Maternal Pulmonary Disorders Complicating Pregnancy



Maternal Pulmonary Disorders Complicating Pregnancy


Steven James Cassady

Janaki Deepak

Neal Dodia

Jeffrey D. Hasday

William Brian Karkowsky

Kathryn S. Robinett



Introduction

Pregnant women can be afflicted by the same respiratory illnesses as nonpregnant women, but these conditions may be complicated by the physiologic changes that occur during pregnancy. In this chapter, we will review the evaluation and diagnosis of lung disease in the pregnant patient, discuss the pertinent physiologic changes of the respiratory system that occur during pregnancy, and discuss specific respiratory illnesses with regard to the pregnant population.


Clinical Assessment of the Pregnant Pulmonary Patient

Pregnant patients should be evaluated for pulmonary disease in a similar manner to those who are nonpregnant. The core evaluation should stem from a thorough history, which can guide the need for serum blood testing, pulmonary function testing, and advanced imaging. Documenting baseline symptoms and function prior to pregnancy can be helpful to quantify change during pregnancy. Dyspnea is a common complaint during pregnancy and affects approximately 60% to 70% of pregnant women during both rest and exertion.1 It is thought to be related largely to elevated circulating progesterone causing larger tidal volume breaths and increased perception of respiratory discomfort from these larger breaths. To a lesser degree, mechanical forces external to the lungs contribute to dyspnea as well.2,3

Differentiating a physiologic change from a pathologic change requires an understanding of the normal physiologic changes that occur during pregnancy and a careful history taking. For example, despite the common complaint of dyspnea, most pregnant patients should not experience a change in exercise tolerance and should not have abnormalities on physical examination. If these findings are present, further workup and potentially pulmonary consultation may be warranted.4,5


Pulmonary Physiology in Pregnancy

Pulmonary physiologic changes that occur naturally in order to accommodate the growing fetus have important implications on how we clinically manage pregnant patients. In this section, we will discuss the mechanical, hormonal, and metabolic changes that affect the respiratory system.


Normal Respiratory Physiology

To understand the mechanical changes that occur in pregnancy, we must first review the respiratory physiology of healthy nonpregnant patients. Lung volume is determined by the balance between the force exerted by the chest wall and the elastic recoil of the lung. In forced exhalation, contraction of the respiratory muscles (eg, the rectus abdominis, transverse abdominis, internal and external obliques, and intercostals) reduces lung volumes until compression of the noncartilagenous segments of the bronchial tree terminates further exhalation (Figure 29.1). The volume remaining in the lung at this point is the residual volume (RV). The lung volume at maximal inspiration, including the RV, is the total lung capacity (TLC). The total volume that can be exhaled from a full inspiration is the vital capacity (VC). The forced VC (FVC) is measured with a forced expiration and is usually the same as when measured during an unforced or
slow VC (SVC). Maintaining RV or TLC requires active work by the respiratory muscles. The volume remaining in the lungs at the end of a normal effortless exhalation when the outward recoil of the relaxed respiratory muscles is balanced by the inward force of elastic recoil is the functional residual capacity (FRC). Abnormal lung volumes may be caused by changes in the shape or compliance of the chest wall or abdomen, changes in respiratory muscle function, reduced pleural compliance or accumulation of pleural fluid, or reduced compliance of lung parenchyma. The flow rates in the airways are determined by airway luminal diameter. Air flow limitation occurs when airway lumens are narrowed by airway wall thickening, bronchoconstriction, or the presence of intraluminal mucus.







Respiratory Physiology Changes During Pregnancy

During pregnancy, FRC decreases by 9.5% to 25% as the gravid uterus gradually displaces the diaphragm upwards.6 However, expansion of the chest wall compensates for loss of volume due to this diaphragmatic displacement so that TLC remains unchanged, and inspiratory capacity and tidal volume usually increase during pregnancy.7,8 Respiratory muscle strength is not affected by the mechanical changes of pregnancy, which may be the result of changes in the curvature of the diaphragm due to uterine enlargement that leads to increased muscle fiber stretch. Measurements of maximal inspiratory and expiratory force also remain preserved. While respiratory muscle strength is preserved, increases in pleural and intra-abdominal pressures increase the respiratory muscle work required to achieve the same level of lung expansion.7,9


