Asthma in Pregnancy

Asthma is a chronic inflammatory disease of the airways that is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli. It is the most common chronic condition in pregnancy. ^[1]

The disease is episodic, being characterized by acute exacerbations intermingled with symptom-free periods. Most asthma attacks prove to be short-lived, lasting minutes to hours. Although patients appear to recover completely clinically, evidence suggests that patients with asthma develop chronic airflow limitations.

The prevalence of asthma in the general population is 4-5%. In pregnancy, the prevalence ranges from 1-4%.

Asthma-related morbidity and mortality rates in pregnant women are comparable to those in the general population. The mortality rate from asthma in the United States is 2.1 persons per 100,000. ^[2]

Outcomes and complications of asthma in pregnancy

Although women with mild asthma are unlikely to have problems, patients with severe asthma are at greater risk of deterioration. The deterioration risk is highest in the last portion of a pregnancy. An increase in asthma exacerbations and in the need for medication is common during the second and third trimesters among women with more severe underlying disease. ^[3]

In fact, severe and/or poorly controlled asthma has been associated with numerous adverse perinatal outcomes, including the following:

• Preeclampsia

• Pregnancy-induced hypertension

• Uterine hemorrhage

• Preterm labor

• Premature birth

• Congenital anomalies

• Fetal growth restriction

• Low birth weight

• Neonatal hypoglycemia, seizures, tachypnea, and neonatal intensive care unit (ICU) admission

This risk of giving birth to a small or preterm infant appears to be small and may be minimized by good control of asthma. Studies have indicated that low-birth-weight infants are more common in women with daily symptoms or low expiratory flow than in women without asthma. In addition, active asthma management during pregnancy has been shown to reduce the risk of neonatal hospitalization and gestational diabetes. ^[3]

Asthma can also lead to the following morbidities in pregnant women:

• Respiratory failure and the need for mechanical ventilation

• Barotrauma

• Complications of (parenteral) steroid use

Death can also occur.

Pregnancy has a significant effect on the respiratory physiology of a woman. While the respiratory rate and vital capacity does not change in pregnancy, tidal volume, minute ventilation (40%), and minute oxygen uptake (20%) increase, with a resultant decrease in functional residual capacity and residual volume of air as a consequence of the elevated diaphragm. In addition, airway conductance is increased and total pulmonary resistance is reduced, possibly as a result of the influence of progesterone.

The consequence of these physiologic changes is a hyperventilatory picture as a normal state of affairs in the later half of pregnancy. This results in the picture of a chronic respiratory alkalosis during pregnancy, with a decreased partial pressure of carbon dioxide (pCO₂), decreased bicarbonate, and increased pH.

A normal pCO₂ in a pregnant patient may signal impending respiratory failure. The increased minute ventilation and improved pulmonary function in pregnancy promote more efficient gas exchange from the maternal lungs to the blood. Therefore, changes in respiratory status occur more rapidly in pregnant patients than in nonpregnant patients.

Asthma is characterized by inflammation of the airways, with an abnormal accumulation of eosinophils, lymphocytes, mast cells, macrophages, dendritic cells, and myofibroblasts. This leads to a reduction in airway diameter caused by smooth muscle contraction, vascular congestion, bronchial wall edema, and thick secretions.

Go to Asthma for more complete information on this topic.

Problems to consider that can mimic asthma in pregnant patients include the following:

• Airway obstruction

• Amniotic fluid embolism

• Acute congestive heart failure (CHF), secondary to peripartum cardiomyopathy

• Physiologic dyspnea of pregnancy

History findings in pregnant and nonpregnant patients may include the following:

• Cough

• Shortness of breath

• Chest tightness

• Noisy breathing

• Nocturnal awakenings

• Recurrent episodes of symptom complex

• Exacerbations possibly provoked by nonspecific stimuli

• Personal or family history of other atopic disease (eg, hay fever, eczema)

General physical examination findings may include the following:

• Tachypnea

• Retraction (sternomastoid, abdominal, pectoralis muscles)

