Pediatric Asthma (Nursing)


Learning Outcome

  • Review etiology and epidemiology of pediatric asthma
  • Consider important history and physical exam findings in childhood asthma
  • List treatment options both for chronic management and acute exacerbations 

Introduction

Asthma is a chronic inflammatory disease of the airways, characterized by recurrent episodes of airflow obstruction resulting from edema, bronchospasm, and increased mucus production. The degree of reversibility of airflow obstruction with bronchodilators can vary.[1]

Patients who have asthma may experience a range of respiratory symptoms, such as wheezing, shortness of breath, cough, and chest tightness. There is a wide range in the frequency and severity of the symptoms, but uncontrolled asthma and acute exacerbations can lead to respiratory failure and death.[1]

Nursing Diagnosis

  • Ineffective breathing pattern
  • Ineffective airway clearance
  • Deficient knowledge
  • Anxiety
  • Activity intolerance
  • Health-seeking behaviors: prevention of asthma attack
  • Interrupted family processes

Causes

The exact etiology of asthma remains unclear and appears to be multifactorial. Both genetic and environmental factors seem to contribute. Positive family history is a risk factor for asthma but is neither necessary nor sufficient for the development of the disease. Multiple environmental exposures, both prenatal and during childhood, are associated with the development of asthma. [2][3]

Risk Factors

Currently, asthma prevalence in the United States is 7.8 % (1) down from 8.4% in 2010.  National surveillance data shows that prevalence varies by age, gender, race, ethnicity, geographic location, and socioeconomic status.[2] See Table 1.

Table 1:  Factors affecting Asthma Prevalence

Factor                                                           Prevalence

Age                                                              Children >. Adults

Gender                                                         Overall Females> males but varied by age   

                                                                     (children:  boys > girls and in adults: women > men)

Race                                                             African American > Caucasian

Ethnicity                                                       Hispanic > Non-Hispanic

Geographic Location                                      Northeastern US > South or Western US

Socioeconomic status                                    Low SES > High SES

Source:  Moorman, JE et al. 2012

In a more recent pediatric study, Akinbami et al. examined trends in asthma prevalence in U.S. children ages 0 to 17 years and noted a plateau after 2009 followed in 2013 by an overall decline in pediatric asthma prevalence. However, subgroups with increasing prevalence were identified, notably in 10-17-year-olds, those living in the southern U.S. and among the poor.[3]

Assessment

Classic Symptoms

Classic symptoms of asthma include cough, wheezing, chest tightness, and shortness of breath. Symptoms are often episodic and can become triggered by numerous factors, including upper respiratory tract infections, exercise, exposure to allergens, and airway irritants such as tobacco smoke. They may also be worse at night.

Physical Examination

The physical examination should focus on three main areas, which will help to develop your differential diagnosis and identify comorbid conditions.  These are the general state of nutrition and body habitus, signs of allergic disease, and signs of airway dysfunction. The physical examination may be completely normal. Features such as digital clubbing, barrel chest, localized wheezing, eczema will suggest other diagnoses or comorbid conditions. 

Making the Diagnosis of Asthma

A diagnosis of asthma should be considered when any of the following key indicators are present: 

  • Wheezing

  • History that includes recurrent episodes of cough, wheezing, difficulty breathing or chest tightness

  • Symptom triggers may include: Upper respiratory tract infections, exercise, exposure to furry animals, dust, mold, tobacco smoke, aerosols among others

  • Symptoms may disrupt sleep

Evaluation

In children over five years of age and adults, pre and post-bronchodilator spirometry can help confirm the diagnosis. Spirometry is a non-invasive, objective test that can be performed in the office setting and is recommended in the EPR 3 guideline as to the preferred lung function test to assign asthma severity.

The baseline spirometry provides the following information FVC (forced vital capacity), FEV1 (forced expiratory volume at 1 sec.),  FEV1/FVC, and F25 to 75 (the difference between the forced expiratory volume at 25% and 75%). Assessment of the bronchodilator response begins with the baseline spirometry followed by the administration of a short-acting bronchodilator (most commonly, albuterol 2 to 4 puffs in adults and older children). According to the ATS/ERS guidelines, reversibility is significant when there is an over 12% improvement from baseline or an increase of greater than 200 ml in FEV1.  In patients who do not demonstrate a significant bronchodilator response and in whom you continue to have a clinical suspicion of asthma, a 2 to 3 week trial of an oral corticosteroid may be a consideration.[4]

Medical Management

STEP Therapy for Asthma

The following discussion will highlight the step therapy proposed by EPR-3. 

