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Asthma treatment during pregnancy

The treatment goal for the pregnant asthma patient is to provide optimal therapy to maintain control of asthma for maternal health and quality of life as well as for normal fetal maturation, as per the National Asthma Education Prevention Program (NAEPP). Asthma control is defined as follows:

  • Minimal or no chronic symptoms day or night
  • Minimal or no exacerbations
  • No limitations on activities
  • Maintenance of normal or near-normal pulmonary function
  • Minimal use of short-acting inhaled β-antagonist
  • Minimal or no adverse effects from medications. Always consult latest NAEPP guidelines.

Table. Maternal cardiovascular physiology.

• Central venous pressure remains unchanged
• 40% increase in maternal cardiac volume
• 40% increase in cardiac output
• Increase in left ventricular mass,compliance,and end-diastolic volume
• Plasma volume increases more than red cell mass: anemia of pregnancy

Table. Fetal physiology.

• Fetus functions by aerobic metabolism
• Mechanisms allowing fetus to thrive
• Increase in hemoglobin content
• Increase in oxygen affinity of fetal hemoglobin
• Preferential blood flow to vital organs
• High cardiac output
• Leftward shift of oxygen dissociation curve
• Acid-base balance important
• Increase in maternal Pco2 may result in fetal acidosis, even with adequate oxygenation

Assessment of Asthma

Pregnant women with asthma should have a thorough assessment of their asthma control. Patients should be asked about their frequency of symptoms (particularly at night), how often symptoms interfere with normal activities, and the usage of short-acting P2-agonists for symptom relief (not for exercise-induced bronchospasm prevention). Validated questionnaires such as the ATAQ, ACQ and the ACT are particularly helpful in classifying the level of asthma control.

In addition, a complete assessment of asthma must include objective measurements. All patients should have pulmonary function testing at their initial evaluation to determine disease severity. Patients should be given a peak flow meter to monitor asthma variability. At subsequent office visits, repeat pulmonary function testing is preferable, but at a minimum, assessment of peak expiratory flow rates (PEFRs) should be checked.

Asthma treatment during pregnancy

Assessment of the Fetus

All pregnant women should be advised to be attentive to fetal activity. Serial ultrasound evaluations beginning at 32-week gestation may be considered for women with moderate to severe asthma and women with poorly controlled asthma. In addition, after a severe exacerbation, an ultrasound evaluation may be reassuring.

Table. Guide to asthma severity.

Category Symptoms/day Symptoms/night FEV, or peak expiratory flow rate peak expiratory flow rate Variability
Intermittent asthma <2 d/wk <2 nights/mo >80% <20%
Mild persistent >2/wk<daily >2 nights/mo >80% >20-30%
Moderate persistent Daily >1 night/wk >60-<80% >30%
Severe persistent Continual Frequent <60% >30%

Reassurance

Patients need to be reassured about the safety of asthma medications and advised that the risks of treatment are much less than the risks of untreated asthma. Concern about side effects in the fetus may interfere with medication adherence and lead to undertreatment of asthma.

Education

All pregnant women with asthma should receive asthma education emphasizing the important benefits of treatment and its impact on the fetus. Written and verbal instructions should be given on the proper use of medications, spacers, and peak-flow meters. Patients should be taught how to monitor inhaler usage to avoid running out of medication.

Smoking

Any patient who is smoking should be advised to quit and be referred to a smoking cessation program. Besides adversely affecting asthma, smoking has deleterious affects on the mother and the fetus.

Triggers

An assessment of common triggers with instructions on avoidance and control should be part of all patient evaluations. Patients should be educated on ways to minimize exposure to dust mites, cockroaches, pets, pollens, irritants, and odors. Studies reporting that high levels of either total serum immunoglobulin E (IgE) or cockroach-specific IgE are associated with worsening asthma underscore the importance of such environmental controls. Patients with exposure to secondary smoke, including wood-burning stoves and fireplaces, should also be counseled on the importance of avoidance.

Viral infections are the most common triggers causing severe exacerbations. Influenza vaccines and frequent handwashing are recommended, particularly during the so-called flu season. In nonpregnant patients, increased body weight and high-panic-fear state can worsen asthma and complicate treatment. Although studies are conflicting in pregnancy, increased body weight and high-panic-fear state should still be considered potential triggers.

Treatment Plans

Together with the patient, providers should develop medication regimens that are effective and easy to follow. Providers need to be aware that pregnant patients with asthma may have difficulty following complicated treatment regimens.

