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Editorials: Point and Counterpoint |

COUNTERPOINT: Is Escalation of the Inhaled Corticosteroid Dose Appropriate for Acute Loss of Asthma Control in an Attempt to Reduce Need for Oral Corticosteroids in Children? No FREE TO VIEW

Miles Weinberger, MD
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURE: None declared.

Professor Emeritus of Pediatrics, University of Iowa, Iowa City, IA

CORRESPONDENCE TO: Miles Weinberger, MD, 450 Sandalwood Ct, Encinitas, CA 92024


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(3):490-492. doi:10.1016/j.chest.2016.06.026
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The proposal to treat loss of asthma control with increased inhaled corticosteroids raises a number of issues that need to be examined. First, just what is meant by loss of control? Is this the same as an exacerbation? If not, what’s the difference? For guidance, I looked at a previously published practice parameter. That document summarizes the goal of what they call the yellow zone as “Responding to the symptoms of acute loss of control in the yellow zone with effective interventions can help prevent deterioration to the red zone, necessitating use of systemic corticosteroids and/or urgent medical care.”(p145)

The yellow zone referred to in the practice parameter included the following: “an increase in asthma symptoms, an increase in use of reliever medications, a peak flow rate (PEFR) decrease of at least 15% OR a PEFR, lower than 80% of personal best, the presence or increase in nocturnal asthma symptoms.”(p149) Now let us dispense with the antiquated inclusion of the peak flow rate. Although the peak flow meter is touted by some as a useful means for monitoring a patient, the weight of evidence indicates that symptom monitoring (and consequent need for intervention with an inhaled agonist) has been demonstrated to be generally equal to, or better, than peak flow monitoring in providing early warning of an exacerbation that requires intervention. The only patients in whom a home peak flow meter might be useful are the occasional under-perceiver, usually with very severe chronic asthma, who does not recognize worsening airway obstruction, or the over-perceiver, who confuses anxiety or hyperventilation attacks with asthma.

So what is meant by loss of asthma control? Does it differ from an exacerbation? Is it essentially a pre-exacerbation? Let us examine the known factors that cause exacerbations, since the loss of control, if not already an exacerbation, is considered to be potential, pending, or imminent but not quite yet an exacerbation. Symptoms requiring increased reliever medication, especially with an increase in nocturnal symptoms, is a full-blown exacerbation by my standards even though that is described as still in the yellow zone and not an actual exacerbation. After all, when the child’s sleep is disturbed, no one else in the home is likely to be sleeping well. As a parent, I would certainly consider that an exacerbation, not just loss of control. Why bother with the yellow zone, something intermediate between loss of control and an exacerbation requiring optimally effective intervention? I will answer that rhetorical question. Do not bother with the yellow zone loss of control. It is a procrastinator’s zone based on wishful thinking and gambling. Gambling that the exacerbation will run a benign course, which it undoubtedly sometimes, but unpredictably, does. A randomized controlled clinical trial of starting an oral corticosteroid or placebo early at the beginning of an exacerbation (ie, loss of control) was associated with about one-half of the placebo treated patients having a relatively benign course. There did not appear to be any identifiable clinical characteristics at the time of early symptoms among those placebo treated patients whose exacerbation progressed and needed rescue compared with those who recovered spontaneously, other than coughing more than those who received the oral corticosteroid. Had those placebo-treated patients received an inhaled corticosteroid, benefit would have been attributed to that treatment. The question is whether inhaled corticosteroids would have been as likely to match the benefit seen from the oral corticosteroids in that study.

Let us look at the evidence regarding what causes exacerbations and how they should be treated. Viral respiratory infections are the major cause of asthma exacerbations at all ages,, and appear to be the major risk factor for the large increase in hospital admissions for asthma that occurs every autumn after school starts. What are the therapeutic options for treating the early symptoms of an exacerbation (yellow zone)? Repeated doses of an inhaled bronchodilator such as the β2-specific bronchodilator albuterol is recommended and is certainly essential to relieve acute symptoms. However, β2 agonists do not alter the inflammatory component of airway obstruction, and so that measure is again gambling that the exacerbation will run a benign course.

