Abstract
A large range of pulmonary and cardiac diseases may affect pregnant patients. The most common causes include acute viral respiratory infections, chronic pulmonary or cardiac conditions and bacterial pneumonia. Asthma is the most common pulmonary disease to complicate pregnancy, and a third of patients experience worsening of asthma control during pregnancy. In patients with chronic obstructive pulmonary disease, cystic fibrosis (CF), non-CF bronchiectasis or interstitial lung disease, and rarely in patients who have a history of lung transplantation, the physiological and biological conditions of pregnancy will not exacerbate the underlying pulmonary disease as much as reduce pulmonary reserve and disease tolerance. Pregnancy is associated with an increased risk of aspiration pneumonitis, pulmonary embolism, cardiomyopathy, acute myocardial infarction and aortic dissection. Often these occur in patients without other known risk factors.
Introduction
A large range of pulmonary and cardiac diseases may affect pregnant patients. The most common causes include acute viral respiratory infections, chronic pulmonary or cardiac conditions and bacterial pneumonia. Asthma is the most common pulmonary disease to complicate pregnancy, and a third of patients experience worsening of asthma control during pregnancy. In patients with chronic obstructive pulmonary disease, cystic fibrosis (CF), non-CF bronchiectasis or interstitial lung disease, and rarely in patients who have a history of lung transplantation, the physiological and biological conditions of pregnancy will not exacerbate the underlying pulmonary disease as much as reduce pulmonary reserve and disease tolerance. Pregnancy is associated with an increased risk of aspiration pneumonitis, pulmonary embolism, cardiomyopathy, acute myocardial infarction and aortic dissection. Often these occur in patients without other known risk factors. Certain conditions of pregnancy also predispose to pulmonary oedema. All of these diseases present with pulmonary symptoms. These symptoms have particular and disease-consistent features, even if symptom severity may vary among patients. In addition, non-pulmonary diseases such as gastro-oesophageal reflux disease can cause pulmonary symptoms, mimicking an underlying cardiopulmonary process.
In the following sections, the burden and evaluation of cough, chest pain and dyspnoea during pregnancy are explored. Hypoxaemia is also reviewed. In contrast to hypoxaemia, the pulmonary symptoms can be associated with benign conditions. However, all of them can also represent serious illness. Eliciting details on the clinical features and utilizing diagnostic testing, as indicated, are key to establishing the diagnosis. This is essential, as early recognition of a serious medical condition can be life-saving for the pregnant woman and her fetus.
Cough
Most studies to elucidate the mechanisms and neural circuits underlying cough in humans have had to rely on animal models. This limitation notwithstanding, cough is understood to begin with irritation or stimulation of thoracic vagal afferent nerves, which relay information to the medulla oblongata. Near to but possibly distinct from the respiratory centre, the precise anatomical details of the ‘cough centre’ in the medulla oblongata are unknown. This cough centre directs an efferent nerve response, resulting in the forceful contraction of the diaphragm and accessory muscles of expiration, interrupting the normal breathing pattern and generating a cough (Figure 3.1). Chronic cough is believed, in most instances, to be due to abnormalities in afferent nerve function, with abnormal or hypersensitive sensing of mechanical changes or chemical irritants. Three main categories of afferent vagal nerves have been identified. C-fibres are the most strongly implicated in the cough reflex although fibres with rapidly adapting pulmonary stretch receptors (RAR) are also likely to be important. In humans, C-fibre afferent nerves are located throughout the airways and the alveolar network, although cough induction appears restricted to stimulation of fibres in the large and medium-sized airways.1 While largely unexplored in research, the pathobiology of cough in pregnant patients should be similar to that of non-pregnant patients. Specifically, the mechanism of cough in pregnant patients should relate to irritant stimulation of C-fibres, mechanical stretch of RAR fibres or both. Compared to men, women demonstrate increased sensitivity to stimulation of cough nerve fibres.2 However, among women, a further increase in sensitivity during pregnancy has not been reported.
Figure 3.1 Cough efferent and afferent loops. In humans, vagus nerve C-fibres and nerve fibres with rapidly adapting receptors transmit information about chemical irritants and mechanical events via stretch fibres around the airways to the brain (left side of figure). The existence of other fibres which may also convey signals to induce cough have yet to be identified. While a discrete cough centre in the brain has not been identified, afferent inputs converge in the medulla oblongata, in regions close to and perhaps directly part of the respiratory control centre. Higher-order brain inputs also converge here, accounting for the ability to consciously induce and suppress cough. Efferent outputs (right side of figure) mediate the forceful exhalations of coughing via contractions of abdominal muscles, the diaphragm and accessory muscles of expiration.
