Asthma in Pregnancy

Uma Munnur

Venkata D. P. Bandi

Introduction

Asthma is one of the most common serious medical problems in pregnancy. Asthma is a risk factor for several maternal and fetal complications posing a special challenge for physicians treating asthmatic pregnant women (1). Evidence suggests a two-fold effect of asthma: It can impact adversely on the outcome of pregnancy, and pregnancy can alter the clinical status of the patient with the disease (2). Pregnant women with asthma are at increased risk of perinatal complications including preeclampsia, low birth weight, and premature delivery (3,4,5). Asthma exacerbations during pregnancy can have detrimental consequences for both mother and fetus. Active asthma management with a view to reduce the exacerbation rate will be clinically useful in reducing the perinatal complications, particularly preterm labor.

Definition

Asthma is a chronic inflammatory disorder of the airways defined by the presence of the following three characteristic findings: Reversible airway obstruction (1), airway inflammation (2), and airway hyperresponsiveness (3). Airway obstruction produces the clinical manifestations of cough, dyspnea, and wheezing. Airway inflammation contributes to airway hyperresponsiveness, airflow limitation, respiratory symptoms, and chest tightness. Airway inflammation modulates the course of asthma by independently producing airway obstruction and enhancing airway responsiveness. Airway hyperresponsiveness is marked by exaggerated responses to a wide variety of bronchoconstrictor stimuli. The interaction of these features of asthma determines the clinical manifestations and severity of asthma and the response to treatment.

Epidemiology

Asthma is a common, potentially serious medical condition that complicates approximately 4% to 8% of pregnancies (6,7,8). In 2009, current asthma prevalence was 8.2% of the US population (24.6 million). It was higher among females, children, non-Hispanic Black and Puerto Rican ethnicity, and people below the poverty level. In 2007, there were 1.75 million asthma-related emergency department visits and 456,000 asthma hospitalizations (9). The prevalence of asthma attacks seems to be elevated among pregnant women who are younger, unmarried, or have a lower annual family income (8). In general, the prevalence and morbidity from asthma are increasing, although asthma mortality rates have decreased in recent years (10). Acute exacerbations that necessitate emergency care or hospitalization have been reported in 9% to 11% of pregnant women cared by asthma specialists (11). Fifty-five percent of women with asthma will experience at least one exacerbation during pregnancy (12).

Pathophysiology and Pathogenesis of Asthma

Asthma is a chronic inflammatory disease characterized by a reversible airway obstruction and airway hyperreactiveness. In addition to increased sensitivity, there is airway narrowing and a deficient response of the airways and a lack of bronchodilatory response of the airways to deep inspiration. Asthmatics also have a progressive loss of airway distensibility due to loss of lung elastic recoil (13).

Airway obstruction may be caused by changes in smooth muscle. Even though the smooth muscle is hypertrophic, it does not show increased constriction when exposed to pharmacologic stimuli. However, the failure of the normal autonomic neural control mechanisms can result in impaired relaxation and subsequent obstruction. Narrowing of the airway lumen can also result from bronchial mucosal edema and inflammatory cell infiltrates. Reversible airway obstruction is defined as an obstruction on spirometry which is documented during acute asthmatic attacks with normal physiology between attacks. Reversibility can also be proven by either partial or complete resolution of obstruction following the administration of a short-acting bronchodilator.

Airway hyperresponsiveness is marked by exaggerated responses to a wide variety of bronchoconstrictor stimuli like methacholine, histamine, or specific antigens, and is the cornerstone feature of this disorder. Multiple factors lead to narrowing of the airway that in turn result in reduced airflow, such as smooth muscle contraction, thickening of the airway wall, and the presence of secretions within the airway lumen (14).

Airway inflammation primarily serves as a modulating influence in asthma. Inflammation is present in nearly all asthmatic patients. The process of inflammation involves the occurrence of airway wall edema and infiltration of the mucosa by a variety of inflammatory cells which include neutrophils, mast cells, helper T lymphocytes, macrophages, and eosinophils. These cells release mediators of inflammation, including histamine, leukotrienes, platelet activating factor, prostaglandins, thromboxanes, cytokines, and serotonin.

The major physiologic abnormality during an asthma attack is air trapping. The patient can inhale air into her lungs, but is not able to exhale it out. This increases the work of breathing as the patient tries to breathe with the hyperinflated lung. The overdistension of normal alveoli causes pressure on capillaries in the alveolar walls, causing decreased perfusion to overdistended alveoli and thus resulting in ventilation–perfusion mismatch. When asthma is severe, pulmonary hypertension results in a leftward shift of the interventricular septum, and there is a decrease in the stroke volume. On deep inspiration, systolic blood pressure decreases, resulting in pulsus paradoxus (13,15).

