Asthma and other recurrent wheezing disorders in children (acute) Search date June 2010 Augusta Okpapi, Amanda J Friend, and Stephen W Turner ABSTRACT INTRODUCTION: Acute childhood asthma is a common clinical emergency presenting across a range of ages and with a range of severities. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute asthma in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 35 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta2 agonists (high-dose nebulised, metered-dose inhaler plus spacer device versus nebuliser, intravenous), corticosteroids (systemic, high-dose inhaled), ipratropium bromide (single- or multiple-dose inhaled), magnesium sulphate, oxygen, and theophylline or aminophylline.

QUESTIONS What are the effects of treatments for acute asthma in children?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 INTERVENTIONS ACUTE ASTHMA

Likely to be beneficial

Beneficial

Theophylline or aminophylline (intravenous) . . . . . 18

Oxygen* . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Beta2 agonists (high-dose inhaled)* . . . . . . . . . . . . . 3 Ipratropium bromide (inhaled) added to beta2 agonists .......................................... 8 Corticosteroids (systemic) . . . . . . . . . . . . . . . . . . . 12 Corticosteroids (high-dose inhaled) . . . . . . . . . . . . 14

Covered elsewhere in Clinical Evidence Bronchiolitis Footnote *In the absence of RCT evidence, categorisation based on observational evidence and strong consensus.

Salbutamol (intravenous) New . . . . . . . . . . . . . . . 22 Magnesium sulphate (intravenous) New . . . . . . . . 27 Key points • Not all acute wheeze is due to asthma/bronchospasm, particularly in children aged 2 years (mean age 4.5 years) with severe acute asthma already receiving conventional therapy (oxygen, beta2 agonist, and corticosteroids) on admission

Length of hospital stay 4.65 hours with salbutamol group (intravenous, 1 microgram/kg)

Between-group significance assessment not reported

6.56 hours with placebo (saline)

The remaining arm assessed magnesium sulphate (intravenous, 50 mg/kg)

No data from the following reference on this outcome.

[38]

Physiological measures No data from the following reference on this outcome.

[38]

[39]

Adverse effects -

© BMJ Publishing Group Ltd 2012. All rights reserved.

..........................................................

23

Child health

Asthma and other recurrent wheezing disorders in children (acute)

Ref (type)

Population

Outcome, Interventions

Results and statistical analysis

Effect size

Favours

Adverse effects [38]

RCT

29 children aged 1 Tremor , 2 hours to 12 years with with salbutamol (intravenous) acute severe asthma with placebo

P 2 years (mean age 4.5 years) with severe acute asthma already receiving conventional therapy (oxygen, beta2 agonist, and corticosteroids) on admission

Respiratory frequency , 1 hour Between-group significance assessment not reported 51.35 with magnesium sulphate (intravenous, 50 mg/kg) 54.63 with placebo (saline)

The remaining arm assessed salbutamol (intravenous, 1 microgram/kg)

Need for bronchodilator [39]

RCT 3-armed trial

50 children aged >2 years (mean age 4.5 years) with severe acute asthma already receiving conventional therapy (oxygen, beta2 agonist, and

Nebulisations of bronchodilator per day

Between-group significance assessment not reported

59.35 with magnesium sulphate (intravenous, 50 mg/kg) 68.1 with placebo (saline)

© BMJ Publishing Group Ltd 2012. All rights reserved.

..........................................................

27

Child health

Asthma and other recurrent wheezing disorders in children (acute)

Ref (type)

Population

Outcome, Interventions

Results and statistical analysis

Effect size

Favours

corticosteroids) on admission The remaining arm assessed salbutamol (intravenous, 1 microgram/kg)

No data from the following reference on this outcome.

[42]

Physiological measures Compared with adding placebo Adding intravenous magnesium sulphate may be more effective at improving pulmonary function (details of measurement not reported), and at decreasing the proportion of children with moderate to severe acute asthma with persistent peak expiratory flow 2 years (mean age 4.5 years) with severe acute asthma already receiving conventional therapy (oxygen, beta2 agonist, and corticosteroids) on admission

59.35 with magnesium sulphate (intravenous, 50 mg/kg) 37.00 with salbutamol (intravenous, 1 microgram/kg)

The remaining arm assessed placebo (saline)

Respiratory rate [39]

RCT 3-armed trial

50 children aged >2 years (mean age 4.5 years) with severe acute asthma already receiving conventional therapy (oxygen, beta2 agonist, and corticosteroids) on admission

Respiratory frequency , 1 hour Between-group significance assessment not reported 51.35 with magnesium sulphate (intravenous, 50 mg/kg) 45.76 with salbutamol (intravenous, 1 microgram/kg)

The remaining arm assessed placebo (saline)

Hospital admission/length of stay Compared with adding intravenous salbutamol We don't know how adding intravenous magnesium sulphate and adding intravenous salbutamol to conventional therapy compare at reducing length of hospital stay in children with severe acute asthma (very low-quality evidence). © BMJ Publishing Group Ltd 2012. All rights reserved.

