Author: Gary T Kitching, Jason B Lee / Editor: Jason M Kendall / Reviewer: Michael Perry / Code: CAP6, HAP6 / Published: 19/10/2017 Review Date: 19/10/2020
In the UK approximately 4 million adults have asthma. In 2004, over 1200 adults died from asthma in the UK and in 2007 hospital episode statistics1 recorded 40,000 adult emergency admissions due to asthma. The overall cost of treatment of patients with asthma in the UK has been estimated to be over 1 billion/ year.
This session focuses on the treatment of adult patients with previously diagnosed asthma that present to the Emergency Department with an acute episode of breathlessness.
The most recent guidelines published by the British Thoracic Society in September 2016 state that patients who died from asthma had a number of factors contributing to their death. These ranged from severity of disease, their medical management and their behaviour or psychosocial status.
These guidelines are evidence based. The 2016 guidelines update forms the basis for the recommendations made in this session. Although childhood asthma is not considered further in this session, adult guidelines for acute asthma are appropriate for use on children aged over 12 years old.
Basic science and patho-physiology
Asthma is a disorder of the airways that is complex and still not fully understood. However, it is characterised by:-
- Bronchial hypersensitivity
- Bronchial inflammation
- Recurring symptoms of reversible airway obstruction that vary in severity
A large number of cells and mediators have been implicated in the airway inflammation pathway, including the following:
- Mast cells
- Adhesion molecules
Increased mucous secretion and bronchial oedema also contribute to airflow obstruction. Chronically, desquamation of the epithelium and smooth muscle hyperplasia may result in airway re-modelling3.
Why do some asthmatics develop a cardiac arrest?
Mucous plugging from severe bronchospasm causing asphyxia is the commonest modality of death in asthmatics.
Prolonged hypoxia can precipitate cardiac arrhythmia causing death.
Because of bronchoconstriction, airway pressures in the lungs in acute asthma are high. Air can enter the lungs, but cannot escape. This leads to breath stacking which causes an increase in intrathoracic pressure. Raised intrathroracic pressure consequently can cause pneumothoraces to develop or decrease venous return to the heart precipitating circulatory collapse.
Reference: Soar, Perkins, Abbas et al. European Resucitation Council Guidelines for Resucitation 2010. Cardiac Arrest in special circumstances: Electrolyte abnormalities, poisoning, drowning, accidential hypothermia, hyperthermia, asthma, anaphylaxis, cardiac surgery, trauma, pregnancy, electrocution.
Asthma is more commonly diagnosed in boys than girls but the sex ratio is reversed by adulthood where females account for 60% of cases in the UK. It is more common in urban areas and in lower socio-economic groups. Strong associations include a family history of asthma (particularly maternal) and a history of another atopic condition (eg eczema, rhinitis).
It has been suggested that aetiological factors (such as those below) that can exacerbate asthma may also be causative but there is no convincing evidence of this:
- Air pollution
- Passive smoking
- Environmental allergen exposure (eg dust mites)
Occupational asthma can be caused by exposure to specific chemicals and may account for up to 15% of adult onset asthma4.
Diagnosis in adults
The British guidelines state that asthma is a clinical diagnosis since no single test, sign or symptom is specific enough to confirm the diagnosis. Although the majority of cases are diagnosed in childhood, approximately 1 in 4 patients are not diagnosed with asthma until adulthood. A number of factors and test results are considered before the diagnosis is made by the GP or respiratory specialist.
Clinical features that increase the probability of adult asthma
More than one of the following symptoms: wheeze, cough, difficulty breathing, chest tightness, particularly if the symptoms:
- are worse at night/early morning
- occur in response to exercise, allergen exposure or cold air
- are triggered by aspirin or beta-blockers
- occur in the absence of a cold
- Personal or family history of atopic disorder or asthma
- Widespread wheeze on chest auscultation
- Otherwise unexplained low FEV1 or PEFR
- Otherwise unexplained peripheral blood eosinophilia
Clinical features that lower the probability of adult asthma
- Symptoms with colds only
- Chronic productive cough without wheeze or breathlessness
- Dizzyness, light-headedness or paraesthesia peripherally
- Voice disturbance
- Cardiac disease
- Significant smoking history (>20 pack years)
- Repeated normal chest examination when symptomatic
- Repeatedly normal PEFR or spirometry when symptomatic
Patients with a high probability of asthma are treated accordingly, whilst patients with low probability for asthma are treated for the more likely diagnosis. Failure of symptoms to improve with treatment should prompt referral for specialist advice.
