Asthma Diagnostics

Laboratory Tests and Ancillaries

Measurements of Lung Function  

Measurement of lung function assesses the severity of airflow limitation, reversibility, and variability, and establishes the diagnosis of asthma. A documented excessive lung function variability AND documented expiratory airflow limitation defined as low FEV₁ and the ratio of FEV₁ to forced vital capacity (FVC) confirm the diagnosis.  

FEV₁ and peak expiratory flow (PEF) are decreased in obstructive airway diseases. Spirometry and peak expiratory flow measurements may be used to evaluate airflow limitation in patients ≥5 years old. PEF can be used as an initial lung function test if spirometry is unavailable. However, PEF is less reliable compared to spirometry but is better than relying on symptoms alone for diagnosis. Predicted values of FEV₁, forced vital capacity, and peak expiratory flow based on age, gender, and height may be used to base a judgment on whether a value is normal or not. Ethnic characteristics and extremes in age should be given consideration.

Spirometry  

Spirometry is the recommended technique in determining airway limitation and reversibility, and in confirming asthma. A spirometer is used to measure FEV₁ and forced vital capacity which is considered a more reliable equipment for FEV₁ measurement as compared to peak expiratory flow meters. It may also be used in the clinic to monitor the activity of asthma and is particularly helpful in assessing improvement in patients with greatly compromised lung function.  

Other lung diseases can result in reduced FEV₁; thus, a better assessment of airflow limitation is by the ratio of FEV₁ to forced vital capacity. In the normal lung, FEV₁/FVC ratios are >75-80% in adults and >90% in children. FEV₁/FVC ratios <70% post-bronchodilator (or any value below the normal limit) are suggestive of airflow limitation. An improvement of >12% in FEV₁ whether spontaneously, after inhalation of bronchodilator, or after 4 weeks of anti-inflammatory treatment suggests a diagnosis of asthma. 

Peak Expiratory Flow (PEF)  

Peak expiratory flow meters are important in aiding the diagnosis and in ensuing treatment of asthma. It is considered in patients who have a tendency to underperceive their symptoms (eg adolescents, have comorbidities with similar symptoms with asthma, elderly) or those likely to overperceive them (eg patients with anxiety).  

If spirometry is unavailable, peak expiratory flow can confirm the presence of variable expiratory airflow limitation. An improvement of ≥20% in peak expiratory flow after inhalation of a bronchodilator suggests a diagnosis of asthma. Peak expiratory flow measurements do not always correspond with other measurements of lung function in asthma. It should ideally be compared to the patient’s own previous best measurements.  

Regular peak expiratory flow measurements throughout the day or over the week up to months can aid in the assessment of asthma severity and response to treatment. The severity of asthma is also reflected in its variability especially across 24 hours. Ideally, peak expiratory flow should be measured first thing in the morning (when values are usually close to their lowest) and 12 hours apart in the evening (when values are usually at their highest). 

Diurnal Peak Expiratory Flow  

Diurnal peak expiratory flow variability is taken as the amplitude (difference between pre-bronchodilator morning value and post-bronchodilator value from the evening before) expressed as a percentage of the mean daily peak expiratory flow value.  

Another method is the minimum morning pre-bronchodilator over 1 week expressed as percent of the recent best (Min%Max). This method has been suggested to be the best peak expiratory flow index of airway liability since it requires only once-a-day reading and correlates better than any other index with airway hyperresponsiveness.  

An average daily diurnal variation in peak expiratory flow of >10% in adults and >13% in children is indicative of asthma. Peak expiratory flow testing should be done prior to treatment since peak expiratory flow variability decreases with corticosteroid treatment as lung function improves.  

Bronchodilator (BD) Reversibility Test  

An increase in FEV₁ or FVC by ≥12% and ≥200 mL from the baseline, 10-15 minutes after a dose of 200-400 mcg of Albuterol or its equivalent or after 4 weeks of treatment with an inhaled corticosteroid, confirms the diagnosis of asthma. Withholding administration of bronchodilators (≥4 hours for short-acting beta₂-agonists, 15 hours for long-acting beta₂-agonists) prior to the test increases the test’s sensitivity. 

Biomarkers of Type 2 Inflammation  

Biomarkers of type 2 inflammation are reflective of type 2 airway inflammation and allergy, as well as the appropriateness of type 2-targeted biologic therapy. These biomarkers are useful in the management of asthma but should be measured and interpreted in the appropriate clinical context, as results may be influenced by multiple factors such as age, sex, time of day, smoking, and allergen exposure, or may be due to non-asthma causes. Elevated levels in diagnosed patients may indicate a higher risk of exacerbations.

Blood Eosinophil Count  

A blood eosinophil count result that is greater than or equal to the upper limit of normal for a given population supports the diagnosis of asthma. In patients with severe asthma, a count of ≥150/uL suggests the presence of type 2 inflammation, while a count of ≥300/uL is the usual threshold for eligibility to receive type 2-targeted biologic therapy.

Functional Concentration of Exhaled Nitric Oxide (FeNO)  

FeNO is increased in eosinophilic conditions such as eosinophilic asthma, eosinophilic bronchitis, atopy, and allergic rhinitis, and it is decreased in smokers, during bronchoconstriction, and in early-onset allergic reactions. A FeNO level of >50 parts per billion (ppb) in steroid-naive adults, ≥25 ppb in patients on medium-dose inhaled corticosteroid, and ≥20 ppb in patients on high-dose inhaled corticosteroid are considered elevated and may be indicative of asthma. High FeNO in a patient presenting with typical asthma symptoms or who is diagnosed with asthma supports a diagnosis of asthma with type 2 inflammation. An elevated FeNO may also be due to poor adherence with inhaled corticosteroid-containing therapy in most patients. FeNO may also be considered in reviewing response to treatment. A FeNO suppression test using the addition of high-dose inhaled corticosteroid to current treatment for 1 week can help identify whether high FeNO is due to poor compliance or type 2 inflammation that is refractory to corticosteroids.  

Allergy Tests  

Allergy tests that can be done include serum total immunoglobulin E (IgE) and allergen-specific IgE. Atopy, which is the most likely cause of respiratory symptoms in allergy-induced asthmatic patients, may be tested by skin prick testing or by measurement of specific IgE (sIgE) in serum. A positive test result increases the probability for allergic asthma. Lastly, sIgE measurement may be preferred for patients who are uncooperative, with widespread skin disease, or if history suggests anaphylaxis risk.

Other Tests  

The following tests may fail to support asthma diagnosis if there is a presence of infrequent symptoms. Surveillance and periodic re-evaluation should be maintained until the diagnostic situation is clearer. It is important to consider the patient’s family history, age, and asthma triggers before deciding on the diagnostic and therapeutic course of action. If in doubt, a trial of treatment with short-acting beta₂-agonists as needed and inhaled corticosteroids assists in establishing the diagnosis of asthma especially if combined with peak expiratory flow monitoring.  

Exercise Challenge Test  

A decrease in FEV₁ by >10% and >200 mL from baseline in adults confirms variable expiratory airway limitation and is indicative of asthma. 

Bronchial Provocation Testing  

An alternative test to assess airway hyperresponsiveness wherein a decrease from FEV₁ baseline of ≥20% with standard doses of methacholine (dose <4 mg/mL) or histamine, or ≥15% with standardized hyperventilation, hypertonic saline, or Mannitol challenge confirms variable expiratory airway limitation and is indicative of asthma. A positive test with methacholine, histamine, or Mannitol can occur in patients with allergic rhinitis, bronchiectasis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF).