Comments
To the Editor:
We read the article regarding time of day and eosinophil biomarkers in asthma by Durrington and colleagues (1) with great interest. Although chronobiology and chronotherapeutic approaches are now being considered in a wide range of diseases, including cardiovascular diseases, neurological diseases, and cancer, the same is rarely observed in airway diseases, especially asthma. At this point, this paper explains clinically important chronobiological aspects of asthma pathobiology, and thus opens up a window of opportunity for using a chronotherapeutic approach for asthma management. However, we want to comment on chronotype determination, which is an essential part of chronobiological studies involving human participants.
Chronotype is the preferred timing of activity and rest of an individual and is categorized into three groups: morning (early wake-up and early bed time, achieve their peak physical and mental activity during the early part of the day), evening (late wake-up and late bedtime, achieve their peak physical and mental activity during the end part of the day), and neither (2). It is important to note that the pattern of any circadian rhythm function can vary largely between different chronotypes. Several studies have shown that the phase lag (phase advance or delay) of circadian rhythm functions can vary up to 12 hours between the two extreme chronotypes (morning and evening types), which means the acrophase (the time at which the peak of a rhythm occurs) attained by a certain circadian rhythm in a morning-type person could be absolutely different than that of the evening-type person, and that may also be associated with temporary or permanent changes in the genetic makeup of those individuals (2, 3).
We noticed that the authors did not determine the chronotype of the patients in their study. Although the authors had measured the circadian pattern of sputum eosinophils and eotaxin levels with a zenith at 4 a.m. and a nadir at 4 p.m., the differences between these two phases were not found to be significant. We believe that the difference could have been influenced by the chronotype effect; that is, the acrophase of sputum eosinophils was different among patients of different chronotypes, and the rhythmicity of those cells was under the influence of different zeitgebers (other than the disease), resulting in a phase shift. We would also like to propose that the authors, if possible, assess the chronotypes of the patients using any available chronotype assessment questionnaire and adjust it for assessing eosinophil patterns across the times of the day.
Although studying the chronobiological patterns in different respiratory conditions, including asthma and obstructive sleep apnea, is now being given priority (4, 5), using chronobiology as a way to determine diagnosis and therapeutic strategy still needs to be considered very carefully. Even though some possible chronotherapeutic strategies are being developed to treat asthma and other diseases, chronotypical assessment of the patients should also be considered, in addition to studying the rhythmicity of symptoms and the biomarkers of the diseases. Diagnosis and therapy based on an improper chronobiological characterization may render a masking effect to the actual pattern of the disease phenomenon, thus making the disease even more difficult to treat.
| 1. | Durrington HJ, Gioan-Tavernier GO, Maidstone RJ, Krakowiak K, Loudon ASI, Blaikley JF, et al. Time of day affects eosinophil biomarkers in asthma: implications for diagnosis and treatment. Am J Respir Crit Care Med [online ahead of print] 29 Aug 2018; DOI: 10.1164/rccm.201807-1289LE. |
| 2. | Adan A, Archer SN, Hidalgo MP, Di Milia L, Natale V, Randler C. Circadian typology: a comprehensive review. Chronobiol Int 2012;29:1153–1175. |
| 3. | Wyatt JK, Stepanski EJ, Kirkby J. Circadian phase in delayed sleep phase syndrome: predictors and temporal stability across multiple assessments. Sleep 2006;29:1075–1080. |
| 4. | Sundar IK, Yao H, Sellix MT, Rahman I. Circadian molecular clock in lung pathophysiology. Am J Physiol Lung Cell Mol Physiol 2015;309:L1056–L1075. |
| 5. | Truong KK, Lam MT, Grandner MA, Sassoon CS, Malhotra A. Timing matters: circadian rhythm in sepsis, obstructive lung disease, obstructive sleep apnea, and cancer. Ann Am Thorac Soc 2016;13:1144–1154. |
Originally Published in Press as DOI: 10.1164/rccm.201809-1630LE on October 22, 2018
Author disclosures are available with the text of this letter at www.atsjournals.org.