The preferred treatment option for intermittent asthma, as well as for quick relief of asthma symptoms and the prevention of exercise-induced bronchoconstriction is a short-acting beta-2 agonist. This is referred to as STEP 1. Albuterol and levalbuterol are examples of short-acting bronchodilators. They have a quick onset of action, within 5 to 15 minutes, and a duration of action of 4 to 6 hours. Their administration is most often by nebulizer or inhaler.

STEPS 2-6 refer to options for persistent asthma. In each of these steps, inhaled corticosteroids are a component of the preferred treatment regimen.

The preferred treatment for step 2 is a low-dose inhaled corticosteroid (ICS). Montelukast can be an alternative. Montelukast is a leukotriene receptor antagonist available in 4 mg granules, or 4 mg and 5 mg chewable tablets, as well as in a 10 mg tablet formulation. Single evening dosing prescribing is by age and FDA approved for asthma control from 12 months of age.

The preferred option for step 3 is a medium dose ICS in the 0 to 4-year-old children. In the 5 to 11 year age group, the preferred option is either a medium-dose ICS or a combination ICS + long-acting beta-agonist (LABA) or leukotriene receptor antagonist (LTRA). For those ages 12 years through adulthood, the preferred choice is a low dose of ICS + LABA or medium-dose ICS. There was a black-box warning on LABAs due to concerns about increasing deaths in patients taking LABAs; however, according to more recent studies, LABAs demonstrated safety when combined with inhaled corticosteroids. LABA monotherapy is indeed associated with an increase in asthma-related mortality and serious adverse events. 

Step 4 in the 0 to 4-year-old age range is a medium dose ICS + either a LABA or montelukast. In ages, 5 to 11 years and 12 and above, a medium dose ICS + LABA is the preferred option.  

Step 5 for 0-4 years is high dose ICS + either LABA or montelukast; in 5-11 years and 12 and above, a high dose ICS + LABA. EPR-3 also recommends consideration of omalizumab for ages 12 and above. Since the publication of these guidelines, Omalizumab has received FDA approval for ages 6 years and above. Omalizumab is a monoclonal antibody indicated for moderate to severe persistent asthma with objective evidence of perennial aeroallergen sensitivity and inadequate control with ICS.

Step 6 for ages 0-4 years is a high dose ICS + either LABA or montelukast or oral corticosteroids; for ages 5-11 years – high dose ICS + LABA + oral systemic corticosteroid; and for ages 12 and up, high dose ICS + LABA + oral corticosteroid are preferred. Omalizumab may be a consideration for appropriate patients with allergy.

Theophylline is a medication that may be an alternative medication in Steps 2 through 6. However, its use requires caution due to its narrow therapeutic range and potential side effects, including diuresis, tremors, and headaches.[5] 

Asthma action plans are recommended for all patients with asthma. These are individualized to and developed in partnership with each patient. They include detailed directions on how to manage asthma with instructions for when the patient is well, beginning to feel symptoms, and in an acute exacerbation that necessitates medical evaluation.[4]

EPR 3 provides guidance for referrals to an asthma specialist. While their recommendations are based on step therapy in different age groups, e.g. step 3 for ages 0 to 4 years and step 4 for those 5 years and older with the flexibility to request a consultation for step 2 in 0 to 4 years and step 3 in ages 5 and older, I find the following listing very helpful. Referrals to an asthma specialist should merit consideration whenever the diagnosis is in question, for specialized testing (e.g., PFTs, allergen skin testing, etc.) or specialized treatment is needed (e.g., allergy shots, anti-IgE medication, etc.), when asthma symptoms are not well controlled and when additional education is necessary.[4]

Nursing Management

Management of Acute Exacerbations

Initial management of a child who presents to the emergency department with an acute asthma exacerbation includes bronchodilators and steroids.

Albuterol:

2.5 - 5 mg of nebulized albuterol should be given as initial management and can be re-dosed every 20 minutes. If the child is 5 years or older, 5 mg is the recommended dose. If a child is experiencing significant respiratory distress and is declining between doses, it may be re-dosed more frequently, or continuous nebulization of albuterol may be required. 

Ipratropium:

Dosing of 250 to 500 mcg of ipratropium should be co-administered with albuterol for three doses in moderate to severe exacerbations.[6] 

Corticosteroids:

Oral and IV steroids have been demonstrated to have equivalent potency in treating acute asthma exacerbations. Patients should be given prednisolone PO or methylprednisolone IV 1 to 2 mg/kg/day or dexamethasone 0.6 mg/kg PO or IV depending on their level of respiratory distress and ability to swallow. Dexamethasone has been shown non-inferior to a short course of prednisone or prednisolone for an acute exacerbation.[7]

Supplemental oxygen can be applied to maintain oxygen saturation above 90 to 92%, and heliox can be considered to aid in delivering oxygen to lower airways. If patients have been treated with all of the above and still are experiencing respiratory distress, non-invasive positive pressure ventilation should be started as it may alleviate muscle fatigue and assist in maximizing inspiration.