There is no debate over whether corticosteroids in some form are indicated for acute loss of control, that is, an exacerbation. There is also convincing data that early aggressive use of systemic steroids provides impressive clinical benefit for children having an acute exacerbation of asthma.,,,, The question then is, can increasing inhaled corticosteroids from a maintenance dose previously associated with control prevent the need for an oral corticosteroid? Doubling the dose of inhaled corticosteroids, as some have recommended, provided no therapeutic advantage. Quadrupling the dose was associated with a modest but not statistically significant decrease in subsequent requirement for oral corticosteroids. The role of inhaled corticosteroids for treating exacerbations was extensively reviewed by Hendeles and Sherman. They found little evidence that even high doses of inhaled corticosteroids substantially altered the course of asthma exacerbations. Although mild symptom relief might occur in some, the frequency of urgent care requirements and hospitalization was not reduced to less than that seen with placebo.

Is there an advantage with regard to safety for a higher dose of inhaled corticosteroid compared with a short course of an oral corticosteroid? Sustained adverse effects from a short course of a corticosteroid has been examined and found to be absent. A Cochrane review of the subject concluded, “Practitioners may prescribe systemic corticosteroids in otherwise healthy children when indicated for the management of acute respiratory conditions (ie, infections or asthma exacerbations) with minimal concern about short-term adverse effects.”(p733) Another Cochrane review demonstrated that administration of an oral corticosteroid by a nurse early during an ED visit (within 1 hour) provided improved benefit compared with delays until evaluation by a physician. I would then argue that even earlier administration at home would be likely to prevent that ED visit.

Based on the evidence, what would you do if your child with chronic asthma who is taking a moderate dose of an inhaled corticosteroid with good control begins to have increased coughing that progresses to dyspnea requiring albuterol and has interference with sleep. Would you gamble by increasing the dose of inhaled corticosteroid, or would you begin a short course of an oral corticosteroid? Although the symptoms may be decreased somewhat by the higher dose of inhaled corticosteroid, and the exacerbation might run a benign self-limited course, a short course of an oral corticosteroid virtually guarantees rapid improvement within 24 to 48 hours and complete clearing of the increased symptoms by 5 to 7 days. Frankly, I like to sleep nights, and if my child were up coughing much of the night, I would not be any happier than my symptomatic child. The reality is that we have an extremely effective and safe means to prevent an exacerbation from progressing using an oral corticosteroid.

However, this discussion would not be complete without acknowledging the occasional exceptions. For patients who typically have mild exacerbations that do not require urgent medical care or hospitalizations, quadrupling the inhaled steroid dose may provide satisfactory relief of symptoms. Additionally, for patients who may experience acute adverse effects from oral steroids, such as a child with diabetes requiring insulin, a trial of increasing the inhaled corticosteroids may be justified. However, a short course of an oral corticosteroid is likely to provide greater assurance of more rapid improvement. For most children who have experienced troublesome exacerbations, a short course of an oral corticosteroid provides an acceptably safe and generally assured means of preventing an exacerbation from progressing.

References

Dinakar C. .Oppenheimer M.D. .Portnoy J. .et al Management of acute loss of asthma control in the yellow zone: a practice parameter. Ann Allergy Asthma Immunol. 2014;113:143-159 [PubMed]journal. [CrossRef] [PubMed]
 
Malo J.L. .L’Archeveque J. .Trudeau C. .d’Aquino C. .Cartier A. . Should we monitor peak expiratory flow rates or record symptoms with a simple diary in the management of asthma? J Allergy Clin Immunol. 1993;91:702-709 [PubMed]journal. [CrossRef] [PubMed]
 
Legge J.S. . Peak-expiratory-flow meters and asthma self-management. Lancet. 1996;347:1709-1710 [PubMed]journal
 
Clough J.B. .Sly P.D. . Association between lower respiratory tract symptoms and falls in peak expiratory flow in children. Eur Respir J. 1995;8:718-722 [PubMed]journal. [PubMed]
 
Chan-Yeung M. .Chang J.H. .Manfreda J. .Ferguson A. .Becker A. . Changes in peak flow, symptom score, and the use of medications during acute exacerbations of asthma. Am J Respir Crit Care Med. 1996;154:889-893 [PubMed]journal. [CrossRef] [PubMed]
 
Harris J.B. .Weinberger M. .Nassif E. .Smith G. .Milavetz G. .Stillerman A. . Early intervention with short courses of prednisone to prevent progression of asthma in ambulatory patients incompletely responsive to bronchodilators. J Pediatr. 1987;110:627-644 [PubMed]journal. [CrossRef] [PubMed]
 
