Asthma, a chronic respiratory disease characterized by variable bronchial inflammation, airflow obstruction, and hyperresponsiveness, is estimated to affect 15.7 million American adults, or 7.2% of the general adult population.1 After the age of 17, women have a 40% higher asthma prevalence rate than men.1 In addition, women experience significantly more asthma attacks and are hospitalized 35% more often for asthma.1 Although asthma mortality has declined slightly since 2000, death rates in 2003 were 200% higher for non-Hispanic blacks compared to non-Hispanic whites, and 45% higher for females than for males.1
Asthma is one of the most common, chronic medical conditions that can complicate pregnancy, affecting between 4% and 8% of this population.2 Adverse pregnancy outcomes can be related to poor asthma control, and severe maternal asthma has been associated with an increased risk of infant death, preeclampsia, premature birth, and low birth weight.3
Improved pregnancy outcomes are closely associated with well-controlled asthma and aggressive treatment of exacerbations during pregnancy. The goal of therapy is to maintain optimal control of asthma for maternal health and well-being, as well as normal fetal maturation throughout gestation.3 Treatment is based on frequency of symptoms and introduced in a stepwise approach similar to asthma management in nonpregnant adults. To help guide the medical community in the management of asthma and improve maternal and fetal outcomes, several national and international groups have published evidence-based recommendations. The American College of Obstetricians and Gynecologists (ACOG) practice bulletin for managing asthma in pregnancy is the most recent set of guidelines published. The ACOG practice bulletin emerged from recommendations published in the Expert Panel 3 Guidelines for the Diagnosis and Management of Asthma 4 and the National Asthma Education and Prevention Program's Asthma and Pregnancy Update 2004.3 The main recommendations from this document are discussed in the following sections.
Asthma diagnosis in pregnancy
In nonpregnant patients, asthma diagnosis begins with a focused exam and detailed history. The history should include specific breathing symptoms, timing of symptoms, frequency, and any aggravating or relieving factors.2 Aggravating factors may include intrinsic triggers such as stress, exercise, menses, and pregnancy, or extrinsic triggers such as pollution, allergens, temperature, and humidity. Comorbid conditions of uncontrolled gastroesophageal reflux disease (GERD), vocal cord dysfunction (VCD), postnasal drip (PND), and chronic sinus disease can mimic the symptoms of asthma and must be considered in the differential when making the diagnosis of asthma.2,4
Spirometry with pre- and postbronchodilation is recommended to evaluate for airflow obstruction and reversibility.2,4 The normal physiologic changes of pregnancy have a minimal effect on the forced expiratory volume in one second (FEV1), making spirometry a useful tool for evaluating most pregnant patients with suspected asthma.3 The test is considered positive for asthma if obstruction is present and FEV1 increases by more than 12% and 200 mL following administration of a bronchodilator.2,4 It should be noted, however, that normal spirometry does not exclude the diagnosis of asthma. Airflow obstruction may be absent if the patient has intermittent or mild asthma and symptoms are not apparant.4 Methacholine challenge testing is often used to exclude asthma in nonpregnant patients with asthma-like symptoms and normal spirometry. However, the risk of bronchospasm associated with methacholine use makes it contraindicated during pregnancy.5
Once asthma is confirmed, medical therapy is initiated based on severity, impairment, and risk (see Classifying asthma severity and initiating treatment in adults and youths age 12 and older).4 The ACOG recommends a trial of asthma therapy if the spirometry is normal but the index of suspicion for asthma is high.2
Asthma assessment during pregnancy
Asthma is a variable disease and the physiologic changes associated with pregnancy may complicate asthma management and control. Factors involving modification of cell-mediated immunity, prostaglandins, and hormonal fluctuations during pregnancy are under investigation but fail to adequately explain why one-third of pregnant women experience worsening asthma, one-third report improvement in overall symptoms, and the remaining one-third are unchanged during the course of pregnancy.6 Additionally, dyspnea is a common symptom of pregnancy and must be differentiated from dyspnea of worsening asthma. Dyspnea of pregnancy is not associated with chest tightness, coughing, wheezing, reductions in peak expiratory flow rates (PEFRs), or other signs of airway obstruction.3
