PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high-dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming 'uncontrolled' or that remains 'uncontrolled' despite this therapy.
Asthma is a common disease and its frequency sometimes detracts from its potential seriousness. In adults with asthma, only 5-10% have severe disease but these individuals carry a substantial proportion of the cost (both in terms of morbidity and economic consideration) and run the highest risk of acute severe exacerbations and death.
Status asthmaticus is severe asthma that does not respond well to immediate care and is a life-threatening medical emergency. Ensuing respiratory failure results in hypoxia, carbon dioxide retention and acidosis. The exact mechanism underlying the development of an acute severe asthma attack remains elusive but there appear to be two phenotypes:
- Gradual-onset - in about 80%, severe attacks develop over more than 48 hours. These are associated with eosinophilic infiltration and slow response to therapy.
- Sudden-onset - often in association with significant allergen exposure. Patients tend to be older and to present between midnight and 8 am. This type of attack is associated with neutrophilic inflammation and a swifter response to therapy.
In deaths from asthma there is often a failure to recognise the full severity of the situation. This can be down to the patient, their family/carers or the healthcare team but often a multitude of factors is involved. Patients frequently have adverse psychosocial factors that interact with the ability to judge or manage their disease or have a diminished perception of their dyspnoea that leads to late presentation. Medical care continues to fail sometimes to treat acute severe asthma aggressively enough or to comply with national guidelines.
- Every emergency consultation for asthma should be regarded as for acute severe asthma* until proven otherwise.
- All patients with acute severe asthma* that has not responded to immediate treatment or life-threatening asthma* must be referred to hospital.
- There were 1,167 deaths from asthma in the UK in 2011.
- An estimated 75% of admissions for asthma are avoidable and as many as 90% of the deaths from asthma are thought to be preventable.
Risk factors for asthma-related death include:
- A background disease pattern of chronic severe asthma.Severe asthma:
- Previous near-fatal asthma.
- Previous admission for asthma, especially in the preceding year.
- Three or more classes of asthma medication.
- Heavy or increasing use of beta2 agonists.
- Frequent emergency contacts for asthma care, especially in the preceding year.
- 'Brittle' asthma.
- Inadequately treated disease +/- inadequate medical monitoring.
- Inappropriate beta-blocker prescription or heavy sedation.
- Non-steroidal anti-inflammatory sensitivity.
- Use of a long-acting beta2 agonist such as salmeterol, especially if not using a steroid inhaler.
- Personal or passive smoking.
- Environmental conditions - air pollution (ozone, sulfur dioxide, nitrogen dioxide and particulates) and pollen levels are thought to influence the rate of hospital admissions.
- Sensitivity to fungi (see 'Severe asthma with fungal sensitisation (SAFS)', below).
- Adverse behavioural/psychosocial factors:
- Non-compliance, frequent failure to attend appointments, self-discharge, denial of illness.
- Psychiatric illness (psychosis, depression, deliberate self-harm), alcohol or street drug use.
- Learning difficulties.
- Employment problems, income problems, social isolation.
- Childhood abuse.
- Severe domestic, marital or legal stress factors.
- Seasonal variation (in the UK, the peak of deaths in those aged under 44 years is in July-August and, in older patients, December-January).
- Pregnancy will exacerbate asthma in about a third of affected women. Treat the asthma - medication should be continued/stepped up where necessary; it is a lesser risk to the fetus than uncontrolled asthma or severe exacerbations.
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Severe asthma with fungal sensitisation (SAFS)
Severe asthma may be caused by sensitisation to fungi. See also separate article Aspergillosis for further details regarding allergic bronchopulmonary aspergillosis (ABPA) and SAFS.
- SAFS refers to patients with severe asthma (despite standard treatment) with evidence of fungal sensitisation who do not meet the criteria for ABPA. The total IgE is usually lower than for patients with ABPA (total IgE <1000 IU/mL).
- Most affected patients only react to one of two fungi, most often Aspergillus fumigatus or Candida albicans.