For patients with an intermediate probability of asthma some of the following tests may be required to elucidate whether asthma is responsible for their symptoms:
An FEV1/FVC <0.7 is strongly suggestive of asthma. Spirometry has significant advantages over PEFR in the stable setting. The result is less effort dependent than PEFR, normal ranges are more robust and airway obstruction can be clearly documented. A PEFR meter is portable and useful for self monitoring (particularly when occupational asthma is suspected) and in the acute setting.
Treatment trials and reversibility testing
A 400ml improvement in FEV1 (or 60l/min. increase in PEFR) in response to either of the following strongly suggests underlying asthma:
- 400mcg inhaled salbutamol
- 6 week trial of steroid inhaler (beclometasone 200mcg bd or equivalent)
Tests that may be requested be respiratory specialists
The following test have a high sensitivity but moderate specificity for asthma:
- Eosinophil count in sputum (eosinophilic inflammation)
- Exhaled nitric oxide concentration (eosinophilic inflammation)
- Methacholine or histamine challenge (airway hyper-responsivity)
Diagnosis of asthma in the ED
Adults are rarely seen in the ED with their first presentation of asthma and they usually are aware of their condition. A confident diagnosis of asthma cannot be made on a single visit to the ED and conditions that may mimic asthma (see below) acutely should be considered.
Differential diagnosis of adult asthma*
- Inhaled foreign body
- Airway stenosis
- Lung cancer
- Obliterative bronchioloitis
- Congestive cardiac failure
- Pulmonary embolus
- Pulmonary fibrosis
- Hyperventilation syndrome
- Gastro-oesophageal reflux
- Chronic cough syndrome
- Vocal cord dysfunction
*Adapted from the British Asthma Guidelines 2011 update
The following information should be obtained when a patient with asthma presents to the ED with shortness of breath or wheeze:
- Time of onset of symptoms
- Onset abrupt or gradual?
- Pleuritic chest pain?
- Cough (and nature of cough)?
- Current medication
- Compliant with medications?
- Specific questioning about current/recent use of steroids
- Frequency of use of 2 agonist
- Any treatment given by emergency responders/ambulance staff?
- Specific questioning about use of aspirin, NSAIDs and beta-blockers
- Previous best PEFR (in the last 2 years)
Deaths in asthmatics continue to be reported following inappropriate prescription of:
- Beta-blockers (contra-indicated)
- NSAIDs (C/I if previous exacerbation related to NSAID or aspirin use)
A NCEPOD report5 into 200 asthma deaths, most of which occurred out of hospital, found that a history of severe asthma and presence of an adverse psychosocial factor was associated with an increased risk of developing near-fatal or fatal asthma. Admission should be considered for patients with these risk factors regardless of the severity of the current episode.
History of severe asthma* (one or more of the following)
- Previous near-fatal asthma (ventilation, ICU)
- Previous admission for asthma in the last year
- Requiring maintenance therapy of 3 or more classes of asthma medication
- Heavy use of 2 agonist
- Repeated ED attendances with asthma
- Brittle asthma (uncontrolled asthma despite maximum maintenance treatment or recurrent sudden severe episodes when asthma well controlled)
- Adverse psychosocial factor* (one or more of the following)
- Non-compliance with treatment
- Failure to attend appointments/ little GP contact
- Frequent home visits
- Self-discharge from hospital
- Psychiatric illness, self harm, depression
- Extreme situational stress (income/ employment/ marital/ legal)
- Alcohol or drug abuse
- Learning difficulties
- Social isolation
- Childhood abuse
*Adapted from the British Asthma Guidelines 2011 update
Admission should be considered for patients with a history of severe asthma and any adverse psychosocial factor regardless of the severity of the current episode.
A thorough examination of the cardio-respiratory system should be made to identify features consistent with an exacerbation of asthma eg wheeze on auscultation of the chest, tachypnoea, absence of pyrexia, absence of crepitations, and tachypnoea. Occasionally, the symptoms and findings on chest examination may point to another trigger for a sudden worsening of an alternative diagnosis such as pneumonia, pulmonary oedema, pneumothorax or pulmonary embolus.
The following adverse clinical features should be noted*:
- Unable to complete sentences in one breath
- Reduced conscious level
- Accessory muscle use
- Signs of exhaustion
- Poor air entry/ silent chest
*The absence of any of the clinical features above does not rule out a severe attack.
