Next Lesson - Chronic Obstructive Pulmonary Disease
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This article follows the joint NICE, BTS and SIGN asthma guideline (NG245, 2024) for diagnosis and chronic asthma, and the BTS and SIGN asthma guideline (SIGN 158, 2019) for acute asthma. The British Thoracic Society guideline pages can be found here: https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma/
Asthma is a chronic disorder of the airways, characterised by intermittent airway obstruction and airway hyper-reactivity (the airways react too easily to triggers). The airway narrowing is usually reversible, either spontaneously or with treatment.
In allergic asthma, an ‘asthma attack’ follows exposure to a trigger (an allergen) that causes a hypersensitivity reaction. Other triggers, such as exercise, can set off an attack without an allergic reaction. The chronic inflammatory process seen in allergic asthma is mainly driven by TH2 cells (a type of helper T lymphocyte). Other types of asthma exist, so this pattern is not found in everyone with asthma. In this process, antigen-presenting cells (cells that show a piece of the trigger to other immune cells), mainly dendritic cells, take up the trigger and present it to T lymphocytes, which activate the TH2 cells. These cells then release cytokines (chemical messengers between immune cells), which attract and activate other inflammatory cells. These include mast cells (immune cells in the airway wall that store histamine), eosinophils and B cells. B cells produce IgE, the antibody that binds allergens.
The reaction usually results in a two-phase response, consisting of an immediate response, which reaches its peak within 30 minutes, and a late phase response, in which the airway narrowing returns after 3-4 hours and reaches its maximum over 6-12 hours.
In the immediate response, allergen binding to IgE antibodies on mast cells causes degranulation (release of the chemicals stored in the cell). The mast cells release mediators (chemical signals) such as histamine, tryptase (an enzyme), prostaglandin D2 and leukotrienes (chemicals that narrow the airways). It is these mediators that then cause the bronchial smooth muscle contraction of the airways, which leads to the bronchoconstriction (narrowing of the airways) seen in an asthma attack. This is an example of type I hypersensitivity.
In the late phase response, the mast cells and eosinophils release mediators and cytokines, which cause airway inflammation. Eosinophils release granule proteins, including major basic protein, which can contribute to airway epithelial injury. Eosinophils also release cysteinyl leukotrienes. These are chemical signals that promote bronchoconstriction and airway inflammation. They act differently from the granule proteins, which damage cells directly. This late phase reaction remains part of a type I hypersensitivity response.
The airway inflammation causes mucosal swelling. Fluid leaks out of the small blood vessels (endothelial leakage) as part of the immune response, which reduces the calibre (width) of the airway. The infiltration of inflammatory cells causes thickening of the bronchial walls. There is an increased production of mucus, which is thick and slow moving, and contains the epithelium shed by the airways.
If the asthma is poorly controlled, there can be permanent remodelling of the airways, which may not be fully reversible. These changes include hypertrophy and hyperplasia of smooth muscle, hypertrophy of mucus glands, and thickening of the basement membrane (the thin layer of connective tissue under the airway lining).
Diagram - Normal airway vs asthmatic airway
Public Domain Source by United States-National Institute of Health: National Heart, Lung, Blood Institute [Public domain]
Many things can trigger asthma. These include allergens, house dust mite faeces, cold air, exercise, fumes, cigarette smoke and perfumes. Certain drugs can also trigger asthma. Examples are NSAIDs (non-steroidal anti-inflammatory drugs, such as ibuprofen and aspirin) and β-blockers (drugs, such as propranolol, that slow the heart and lower blood pressure). Examples of allergens include pollen and animal hair or dander (tiny flakes of skin).
The inflammatory changes seen in asthma cause the airways to become hyper-responsive, meaning an asthma attack can be triggered in response to non-allergic stimuli.
Asthma usually starts in childhood, but it can start at any age.
Common symptoms of an asthma attack are:
- Dry cough - that is more common at night, partly due to increased vagal activity.
- Expiratory wheeze (a high-pitched whistling sound made when breathing out) - heard either audibly or through a stethoscope.
- Breathlessness
- Chest tightness
Someone who presents with asthma for the first time may describe earlier attacks, or milder versions of the symptoms above that have gone on for some time. Symptoms usually come and go, and they may be worse at night and early in the morning.
The patient may also have a history of atopy (a tendency to develop allergic conditions) such as hayfever, eczema or food allergy.
Examination can be normal, and normal findings do not rule out asthma. During an acute attack, the patient may have an increased respiratory rate, an increased heart rate and decreased oxygen saturations. There may also be an expiratory wheeze on auscultation (listening to the chest with a stethoscope).