- Patients with SAFS usually suffer with chronic severe asthma symptoms despite maximal treatment, including steroids.
- Treatment of SAFS should initially be similar to that of severe asthma.
- Antifungal therapy with itraconazole is beneficial (fluconazole may be beneficial in those sensitised to Trichophyton spp.). The duration of antifungal therapy required is not yet fully established.
- Shortness of breath may develop over hours or days but is usually progressive rather than sudden.
- A history of poor control is common.
- Often there has been a recent increase in use of reliever inhalers, with decreasing response.
- Possible respiratory tract infection or exposure to an allergen or trigger.
- The patient will usually appear pink. Cyanosis is a serious sign.
- Their respiratory rate is raised.
- Tachycardia is usual and may be increased by use of beta2 agonists.
- Accessory muscles of respiration are employed (best assessed by palpation of the neck muscles) and the chest appears hyper-inflated.
- In normal breathing, the ratio of the duration of inspiration to expiration is about 1:2 but, as asthma becomes more severe, the expiratory phase becomes relatively more prolonged.
- Wheeze is usually expiratory, but may also be inspiratory in more severe asthma.Pitfalls:
- A very tight chest may not wheeze at all due to poor air entry. Beware the silent chest.
- Patients with severe or life-threatening asthma may not appear distressed.
- The presence of any relevant abnormality should alert the doctor.
- Where signs/symptoms cross categories of severity, always assign the most severe category.
- Pulsus paradoxus is no longer recommended as a reliable indicator of the severity of an asthma attack.
Status asthmaticus must be distinguished from other causes of acute breathlessness, including:
- Wheezing in children, which can be caused by a variety of infective conditions - eg, respiratory syncytial virus - causing bronchiolitis.
- Foreign body inhalation and other causes of stridor (eg, epiglottitis, croup, tracheitis, vascular ring, tracheomalacia, etc).
- Allergic reaction, anaphylaxis.
- Primary pulmonary hypertension.
- Pneumothorax with or without asthma.
- Inhalation injury.
- Acute exacerbations of chronic obstructive pulmonary disease (COPD).
- Lung cancer.
- Cardiac failure ('cardiac asthma').
The following summary applies to adults. See the separate article for Management of Childhood Asthma.
- Take a very quick history and brief examination (conscious level, colour, pulse, blood pressure, respiratory rate, listening to chest, etc).
- Supplement with objective bedside investigations if available:
- Peak expiratory flow rate (PEFR) - this can be useful as an objective measurement and should be attempted, but can be unreliable due to distress or poor co-operation. PEFR should be compared with a personal best PEFR done within the previous two years and when clinically well controlled.
- Pulse oximetry - a good quick measure of oxygenation.
Assessment of severity
If a patient has signs and symptoms across categories, always treat according to their most severe features.
- Moderate asthma exacerbation:
- Increasing symptoms.
- PEFR >50-75% best or predicted.
- No features of acute severe asthma.
- Acute severe asthma - any one of:
- PEFR 33-50% best or predicted.
- Respiratory rate ≥25 breaths/minute.
- Heart rate ≥110 beats/minute.
- Inability to complete sentences in one breath.
- Life-threatening asthma - any one of the following in a patient with severe asthma:
- Clinical signs: altered conscious level, exhaustion, arrhythmia, hypotension, cyanosis, silent chest, poor respiratory effort.
- Measurements: PEFR <33% best or predicted, SpO2 <92%, PaO2 <8 kPa, 'normal' PaCO2 (4.6-6.0 kPa).
- Consider the need for immediate transfer to hospital - arrange 999/112/911 ambulance.
- Give supplementary oxygen to all hypoxaemic patients with acute severe asthma to maintain an SpO2 level of 94-98%. Lack of pulse oximetry should not prevent the use of oxygen.
- Beta2 agonist bronchodilators:
- Outside hospital, high-dose beta2 agonists may be given via large spacer devices (4-10 puffs inhaled individually) or nebulisers once available (this should be oxygen-driven where available). Repeat doses of beta2 agonists at 15- to 30-minute intervals. There is no evidence for any difference in efficacy between salbutamol and terbutaline.