..........................................................

29

Child health

Asthma and other recurrent wheezing disorders in children (acute)

Ref (type)

Population

Results and statistical analysis

Outcome, Interventions

Effect size

Favours

Length of hospital stay [39]

RCT 3-armed trial

50 children aged >2 years (mean age 4.5 years) with severe acute asthma already receiving conventional therapy (oxygen, beta2 agonist, and corticosteroids) on admission

Length of hospital stay

Between-group significance assessment not reported

6.12 days with magnesium sulphate (intravenous, 50 mg/kg) 4.65 days with salbutamol (intravenous, 1 microgram/kg)

The remaining arm assessed placebo (saline)

Physiological measures No data from the following reference on this outcome.

[39]

Further information on studies [39]

[43]

Compared with placebo, magnesium was associated with an average drop in systolic blood pressure of 6 mmHg and salbutamol with a mean rise of the same order. [42]

The reviews did not assess the reason for the statistical heterogeneity found.

Comment:

None.

GLOSSARY Aminophylline A stable combination of theophylline and ethylenediamine; the ethylenediamine is added to increase the solubility of theophylline in water. Forced expiratory volume in 1 second (FEV1) The volume breathed out in the first second of forceful blowing into a spirometer, measured in litres. Low-quality evidence Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Moderate-quality evidence Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Peak expiratory flow rate (PEFR) The maximum rate that gas is expired from the lungs when blowing into a peak flow meter or a spirometer. It is measured at an instant, but the units are expressed as litres per minute. Salbutamol This is known as albuterol in the USA; it is a short-acting selective beta2 agonist. Very low-quality evidence Any estimate of effect is very uncertain.

SUBSTANTIVE CHANGES Salbutamol (intravenous) New option added.

[19]

[38]

[40]

Magnesium sulphate (intravenous) New option added.

Categorised as Beneficial.

[39]

[42]

[43]

Categorised as Beneficial.

Beta2 agonists (high-dose inhaled) Search updated for one already included systematic review comparing contin[10] uous versus intermittent nebulised beta2 agonist administration; no new studies found. Search updated for another already included systematic review comparing a spacer/holding chamber attached to a metered-dose inhaler versus [12] nebuliser for delivery of beta2 agonists; new evidence added. Categorisation unchanged (Beneficial). © BMJ Publishing Group Ltd 2012. All rights reserved.

..........................................................

30

Child health

Asthma and other recurrent wheezing disorders in children (acute)

Corticosteroids (high-dose inhaled) Search updated for already included systematic review; new evidence added. [25] [26] New evidence added. Categorisation unchanged (Beneficial). Corticosteroids (systemic) Search updated for already included systematic review comparing high-dose nebulised [25] [26] corticosteroid versus oral corticosteroids; new evidence added. New evidence added. Categorisation unchanged (Beneficial). Theophylline (intravenous) Search updated for already included systematic review; no new evidence added. [36] [37] New evidence added. Categorisation unchanged (Likely to be beneficial) Ipratropium bromide (inhaled) added to beta2 agonists New evidence added Existing evidence re-evaluated. Categorised as Beneficial.

[16]

[17]

[19]

[35]

and option restructured.

REFERENCES 1.

Scottish Intercollegiate Guidelines Network, British Thoracic Society. British guideline on the management of asthma. 2008. Available at http://www.sign.ac.uk/guidelines/fulltext/101/index.html (accessed 5 July 2012).

23.

Chang AB, Clark R, Sloots TP, et al. A 5- versus 3-day course of oral corticosteroids for children with asthma exacerbations who are not hospitalised: a randomised controlled trial. Med J Aust 2008;189:306–310.[PubMed]

2.

Fleming DM, Sunderland R, Cross KW, et al. Declining incidence of episodes of asthma: a study of trends in new episodes presenting to general practitioners in the period 1989–98. Thorax 2000;55:657–661.[PubMed]

24.

Patel H, Macarthur C, Johnson D. Recent corticosteroids use and the risk of complicated varicella in otherwise immunocompetent children. Arch Pediatr Adolesc Med 1996;150:409–414.[PubMed]

3.

Turner S, Thomas M, von Ziegenweidt J, et al. Prescribing trends in asthma: a longitudinal observational study. Arch Dis Child 2009;94:16–22.[PubMed]

25.