A severe asthma attack cannot be excluded by clinical examination alone
Chest percussion and tracheal position should be assessed since asthmatics are at risk of developing secondary spontaneous pneumothoraces. Failure to recognise a pneumothorax or tension pneumothorax as the cause of sudden deterioration in asthmatics is associated with a significant mortality. This will be exacerbated if the patient is intubated and ventilated.
In order to adequately risk stratify patients and assess response to therapy, the following parameters should be recorded:
- Blood pressure
- Respiratory rate
- Oxygen saturations (pulse oximetry)
- PEFR (if feasible)
Systolic paradox (pulsus paradoxus), an historical marker of severity of asthma, is unhelpful and wastes valuable time6.
Always consider a spontaneous pneumothorax as a cause of sudden deterioration in asthmatics.
Peak Expiratory Flow Rate
Peak expiratory flow (PEF) measurement should be performed on all patients that are capable of performing the test. PEFR is effort dependent and the best of three attempts should be recorded. This process should not be performed in hypoxic patients and should be stopped if a patient becomes hypoxic during testing. Serial measurements allow response to therapy to be assessed.
The benchmark for comparison should be the patients best PEFR in the last 2 years. Patients commonly cannot recall their best PEFR and this may have to be predicted from charts based on their age, sex and height.
Pulse oximetry and PEFR aside, no other investigations are mandatory for patients with acute asthma exacerbations. However, adjuncts to clinical assessment become progressively more important as the severity of the episode increase.
Arterial Blood Gas
The British Thoracic Society guidelines recommend that ABGs should only be performed for patients with oxygen saturations below 92% and those with other life threatening features of asthma. Oxygen saturations below 92% are associated with an increased risk of hypercapnia.
Haematology and biochemical results will not be available in the first hour of an exacerbation and cannot, therefore, guide initial therapy. The white blood cell count may be elevated if the patient is on steroids or has intercurrent infection and hypokalaemia may be caused by 2-agonist treatment (beta-agonists decrease potassium by an average of 0.4mmol/l). Although hypokalaemia rarely produces any clinically significant effects it is best corrected if marked or associated with ECG changes. For patients treated with oral theophyllines who are admitted with severe asthma, a serum theophylline level taken in the ED may identify toxicity or reveal non-compliance.
Chest radiographs should not be routinely requested for patients with acute asthma exacerbations but are recommended in the following settings.
- Suspected pneumothorax, pneumomediastinum, pneumonia
- Life threatening features
- Failure to respond to standard treatment
- Patients requiring ventilation
An ECG should be performed if patients have severe symptoms, an irregular pulse or persistent tachycardia despite treatment. Sinus tachycardias and evidence of right heart strain are common. Rarely, the ECG may show changes suggestive of hypokalaemia (flat T waves, ST depression, long QT, U wave) which if confirmed should be corrected.
The British Asthma guidelines risk stratify adults with acute asthmatic exacerbations into one of the following categories:
- Near fatal asthma
- Life-threatening asthma
- Acute severe asthma
- Moderate asthma exacerbation
- Mild asthma exacerbation
Risk stratification helps guide initial treatment, investigation and management of patients. The BTS/SIGN guidelines contain a flow chart that is clinically useful in managing patients with acute asthma2. It is vital that the ambulance Patient Report Form is read to determine the initial severity of the attack, particularly when 2 agonists and oxygen have been administered prior to hospital. Patients with initially life-threatening asthma may improve sufficiently that they are erroneously categorised as moderate asthma when reviewed in the ED. The British asthma guidelines recommend extended observation of these patients before discharge is considered.
Proformas incorporating this guidance have been demonstrated to improve the management of patients with asthma in the ED7 and their use is strongly recommended.
To ensure correct classification of asthma severity for patients arriving by ambulance, the ambulance Patient Report Form must be reviewed
Near fatal asthma
Raised PaCO2 and/or needing high inflation pressures if ventilated
Life threatening asthma
The presence of any one of the following signs or results indicates that the current exacerbation is life-threatening.
- Reduced conscious level
- Signs of exhaustion
- Poor air entry/ poor respiratory effort
- Silent chest
- PEFR <33% best or predicted
- SpO2 <92% or PaCO2 normal (4.6-6.0 kPa)
Acute severe asthma
The absence of any life-threatening feature and presence of any one of the following factors indicates that the current exacerbation is severe.
- PEFR <50% best or predicted
- Respiratory rate 25/min.
- Heart rate 110/min.
