Asthma Management Handbook

Providing post-acute care

Recommendations

After respiratory distress or increased work of breathing has resolved and symptoms have stabilised, observe the patient for at least 4 hours.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

For adults, adolescents and children old enough to perform spirometry, record spirometry again before discharge.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

At discharge, check if the patient has a preventer that contains an inhaled corticosteroid:

  • If the person is already using (or has been prescribed) inhaled corticosteroids, check adherence and inhaler technique, and instruct the patient or parent/carer to continue their inhaled corticosteroid.
  • For adults and older adolescents with asthma who have not been prescribed inhaled corticosteroids, prescribe an inhaled corticosteroid at a low dose, demonstrate correct inhaler technique, and arrange review of treatment at comprehensive follow-up.
  • For children younger than 12 years with asthma who are not currently taking a preventer, consider whether preventer treatment is indicated and arrange review of treatment at comprehensive follow-up.

Note: Regular low-dose inhaled corticosteroid treatment is indicated for all adults and adolescents over 12 years who have had an asthma flare-up in the previous 12 months.

  • For all inhalers: Train the patient or parent/carer how to use their inhaler correctly. A physical demonstration is essential.
How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

Routine treatment with antibiotics is not recommended after acute asthma.

 

How this recommendation was developed

Consensus following inconclusive literature search

Based on clinical experience and expert opinion after literature review yielded insufficient evidence for an evidence-based recommendation.

Key evidence considered:

  • Normansell et al. 20181
  • Johnston et al. 20162
  • Stokholm et al. 20163

Last reviewed version 2.0

For patients treated in acute care services, complete all of the following before discharge:

  • Ensure that the patient (or parent/carer) is able to monitor and manage asthma at home.
  • Check the patient (or parent/carer) has a reliever medicine and assess their inhaler technique.
  • Provide a spacer, if needed. Make sure the patient (or parent/carer) knows how to use it.
  • Check that the person has a course of oral prednisolone and understands when and how long to take it (if indicated).
  • Check the patient (or parent/carer) has a preventer medicine (if indicated) and assess their inhaler technique.
  • Check that parent/carer knows how to recognise asthma symptoms.
  • Check the patient (or parent/carer) knows what to do if asthma symptoms worsen or do not improve.
  • Advise patient (or parent/carer) to make an appointment with their usual GP in 3 days and a second appointment within 2–4 weeks.
  • For patients of all ages with severe acute asthma or a previous presentation, consider arranging referral to a consultant/respiratory physician.
  • Provide an asthma discharge plan (interim written asthma action plan), that includes instructions on when and how to use reliever, when and how to use preventer (if indicated), when and how to use systemic corticosteroids, what to do if their asthma deteriorates, and when to call 000 for emergency care.
  • Explain that the patient needs their own written asthma action plan prepared by their usual doctor (e.g. GP or respiratory physician).
  • Provide a copy of the discharge summary to the patient’s usual GP.
  • Clearly explain that reliever should only be used as needed for symptoms (or before exercise, if indicated), not regularly. Include this in written information.
How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

Arrange follow-up, including:

  • recheck within 3 days by usual GP
  • comprehensive assessment in 2–4 weeks to review the treatment regimen (e.g. refer to person’s GP or arrange specialist assessment).
How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

At the follow-up review, the patient’s usual doctor (e.g. GP) should:

  • try to identify trigger factors associated with the acute asthma episode
  • review the person’s written asthma action plan
  • review the person's reliever use and give instructions to use reliever only as needed
  • review the treatment regimen and prescribe or adjust inhaled corticosteroid-containing preventer, if indicated
  • check inhaler technique and correct it, if necessary
  • assess whether the person has other risk factors for asthma flare-ups
  • offer specialist review if the person has had more than one emergency visit to health services for acute asthma within the previous 12 months or repeated corticosteroid treatments.

Note: Regular inhaled corticosteroid treatment is indicated for all adults and adolescents over 12 years who have had an asthma flare-up in the previous 12 months.

  • For all inhalers: Train the patient or parent/carer how to use their inhaler correctly. A physical demonstration is essential.
  • Clearly explain that when asthma is back under control the reliever should only be used as needed for symptoms (or before exercise, if indicated), not regularly. Include this in written information.
How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

More information

The 1-hour assessment

Very little evidence is available to determine when it is safe to discharge a patient with severe acute asthma from the emergency department. Few studies have correlated features of clinical history, examination, response to medications  or objective measures of airflow obstruction with outcomes after discharge including relapse.