McIntosh K. .Ellis E.F. .Hoffman L.S. .Lybass T.G. .Eller J.J. .Fulginiti V.A. . The association of viral and bacterial respiratory infections with exacerbations of wheezing in young asthmatic children. J Pediatr. 1973;82:578-590 [PubMed]journal. [CrossRef] [PubMed]
 
Minor T.E. .Dick E.C. .DeMeo A.N. .Ouellette J.J. .Cohen M. .Reed C.E. . Viruses as precipitants of asthmatic attacks in children. JAMA. 1974;227:292-298 [PubMed]journal. [CrossRef] [PubMed]
 
Johnston S.L. .Pattemore P.K. .Sanderson G. .et al Community study of role of viral infections in exacerbations of asthma in 9-11 year old children. BMJ. 1995;310:1225-1229 [PubMed]journal. [CrossRef] [PubMed]
 
Dales R.E. .Schweitzer I. .Toogood J.H. .et al Respiratory infections and the autumn increase in asthma morbidity. Eur Respir J. 1996;9:72-77 [PubMed]journal. [CrossRef] [PubMed]
 
Storr J. .Barrell E. .Barry W. .Lenney W. .Hatcher G. . Effect of a single oral dose of prednisolone in acute childhood asthma. Lancet. 1987;1:879-882 [PubMed]journal. [PubMed]
 
Tal A. .Levy N. .Bearman J.E. . Methylprednisolone therapy for acute asthma in infants and toddlers: a controlled clinical trial. Pediatrics. 1990;86:350-356 [PubMed]journal. [PubMed]
 
Scarfone R.J. .Fuchs S.M. .Nager A.L. .Shane S.A. . Controlled trial of oral prednisone in the emergency department treatment of children with acute asthma. Pediatrics. 1993;92:513-518 [PubMed]journal. [PubMed]
 
Brunette M.G. .Lands L. .Thibodeau L.P. . Childhood asthma: prevention of attacks with short-term corticosteroid treatment of upper respiratory tract infection. Pediatrics. 1988;81:624-629 [PubMed]journal. [PubMed]
 
Harrison T.W. .Oborne J. .Newton S. .Tattersfield A.E. . Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial. Lancet. 2004;363:271-275 [PubMed]journal. [CrossRef] [PubMed]
 
Oborne J. .Mortimer K. .Hubbard R.B. .Tattersfield A.E. .Harrison T.W. . Quadrupling the dose of inhaled corticosteroid to prevent asthma exacerbations: a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Am J Respir Crit Care Med. 2009;180:598-602 [PubMed]journal. [CrossRef] [PubMed]
 
Hendeles L. .Sherman J. . Are inhaled corticosteroid effective for acute exacerbations of asthma in children? J Pediatr. 2003;142:S26-S33 [PubMed]journal. [CrossRef] [PubMed]
 
Ducharme F.M. .Chabot G. .Polychronakos C. .Glorieux F. .Mazer B. . Safety profile of frequent short courses of oral glucocorticoids in acute pediatric asthma: impact on bone metabolism, bone density, and adrenal function. Pediatrics. 2003;111:376-383 [PubMed]journal. [CrossRef] [PubMed]
 
The Cochrane Library and safety of systemic corticosteroids for acute respiratory conditions in children: an overview of reviews. Evid-Based Child Health. 2014;9:733-747 [PubMed]journal. [CrossRef] [PubMed]
 
Zemek R. .Plint A. .Osmond M.H. .et al Initiation of corticosteroids in pediatric asthma is associated with improved emergency department efficiency. Pediatrics. 2012;129:671-680 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Tables

References

Dinakar C. .Oppenheimer M.D. .Portnoy J. .et al Management of acute loss of asthma control in the yellow zone: a practice parameter. Ann Allergy Asthma Immunol. 2014;113:143-159 [PubMed]journal. [CrossRef] [PubMed]
 
Malo J.L. .L’Archeveque J. .Trudeau C. .d’Aquino C. .Cartier A. . Should we monitor peak expiratory flow rates or record symptoms with a simple diary in the management of asthma? J Allergy Clin Immunol. 1993;91:702-709 [PubMed]journal. [CrossRef] [PubMed]
 
Legge J.S. . Peak-expiratory-flow meters and asthma self-management. Lancet. 1996;347:1709-1710 [PubMed]journal
 
Clough J.B. .Sly P.D. . Association between lower respiratory tract symptoms and falls in peak expiratory flow in children. Eur Respir J. 1995;8:718-722 [PubMed]journal. [PubMed]
 