4.

Panickar JR, Dodd SR, Smyth RL, et al. Trends in deaths from respiratory illness in children in England and Wales from 1968 to 2000. Thorax 2005;60:1035–1038.[PubMed]

Edmonds ML, Camargo CA Jr, Pollack CV Jr, et al. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. In: The Cochrane Library, Issue 3, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2005.

26.

5.

Johnston SL, Pattemore PK, 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]

Schuh S, Dick PT, Stephens D, et al. High-dose inhaled fluticasone does not replace oral prednisolone in children with mild to moderate acute asthma. Pediatrics 2006;118:644–650.[PubMed]

27.

6.

Ordonez GA, Phelan PD, Olinsky A, et al. Preventable factors in hospital admissions for asthma. Arch Dis Child 1998;78:143–147.[PubMed]

Manjra AI, Price J, Lenney W, et al. Efficacy of nebulised fluticasone propionate compared with oral prednisolone in children with an acute exacerbation of asthma. Respir Med 2000;94:1206–1214.[PubMed]

7.

Park ES, Golding J, Carswell F, et al. Pre-school wheezing and prognosis at 10. Arch Dis Child 1986;61:642–646.[PubMed]

28.

8.

Kelly WJW, Hudson I, Phelan PD, et al. Childhood asthma in adult life: a further study at 28 years of age. BMJ 1987;294:1059–1062.[PubMed]

Matthews EE, Curtis PD, McLain B, et al. Nebulized budesonide versus oral steroid in severe exacerbations of childhood asthma. Acta Paediatr 1999;88:841–843.[PubMed]

29.

9.

Geelhoed GC, Landau LI, Le Souef PN. Evaluation of SaO2 as a predictor of outcome in 280 children presenting with acute asthma. Ann Emerg Med 1994;23:1236–1241.[PubMed]

Milani GK, Rasrio Filho NA, Riedi CA, et al. Nebulized budesonide to treat acute asthma in children. J Pediatr (Rio J)2004;80:106–112.[in Portuguese][PubMed]

30.

10.

Camargo CA, Jr, Spooner CH, Rowe BH. Continuous versus intermittent betaagonists for acute asthma. In: The Cochrane Library, Issue 3, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2009.

Schuh S, Resiman J, Alshehri M, et al. A comparison of inhaled fluticasone and oral prednisone for children with severe acute asthma. N Engl J Med 2000;343:689–694.[PubMed]

31.

11.

Khine H, Fuchs SM, Saville AL. Continuous vs intermittent nebulized albuterol for emergency management of asthma. Acad Emerg Med 1996;3:1019–1024. [PubMed]

Scarfone RJ, Loiselle JM, Wiley JF II, et al. Nebulized dexamethasone versus oral prednisone in the emergency treatment of asthmatic children. Ann Emerg Med 1995;26:480–486.[PubMed]

32.

12.

Cates CJ, Crilly JA, Rowe BH. Holding chambers versus nebulisers for beta-agonist treatment of acute asthma. In: The Cochrane Library, Issue 3, 2010. Chichester, UK: John Wiley & Sons Ltd. Search date 2008.

Devidayal S, Singhi S, Kumar L, et al. Efficacy of nebulized budesonide compared to oral prednisolone in acute bronchial asthma. Acta Paediatr 1999;88:835–840. [PubMed]

33.

13.

Deerojanawong J, Manuyakorn W, Prapphal N, et al. Randomized controlled trial of salbutamol aerosol therapy via metered dose inhaler-spacer vs. jet nebulizer in young children with wheezing. Pediat Pulmonol 2005;39:466–472.[PubMed]

Volovitz B, Bentur L, Finkelstein Y, et al. Effectiveness and safety of inhaled corticosteroids in controlling acute asthma attacks in children who were treated in the emergency department: a controlled comparative study with oral prednisolone. J Allergy Clin Immunol 1998;102:605–609.[PubMed]

34.

14.

Nielsen KG, Bisgaard H. Bronchodilation and bronchoprotection in asthmatic preschool children from formoterol administered by mechanically actuated drypowder inhaler and spacer. Am J Respir Crit Care Med 2001;164:256–259.[PubMed]

Decimo F, Maiello N, Miraglia Del Giudice M, et al. High-dose inhaled flunisolide versus budesonide in the treatment of acute asthma exacerbations in preschoolage children. Int J Immunopathol Pharmacol 2009;22:363–370.[PubMed]

35.

Mitra A, Bassler D, Ducharme, FM. Intravenous aminophylline for acute severe asthma in children over 2 years using inhaled bronchodilators. In: The Cochrane Library, Issue 3, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2007.