Timing of decision to admit or discharge

An Australian ‘real world’ prospective observational study,4 which included children and adults aged 1–55 years with acute asthma presenting to emergency departments, correlated severity class assessed at initial presentation and at the 1-hour assessment with clinicians’ assessment of need for hospital admission or intensive care unit admission. Compared with assessed severity class at initial presentation, severity class assessed at 1 hour better predicted:4

  • the decision for hospital admission among patients initially assessed as having ‘moderate’ acute asthma (e.g. able to speak in phrases, oxygen saturation 92–95%, FEV1 50–75% predicted, pulse rate 100–120/min)
  • the decision to admit to the intensive care unit among patients initially assessed as having ‘severe’ acute asthma (e.g. physical exhaustion, unable to speak more than a word at time, oxygen saturation < 92%, FEV1 < 50% or <1 L, pulse rate >120/min).

The ‘lie flat’ test (adults)

In adults, at 1 hour after initial treatment, the ability to lie flat without dyspnoea may be a useful indicator of adequate recovery without the need for hospital admission, particularly when combined with adequate improvement in FEV1 measured by spirometry.5

Spirometry

A study in adults with acute asthma found that, on its own, FEV1 (measured by spirometry) at 1 hour after admission to the emergency department did not closely correlate with clinicians’ decision for or against hospital admission, as assessed clinically.5 However, the combination at 1 hour of FEV1 and the ‘lie flat’ test was significantly predictive of the decision for hospital admission.5

Most adults with acute asthma can perform spirometry within the first hour of admission to the emergency department.6

Table. Tips for performing spirometry in patients with acute asthma

  • Ask the patient to sit straight upright, either in a chair or on a stretcher with their legs over the side.
  • Make sure the person forms a tight seal around the mouthpiece.
  • Tell the patient to take as deep a breath as possible, then blast out air as fast and hard as they can, then keep blowing until asked to stop. Aim for exhalation of maximal force for at least 2 seconds (6 seconds if FVC is measured).

You may need to give the patient lots of coaching, repeat instructions, and give immediate feedback on technique.

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Asthma discharge plans (interim asthma action plans)

An asthma discharge plan is an interim action plan provided after treatment for acute asthma at discharge from an emergency department or hospital admission. Its purpose is to provide written instructions until the person returns to their usual doctor or nurse practitioner for review of their written asthma action plan.

It should include (all of):

  • the patient’s name
  • instructions for oral corticosteroid course (dose, duration, when to take)
  • instructions for reliever dose in immediate post-acute period (dose, how to take including use of spacer, duration of this dose)
  • instructions for going back to usual as-needed reliever regimen (clearly state the number of actuations to be taken as needed)
  • instructions for preventer
  • what to do if symptoms getting worse or recur within hours of taking reliever
  • instruction to make appointment with usual doctor e.g. GP.

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Systemic corticosteroids in acute asthma

Systemic corticosteroids in acute asthma

In adults and school-aged children with acute asthma, systemic corticosteroids given within 1 hour of presentation to an emergency department reduce the need for hospital admission.7 In children admitted to hospital with acute asthma, systemic corticosteroid treatment may achieve earlier discharge and fewer relapses.8

In preschool children with acute viral-induced wheezing, there is inconsistent evidence for the benefits of systemic corticosteroids.9, 10, 11 Oral corticosteroids may be beneficial in children younger than 6 years with frequent acute wheezing or asthma, but current evidence does not strongly support their use in this age group.12 The Thoracic Society of Australia and New Zealand position statement on the use of corticosteroids in children13 recommends that the use of systemic corticosteroids in preschool children, particularly those with intermittent viral induced wheezing, should be limited to those with wheeze severe enough to need admission to hospital.

After an acute asthma episode, treatment with systemic corticosteroids (intramuscular corticosteroids, oral prednisone/prednisolone, or oral dexamethasone) at discharge from the emergency department reduces the risk of relapse in adults14 and children.15, 16

Formulation and route of administration

In adults and children with acute asthma, oral prednisone/prednisolone is as effective as intravenous or intramuscular corticosteroids.7, 17

Oral dexamethasone is as effective as prednisone/prednisolone in adults and children18, 19, 20, 21, 22, 23, 24, 25, 26

Dose

In adults, 40 mg per day prednisolone/prednisone,27  up to 80 mg/day methylprednisolone, or up to 400 mg/day hydrocortisone28 are adequate.