Respiratory Infections
All of the pulmonary diseases listed in the introduction can cause cough, in pregnant and non-pregnant patients alike. Cough related to infection is likely the most common cause of acute (<3 weeks) and subacute (3–8 weeks) cough among pregnant patients. Upper respiratory tract infections are common, and in one study was estimated to afflict nearly half of pregnant patients.3 Due to changes in the systemic immune system during pregnancy, including suppression of T-effector cell responses and enhanced regulatory T-cell inhibitory responses, pregnant patients are at increased risk for respiratory viral infections. In addition to influenza, rhinovirus, coronavirus and adenovirus are important causes of illness during pregnancy. There is growing appreciation that pregnant women may also be at particular risk for respiratory syncytial virus infection and pertussis (often called whooping cough), caused by Bordetella pertussis infection.4,5 In contrast to children, adults are less likely to present with a whoop, but an unrelenting cough marked by severe coughing fits is an indication to test for recent pertussis infection, typically established by elevated antibody titres. For all of these respiratory infections, the infectious phase of the illness may have been mild or poorly registered by the patient, and a lingering cough may be the only complaint volunteered; a careful retrospective review of infectious symptoms is important. Bacterial pneumonia may also present with cough as the main symptom. Infectious symptoms such as fever, night sweats or purulent sputum are often present in bacterial pneumonia, though less reliably so in pregnant patients.6 The microbial agents associated with pneumonia during pregnancy, as well as clinical management, are addressed in Chapter 6, Pulmonary Infections in Pregnancy. As an additional comment here, pregnant women are not immune from emerging, rare or exotic infections, and local epidemiologic trends, as well as travel history, should be considered in all patients presenting with pneumonia. In particular, the normal reduction in immune function associated with pregnancy can dampen the systemic symptoms of active tuberculosis, and clinicians should be aware of the potential for an altered clinical presentation, including that of cough-predominant disease. Cough in active tuberculosis is often productive and bothersome, though rarely hacking. It will be chronic so long as disease is untreated. The rate of TB diagnosis is increased during pregnancy and particularly in the post-partum period, and tuberculosis should be considered in the setting of unexplained cough if risk factors are present.7 Specifically, patients from areas with a high prevalence of tuberculosis, or patients with other risk factors for exposure should be considered for tuberculosis screening.
Non-Infectious Cough
In contrast to acute cough, and with the exceptions of pertussis and tuberculosis, chronic cough during pregnancy is most often due to non-pulmonary conditions. As angiotensin converting enzyme (ACE) inhibitors are contraindicated during pregnancy, use of these medications will not be a common cause of cough among pregnant patients. Otherwise, the most common causes of chronic cough should be similar for pregnant and non-pregnant patients, although studies of cough during pregnancy to definitively establish this are lacking. Gastro-oesophageal reflux disease (GERD), chronic rhinosinusitis and asthma are universally cited as the most common non-infectious causes of chronic cough. During pregnancy, new onset, cough-variant asthma may occur. However, biological changes associated with pregnancy foster development of both GERD and rhinosinusitis. While often benign in regards to long-term outcomes, both have been implicated in cough during pregnancy, which can be associated with a reduced quality of life.
The features of allergic and pregnancy-associated rhinitis are explored in Table 3.1; in contrast to allergic rhinosinusitis, pregnancy rhinitis is not associated with nasal discharge, and is therefore not as clearly associated with cough. GERD occurs in approximately half of all pregnancies, with the presence and severity of symptoms increasing with each trimester.8 Hormonally mediated relaxation of the lower oesophageal sphincter is the main mechanism of pregnancy-associated GERD and lower oesophageal sphincter pressure declines as pregnancy progresses.9 In the absence of non-invasive modalities to test for GERD, the use of a validated questionnaire is a commonly utilized diagnostic tool in clinical practice. However, validation cohorts have largely excluded pregnant patients, and these questionnaires do not include cough as a GERD-related symptom of interest. Nevertheless, GERD is implicated – by association or by clinical response to treatment – in the pathophysiology of chronic cough.10 There is little data on whether pregnancy affects the manifestations of GERD, including that of cough. An exception is one study which specifically evaluated extra-oesophageal GERD symptoms in pregnant patients, where the diagnosis of GERD was established by questionnaire data.11 Several notable findings were reported, which included a high rate of GERD among pregnant patients, similar to what has been demonstrated in other cohort studies. In addition, the prevalence of cough was low (1.2%) among pregnant patients, including those with GERD. Validation by other studies is needed, but the findings in this cohort study seem to suggest that cough is rare in pregnancy, with reported rates lower than that of the baseline non-pregnant population. These findings also suggest that cough is rarely associated with GERD in pregnancy. Why only a subset of patients with GERD develop cough, in this study and beyond, is not clear. GERD may serve as a stimulus for cough in patients with co-existing vagal afferent hypersensitivity.10 For patients with typical GERD symptoms and a progressive cough which tracks with reflux symptoms, a trial of antacid therapy is warranted for diagnostic as well as therapeutic purposes.
