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November 2012

Respiratory Symptoms Vary According to Stage of Menstrual Cycle

Respiratory symptoms vary significantly during different stages of the menstrual cycle, with higher frequencies during the mid-luteal to mid-follicular stages, according to a new study.

“The effects of the menstrual cycle on respiratory symptoms in the general population have not been well studied,” said lead author Ferenc Macsali, MD, of the Haukeland University Hospital in Bergen, Norway. “In a cohort of nearly 4,000 women, we found large and consistent changes in respiratory symptoms according to menstrual cycle phase, and, in addition, these patterns varied according to body mass index (BMI), asthma, and smoking status.”

The findings were published online ahead of print publication in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

A total of 3,926 women with regular cycles who were not taking exogenous sex hormones were enrolled in the study. Menstrual cycles, respiratory symptoms, BMI, asthma, and smoking status were determined by postal questionnaire.

Significant variations over the menstrual cycle were found for each symptom assessed in all subjects and subgroups. Reported wheezing was higher on cycle days 10-22, with a mid-cycle dip near the putative time of ovulation (~days 14-16) in most subgroups. Shortness of breath was highest on days 7-21, with a dip just prior to mid-cycle in a number of subgroups. The incidence of cough was higher just after putative ovulation for asthmatics, subjects with BMI ≥ 23kg/m2, and smokers, or just prior to ovulation and the onset of menses in subgroups with a low incidence of symptoms.

“Our finding that respiratory symptoms vary according to the stage of the menstrual cycle is novel, as is our finding that these patterns vary according to BMI and smoking status,” said Dr. Mascali. “These relationships indicate a link between respiratory symptoms and hormonal changes through the menstrual cycle.”

The study had a few limitations, including the use of questionnaires to gather data and variation in the length of menstrual cycles in the study population, which may affect the accuracy of determining menstrual cycle stage.

“Our results point to the potential for individualizing therapy for respiratory diseases according to individual symptom patterns,” concluded Dr. Mascali. “Adjusting asthma medication, for example, according to a woman’s menstrual cycle might improve its efficacy and help reduce disability and the costs of care.”

Contact for article: Ferenc Macsali, Department of Gynecology and Obstetrics, Haukeland University Hospital, 5021 Bergen, Norway
Phone: + 47 55 974200
Email: ferenc.macsali@med.uib.no

Mechanism of Breathing Muscle 'Paralysis' in Dreaming Sleep Identified

A novel brain mechanism mediating the inhibition of the critical breathing muscles during rapid eye movement (REM) sleep has been identified for the first time in a new study, offering the possibility of a new treatment target for sleep-related breathing problems.  

The findings were published online ahead of print publication in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

“REM sleep is accompanied by profound inhibition of muscle activity,” said researcher Richard Horner, PhD, professor of medicine and physiology at the University of Toronto This “paralysis” affects  breathing muscles and “is a cause of snoring and other breathing problems in sleep, especially obstructive sleep apnea.”

Sleep apnea is a common and serious problem that increases the risk for heart attacks, high blood pressure, stroke, diabetes and daytime sleepiness.

According to Dr. Horner, “the brain mechanism mediating inhibition of the critical breathing muscles in REM sleep was unknown, but a novel and powerful inhibitory mechanism is identified for the first time in our study.”

In the study, performed by PhD student Kevin Grace, rats were studied across sleep-wake states. The researchers targeted manipulation of the brain region that controls tongue muscles during sleep.

The tongue is an important breathing muscle because its activity keeps the airspace open behind the tongue to allow for the effective passage of air into the lungs. Inhibition of tongue muscle activity in sleep in some people leads to backward movement of the tongue and blockage of the airspace. This blockage in sleep leads to episodes of self-suffocation (sleep apnea) that are rescued by waking up from sleep. Such episodes can occur hundreds of times a night. 

Importantly, the muscle activating effects of these interventions were largest during REM sleep and minimal or absent in other sleep-wake states. The brain chemical mediating this powerful inhibition of breathing muscle activity in REM sleep is acetylcholine, acting via muscarinic receptors that are functionally linked to a particular class of potassium channel.

"Since REM sleep recruits mechanisms that can abolish or suppress tongue muscle activity during periods of REM sleep and cause obstructive sleep apnea, identification of a mechanism mediating this inhibition is a significant discovery," said Dr. Horner.

 “This newly identified process has fundamental implications for understanding the common and serious problems of snoring and other breathing problems such as obstructive sleep apnea, which are worse in REM sleep,” said Dr. Horner. “Moreover, identifying the fundamental mechanism responsible for the shutting down of a muscle in sleep that is critical for effective breathing also identifies a rational drug target designed to prevent this inactivity and so prevent obstructive sleep apnea and other sleep-related breathing problems.”


Contact for article: Richard L. Horner, Ph.D., Room 3206 Medical Sciences Building, 1 King’s College Circle, Toronto, ON, Canada, M5S 1A8
Phone: 416-946-3781
Email: richard.horner@utoronto.ca