Hormonal and Metabolic Changes During Pregnancy

The increases in progesterone and estrogen levels that occur during normal pregnancy modify respiratory drive. Total respiration, often quantified as the minute ventilation (MV), the product of the respiratory rate (RR), and tidal volume (TV or VT), is managed both consciously and unconsciously. Unconscious regulation is controlled by central respiratory centers in the medulla that primarily respond to blood levels of carbon dioxide (CO2). Progesterone acts on receptors present in the central respiratory centers to increase sensitivity to CO2, thereby increasing TV and MV and reducing blood partial pressure of CO2 (PCO2). Estrogen can augment the effect of progesterone on respiratory drive by increasing the sensitivity and number of
progesterone receptors. In addition to its effects on MV, progesterone can cause mucosal edema of the upper airways, which can contribute to upper airway obstruction.6,8,10

Prostaglandins circulate throughout pregnancy and can have various effects on the respiratory system. Prostaglandins E1 and E2 have a dilatory effect on the bronchial smooth muscle, whereas prostaglandin F, a uterine smooth muscle stimulant during labor, causes bronchial smooth muscle constriction. The increase in airway resistance caused by prostaglandin F may not be detectable by the healthy pregnant patient but may worsen preexisting asthma or other types of obstructive lung disease during pregnancy (see later discussion).8

Due to demand from the growing fetus, total metabolism and oxygen consumption increase during pregnancy. The basal metabolic rate can increase by up to 15%, and oxygen consumption increases by 20%.11 Due to the increase in fetal oxygen demand, the oxygen reserve of the pregnant mother decreases. However, because of hormonal and mechanical changes, the increase in TV and MV more than compensates for the increased metabolic demand so that partial pressure of oxygen (PaO2) levels may actually be higher in pregnant women than nonpregnant women.6


Screening


Blood Gas Evaluation

Measuring serum venous or arterial blood can be a useful determinant of acid-base status, and the latter can provide detailed information about maternal oxygenation. Venous blood gases (VBG) can provide a close estimate of arterial pH but do not evaluate oxygenation. VBGs have the benefit of being easier and less painful to obtain than arterial blood gases (ABGs) and carry less risk of vessel injury.12,13

If a precise measurement of the pH and arterial PCO2 (PaCO2) or an evaluation of the PaO2 is required, then an ABG may be indicated. ABG values can be useful in determining an underlying diagnosis of respiratory failure and triaging patients. Normal values for blood gas measurements differ between nonpregnant and pregnant patients (Table 29.1).11 Overall, respiratory changes during pregnancy result in a respiratory alkalosis with slightly increased PaO2 or arterial oxygen tension. Both are normal physiologic changes that result from the increase in ventilation that occurs primarily due to circulating progesterone; this mechanism is further described in the physiology section of the chapter.13 It is important to understand that results from the blood gas tests may be reported as abnormal because most testing laboratories do not change normal values for pregnant patients.









Pulmonary Function Testing

Pulmonary function testing (PFT) is an important objective test to diagnose lung disease and monitor lung function. PFTs include spirometry, lung volumes, and diffusion capacity. Spirometry provides measurements of lung volumes and flow rates, including FVC and the exhaled volume in the first second of a forced expiration, known as the forced expiratory volume in 1 second (FEV1), which can help identify and distinguish between obstructive and restrictive disease.

A ratio of the FEV1/FVC ratio of less than 0.70 is generally considered diagnostic for obstruction or the presence of airflow limitation, although subtler findings on spirometry, such as “scooping” of the expiratory limb of the flow volume loop, may suggest obstruction with borderline values for FEV1/FVC ratio. Once obstruction is established, its severity can then be determined based on the patient’s FEV1 result as it compares to normal values.14 Restrictive lung disease is suggested by a decrease in the FVC below 80% of predicted without evidence of obstruction (ie, FEV1/FVC ratio > 0.70).

