Investigations
1st investigations to order
spirometry (FEV₁/FVC ratio and BDR)
Test
Spirometry is the investigation of choice for identification of airflow obstruction.[55][56] It is usual clinical practice in the UK to arrange spirometry for every patient presenting with suspected asthma.
This is in line with National Institute for Health and Care Excellence (NICE) guidelines, which specify that you should not use symptoms alone to diagnose asthma, and that you should always use an objective test if you suspect asthma following a structured clinical assessment.[56] NICE recommends fractional exhaled nitric oxide (FeNO) followed by spirometry as essential tests for any adult with asthma symptoms.[56] Bronchodilator reversibility (BDR) testing is recommended by NICE if spirometry shows obstruction. NICE advises that peak expiratory flow (PEF) monitoring over 2-4 weeks may be needed if there is diagnostic uncertainty after FeNO and spirometry.[56] Bear in mind, however, that British Thoracic Society/Scottish Intercollegiate Guidelines Network (BTS/SIGN) recommend that people who clearly have a high probability of asthma (coded as 'suspected asthma') may start an objectively monitored initiation of treatment (e.g., with PEF, validated questionnaires, and/or spirometry), and subsequently receive a confirmed diagnosis of asthma without necessarily performing spirometry or FeNO.[55] BTS/SIGN guidance does recommend spirometry for any patient assessed as having an intermediate probability of asthma, with BDR testing if airway obstruction is confirmed.[55]
The FEV₁ and forced vital capacity (FVC) can be used to demonstrate airflow limitation. Use the lower limit of normal (LLN) for the FEV₁/FVC ratio rather than a fixed FEV₁/FVC ratio of 0.7; LLN is a functionality that is increasingly available through software built into spirometers.[55]
Use of a fixed ratio can lead to overdiagnosis of obstruction in adults owing to variability of the ratio with age.[55] In adults over 40 years of age, levels below 70% may be normal and use of a 70% threshold will overestimate obstruction. NICE recommends using the LLN for diagnosis if available; otherwise, NICE also recommends using a fixed FEV₁/FVC ratio of 70%.[56]
Use a BDR test to demonstrate reversibility of airflow obstruction in response to short-acting bronchodilators. BTS/SIGN and NICE agree that in adults with obstructive spirometry, an improvement in FEV₁ of 12% or more in response to beta agonists (or to a treatment trial with corticosteroids), together with an increase in volume of 200 mL or more, is regarded as a positive test.[55][56] BTS/SIGN further recommend that an improvement of greater than 400 mL in FEV₁ strongly suggests underlying asthma.[55]
Bear in mind that normal spirometry in an asymptomatic patient does not rule out a diagnosis of asthma.[55] The false negative rate of spirometry as a diagnostic test for asthma is at least 50%.[56][57]
Confirmation of an asthma diagnosis relies on demonstration of airflow variability over short periods of time.[55]
BTS/SIGN recommend that people who clearly have a high probability of asthma (coded as 'suspected asthma') may start an objectively monitored initiation of treatment (e.g., with PEF, validated questionnaires, and/or spirometry), and subsequently receive a confirmed diagnosis of asthma without necessarily performing spirometry or FeNO.[55] BTS/SIGN guidance does recommend spirometry for any patient assessed as having an intermediate probability of asthma, with BDR testing if airway obstruction is confirmed.[55]
Check your local guidance on the indications for spirometry in patients with suspected asthma.
A guide on how to perform and interpret spirometry, including common pitfalls.
Result
FEV₁/FVC ratio: below the LLN (if available) or <70% (if LLN not available) is positive for airflow obstruction; BDR test: improvement in FEV₁ of 12% or more in response to beta agonists (or to a treatment trial with corticosteroids), together with an increase in volume of 200 mL or more is positive for reversibility of airway obstruction
peak expiratory flow (PEF)
Test
Record peak expiratory flow (PEF) as the best of three forced expiratory blows from total lung capacity with a maximum pause of 2 seconds before blowing.[55] The patient can be standing or sitting. Record further blows if the largest two PEFs are not within 40 L/minute.
