Maintaining asthma control lessens risk for asthma complications in pregnant patients

Key takeaways:

• Staying on asthma medications is usually encouraged during pregnancy.
• Medication nonadherence is a large problem among pregnant patients.
• Asthma education may be beneficial.

BOSTON — Asthma control during pregnancy lowers the risk for complications, according to a presentation at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.

Suzanne Ngo, MD, allergist/immunologist at Children’s Hospital Colorado, explained that about 3% to 10% of women of reproductive age have asthma in the U.S.

“Severe or uncontrolled asthma has been associated with complications for both mom and baby,” Ngo said during her presentation. “This includes things like preeclampsia, gestational diabetes, spontaneous abortions, preterm delivery, fetal growth restriction, as well as congenital abnormalities.

“Some of the proposed causes for why we see this includes hypoxia, particularly if there is uncontrolled asthma,” she continued.

Asthma control

Ngo cited a study by Stevens and colleagues that showed asthma symptoms in pregnant women became worse in 40% of the study group, whereas 60% stayed the same and none reported getting better. Symptoms peaked in the middle portion of the pregnancy term.

“What’s been consistently seen in the literature is that exacerbations and symptoms of asthma increase in that second trimester and that will continue through part of the third trimester before decreasing in those last few weeks of pregnancy,” Ngo said.

She also pointed out some risk factors that can be predictors of an exacerbation. These included maternal factors such as older maternal age, higher BMI, cigarette smoking, Black race in the U.S. and anxiety/depression. Some pregnancy factors included less pregnancy weight gain, multiparity and multiple pregnancy. Asthma factors included having a history of prior moderate or severe asthma, a history of pre-pregnancy exacerbations, the use of inhaled corticosteroids (ICS) and decreased FEV₁ percent predicted.

“Focusing on some of these factors and making sure these patients are well controlled before that second trimester has actually been shown to improve or reduce the risk of exacerbations for the rest of their pregnancy,” Ngo said.

To diagnose and monitor asthma during pregnancy, it is safe to do pulmonary functioning testing, Ngo noted. However, she warned against methacholine or any other broncho provocation testing because of the risk for bronchoconstriction.

Using asthma medications during pregnancy

Continuing asthma medications during pregnancy is recommended, according to Ngo, although some studies show that about 40% of pregnant patients stop adhering to ICS medications during pregnancy and some even report a perception that asthma medications may harm a fetus.

When speaking on the topic of medication safety during pregnancy, Ngo cited a summary by the European Respiratory Society as well as the Thoracic Society of Australia and New Zealand.

Ngo explained that short-acting beta agonists (SABA) such as albuterol are usually safe during pregnancy, although excessive use is discouraged. However, long-acting beta agonists are mostly safe. Despite limited human studies, animal studies suggest that long-acting muscarinic antagonists are safe except at very high doses. ICS are mostly safe with no harmful effects. Leukotriene receptor antagonists are safe, although more data are needed. Oral steroids have mixed safety data.

“Biologics are a big thing to consider as well because there are concerns for what the safety of these medications are as we’re using them more and more for asthma,” Ngo said.

Ngo noted that the only human study data available right now for biologics is the omalizumab (Xolair; Genentech, Novartis) EXPECT trial, which showed significant differences between treatment groups.

She also cited a recent international consensus by Naftel and colleagues on the use of asthma biologics in pregnancy. Some highlights include the importance of shared decision-making with the pregnant patient’s allergist and placing the patients onto a registry in order to collect more data on the effect of biologics.

“If you have someone who’s well controlled on a particular regimen prior to pregnancy, shared decision-making to continue this regimen should be employed as opposed to making a lot of changes just to get to some of these more preferred or better studied medications,” Ngo said.

Asthma therapies

“We still want to continue a guidelines-based step therapy,” Ngo said.

She described this as establishing how controlled a patient is based on their symptoms and then deciding whether to step up or down a therapy.

Maintenance and reliever therapy and air therapy currently have very limited data, Ngo also noted. It is unknown whether ICS should be continued at the same time as bronchodilators for rescue therapy.

Treatment approaches

There are three central themes when it comes to studies on asthma treatment approaches in pregnant patients, according to Ngo. These included asthma education, more frequent visits and data monitoring with feedback.

She first cited a 2005 study by Murphy and colleagues that showed a significant improvement in medication adherence in severe asthma patients after two sessions with a nursing educator. The effect was less noticeable in mild to moderate patients.

She then cited the 2016 MASTERY study by Zairina and colleagues that focused on data monitoring and feedback. They used a mobile phone app to monitor lung function, asthma symptoms and medication usage. Automated feedback was given based on N-acetylcysteine and Global Initiative for Asthma guidelines on medication changes or asthma visits. Study results showed a significant reduction in Asthma Control Questionnaire (ACQ) scores at 6 months.

But Ngo commented that the decrease in ACQ scores was only by 0.3 and that “there weren’t any significant outcomes for the other secondary outcomes they looked at. So again, some benefit but not significant ones.”

The MAMMA study by Lim and colleagues used all three treatment themes. This randomized controlled trial had pharmacists provide asthma education at baseline and a monthly monitoring of ACQ and FEV₁ to coordinate need for step-up therapy.

Results showed a significant reduction in ACQ scores after 6 months of intervention. It also had more patients with adequately controlled asthma based on an ACQ score of less than 1.5.

Lastly, Ngo mentioned the 2011 MAP trial by Powell and colleagues, which focused on FeNO-guided management. This was a double-blind randomized control trial where patients in the intervention group had monthly visits to determine changes in treatment based off of their FeNO levels.

“Looking at the algorithm for how these changes were made, this did show significant reduction in asthma exacerbations, reduced SABA use, improved quality of life, as well as a trend towards better perinatal outcomes,” Ngo said.

The MAP study was repeated with a larger population in the Breathing for Life trial in 2022 by Murphy and colleagues, but this time, results showed no significant differences.

A new paradigm

Ngo stressed the importance of addressing comorbidities and a new paradigm for treating asthma and other airway diseases during pregnancy.

“This is a personalized care approach based on identification of treatable traits to guide management,” she said.

These traits include things such as airway inflammation, behavioral risk factor changes, asthma management skills, smoking and many more.

“For each of these, there are different markers that you can look at that can help you determine if further management for these different domains are necessary,” Ngo said. “Hopefully, with this more personalized approach for such a heterogeneous disease, we can get more data.”

References:

• Lim AS, et al. CHEST. 2014;doi:10.1378/chest.13-2276.
• Middleton PG, et al. Eur Respir J. 2020;doi:10.1183/13993003.01208-2019.
• Murphy VE, et al. Eur Respir J. 2005;doi:10.1183/09031936.05.00135604.
• Naftel J, et al. Lancet Respir Med. 2024;doi:10.1016/S2213-2600(24)00174-7.
• Powell H, et al. Lancet. 2011;doi:10.1016/S0140-6736(11)60971-9.
• Stevens DR, et al. J Allergy Clin Immunol Pract. 2021;doi:10.1016/j.jaip.2021.09.048.
• Zairina E, et al. Respirology. 2016;doi:10.1111/resp.12773.