• Agitation, usually a sign of hypoxia or respiratory distress

• Pulsus paradoxicus (>20 mm Hg)

Pulmonary findings are as follows:

• Diffuse wheezes - Long, high-pitched sounds on expiration and, occasionally, on inspiration)

• Diffuse rhonchi - Short, high- or low-pitched squeaks or gurgles on inspiration and/or expiration

• Bronchovesicular sounds

• Expiratory phase of respiration equal to or more prominent than inspiratory phase

Signs of fatigue and near-respiratory arrest are as follows:

• Alteration in the level of consciousness, such as lethargy, which is a sign of respiratory acidosis and fatigue

• Abdominal breathing

• Inability to speak in complete sentences

Signs of complicated asthma are as follows:

• Equality of breath sounds: Check for equality of breath sounds (pneumonia, mucous plugs, barotrauma). The amount of wheezing does not always correlate with the severity of the attack. A silent chest in someone in distress is more worrisome.

• Jugular venous distension from increased intrathoracic pressure (from a coexistent pneumothorax)

• Hypotension and tachycardia (think tension pneumothorax)

• Fever, a sign of upper or lower respiratory infections

Asthma Control Questionnaire/ Test

The Asthma Control Questionnaire (ACQ)/Test (ACT) is a 7-item, primarily self-administered, validated questionnaire (patients: 6 items; clinicians: 1 item) that is used to gauge the adequacy and change in asthma control in patients. ^[4] Symptoms (5 items), use of a rescue bronchodilator (1 item), and clinically measured of forced expiratory volume (FEV ₁ ) (1 item) are scored on a 7-point scale (0 = completely controlled; 6 = severely uncontrolled).

A Brazilian study reported that the ACQ/ACT is also reliable and valid in pregnant women with asthma on the basis of findings on clinical evaluations and pulmonary function tests and ACQ/ACT results in 40 pregnant asthmatic women over a total of 113 medical visits. ^[5]

Go to Pediatric Asthma for more information on this topic.

Asthma results from a complex and poorly defined interaction of genetic predisposition and environmental stimulation. The basic mechanism for nonspecific bronchial hyperresponsiveness is unknown. Airway inflammation is the most popular hypothesis.

Implicated stimuli include the following:

• Allergens, including pollens, house-dust mites, cockroach antigen, animal dander, molds, and Hymenoptera stings

• Irritants, including cigarette smoke, wood smoke, air pollution, strong odors, occupational dust, and chemicals

• Medical conditions, including viral upper respiratory tract infections, sinusitis, esophageal reflux, and Ascaris infestations

• Drugs and chemicals, including aspirin, nonsteroidal anti-inflammatory drugs, beta blockers, radiocontrast media, and sulfites

• Exercise (see Exercise-Induced Asthma.)

• Cold air

• Menses

• Emotional stress

Complete blood count with differential

A complete blood count (CBC) is performed to assess the degree of nonspecific inflammation and the possibility of a comorbid anemia or thrombocytopenia. Leukocytosis may be the result of a physiologic response to pregnancy, steroid therapy, upper respiratory tract infections, or the stress of an asthma attack.

Arterial blood gas level

Arterial blood gas (ABG) analysis indicates the level of oxygenation and respiratory compensation, giving objective information to the patient's clinical presentation. Partial pressure of carbon dioxide in the arterial blood (PaCO₂) is generally low in the early stages of an exacerbation as a result of hyperventilation. An increase in PaCO₂ can be a sign of impending respiratory failure. ABG results often show a decrease in PaO₂. Physiologic changes that accompany pregnancy in the pulmonary system slightly alter normal ABG values: pH = 7.4-7.45, pO₂ = 95-105 mm Hg, pCO₂ = 28-32 mm Hg, and bicarbonate = 18-31 mEq/L.

Blood cultures

These must be obtained in patients in whom pneumonia is found or reasonably suggested.