When To Seek Help

Patients who are not improving with nebulized treatments or are becoming more somnolent warrant escalation of care.

Health Teaching and Health Promotion

Older children with asthma should be warned against smoking and exposure to environments that trigger attacks.

Discharge Planning

All children with asthma should have an asthma action plan updated at every office visit and revisited at any emergent or unscheduled visit. [4]

Pearls and Other issues

Pitfalls:

  • Asthma can be diagnosed at any age. 
  • There is a broad and diverse differential diagnosis for wheezing in children.



(Click Image to Enlarge)
<p>Pathophysiology of Asthma

Pathophysiology of Asthma. Figure A displays the location of the lungs and airways in the body. Figure B shows a cross section of a normal airway. Figure C illustrates a cross section of an airway during asthma symptoms


National Institutes of Health

Details

Nurse Editor

Chaddie Doerr

Editor:

Sara Cortes

Updated:

5/4/2024 3:43:33 AM

References

[1]

Vonk JM, Postma DS, Boezen HM, Grol MH, Schouten JP, Koëter GH, Gerritsen J. Childhood factors associated with asthma remission after 30 year follow up. Thorax. 2004 Nov:59(11):925-9     [PubMed PMID: 15516465]

[2]

Stern DA, Morgan WJ, Halonen M, Wright AL, Martinez FD. Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study. Lancet (London, England). 2008 Sep 20:372(9643):1058-64. doi: 10.1016/S0140-6736(08)61447-6. Epub     [PubMed PMID: 18805334]

[3]

Matricardi PM, Illi S, Grüber C, Keil T, Nickel R, Wahn U, Lau S. Wheezing in childhood: incidence, longitudinal patterns and factors predicting persistence. The European respiratory journal. 2008 Sep:32(3):585-92. doi: 10.1183/09031936.00066307. Epub 2008 May 14     [PubMed PMID: 18480107]

[4]

Bisgaard H, Bønnelykke K. Long-term studies of the natural history of asthma in childhood. The Journal of allergy and clinical immunology. 2010 Aug:126(2):187-97; quiz 198-9. doi: 10.1016/j.jaci.2010.07.011. Epub     [PubMed PMID: 20688204]

[5]

Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), Cloutier MM, Baptist AP, Blake KV, Brooks EG, Bryant-Stephens T, DiMango E, Dixon AE, Elward KS, Hartert T, Krishnan JA, Lemanske RF Jr, Ouellette DR, Pace WD, Schatz M, Skolnik NS, Stout JW, Teach SJ, Umscheid CA, Walsh CG. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. The Journal of allergy and clinical immunology. 2020 Dec:146(6):1217-1270. doi: 10.1016/j.jaci.2020.10.003. Epub     [PubMed PMID: 33280709]

[6]

Meyers DA. Approaches to genetic studies of asthma. American journal of respiratory and critical care medicine. 1994 Nov:150(5 Pt 2):S91-3     [PubMed PMID: 7952602]

[7]

Moffatt MF, Kabesch M, Liang L, Dixon AL, Strachan D, Heath S, Depner M, von Berg A, Bufe A, Rietschel E, Heinzmann A, Simma B, Frischer T, Willis-Owen SA, Wong KC, Illig T, Vogelberg C, Weiland SK, von Mutius E, Abecasis GR, Farrall M, Gut IG, Lathrop GM, Cookson WO. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature. 2007 Jul 26:448(7152):470-3     [PubMed PMID: 17611496]

[8]

Torgerson DG, Ampleford EJ, Chiu GY, Gauderman WJ, Gignoux CR, Graves PE, Himes BE, Levin AM, Mathias RA, Hancock DB, Baurley JW, Eng C, Stern DA, Celedón JC, Rafaels N, Capurso D, Conti DV, Roth LA, Soto-Quiros M, Togias A, Li X, Myers RA, Romieu I, Van Den Berg DJ, Hu D, Hansel NN, Hernandez RD, Israel E, Salam MT, Galanter J, Avila PC, Avila L, Rodriquez-Santana JR, Chapela R, Rodriguez-Cintron W, Diette GB, Adkinson NF, Abel RA, Ross KD, Shi M, Faruque MU, Dunston GM, Watson HR, Mantese VJ, Ezurum SC, Liang L, Ruczinski I, Ford JG, Huntsman S, Chung KF, Vora H, Li X, Calhoun WJ, Castro M, Sienra-Monge JJ, del Rio-Navarro B, Deichmann KA, Heinzmann A, Wenzel SE, Busse WW, Gern JE, Lemanske RF Jr, Beaty TH, Bleecker ER, Raby BA, Meyers DA, London SJ, Mexico City Childhood Asthma Study (MCAAS), Gilliland FD, Children's Health Study (CHS) and HARBORS study, Burchard EG, Genetics of Asthma in Latino Americans (GALA) Study, Study of Genes-Environment and Admixture in Latino Americans (GALA2) and Study of African Americans, Asthma, Genes & Environments (SAGE), Martinez FD, Childhood Asthma Research and Education (CARE) Network, Weiss ST, Childhood Asthma Management Program (CAMP), Williams LK, Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE), Barnes KC, Genetic Research on Asthma in African Diaspora (GRAAD) Study, Ober C, Nicolae DL. Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nature genetics. 2011 Jul 31:43(9):887-92. doi: 10.1038/ng.888. Epub 2011 Jul 31     [PubMed PMID: 21804549]

