Asthma is a heterogeneous inflammatory disease of the respiratory tract involving a number of cells and substances they produce (eosinophil, mast cell and T-cell infiltration). Chronic inflammation causes bronchial hyperreactivity leading to characteristic, recurrent clinical manifestations such as wheezing, dyspnoea, chest tightness and cough, which usually occur at night and early in the morning. These episodes are usually accompanied by diffuse bronchial obstruction of varying severity, associated with various degrees of impairment in exhaust airflow through the respiratory tract. Airflow obstruction is due to smooth muscle contraction and bronchial mucosal oedema, formation of mucosal plugs and bronchial remodelling (1, 2).

Asthma is the most common respiratory disease during pregnancy and affects 3-12% of women. Due to the increasing number of cases, asthma in pregnancy has become an important clinical problem posing a challenge for attending physicians (3-6). The clinical classification of asthma depends on the frequency of symptoms, forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF). Furthermore, classification into atopic (extrinsic) and non-atopic (intrinsic) asthma, which takes into account whether exacerbation is due to allergens (atopic) or not (non-atopic), is also useful.

NAEPP (National Asthma Education and Prevention Program) classification is shown in table 1 (7).

Diagnosis is usually made prior to pregnancy. If new symptoms occur during pregnancy, additional tests may be needed, with the simplest and most common being the spirometry. It should be noted, however, that bronchial hyperresponsiveness tests are contraindicated in pregnancy due to insufficient data on their safety. Allergy skin tests are also not recommended due to the potential risk of systemic anaphylactic reaction, which poses a threat for both the mother and the foetus (6, 8).

Mucosal oedema and hyperaemia virtually over the entire length of the airway due to capillary dilation occur during pregnancy. Placental growth hormone is primarily responsible for this phenomenon, whereas progesterone has dilatory effects on the trachea and bronchi, which results in an increased alveolar ventilation. There are also changes in the configuration of the chest. The diaphragm is raised by the growing uterus by approx. 4-5 cm, which results in a broader setting of the ribs and, consequently, increased transverse dimensions of the chest by about 6 cm. Elevation of the diaphragm has no significant effects on its mobility and no respiratory muscle weakness is observed. The tidial volume (TV) increases by 35-50% and the inspiratory capacity (IC) increases by an average of 5-10% with the progress of pregnancy. The altered setting of the convexity of the diaphragm, which is not fully compensated by the widening of the lower costal arch, results in a reduced functional residual capacity (FRC) by about 18%, i.e. 300-500 mL, with a uniform reduction in its components: expiratory reserve volume (ERV) and residual volume (RV). In most cases, no significant changes occur in the total lung capacity (TLC) or vital capacity (VC) during pregnancy. Increased tidal volume and reduced residual volume elevate alveolar ventilation by 65%. There is an increase in the central respiratory drive from week 13 of pregnancy, which is not normalised until 24 weeks after delivery. Both, oxygen consumption and metabolic rate increase with advancing gestational age, which forces an increase in minute ventilation by up to 50%. This change, together with pregnancy-associated physiological respiratory alkalosis, is one of the fundamental changes in the acid-base balance. Maternal hyperventilation, which is probably due to the effects of progesterone on the respiratory centre and the susceptibility of the peripheral chemoreceptors (carotid bodies), also occurs (3, 6, 8, 9). Normal blood gas results in a pregnant woman are as folows: pH – 7.40-7.45, pO₂ – 100 mmHg, pCO₂ – 25-32 mmHg, HCO₃ – 18-21 mEq/L (3, 6).

Different studies have shown that a stable course of disease may be expected in 22-41% of patients, clinical condition improvement will occur in 18-36% of patients and symptom exacerbation will affect 22-42% of patients. The percentages can be summarised as follows: pregnancy has no effects on asthma in 1/3 of women, the disease becomes milder in 1/3 of patients while aggravation occurs in 1/3 of women. The third group includes women with poorly controlled asthma before pregnancy. The clinical symptoms do not differ significantly during subsequent pregnancies in the same patient (2, 3, 6, 9). Although it is not fully understood why pregnancy has an effect on asthma, hormonal changes are considered the main cause.

Factors accounting for asthma improvement:

– an increase in minute ventilation due to elevated progesterone levels allowing for respiratory centre function in response to pCO₂,

– an increase in tidal volume and a decrease in residual volume,

– reduced pulmonary resistance and increased pulmonary compliance (18-50%),

– increased synthesis of the natriuretic hormone and prostaglandin E (PGE₂) – a substance with bronchodilator effects,

– increased beta-adrenergic response due to increased synthesis of progesterone and free cortisol.

Factors accounting for asthma exacerbation:

– decreased functional residual capacity (FCR), which means that even minor bronchial obstruction significantly impairs the ventilation/perfusion ratio,

– reduced pulmonary reactivity to cortisol as a result of competitive binding of progesterone to glucocorticoid receptors,

– increased synthesis of PGF_2α showing the strongest bronchospasm activity,

– increased susceptibility to viral and bacterial infections,

– susceptibility to gastro-oesophageal reflux (3).

Although the course of asthma in pregnancy may be unpredictable, it depends on the pre-conception asthma severity – severe asthma is the most important risk factor for exacerbations during pregnancy. Exacerbations most often occur between 24 and 36 weeks gestation. Asthma attacks during labour are rare, which may be related to symptom reduction and milder disease during the last 4 weeks of pregnancy (2, 6).

A number of studies have shown an increased risk of miscarriage, preterm birth, pregnancy induced hypertension and eclampsia as well as haemorrhage, hyperemesis gravidarum or perinatal maternal complications (respiratory arrest, mediastinal emphysema) in pregnant patients with asthma. The incidence of these complications is closely related to the level of asthma control during pregnancy (3, 6, 9).

An increased incidence of intrauterine growth retardation (IUGR), foetal distress, intrauterine foetal death as well as low birth weight < 2,500 g and higher rates of perinatal mortality of newborns has been shown among pregnant patients with asthma, particularly those non-compliant with or modifying treatment regimen for fear of therapy-induced adverse effects (3, 6, 9). The various above described respiratory changes occurring in pregnancy significantly compensate for the increased oxygen demand. Limited airflow due to bronchial obstruction and an increased physiological respiratory alkalosis in a pregnant patient lead to an impaired uterine blood flow, therefore maternal hypoxia is much more dangerous for the developing foetus than for the patient herself (6). Since the foetal respiratory reserve is relatively small, an increased physiological hyperventilation, which has significant effects on reduced maternal venous return, is an additional factor promoting intrauterine foetal hypoxia.

An effective control of asthma during pregnancy is based on four integral principles for the medical management:

Objective methods for the assessment of the clinical status of the patient and treatment monitoring.

Avoidance or complete elimination of exposure to factors that exacerbate the disease (inhalant allergens, tobacco smoke, intense odours or air pollution).

Proper patient education aiming at a partnership between the doctor, the patient and patient’s family.

Adequate pharmacotherapy to reduce respiratory inflammation and treat asthma exacerbations (1, 6, 7).