ASTHMA IN

PREGNANCY

- Dr. PRAPULLA CHANDRA D

• INTRODUCTION

• RESPIRATORY CHANGES DURING PREGNANCY

• EFFECT OF PREGNANCY ON ASTHMA

• EFFECT OF ASTHMA ON PREGNANCY

• MANAGING ASTHMA DURING PREGNANCY

• MANAGING ASTHMA DURING LABOUR

• PERIPARTUM CARE

• SUMMARY

INTRODUCTION

• Asthma is one of the most common chronic medical conditions that may complicate pregnancy, with a prevalence of 3.7 - 8.4% of all pregnancies .

• Exacerbations are major clinical problem in pregnants with asthma occurring in 20-36%.

• Asthma course improves in one-third, worsens in one-third and remains unchanged in one-third of women during pregnancy.

• Pregnant women with asthma represent a special challenge for asthma specialists and allergists. Asthma influences the outcome of pregnancy and, vice versa, pregnancy affects asthma severity.

RESPIRATORY CHANGES DURING PREGNACY

• ANATOMICAL CHANGES:

- Upper respiratory mucosal hyperemia and edema, glandular hyperactivity.

- Thorax and Diaphragm :

- In the 1st trimester, subcostal angle can increase from 68-103 degrees.

- Diaphragm rises by upto 4cm

Airway edema,

Friability

Widened AP and

transverse diam.

Elevated

Diaphragm

Widened subcostal

Angle

Enlarging uterus

ANATOMIC EFFECTS

FUNCTIONAL CHANGES :

• The most striking changes are in the respiratory drive and minute ventilation.

• Central respiratory drive, is increased by 13 weeks and continues to increase to 37 weeks of gestation, returning to normal by 24 weeks after delivery. These serial changes in respiratory drive appears to correlate with changes in serum progesterone levels which either stimulate respiration directly or increase the sensitivity of the respiratory center to PCO2

• Increased minute ventilation is due to increased Tidal Volume.

• Respiratory rate is unchanged early and raises only above 10%, later in pregnancy.

• O2 consumption increases 20%-30% in pregnancy owing to both maternal and foetal demands.

LUNG VOLUME CHANGES :Lung volume changes associated with pregnancy:

• Decreases : FRC(10-25%)

ERV(8-40%)

RV(7-22%)

• Increases : IC

• No change : TLC

VC

• Physiologic tests of large airway function including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, mean forced expiratory flow during middle half of forced vital capacity (FEF25–75), and peak expiratory flow rate (PEFR) remain unaffected by pregnancy.

• These physiological parameters are useful indicators of asthma control, and also helpful in differentiating dyspnea caused by asthma from dyspnea caused by hyperventilation or pressure on the diaphragm with late pregnancy.

EFFECT OF HORMONES ON RESPIRATORY SYSTEM

• Hormonal changes in pregnancy affect the upper respiratory tract and

airway mucosa, producing hyperemia, mucosal edema, hypersecretion,

and increased mucosal friability.

• Estrogen is probably responsible for producing tissue edema, capillary

congestion, and hyperplasia of mucous glands.

• Progesterone may contribute to improved asthma via increased

minute ventilation, smooth muscle relaxation or cAMP induced bronchodilation.

• On the other hand , progesterone may contribute to worsening asthma via changes in b2-adrenoreceptor responsiveness and airway inflammation

• Progesterone can act as partial glucocorticoid agonist and suppress histamine release from basophils.

• Maternal plasma cortisol levels increase during pregnancy, which may result in improvement in asthma control and reduced steroid requirements. But the effects are variable.

• During pregnancy, amniotic fluid contains different prostaglandins (PGE2, PGD2, PGF2-alfa). PGE2 is a bronchodilator where as the others are bronchoconstrictors.

• But the relationship between increased levels of PGF2-alfa in pregnancy and asthma exacerbations is not established.

EFFECT OF PREGNANCY ON ASTHMA

• Asthma course may worsen, improve or remain unchanged in pregnancy occurring with equal frequency.

• General trends :

- Asthma was generally less severe during the last four weeks of pregnancy

- In women who improved, the improvement was gradual as pregnancy progressed

- In women whose asthma worsened, the increase in symptoms was most prominent between 29-36 weeks of gestation

- only 10% women showed asthma symptoms during labor and delivery

- The course of asthma in successive pregnancies in an individual patient tends to be similar.

ACUTE EXACERBATIONS :• Asthma exacerbations occur in 20 to 36 percent of pregnant asthmatic

patients.

• These exacerbations are not uniformly distributed over the course of pregnancy.

• Exacerbations occurred most frequently during 17-24 weeks of pregnancy.