Because spirometry can only measure exhaled volume, lung volume testing is required for measurement of RV and the volume measures that incorporate the RV, including the FRC and TLC. Values for TLC less than 80% of predicted confirm the presence of a restrictive defect. In some
cases, spirometry and lung volumes may indicate the presence of both obstructive and restrictive defects.15


Imaging

Radiographic imaging is frequently obtained to assist with the evaluation and diagnosis of pulmonary disease. A justified concern for many pregnant patients is whether radiation exposure is safe for the fetus. Fortunately, in most circumstances, radiation exposure from chest imaging does not pose a significant risk to the mother or fetus. The risk for radiation-associated fetal abnormalities is greatest in the first trimester and early second trimester, but the doses of radiation used for standard x-ray or computed tomography (CT) imaging are well below the threshold level for causing fetal abnormalities. For example, conservative estimates place 50 mGy as a potential threshold of radiation exposure to cause embryonic death, whereas a complete chest CT scan exposes a fetus to only 0.01 to 0.66 mGy. Overall, the consensus is that chest imaging should not be withheld in the pregnant patient if it is clinically indicated.16 See Chapter 9 for detailed discussion on radiation in pregnancy.

Chest x-rays remain an effective modality for diagnosing a myriad of pulmonary conditions, including pneumonia, pulmonary edema, and pneumothorax. However, a CT of the chest may be required for higher resolution imaging of the lung parenchyma. CT angiography of the chest using intravenous contrast can be performed safely in pregnancy to evaluate vascular structures and diagnose pulmonary embolism.17 Animal studies and observational reports have not shown any negative impacts of intravenous contrast on fetal development.16


Effects of Pulmonary Disorders on Pregnancy


Asthma


Clinical Presentation

Asthma is a common lung disorder characterized by the classic clinical manifestations of bronchospasm, such as wheezing, shortness of breath, chest tightness, and cough in response to triggers. Because airway resistance is often variable in asthma, patients with asthma may have normal expiratory airflow on PFT. If suspicion of asthma is high and PFTs fail to show an obstructive pattern, repeated home measurements of peak flow rates may identify asthma by demonstrating peak flow rate variability.


Epidemiology

Asthma is the most common chronic disease in women during their childbearing years and is the most common chronic disease affecting pregnant women.18 The prevalence of asthma in pregnant woman is between 8% and 13%.18 Asthma has a significant impact on 1% to 4% of pregnancies with life-threatening exacerbations occurring in between 0.5% and 5% of pregnancies.18 Women often experience changes in their asthma control during pregnancy, and there is a general “rule of thirds” that one-third of women experience improved asthma control, one-third of women experience worsening control, and one-third of women have unchanged control.19 The burden of asthma-related complications in pregnancy is greater for African-American women, who have higher rates of morbidity and mortality associated with asthma.18,20 Fortunately, if asthma is well controlled during pregnancy, there is almost no increased risk of complication for the mother or fetus.20


Etiology

It is now well accepted that asthma results from the intersection of complex and often overlapping pathways leading to chronic airway inflammation.21 Inflammation typically results in the pulmonary symptoms of wheezing, shortness of breath, chest tightness, and cough, which can be incited by any number of triggers. Common triggers include exercise, cold air, viral infections, and exposure to aeroallergens and irritants. By definition, these symptoms will be episodic and relapse and remit depending on the duration of exposure, degree of reaction, and onset of treatments. Although not necessarily present in all patients, a personal or family history of atopic dermatitis, seasonal allergies, and allergic rhinitis is commonly found in individuals with asthma.

Although biopsies are rarely performed, the histopathology of the asthmatic airway is characterized by multiple changes, including epithelial detachment, mucus gland hyperplasia, epithelial fibrosis, bronchial smooth muscle hypertrophy, vascular changes, and inflammatory cell infiltrates.22 At the microscopic level, asthmatic airway inflammation demonstrates increased amounts
of eosinophils, mast cells, monocytes, dendritic cells, natural killer T (NKT) cells, and basophils. The response to bronchoprovocation leading to an asthma exacerbation can be divided into early and late phases. Mast cell release of mediators that induce bronchoconstriction, including histamine, prostaglandins, leukotrienes, and tumor necrosis factor-α (TNF-α), drives the early phase. The late-phase response, occurring hours to days following the initial trigger, tends to result in recruitment of innate and adaptive immune cells able to propagate a continued inflammatory response.

