By Reshma Kolala, Microbiology ‘22

Author’s Note: Adolescents are notorious for not getting enough sleep, but can that impact how the cells of our immune system operate? The following study reinforces the significance of maintaining a natural sleep schedule in adolescents and unveils a new area of research where sleep-wake patterns could be used as a diagnostic when screening for respiratory illnesses.

Our circadian rhythm regulates a myriad of biological activity, ranging from metabolism and cell signaling pathways to various psychological and behavioral patterns. The circadian rhythm is defined as endogenous (built-in mechanism) and entrainable (adjusted to external stimuli such as temperature and light) [1]. Together, these factors manifest into a unique chronotype which describe an individual’s propensity to sleep and wake at a particular time [2]. Recent studies have examined this biological pattern in relation to respiratory illness, revealing how disruption in the circadian rhythm plays a critical role in the pathogenesis of airway inflammation and physiology. The following study aims to further elucidate the relationship between an individual’s chronotype and their susceptibility to asthma or allergic diseases, particularly in the adolescent population. 

The study conducted by Halder et al. analyzed data from 1684 adolescents, ranging from ages 13-14, from the Prevalence and Risk Factors of Asthma and Allergy-Related Diseases among Adolescents (PERFORMANCE) study. Each individual was administered the International Study of Asthma and Allergy in Childhood (ISAAC) Phase III questionnaire to determine each adolescent’s disposition to respiratory illness, with particular emphasis on wheeze, rhinitis, rhinoconjunctivitis, and asthma. This data was analyzed against responses from the reduced Morningness–Eveningness Questionnaire (rMEQ), which was used to determine each participant’s chronotype. An individual’s chronotype was classified into one of three categories: morning, evening and intermediate types. External factors such as demographics, social characteristics, and neighborhood environment (rural, industrial suburban, nonindustrial suburban and urban) were also considered as potential influences that may enhance asthma/allergy symptoms. Results revealed that an “individual’s chronotype was associated with respiratory symptoms among adolescents”. More specifically, those that were evening types, and intermediate types to a lesser extent, had a higher risk of current wheeze and current or ever rhinitis when compared to morning types. Intermediate types also demonstrated higher levels of Rhinoconjunctivitis when compared to morning types. Overall, individuals that were identified as evening types had a consistently higher prevalence of respiratory symptoms when compared to morning types. Those identified as morning types did not exhibit significant correlation with respiratory symptoms. This association between respiratory symptoms and chronotype was paralleled, though to a lower degree, in individuals identified as intermediate types as well [3]. 

The wide pathophysiology of asthma and allergy makes it challenging to pinpoint a particular cellular process to explain this finding [4]. Previous studies have shown that asthma/allergy symptoms worsen at night which can be attributed to multiple immunological factors. A study by Christ et al. in 2018 observed the link between mast cell responsiveness, function in allergic diseases, and the circadian rhythm. Mast cells possess a high affinity for IgE antibody, which is produced by the immune system in response to allergen recognition. When activated by bound IgE, mast cells release chemokines, cytokines, and other inflammatory mediators such as histamine, which exhibit diurnal character (are active during the daytime). This study illustrates how mast cell signaling, critically involved in the inflammatory response, operates on a circadian rhythm. This is due to the fact that inflammatory mediators are governed by diurnal (active during the day) behavior. [5]. This study focused on mast cell signaling by Christ et al. may provide some reasoning behind the results observed in the aforementioned study conducted by Halder et al. The Christ et al. study shows how dysregulation of the sleep-wake cycle interferes with how the immune system responds to the presence of allergens, which could potentially aggravate the respiratory symptoms detailed in the Halder et al. study. For example, those identified as “evening-types” are “more easily prone to circadian misalignments that could eventually lead to circadian clock dysfunction which triggers several down-stream mechanisms including altered immune systems in the lungs”.

Melatonin production is also a significant factor in the inflammatory immune response. Evening type individuals are exposed to higher levels of artificial light at night (ALAN) which disrupts daily rhythms and suppresses nocturnal melatonin production [6]. Melatonin, known as the sleep hormone, plays a vital role in immunomodulation. Immunomodulation is responsible for orchestrating the events of cellular and humoral immunity [7]. Recent studies have identified melatonin as a key player in asthma and allergy-related disease when the circadian rhythm is misregulated by abnormal sleep-wake patterns. 

This study is the first to find an association between chronotype and respiratory symptoms in adolescents. As this is a cross-sectional study, researchers in this study are unable to make a causal statement that directly links sleeping patterns to respiratory illness. However, results from this study warrant further investigation into the cellular and behavioral effects of individuals who possess “intermediate” and “evening type” chronotypes. This finding uncovers a new outlet of healthcare, where an individual’s unique chronotype is utilized as a tool in patient diagnosis for various metabolic, behavioral, and respiratory illnesses.

References:

1. Circadian rhythm. (2020, November 09). Retrieved November 12, 2020, from https://en.wikipedia.org/wiki/Circadian_rhythm
2. Chronotype. (2020, November 08). Retrieved November 12, 2020, from https://en.wikipedia.org/wiki/Chronotype
3. Haldar, P., Carsin, A., Debnath, S., Maity, S., Annesi-Maesano, I., Garcia-Aymerich, J., . . . Moitra, S. (2020, April 01). Individual circadian preference (chronotype) is associated with asthma and allergic symptoms among adolescents. Retrieved November 12, 2020, from https://openres.ersjournals.com/content/6/2/00226-2020
4. Huang, R., E. Callaway, H., Burki, T., RS. Edgar, A., JE. Long, M., D. Montaigne, X., . . . LK. Williams, M. (1970, January 01). The Role of the Body Clock in Asthma and COPD: Implication for Treatment. Retrieved November 12, 2020, from https://link.springer.com/article/10.1007/s41030-018-0058-6
5. Christ, P., Sowa, A., Froy, O., & Lorentz, A. (2018, July 6). The Circadian Clock Drives Mast Cell Functions in Allergic Reactions. Retrieved November 12, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043637/
6. Haim, A., & Zubidat, A. (2015, May 5). Artificial light at night: Melatonin as a mediator between the environment and epigenome. Retrieved November 12, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375362/
7. Srinivasan V;Spence DW;Trakht I;Pandi-Perumal SR;Cardinali DP;Maestroni GJ;. (n.d.). Immunomodulation by melatonin: Its significance for seasonally occurring diseases. Retrieved November 12, 2020, from https://pubmed.ncbi.nlm.nih.gov/18679047/