Comprehensive assessment and early intervention for worsening asthma minimizes maternal and fetal risk. Asthma control assessment and pulmonary function testing are recommended every month during pregnancy.4 Subjective evaluation includes asking the patient how often asthma symptoms affect daytime activities or sleep, and how many puffs of rescue therapy they are using.4 Assessment of subjective symptoms is best accomplished using a standardized asthma control questionnaire administered at each follow-up visit as patients tend to overestimate their degree of asthma control.7 A standardized form ensures consistent assessment of all elements of asthma control. A self-administered validated questionnaire such as the Asthma Therapy Assessment Questionnaire (ATAQ),8 Asthma Control Questionnaire (ACQ),9 Asthma Control Test (ACT),10 or use of a symptom diary is recommended.4
Pregnancy minimally affects the FEV1 or PEFR; therefore, spirometry or peak flow meters are acceptable objective monitoring tools for worsening asthma.3 Spirometry is the preferred method in the clinical setting. The usefulness of peak flow meters is limited due to variability between meters and reliance on patients for accurate readings.4 However, peak flow meters are recommended for home monitoring in patients with difficulty perceiving worsening asthma or for those with moderate-to-severe asthma.4
The importance of risk assessment was first introduced in the Expert Panel 3 Guidelines for the Diagnosis and Management of Asthma in 2007, to identify those at increased risk of death from asthma.4 Risk factors include patients who have been to the ED three or more times or hospitalized two or more times in the last 12 months for asthma, patients hospitalized or who have been to the ED in the previous month for asthma, patients that required intubation or an ICU admission in the past, or patients who use two or more canisters of short-acting beta-agonists (SABAs) per month. Asthma patients without a written asthma action plan and those of low socioeconomic status or with significant comorbidites are also at risk.4 Patients at high risk for a fatal attack require close medical monitoring and education regarding early identification and management of worsening asthma.4
Two or more asthma exacerbations over a 12-month period treated with oral corticosteroids categorizes the patient as having persistent asthma and indicates a need for a step-up in therapy (see Stepwise approach for asthma therapy in adults and youths age 12 and older).4
SABAs, such as albuterol (Proventil HFA, Ventolin HFA), are the preferred rescue medications during pregnancy.2 All patients with known asthma require a prescription for SABA. A nebulized treatment of a SABA, or two to six puffs of a metered dose inhaler (MDI), is recommended as soon as asthma symptoms are recognized or there is a 20% decline in peak flow readings.2,4 This treatment can be repeated 20 minutes later if symptoms persist.2,4 Emergency care is needed if there is no response to the SABA, there is a decline in fetal activity, or the patient is known to be at high risk for a fatal attack.2,4 If the asthma symptoms are alleviated (peak flow over 80%), the SABA is continued every 4 to 6 hours for 24 to 48 hours.4
Adjusting therapy during pregnancy
A stepwise approach to asthma therapy is recommended based on asthma control. Patients with uncontrolled asthma should receive a step-up in medication. When control has been achieved and sustained for several months, a step-down in medications may be considered.2,4 A step-down in therapy should be approached with caution during pregnancy to prevent an asthma exacerbation. Some healthcare providers may choose to postpone a reduction in medications until after delivery.2,4
Patients who experience asthma symptoms more than 2 days per week or nighttime awakenings due to asthma more than twice a month, patients who require rescue SABA more than 2 days per week, or patients who report limitations in activities are not considered well controlled and require a step-up in asthma therapy.4 A follow-up evaluation is recommended within 2 to 6 weeks after medication adjustments.4
First-line controller therapy
Inhaled corticosteroids (ICSs) are the preferred controller medications for those exhibiting persistent asthma symptoms. Budesonide (Pulmicort Flexhaler) is the preferred ICS during pregnancy.4 However, the overall safety profile of ICS supports continuing any ICS effective in controlling the patient's symptoms.4
Despite the documented safety of ICS for asthma management during pregnancy, a significant percentage of pregnant women on ICS do not take their medication consistently. A large cohort study of 9,154 pregnant Tennessee Medicaid patients with asthma found that less than 25% of the women were on ICS and 72% of this group filled their prescription only once during pregnancy.11 SABAs were dispensed 3.4 times more often than asthma controller medications.11 During pregnancy, 23% of white women and 40% of African American women required hospitalization or an ED visit for uncontrolled asthma, yet only 6.5% filled two or more prescriptions for controller medications.11 This study did not investigate specific reasons a controller medication was not obtained by those with asthma. It is unknown whether the women were not prescribed controller medication or were noncompliant with prescribed controller medication.