[9]

Stein MM, Thompson EE, Schoettler N, Helling BA, Magnaye KM, Stanhope C, Igartua C, Morin A, Washington C 3rd, Nicolae D, Bønnelykke K, Ober C. A decade of research on the 17q12-21 asthma locus: Piecing together the puzzle. The Journal of allergy and clinical immunology. 2018 Sep:142(3):749-764.e3. doi: 10.1016/j.jaci.2017.12.974. Epub 2018 Jan 4     [PubMed PMID: 29307657]

[10]

Demenais F, Margaritte-Jeannin P, Barnes KC, Cookson WOC, Altmüller J, Ang W, Barr RG, Beaty TH, Becker AB, Beilby J, Bisgaard H, Bjornsdottir US, Bleecker E, Bønnelykke K, Boomsma DI, Bouzigon E, Brightling CE, Brossard M, Brusselle GG, Burchard E, Burkart KM, Bush A, Chan-Yeung M, Chung KF, Couto Alves A, Curtin JA, Custovic A, Daley D, de Jongste JC, Del-Rio-Navarro BE, Donohue KM, Duijts L, Eng C, Eriksson JG, Farrall M, Fedorova Y, Feenstra B, Ferreira MA, Australian Asthma Genetics Consortium (AAGC) collaborators, Freidin MB, Gajdos Z, Gauderman J, Gehring U, Geller F, Genuneit J, Gharib SA, Gilliland F, Granell R, Graves PE, Gudbjartsson DF, Haahtela T, Heckbert SR, Heederik D, Heinrich J, Heliövaara M, Henderson J, Himes BE, Hirose H, Hirschhorn JN, Hofman A, Holt P, Hottenga J, Hudson TJ, Hui J, Imboden M, Ivanov V, Jaddoe VWV, James A, Janson C, Jarvelin MR, Jarvis D, Jones G, Jonsdottir I, Jousilahti P, Kabesch M, Kähönen M, Kantor DB, Karunas AS, Khusnutdinova E, Koppelman GH, Kozyrskyj AL, Kreiner E, Kubo M, Kumar R, Kumar A, Kuokkanen M, Lahousse L, Laitinen T, Laprise C, Lathrop M, Lau S, Lee YA, Lehtimäki T, Letort S, Levin AM, Li G, Liang L, Loehr LR, London SJ, Loth DW, Manichaikul A, Marenholz I, Martinez FJ, Matheson MC, Mathias RA, Matsumoto K, Mbarek H, McArdle WL, Melbye M, Melén E, Meyers D, Michel S, Mohamdi H, Musk AW, Myers RA, Nieuwenhuis MAE, Noguchi E, O'Connor GT, Ogorodova LM, Palmer CD, Palotie A, Park JE, Pennell CE, Pershagen G, Polonikov A, Postma DS, Probst-Hensch N, Puzyrev VP, Raby BA, Raitakari OT, Ramasamy A, Rich SS, Robertson CF, Romieu I, Salam MT, Salomaa V, Schlünssen V, Scott R, Selivanova PA, Sigsgaard T, Simpson A, Siroux V, Smith LJ, Solodilova M, Standl M, Stefansson K, Strachan DP, Stricker BH, Takahashi A, Thompson PJ, Thorleifsson G, Thorsteinsdottir U, Tiesler CMT, Torgerson DG, Tsunoda T, Uitterlinden AG, van der Valk RJP, Vaysse A, Vedantam S, von Berg A, von Mutius E, Vonk JM, Waage J, Wareham NJ, Weiss ST, White WB, Wickman M, Widén E, Willemsen G, Williams LK, Wouters IM, Yang JJ, Zhao JH, Moffatt MF, Ober C, Nicolae DL. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks. Nature genetics. 2018 Jan:50(1):42-53. doi: 10.1038/s41588-017-0014-7. Epub 2017 Dec 22     [PubMed PMID: 29273806]