Regard a value of more than 20% variability as a positive test.[55][56] The upper limit of the normal range for variability is around 20% using four or more PEF readings per day.[61][62]
British Thoracic Society/Scottish Intercollegiate Guidelines Network (BTS/SIGN) recommend using PEF to estimate variability of airflow from multiple measurements made over 2-4 weeks.[55] Increased variability may be evident from twice-daily readings.[55] Bear in mind that although more frequent readings will result in a better estimate, they require improved patient adherence. If available, electronic meters and diaries with time and date stamps can improve adherence and accuracy if recording PEF in paper diaries.[55] PEF variability is usually calculated as the difference between the highest and lowest PEF expressed as a percentage of the average PEF.[61][62][63] However, one study showed that three or more days a week with significant variability was more sensitive and specific than calculating mean differences.[64]
BTS/SIGN recommend to confirm variability by comparing a PEF recorded when the patient is symptomatic (e.g., during the assessment of an asthma attack) with a PEF when asymptomatic (e.g., after recovery from an asthma attack).[55]
The National Institute for Health and Care Excellence (NICE) recommends PEF charting over 2-4 weeks if there is diagnostic uncertainty after initial assessment and a fractional exhaled nitric oxide (FeNO) test and the patient has either: normal spirometry; or obstructive spirometry, reversible airways obstruction (positive bronchodilator reversibility [BDR]) but a FeNO level of 39 parts per billion (ppb) or less.[56] NICE also recommends PEF charting over 2-4 weeks if there is diagnostic uncertainty after initial assessment and the patient has: obstructive spirometry and irreversible airways obstruction (negative BDR) and a FeNO level between 25 ppb and 39 ppb.[56]
PEF diaries also have an important role in the ongoing monitoring of asthma control. See Monitoring section for more details.
How to use a peak flow meter to obtain a peak expiratory flow measurement.
Result
>20% variability
Investigations to consider
CXR
Test
Indicated in first presentation to exclude other pathologies.
May also show signs of infection in acute exacerbation or pneumothorax. See Acute asthma exacerbation in adults.
Result
normal or hyper-inflated
FBC with differential
Test
Indicated in first presentation when complicating factors are suspected from history and examination.
An elevated blood eosinophil count is typically associated with more severe exacerbations and poorer asthma control.[60] See Acute asthma exacerbation in adults.
Result
normal or raised eosinophils and/or neutrophilia
fractional exhaled nitric oxide (FeNO)
Test
FeNO measurement can be used to find evidence of eosinophilic inflammation.[55][56] FeNO testing is not widely available in primary care in the UK (although arrangements to change this are underway). A positive test provides supportive, but not conclusive, evidence for a diagnosis of asthma; therefore, a negative test does not exclude the diagnosis.[55]
In corticosteroid-naive adults, a FeNO level of 40 parts per billion (ppb) or more is regarded as positive.[55][56] Data from adult patients in secondary care suggest that approximately one in five people with a positive FeNO test will not have asthma (false positives), and conversely one in five people with a negative FeNO test will have asthma (false negatives).[55]
Bear in mind that FeNO levels are: increased in patients with allergic rhinitis exposed to allergen, even without any respiratory symptoms; increased by rhinovirus infection in healthy individuals, but this effect is inconsistent in people with asthma; higher in men and tall people.[55][68][69][70] FeNO levels are lower in children, reduced (acutely and cumulatively) in people who smoke cigarettes, reduced by inhaled or oral corticosteroids, and increased by consumption of dietary nitrates.[55][56][68][69][70]
British Thoracic Society/Scottish Intercollegiate Guidelines Network (BTS/SIGN) and National Institute for Health and Care Excellence (NICE) guidelines differ in their recommendations on the role of FeNO testing in diagnosing asthma. BTS/SIGN recommend FeNO testing as an option, if available, for adults with an intermediary probability of asthma and normal spirometry results. In this scenario, a positive FeNO test increases the probability of asthma.[55] By contrast, NICE recommends FeNO as the first-line investigation (along with spirometry) for any adult in whom a diagnosis of asthma is being considered.[56]
Recommendations from international guidelines differ. The American Thoracic Society (ATS) recommends FeNO as a supportive test for asthma diagnosis, stating that it should be performed if equipment is available.[71] The European Respiratory Society (ERS) agrees that FeNO can be used in addition to standard tests to aid diagnosis of asthma.[72] The Global Initiative for Asthma (GINA), however, does not recommend FeNO as a test for ruling in or ruling out a diagnosis of asthma. GINA cites the overlap between FeNO levels among people with and without asthma as the basis for this recommendation. GINA asserts that the main role of FeNO is to guide treatment decisions in patients with severe asthma.[1]
FeNO, when used in combination with sputum eosinophilia, has a high sensitivity and specificity.[55][71][73][74] However, sputum eosinophilia is also not a standard test in primary care in the UK at present.