Unable to complete sentences in one breath
Moderate asthma exacerbation
- PEFR 51-75% best or predicted
- No features of acute severe asthma
Mild asthma exacerbation
- PEFR >75% best or predicted
- No features of acute severe asthma
Treatment of acute asthma in adults
Oxygen should be administered to any patient with oxygen saturations below 94% and where pulse oximetry is not immediately available. The oxygen should be titrated to maintain saturations between 94 and 98%. Nebulisers should be driven by oxygen (at least 6l/min.) since there is a risk of desaturation if air-driven systems are used.
Metered dose 2 agonist inhalers with spacers (4 puffs of salbutamol then 2puffs every 2 minutes up to a maximum of 10 puffs) should be used in patients with moderate exacerbations.
Nebulisers may provide superior drug delivery for patients with severe exacerbations and allow concurrent oxygen administration. Repeat doses of 5mg salbutamol nebulisers can be used when the initial response is inadequate. This is sometimes termed back to back nebulisers . In practice a nebuliser takes 15-30 minutes to fully administer the drug. Administering more than 10mg of salbutamol per hour is unlikely to improve effectiveness but may increase side effects, which include tremor and tachycardia. Special delivery systems can deliver continuous nebulisers at 10mg per hour but are not usually available in the ED.
Meta-analyses have not demonstrated superiority of intravenous over nebulised salbutamol in acute asthma. However, intravenous 2 agonists may be beneficial when nebulisers cannot deliver the drug effectively (patient pulling mask off/poor air entry). Nebulised adrenaline has not shown superiority to salbutamol and is a less selective agonist.
An Inhaler with a spacer is the preferred delivery system for patients with moderate severity asthma
Anticholinergic nebulisers may not be beneficial for mild exacerbations of asthma and the British asthma guidelines only advocate their use (Ipratropium Bromide 500 micrograms nebuliser) in cases which are severe, life-threatening, or poorly responsive to 2 agonist therapy.
Side effects are uncommon but include dry mouth, dry eyes, blurred vision, tachycardia, flushing, confusion and urinary retention. Ipratropium bromide is long acting and should not be given more frequently than 4 hourly. If it is given more frequently, the risk of side-effects is increased, particularly in the elderly.
If Ipratropium Bromide has been given by nebuliser in the ambulance it should not be repeated in the first 4 hours in the ED
Early steroid administration in acute severe asthmatic exacerbations is associated with a reduced need for hospital admission8. They should be given acutely to patients with the following features:
PEFR <75% best or predicted after initial salbutamol treatment (5mg nebuliser or spacer as appropriate)
Any indicator of severe asthma after initial appropriate salbutamol therapy
Taking two 25mg tablets or soluble prednisolone is preferable to eight or ten 5mg tablets for patients who are at risk of hypoxia when the oxygen mask is removed. Intravenous hydrocortisone (100mg qds) does not work faster than oral steroids but can be used for patients who are too breathless to swallow or who are vomiting.
A course of steroids should be prescribed for adults whose PEFR was initially <50% best or predicted that have improved sufficiently with treatment to be considered suitable for discharge. Steroids can be stopped abruptly after 5 days as long as the patient continues inhaled steroids. Longer courses are indicated if the patient remains symptomatic or is on long term steroid maintenance therapy. In 2008, a small randomised trial9reported that adults attending an Israeli ED had significantly higher rates of discharge from the ED at 2 hours when inhaled steroids were administered acutely. Use of inhaled steroids, either alone or in conjunction with intravenous steroids, was associated with improved lung function at 2 hours compared to use of intravenous steroids alone. Pulmonary vasoconstriction has been postulated as a possible explanation for inhaled steroid effect in such a short timeframe. It is unclear whether this outcome will be replicated in larger trials but the British guidelines advise that inhaled steroids be started, or continued, as soon as possible after an acute attack. Learning bite: Early steroid administration in acute severe asthmatic exacerbations is associated with a reduced need for hospital admission
The British Asthma Guidelines consider the evidence that magnesium is an effective bronchodilator (muscle relaxant) for the treatment of asthma to be weak. However, they recommend senior medical input to consider its use for patients with life-threatening asthma and those not responding to treatment. The potential side effect of respiratory muscle weakness does not appear to occur in clinical practice when the following regime is used: 2g Magnesium Sulphate in 100mls of normal saline given intravenously over 20 minutes. The 3MG study (due to conclude in 2012) is an ongoing randomised controlled trial that may answer the question of whether magnesium is effective when given to adults with severe asthma in the ED. It is also aiming to determine whether the nebulised route is as effective as the intravenous route.