Although the data cannot be generalized, they raise awareness for a possible disparity in the management of asthma during pregnancy. Failure to follow the asthma guidelines and educate women on the safety of asthma medications increases the risk of inadequate asthma control.
Use of ICS during pregnancy has not been associated with major birth defects, preterm delivery, low birth weight, or pregnancy-induced hypertension.12 However, only budesonide has a pregnancy risk category B classification.4 Alternative therapy may include use of mast cell stabilizers (Intal), leukotriene receptor antagonists (LTRAs) (Singulair, Accolate), or theophylline (Theo-24, Uniphyl). However, mast cell stabilizers and LTRAs provide inferior control of asthma symptoms when compared with ICS.4,13 Theophylline is safe for use in pregnancy when dosed within the recommended therapeutic serum concentrations.3,4 When compared with ICS, theophylline has a similar effect on asthma exacerbations and maternal outcomes, but it has been associated with more adverse reactions, higher discontinuation rates, and lower FEV1 than ICS.3 Additionally, drug clearance may be reduced during the third trimester, necessitating frequent monitoring of serum theophylline levels and adjustment of drug dosage.14
Appropriate add-on controller therapy
Long-acting beta2-agonists (LABAs) in combination with ICS (Advair, Symbicort) is the recommended add-on therapy for patients not controlled on a medium-dose ICS alone.2,4 Theophylline and LTRA are considered alternative add-on therapies. However, LABAs provide better asthma control than either of these agents and have fewer adverse reactions than theophylline.4 If asthma symptoms are not controlled on medium-dose ICS and LABA (or alternatives), then therapy should be advanced to high-dose ICS and LABA. Those with severe asthma not controlled on high-dose ICS and LABA may require daily oral corticosteroids.2,4
LABAs (Serevent Diskus, Foradil) are recommended as add-on therapy in those uncontrolled on a moderate dose of ICS, but they should never be used as monotherapy in asthma.4,15 Although some safety concerns have been raised regarding the use of LABAs, they remain the drug of choice for patients with moderate-to-severe persistent asthma.15-17 Healthcare providers must educate patients and weigh the potential risk associated with LABA use with the fact that combination therapy with ICS and LABA provides the most effective treatment of moderate-to-severe persistent asthma and prevention of severe exacerbations.4,18 There are limited data on the use of LABAs in pregnancy, but LABAs are believed to have a safety profile similar to a SABA.4 Patients with uncontrolled asthma on medium doses of ICS and who are unable to tolerate a LABA, are candidates for alternative add-on medications.