• A peak incidence of severe asthma exacerbations during 14-24 weeks of pregnancy and a peak incidence of mild asthma exacerbations during 25-32 weeks of pregnancy.

EFFECT OF ASTHMA ON PREGNANCY

• Asthma during pregnancy is associated with an increased incidence of

- perinatal mortality

- increased risks of spontaneous abortion

- hyperemesis

- preeclampsia

- prematurity and

- low birthweight infants

• Possible mechanisms for increased perinatal risks in pregnant asthmatics are :

- chronic hypoxia and other physiological consequences of poorly controlled asthma

- medications used to treat asthma

- Pathogenic or demographic factors associated with asthma but actually not caused by the disease or its treatment, such as abnormalplacental function.

ASTHMA & PREGNANCY MANAGEMENT

Goals:

• Control symptoms, including nocturnal symptoms

• Prevent acute exacerbations

• No limitations on activities

• Maintain (near) normal pulmonary function

• Minimal use short-acting inhaled beta2- agonists

• Protect the mother and fetus from adverse effects

General Principles

• Preconception :

− Optimize asthma management.

• Few changes in treatment regimen are needed in pregnancy especially if asthma is controlled.

- Avoid recently introduced medications whose safety in pregnancy is not established.

- Use adequate doses of medications to control symptoms and avoid hypoxia.

- It is essential to maintain adequate oxygenation to the fetus.

COMPONENTS OF ASTHMA MANAGEMENT

• Objective measures for assessment and monitoring

• Patient education

• Avoidance of factors contributing to asthma severity

• Pharmacologic therapy

• Diagnose and treat rhinitis, sinusitis or gastroesophageal reflux disease if present

The two primary goals of asthma management are

- optimization of ongoing asthma control

- prevention of acute exacerbations

• The general principles of pharmacologic therapy for asthma during pregnancy are similar to those in non-pregnant patients and involve a stepwise approach to achieve and maintain asthma control.

STEPWISE APPROACH FOR THE MANAGEMENT OF ASTHMA DURING PREGNANCY

STEP 1 – MILD INTERMITTENT ASTHMAClinical Presentation

• Symptoms : < 2 days/week

< 2 nights /month

• PEF or FEV1 : > 80%

• PEF variability : >20%

• TREATMENT :

- 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.

STEP 2 – MILD PERSISTENT ASTHMA

Clinical Presentation

• Symptoms > 2 days/wk but < daily

> 2 nights/month

• PEF or FEV1 : > 80% predicted

• PEF variability : 20-30%

• PREFERRED TREATMENT : low dose inhaled corticosteroid

• Alternative : cromolyn, Leukotriene receptor antagonists or sustained release theophylline to serum conc. Of 5-12 mcg/ml

STEP 3 – MODERATE PERSISTENT ASTHMA

• Daily symptoms, > 1 night/week

• PEF or FEV1 : 60 – 80% predicted

• PEF variability : > 30%

• PREFERRED TREATMENT :

Low-dose inhaled corticosteroid and long-acting beta2-agonist

OR

Medium-dose inhaled corticosteroid

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

- Medium-dose inhaled corticosteroid and long acting inhaled beta2-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 4 – SEVERE PERSISTENT ASTHMA

Clinical Presentation

• Daily and frequent night symptoms

• PEF or FEV1 is: ≤ 60% predicted

• PEF variability : >30%

• PREFERRED TREATMENT:

- High-dose inhaled corticosteroid AND Long-acting inhaled beta2-agonist

AND, if needed,

- Corticosteroid tablets or syrup long term (2 mg/kg per day, 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 mcg/mL.

• QUICK RELIEF FOR ALL PATIENTS :

- Short-acting bronchodilator: 2–4 puffs short-acting inhaled beta2-agonist as needed for symptoms.

- Intensity of treatment will depend on severity of exacerbation; up to 3 times at 20-minute intervals or a single nebulizer treatment as needed. Course of systemic corticosteroid may be needed.

- Use of short-acting inhaled beta2-agonist >2 times a week in intermittent asthma (daily, or increasing use in persistent asthma) may indicate the need to initiate (increase) long-term-control therapy.

ASSESSING DRUG SAFETY IN PREGNANCY

ANTI-INFLAMMATORY

INHALED STEROIDS

ORAL STEROIDS

LUKOTRIENE MODIFIERS

ANTI-HISTAMINES

INHALED B2 AGONISTS• The majority of reports provide reassurance regarding the use of

inhaled beta-agonists during pregnancy. Clinical experience is greater with the older agents (eg albuterol) than with the newer ones (egformoterol, salmeterol).