Table 31-1 Diagnosis of Asthma

Symptoms	Wheezing, Cough, Chest Tightness
Signs	Wheezing on auscultation (absent when limited airflow movement)
Diagnosis confirmation	Airway obstruction that is partially or completely reversible >12% increase in FEV₁ after administration of bronchodilator

Diagnosis of Asthma

Medical History

Diagnosis of asthma in pregnancy is no different than for a nonpregnant patient (Table 31-1). The classic symptoms of asthma include dyspnea, wheezing, cough, and chest tightness. The medical history should also include information about the pattern and severity of the symptoms, precipitating and aggravating factors, duration and course of the symptoms along with hospitalization, and mechanical ventilation. The diagnosis of asthma is usually straightforward since most patients have a history of asthma prior to conception. However, diagnostic testing is required in patients with clinical picture or response to therapy is atypical and also in patients who present with respiratory symptoms for the first time in pregnancy (16).

Current asthma control should be assessed according to the frequency, severity of symptoms, frequency of use of rescue therapy, history of exacerbations requiring the use of systemic corticosteroids, and the result of pulmonary function tests. Forced expiratory volume of air expired in one second (FEV₁) and peak flow rates do not change significantly during pregnancy and so can be used for assessing asthma control. Patients who have asthma that is well controlled and who are not receiving controller medications can be classified as having intermittent rather than persistent asthma (16).

Physical Examination

Important aspects of the examination are assessment of respiratory rate, speech (number of words between breaths), use of accessory muscles, ability to lie flat, and presence of pulsus paradoxus. Auscultation of the chest will reveal wheezing and a prolonged phase of expiration (which may be absent when there is limited airflow during an exacerbation).

Laboratory Studies

After obtaining a thorough history and examining the patient, pulmonary function tests are useful to document the severity and establish the reversibility of obstruction. Diagnostic testing is warranted in patients whose clinical picture or response to therapy is atypical or in patients who present with respiratory symptoms during pregnancy without history of asthma. Bronchoprovocation tests (with histamine) are used when the history and physical examination strongly suggest the presence of asthma but spirometry fails to reveal airway obstruction. FEV₁ is a standardized measure of airway obstruction and is used to reflect both asthma severity and degree of asthma control (16). Methacholine, which is used to confirm hyperreactivity, is contraindicated during pregnancy because of the lack of data on the safety of such testing in pregnant patients. The demonstration of a reduced FEV₁ to forced vital capacity ratio along with a 12% or greater improvement in FEV₁ after the administration of inhaled albuterol confirms a diagnosis of asthma during pregnancy (16).

Patients with asthma, who have not been tested before for allergens, should undergo serologic testing for IgE antibodies to allergens such as dust mites, cockroaches, mold spores, and pets. Skin tests are generally not recommended during pregnancy because the potent antigens may be associated with significant systemic reactions (16). Bronchial provocation tests are infrequently done in pregnancy. If the patient has a prior history of physician-diagnosed asthma, she usually is managed as an asthmatic (13).

Effects of Asthma on Pregnancy and Fetus

Women with asthma have been reported to have higher risk for several complications of pregnancy which include preeclampsia, preterm birth, intrauterine growth retardation, congenital malformations, and perinatal mortality (17,18). Other adverse outcomes that appear to be increased in asthmatics include postpartum hemorrhage, preterm labor, premature rupture of membranes, neonatal hypoxia, and transient tachypnea of the newborn. Data regarding the effect of maternal asthma on pregnancy have been conflicting, but the largest Swedish population based study on pregnant women with asthma found an association of preeclampsia, preterm birth, and lower birth weight (19). The potential mechanisms proposed for this increased risk are: (1) Poor maternal asthma control leading to exacerbations and fetal hypoxia, (2) asthma medications like corticosteroids, and (3) common pathogenetic factors that cause both asthma and perinatal complications.

The need to induce labor and the rate of cesarean delivery also tend to be higher in asthmatic parturients (20). Data suggests a strong association between poor asthma control with these increased risks. Better asthma control in pregnancy may improve pregnancy outcomes (16,17,21). As a general rule, mild asthma is unchanged in pregnancy and severe asthma tends to worsen (22).