- Higher bolus doses (eg, 10 mg of salbutamol) are unlikely to be more effective.
- Reserve intravenous beta2 agonists for those patients in whom inhaled therapy cannot be used reliably.
- For adults with severe asthma that is poorly responsive to an initial bolus dose of beta2 agonist, consider continuous nebulisation of salbutamol at 5-10 mg/hour with an appropriate nebuliser. Continuous nebulised beta2 agonists are of no greater benefit than the use of frequent intermittent doses in the treatment of children with acute asthma.
- Ipratropium bromide:
- Add nebulised ipratropium bromide (0.5 mg 4- to 6-hourly) to beta2 agonist treatment for adults with acute severe or life-threatening asthma, or those with a poor initial response to beta2 agonist therapy.
- Corticosteroids reduce mortality and should be given as early in the acute attack as possible. Give steroids in adequate doses in all cases of acute asthma. Steroid tablets are as effective as injected steroids, provided they can be swallowed and retained.
- Give oral prednisolone in all cases of acute asthma attack in adults. Higher doses of steroids don't appear to have any advantage.
- Continue prednisolone 40-50 mg daily for at least five days or until recovery.
- Consider giving an infusion of IV magnesium sulfate (only after consultation with senior medical staff) for patients with life-threatening or near-fatal asthma, or with acute severe asthma who have not had a good initial response to inhaled bronchodilator therapy.
- Antibiotics are not routinely indicated.
Criteria for admission
- Any feature of life-threatening or near-fatal attack.
- Any feature of severe attack persisting after initial treatment.
- Patients with PEFR >75% best or predicted, one hour after initial treatment but where:
- There are significant symptoms.
- There are concerns about compliance.
- The patient is socially isolated/lives alone.
- Psychological problems exist.
- There is physical disability or learning difficulties exist.
- There is previous near-fatal or brittle asthma.
- There has been exacerbation despite the adequate dose of oral steroid tablets prior to presentation.
- Presentation is at night.
- Any patient requiring ventilatory support or with acute severe or life-threatening asthma who fails to respond to treatment as summarised above will need referral to intensive care.
- Arrange a 999/112/911 ambulance if there is any feature of life-threatening or worsening acute severe asthma.
- Stay with the patient until the ambulance arrives. Maintaining calm in the patient and their family is very important - patients with acute asthma are often highly anxious.
- Continue treating (high-dose short-acting beta2 agonist via oxygen-driven nebuliser) and regularly reassessing the patient (at least every 15 minutes) until the transfer to hospital has been achieved.
- Send written assessment and referral details with the patient.
Further hospital-based management
Monitoring and investigations
- Continue regular monitoring - PEFR following nebulised or inhaled beta2 agonists, continuous oxygen saturation monitoring, pulse, respiratory rate.
- Blood tests - FBC, serum potassium and glucose, serum theophylline (where aminophylline is used for more than 24 hours).
- Arterial blood gases should be checked where there are life-threatening features. The four stages of blood gas progression in status asthmaticus are as follows:
- The first stage is characterised by hyperventilation with a normal pO2 and low pCO2.
- The second stage has hyperventilation but hypoxaemia so that both pO2 and pCO2 are low.
- The third stage gives a 'false-normal' pCO2 as ventilation has decreased. This is extremely serious and indicates respiratory muscle fatigue with the need for admission to the ICU and, probably, intubation with mechanical ventilation.
- The fourth stage has a low pO2 and a high pCO2 as respiratory muscles fail.
- The initial pO2 is <8 kPa unless SaO2 is >92%.
- The initial pCO2 is normal or raised.
- The patient's condition deteriorates.
- The third and fourth stages require admission to ICU.
- Consider the need for CXR - routine use is not recommended but it may be used to exclude consolidation or pneumothorax and is needed prior to mechanical ventilation.
Further hospital treatment
- IV fluids where the patient is dehydrated and correction of hypokalaemia (caused/exacerbated by beta2 agonist and steroid regimes).