• SHORT-ACTING BETA-ADRENERGIC AGONISTS —

- The SABAs are used to provide quick relief of asthma symptoms and appear to be relatively safe during pregnancy.

- Albuterol is recommended as the short-acting beta agonist of choice.

- SABA use is a marker for poorly-controlled asthma and more frequent exacerbations, which may independently contribute to the development of congenital anomalies

LONG ACTING B2 AGONISTS

• A retrospective study showed that salmeterol and formoterol do not increase the risk of delivering low birth weight, small for gestational age, or preterm infants.

• So, continuation of a LABA during pregnancy is reasonable if a LABA isneeded (in combination with an inhaled glucocorticoid) to achieve asthma control before pregnancy.

• Human safety data for newer LABAs, such as indacaterol, olodaterol, and vilanterol are lacking.

• When comparing a combination LABA plus ICS versus monotherapy with a higher dose of the inhaled glucocorticoid, the risk of congenital malformations appears similar.

ORAL / SYSTEMIC CORTICOSTEROIDS

• Systemic glucocorticoids have been used extensively during pregnancy to treat asthma exacerbations and rarely for control of severe asthma.

• The potential risks of gestational oral glucocorticoids must be balanced against the risks to the mother or infant of inadequately treated asthma.

• As the risks of severe uncontrolled asthma include maternal or fetalmortality, these risks are considered to be greater than the potential risk of systemic glucocorticoids.

• May cause Congenital malformations (primarily cleft palate), preeclampsia, gestational diabetes, low birth weight, and neonatal adrenal insufficiency.

INHALED CORTICOSTEROIDS

• Budesonide is the preferred inhaled glucocorticoid for use during pregnancy, as more published gestational human data are available for that medication.

• other inhaled glucocorticoids could be continued if the patient was well controlled on one of these medications prior to pregnancy.

• The rate of congenital malformations with the use of inhaled budesonide is same as that of the general population.

ANTI-CHOLINERGIC AGENTS

• Anticholinergic agents such as ipratropium, glycopyrrolate, and tiotropium, are not generally used as a primary form of therapy forasthma.

• LAMAs are usually reserved for patients with moderate-to severeasthma that is not controlled with a LABA-inhaled glucocorticoid combination.

• Inhaled ipratropium, with minimal chronotropic effects on fetus, is commonly used, and is considered to be safe during pregnancy.

• The safety of inhaled tiotropium, aclidinium, glycopyrrolate, and umeclidinium during pregnancy is uncertain.

LEUKOTRIENE MODIFIERS

• Montelukast or zafirlukast considered as alternative but NOT preferred therapy for mild persistent asthma or as add-on therapy to inhaled glucocorticoids, especially for patients who have shown a uniquely favorable response prior to pregnancy.

• Zileuton is not recommended as adverse effects were noted.

METHYL XANTHINES

• The clinical use of methyl xanthines (theophylline, aminophylline) during pregnancy is limited because of the potential for altered metabolism during pregnancy, the need for drug level monitoring, and the potential for fetal tachycardia and irritability at the time of delivery.

• Theophylline does not increase the risk of fetal anomalies.

IMMUNOTHERAPY

• The initiation of subcutaneous or sublingual immunotherapy is not recommended during pregnancy due to the potential harm to the fetus, if any systemic allergic reaction occur.

• However, patients who are tolerating maintenance immunotherapy and deriving benefit may continue it.

NON-PHARMACOLOGICAL MANAGEMENT

• Includes :

- Patient education,

- Avoidance of irritant (eg, cigarette smoke)

- Control of allergenic triggers of asthma.

1. PATIENT EDUCATION

• The patients should be clearly explained, that it is safer for pregnant women with asthma to take asthma medications than to have ongoing symptoms or exacerbations of asthma.

• Reassurance that safe and adequate asthma treatment is possible during pregnancy and that good asthma control can help to minimize the risk of complications.

2. SMOKING CESSATION• smoking may predispose the patient to asthma exacerbations, bronchitis or

sinusitis, and therefore necessitate an increased need for medication.

• cigarette smoking is associated with numerous adverse pregnancy outcomes, including

- spontaneous pregnancy loss,

- placental abruption,

- preterm premature rupture of membranes(PPROM),

- placenta previa,

- preterm labor and delivery,

- low birth weight,

- ectopic pregnancy.

3. CONTROL OF ENVIRONMENTAL TRIGGERS

• It helps to reduce the need for pharmacologic intervention.

• This includes avoiding exposure to allergens and to nonspecific airway irritants, such as tobacco smoke, dust, and environmental pollutants.

• Particular allergens of concern are dander from pets and antigens from household dust mites.

