How is asthma diagnosed if pulmonary function tests (PFT) are normal?

Diagnosing Asthma When PFT is Normal

When baseline pulmonary function tests are normal but asthma is suspected, bronchial provocation testing (methacholine challenge) is the most valuable diagnostic tool, with 96.5% sensitivity for confirming asthma. 1

Why Baseline PFTs Are Often Normal in Asthma

• Baseline PFTs have poor diagnostic accuracy for asthma across all age groups due to substantial overlap between measurements in healthy individuals and those with mild or intermittent asthma 2
• Many asthma patients present between symptomatic episodes with completely normal pulmonary examinations and spirometry 3
• The diagnostic accuracy of baseline PFT is generally very poor in any age group because of this overlap 2

Recommended Diagnostic Approach

First-Line Testing: Bronchodilator Responsiveness

• Bronchodilator responsiveness (BDR) testing provides a much better diagnostic profile than baseline lung function data alone 2
• A positive reversibility test (≥12% and ≥200 mL improvement in FEV1 post-bronchodilator) is the most specific test for asthma 1
• However, BDR has the highest correlation with a positive asthma diagnosis when present 1

Second-Line Testing: Bronchial Challenge Testing

• Methacholine challenge testing is the most valuable diagnostic tool when baseline PFTs and BDR are normal, with 96.5% sensitivity and 78.4% specificity 1
• This test demonstrates bronchial hyperresponsiveness, a hallmark feature of asthma 2, 1
• The methacholine challenge has the highest correlation with a negative result, effectively ruling out asthma when negative 1
• National and international guidelines stipulate the need to confirm clinical suspicion of asthma with objective measures of lung function consistent with asthma 2

Alternative Testing: Exercise Challenge

• For suspected exercise-induced bronchoconstriction (EIB), exercise testing achieving ≥85% maximum heart rate for 6 minutes is recommended 4
• A ≥10% fall in FEV1 post-exercise confirms EIB 4
• This is particularly useful when symptoms occur primarily with exertion 4

Advanced Testing: Cardiopulmonary Exercise Testing (CPET)

• CPET is recommended for patients with intermittent dyspnea and normal PFTs to identify exercise-induced limitations and differentiate between cardiac, pulmonary, deconditioning, and other causes 4
• CPET can detect pulmonary gas exchange abnormalities, exercise-induced hypoxemia, and ventilatory inefficiency not apparent at rest 4
• This testing requires continuous ECG monitoring, blood pressure measurement, pulse oximetry, and breath-by-breath gas exchange analysis 4

Supporting Diagnostic Elements

Clinical History

• The most sensitive symptom question is: "Have you had an attack of shortness of breath that came on following strenuous activity?" 1
• The most specific symptom question is: "Have you had an attack of shortness of breath that came on during the day when you were at rest?" 1
• Symptoms such as wheezing, chest tightness, and difficulty taking a deep breath suggest asthma 5
• Clinical judgement and atopic status testing must complement PFT results 2

Peak Flow Monitoring

• Two weeks of peak expiratory flow (PEF) variability monitoring can support the diagnosis by demonstrating variability in airway obstruction 1, 6
• This is relatively simple to implement in clinical and home settings 6

Atopy Assessment

• Skin prick testing with common aeroallergens, serum total IgE, and blood eosinophil counts have low sensitivity but moderate specificity for asthma 1
• Fractional exhaled nitric oxide (FeNO) measurement may be supportive of atopic asthma but has limited diagnostic utility, particularly in nonatopic asthma 6

Critical Pitfalls to Avoid

• Asthma is frequently overdiagnosed when objective measures are not used: one-third of patients with physician-diagnosed asthma show no evidence of asthma on spirometry and/or methacholine challenge testing 2
• Physicians correctly diagnose asthma based on clinical examination alone only 63-74% of the time 5
• Mild intermittent asthma is often wrongly diagnosed, with persistent isolated cough being the main alternative diagnosis 2
• Objective measures of lung function are necessary for accurate diagnosis of asthma 5
• Repetition of testing over several time points may be necessary to confirm airway obstruction and variability 6