A new study found why asthma severity gets worse at night. While scientists have observed this occurrence for centuries, they’ve been baffled about what caused it until recently. A team from Brigham and Women’s Hospital and Oregon Health and Science University investigated this phenomenon. They discovered that the body’s internal circadian clock might contribute to worsening nighttime asthma symptoms.
Scientists previously believed that certain behaviors increased asthma attacks, like sleep, body posture, and physical activities. However, the team discovered that the body’s biological clock is the most significant contributing factor. By gaining insight into the mechanisms that cause worsening asthma, scientists could unveil new treatments in the future.
The study was published in The Proceedings of the National Academy of Sciences.
Asthma, a chronic lung disease, causes airways to become inflamed, swollen, and narrow. Symptoms include difficulty breathing, chest pain, cough, wheezing, and mucus buildup. While it affects people throughout the day, doctors noticed nocturnal asthma for centuries.
For instance, in 1698, the physician Sir John Floyer experienced this phenomenon firsthand. He noticed increasing asthma severity at about 1 or 2 AM compared to daytime symptoms. Scientists have found evidence to support these prior reports, discovering that peak expiratory flow (PEF) can vary between night and day by up to 50%. PEF refers to the maximum flow rate generated during a forceful exhalation, beginning with total lung inflation.
The highest rate of respiratory failure or death due to asthma occurs at nighttime since patients can’t monitor symptoms. So, understanding the mechanisms driving daily variability in asthma severity could have significant implications for treatments.
Patients had to use their inhalers four times as often during the night.
“This is one of the first studies to carefully isolate the influence of the circadian system from the other factors that are behavioral and environmental, including sleep,” said co-corresponding author Frank A.J.L. Scheer, Ph.D., MSc, director of the Medical Chronobiology Program in the Division of Sleep and Circadian Disorders at the Brigham. Co-corresponding author Steven A. Shea, Ph.D., professor, and director at Oregon Institute of Occupational Health Sciences, added the following:
“We observed that those people who have the worst asthma, in general, are the ones who suffer from the greatest circadian-induced drops in pulmonary function at night, and also had the greatest changes induced by behaviors, including sleep. We also found that these results are clinically important because, when studied in the laboratory, symptom-driven bronchodilator inhaler use was as much as four times more often during the circadian night than during the day.”
Around 75% of people living with asthma, or twenty million US citizens, report increasing asthma severity at night. Various behavioral and environmental factors, such as exercise, air temperature, sleep environment, and body posture, have been known to affect asthma severity.
The study on why asthma severity worsens at night
The team wanted to study how the body’s internal clock may contribute to these factors. The circadian rhythm consists of a central pacemaker in the hypothalamus called the suprachiasmatic nucleus. In addition, most organs and tissues in the body have circadian oscillators or networks of biochemical feedback loops that generate 24-hour cycles in all organisms. This vital system helps coordinate bodily functions and predicts daily cycling environmental and behavioral demands.
The team then set out to determine how much the circadian rhythm dictates asthma severity compared to behavioral/environmental factors. They gathered 17 participants with asthma who did not take steroid medications but did use bronchodilator inhalers to manage their symptoms. Then, the scientists separated them into two complementary laboratory protocols and assessed their lung functions, asthma symptoms, and bronchodilator use.
In the “constant routine” protocol, participants stayed awake for 38 hours, maintaining a constant posture under dim lighting. Researchers gave them snacks every two hours. In the “forced desynchrony” protocol, scientists placed participants on a 28-hour sleep/wake cycle for a week under dim light conditions. They scheduled all behaviors evenly throughout the study period.
The researchers found that both groups had their lowest lung function during the night at around 4 AM. They explained that the worsening asthma severity might typically go unnoticed during sleep. Using a mathematical model, the team discovered that the circadian rhythm and the behavioral sleep/wake cycle affected asthma symptoms. This suggests that both internal mechanisms and sleep behaviors may contribute to increased asthma severity.
More studies necessary in the future
“Our findings point to a phenomenon of ‘silent’ asthma,” said Scheer. “A person’s airway resistance may be worse at night, due to the combined effects of the circadian system and the behavioral sleep/wake cycle, but they are generally unaware of this unless it is so severe that it wakes them up.”
However, the team says that their study contains certain limitations. They will need to investigate how other behaviors like exercise and temperature changes influence asthma in the future. In addition, the team will need to test their findings against patients taking other asthma medications like inhaled corticosteroids.
“These highly standardized protocols revealed that the internal circadian system plays a significant role in modulating lung function and asthma severity and that these influences summate with other daily behavioral and environmental effects to drive asthma to be worst at night,” said Scheer. “Uncovering a key role of the biological clock in asthma severity may help in the development of novel therapeutic approaches for asthma,” concluded Shea.
A small study reveals that asthma severity increases at night because of changes in the sleep cycle. This research could have important implications for future treatments since most asthma deaths occur at night—around 75% of people living with asthma in the US report worsening nighttime symptoms. While behavioral and environmental factors like posture, air temperature, and exercise contribute to symptom severity, the internal biological clock plays a significant role.
Researchers will expand upon this study in the future to investigate how other factors, like other asthma medications and exercise habits, affect asthma severity.