MONITORING

• In pregnant asthmatics

Asthma control is monitored by

- SPIROMETRY – MONTHLY

- In severe Asthma,

PEAK FLOW METRY - Twice daily

Upon waking up &

After 12 hr

ACUTE EXACERBATIONS

• Acute asthma exacerbations are common during pregnancy andincrease the risk of pre-eclampsia, gestational diabetes, placental abruption and placenta previa.

• The recommended pharmacotherapy of acute asthma during pregnancy does not differ substantially from the management in non-pregnant patients.

• Intensive monitoring of both mother and fetus is essential.

MATERNAL MONITORING

• Continuous measurement of oxygen saturation by pulse oximetry(SpO2 ) is essential, aiming for a SpO2 ≥95 percent.

• Measurement of expiratory airflow with a peak flowmeter (or spirometer) is the best method for objective assessment of the severity of an asthma attack.

• A chest radiograph is not routinely indicated for the majority of asthma exacerbations and is reserved for patients with suspected pneumonia, pneumothorax, or impending or actual respiratory failure.

FETAL MONITORING

• Fetal heart rate monitoring is the best available method for determining whether the fetus is adequately oxygenated.

• After 23-24 weeks of gestation, non-invasive fetal heart rate monitoring is appropriate during asthma exacerbations requiring emergency department treatment or hospitalization and biophysical profile of fetus is noted.

SUPPORTIVE CARE• Maternal positioning – In general, pregnant patients with acute

asthma should rest in a seated or lateral position, rather than supine, particularly in the third trimester, to avoid aortocaval compression by the gravid uterus.

• Hydration – Intravenous fluids are not necessary unless the patient is unable to maintain oral hydration.

• Supplemental oxygen — Supplemental oxygen (initially 3 to 4 L/min by nasal cannula) should be administered, adjusting the fraction of inspired oxygen (FiO2 ) to maintain a PaO2 of at least 70 mmHgand/or oxygen saturation by pulse oximetry of 95 percent or greater

PHARMACOTHERAPY IN EXACERBATIONS

• The recommended agents for management of acute asthma exacerbations in pregnant patients are the same as for asthma exacerbations in non-pregnants.

• These agents include inhaled short-acting beta agonists, inhaled anticholinergic agents, oral or intravenous glucocorticoids, and, if appropriate, intravenous magnesium sulphate.

• Systemic glucocorticoids : Patients should be reassured that the benefits of oral glucocorticoids in preventing exacerbations frombecoming life-threatening asthma outweigh any risk to the mother or fetus.

• Ipratropium – Ipratropium is often used to treat severe acute asthma exacerbations.

• Intravenous magnesium sulfate – Intravenous magnesium sulfatemay be beneficial in acute severe asthma as an adjunct to inhaled beta agonists and intravenous glucocorticoids.

ASTHMA MANAGEMENT DURING LABOR AND DELIVERY

• Only about 10% to 20% of women develop an exacerbation of asthma during labor and delivery.

• Asthma medications should be continued during labor and delivery.

• If a systemic steroid has been used in the previous month, then stress-dose steroid should be administered during labor to prevent maternal adrenal crisis.

PERIPARTUM CARE

• Oxytocin is the drug of choice for induction of labor and control of postpartum haemorrhage.

• Analogs of prostaglandin F2-alpha can cause bronchoconstriction, and should not be used for termination of pregnancy, cervical ripening, induction of labor, or control of uterine hemorrhage. Prostaglandin E2 (in gel or suppository form) and prostaglandin E1 (misoprostol) are safer.

• For peripartum pain control, morphine and meperidine should be avoided, as they can induce histamine release from skin mast cells. Fentanyl or Butorphemol are alternatives.

• Epidural Anaesthesia is preferred. If general, Ketamine is used because of its bronchodilatory effect.

• Ergot derivatives are avoided.

• If high doses of SABA have been given during labor and delivery, blood glucose levels should be monitored in the baby (especially if preterm) for the first 24 hours.

SUMMARY• Asthma is one of the most common chronic medical conditions that

may complicate pregnancy, with a prevalence of 3.7 - 8.4% of all pregnancies .

• Asthma may improve, worsen, or remain unchanged in severity during pregnancy.

• The two primary goals of asthma therapy during pregnancy are the prevention of acute exacerbations and optimization of ongoing pulmonary function.

• The four important components of effective asthma therapy during pregnancy are:

- Objective monitoring of maternal lung function and fetal well being as a guide to therapy.

- Proper control of environmental and other triggers for asthma

- Patient education

- Pharmacologic therapy

• The general principles of pharmacologic therapy for asthma during pregnancy are similar to those in nonpregnant patients and involve a step-wise approach.