Asthma diagnosis: into the fourth dimension

Abstract

Asthma is the most common chronic respiratory disease in the UK; however, the misdiagnosis rate is substantial. The lack of consistency in national guidelines and the paucity of data on the performance of diagnostic algorithms compound the challenges in asthma diagnosis. Asthma is a highly rhythmic disease, characterised by diurnal variability in clinical symptoms and pathogenesis. Asthma also varies day to day, seasonally and from year to year. As much as it is a hallmark for asthma, this variability also poses significant challenges to asthma diagnosis. Almost all established asthma diagnostic tools demonstrate diurnal variation, yet few are performed with standardised timing of measurements. The dichotomous interpretation of diagnostic outcomes using fixed cut-off values may further limit the accuracy of the tests, particularly when diurnal variability straddles cut-off values within a day, and careful interpretation beyond the ‘positive’ and ‘negative’ outcome is needed. The day-to-day and more long-term variations are less predictable and it is unclear whether performing asthma diagnostic tests during asymptomatic periods may influence diagnostic sensitivities. With the evolution of asthma diagnostic tools, home monitoring and digital apps, novel strategies are needed to bridge these gaps in knowledge, and circadian variability should be considered during the standardisation process. This review summarises the biological mechanisms of circadian rhythms in asthma and highlights novel data on the significance of time (the fourth dimension) in asthma diagnosis.

Defining the normal range of fractional exhaled nitric oxide in children: one size does not fit all

“…Moreover, it is well-established that F ENO demonstrates diurnal and day-to-day variabilities in patients with asthma [ 36 ]. Whilst diurnal variation may be predictable in some patients, the day-to-day and longer-term variations may be less so.…”

“…Therefore the types and manufactures of the analysers used should be taken into consideration in the future work. Moreover, it is well-established that FeNO demonstrate diurnal and day-to-day variabilities in patients with asthma [36]. Whilst diurnal variation may be predictable in some patients, the day to day and longer term variations may be less so.…”

Glucocorticoid circadian rhythms in immune function

“…In the clinical diagnosis of asthma variability in airflow obstruction by time-of-day results in peak symptoms during the night, affecting sleep. In addition, markers of airway inflammation show strong diurnal variability, with implications for diagnosis, and for disease activity monitoring [98]. One striking finding is that dosing of oral prednisolone, a synthetic glucocorticoid, was found to be affected by time of administration, with peak benefit obtained at 3pm, at which time there was also a marked drop in markers of airway inflammation.…”

Prevalence, Economic Burden, and Neurophenotype of Asthma

“…Chronic inflammation is associated with airway hyperresponsiveness often with widespread and variable reversible expiratory airflow limitation, thus resulting in recurrent wheezing, shortness of breath, chest tightness, and coughing. 1 Cyclic asthma symptoms often lead to insomnia, daytime fatigue, reduced activity, and disruption to school and work. 2 We summarized the prevalence, economic burden, neurophenotype, and future direction of asthma to emphasize its importance in the population.…”