A normal chest radiograph in late pregnancy typically reveals an enlarged heart and some prominent lung markings from elevation of the diaphragm. Chest radiography is indicated when the other coexistent conditions, such as pneumonia, barotrauma, CHF, or chronic obstructive pulmonary disease, are likely. Chest radiographs (2 views) with a shielded maternal abdomen expose the fetus to approximately 0.00005 rad.

Go to Imaging in Asthma for more complete information on this topic.

Hand-held peak flow meters are available in most emergency departments (EDs). If the patient’s baseline is known, clinicians can use measurement to assess the severity of an attack and the patient’s response to medications.

Reversible airflow obstruction is central to the diagnosis and assessment of asthma.

Changes in pulmonary function during acute asthma include the following:

• Decreased peak expiratory flow rate (PEFR) and forced expiratory volume in 1 second (FEV₁)

• Mild reduction in the forced vital capacity (FVC)

• An increased residual volume (RV), functional residual capacity (FRC), and total lung capacity (TLC)

• Normal diffusing capacity

Patients with asthma usually demonstrate a greater than 15% increase in FEV₁, FVC, and PEFR when treated with bronchodilators.

Go to Peak Flow Rate Measurement for more complete information on this topic.

Almost all antiasthma drugs are safe to use in pregnancy and during breastfeeding. In fact, undertreatment of the pregnant patient is a frequent occurrence, because such patients are worried about medication effects on the fetus. ^{[1, 6]}

Outpatient management of asthma is similar for the pregnant patient as it is for the nonpregnant patient. Beta-adrenergic agonists remain the mainstay of treating exacerbations and handling mild forms of asthma. Early research suggests a management algorithm for asthma in pregnancy based on fraction of exhaled nitric oxide (F_E NO) and symptoms significantly reduces asthma exacerbations. ^[7]

For moderate-persistent asthma, a beta-adrenergic agonist combined with an inhaled anti-inflammatory agent or inhaled corticosteroid is recommended for treatment. In severe asthma, oral corticosteroids and beta agonists are recommended.

Corticosteroids can be used in the acute and outpatient setting and have been shown to be relatively safe in pregnancy. The intravenous, intramuscular, and oral preparations can be used for acute exacerbations, whereas the inhaled preparations are reserved for outpatient maintenance therapy. Recent data on inhaled glucocorticoids support its relative safety although there is the potential risk for offspring endocrine and metabolic disturbances. ^[8]  Some studies suggest the “sustained” use of systemic steroids may cause a slight increase in congenital malformation (mainly clef lip), prematurity, low birth weight, preeclampsia, gestational diabetes, and neonatal insufficiency. ^{[9, 10, 11, 12, 13, 14]} However, randomized trials have not been performed.

A longer-acting beta2-adrenoreceptor agonist (eg, salmeterol), the bronchodilator effects of which last at least 12 hours, is an effective treatment for nocturnal asthma.

Historically, methylxanthines and oral beta agonists have been used to treat asthma. Both have been shown to be safe in pregnancy but have fallen out of favor for newer medicines and the inhaled forms, respectively.

Magnesium sulfate is another medication that is safe to use in pregnancy. It works as a smooth-muscle relaxant of the airway.

Epinephrine use should be avoided in the pregnant patient. In general, epinephrine is used only in the most severe asthma exacerbations. In pregnancy, employment of the drug can lead to possible congenital malformations, fetal tachycardia, and vasoconstriction of the uteroplacental circulation. In rare cases where a systemic beta-agonist is needed, SQ use of terbutaline may be considered. ^[15]

A case-control study by Gidaya et al investigated associations between use of β-2-adrenergic receptor (B2AR) agonist drugs during pregnancy and risk for autism spectrum disorders by using Denmark's health and population registers. The study found that B2AR agonist exposure during pregnancy may be associated with an increased risk for ASD however any intervention must be balanced against benefits of indicated medication use by pregnant women. ^{[16, 17]}

Go to Use of Metered Dose Inhalers, Spacers, and Nebulizers for more complete information on this topic.

Prehospital asthma treatment

Prior to arriving at the ED, address the patient’s airway status as needed. Provide early institution of beta-agonist inhalational therapy. Provide supplemental oxygen.

