The impact of time-of-day on the diagnostic performance of tests for asthma

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Introduction: Asthma is a highly rhythmic disease with most patients experiencing nocturnal worsening. Clinical tests for asthma show diurnal variation, yet current diagnostic strategies do not take this into account. Aim: To investigate the impact of time-of-day on the performance of key diagnostic tests for asthma. Method: Symptomatic and treatment-naive patients were recruited from primary care. Clinical history was taken. Fractional exhaled nitric oxide (FeNO), spirometry, bronchodilator reversibility (BDR), and bronchial challenge tests were carried out. The tests were repeated following 6-8 weeks of inhaled corticosteroid treatment. An asthma diagnosis was confirmed or refuted by at least two asthma specialists using all available data. Results: Of 140 adults, 118 (84%, median (IQR) age: 32.0 (26.5-43.5) years, 37% male) had a definitive diagnostic outcome (59% asthma, 41% not asthma). Most patients reported within-day variability in symptoms (84% in asthmatics, 68% in non-asthmatics). Patients experienced fewest symptoms between 10am and 5pm. Median BDR was highest in the morning and lower during the course of the day (β=-0.91, 95% CI: (-1.52, -0.15), p=0.018), as was FeNO levels (in atopic patients only; β=-6.2, 95% CI: [-10.4, -2.1], p=0.028). Positive FeNO and BDR tests occurred more frequently in the morning (49% and 31% before 11am) and decreased as the day went on (13% and 15% after 3pm, respectively). Conclusion: The timing of asthma diagnostic tests impact on outcome should not be overlooked in the diagnostic setting and may have health-economic implications. Whether testing at the time-of-day when patients are most symptomatic improves diagnostic efficiency warrants further investigation.

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