In children the majority of studies in children have used 1–2 mg/kg of oral prednisolone (maximum 60 mg) given initially then 1 mg/kg per day. Current evidence does not support the use of higher doses.17

Studies evaluating oral dexamethasone in adults have used a single dose of 12 mg18 or 16 mg on 2 consecutive days.26 Most studies evaluating oral dexamethasone in children have used 0.6 mg/kg per dose on one or two consecutive days.21

Duration

In adults, an oral or intramuscular corticosteroid course of at least 7 days appears more effective than a shorter course in preventing relapse within 10 days of discharge after acute asthma,14 although one clinical trial evaluating prednisone reported that 5 days was as effective as 10 days.29 Courses less than 5 days are not recommended.

In children, a 3-day course of prednisone/prednisolone is generally as effective as a 5-day course,30 but 5 days may be needed for children with severe or life-threatening acute asthma.13

It is not necessary to taper the dose after a short course of oral prednisone/prednisolone.14, 31, 32

Dexamethasone has a longer half-life than prednisone/prednisolone. Longer courses may more pronounced mineralocorticoid adverse effects. Oral dexamethasone treatment in adults or children should not exceed 2 days.

Adverse effects

Short-term use of oral corticosteroids to treat acute asthma is often well tolerated in children and adults,7, 8, 10, 25 but many patients report significant adverse effects, particularly mood changes, gastrointestinal disturbances,34 nocturia, and difficulty sleeping. While short courses of high-dose systemic treatment cause fewer adverse effects than prolonged courses of lower doses,35 more recent analyses have shown a significant association between short courses of oral corticosteroids and sepsis, thromboembolism and fracture.36, 37

Oral dexamethasone appears to be well tolerated in adults.18 In children it may be associated with less vomiting than prednisone/prednisolone.19, 20, 21, 22, 22, 23, 24 The risk of unwanted mineralocorticoid effects are increased if dexamethasone is taken for more than 2 days.

In people with diabetes or impaired glucose tolerance, corticosteroids increase blood glucose levels. Impaired glucose tolerance is common among people aged over 65 years. In patients with diabetes or impaired glucose tolerance, blood glucose monitoring (e.g. morning and evening samples) may be indicated during treatment with oral corticosteroids.

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Inhaled corticosteroids in acute asthma

Inhaled corticosteroid treatment in acute care

Clinical trial evidence does not support the use of inhaled corticosteroids in place of systemic corticosteroid treatment in the treatment of acute asthma.38

Some randomised clinical trials suggest that inhaled corticosteroid treatment may reduce hospital admission rates when given in addition to systemic corticosteroids, but the evidence is conflicting.38 Overall, evidence from randomised clinical trials does not show that inhaled corticosteroid therapy achieves clinically important improvement in lung function or clinical scores when used in acute asthma in addition to systemic corticosteroids.38

Inhaled corticosteroid treatment in post-acute care - short term effects

Current standard follow-up treatment after acute asthma includes a course of systemic corticosteroids, and continuation of inhaled corticosteroids for patients already taking this treatment.

Overall, evidence from short term randomised clinical trials suggests that inhaled corticosteroid treatment, given at discharge from the emergency department after acute asthma, does not provide additional short-term benefit in patients who are also receiving oral corticosteroids.39

Some randomised clinical trials suggest that high-dose inhaled corticosteroid treatment at discharge from the emergency department may be as effective as oral corticosteroids in patients with mild acute asthma, but overall evidence does not support replacing oral corticosteroids with inhaled corticosteroids.39

These clinical trials were designed to assess short term effects of inhaled corticosteroid in managing the current acute asthma episode. This evidence does not suggest that inhaled corticosteroids should be stopped after or during an acute asthma episode.39 Regular inhaled corticosteroid treatment is highly effective for preventing asthma flare-ups, including in patients with a recent asthma hospitalisation. A large case-control study showed that, after hospitalisation for asthma, regular ICS were associated with a 39% reduction in the risk of re-hospitalisation within the following 12 months.

Rationale for prescribing inhaled corticosteroids at discharge from acute care

Inhaled corticosteroid treatment reduces the frequency and severity of asthma flare-ups, reduces the risk of asthma hospitalisation and rehospitalisation, and reduces the risk of death due to asthma.40, 41

Regular inhaled corticosteroid treatment is therefore indicated for all adults and older adolescents who have experienced a flare-up within the last 12 months, as well as for those with asthma that is not well controlled (asthma symptoms twice or more during the past month, or waking due to asthma symptoms once or more during the past month).

At the time of discharge from the emergency department or hospital, there is an opportunity to start inhaled corticosteroid treatment and to ensure that the patient's usual GP will review the treatment regiment at the follow-up visit.

