Asthma and pregnancy : a comprehensive approach

Asthma is a chronic inflammatory disease characterized by bronchial hyper-reactivity to various stimuli, culminating with bronchospasm crises. Poorly controlled asthma during pregnancy can lead to hypoxia and the consequent increase in maternal and perinatal mortality, prematurity and fetal growth retardation, hyperemesis, and preeclampsia. The course of asthma during pregnancy is not predictable and improvements, worsening, or stabilization of the framework can occur. The treatment of asthma during pregnancy is similar to the usual treatment. The main objectives of treatment are: to control symptoms by avoiding fetal hypoxia, guide the pregnant women about symptoms and how to avoid triggering factors, treatment of crises and maintenance of a normal or near-normal lung function. Asthma during pregnancy should be monitored monthly, with spirometry in the first prenatal consultation and evaluation of peak flow (peak-flow) in subsequent consultations. The medicines used for asthma are divided into two categories: medications for improving a crisis (acute symptoms) and maintenance medications (avoiding exacerbations-controlling symptoms). The ultrasound should be performed early for adequate pregnancy dating enabling appropriate follow-up of fetal growth. Serial exams on the 2nd and 3rd trimesters are essential if the pregnant woman has moderate or severe Asthma and pregnancy: a comprehensive approach Mayra Sette Rotsen Junqueira1, Claudia Vaz de Melo Sette2, Christiane Salgado Sette2, José Helvécio Kalil de Souza3 1 Médica Ginecologista e Obstetra, Uroginecologia do Hospital Socor. Belo Horizonte, MG – Brasil. 2 Médica Generalista. Hospital Socor. Belo Horizonte, MG – Brasil. 3 Oncologista Ginecologista. Professor Substituto do Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina da Universidade Federal de Minas Gerais – UFMG. Belo Horizonte, MG – Brasil. Asma e gravidez: uma abordagem completa DOI: 10.5935/2238-3182.20140104


DIAGNOSIS
The diagnosis of asthma must be based on clinical and functional conditions and evaluation of triggering factors of crises.
It is important to evaluate previous history of asthma, frequency, intensity of asthma attacks, and the need to use medicines. 1

CLINICAL DIAGNOSIS
■ symptoms of dyspnea, chronic cough, wheezing, and chest discomfort (one or more symptoms), especially at night and when waking up; 11 ■ pulmonary auscultation evidencing wheezing; ■ episodic symptoms with spontaneous or drug related improvement; ■ crises often triggered by exposure to allergens, physical exercise, climate alterations, or respiratory infections.

INTRODUCTION
Asthma is a chronic inflammatory disease characterized by bronchial hyper-reactivity to various stimuli including allergens, climate alterations, drugs, and infections.It has an intermittent and reversible character. 1sthma is the most common obstructive pneumopathy in pregnancy, reaching 3.7 to 8.4% of pregnancies; 0.05 to 2% of pregnant women have severe asthmatic crisis. 2 Based on this important incidence, we decided to delve into the topic asthma and pregnancy through an extensive review of the literature.After review of articles in Medline (1998-2010), meta-analyses were selected first, which are studies that summarize data from other studies using structured methods.Subsequently, clinical trials and observational cohort studies that compared different types of drugs for treatment of asthma in pregnancy, as well as their side effects and clinical efficacy were evaluated, and studies on pathophysiology of asthma and perinatal results in asthmatic patients comparing with nonasthmatic patients.Brazilian consensus and literature reviews on the subject were also evaluated.
][5] The course of asthma is not predictable during pregnancy and improvement (1/3 of pregnant women), worsening (1/3 of pregnant women), or clinical stabilization can occur.However, patients with severe asthma tend to worsen and those with the mild form tend to improve.There is a trend of exacerbation between 24 and 36 gestational weeks, whereas crises are unusual during labor due to the elevation of prostaglandins (PGE) and cortisol. 6,7

PATHOGENESIS
Bronchial inflammation is the main physical pathogenic factor of asthma.It results from complex interactions between mediating inflammatory cells

CLASSIFICATION OF ASTHMA
It is essential to classify asthma for an improved approach to the disease and consequent control avoiding maternal and fetal complications.Asthma is classified as intermittent, mild persistent, moderate persistent, and severe persistent. 1,2(Table 2)

DIFFERENTIAL DIAGNOSIS IN PREGNANCY
Other diseases presenting acute dyspnea must be considered: 12 ■ hyperventilation in pregnancy -can be associated with dyspnea, however, without other symptoms of asthma; Blood tests and chest x-rays are important to ward off associated lung infections.

FUNCTIONAL DIAGNOSTICS -SPIROMETRY
Performance of pulmonary function test using a spirometer.
The functional evaluation of asthma in pregnancy is based on parameters that do not change as a function of gestation: 1 ■ FEV1 -forced expiratory volume in the 1 st second; ■ FVC -forced vital capacity (after inspiring to total lung capacity, expires quickly and intensely); ■ PEF -peak expiratory flow (can be evaluated through a portable flowmeter, "peak-flow").
Are indicative of asthma: 1 ■ obstruction of the airflow with FEV1 < 80% of predicted (predicted = 380-550 L/min) and FEV1/FVC ratio less than 75; ■ obstruction of the airflow that improves significantly after using short-duration bronchodilator; ■ 20% increase in FEV1 after using corticosteroids for two weeks; ■ diurnal variation in peak expiratory flow (PEF) -difference between PEF measurement in the morning and at night > 20% (calculate average of three measures at every evaluation round in 2-3 weeks); ■ increase of 20% in PEF after using short-duration bronchodilator; ■ bronchial provocation test with bronchoconstricting agents (histamine or methacholine) positive, performed if normal spirometry in pregnant women with asthma symptoms -it is considered positive if 20% reduction in the value of FEV1 is observed.Asthma and pregnancy: a comprehensive approach The early use of anti-inflammatory drugs can result in greater lung preservation by preventing the remodeling of airways. 1,145][16][17] (Table 3)