[11]

Gómez Real F, Burgess JA, Villani S, Dratva J, Heinrich J, Janson C, Jarvis D, Koplin J, Leynaert B, Lodge C, Lærum BN, Matheson MC, Norbäck D, Omenaas ER, Skulstad SM, Sunyer J, Dharmage SC, Svanes C. Maternal age at delivery, lung function and asthma in offspring: a population-based survey. The European respiratory journal. 2018 Jun:51(6):. pii: 1601611. doi: 10.1183/13993003.01611-2016. Epub 2018 Jun 7     [PubMed PMID: 29880541]

[12]

Laerum BN, Svanes C, Wentzel-Larsen T, Gulsvik A, Torén K, Norrman E, Gíslason T, Janson C, Omenaas E. Young maternal age at delivery is associated with asthma in adult offspring. Respiratory medicine. 2007 Jul:101(7):1431-8     [PubMed PMID: 17350816]

[13]

Venter C, Agostoni C, Arshad SH, Ben-Abdallah M, Du Toit G, Fleischer DM, Greenhawt M, Glueck DH, Groetch M, Lunjani N, Maslin K, Maiorella A, Meyer R, Antonella M, Netting MJ, Ibeabughichi Nwaru B, Palmer DJ, Palumbo MP, Roberts G, Roduit C, Smith P, Untersmayr E, Vanderlinden LA, O'Mahony L. Dietary factors during pregnancy and atopic outcomes in childhood: A systematic review from the European Academy of Allergy and Clinical Immunology. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2020 Nov:31(8):889-912. doi: 10.1111/pai.13303. Epub 2020 Aug 6     [PubMed PMID: 32524677]

[14]

Wolsk HM, Chawes BL, Litonjua AA, Hollis BW, Waage J, Stokholm J, Bønnelykke K, Bisgaard H, Weiss ST. Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: A combined analysis of two randomized controlled trials. PloS one. 2017:12(10):e0186657. doi: 10.1371/journal.pone.0186657. Epub 2017 Oct 27     [PubMed PMID: 29077711]

[15]

Bisgaard H, Stokholm J, Chawes BL, Vissing NH, Bjarnadóttir E, Schoos AM, Wolsk HM, Pedersen TM, Vinding RK, Thorsteinsdóttir S, Følsgaard NV, Fink NR, Thorsen J, Pedersen AG, Waage J, Rasmussen MA, Stark KD, Olsen SF, Bønnelykke K. Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring. The New England journal of medicine. 2016 Dec 29:375(26):2530-9. doi: 10.1056/NEJMoa1503734. Epub     [PubMed PMID: 28029926]

[16]

McEvoy CT, Shorey-Kendrick LE, Milner K, Schilling D, Tiller C, Vuylsteke B, Scherman A, Jackson K, Haas DM, Harris J, Schuff R, Park BS, Vu A, Kraemer DF, Mitchell J, Metz J, Gonzales D, Bunten C, Spindel ER, Tepper RS, Morris CD. Oral Vitamin C (500 mg/d) to Pregnant Smokers Improves Infant Airway Function at 3 Months (VCSIP). A Randomized Trial. American journal of respiratory and critical care medicine. 2019 May 1:199(9):1139-1147. doi: 10.1164/rccm.201805-1011OC. Epub     [PubMed PMID: 30522343]

[17]

McEvoy CT, Shorey-Kendrick LE, Milner K, Schilling D, Tiller C, Vuylsteke B, Scherman A, Jackson K, Haas DM, Harris J, Park BS, Vu A, Kraemer DF, Gonzales D, Bunten C, Spindel ER, Morris CD, Tepper RS. Vitamin C to Pregnant Smokers Persistently Improves Infant Airway Function to 12 Months of Age: A Randomised Trial. The European respiratory journal. 2020 Jul 2:():. doi: 10.1183/13993003.02208-2019. Epub 2020 Jul 2     [PubMed PMID: 32616589]

[18]

Macsali F, Real FG, Plana E, Sunyer J, Anto J, Dratva J, Janson C, Jarvis D, Omenaas ER, Zemp E, Wjst M, Leynaert B, Svanes C. Early age at menarche, lung function, and adult asthma. American journal of respiratory and critical care medicine. 2011 Jan 1:183(1):8-14. doi: 10.1164/rccm.200912-1886OC. Epub 2010 Aug 23     [PubMed PMID: 20732985]

[19]