All patients should receive a written self-management plan. The plan should emphasize home management of exacerbations, including instructions on when to start oral steroids and when and where to call for help. Ideally, these plans should be based on both symptoms and peak-flow meter.

In addition, it is important to include the obstetrical provider from the beginning. The obstetrical provider will be assessing the patient more regularly, and their involvement in the asthma care team is critical, particularly in reassuring the patient on the safety of the medications.

Medications

Inhaled Short-Acting P2-Agonists

Inhaled short-acting P2-agonists are one of the mainstays of therapy and should be administered only as needed. The preferred medication is albuterol, based on more published data on safety.

Inhaled Long-Acting P2-Agonists

Inhaled long-acting P2-agonists have a profile similar to the inhaled short-acting P2-agonists with the exception that these drugs are retained longer in the lungs. The preferred medication is salmeterol (Serevent), due to the longer availability of the drug in the United States.

There has been a recent controversy about inhaled long-acting   P2-agonists  paradoxically  increasing  the risks of hospitalization and death in asthmatics. It would be prudent to use inhaled long-acting P2-agonists only as add-on therapy to medium- or high-dose inhaled corticosteroids, if asthma remains poorly controlled.

Table. Summary of control measures for environmental factors that can make asthma worse.

Allergens
Reduce or eliminate exposure to the allergen(s) the patient is sensitive to, including:
 Animal dander:
Remove animal from house, or,at the minimum, keep animal out of patient’s bedroom and seal or cover with a filter the air ducts that lead to the bedroom.
 House dust mites:
 Essential:

  • Encase mattress in an allergen-impermeable cover;
  • encase pillow in an allergen-impermeable cover or wash it weekly;
  • wash sheets and blankets on the patient’s bed in hot water weekly (water temperature of >130°F is necessary for killing mites).
Desirable:

  • Reduce indoor humidity to less than 50%;
  • remove carpets from the bedroom;
  • avoid sleeping or lying on upholstered furniture;
  • remove carpets that are laid on concrete.
Cockroaches:
Use poison bait or traps to control. Do not leave food or garbage exposed.
Pollens (from trees, grass, or weeds) and outdoor molds:

  • To avoid exposure, adults should stay indoors, especially during the afternoon, with the windows closed during the season in which they have problems with outdoor allergens.
Indoor mold:

  • Fix all leaks and eliminate water sources associated with mold growth;
  • clean moldy surfaces.
    Consider reducing indoor humidity to less than 50%.
Tobacco Smoke
Advise patients and others in the home who smoke to stop smoking or to smoke outside the home. Discuss ways to reduce exposure to other sources of tobacco smoke, such as from child care providers and the workplace.
Indoor/Outdoor Pollutants and Irritants
Discuss ways to reduce exposures to the following:
  • Wood-burning stoves or fireplaces
  • Unvented stoves or heaters
  • Other irritants (e.g., perfumes, cleaning agents, sprays)

Inhaled Corticosteroids

Inhaled corticosteroids are the cornerstone of therapy for the pregnant woman with persistent asthma. Multiple studies have emphasized the decrease in asthma exacerbations and the improvement in FEVj with the use of inhaled corticosteroids. Even studies in large birth registries have failed to relate the use of inhaled corticosteroids to any unfavorable perinatal outcome, including increased incidence of congenital malformations. The preferred medication is budesonide (Pulmicort), based on more recently published data.

Oral Corticosteroids

Studies have shown that oral corticosteroid use has been associated with a decrease in birth weight of approximately 200 g, although without an increased incidence of small for gestational age infants. In addition, there is an association with an increased incidence of isolated cleft lip (without cleft palate) especially when taken during the first trimester (0.3% vs. 0.1% in the general population). The preferred drugs are prednisone and prednisolone because they have limited placental transfer. Oral corticosteroids are used in the treatment of poorly controlled severe persistent asthma or for the treatment of asthma exacerbations. On occasion, a short course of oral corticosteroids may be necessary to gain control of asthma.

Cromolyn Sodium

Cromolyn sodium is safe for pregnancy. It is considered an alternative but not a preferred option for mild persistent asthma.

Theophylline

Theophylline is safe for pregnancy in the usual therapeutic serum level range of 5 to 12 µg/mL. However, theophylline has many side effects and drug-drug interactions. Studies have shown that women treated with theophylline have a high rate of discontinuance of the drug, and there is an increase in the proportion of women with FEVj less than 80% of predicted. Oral theophylline is an alternative but not a preferred option for mild, moderate, or severe persistent asthma.

Table. Usual dosages for long-term-control medications during pregnancy and lactation.