Two Cochrane systematic reviews looking at tailoring asthma therapy to either sputum eosinophils or FeNO levels showed fewer exacerbations in each group, but no significant difference in all other outcomes, including quality of life, FeNO levels, or inhaled corticosteroid dose.[75][76]
Result
increased: ≥40 ppb in a corticosteroid-naive adult
bronchial challenge test
Test
British Thoracic Society/Scottish Intercollegiate Guidelines Network (BTS/SIGN) recommend to consider referring the patient for direct challenge tests if there is no evidence of airflow obstruction on initial assessment and other objective tests are inconclusive but asthma remains an intermediate possibility.[55] Challenge tests are categorised as direct and indirect.
Direct challenge tests are the most widely used method of measuring airway responsiveness. They measure response in terms of change in FEV₁ a set time after the patient has inhaled increasing concentrations of bronchoconstrictor (histamine or methacholine).[55] A provocative concentration (PC20) of bronchoconstrictor of 8 mg/mL or less is regarded as positive.[55][56]
The National Institute for Health and Care Excellence (NICE) recommends a direct bronchial challenge test if there is diagnostic uncertainty after a normal spirometry and either a fractional exhaled nitric oxide (FeNO) level of 40 parts per billion (ppb) or more and no variability in peak expiratory flow (PEF) readings, or a FeNO level of 39 ppb or less with variability in PEF readings.[56] NICE recommends to consider a direct challenge test with histamine or methacholine in people with all of the following: obstructive spirometry without bronchodilator reversibility; a FeNO level between 25 ppb and 39 ppb; no variability in PEF readings (less than 20% variability over 2-4 weeks).[56] NICE does not recommend indirect challenges with exercise as diagnostic tests.[56]
Result
positive
allergen testing
Test
Although not recommended as routine diagnostic tests, British Thoracic Society/Scottish Intercollegiate Guidelines Network (BTS/SIGN) advise using a previous record of skin-prick tests, blood eosinophilia of 4% or more, or a raised allergen-specific immunoglobulin E (IgE) to corroborate a history of atopic status.[55] The National Institute for Health and Care Excellence (NICE) also does not recommend these as routine diagnostic tests but suggests using skin-prick tests to aeroallergens or specific IgE tests to identify triggers after a formal diagnosis of asthma has been made.[56]
In clinical practice, specific allergen sensitivity screening should be considered to confirm allergy in patients with a history suggestive of an allergic trigger.
If you suspect an occupational cause, see Occupational asthma.
Result
positive for allergen
Emerging tests
sputum eosinophilia
Test
Increased with T-helper type 2 inflammation.
Reflects the level of inflammation in the airway and the response to inhaled corticosteroid.
Limited by patient's ability to produce sputum after induction.
A combination of fractional exhaled nitric oxide (FeNO) and sputum eosinophilia has a high specificity and sensitivity.[55][71][73][74]
Not a standard test in primary care in the UK at present.
Result
increased
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