Kirjavainen PV, Karvonen AM, Adams RI, Täubel M, Roponen M, Tuoresmäki P, Loss G, Jayaprakash B, Depner M, Ege MJ, Renz H, Pfefferle PI, Schaub B, Lauener R, Hyvärinen A, Knight R, Heederik DJJ, von Mutius E, Pekkanen J. Farm-like indoor microbiota in non-farm homes protects children from asthma development. Nature medicine. 2019 Jul:25(7):1089-1095. doi: 10.1038/s41591-019-0469-4. Epub 2019 Jun 17     [PubMed PMID: 31209334]

[20]

Subbarao P, Mandhane PJ, Sears MR. Asthma: epidemiology, etiology and risk factors. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2009 Oct 27:181(9):E181-90. doi: 10.1503/cmaj.080612. Epub 2009 Sep 14     [PubMed PMID: 19752106]

[21]

Burke W, Fesinmeyer M, Reed K, Hampson L, Carlsten C. Family history as a predictor of asthma risk. American journal of preventive medicine. 2003 Feb:24(2):160-9     [PubMed PMID: 12568822]

[22]

Dharmage SC, Perret JL, Custovic A. Epidemiology of Asthma in Children and Adults. Frontiers in pediatrics. 2019:7():246. doi: 10.3389/fped.2019.00246. Epub 2019 Jun 18     [PubMed PMID: 31275909]

[23]

O'Toole J, Mikulic L, Kaminsky DA. Epidemiology and Pulmonary Physiology of Severe Asthma. Immunology and allergy clinics of North America. 2016 Aug:36(3):425-38. doi: 10.1016/j.iac.2016.03.001. Epub 2016 Jun 2     [PubMed PMID: 27401616]

[24]

Liu MC, Hubbard WC, Proud D, Stealey BA, Galli SJ, Kagey-Sobotka A, Bleecker ER, Lichtenstein LM. Immediate and late inflammatory responses to ragweed antigen challenge of the peripheral airways in allergic asthmatics. Cellular, mediator, and permeability changes. The American review of respiratory disease. 1991 Jul:144(1):51-8     [PubMed PMID: 2064141]

[25]

Riccio MM, Proud D. Evidence that enhanced nasal reactivity to bradykinin in patients with symptomatic allergy is mediated by neural reflexes. The Journal of allergy and clinical immunology. 1996 Jun:97(6):1252-63     [PubMed PMID: 8648021]

[26]

Brown RH, Croisille P, Mudge B, Diemer FB, Permutt S, Togias A. Airway narrowing in healthy humans inhaling methacholine without deep inspirations demonstrated by HRCT. American journal of respiratory and critical care medicine. 2000 Apr:161(4 Pt 1):1256-63     [PubMed PMID: 10764321]

[27]

Aysola RS, Hoffman EA, Gierada D, Wenzel S, Cook-Granroth J, Tarsi J, Zheng J, Schechtman KB, Ramkumar TP, Cochran R, Xueping E, Christie C, Newell J, Fain S, Altes TA, Castro M. Airway remodeling measured by multidetector CT is increased in severe asthma and correlates with pathology. Chest. 2008 Dec:134(6):1183-1191. doi: 10.1378/chest.07-2779. Epub 2008 Jul 18     [PubMed PMID: 18641116]

[28]

Barbato A, Turato G, Baraldo S, Bazzan E, Calabrese F, Panizzolo C, Zanin ME, Zuin R, Maestrelli P, Fabbri LM, Saetta M. Epithelial damage and angiogenesis in the airways of children with asthma. American journal of respiratory and critical care medicine. 2006 Nov 1:174(9):975-81     [PubMed PMID: 16917118]

[29]

Lommatzsch M, Virchow JC. Severe asthma: definition, diagnosis and treatment. Deutsches Arzteblatt international. 2014 Dec 12:111(50):847-55. doi: 10.3238/arztebl.2014.0847. Epub     [PubMed PMID: 25585581]

[30]

Aggarwal B, Mulgirigama A, Berend N. Exercise-induced bronchoconstriction: prevalence, pathophysiology, patient impact, diagnosis and management. NPJ primary care respiratory medicine. 2018 Aug 14:28(1):31. doi: 10.1038/s41533-018-0098-2. Epub 2018 Aug 14     [PubMed PMID: 30108224]

[31]

Tse SM, Gold DR, Sordillo JE, Hoffman EB, Gillman MW, Rifas-Shiman SL, Fuhlbrigge AL, Tantisira KG, Weiss ST, Litonjua AA. Diagnostic accuracy of the bronchodilator response in children. The Journal of allergy and clinical immunology. 2013 Sep:132(3):554-559.e5. doi: 10.1016/j.jaci.2013.03.031. Epub 2013 May 14     [PubMed PMID: 23683464]

[32]