Typically, an initial allergen exposure induces secretion of IgE antibodies from plasma cells, which can, on subsequent exposure, lead to cross-linking of IgE on mast cell surface receptors and rapid degranulation and release of histamine, prostaglandin D2, cysteinyl leukotrienes (LTC4, D4, and E4) and TNF-α. Hours later, an influx of inflammatory cells, including eosinophils, neutrophils, helper memory T cells, basophils, and dendritic cells, will occur, propagating the inflammatory response. Cellular-mediated inflammation leads to acute contraction of airway smooth muscle and bronchoconstriction, which then results in airflow obstruction, air trapping, dynamic hyperinflation, and bronchial hyperresponsiveness. Over time, prolonged exposure to unfettered inflammation can lead to airway remodeling and structural changes that can physiologically result in irreversible airflow obstruction most often characterized on PFT as decreased FEV1 and FEV1/FVC ratio and increased FVC, TLC, and RV.


Maternal Risk From Asthma

There are a variety of reasons why asthma may worsen symptomatically during pregnancy, including the effects of the normal physiological changes that during pregnancy. Pregnant women have significant hormonal changes that affect respiratory drive and gravidae are more susceptible to viral respiratory infections, such as influenza, both of which can lead to increased frequency of asthma exacerbations, especially in the second trimester.23,24 An important cause of pregnancy-related asthma exacerbations is inadequate treatment of underlying asthma due to unwarranted concerns of adverse medication effects by patients and/or their healthcare clinicians. However, undertreatment of asthma poses a greater risk for mother and fetus and can result in asthma exacerbations, preeclampsia, preterm delivery, low birth weight, and increased perinatal mortality, as discussed in the section on fetal risk below.18,23


Fetal Complications of Maternal Asthma

Concerns regarding the risks to the fetus associated with maternal asthma include the impact of suboptimal asthma control and the potential adverse effects of asthma treatments. With regard to the former, several large cohort studies clearly demonstrate a consistent association between poor asthma control and numerous obstetric and neonatal complications. The largest of these studies, which evaluated pregnancy outcomes in 37,585 pregnant women with asthma and 243,434 pregnant women without asthma, demonstrated a small but statistically significant increase in the incidence of miscarriage, antepartum hemorrhage, postpartum hemorrhage, anemia, depression, and need for cesarean delivery in patients with asthma.22 A large retrospective US-based cohort study evaluated the effect of asthma in 223,512 singleton pregnancies on multiple pregnancy-related complications and found that, after adjustment for multiple variables, pregnant women with asthma have higher odds of preeclampsia, pulmonary embolism, and preterm labor compared to those without asthma.21 A meta-analysis of 21 studies comparing pregnancies in women with and without asthma found that the risk of congenital malformations was slightly increased in women with asthma, although this increased risk was not seen when controlling for women receiving active asthma management, suggesting that control of underlying asthma mitigated this risk.25

The underlying mechanisms driving the risk of obstetrical complications in pregnant women with poorly controlled asthma have not been conclusively defined, but may include maternal hypoxia, disruptions of uteroplacental blood flow, or increased administration of systemic oral corticosteroids. A large analysis of pregnant women with asthma found that poorly controlled asthma increased the risk of spontaneous abortion by 26%.26 Interestingly, no association was found between asthma severity and spontaneous or induced abortion.26 Similarly, maternal asthma exacerbations and oral corticosteroid use were associated with low birth weight and preterm delivery. Moderate to severe asthma during pregnancy was associated with an increased risk of small for gestational age and low birth weight infants.26



Management of Asthma Exacerbations in Pregnancy

Management of asthma exacerbations in pregnant women does not differ substantially from that of the nonpregnant patient. Treatment plans should emphasize appropriate maternal and fetal monitoring, identification of triggers (including infections and medication nonadherence), appropriate supportive care, and prompt initiation of severity-dependent pharmacologic therapies. As mentioned previously, because the risks associated with asthma exacerbations far exceed maternal or fetal risks from the adverse effects of pharmacologic therapies, prompt treatment of exacerbations is crucial.

Definitions of asthma exacerbation are neither uniform nor comprehensive, but broadly include worsening respiratory symptoms of breathlessness, wheezing, chest tightness, or cough, along with evidence of airflow obstruction by peak flow monitoring. Once a reasonable suspicion for asthma exacerbation exists, rapid assessment of severity should ensue with a focused evaluation for evidence of labored breathing, respiratory distress, and inadequate oxygenation or ventilation. In urgent care and emergency settings, appropriate monitoring of mother and fetus, including pulse oximetry and fetal heart monitoring, should be initiated.


