In patients with clinically suspected asthma, which of the following statements are correct: (a) methacholine challenge causes a ≥12% and ≥200 mL fall in forced expiratory volume in one second (FEV1), (b) a normal chest radiograph rules out asthma, (c) elevated serum immunoglobulin E (IgE) confirms asthma, (d) exhaled nitric oxide may be increased, (e) daily peak expiratory flow variability >20% over several weeks is a diagnostic criterion?

Diagnostic Features of Clinically Suspected Asthma

Options (d) and (e) are correct: increased exhaled nitric oxide (NO) may be observed in asthma patients, and daily PEF variability >20% over several weeks is a diagnostic criterion.

Analysis of Each Statement

a. Methacholine administration increases FEV1 >12% and 200 ml - INCORRECT

• Methacholine causes bronchoconstriction, not bronchodilation. A positive methacholine challenge test is defined as a ≥20% reduction in FEV1 compared to baseline, not an increase 1
• The provocative concentration causing a 20% fall in FEV1 (PC20) is used to demonstrate bronchial hyperresponsiveness, which is associated with symptomatic asthma 2
• Increased bronchial responsiveness to methacholine is common in asthma, though it can also occur in COPD and the general population 2
• Critical pitfall: Confusing methacholine challenge (which provokes bronchoconstriction) with bronchodilator reversibility testing (which uses β2-agonists to reverse obstruction) 2

b. Normal chest X-ray rules out diagnosis - INCORRECT

• A normal chest X-ray does not exclude asthma. The British Thoracic Society guidelines recommend performing chest X-rays in patients with atypical symptoms, not as a routine diagnostic test 2
• Chest radiography is used to identify alternative or additional diagnoses, not to confirm or exclude asthma 2
• Asthma diagnosis relies on demonstrating variable airflow limitation through spirometry, bronchodilator reversibility, or peak flow variability—not imaging 2

c. High IgE confirms the diagnosis - INCORRECT

• Elevated IgE does not confirm asthma. The European Respiratory Society explicitly recommends against using allergy testing (including IgE) to diagnose asthma due to low specificity 2
• Allergy tests may help identify triggers and establish atopy, but the presence of allergy is not essential to the diagnosis of asthma 2
• The absence of allergy in a child with asthma-like symptoms should prompt consideration of alternative diagnoses, but many patients have non-atopic asthma 2

d. Increased NO in exhaled air may be observed - CORRECT

• Exhaled nitric oxide (FeNO) is frequently elevated in asthma patients. The European Respiratory Society recommends FeNO ≥25 ppb as supporting evidence for asthma diagnosis 2
• FeNO reflects eosinophilic airway inflammation and is particularly useful when spirometry is normal 2
• Research demonstrates that exhaled NO is significantly elevated in asthmatic patients (301 ± 26 ppb) compared to normal subjects (78 ± 3 ppb), with the increase predominantly derived from the lower respiratory tract 3
• High FeNO levels (>47 ppb) predict steroid responsiveness with 89% negative predictive value 2
• Important caveat: FeNO may be falsely negative in patients already treated with inhaled corticosteroids, as steroids reduce FeNO levels 2, 4

e. Daily PEF variability >20% over several weeks is a diagnostic criterion - CORRECT

• PEF variability ≥20% (amplitude % best) over several weeks is highly suggestive of asthma. The British Thoracic Society guidelines specify that 20% or greater variability with a minimum change of at least 60 L/min, ideally for three days in a week for two weeks, strongly supports asthma diagnosis 2
• The calculation method is: amplitude % best = (highest – lowest)/highest × 100 2
• Critical nuance: This 20% threshold applies to the amplitude % best calculation over extended monitoring, not to twice-daily measurements. For twice-daily PEF monitoring, the upper limit of normal is only 8% (or 9.3% in adolescents) 2
• Many asthma patients demonstrate variability below 20%, making this a reasonably specific but insensitive test—marked variability confirms asthma, but smaller changes do not exclude it 2
• The European Respiratory Society guidelines for children aged 5-16 years use a lower threshold of ≥12% variability over 2 weeks as a diagnostic criterion 2

Diagnostic Algorithm Considerations

The European Respiratory Society strongly recommends that asthma diagnosis requires at least two abnormal objective tests 2. First-line tests include:

• Spirometry (FEV1/FVC <80% or below lower limit of normal) 2
• Bronchodilator reversibility (≥12% and/or ≥200 mL increase in FEV1) 2
• FeNO measurement (≥25 ppb) 2

When these are inconclusive, PEF variability or bronchial challenge testing should be performed 2.