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References

  1. Normansell R, Sayer B, Waterson S et al. Antibiotics for exacerbations of asthma. Cochrane Database Syst Rev 2018; 6: CD002741. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29938789/
  2. Johnston SL, Szigeti M, Cross M et al. Azithromycin for acute exacerbations of asthma : the AZALEA randomized clinical trial. JAMA Intern Med 2016; 176: 1630-7. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27653939/.
  3. Stokholm J, Chawes BL, Vissing NH et al. Azithromycin for episodes with asthma-like symptoms in young children aged 1-3 years: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2016; 4: 19-26. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26704020/.
  4. Kelly, A. M., Kerr, D., Powell, C.. Is severity assessment after one hour of treatment better for predicting the need for admission in acute asthma?. Respir Med. 2004; 98: 777-81. Available from: https://www.resmedjournal.com/article/S0954-6111(04)00042-3/fulltext
  5. Wilson MM, Irwin RS, Connolly AE, et al. A prospective evaluation of the 1-hour decision point for admission versus discharge in acute asthma. J Intensive Care Med. 2003; 18: 275-285. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15035763
  6. Silverman RA, Flaster E, Enright PL, Simonson SG. FEV1 performance among patients with acute asthma: results from a multicenter clinical trial. Chest. 2007; 131: 164-171. Available from: https://www.ncbi.nlm.nih.gov/pubmed/17218571
  7. Rowe BH, Spooner C, Ducharme F, et al. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev. 2001; Issue 1: CD002178. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11279756
  8. Smith M, Iqbal S, Elliot TM et al. Corticosteroids for hospitalised children with acute asthma. Cochrane Database Syst Rev. 2003; Issue 2: CD002886. Available from: https://www.ncbi.nlm.nih.gov/pubmed/12804441
  9. Foster SJ, Cooper MN, Oosterhof S, Borland ML. Oral prednisolone in preschool children with virus-associated wheeze: a prospective, randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2018; 6: 97-106. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29373235
  10. Panickar J, Lakhanpaul M, Lambert PC, et al. Oral prednisolone for preschool children with acute virus-induced wheezing. N Engl J Med. 2009; 360: 329-328. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19164186
  11. Therapeutic guidelines [Electronic book]: Therapeutic Guidelines Limited; 2018 [cited 2018 April].
  12. Castro-Rodriguez JA, Beckhaus AA, Forno E. Efficacy of oral corticosteroids in the treatment of acute wheezing episodes in asthmatic preschoolers: Systematic review with meta-analysis. Pediatric pulmonology 2016; 51: 868-76. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27074244
  13. van Asperen PP, Mellis CM, Sly PD, Robertson C. The role of corticosteroids in the management of childhood asthma. The Thoracic Society of Australia and New Zealand, 2010. Available from: https://www.thoracic.org.au/journal-publishing/command/download_file/id/25/filename/The_role_of_corticosteroids_in_the_management_of_childhood_asthma_-_2010.pdf
  14. Rowe BH, Kirkland SW, Vandermeer B et al. Prioritizing systemic corticosteroid treatments to mitigate relapse in adults with acute asthma: a systematic review and network meta-analysis. Acad Emerg Med. 2017; 24: 371-81. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27664401/
  15. Castro-Rodriguez, J. A., Rodrigo, G. J., Rodriguez-Martinez, C. E.. Principal findings of systematic reviews for chronic treatment in childhood asthma. J Asthma. 2015; 52: 1038-45. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26303207
  16. Kirkland SW, Vandermeer B, Campbell S et al. Evaluating the effectiveness of systemic corticosteroids to mitigate relapse in children assessed and treated for acute asthma: A network meta-analysis. J Asthma 2018: 1-12. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29693459/
  17. Normansell R, Kew KM, Mansour G. Different oral corticosteroid regimens for acute asthma. Cochrane Database Syst Rev 2016; Issue 5: CD011801. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27176676/
  18. Rehrer MW, Liu B, Rodriguez M et al. A randomized controlled noninferiority trial of single dose of oral dexamethasone versus 5 Days of oral prednisone in acute adult asthma. Ann Emerg Med. 2016; 68: 608-13. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27117874/
  19. Walia MK. Oral dexamethasone versus oral prednisolone in acute asthma: a new randomized controlled trial and updated meta-analysis: pediatric pulmonologist's viewpoint. Indian Pediatr. 2018; 55: 159. Available from: https://www.indianpediatrics.net/feb2018/159.pdf/