Asthma is diagnosed from a suggestive history plus an objective test. In adults, NICE, BTS and SIGN advise testing in this order. First, measure the blood eosinophil count (eosinophils are a type of white blood cell) or the FeNO (fractional exhaled nitric oxide, a breath test that measures airway inflammation). Asthma is diagnosed if the eosinophil count is above the laboratory reference range or the FeNO is 50 ppb (parts per billion) or more. If this does not confirm asthma, measure bronchodilator reversibility using spirometry (see below). If spirometry is not available or is delayed, measure peak expiratory flow (PEF, the fastest speed at which a person can blow air out) twice a day for 2 weeks. In children aged 5 to 16, a FeNO of 35 ppb or more is checked first. A peak flow meter can be used in a GP setting, or by the patient at home.
To use a peak flow meter correctly, there should be a ‘best of three’ approach, where the patient takes three peak flow readings and records the highest. A reading can be compared with the value expected for someone of the same age, sex and height. A single reading does not diagnose asthma. What supports asthma is variability: readings taken twice a day for 2 weeks that vary by 20% or more.
NICE, BTS and SIGN advise against regular peak flow monitoring to assess how well asthma is controlled, unless there is a person-specific reason. One example is when peak flow measurement is part of the person’s personalised asthma action plan (a written plan agreed with their healthcare professional). Airflow obstruction in asthma varies, and spirometry may be normal, particularly between episodes or after treatment. In an adult with a suggestive history, if eosinophil count or FeNO has not confirmed asthma, NICE recommends bronchodilator reversibility testing: spirometry is done before and after a bronchodilator (a medicine that widens the airways). An increase in FEV1 (forced expiratory volume in one second, the amount of air that can be blown out in the first second of a forced breath out) of ≥12% and ≥200 mL from baseline, or ≥10% of predicted FEV1, supports the diagnosis. FVC (forced vital capacity) is the total amount of air that can be blown out. A person with asthma does not need to have a reduced FEV1/FVC ratio, because spirometry can be normal. Reversibility is a useful contrast with COPD (chronic obstructive pulmonary disease), in which airflow obstruction is typically not fully reversible after a β-agonist is given.
Management of chronic asthma is achieved through secondary prevention (stopping attacks in someone who already has asthma), by removing triggers from the home if possible, and through medication.
The use of medication for asthma follows the stepwise management pathway, in which the patient’s medication is reviewed regularly, and then may be stepped up or down depending on symptoms. The aim is to give the least treatment needed to control symptoms and prevent an acute exacerbation (a sudden worsening, or ‘attack’).
The treatment pathway for people aged 12 and over is outlined below. Children under 12 follow separate pathways. Before escalation, it is important to check adherence (whether the patient takes the treatment as prescribed) and inhaler technique, as improving these may be more effective than changing the medication.
- Step 1 - offer a low-dose ICS/formoterol combination inhaler to be taken as needed for symptom relief (as-needed AIR therapy, short for anti-inflammatory reliever). ICS means inhaled corticosteroid, an anti-inflammatory steroid. Formoterol is a long-acting β2 agonist, a medicine that relaxes the airway muscle. A short-acting β2 agonist (SABA) reliever, such as salbutamol, must not be prescribed without an ICS. If a patient is highly symptomatic (for example, waking regularly at night) or has a severe exacerbation, start low-dose MART (maintenance and reliever therapy, described in Step 2) instead.
- Step 2 - if asthma is not controlled on as-needed AIR therapy, offer low-dose MART (maintenance and reliever therapy). In MART, one ICS/formoterol inhaler is taken regularly to prevent symptoms and is also used as needed to relieve them.
- Step 3 - if asthma is still not controlled on low-dose MART, offer moderate-dose MART. LABAs (long-acting β2 agonists) such as formoterol and salmeterol are not anti-inflammatory on their own, so they must always be prescribed with an ICS, commonly in one inhaler.
- Step 4 - if asthma is not controlled on moderate-dose MART despite good adherence, check the FeNO and the blood eosinophil count. If either is raised, refer to a specialist in asthma care. If neither is raised, consider a trial of a leukotriene receptor antagonist (LTRA, for example montelukast) or a long-acting muscarinic receptor antagonist (LAMA, for example tiotropium) added to moderate-dose MART. Each trial lasts 8 to 12 weeks. If control improves but is still inadequate, continue it and trial the other medicine. If there is no improvement, stop it and trial the other medicine. Follow the MHRA (the UK medicines regulator) safety advice on neuropsychiatric reactions (effects on mood and behaviour) with montelukast.
- Step 5 - if asthma is still not controlled after moderate-dose MART and trials of both an LTRA and a LAMA, refer to a specialist in asthma care. Specialist care can involve oral steroids and/or biological therapies (antibody medicines that block specific parts of the inflammatory process).
Asthma is uncontrolled, and the next step should be considered, if the patient has had an exacerbation needing oral steroids, or has frequent regular symptoms. Examples of frequent symptoms are needing a reliever (symptom-relief) inhaler on 3 or more days a week, or being woken from sleep by asthma 1 or more times a week. Before stepping up, address the possible reasons for poor control, such as adherence, inhaler technique, smoking and other triggers. Review the response to any change in treatment after 8 to 12 weeks.