Pharmacologic and Nonpharmacologic Treatment of Stable Asthma

Fortunately, treatment of asthma with nonpharmacologic and pharmacologic therapies effectively mitigates the risks of obstetrical complications with a favorable safety profile. The mainstay of nonpharmacologic therapies includes appropriate patient education on respiratory trigger avoidance and smoking cessation. In terms of pharmacologic management, the cornerstone for rapid reversal of acute asthma symptoms remains short-acting beta-agonists (SABAs) such as albuterol. Some case-controlled studies have shown a small increase in the risk of some congenital malformations, including gastroschisis, cleft palate, and cardiac defects, associated with SABA use, but the general consensus is that this class of drugs is safe to use during pregnancy.27,28,29 The risk of these associated defects appears to be small, and these studies are difficult to interpret because SABA use itself is an indicator of suboptimal asthma control. Long-acting beta-agonist (LABA) bronchodilators also appear to be quite safe for use in pregnancy, with most of the safety data generated for salmeterol and formoterol.30

In general, oral corticosteroids are best reserved for salvage therapy or for patients experiencing a severe respiratory exacerbation. Systemic corticosteroids have been associated with distinct congenital malformations, specifically cleft palate, preterm birth, and low birth weights.27 Inhaled corticosteroids as a stand-alone therapy or in combination with an LABA are associated with a much lower risk of fetal abnormalities than systemic corticosteroids. Use of inhaled budesonide was found not to be associated with an increased rate of congenital malformations in a Swedish registry of nearly 3000 pregnant women.31 Similar to the results with budesonide, the use of fluticasone did not affect rates of low birth weight, small for gestational age births, and preterm delivery.30

Studies of leukotriene modifiers, including leukotriene receptor antagonists such as montelukast and zafirlukast, have shown no increase in major birth defects or other adverse outcomes in women taking these medications during pregnancy.32,33,34 In the last decade, treatment of asthma has expanded to include an array of monoclonal antibodies, including anti-immunoglobulin (Ig) E, anti-interleukin (IL)-5, and anti-IL-4 therapies. To date, no significant teratogenicity has been observed with the use of these medications, but it remains too early to assure the safety of these medications during pregnancy as these antibodies likely cross the placenta and are not approved for use in pregnancy by the U.S. Food and Drug Administration (FDA). However, omalizumab is categorized as pregnancy category B by the FDA based on the publication of an omalizumab pregnancy registry.35

Supplemental oxygen may be beneficial in individuals who are unable to maintain oxygen saturations above 95% or a PaO2 of greater than 80 mm Hg. It is worth emphasizing that a near-“normal” PacO2 on an ABG measurement based on nonpregnant normal values may fail to identify relative decompensation and impaired ventilatory reserve when superimposed on the typical alkalosis that occurs during pregnancy.

Medications typically used for acute asthma exacerbations include systemic corticosteroids, short-acting bronchodilator agents, and intravenous magnesium sulfate. Doses and routes of systemic corticosteroids need not differ substantially
from that used in non-pregnant females, but optimal doses during pregnancy have not been conclusively identified. Standard doses of systemic corticosteroids range between 40 and 60 mg for prednisone or the equivalent dose of methylprednisolone (32-48 mg). Higher doses of corticosteroids are often used in patients with particularly severe asthma exacerbations or for those who are critically ill. Short-acting bronchodilators, such as albuterol and ipratropium, are used similarly in pregnant and nonpregnant patients and are typically administered as a nebulized form during acute exacerbations. Given its well-studied safety profile, intravenous magnesium sulfate is often given for its bronchodilator effects. Use of the intravenous beta-agonist epinephrine is generally avoided during pregnancy due to concerns for potential circulatory effects on uteroplacental blood flow.

In summary, asthma is the most common chronic disease occurring in pregnant women and carries potential health hazards for both mother and fetus. During all stages of pregnancy, it is important to maintain patients with asthma on their controller medications and to aggressively manage exacerbations. There is increasing evidence that keeping women on their injected monoclonal antibody treatments is likely safe throughout pregnancy. An aggressive approach to maintenance therapy in asthmatic patients can decrease exacerbations and oral corticosteroid administration, which have well-documented negative consequences.