Galant SP, Morphew T, Amaro S, Liao O. Value of the bronchodilator response in assessing controller naïve asthmatic children. The Journal of pediatrics. 2007 Nov:151(5):457-62, 462.e1     [PubMed PMID: 17961685]

[33]

Reddel HK, Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, Casale TB, Chanez P, Enright PL, Gibson PG, de Jongste JC, Kerstjens HA, Lazarus SC, Levy ML, O'Byrne PM, Partridge MR, Pavord ID, Sears MR, Sterk PJ, Stoloff SW, Sullivan SD, Szefler SJ, Thomas MD, Wenzel SE, American Thoracic Society/European Respiratory Society Task Force on Asthma Control and Exacerbations. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. American journal of respiratory and critical care medicine. 2009 Jul 1:180(1):59-99. doi: 10.1164/rccm.200801-060ST. Epub     [PubMed PMID: 19535666]

[34]

Arnold DH, Gebretsadik T, Abramo TJ, Moons KG, Sheller JR, Hartert TV. The RAD score: a simple acute asthma severity score compares favorably to more complex scores. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2011 Jul:107(1):22-8. doi: 10.1016/j.anai.2011.03.011. Epub 2011 Apr 22     [PubMed PMID: 21704881]

[35]

Tesse R, Borrelli G, Mongelli G, Mastrorilli V, Cardinale F. Treating Pediatric Asthma According Guidelines. Frontiers in pediatrics. 2018:6():234. doi: 10.3389/fped.2018.00234. Epub 2018 Aug 23     [PubMed PMID: 30191146]

[36]

National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. The Journal of allergy and clinical immunology. 2007 Nov:120(5 Suppl):S94-138     [PubMed PMID: 17983880]

[37]

Rodrigo GJ, Rodriquez Verde M, Peregalli V, Rodrigo C. Effects of short-term 28% and 100% oxygen on PaCO2 and peak expiratory flow rate in acute asthma: a randomized trial. Chest. 2003 Oct:124(4):1312-7     [PubMed PMID: 14555560]

[38]

Castro-Rodriguez JA, Rodrigo GJ. beta-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. The Journal of pediatrics. 2004 Aug:145(2):172-7     [PubMed PMID: 15289762]

[39]

Koh HP, Shamsudin NS, Tan MMY, Mohd Pauzi Z. The outcomes and acceptance of pressurized metered-dose inhaler bronchodilators with venturi mask modified spacer in the outpatient emergency department during the COVID-19 pandemic. Journal of clinical pharmacy and therapeutics. 2021 Aug:46(4):1129-1138. doi: 10.1111/jcpt.13410. Epub 2021 Mar 25     [PubMed PMID: 33768601]

[40]

Brocklebank D, Ram F, Wright J, Barry P, Cates C, Davies L, Douglas G, Muers M, Smith D, White J. Comparison of the effectiveness of inhaler devices in asthma and chronic obstructive airways disease: a systematic review of the literature. Health technology assessment (Winchester, England). 2001:5(26):1-149     [PubMed PMID: 11701099]

[41]

Griffiths B, Ducharme FM. Combined inhaled anticholinergics and short-acting beta2-agonists for initial treatment of acute asthma in children. The Cochrane database of systematic reviews. 2013 Aug 21:(8):CD000060. doi: 10.1002/14651858.CD000060.pub2. Epub 2013 Aug 21     [PubMed PMID: 23966133]

[42]

Rowe BH, Bretzlaff JA, Bourdon C, Bota GW, Camargo CA Jr. Intravenous magnesium sulfate treatment for acute asthma in the emergency department: a systematic review of the literature. Annals of emergency medicine. 2000 Sep:36(3):181-90     [PubMed PMID: 10969218]

[43]

Rowe BH, Bretzlaff JA, Bourdon C, Bota GW, Camargo CA Jr. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. The Cochrane database of systematic reviews. 2000:2000(2):CD001490     [PubMed PMID: 10796650]

[44]

Cheuk DK, Chau TC, Lee SL. A meta-analysis on intravenous magnesium sulphate for treating acute asthma. Archives of disease in childhood. 2005 Jan:90(1):74-7     [PubMed PMID: 15613519]

[45]

Griffiths B, Kew KM. Intravenous magnesium sulfate for treating children with acute asthma in the emergency department. The Cochrane database of systematic reviews. 2016 Apr 29:4(4):CD011050. doi: 10.1002/14651858.CD011050.pub2. Epub 2016 Apr 29     [PubMed PMID: 27126744]

[46]

Bleecker ER, Menzies-Gow AN, Price DB, Bourdin A, Sweet S, Martin AL, Alacqua M, Tran TN. Systematic Literature Review of Systemic Corticosteroid Use for Asthma Management. American journal of respiratory and critical care medicine. 2020 Feb 1:201(3):276-293. doi: 10.1164/rccm.201904-0903SO. Epub     [PubMed PMID: 31525297]