Acute exacerbations and follow-up
Regardless of classification, all patients with asthma are at risk for an acute asthma exacerbation. Acute asthma exacerbations requiring medical intervention occur in approximately 20% of susceptible women during pregnancy and are more common during the second trimester.19 The most common causative factors include viral infections and nonadherence to medical therapy.4
Patients must be educated to identify signs of worsening asthma control, and home treatment should be initiated at the start of symptoms (see Management of asthma exacerbations at home). If there is an inadequate response to initial treatment, use of oral systemic corticosteroids such as prednisone at a dose of 40 to 60 mg (or equivalent) in single or divided doses for a total of 5 to 10 days is indicated. Use of a SABA every 3 to 4 hours should also be continued. Doubling the dose of inhaled corticosteroids is no longer recommended for home treatment of acute exacerbations. If a patient fails home treatment, emergency care is indicated.4
An asthma action plan serves as a patient guide for early recognition and treatment of an exacerbation.4 Action plans containing personalized instructions regarding medications to add, criteria for adding the medication, duration of use, and when to seek medical help when the patient is symptomatic have been associated with a 40% reduction in hospital admissions and a 20% reduction in ED visits in general asthma populations.23
Early intervention during an exacerbation is imperative. An acute exacerbation that causes maternal hypoxemia may reduce uterine blood flow, which can result in an increase in fetal systemic and pulmonary vascular resistance, ultimately leading to a reduction in fetal cardiac output and hypoxia.20 Recommendations for ED and hospital treatment are discussed in The Guidelines for the Diagnosis and Management of Asthma.4
During an acute asthma exacerbation, the mother and fetus must be quickly assessed. This includes a brief history, physical exam, spirometry or peak flow readings, oxygen saturation, and fetal well-being.2 If the fetus has reached the stage of viability, continuous electronic monitoring or a biophysical profile should be considered.2
Following treatment in an urgent care or ED, the mother may be released for home management if her asthma symptoms have resolved, the FEV1 or peak flow reading is 70% or greater of predicted, and the fetus is stable an hour after the last administered treatment.2 An incomplete response to therapy indicates the need for continued treatment performed in the hospital or at home depending on the patient.2 However, if the response to therapy is poor (FEV1 or peak flow measurements less than 50% predicted), or the patient experiences associated symptoms of drowsiness, confusion, or a Paco2 level greater than 42 mm Hg, hospital admission is indicated.2
Home management following an exacerbation typically includes oral corticosteroids and two to four puffs of a SABA every 3 to 4 hours as needed.2 A follow-up appointment is recommended within 5 days of an acute hospital visit.2 The appointment provides an opportunity to assess asthma control and adjust therapy if indicated. Pregnant women may experience prolonged symptoms after an exacerbation because they are less likely to be treated with oral corticosteroids in the ED or following a hospitalization for an asthma exacerbation compared with their nonpregnant counterparts.21,22 Inadequate treatment of an acute exacerbation leads to uncontrolled asthma, which may increase the risk to mother and fetus.
Allergy treatment and allergy shots
Immunotherapy may be continued if the patient is stable on the medication and receiving maintenance or near-maintenance doses.2 Starting immunotherapy or advancing the dose is not recommended during pregnancy due to the risk of anaphylaxis.2
Allergic rhinitis is a potent trigger of asthma symptoms. Pregnancy can worsen symptoms of allergic rhinitis, which in turn may result in uncontrolled asthma.14 Allergic rhinitis is generally treated with antihistamines and/or an intranasal corticosteroid. Intranasal corticosteroids are the preferred treatment for allergic rhinitis due to their low risk of systemic absorption.4 The majority of data has been collected on budesonide, which is pregnancy risk category B (see Pregnancy categories for frequently prescribed allergy and asthma medications). However, the overall safety profile of intranasal corticosteroids supports continuing any brand effective in controlling the patient's symptoms.14
Recommended antihistamines include first-generation diphenhydramine and second-generation loratadine or cetirizine.4 The second-generation antihistamines have the added benefit of less sedation. Decongestants have been associated with an increased occurrence of gastroschisis when taken during the first trimester and should be avoided.24
Identifying and controlling factors known to exacerbate asthma can lead to improved asthma control and minimized medication use.2 If patients are allergic to a known allergen, removing or reducing exposure to the allergen may lessen symptoms. Irritants such as wood smoke, tobacco smoke, fumes, pollution, and particulate matter are strong triggers for asthma symptoms and should be avoided when possible.4 Additionally, exposure to tobacco smoke has been linked to sudden infant death syndrome, asthma, and other respiratory infections in children.23