Chan-Yeung M. .Chang J.H. .Manfreda J. .Ferguson A. .Becker A. . Changes in peak flow, symptom score, and the use of medications during acute exacerbations of asthma. Am J Respir Crit Care Med. 1996;154:889-893 [PubMed]journal. [CrossRef] [PubMed]
 
Harris J.B. .Weinberger M. .Nassif E. .Smith G. .Milavetz G. .Stillerman A. . Early intervention with short courses of prednisone to prevent progression of asthma in ambulatory patients incompletely responsive to bronchodilators. J Pediatr. 1987;110:627-644 [PubMed]journal. [CrossRef] [PubMed]
 
McIntosh K. .Ellis E.F. .Hoffman L.S. .Lybass T.G. .Eller J.J. .Fulginiti V.A. . The association of viral and bacterial respiratory infections with exacerbations of wheezing in young asthmatic children. J Pediatr. 1973;82:578-590 [PubMed]journal. [CrossRef] [PubMed]
 
Minor T.E. .Dick E.C. .DeMeo A.N. .Ouellette J.J. .Cohen M. .Reed C.E. . Viruses as precipitants of asthmatic attacks in children. JAMA. 1974;227:292-298 [PubMed]journal. [CrossRef] [PubMed]
 
Johnston S.L. .Pattemore P.K. .Sanderson G. .et al Community study of role of viral infections in exacerbations of asthma in 9-11 year old children. BMJ. 1995;310:1225-1229 [PubMed]journal. [CrossRef] [PubMed]
 
Dales R.E. .Schweitzer I. .Toogood J.H. .et al Respiratory infections and the autumn increase in asthma morbidity. Eur Respir J. 1996;9:72-77 [PubMed]journal. [CrossRef] [PubMed]
 
Storr J. .Barrell E. .Barry W. .Lenney W. .Hatcher G. . Effect of a single oral dose of prednisolone in acute childhood asthma. Lancet. 1987;1:879-882 [PubMed]journal. [PubMed]
 
Tal A. .Levy N. .Bearman J.E. . Methylprednisolone therapy for acute asthma in infants and toddlers: a controlled clinical trial. Pediatrics. 1990;86:350-356 [PubMed]journal. [PubMed]
 
Scarfone R.J. .Fuchs S.M. .Nager A.L. .Shane S.A. . Controlled trial of oral prednisone in the emergency department treatment of children with acute asthma. Pediatrics. 1993;92:513-518 [PubMed]journal. [PubMed]
 
Brunette M.G. .Lands L. .Thibodeau L.P. . Childhood asthma: prevention of attacks with short-term corticosteroid treatment of upper respiratory tract infection. Pediatrics. 1988;81:624-629 [PubMed]journal. [PubMed]
 
Harrison T.W. .Oborne J. .Newton S. .Tattersfield A.E. . Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial. Lancet. 2004;363:271-275 [PubMed]journal. [CrossRef] [PubMed]
 
Oborne J. .Mortimer K. .Hubbard R.B. .Tattersfield A.E. .Harrison T.W. . Quadrupling the dose of inhaled corticosteroid to prevent asthma exacerbations: a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Am J Respir Crit Care Med. 2009;180:598-602 [PubMed]journal. [CrossRef] [PubMed]
 
Hendeles L. .Sherman J. . Are inhaled corticosteroid effective for acute exacerbations of asthma in children? J Pediatr. 2003;142:S26-S33 [PubMed]journal. [CrossRef] [PubMed]
 
Ducharme F.M. .Chabot G. .Polychronakos C. .Glorieux F. .Mazer B. . Safety profile of frequent short courses of oral glucocorticoids in acute pediatric asthma: impact on bone metabolism, bone density, and adrenal function. Pediatrics. 2003;111:376-383 [PubMed]journal. [CrossRef] [PubMed]
 
The Cochrane Library and safety of systemic corticosteroids for acute respiratory conditions in children: an overview of reviews. Evid-Based Child Health. 2014;9:733-747 [PubMed]journal. [CrossRef] [PubMed]
 
Zemek R. .Plint A. .Osmond M.H. .et al Initiation of corticosteroids in pediatric asthma is associated with improved emergency department efficiency. Pediatrics. 2012;129:671-680 [PubMed]journal. [CrossRef] [PubMed]
 
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