15.

Plotnick LH, Ducharme FM. Combined inhaled anticholinergics and beta, 2 agonists for initial treatment of acute asthma in children. In: The Cochrane Library, Issue 3, 2010. Chichester, UK: John Wiley & Sons Ltd. Search date 2000.

36.

16.

Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Thorax 2005;60:740–746.[PubMed]

Vieira SE, Lotufo JP, Ejzenberg B, et al. Efficacy of IV aminophylline as a supplemental therapy in moderate broncho-obstructive crisis in infants and preschool children. Pulm Pharmacol Ther 2000;13:189–194.[PubMed]

37.

17.

Watanasomsiri A, Phipatanakul W. Comparison of nebulized ipratropium bromide with salbutamol vs salbutamol alone in acute asthma exacerbation in children. Ann Allergy Asthma Immunol 2006;96:701–706.[PubMed]

D'Avila RS, Piva JP, Marostica PJ, et al. Early administration of two intravenous bolus of aminophylline added to the standard treatment of children with acute asthma. Respir Med 2008;102:156–161.[PubMed]

38.

18.

Goggin N, Macarthur C, Parkin PC. Randomized trial of the addition of ipratropium bromide to albuterol and corticosteroid therapy in children hospitalized because of an acute asthma exacerbation. Arch Pediatr Adolesc Med 2001;155:1329–1334. [PubMed]

Browne GJ, Penna AS, Phung X, et al. Randomised trial of intravenous salbutamol in early management of acute severe asthma in children. Lancet 1997;349:301–305.[PubMed]

39.

Santana JC, Barreto SS, Piva JP, et al. Randomized clinical trial of intravenous magnesium sulfate versus salbutamol in the early management of severe acute asthma in children. J Pediatr 2001;77:279–287.[PubMed]

40.

Roberts G, Newsom D, Gomez K, et al. Intravenous salbutamol bolus compared with an aminophylline infusion in children with severe asthma: a randomised controlled trial. Thorax 2003;58:306–310.[PubMed]

19.

Browne GJ, Trieu L, Van Asperen P, et al. Randomized, double-blind, placebocontrolled trial of intravenous salbutamol and nebulized ipratropium bromide in early management of severe acute asthma in children presenting to an emergency department. Crit Care Med 2002;30:448–453.[PubMed]

20.

Smith M Iqbal S, Elliott TM, et al. Corticosteroids for hospitalised children with acute asthma (Cochrane Review). In: The Cochrane Library, Issue 3, 2010. Chichester, UK: John Wiley and Sons Ltd. Search date 2002.

41.

Hambleton G, Stone MJ. Comparison of IV salbutamol with IV aminophylline in the treatment of severe, acute asthma in childhood. Arch Dis Child 1979;54:391–392.[PubMed]

21.

Vuillermin PJ, Robertson CF, Carlin JB, et al. Parent initiated prednisolone for acute asthma in children of school age: randomised controlled crossover trial. BMJ 2010;340:c843.[PubMed]

42.

Mohammed S, Goodacre S. Intravenous and nebulised magnesium sulphate for acute asthma: systematic review and meta-analysis. Emerg Med J 2007;24:823–830.[PubMed]

22.

Altamimi S, Robertson G, Jastaniah W, et al. Single-dose oral dexamethasone in the emergency management of children with exacerbations of mild to moderate asthma. Pediatr Emerg Care 2006;22:786–793.[PubMed]

43.

Cheuk DK, Chau TC, Lee SL. A meta-analysis on intravenous magnesium sulphate for treating acute asthma. Arch Dis Child 2005;90:74–77.[PubMed]

Augusta Okpapi Speciality Trainee in Paediatrics Royal Aberdeen Children's Hospital Aberdeen UK © BMJ Publishing Group Ltd 2012. All rights reserved.

..........................................................

31

Child health

Asthma and other recurrent wheezing disorders in children (acute)

Amanda Jane Friend University of Aberdeen Aberdeen UK Stephen William Turner Senior Clinical Lecturer in Child Health and Honorary Consultant Paediatrician University of Aberdeen Aberdeen UK Competing interests: AO, AJF, and SWT declare that they have no competing interests. We would like to acknowledge the previous contributors of this review: Duncan Keeley and Michael McKean.

Disclaimer The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

© BMJ Publishing Group Ltd 2012. All rights reserved.

..........................................................

32

Child health

Asthma and other recurrent wheezing disorders in children (acute)

GRADE

Evaluation of interventions for Asthma and other recurrent wheezing disorders in children (acute).