- IV aminophylline - this is only used in patients with near-fatal or life-threatening asthma with poor response to initial treatment, after consultation with senior staff. Side-effects (eg, arrhythmias and vomiting) increase with its use.
- Where patients are failing to respond to treatment, they require transfer to ICU or high-dependency unit (HDU) conditions.
- Those with worsening hypoxia, hypercapnoea, drowsiness or unconsciousness and those experiencing a respiratory arrest require intubation. This is technically difficult and and should be undertaken by an anaesthetist or ICU consultant.
- The use of non-invasive positive pressure ventilation (NIPPV) in status asthmaticus remains controversial.
- Evidence on the efficacy of bronchial thermoplasty for severe asthma shows some improvement in symptoms and quality of life, and reduced exacerbations and admission to hospital.
Complications of status asthmaticus include:
- Aspiration pneumonia.
- Respiratory failure and arrest.
- Cardiac arrest.
- Hypoxic-ischaemic brain injury.
The risk of death is increased where there is delay in getting treatment, particularly time to starting steroids, comorbidities such as congestive heart failure or COPD and in smokers. Mortality is highest in the very young and the very old.
- All patients with asthma, but especially those with poorly controlled disease, should have access to education about their condition and to regular review, and should have an asthma action plan.
- In addition to an asthma register, an 'at-risk' asthma register may help. If 'at-risk' patients fail to attend for appointments this should be actively followed up.
- Those who are difficult to control need referral to specialist services.
- Be especially vigilant about those with psychosocial adverse factors too.
- Beta2 agonist therapy used in isolation is only appropriate for those with the mildest variant of asthma.
- Receptionists, ambulance control workers and those who are first point of contact by patients must appreciate that an asthmatic having difficulty breathing needs to be seen as an emergency.
- Hospital admission should be an opportunity to review the patient's care plan.
- Anyone who has required admission should be followed up by a respiratory physician for at least a year.
- Patients who have had near-fatal asthma or brittle asthma should remain under specialist care indefinitely.
Further reading & references
- International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma; European Respiratory Society (2014)
- Holgate ST, Polosa R; The mechanisms, diagnosis, and management of severe asthma in adults. Lancet. 2006 Aug 26;368(9537):780-93.
- Restrepo RD, Peters J; Near-fatal asthma: recognition and management. Curr Opin Pulm Med. 2008 Jan;14(1):13-23.
- Ramnath VR, Clark S, Camargo CA Jr; Multicenter study of clinical features of sudden-onset versus slower-onset asthma exacerbations requiring hospitalization. Respir Care. 2007 Aug;52(8):1013-20.
- British guideline on the management of asthma; Scottish Intercollegiate Guidelines Network - SIGN (Oct 2014)
- Asthma facts and FAQs; Asthma UK, 2014
- Hancox RJ; Concluding remarks: can we explain the association of beta-agonists with asthma mortality? A hypothesis. Clin Rev Allergy Immunol. 2006 Oct-Dec;31(2-3):279-88.
- Hogan C, Denning DW; Allergic bronchopulmonary aspergillosis and related allergic syndromes. Semin Respir Crit Care Med. 2011 Dec;32(6):682-92. Epub 2011 Dec 13.
- Agarwal R; Severe asthma with fungal sensitization. Curr Allergy Asthma Rep. 2011 Oct;11(5):403-13.
- Denning DW, O'Driscoll BR, Powell G, et al; Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: The Fungal Asthma Sensitization Trial (FAST) study. Am J Respir Crit Care Med. 2009 Jan 1;179(1):11-8. Epub 2008 Oct 23.
- Lim WJ, Mohammed Akram R, Carson KV, et al; Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Database Syst Rev. 2012 Dec 12;12:CD004360. doi: 10.1002/14651858.CD004360.pub4.
- Bronchial thermoplasty for severe asthma; NICE Interventional Procedures, January 2012
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.
Dr Chloe Borton
Dr Colin Tidy
Prof Cathy Jackson