Infections are a significant trigger of acute asthma exacerbations. Exposure can be reduced by regular handwashing and avoiding those who are ill. Vaccines containing inactivated virus, bacterial vaccines, or toxoids are generally considered safe for administration during pregnancy.25 Immunization with the inactivated seasonal flu and 2009 H1N1 vaccines is recommended if the pregnancy occurs during influenza season.25 Contraindications to the seasonal influenza vaccine include severe allergy to chicken eggs, history of previous allergic reaction to the vaccine, history of Guillain-Barré syndrome, or a moderate-to-severe febrile illness on the day of the injection.25 Hepatitis B, tetanus-diphtheria, meningococcal, and rabies may be given during pregnancy if exposure risk is high.25
Self-management skills are critical for patient success in the control and management of asthma.4 Start asthma education at the time of diagnosis and reinforce patient understanding at each follow-up visit. Education is most effective if individualized to each patient and includes (a) basic asthma facts, (b) definition of controlled and uncontrolled asthma and the patient's current level of control, (c) action of medications, (d) proper medication administration, (e) action to take when asthma worsens, and (f) environmental control measures. Additionally, all patients should have an asthma action plan that includes daily management and actions to take if asthma worsens.4
An ultrasound exam is recommended between 12 and 20 weeks to serve as a baseline for evaluation of fetal growth restriction and the risk of preterm birth.2,14 Serial ultrasound exams to evaluate fetal activity and growth should be considered at 32 weeks gestation in women with poorly controlled asthma, moderate-to-severe asthma, and for women recovering from a severe asthma exacerbation.2 Also, consider antenatal surveillance of fetal well-being and instruct all patients in monitoring fetal activity.2
Continue asthma medication throughout labor and delivery. Keep the mother well-hydrated and provide adequate anesthesia to prevent bronchospasm.2 Lumbar anesthesia can reduce oxygen consumption and minute ventilation during labor.2 However, avoid high levels of analgesia that may cause airway compromise in those with lung disease.26 Cesarean section is rarely needed for an acute exacerbation; however, delivery may improve the mother's respiratory status.2 Ergot alkaloids such as methylergonovine, which are sometimes used to prevent or treat intrauterine bleeding after childbirth or abortion, have been associated with an increase risk of bronchospasm in the asthmatic patient and should be avoided when possible.3,26
Pain is the most potent trigger of the hypothalamic-pituitary-adrenal (HPA) axis and can stimulate cortisol levels up to 100 mg daily with major surgery.27 The process of labor can potentially induce adrenal crisis in those with suppression of the HPA axis. High-risk patients include those taking more than 20 mg daily of prednisone (or equivalent) for more than 3 weeks and those who appear cushingoid.27 HPA axis suppression may occur on intermediate doses of oral corticosteroids or high doses of ICS.4 Therefore, the clinician must monitor for signs and symptoms during labor, delivery, and the early postpartum period. Those at risk should receive a stress dose of hydrocortisone 100 mg every 8 hours during labor and for 24 hours after delivery to prevent adrenal crisis.2
Only small amounts of asthma medications enter breast milk and are not contraindicated during breastfeeding. Prednisone, theophylline, antihistamines, ICSs, beta-agonists, and cromolyn are considered safe to use while breastfeeding.3 However, maternal use of antihistamines has been associated with infant paradoxical central nervous stimulation depending on the dose, frequency, and timing of the medication. While breastfeeding, women should be encouraged to use the least amount of medication effective for controlling their symptoms and take medications just after breastfeeding when possible to minimize infant exposure.28
Healthcare providers are pivotal in improving outcomes for the mother and fetus by instituting evidence-based practice guidelines for the care and management of their asthmatic patients. Optimal asthma control is dependent on healthcare providers performing symptom assessment, objective testing, stepwise medication adjustment, and education at each visit. Patients should receive an asthma action plan and education on self-management skills for the early identification and treatment of worsening asthma. Each plan should be specific and tailored to the individual patient. Pregnant women and those contemplating pregnancy will likely require frequent and consistent education about the safety and importance of their asthma therapy.
The authors gratefully acknowledge the assistance of Tim Eubanks, PhD, for developing the figures used in the article and Jonathan Parsons, MD, MSc, for manuscript review and recommendations.
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