Asthma

Asthma is the commonest chronic medical illness to complicate pregnancy, affecting up to 7% of women of childbearing age. It is often undiagnosed and when recognized, may be undertreated.

Reversible bronchoconstriction is caused by smooth-muscle spasm in the airway walls and inflammation with swelling and ex­cessive production of mucus. The clinical features include cough, breathlessness, wheezy breathing, and chest tightness. Symptoms demonstrate diurnal variation and are commonly worse at night and in the early morning. There may be clear provoking trigger fac­tors, such as pollen, animal dander, dust, exercise, cold, emotion, and upper respiratory tract infections. Signs are often absent but during an acute attack there may be increased respiratory rate, in­ability to complete sentences, wheeze, use of accessory muscles, and tachycardia.

Diagnosis is based on the recognition of a characteristic pattern of symptoms and signs in the absence of an alternative explan­ation. Eliciting a careful history is key. A personal or family history of asthma or atopy makes the diagnosis more likely. A hallmark of asthma is variability and reversibility of the bronchoconstriction. The degree of broncho constriction is measured with a peak expiratory flow rate (PEFR) or more preferably spirometry to measure FEVi and forced vital capacity (FVC). Where the history suggests a high probability of asthma, or the FEVi/FVC ratio is less than 0.7, a trial of treatment is indicated. A typical feature is morning ‘dipping' in the peak flow. A greater than 20% diurnal variation in PEFR for 3 or more days a week during a 2-week PEFR diary is diagnostic. Other diagnostic features include a greater than 15% improvement in FEVi following inhalation of a β-sympathomimetic broncho dilator and/or a greater than 15% fall in FEVi following 6 minutes of exercise.

Pregnancy itself does not usually influence the severity of asthma. Asthma may improve, deteriorate, or remain unchanged during pregnancy. Women with only mild disease are unlikely to experi­ence problems, whereas those with severe asthma are at greater risk of deterioration, particularly late in pregnancy. Women whose symptoms improve during the last trimester of pregnancy may ex­perience postnatal deterioration. Acute asthma in labour is unlikely because of increased endogenous steroids at this time. Deterioration in disease control is commonly caused by reduction or even com­plete cessation of medication due to fears about its safety.

For the majority of women, asthma has no adverse effect on preg­nancy outcome, and women should be reassured accordingly. Severe, poorly controlled asthma, associated with chronic or intermittent maternal hypoxaemia, may adversely affect the fetus. Retrospective, uncontrolled or small studies have demonstrated associations be­tween maternal asthma and pregnancy-induced hypertension/ pre-eclampsia, preterm births and preterm labour, low-birthweight infants, fetal growth restriction, and neonatal morbidity, including transient tachypnoea of the newborn, neonatal hypoglycaemia, neo­natal seizures, and admission to the neonatal intensive care unit

(18). In general, adverse effects on pregnancy outcome are small and related to the severity and control of the asthma. Most of the above­mentioned associations are uncommon in clinical practice and women should be reassured that those with well-controlled asthma mostly have normal pregnancies with healthy babies.

Poorly controlled severe asthma presents more of a risk to the pregnancy than the medication used to prevent or treat it. This small risk is minimized with good control. Women should be advised that their asthma is unlikely to adversely affect their pregnancy and maintaining good control of asthma throughout pregnancy is im­portant. Emphasis in the management of asthma is on the preven­tion, rather than the treatment, of acute attacks.

Management follows a stepwise approach and readers are dir­ected to the British Thoracic Society/S cottish Intercollegiate Guidelines Network guideline on the management of asthma

(19). Mild intermittent asthma is managed with inhaled short­acting ‘reliever' (β2-agonist) medication as required (step 1). If usage of a ‘reliever' (β2-agonist) inhaler exceeds three times/week, regular inhaled anti-inflammatory medication with a steroid ‘pre­venter' (e.g. beclomethasone, budesonide) inhaler (400 mcg/day) should be commenced (step 2). The next step up in therapy is either the addition of a long-acting ‘reliever' β2-agonist (LABA;

e.g. salmeterol), or an increase in the dose of inhaled steroid (800 mcg/day) (step 3). Further steps involve a trial of additional ther­apies such as leukotriene receptor antagonist (see ‘Safety pro­file of medications used to treat asthma'). Alternatively the dose of inhaled steroid can be increased to 2000 mcg/day (step 4). If these measures fail to achieve adequate control then continuous or frequent use of oral steroids becomes necessary. The lowest dose providing adequate control should be used, if necessary with steroid-sparing agents (step 5).