  20. Bravo-Soto GA, Harismendy C, Rojas P et al. Is dexamethasone as effective as other corticosteroids for acute asthma exacerbation in children? Medwave. 2017; 17: e6931. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28430773/
  21. Meyer JS, Riese J, Biondi E. Is dexamethasone an effective alternative to oral prednisone in the treatment of pediatric asthma exacerbations? Hosp Pediatr. 2014; 4: 172-80. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24785562/
  22. Keeney GE, Gray MP, Morrison AK et al. Dexamethasone for acute asthma exacerbations in children: a meta-analysis. Pediatrics. 2014; 133: 493-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24515516/
  23. Cronin JJ, McCoy S, Kennedy U et al. A randomized trial of single-dose oral dexamethasone versus multidose prednisolone for acute exacerbations of asthma in children who attend the emergency department. Ann Emerg Med 2016; 67: 593-601.e3. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26460983/
  24. Cronin J, Kennedy U, McCoy S 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. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22909281/
  25. Rowe BH, Spooner C, Ducharme F, et al. Corticosteroids for preventing relapse following acute exacerbations of asthma. Cochrane Database Syst Rev. 2007; Issue 3: CD000195. Available from: https://www.ncbi.nlm.nih.gov/pubmed/17636617
  26. Kravitz J, Dominici P, Ufberg J, et al. Two days of dexamethasone versus 5 days of prednisone in the treatment of acute asthma: a randomized controlled trial. Ann Emerg Med. 2011; 58: 200-204. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21334098
  27. Rodrigo GJ, Nannini LJ. Comparison between nebulized adrenaline and beta2 agonists for the treatment of acute asthma. A meta-analysis of randomized trials. Am J Emerg Med 2006; 24: 217-22. Available from: https://www.ncbi.nlm.nih.gov/pubmed/16490653/
  28. Manser R, Reid D, Abramson MJ. Corticosteroids for acute severe asthma in hospitalised patients. Cochrane Database Syst Rev. 2001; Issue 1: CD001740. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11279726
  29. Jones AM, Munavvar M, Vail A, et al. Prospective, placebo-controlled trial of 5 vs 10 days of oral prednisolone in acute adult asthma. Respir Med. 2002; 96: 950-954. Available from: http://www.resmedjournal.com/article/S0954-6111(02)91369-7/abstract
  30. Chang, A B, Clark, R, Sloots, T P, 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.Available from: https://www.ncbi.nlm.nih.gov/pubmed/18803532/
  31. Cydulka RK, Emerman CL. A pilot study of steroid therapy after emergency department treatment of acute asthma: is a taper needed?. J Emerg Med. 1998; 16: 15-19. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9472754
  32. O'Driscoll BR, Kalra S, Wilson M, et al. Double-blind trial of steroid tapering in acute asthma. Lancet. 1993; 341: 324-327. Available from: http://www.sciencedirect.com/science/article/pii/0140673693901343
  33. Grzelewski, T, Stelmach, I. Exercise-induced bronchoconstriction in asthmatic children: a comparative systematic review of the available treatment options. Drugs. 2009; 69: 1533-1553. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19678711
  34. Berthon BS, Gibson PG, McElduff P et al. Effects of short-term oral corticosteroid intake on dietary intake, body weight and body composition in adults with asthma - a randomized controlled trial. Clin Exp Allergy 2015; 45: 908-19. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25640664/
  35. Australian Medicines Handbook. Last modified July 2018: Australian Medicines Handbook Pty Ltd. 2018
  36. Lefebvre P, Duh MS, Lafeuille MH et al. Acute and chronic systemic corticosteroid-related complications in patients with severe asthma. J Allergy Clin Immunol 2015; 136: 1488-95. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26414880/
  37. Waljee AK, Rogers MA, Lin P et al. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ 2017; 357: j1415. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28404617/
  38. Edmonds ML, Milan SJ, Camargo CA, et al. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database Syst Rev. 2012; 12: CD002308. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002308.pub2/full
  39. Edmonds ML, Milan SJ, Brenner BE, et al. Inhaled steroids for acute asthma following emergency department discharge. Cochrane Database Syst Rev. 2012; 12: CD002316. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002316.pub2/full
  40. Suissa S, Ernst P, Kezouh A. Regular use of inhaled corticosteroids and the long term prevention of hospitalisation for asthma. Thorax. 2002; 57: 880-884.
  41. Suissa, S, Ernst, P, Benayoun, S, et al. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med. 2000; 343: 332-336.