Aminophylline is of unproven benefit in life-threatening asthma and, unlike magnesium, is pro-arrhythmic. The British asthma guidelines state that it should only be administered for life threatening asthma on the recommendation of senior medical staff. If the patient is on maintenance oral therapy a baseline theophylline/ aminophylline level should be taken before a maintenance infusion of intravenous aminophylline infusion is started. If the patient is not on maintenance therapy, a loading dose infusion should be given first.
Intravenous aminophylline 5mg/kg over 20 minutes
Intravenous aminophylline infusion of 0.6 mg/kg/hour
There is no evidence to suggest that routine intravenous fluid improves outcome in acute asthma. There is a role for fluid when patients are dehydrated or have electrolyte imbalance (hypokalaemia).
The British asthma guideline discourages routine antibiotic prescription in acute asthma. Infective triggers are most commonly viral.
Research is ongoing but there is no current evidence to support the use of leukotriene antagonists in acute asthma.
Inhaling heliox has theoretical benefits since its low density reduces the work of breathing and should improve bronchodilator delivery. However, its use is impractical and existing studies have failed to demonstrate convincing improvements in pulmonary function. Its use not recommended outside of clinical trials.
A theoretical bronchodilator of research interest. To date, nebulised furosemide has not been shown to be significantly better than nebulised 2 agonists.
Ongoing monitoring/ investigations in the ED
- Heart rate, respiratory rate, BP and PEFR should be recorded 15-30 minutes after starting treatment and serially according to response
- Patients that stabilise with treatment should be reassessed at one hour and 2 hours after initial treatment
- Oxygen saturations should be maintained at 94-98%
- Urgent senior medical input should be sought for any patient that fails to improve or deteriorate after initial therapy
- The potassium level should be reviewed when the U&E results are available
- In cases where there is an indication for arterial blood gas sampling, this should be repeated within one hour of starting treatment
Indication for intensive care referral
The British asthma guidelines recommend that the 5-10% patients with acute asthma that have one the following features should be managed on high dependency/ intensive care units:
- Deteriorating PEFR
- Persistent or worsening hypoxia
- Hypercapnea (or falling pH on arterial gas sample)
- Exhaustion, feeble respiration
- Reduced conscious level
- Respiratory arrest
Sedation, intubation and ventilation of asthmatic patients is challenging with many potential pitfalls. Ideally, this should only be performed by a senior anaesthetists or ICU consultant. With increased availability of NIV in the ED, limited evidence has emerged of its potential use for patients with life-threatening asthma10. However, this is not currently supported by the British Thoracic Society and if NIV is to be used in the resuscitation room the patient must be supervised by the intensivist that can proceed immediately to intubation.
NIV should only be considered as a treatment for life threatening asthma when a senior intensivist/ anaesthetist that can proceed directly to intubation is present with the patient in the ED
Indication for admission
Patients with any of the following characteristics should be admitted:
- Life-threatening features at any time
- Signs of severe asthma persisting after initial treatment
Patients suitable for discharge from the ED
Patients considered for discharge should meet all of the following criteria :
1 No life threatening features at any point (including pre-hospital)
2 No features of severe asthma after initial treatment
3 PEFR >75% best or predicted and stable one hour after initial treatment
PEFR >50% best or predicted and stable two hours after initial treatment
Regardless of the PEFR, when any of the following features are present, admission may be appropriate:
- Still have significant symptoms
- Concern over compliance
- Lives alone
- Psychosocial problems
- Physical disability or learning difficulties
- History of severe asthma
- Presentation at night
- Exacerbation despite adequate dose steroids pre-presentation
A decision to discharge a patient with any of the features above should only be made by a senior doctor after discussion with the patient.
Caution should be exercised in discharging patients that present late in the evening or early hours of the morning since the airways are naturally at their narrowest at around 4am.
Ideally, a proforma should be used as an aide-memoire to ensure that the following issues are checked prior to discharge.
Patients that had an initial PEFR of <50% best (or predicted) should be prescribed prednisolone (40-50mg) for 5 days if discharged. If the patient has a steroid inhaler they should be advised to use it twice a day. A new inhaler should be prescribed if they have lost it, it is nearly empty, or have not previously used one.
A check should be made to confirm that the patient has an adequate supply of a 2 agonist inhaler on their person. If not, or if the inhaler is well used, a repeat inhaler should be prescribed. The patients inhaler technique should be checked before discharge and if technique is poor, a spacer should be dispensed.