The aim of treatment is to achieve virtual total freedom from symptoms, such that the lifestyle of the individual is not affected. Regrettably, many people with asthma accept chronic symptoms such as wheezing or ‘chest tightness' on waking as an inevitable con­sequence of their disease.

The treatment of asthma in pregnancy is essentially no different from the treatment of asthma in non-pregnant women. All the drugs in widespread use to treat asthma, including systemic ster­oids, appear to be safe in pregnancy and during lactation (see ‘Safety profile of medications used to treat asthma'). The challenge in the management of pregnant women with asthma is to ensure adequate preconception or early pregnancy counselling so that women do not stop important anti-inflammatory inhaled therapy. Education and reassurance, ideally prior to pregnancy, concerning the safety of asthma medications during pregnancy are integral parts of management.

Safety profile of medications used to treat asthma β2-agonists from the systemic circulation cross the placenta rapidly, but very little of a given inhaled dose reaches the lungs, and only a minute fraction of this reaches the systemic circulation. Studies show no difference in perinatal mortality, congenital malformations, birthweight, Apgar scores, or delivery complications when pregnant women with asthma treated with inhaled β2-agonists are compared with women with asthma not using β2-agonists and non-asthmatic controls. The LABAs such as salmeterol (Serevent) are also safe in pregnancy (20). Long-acting β-agonists should only be used con­currently with long-acting inhaled corticosteroids.

Use of both inhaled and oral steroids is safe in pregnancy. Only minimal amounts of inhaled corticosteroid preparations are sys­temically absorbed. There is no evidence for an increased incidence of congenital malformations or adverse fetal effects attributable to the use of inhaled beclomethasone (Becotide) or budesonide (Pulmicort). Fluticasone propionate (Flixotide) is a longer-acting inhaled corticosteroid that may be used for those requiring high doses of inhaled steroids.

Combination inhalers of corticosteroids plus LABA, for example, budesonide/formoterol (Symbicort) and fluticasone/salmeterol (Seretide), are widely available and may aid compliance. They also ensure that the LABA is not taken without an inhaled steroid al­though to increase the dose of inhaled steroid without exceeding the maximum dose of LABA may necessitate changing the strength of the inhaler rather than asking the patient to take more puffs. The addition of systemic corticosteroids to control exacerbations of asthma is safe, and these must not be withheld if current medica­tions are inadequate. Prednisolone is metabolized by the placenta, and very little (10%) active drug reaches the fetus. Although some workers have found an increased incidence of cleft palate with first- trimester exposure to steroids, this finding is refuted in larger pro­spective case-control studies and database linkage studies (21). There is no evidence of an increased risk of miscarriage, stillbirth, other congenital malformations, or neonatal death attributable to maternal steroid therapy.

There is a non-significant increase in the relative risk of pre­eclampsia in women with asthma treated with oral but not inhaled steroids. However, it is unclear whether this is an effect of steroids or asthma control and severity. Although suppression of the fetal hypothalamic-p ituitary-adrenal axis is a theoretical possibility with maternal systemic steroid therapy, there is little evidence from clinical practice to support this.

It is important to treat any gastroesophageal reflux as this can ex­acerbate asthma. No adverse fetal effects have been reported with the use of inhaled chromoglycates (e.g. disodium cromoglycate (Intal) and nedocromil (Tilade)) or inhaled anticholinergic drugs (e.g. ipratropium bromide (Atrovent)).

Methylxanthines are no longer recommended as a first-line treat­ment of asthma, but have been used extensively in the past. No significant association has been demonstrated between major con­genital malformations or adverse perinatal outcome and exposure to methylxanthines. In those few women who are dependent on theo­phylline, alterations in dose should be guided by drug levels. Both theophylline and aminophylline readily cross the placenta and fetal theophylline levels are similar to those of the mother.

Leukotriene receptor antagonists (e.g. montelukast and zafirlukast) block the effects of cysteinyl leukotrienes in the air­ways. Studies do not suggest any increased risk of congenital mal­formations or other adverse outcomes with their use in pregnancy. If leukotriene antagonists are required to achieve adequate control of asthma then they should not be withheld or discontinued in pregnancy (19).