Important outcomes Studies (Participants)

Adverse effects, Hospital admission/length of stay, Physiological measures, Symptom improvement (acute clinical assessments)

Outcome

Comparison

Type of evidence

Quality

Consistency

Directness

Effect size

GRADE

Comment

What are the effects of treatments for acute asthma in children? 1 (70)

[11]

Hospital admission/length of stay

Continuous versus intermittent nebulised beta2 agonists

4

–1

0

–1

0

Low

Quality point deducted for sparse data. Directness point deducted for small number of comparisons

7 (538)

[12]

[13]

Symptom improvement (acute clinical assessments)

Metered-dose inhaler plus spacer devices versus nebulisers for delivering beta2 agonists

4

–1

0

0

0

Moderate

Quality point deducted for incomplete reporting of results

4 (281)

[12]

[13]

Physiological measures

Metered-dose inhaler plus spacer devices versus nebulisers for delivering beta2 agonists

4

–2

0

0

0

Low

Quality points deducted for incomplete reporting of results and methodological flaws in included RCTs

Hospital admission/length of stay

Metered-dose inhaler plus spacer devices versus nebulisers for delivering beta2 agonists

4

–1

0

–1

0

Low

Quality point deducted for incomplete reporting of results. Directness point deducted for unclear clinical relevance of 1 outcome

Adverse effects

Metered-dose inhaler plus spacer devices versus nebulisers for delivering beta2 agonists

4

–2

0

0

0

Low

Quality points deducted for incomplete reporting of results, and unclear outcome measures

Symptom improvement (acute clinical assessments)

Ipratropium bromide (inhaled) added to beta2 agonists versus beta2 agonists alone

4

–1

–1

–1

0

Very low

Quality point deducted for incomplete reporting of results. Consistency point deducted for different results between studies. Directness point deducted for uncertainty about assessment of clinical response and additional treatments in 1 RCT

at least 10 (not re[15] ported, >74)

Physiological measures

Ipratropium bromide (inhaled) added to beta2 agonists versus beta2 agonists alone

4

–1

0

0

0

Moderate

Quality point deducted for incomplete reporting of results

at least 11 (at least [15] [16] [17] 1860)

Hospital admission/length of stay

Ipratropium bromide (inhaled) added to beta2 agonists versus beta2 agonists alone

4

–1

–1

0

0

Low

Quality point deducted for incomplete reporting of results. Consistency point deducted for different results for different dosage protocols

Physiological measures

Systemic corticosteroids versus placebo

4

–2

0

0

0

Low

Quality points deducted for sparse data and incomplete reporting of results

Hospital admission/length of stay

Systemic corticosteroids versus placebo

4

–1

–1

0

0

Low

Quality point deducted for incomplete reporting of results. Consistency point deducted for different results for different outcome measures

Symptom improvement (acute clinical assessments)

High-dose inhaled corticosteroids versus oral corticosteroids

4

–1

–1

0

0

Low

Quality point deducted for incomplete reporting of results. Consistency point deducted for different results for different outcomes

11 (1008)

[12]

at least 8 (at least [12] [13] 620) 4 (>74)

[16]

[16]

[17]

[17]

2 (64)

[20]

5 (342)

[20]

2 (370)

[27]

[29]

© BMJ Publishing Group Ltd 2012. All rights reserved.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

Child health

Asthma and other recurrent wheezing disorders in children (acute)

Important outcomes Studies (Participants) 4 (539)

[26]

5 (404)

[26]

[28]

[31]

[36]

Consistency

Directness

Effect size

GRADE

Comment

High-dose inhaled corticosteroids versus oral corticosteroids

4

–1

–1

0

0

Low

Quality point deducted for incomplete reporting of results. Consistency point deducted for different results at different time points and for different physiological measures

[30]

Hospital admission/length of stay

High-dose inhaled corticosteroids versus oral corticosteroids

4

–1

–1

0

0

Low

Quality point deducted for incomplete reporting of results. Consistency point deducted for different results between RCTs

Symptom improvement (acute clinical assessments)

Intravenous aminophylline versus placebo

4

–1

0

–1

0

Low

Quality point deducted for incomplete reporting of results. Directness point deducted for restricted population

Physiological measures

Intravenous aminophylline versus placebo

4

–1

0

–1

0

Low

Quality point deducted for incomplete reporting of results. Directness point deducted for restricted population

at least 5 (322)

[35]

[37]

at least 4 (not clear, [35]

Asthma and other recurrent wheezing disorders in children (acute).

Acute childhood asthma is a common clinical emergency presenting across a range of ages and with a range of severities...
292KB Sizes 1 Downloads 3 Views