Telling Time by Asthma, Allergy Symptom Severity

The 2017 Nobel Prize in medicine for molecular mechanisms regulating the circadian rhythm rekindled interest in the study of biological clocks responsible for sleep, eating, peak activity, metabolism, and endocrine and immune functions.^1,2 Now clinicians are gaining a better understanding of how asthma and allergies are regulated by the circadian clock.³ The more clinicians and researchers become knowledgeable about this phenomenon, the more people with allergies can better alleviate their symptoms.³

The body’s master clock resides in the suprachiasmatic nucleus neurons within the hypothalamus, the body’s central clock, and in the peripheral oscillators in most cells. The retina innervates the suprachiasmatic nucleus, which accounts for light/dark cycles.³ The suprachiasmatic nucleus communicates information to the peripheral clocks via the hypothalamus-pituitary-adrenal axis and the autonomic nervous system.³ Disruptions in the circadian rhythm from jet lag, shift work, stress, temperature, and exercise can alter the severity of symptoms in people with allergies.³

Nocturnal Asthma Flares May Be Alleviated With Bedtime Dosing

Early-morning asthma attacks are not the result of the circadian dysregulation, but the result of a normally functioning clock.³ Evidence suggests that clock genes may influence fibrosis, lung inflammation, immunity, and glucocorticoid responses, although they have not been linked directly to asthma.⁴

To test this hypothesis, Ehlers and colleagues sought to determine whether certain genes are key to circadian regulation in asthma.⁴ Mice whose clock gene BMAL1 was knocked out after birth tended to experience more asthma exacerbations resulting from the circadian disruption than mice with the intact gene.⁴ The absence of the gene was also implicated in the mice’s inability to resist viral illness, specifically acute viral bronchiolitis caused by Sendai virus and influenza A virus, which increased airway resistance and mucus production.⁴ Similar phenomena occurred in humans in an experiment in which samples from patients with asthma demonstrated a propensity for viral asthma attacks when their clock genes were altered.⁴

“We are still figuring out the molecular biology connecting circadian rhythms to asthma and allergic disease,” said pulmonologist and critical care specialist Jeffrey A. Haspel, MD, PhD, assistant professor of medicine, Washington University School of Medicine, St. Louis, Missouri. “We’ve always known that atopic diseases like asthma are often worse at night, but we [are] now recognizing that it may be possible to improve symptom control by considering biological rhythms when forming a treatment plan. It may be possible to minimize inhaled corticosteroid doses, and improve compliance, by teaching patients to self-administer before bedtime. It might be worthwhile for clinicians to dedicate some time to counsel their patients about better sleep hygiene. This may lead to better asthma control by reinforcing circadian rhythms in immune function, particularly for teenagers and adults who do [not] get enough sleep.”

Allergic Rhinitis Peaks in the Morning

Similar to asthma, allergic rhinitis has an early morning peak of activity.³

CD203c, a basophil cell surface marker, is responsible for time-dependent activation in people with seasonal allergic rhinitis.³ Allergic rhinitis disrupts the circadian rhythm of salivary melatonin and cortisol.² In mice, endogenous glucocorticoids regulate the nasal peripheral clock, and those given intranasal steroids had temporal shifts in their nasal mucosa.² Extrapolating these findings to humans means that patients with allergic rhinitis should ideally take nasal steroids in the early evening to gain the most benefit.²

Researchers have conjectured that allergic rhinitis may be aggravated by irregular meal times, which may lead to immunoglobulin E/mast cell-influenced symptoms.³ Having patients maintain regular eating patterns may help regulate the mast cell clock and reduce allergic rhinitis exacerbations.³