Medication Dosage form Adult Dose
Inhaled Corticosteroids
Systemic Corticosteroids (Applies to all three corticosteroids.)
Methylprednisolone 2-,4-,8-, 16-, 32-mg tablets 7.5-60 mg daily in a single dose in am or qod asneeded for control

Short-course”burst”to achieve control:40-60 mg/d as single dose or two divided doses for 3-10 d

Prednisolone 5-mg tablets, 5 mg/5 mL, 15 mg/5 mL
Prednisone 1 -, 2.5-, 5-, 10-, 20-, 50-mg tablets 5 mg/mL, 5 mg/5 mL
Long-Acting Inhaled inhaled β2-Agonists(Note: Should not be used for symptom relief or for exacerbations. Use with corticosteroi ids.)
Salmeterol DPI 50 µg/blister 1 blister q12h
Formoterol DP112 µg/single-use capsule 1 capsule q12h
Combined Medication
Fluticasone/ DPI 100,250, or 1 inhalation bid;
dose depends on severity of asthma. 2 puffs bid;
dose depends on severity of asthma
Salmeterol 500µg/50µg,HFA45, 115or230µg/21µg
Budesonide/ HFA MDI 80mg or 2 inhalations bid;
dose depends on severity of asthma
Formoterol 160 mcg/4.5 meg puff
Cromolyn
Cromolyn metered-dose inhaler 800 u/puff 2-4 puffs tid-qid
Nebulizer 20 mg/ampule 1 ampule tid-qid
Leukotriene Receptoir Antagonists
Montelukast 10-mg tablet 10 mg qhs
Zafirlukast 20-mg tablet 40 mg daily (20-mg tablet bid)
Methylxanthines (Serum monitoring is important [serum concentration of 5-12 µg/mL at steady state].)
Theophylline Liquids, sustained-release tablets,and capsules Starting dose, 10 mg/kg/d up to 300 mg max;
usual max 800 mg/d
       

Leukotriene Receptor Antagonists

There are limited studies on leukotriene receptor antagonists available for review, but they appear to be safe in pregnancy. Consequently, leukotriene receptor antagonists would be an alternative but not preferred option for the treatment of mild or moderate persistent asthma.

Ipratropium

Although there are reassuring animal studies for ipratropium (Atrovent, Atrovent HFA), it should only be used in the treatment of severe asthma exacerbations. In the emergency department, usage is indicated only when the FEVj is less than 50% or there is impending respiratory arrest.

Table. Estimated comparative daily dosages for inhaled corticosteroid.

Drug Low Daily Dose Adult Medium Daily Dose Adult High Daily Dose Adult
Beclomethasone HFA40 or 80 ng/puff 80-240 µg > 240-480 µg >480 µg
Budesonide DPI90 or 180 µg/inhalation 180-540 µg >540-1080µg >1080µg
Flunisolide250 µg/puff 500-1000 µg 1000-2000 µg >2000 µg
Fluticasonemetered-dose inhaler:44,110,or220µg/puff DPI: 50,100, or 250 µg/inhalation 88-264 µg 100-300 µg 264-440 µg 300-500 µg >440 µg >500 µg
Triamcinolone acetonide75 µg/puff 300-750 µg 750-1500 µg >1500µg
Mometasone DPI220µg/inhalation 220 µg 440 µg >440 µg

Treatment Guidelines

The NAEPP has proposed a pharmacologic treatment approach for pregnant women with asthma based on stepwise asthma care. This approach follows established guidelines for intermittent asthma and mild, moderate, and severe persistent asthma. It recommends controller medications for all levels of persistent asthma. These guidelines may be modified to fit the needs of individual patients.

Intermittent Asthma

Patients with intermittent asthma should be treated with inhaled short-acting P2-agonists, preferably albuterol, as needed. However, it is important to note that even patients with intermittent asthma can experience life-threatening exacerbations and should have treatment plans for exacerbations that include oral corticosteroids .

Mild Persistent Asthma

Patients with mild persistent asthma should be treated with low-dose inhaled corticosteroids, preferably budesonide (Pulmicort), with inhaled short-acting β2-agonists, preferably albuterol, used as needed.

Alternative but less-preferable treatments include cromolyn, leukotriene receptor antagonists, and sustained-release theophylline.

Moderate Persistent Asthma

Patients with moderate persistent asthma should be treated with medium-dose inhaled corticosteroids, preferably budesonide (Pulmicort). If control is difficult or cannot be achieved, inhaled corticosteroids can be supplemented with an inhaled long-acting β2-agonist, preferably salmeterol (Serevent). Inhaled short-acting β2-agonists, preferably albuterol, should be added as needed. Alternative, but-less preferable treatments include either low-dose or medium-dose inhaled corticosteroids with the addition of sustained-release theophylline or leukotriene receptor antagonist therapy.