[47]

Normansell R, Kew KM, Mansour G. Different oral corticosteroid regimens for acute asthma. The Cochrane database of systematic reviews. 2016 May 13:2016(5):CD011801. doi: 10.1002/14651858.CD011801.pub2. Epub 2016 May 13     [PubMed PMID: 27176676]

[48]

Keeney GE, Gray MP, Morrison AK, Levas MN, Kessler EA, Hill GD, Gorelick MH, Jackson JL. Dexamethasone for acute asthma exacerbations in children: a meta-analysis. Pediatrics. 2014 Mar:133(3):493-9. doi: 10.1542/peds.2013-2273. Epub 2014 Feb 10     [PubMed PMID: 24515516]

[49]

Piloni D, Tirelli C, Domenica RD, Conio V, Grosso A, Ronzoni V, Antonacci F, Totaro P, Corsico AG. Asthma-like symptoms: is it always a pulmonary issue? Multidisciplinary respiratory medicine. 2018:13():21. doi: 10.1186/s40248-018-0136-5. Epub 2018 Aug 3     [PubMed PMID: 30123502]

[50]

Bui DS, Lodge CJ, Perret JL, Lowe A, Hamilton GS, Thompson B, Giles G, Tan D, Erbas B, Pirkis J, Cicuttini F, Cassim R, Bowatte G, Thomas P, Garcia-Aymerich J, Hopper J, Abramson MJ, Walters EH, Dharmage SC. Trajectories of asthma and allergies from 7 years to 53 years and associations with lung function and extrapulmonary comorbidity profiles: a prospective cohort study. The Lancet. Respiratory medicine. 2021 Apr:9(4):387-396. doi: 10.1016/S2213-2600(20)30413-6. Epub 2020 Nov 17     [PubMed PMID: 33217367]

[51]

Kapadia CR, Nebesio TD, Myers SE, Willi S, Miller BS, Allen DB, Jacobson-Dickman E, Drugs and Therapeutics Committee of the Pediatric Endocrine Society. Endocrine Effects of Inhaled Corticosteroids in Children. JAMA pediatrics. 2016 Feb:170(2):163-70. doi: 10.1001/jamapediatrics.2015.3526. Epub     [PubMed PMID: 26720105]

[52]

Childhood Asthma Management Program Research Group, Szefler S, Weiss S, Tonascia J, Adkinson NF, Bender B, Cherniack R, Donithan M, Kelly HW, Reisman J, Shapiro GG, Sternberg AL, Strunk R, Taggart V, Van Natta M, Wise R, Wu M, Zeiger R. Long-term effects of budesonide or nedocromil in children with asthma. The New England journal of medicine. 2000 Oct 12:343(15):1054-63     [PubMed PMID: 11027739]

[53]

Guhan AR, Cooper S, Oborne J, Lewis S, Bennett J, Tattersfield AE. Systemic effects of formoterol and salmeterol: a dose-response comparison in healthy subjects. Thorax. 2000 Aug:55(8):650-6     [PubMed PMID: 10899240]

[54]

Osuorji I, Williams C, Hessney J, Patel T, Hsi D. Acute stress cardiomyopathy following treatment of status asthmaticus. Southern medical journal. 2009 Mar:102(3):301-3. doi: 10.1097/SMJ.0b013e31818f5bd8. Epub     [PubMed PMID: 19204641]

[55]

Bernstein JA, Mansfield L. Step-up and step-down treatments for optimal asthma control in children and adolescents. The Journal of asthma : official journal of the Association for the Care of Asthma. 2019 Jul:56(7):758-770. doi: 10.1080/02770903.2018.1490752. Epub 2018 Sep 12     [PubMed PMID: 29972079]

[56]

Lou Y, Atherly A, Johnson T, Anderson M, Valdez C, Sabalot S. The impact of care management for high-risk pediatric asthmatics on healthcare utilization. The Journal of asthma : official journal of the Association for the Care of Asthma. 2021 Jan:58(1):133-140. doi: 10.1080/02770903.2019.1659311. Epub 2019 Sep 9     [PubMed PMID: 31496315]

[57]

Cook J, Beresford F, Fainardi V, Hall P, Housley G, Jamalzadeh A, Nightingale M, Winch D, Bush A, Fleming L, Saglani S. Managing the pediatric patient with refractory asthma: a multidisciplinary approach. Journal of asthma and allergy. 2017:10():123-130. doi: 10.2147/JAA.S129159. Epub 2017 Apr 20     [PubMed PMID: 28461761]