Aspiration in Pregnancy


Clinical Presentation

Aspiration of low pH gastric contents into the tracheobronchial tree can lead to a chemical pneumonitis and bacterial pneumonia. A number of physiological factors predispose pregnant women to aspiration, including elevated intragastric pressure due to the gravid uterus and increased prevalence of gastroesophageal reflux disease (GERD) due to the negative effects of circulating estradiol and progesterone on lower esophageal sphincter tone.36 The risks of aspiration are highest during and immediately following labor and are further increased by the use of sedation and analgesic medications, repositioning during labor, and by tracheal intubation if general anesthesia is required.

Chemical pneumonitis due to aspiration of gastric contents with a pH 2.5 or lower is characterized by early alveolar injury, hemorrhage, and edema followed by acute inflammation and formation of hyaline membranes. Patients may develop fever, abrupt-onset dyspnea, diffuse crackles on lung examination, and potentially marked hypoxemia. Chest x-ray or CT chest imaging may demonstrate consolidation in the region portion of the lung. Severe cases of aspiration pneumonitis may progress to respiratory failure or acute respiratory distress syndrome (ARDS).

Aspiration pneumonia, which may develop as a superimposed infection of the injured lung, usually presents with a similar symptom profile as other forms of bacterial pneumonia (see below), including fever, dyspnea, and cough productive of purulent sputum. However, because the causative pathogens in aspiration pneumonia are usually anaerobic bacteria and other oral flora that are more indolent than the pathogens responsible for typical bacterial pneumonia, the course of the illness is less acute, developing over days to weeks.



Management of Aspiration in Pregnancy

Aspiration prophylaxis is frequently used in pregnant women who are to undergo cesarean delivery or other surgery under general anesthesia, although there are little empiric data about its effectiveness.39 Nonparticulate antacids, H2 receptor antagonists, and proton-pump inhibitors are all viable options. An effective reduction in gastric acidity to a pH of
above 2.5 has been demonstrated with the combination of antacids and H2 receptor antagonists, with more limited data available regarding the use of proton-pump inhibitors.3 Other prophylactic measures include preoperative fasting, including 6 hours of preoperative fasting for solid food prior to the planned procedure.


Infectious Pulmonary Diseases in Pregnancy


Influenza


Epidemiology

Influenza infection is common during pregnancy and has been associated with a high risk of maternal mortality, especially late in the third trimester and with advanced maternal age. High influenza-associated mortality rates in pregnant women have occurred in historical pandemics, such as the 1918-1919 influenza pandemic, and more recent endemics, such as the H1N1 virus in 2009, where pregnant women comprised 5% of influenza-related deaths.40


Clinical Presentation

Influenza typically presents with systemic symptoms including fever, headache, myalgias, malaise, and upper respiratory symptoms such as rhinorrhea, sore throat, and a nonproductive cough. Severe cases may involve the lower respiratory tract infection and must be distinguished from superimposed bacterial pneumonia. In some cases, influenza can directly cause pneumonia, which can progress to ARDS and cause respiratory failure.

Influenza can also be complicated by secondary bacterial infections, classically due to Streptococcus pneumoniae, Staphylococcus aureus, or Haemophilus influenzae.41 MRSA is an emerging concern in postinfluenza pneumonia and should be considered as a potential pathogen, especially in severe cases of pneumonia or patients with positive nares surveillance testing for MRSA.


Clinical Assessment

Physical examination findings are variable and may include postnasal discharge, cervical adenopathy, and rhonchi, wheezes, and/or rales on chest examinations. If influenza is suspected in a pregnant or recently postpartum patient, testing should be performed expeditiously to confirm the diagnosis. Polymerase chain reaction (PCR)-based tests are preferred over rapid antigen tests due to their superior sensitivity.



Management of Influenza in Pregnancy

Current recommendations advise influenza vaccination for all persons aged 6 months or older without contraindications, which includes pregnant women or women who plan to become pregnant. Pregnant women should be given inactivated vaccines rather than live-attenuated vaccines due to concern over their safety during pregnancy. Unfortunately, rates of vaccination in pregnant women remain relatively low, with rates of 49% reported in 2017-2018.43

Jun 19, 2022 | Posted by in OBSTETRICS | Comments Off on Maternal Pulmonary Disorders Complicating Pregnancy
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