During acute exacerbations, potential mechanisms of increased perinatal morbidity and mortality include hypoxemia and hypocapnia (23). Maternal hypocapnia can produce uterine vasoconstriction and hypoxemia can diminish fetal oxygen delivery, both of which are detrimental to the fetus.

Effect of Pregnancy on Asthma

The effect of pregnancy on asthma is unpredictable. The course of asthma may improve, deteriorate, or remain unchanged during pregnancy. Asthma exacerbations can occur at any time during pregnancy, but are more common in the second and third trimesters. Asthma exacerbation is rare during labor and the peripartum period. Monitoring of asthma status during prenatal visits is encouraged. Monthly evaluation of asthma history and pulmonary function (spirometry or measurement with a peak flow meter) is recommended.

Some asthmatic pregnant women experience improvement in their symptoms during pregnancy. This is probably due to the increase in progesterone with advancing gestation which contributes to cyclic adenosine monophosphate (cAMP)-induced bronchodilation, thereby improving asthma and peak flow rates (24). In the last 4 weeks of pregnancy, asthmatics have reduced wheezing, sleep interference, and interference with daily activities, most likely due to the hormonal changes.

The mechanism for asthma exacerbation during pregnancy is not very clear. Maternal cell-mediated immunosuppression may increase maternal susceptibility to viral infections,
which seem to be the most common precipitators of severe asthma during pregnancy. Increase in progesterone during pregnancy has been associated with relaxation of smooth muscle of the lower esophageal sphincter tone which causes gastroesophageal reflux (GER). GER occurs in 45% to 89% of patients with asthma. In essence, some of the obvious factors responsible for the exacerbation include smoking, GER, and reducing asthma medications for fear of causing harm to the fetus.

Management of Asthma

The general principles of asthma management during pregnancy do not significantly vary from the management of nonpregnant asthmatics. The ultimate goal for the asthmatic parturient is to have no limitation of activity, minimal symptoms, avoid exacerbations, maintain normal pulmonary function, minimal adverse effects of medications, and ultimately deliver a healthy neonate. The physician should be able to provide optimal therapy to maintain asthma control that improves maternal quality of life and allows for normal progression of pregnancy. Routinely, the anesthesiologist may not be responsible for the management of asthma, but having the knowledge of the currently available treatment options will improve the care during delivery. The anesthesiologist should be able to distinguish between asthma and other causes of wheezing and also should avoid drugs that could exacerbate asthma.

Good asthma control is defined as: (1) Minimal or no chronic symptoms day or night, (2) minimal or no exacerbations, (3) no limitation on activities, (4) maintenance of near normal pulmonary function, (5) minimal use of short-acting inhaled β-2 agonist, and (6) minimal or no adverse effects from medications (25).

Acute symptoms of asthma usually arise from bronchospasm and respond well to bronchodilator therapy. Acute and chronic inflammation can affect not only the airway caliber and airflow but also underlying bronchial hyperresponsiveness which enhances susceptibility to bronchospasm. Consultation with an asthma specialist is appropriate in moderate to severe asthmatic patients. The effective management of asthma during pregnancy relies on four basic components: (1) Objective measures for assessment and monitoring, (2) patient education, (3) avoidance of asthma triggers, and (4) pharmacologic therapy.

Table 31-2 Assessment of Asthma Control in Pregnant Women

Variable	Well-controlled Asthma Mild Intermittent	Asthma not Well Controlled Mild/Moderate Persistent	Very Poorly Controlled Asthma Severe Persistent
Frequency of symptoms	≤2 days/wk	>2 days/wk	Throughout the day
Frequency of nighttime awakening	≤2 times/mo	1–3 times/wk	≥4 times/wk
Interference with normal activity	None	Some	Extreme
Use of short-acting β-agonist for symptom control	≤2 days/wk	>2 days/wk	Several times/day
FEV₁ or peak flow (% of the predicted or personal best value)	>80	60–80	<60
Exacerbations requiring use of systemic corticosteroid (no.)	0–1 in past 12 mos	≥2 in past 12 mos
Data from: the National Asthma Education and Prevention Program: National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD: National Institutes of Health; 2007. URL: http://www.nhlbi.nih.gov.easyaccess1.lib.cuhk.edu.hk/guidelines/asthma/asthgdln.htm Last accessed Feb 19, 2012.