Treatment in the emergency department

Pregnant patients who present with typical mild exacerbations of asthma may be treated in the same way that a regular asthmatic patient with similar symptoms would be, with bronchodilator therapy and steroids.

Special attention must be given to pregnant patients who present with severe asthma exacerbations, because the resulting maternal hypoxia can have devastating consequences on the fetus.

The American College of Obstetricians and Gynecologists has issued practice guidelines for the management of asthma during pregnancy, Asthma in Pregnancy. ^[18]

As always in the ED, address the ABCs. The patient should be placed on a cardiac monitor and pulse oximetry. The threshold of intubation should be low to prevent/limit hypoxic episodes to the fetus. Intubate and mechanically ventilate patients who are in or near respiratory arrest and patients who do not respond to treatment as evidenced by the following:

• Hypoxemia despite supplemental oxygen

• Increasing carbon dioxide retention

• Persistent/worsening level of consciousness

• Hemodynamic instability

The key to treating asthma in the pregnant patient is to frequently assess the patient, the severity of the attack, and the response to treatment.

Hypoxia, acidosis, unequal breath sounds, pneumothorax, and atypical features serve as warning signs of severe exacerbations.

Inhaled beta2-agonists are the mainstay of treatment. The beta2-agonist, inhaled and/or subcutaneous, is typically given in 3 doses over 60-90 minutes. Beta-adrenergic blocking agents should be avoided owing to bronchospastic effect.

The early use of systemic steroids has been shown to reduce the length of stay in the ED and the admission rate; the effect of steroids is seen within 4-6 hours of the institution of therapy.

Supply supplemental oxygen to maintain oxygen saturation higher than 95%. Intravenous fluids can help to loosen and clear secretions.

Fetal monitoring becomes important after 20 weeks of gestation in severe cases.

Tranquilizers and sedatives should be avoided because of their respiratory depressant effect. Antihistamines are not useful in the treatment of asthma. Mucolytic agents increase bronchospasm.

Less than 1% of all asthmatic patients require mechanical ventilation. Asthmatic patients have higher complication rates from mechanical ventilation. Increased airway resistance may result in extremely high peak airway pressures, barotraumas, and hemodynamic impairment. Mucous plugging is common, increasing airway resistance, atelectasis, and the incidence of secondary pneumonia. Paradoxical increases in bronchospasm may occur from aggravation by the endotracheal tube.

Typical ventilator settings may lead to stacked breaths and increased airway pressures. Decrease the ratio of the duration of inspiration to the duration of expiration (I:E ratio), and set a low respiratory rate to allow for adequate expiration.

Go to Status Asthmaticus for more complete information on this topic.

Criteria for hospital admission are as follows:

• Inadequate response to ED therapy

• pO₂ less than 70 mm Hg

• Signs of fetal distress (eg, decreased movement, abnormal cardio tocodynamometry, uterine contractions)

• Multiple medication use (ie, requiring 3 or more medications simultaneously)

• A protracted course with poor response to outpatient therapy thus far instituted or a history of severe asthma requiring intubation or ICU admission

• Inadequate home conditions and transport/access to ED care

Criteria for ICU admission are as follows:

• Altered level of consciousness

• Poor air flow

• Signs of fatigue, a downhill course, or a need for mechanical ventilation

• PEFR/FEV₁ less than 25% of predicted or pCO₂ greater than 35 mm Hg

Criteria for home discharge include the following:

• Greatly improved symptoms and physical examination findings

• Ability of the patient to walk out of the ED without obvious distress

• PEFR/FEV₁ greater than 70% baseline

• No fetal distress

• Good follow-up and access to ED in case of relapse

A follow-up appointment 2-4 days following the ED visit is recommended. Consider referral to an asthma specialist; in addition, involvement of a multidisciplinary team that includes a pulmonologist, neonatologist, obstetrician, and possibly an allergologist should be considered in the follow-up of a pregnant asthma woman. ^[19] Glucocorticoids at the time of discharge have proven to be useful and to reduce the incidence of ED visits.