TREATMENT DURING CRISIS
Terbutaline is considered the safest β 2-agonist (category B), unlike others, category C by the Food and Drug Administration (FDA). 18ntravenous hydration is very important during an asthmatic crisis to avoid dehydration.
Pregnancy interruption is indicated if there is maternal-fetal complication.
Crises may occur during labor and should be treated in the same way as those occurring at other times. 2nalgesia during labor is crucial because the pain may trigger bronchospasm crises. 2 The use of EV corticosteroid (hydrocortisone 100 mg 8/8 h) is essential for 24 h after childbirth if the patient received systemic corticosteroid during the previous four weeks.
The use of ergotamine and F2 α prostaglandin can cause bronchospasm. 19

TREATMENT
The treatment of asthma during pregnancy is similar to the usual treatment.
The main goals of treatment are to: control symptoms avoiding fetal hypoxia, guide the pregnant woman about symptoms and how to avoid triggering factors, treatment of crisis, and maintenance to sustain normal or near-normal lung function. 2sthma in pregnancy should be monitored monthly, with spirometry in the first prenatal consultation and evaluation of peak flow (peak-flow) in subsequent consultations.Pregnant women with moderate and severe asthma should evaluate the peak flow at home.The ideal control is considered as PEF ≥ 80%.The expectant mother must schedule an appointment if PEF is 50-80% and seek emergency care if < 50%.Patients with severe asthma must be monitored jointly by the obstetrician and pulmonologist. 2,13he medicines used for asthma are divided into two categories: medicines for improving crisis (acute symptoms) and maintenance medications (to avoid exacerbations-control of symptoms).The most widely used bronchodilators are β2-agonists, which provide adequate effect in crises; however, because they do not have an anti-inflammatory effect, they are not indicated as maintenance treatment if used in isolation.
If symptoms persist, associate anti-leukotrienes or slow-release theophylline or β 2-agonist of long duration.
In the case of bleeding, opt for oxytocin as the first choice and, if necessary, misoprostol (E1prostaglandin does not trigger bronchospasm). 20

Response between one and four hours
Asthma and pregnancy: a comprehensive approach Medicines for asthma in pregnancy, sorted into categories by the FDA are shown. 1,2(Table 4)

FETAL MONITORING
The ultrasound should be performed early for adequate pregnancy dating allowing the appropriate monitoring of fetal growth.Serial exams on the 2 nd and 3 rd trimesters are essential if the pregnant woman has moderate or severe asthma or if there is suspicion of fetal growth restriction.
Cardiotocography and evaluation of the fetal biophysical profile should be performed routinely after 32 weeks in moderate and severe asthma.
In the case of asthma exacerbation, ultrasound is always recommended after recovery.
Breastfeeding in the postpartum should be encouraged.There is no contraindication to the use of corticosteroid, β2-agonist, and theophylline during breastfeeding.Occasionally, theophyllines can cause irritability in children. 24
Inhaled corticosteroid may be used during pregnancy; beclomethasone is the most studied in pregnancy and considered safe.The FDA recently approved budesonide as category B, being the only inhaled corticosteroid in that category, constituting the best therapeutic option for an early treatment. 1,21,22,23here is a preference for prednisone and prednisolone during pregnancy.Dexamethasone and betamethasone should be avoided due to crossing the placenta in high concentrations, which can induce adrenal suppression in the fetus. 1 Although not routinely recommended in pregnancy, theophylline is not associated with fetal malformation.However, it is associated with worsening of digestive symptoms (nausea, vomiting, and gastro esophageal reflux). 1 If the patient remains stable for a period of three months, dose reduction can be considered.

■
pneumonia -there are signs of infection; ■ perinatal cardiomyopathy -always perform in severe dyspnea clinical frames, cardiac and imaging clinical evaluation; ■ acute lung edema -search for tocolytic therapy; ■ pulmonary embolism; ■ amniotic fluid embolism.
β2 Agonist, co-adjuvant in severe crisis • Ipratropium bromide Bronchodilator long duration β2 agonist (12 h of action) • Salmeterol: active in 20 min • Formoterol: fast action, similar to those of short duration Xanthines Low potency and high risk of side effects Broncho-dilating action and light anti-inflammatory • Aminophylline -Co-adjuvant during crisis, restricted to hospitalized patient Antagonist for leukotrienes Anti-inflammatories co-adjuvant Montelukast • Zafirlukast Xanthines Low potency and high risk of side effects Broncho-dilating action and light anti-inflammatory • Theophylline of slow action Cromones Anti-inflammatories co-adjuvant -modest action • Cromolyn sodium: unfavorable posology (4 x/day) • Nedocromil: not available

Figure 1 -
Figure 1 -Treatment algorithm of asthma crises -III Brazilian Consensus for Asthma Management 2002.
(potential benefits justify potential risk)DPositive evidence of risk (research data show risk for fetus but potential benefits can outweigh risk) X Contraindicated in pregnancy (fetal risk clearly greater than potential benefits)

Table 2 -
Classification of asthma