Objective Measures for Assessment and Monitoring

Monitoring of asthma status during prenatal visits is strongly recommended. Since the course of asthma is usually unpredictable, it improves for about one-third of women, unchanged in one-third, and worsens for one-third of women during pregnancy, monthly evaluations of asthma history and pulmonary function (spirometry is generally preferred but measurement with a peak flow meter is usually sufficient) are recommended. See Table 31-2 for assessment of control and severity classification. The peak expiratory flow rate (PEFR) correlates well with the FEV₁, and has the advantages that it can be measured reliably with inexpensive, disposable, portable peak flow meters. Self-monitoring of PEFR will provide valuable insight regarding the course of asthma throughout the day. In moderate to severe asthmatic patients, it would be important to use a peak flow meter twice daily to have an objective measure of the lung function. This evaluation will provide the treating physicians with objective evidence to either step down treatment, or to increase treatment as needed. Serial ultrasound examinations starting at 32 weeks’ gestation may be considered for patients who have sub-optimally controlled asthma (25).

Patient Education

Patient education regarding diagnosis and treatment of asthma is more important than ever during pregnancy. The patient must be able to understand the potential adverse effects of uncontrolled asthma on the well-being of the fetus, and that treating asthma with medications is safer than under treatment of asthma which may lead to both maternal and fetal hypoxia. Above all, the patient should be able to recognize symptoms of worsening asthma and be able to obtain appropriate treatment when need arises (Table 31-3). This requires an individualized management plan that is based on a joint agreement between the patient and the treating physician. Correct inhaler technique should be assured, and the patient also should understand how she can reduce her exposure and control the factors that exacerbate her asthma (26). Women who smoke must be informed regarding the adverse effects on the fetus along with fetal effects of uncontrolled asthma, and they should be strongly encouraged to quit smoking (17). They should also be advised to avoid exposure to second hand smoking if at all possible.

Table 31-3 Patient Education for Treatment of Asthma during Pregnancy

Topic	Recommendation
General information	Provide basic information about asthma and explain how asthma affects pregnancy and pregnancy affects asthma
Use of inhaler/technique	Demonstrate proper technique for specific device and ask patient to perform the technique
Adherence to treatment	Discuss self-reported adherence to treatment with controller medication and address barriers to optimal adherence like cost, convenience, concern about side effects of medications
Self-treatment plan	Provide schedule for maintenance medication and doses of rescue therapy for increased symptoms; explain how to recognize a severe exacerbation and when and how to seek urgent or emergency care
Adapted from: Schatz M, Dombrowski MP. Clinical practice: asthma in pregnancy. N Engl J Med 2009; 360(18):1862–1869.

Avoidance of Asthma Triggers

Limiting adverse environmental exposure during pregnancy is very important for controlling asthma. Avoiding or controlling triggers can reduce asthma symptoms, airway hyperresponsiveness, and the need for pharmacologic therapy. Approximately 75% to 85% of patients with asthma have positive skin tests to common allergens (17). The most common asthma triggers are animal dander, dust mites, cockroach antigens, pollens, and molds. Nonimmune triggers are tobacco smoke, air pollutants, drugs like aspirin and β-blockers. In patients with exercise-triggered asthma, use of a short-acting bronchodilator inhaler 5 to 60 minutes prior to exercise can significantly reduce the occurrence of exacerbations. All patients should be strongly encouraged to stop smoking (Table 31-4).

In 1993, the National Asthma Education and Prevention Program Expert Panel Report (NAEPP) published the Report of the Working Group on Asthma and Pregnancy, which reviewed the data from available studies, and presented recommendations for the pharmacologic management of asthma during pregnancy. Since then there have been new developments with introduction of new medications, availability of additional safety data, and treatment guidelines. All of these developments led to the update of the previous report and is published in NAEPP Working Group Report on Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment-Update 2004 (25).

Table 31-4 Asthma Triggers

Exercise

Viral infection

Animal with fur

Dust mites

Mold

Tobacco smoke

Pollen

Changes in weather

Strong emotional expression (laughing or crying hard)

Dust

Menstrual cycles

Pharmacologic Therapy

Pharmacologic therapy of asthma during pregnancy is geared toward avoiding exacerbations and status asthmaticus. Management should begin prior to conception. Medications that are used to treat asthma fall into two main categories— bronchodilators and anti-inflammatory agents. The prophylactic use of antibiotics is not necessary. The goals of asthma therapy include: (1) Relieve bronchospasm; (2) protect the airways from irritant stimuli; (3) mitigate inflammatory response to an allergen exposure; and (4) resolve the inflammatory process in the airways reducing airway hyperresponsiveness (Table 31-5).

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