It is important to consider the possibility of ‘aspirin sensitivity' and severe bronchospasm in a minority of women with asthma. Low-dose aspirin is indicated in pregnancy as prophylaxis for women at high risk of pre-eclampsia and in women with antiphospholipid syndrome. Pregnant women with asthma should be asked about a history of aspirin sensitivity before being advised to take low-dose aspirin and before using non-steroidal anti-inflammatory drugs for pain relief postpartum.

Acute severe attacks of asthma are dangerous and should be vig­orously managed in hospital. The treatment is no different from the emergency management of acute severe asthma in the non-pregnant patient. Deaths in women with severe asthma are often linked to one or more adverse psychosocial factors including psychiatric illness, drug or alcohol abuse, unemployment, and denial regarding their diagnosis.

The features of acute severe asthma are a PEFR of 33-50% of best/ predicted, respiratory rate greater than 25 breaths per minute, heart rate greater than 110 beats per minute and inability to complete sentences in one breath. The management of acute severe asthma should include high-flow oxygen, and β2-agonists (e.g. salbutamol 5 mg) administered via a nebulizer driven by oxygen. β2 agonists can be administered by repeated activations of a metered dose inhaler via an appropriate large-volume spacer. Repeated doses or con­tinuous nebulization (salbutamol 5-10 mg/hour) may be indicated for those with a poor response. Nebulized ipratropium bromide (0.5 mg 4-6-hourly) should be added for severe or poorly responding asthma. Corticosteroids (intravenous (hydrocortisone 100 mg) and/ or oral (40-50 mg prednisolone) should be given without delay and continued for at least 5 days. Intravenous rehydration is often ap­propriate. Chest radiography should be performed if there is any clinical suspicion of pneumonia or pneumothorax, or if the woman fails to improve. If the PEFR does not improve to greater than75% predicted, the woman should be admitted to hospital. If she is dis­charged, this must be with a course of oral steroids and arrangements for review. Steroids are more likely to be withheld from pregnant than non-pregnant women with asthma presenting via emergency departments. This is inappropriate and leads to an increase in on­going exacerbation of asthma.

The clinical features of life-threatening asthma are a PEFR less than 33% predicted, oxygen saturation less than 92%, PO2 less than 8 kPa, and a normal or raised PCO2 greater than 4.6 kPa. There may be absent breath sounds, cyanosis, feeble respiratory effort, brady­cardia, arrhythmia, hypotension, exhaustion, confusion, and coma. Management of life-threatening or acute severe asthma that fails to respond should involve consultation with the critical care team and consideration should be given to intravenous β2-agonists, intra­venous magnesium sulphate 1.2-2 g infusion over 20 minutes, and/ or intravenous aminophylline (19). If intubation and ventilation is required then strong consideration should be given to delivery by caesarean section depending on gestational age.

Asthma attacks in labour are exceedingly rare because of en­dogenous steroid production. Women should not discontinue their inhalers during labour, and there is no evidence to suggest that β2-agonists given via the inhaled route impair uterine contrac­tion or delay the onset of labour. Women receiving oral steroids (prednisolone >7.5 mg/day for >2 weeks prior to delivery), should receive parenteral hydrocortisone (50-100 mg three or four times/ day) to cover the stress of labour, and until oral medication is re­started. Prostaglandin E2, used to induce labour, to ripen the cervix, and prostaglandin Ei (misoprostol) for termination of pregnancy or for treatment or prevention of postpartum haemorrhage, are bron­chodilators and are safe to use. The use of prostaglandin F2α to treat life-threatening postpartum haemorrhage may be unavoidable, but it can cause bronchospasm and should be used with caution in women with asthma. All forms of pain relief in labour, including epidural analgesia and Entonox can be used safely by women with asthma, although in the unlikely event of an acute severe asthmatic attack, opiates for pain relief should only be used with extreme cau­tion. Epidural, rather than general, anaesthesia is preferable because of the decreased risk of chest infection and atelectasis. Ergometrine has been reported to cause bronchospasm, in particular in associ­ation with general anaesthesia, but this does not seem to be a prac­tical problem when Syntometrine (oxytocin and ergometrine) is used for the prophylaxis of postpartum haemorrhage.

All the drugs previously discussed, including oral steroids, are safe to use in breastfeeding mothers. Prednisolone is secreted in breast milk, but there have been no reported adverse clinical effects in infants breastfed by mothers receiving prednisolone. Concerns re­garding neonatal adrenal function are unwarranted with doses less than 30 mg/day.