Everyone with asthma should be offered a personalised asthma action plan (a self-management plan). This is a written plan agreed between the patient and a healthcare professional. It explains how to take treatment day to day, what to do when symptoms get worse, and when to seek urgent medical help. This leads to better outcomes in terms of day-to-day control, frequency and severity of exacerbations.
Diagram - An older US (NHLBI) stepwise ladder for asthma. It does not match the current UK pathway in the list above.
Creative commons source by National Heart, Blood, and Lung Institute [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
An exacerbation of asthma (an ‘asthma attack’) is graded by severity as moderate, acute severe, life-threatening or near-fatal. It is important to distinguish between these grades in order to arrange the most appropriate treatment for the patient. The following information can be used to grade the severity of an attack in adults, in accordance with the BTS and SIGN guideline. Children have different thresholds, for example for heart rate and breathing rate.
Classifications of Asthma Exacerbations According to the British Thoracic Society
The BTS and SIGN classification has no separate ‘mild’ grade. The lowest grade is moderate asthma.
Moderate Asthma:
- PEF >50% to 75% of recent best (their highest recent reading when their symptoms were under control), or predicted if a recent best is not known
- The patient still has no features of acute severe asthma
- Their symptoms are worse than normal
Acute Severe Asthma - present if the patient has any one of the following features:
- PEF between 33 and 50% of their best or predicted value
- Respiratory rate ≥25/min
- Heart rate ≥110/min
- Unable to finish sentences in one breath
Life-threatening Asthma - suspected if a patient with acute severe asthma has any one of the following features:
- PEF <33% of their best or predicted value
- O2 saturation <92%
- PaO2 <8 kPa (the pressure of oxygen in arterial blood, in kilopascals)
- Silent chest (no wheeze is heard, because very little air is moving)
- Poor respiratory effort
- Arrhythmia (an abnormal heart rhythm)
- Hypotension
- Altered level of consciousness (for example confusion or drowsiness)
- Exhaustion
- Cyanosis (a blue colour of the lips or skin)
- ‘Normal’ PaCO2 (the pressure of carbon dioxide in arterial blood; 4.6–6.0 kPa) in a severe attack is a life-threatening marker. Patients in a severe attack usually breathe fast and blow off carbon dioxide, so PaCO2 is usually low, and a normal value is a warning sign. A low PaCO2 can accompany hyperventilation (breathing faster and deeper than normal) and is not, by itself, a life-threatening feature.
Near-fatal Asthma:
- Raised PaCO2 (carbon dioxide is building up in the blood) is a near-fatal feature. It needs emergency specialist or anaesthetic help, because the patient may need ventilatory support (a machine to help with breathing)
- Need for mechanical ventilation (a machine that breathes for the patient) with raised inflation pressures
Consequences of Asthma Attacks
Airway narrowing according to the pathophysiology above can lead to reduced ventilation of some of the alveoli (air sacs), while blood flow (perfusion) to them continues. This causes V/Q (ventilation/perfusion) mismatch, which lowers the oxygen level in the blood (hypoxia). The patient breathes faster and deeper (hyperventilation). This blows off extra CO2, so the CO2 level in the blood falls. Breathing faster does not fully correct the hypoxia.
This means that in mild to moderate asthma pCO2 falls (↓pCO2) because of hyperventilation, and pO2 can fall (↓pO2) because of V/Q mismatch. A low pO2 with a low pCO2 is a pattern of type 1 respiratory failure (lung failure, causing a low oxygen level in the blood).
In near-fatal attacks, more of the airways are involved and the patient becomes exhausted. This limits the respiratory rate, so less CO2 is breathed out. CO2 builds up, giving ↑pCO2 with ↓pO2. This is type 2 respiratory failure (failure of ventilation, with a raised pCO2). A ‘normal’ pCO2 in a severe attack is therefore a warning sign.
All patients with any symptoms of a life-threatening asthma attack should be admitted to hospital, as should anyone with symptoms of an acute severe asthma attack whose symptoms aren’t responding to bronchodilators.
Management of Acute Asthma Attack
Treatment of an acute severe asthma attack includes oxygen, adjusted to keep the oxygen saturation at 94 to 98% (too much oxygen can be harmful), nebulised salbutamol (a short-acting β2 agonist given as a mist through a mask, preferably driven by oxygen) and oral prednisolone (a steroid, 40 to 50 mg, continued until recovery and for at least 5 days). Nebulised ipratropium bromide (a second type of bronchodilator, a medicine that widens the airways) is added for acute severe or life-threatening asthma, or if the first response to salbutamol is poor. A single dose of intravenous magnesium sulphate may be considered if an acute severe attack has not responded well to inhaled bronchodilators. It should only be given after talking to senior medical staff. Before discharge, follow-up should be arranged with the patient’s GP or asthma nurse within 2 working days, and with a hospital specialist asthma nurse or respiratory physician at about 1 month after admission.
Edited by: Dr. Maddie Swannack
Reviewed by: Dr. Thomas Burnell and Dr. Marcus Judge
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