Severe Persistent Asthma

For patients with severe persistent asthma, the treatment of choice is high-dose inhaled corticosteroid therapy, preferably budesonide (Pulmicort), and an inhaled long-acting β2-agonist, preferably salmeterol (Serevent). Inhakd short-acting β2-agonists, preferably albuterol, should be added as needed. Alternative but less-preferable treatment would be high-dose inhaled corticosteroids with  sustained-release theophylline. If control cannot be achieved with these drugs, oral corti-costeroids should be added, as needed, to maintain control.

Assignment of Severity Step

All patients should be assigned to the highest step, in which any single feature occurs. For example, nighttime symptoms twice a week will increase the severity assignment to moderate persistent asthma, even if all other symptoms and objective measures are in the mild persistent asthma category.

Overuse of Albuterol

Patients need to be specifically asked about their use of albuterol or other inhaled short-acting bronchodilators. Overuse of albuterol indicates inadequate asthma control and the need to increase the asthma severity assignment to a higher level. Pharmacy records, if available, can be invaluable in analyzing refill patterns and determining if patients are refilling their inhaled short-acting β2-agonists too frequently.

The extent of albuterol overuse can be easily estimated by multiplying the number of canisters used by 200 (puffs per canister) and dividing the result by the number of days between refills. Even the use of one canister, every 2 months, indicates an average of more than 3 puffs of albuterol per day, suggesting suboptimal control that should be evaluated.

Patients often experience worsening of asthma symptoms during exercise. These patients may require albuterol use prior to exercise. In some cases, alteration of medication regimens may be required to allow for exercise.

Table. Stepwise approach for managing asthma during pregnancy and lactation: treatment.

Classify Severity: Clinical Features Before Treatment or Adequate Control Medications Required to Maintain Long-Term Control
  Symptoms/Day PFEForFEV, Symptoms/Night         peak expiratory flow Variability Daily Medications
Step 4 Severe Persistent Continual                     Frequent <60%>30%
  • Preferred treatment:
  • High-dose inhaled corticosteroid AND
  • Long-acting inhaled β2-agonist AND, if needed,
  • Corticosteroid tablets or syrup long term (2 mg/kg/d, generally not to exceed 60 mg per day). (Make repeat attempts to reduce systemic corticosteroid and maintain control with high-dose inhaled corticosteroid.)
  • Alternative treatment:
  • High-dose inhaled corticosteroid AND
  • Sustained-release theophylline to serum concentration of 5-12 µg/mL.
Step 3Moderate

Persistent

Daily                        >1 night/wk >60%-<80%>30%

Preferred treatment:

  • Medium-dose inhaled corticosteroid

If needed (particularly in patients with recurring severe exacerbations):

  • Medium-dose inhaled corticosteroid and long-acting inhaled β2-agonist.

Alternative treatment:

  • Low-dose inhaled corticosteroid and either theophylline or leukotriene receptor antagonist.

If needed:

  • Medium-dose inhaled corticosteroid and either theophylline or leukotriene receptor antagonist.
Step 2Mild

Persistent

>2d/wk but<daily         >2 nights/mo >80%>20-30%

Preferred treatment:

  • Low-dose inhaled corticosteroid

Alternative treatment (listed alphabetically):

  • cromolyn, leukotriene receptor antagonist, OR
  • sustained-release theophylline to serum concentration of 5-12 µg/mL.
Step 1Mild

Intermittent

<2 d/wk                     <2 nights/mo >80%<20%

No daily medication needed.

Severe exacerbations may occur, separated by long periods of normal lung function and no symptoms. A course of systemic corticosteroid is recommended.

Gaining Control of Asthma

Most asthma specialists start a patient at a higher dose of medication to gain control quickly and even consider a short course of oral steroids. Once control is gained, the dosage should be lowered to the minimal medication needed to maintain good control. Reassessment should occur frequently to determine if control can be maintained at a lower dose of medications.

Specialty Care

The NAEPP Guidelines recommends that pregnant women with asthma be referred to an asthma specialist if there is difficulty controlling their asthma. The guidelines specifically advise that patients with severe persistent asthma or those requiring step 4 treatment be referred to an asthma clinic or to a specialist. Patients with moderate persistent asthma or who require step 3 treatment may also be considered for referral.

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