GP/asthma nurse follow up
The patient should be told to see the GP after 48 hours or return to the ED sooner if they feel that their symptoms are getting worse. A discharge letter should be e-mailed or faxed to the GP practice and, ideally, a GP appointment made for the patient before they leave the ED.
Smoking is associated with increased incidence of relapse following an acute episode, and long term is strongly associated with declining lung function. Patients should be advised to discuss strategies to help them stop when they see their GP. Obese patients should be encouraged to lose weight since in asthmatics this is associated with better symptom control.
No drug treatment used in the treatment of adult patients with acute asthma has been demonstrated to be teratogenic. Oxygen saturations levels should be maintained in the range 94-98%.
The only difference in management of pregnant patients is that obstetrician input is recommended in cases of severe asthma and continuous foetal monitoring commenced.
The British guidelines encourage women with asthma to breastfeed. Although drugs used in the treatment of asthma (salbutamol/ ipratropium/ steroids/ theophyllines) are excreted in breast milk the minute levels are not considered to pose clinical risk to the baby. Experience with newer agents (eg leukotriene antagonists) is less and manufacturers recommendations should be followed.
- Failure to appreciate the severity of the episode before ambulance treatment
- Allowing hypoxia by driving nebulisers with air
- Failure to recognise the patient who has deteriorated secondary to a spontaneous pneumothorax
- Failure to acknowledge the increased mortality risk of patients with a history of severe asthma and an adverse psychosocial factor
- Discharging asthmatic patients late at night
- Failure to arrange GP follow up after discharge
- Prescribing NSAIDs to asthmatics in the ED without first checking about prior use and exacerbations
MedicoLegal and other considerations
Key learning points
- The ED physician should be aware of any treatment given prior to their clinical assessment of the patient in the ED in order to avoid underestimating the severity of the current exacerbation (level five evidence)
- Accurate categorisation of asthma severity allows appropriate treatment to be delivered. (level two evidence)
- Use of acute asthma proformas have been associated with improved patient management. (level three evidence)
- Predicted PEFR should be used as the comparator unless the patients best PEFR was recorded in the last 2 years. (level three evidence)
- Patients whose PEFR was initially <50% best or predicted should be prescribed oral steroids if discharged. (level one evidence)
- Patients with a history of severe asthma and any adverse psychosocial factor are at increased risk of death regardless of the severity of the current episode. (level three evidence)
- Deaths in asthmatics continue to be reported following inappropriate prescription of beta-blockers (contra-indicated) and NSAIDs (C/I if previous exacerbation related to NSAID or aspirin use).
British Thoracic Society/Scottish Intercollegiate Guideline Network: British Guideline on the Management of Asthma. 2011 Guideline. http://www.britthoracic.org.uk/Portals/0/Guidelines/AsthmaGuidelines/sign101%20Sept%202011.pdf
- Hospital Episode Statistics, 2006-2007. Department of Health.
- British Thoracic Society/ SIGN Guidelines for the Management of Asthma 2011 Guidelines. May 2008 (revised May 2011).
- Busse WW, Calhoun WF, Sedgwick JD. Mechanism of airway inflammation in asthma. Am Rev Respir Dis. Jun 1993;147(6 Pt 2):S20-4.
- Blanc PD, Toren K. How much adult asthma can be attributed to occupational factors? Am.J.Med.1999;107(6):580-7.
- Harrison BDW, Slack R, Berrill WT, et al. Results of a national confidential enquiry into asthma deaths. Asthma J. 2000;5(4);180-6
- Pearson MG, Spence DP, Ryland I, et al. Value of assessing pulsus paradox in assessing acute severe asthma. BMJ 1993;307(6905):659
- Robinson SR, Harrison BD, Lambert MA. Effect of a pre-printed form on the management of acute asthma in an accident and emergency department. J Accid Emerg Med. 1996;13(2):93-97
- Rowe BH, Spooner C, Ducharme FM, et al. Early emergency department treatment of acute asthma with systemic corticosteroids. The Cochrane Library 2001;Issue3
- Starobin D, Bolotinsky L, Or J, et al. Efficacy of nebulized fluticasone propionate in adult patients admitted to the emergency department due to bronchial asthma attack. Isr Med Assoc J. 2008;10(8-9):568-71
- Soroksky A, Stav D, Shpirer I. A Pilot Prospective, Randomized, Placebo Controlled Trial of Bilevel Positive Airway Pressure in Acute Asthmatic Attack. Chest 2003;123:1018-1025