PMID: 18801966.

Practice Based Learning: Evidence for the use of anticholinergic therapy in pediatric acute asthma exacerbation

Kristina Betters, MD

Presented by Kristina Betters, MD

Clinical Question:

Does Atrovent (ipratropium bromide) improve outcomes in pediatric acute asthma exacerbation?

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Practice Based Learning: Are there any benefits to using dexamethasone vs. prednisone in treatment of acute asthma exacerbations?

Mahnaz Faroqui, MD

Presented by Mahnaz Faroqui, MD

Key Points:

  1. No difference in rates of hospitalization between patients treated with dexamethasone vs prednisone
  2. Better compliance rates with oral dexamethasone than with oral prednisone
  3. Dexamethasone predicted to be more cost-effective by  improving compliance, thus leading to fewer re-admissions to the hospital

Bottom Line:

Oral dexamethasone increases compliance with steroids for acute asthma exacerbations and has been shown to be equally as effective. The main difficulty in administering this medicine is its lack of availability in an oral formulation.


Altamimi, Saleh. Et Al. “Single-Dose Oral Dexamethasone in the Emergency Management of Children With Exacerbations of Mild to Moderate Asthma.” Pediatric Emergency Care. 22 (12), Dec 2006, 786-793.

Bhogal, Sanjit K. “A question of time: systemic corticosteroids in managing acute asthma in children.” Current Opinion in Pulmonary Medicine. Volume 19(1) Jan 2013 p 73-78.

Cronin, John. Et, al. “Single dose oral dexamethasone versus multi-dose prednisolone in the treatment of acute exacerbations of asthma in children who attend the emergency department: study protocol for a randomized controlled trial.” Trials. 2012; 13: 141.

Gordon, Stephen. Et, al. “Randomized Trial of Single-Dose Intramuscular Dexamethasone Compared With Prednisolone for Children With Acute Asthma.” Pediatric Emergency Care. 23(8), August 2007, 521-527.

Williams, Kelli W. et al. “Parental Preference for Short- Versus Long-Course Corticosteroid Therapy in Children With Asthma Presenting to the Pediatric Emergency Department.”  Clinical Pediatrics. Jan 2013. 52(1), 30-34.

Diagnosis of wheezing in children

Respiratory Noises: How Useful are They Clinically? (2009)

“Although clinicians place considerable weight on the identification of the various forms of noisy breathing, there are serious questions regarding both the accuracy (validity) and the reliability (repeatability) of these noises. To avoid diagnostic errors, clinicians need to consider the whole constellation of symptoms and signs, and not focus on the specific “type” of noise. Given the high error rate with “parent-reported wheeze” there is a need to reexamine the extensive literature on the epidemiology of wheeze in infants and young children, because parent-reported wheeze is unconfirmed by a clinician. It is obvious we need more high-quality research evidence to derive better evidence on the clinical utility of these noises, and their natural history.”

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Differential diagnosis and treatment of wheezing and asthma in young children. (2008)

“Establishing a diagnosis of asthma in young wheezing patients can be challenging because the type, severity, and frequency of asthma signs and
symptoms vary widely among, and sometimes within, individual children. Knowing when and how to treat episodic wheeze, assessing the risk of asthma progression in wheezing patients, choosing the most
effective controller regimen in patients once asthma is diagnosed, and deciding when to terminate controller therapy also can be difficult decisions for physicians. This review provides literature-based and clinical experience-based recommendations for the management of wheeze and diagnosis and management of asthma in young children.”

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The diagnosis of wheezing in children. (2008)

“Wheezing in children is a common problem encountered by family physicians. Approximately 25 to 30 percent of infants will have at least one wheezing episode, and nearly one half of children have a history of wheezing by six years of age. The most common causes of wheezing in children include asthma, allergies, infections, gastroesophageal reflux disease, and obstructive sleep apnea. Less common causes include congenital abnormalities, foreign body aspiration, and cystic fibrosis. Historical data that help in the diagnosis include family history, age at onset, pattern of wheezing, seasonality, suddenness of onset, and association with feeding, cough, respiratory illnesses, and positional changes. A focused examination and targeted diagnostic testing guided by clinical suspicion also provide useful information. Children with recurrent wheezing or a single episode of unexplained wheezing that does not respond to bronchodilators should undergo chest radiography. Children whose history or physical examination findings suggest asthma should undergo diagnostic pulmonary function testing.”

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The wheezing infant: diagnosis and treatment. (2003)

1. Describe the natural history of the wheezing infant once other underlying causes of wheezing have been ruled out.

2. Determine factors that can be determined on history that increase the risk of persistent asthma in a wheezing infant.

3. In children with an increased risk for persistent asthma, describe factors that have been associated with a better response to inhaled corticosteroids.

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Practice Based Learning: Is there a difference in clinical outcomes using MDI + spacer vs. nebulizer in management of acute asthma exacerbation?

Bhavya Doshi

Presented by Bhavya Doshi, MD. 

Key Points:

  1. Children > 5 years should be on an MDI + spacer for asthma treatment.
  2. Children < 5 years can be treated with an MDI + spacer instead of nebulized albuterol.
  3. In the ED setting, MDIs reduced the clinical asthma score and hospital admission rate.
  4. Children 1-24 months of age may respond to an MDI + spacer as well as they respond to nebulized albuterol.

Bottom Line:

Nebulized albuterol is no better than MDI with spacer for management of acute asthma exacerbation.  In fact, MDIs might result in better outcomes (LOS, hospital admission rate, clinical asthma score).


Closa RM, Ceballos JM, Gómez-Papí A, Galiana AS, Gutiérrez C, Martí-Henneber.  C. Efficacy of bronchodilators administered by nebulizers versus spacer devices in infants with acute wheezing. Pediatr Pulmonol. 1998 Nov;26(5):344-8.

Castro-Rodriguez, JA.  Rodrigo, GJ.  b-Agonists through metered dose inhaler with valved holding chamber versus nebulizer for acute exacerbation of wheezing or asthma in children under 5 years of age: a systematic review with meta-analysis.  J Pediatr 2004; 145: 172-7.