Panel examines sex-related differences of asthma in women

Stephen Kirkby, MD
Stephen Kirkby, MD

Asthma is not a gender-neutral disease. In childhood, boys are more likely to have asthma symptoms than girls, but that prevalence is reversed during puberty. Among US residents 18 and older, 8.6% of females have asthma compared with 5.2% of males.

“Females with asthma have more frequent symptoms, poorer quality of life, greater healthcare utilization, and more frequent courses of systemic corticosteroids,” said Stephen Kirkby, MD, Associate Professor of Pediatrics and Internal Medicine at Nationwide Children’s Hospital and Ohio State University.

“Gender and sex hormones play a clear role in asthma, starting at puberty. Estrogen and progesterone increase bronchial hyperreactivity (BHR), activate multiple inflammatory pathways, and increase nitrogen oxide production. Testosterone seems to suppress some of these pathways and have a protective effect.”

Dr. Kirkby discussed the latest findings on asthma in female children and adolescents during Across the Lifespan: Asthma in Women. The session is available on demand to registered CHEST 2021 attendees through October 1, 2022.

Obesity can contribute to asthma symptoms in both males and females, but females appear to be more adversely affected, Dr. Kirkby continued. Females who are obese are more likely to have asthma and are more sensitive to smoke and environmental insults than obese males and more likely to develop BHR.

Young women are also more likely to develop exercise-induced asthma, which may be related to hormonal changes during the menstrual cycle.

Amik Sodhi, MBBS, FCCP
Amik Sodhi, MBBS, FCCP

But what appears to be asthma in young women may not be. Vocal cord dysfunction, for example, is more often seen in young women than men.

“Vocal cord dysfunction has all the symptoms of asthma, but it’s not asthma,” Dr. Kirkby said. “Treatment is not with asthma therapy, but with speech and laryngeal control therapy.”

The menstrual cycle can have a dramatic impact on asthma symptoms. Depending on the reporting method, between 10% and 100% of women with asthma have perimenstrual asthma (PMA), with symptoms worsening during the luteal period after ovulation and peaking a few days before menstruation.

“Women may not be aware that their symptoms have a cyclic pattern,” said Amik Sodhi, MBBS, FCCP, Associate Professor of Medicine and Medical Director, Critical Care Services, at the University of Wisconsin. “Increasing progesterone levels during the luteal phase produce elevated levels of mast cells in the uterine lining, leading to menses. This may also affect mast cells in the airways, leading to increased bronchial hyperactivity and asthma symptoms. We don’t really know the mechanism, but there is probably a biologic mechanism that is related to levels of progesterone.”

While women with PMA tend to have more steroid bursts, more ED visits, more hospitalizations, and more ICU admissions than other women with asthma, treatment is similar. GINA guideline therapy is the first-line approach, Dr. Sodhi said. Progesterone-containing oral contraceptives and leukotriene receptor antagonists may also improve symptom control in more severe PMA.

GINA guidelines are also the basis for treating asthma during pregnancy, which affects about 8% of pregnant women in the US and up to 13% globally.

Sumita Khatri, MD, MS, FCCP
Sumita Khatri, MD, MS, FCCP

“We don’t often give asthma during pregnancy the attention it needs,” said Sumita Khatri, MD, MS, FCCP, Co-Director of the Cleveland Clinic Foundation Asthma Center. “Asthma during pregnancy is associated with worse outcomes for both mother and child. We have to be prepared to take care of them.”

Women with asthma who are planning pregnancy should first get their asthma under control, Dr. Khatri advised.

“More importantly, keep them stable during pregnancy,” she said. “Severity of asthma is positively related to exacerbations rates and hospitalizations. Remember that you have two people to take care of.”

Severe asthma and exacerbations during pregnancy are also associated with increased risk of neonatal death, hospitalization, and congenital malformations such as cleft lip or cleft palate, Dr. Khatri noted. And children born to mothers with poorly controlled asthma are more likely to develop asthma themselves.

One of the key problems is women who reduce or discontinue asthma medication during pregnancy in an attempt to protect the fetus. The reality, Dr. Khatri said, is that the risk of adverse outcomes to both child and mother is far higher with uncontrolled asthma than the medication risk associated with well-controlled asthma.

“Severe asthma puts mother and baby at risk,” she warned. “Adherence and lack of access to asthma medications and care put both at risk. This should be fixable if we all work together.”