| Conditions associated with cough | Clinical pearls of these conditions |
|---|---|
| Gastro-oesophageal reflux |
|
| Asthma |
|
| Pregnancy rhinitis |
|
| Allergic rhinosinusitis |
|
| Post-viral syndrome |
|
| Pertussis |
|
| Congestive heart failure (CHF) |
|
| Other: foreign body aspiration, bronchopulmonary mass, interstitial lung disease (ILD) |
|
Assessment and Management of Cough
The evaluation of cough during pregnancy begins with a meticulous history. Nearly all causes of cough (Table 3.1) are associated with additional signs or symptoms. In addition to a comprehensive review of symptoms, patients should be asked about the nature of their cough (Table 3.2). For patients with a new, persistent cough and only a questionable diagnosis of GERD or allergic rhinitis, imaging is often required to rule out a more concerning process.
Table 3.2 Cough features which help in aetiologic assessment
| Nature of cough | Specific details to query |
|---|---|
| Type of cough |
|
| Cough triggers |
|
| Cough chronicity |
|
| Features of cough trajectory related to specific diagnoses |
|
| Associated symptoms | Imaging is indicated when cough is associated with haemoptysis, fever, dyspnoea, chest pain (non-costochodritic) and/or failure to gain weight during pregnancy |
The management of cough during pregnancy requires identifying the likely cause and, when considering treatment, being aware of the teratogenic profiles of medications. Common over-the-counter medications for cough include dextromethorphan and guaifenesin, which act, respectively, as a cough suppressant and a mucolytic in upper respiratory infections with bronchitis features. The efficacy of these medications is variable. However, both appear to be safe during pregnancy when used for short periods of time.12,13 Active tuberculosis during pregnancy must be treated, and most tuberculosis medications are considered safe to use during pregnancy (see Chapter 6, Respiratory Infections in Pregnancy). Most GERD therapies are safe for pregnant women.14 Whether pregnant patients with cough without reflux symptoms benefit from a trial of GERD therapy is unknown, although such a trial is generally of low risk. Finally, in contrast to allergic rhinitis, pregnancy rhinitis from increased vascular congestion does not respond to intranasal corticosteroids, and distinguishing between these two conditions has important therapeutic and prognostic implications.
Dyspnoea
Unlike cough, dyspnoea is a perceived sensation and not a measurable event. However, like cough, the development of dyspnoea involves the central processing and integration of sensory inputs. These inputs include signals from thoracic afferent nerves, chemoreceptors (central and peripheral), mechanoreceptors from working muscles, and metabolic byproducts.15 Afferent fibres project to the medulla oblongata, converging on the nucleus tractus solitarius, which in turn communicates with and is modified by the limbic system and cortical areas.16 Normally, an increase in afferent signalling during light exertion is met by an ability to readily increase ventilatory effort to maintain physiologic homeostasis. This ability to comfortably and subconsciously accommodate an increase in demand is the mark of a healthy thoracic system. As such, dyspnoea is not typically associated with brief bouts of voluntary hyperventilation, normal exertions of daily living or with exercise when exertion does not exceed an individual’s level of conditioning. In contrast, an inability to comfortably meet the demands for increased ventilation underlies pathological dyspnoea. In patients with cardiopulmonary disease or profound deconditioning, dyspnoea from neuro-mechanical mismatch occurs with seemingly non-strenuous activities, impairing functionality and quality of life. In some patients, there may be an affective aspect of dyspnoea, and anxiety and other conditions of negative emotion enhance the sensation of dyspnoea. A feed-forward loop may develop, where anxiety is a common response to dyspnoea, and anxiety can heighten the sensation of dyspnoea. In addition, the perception of dyspnoea for a given load (in experimental conditions) varies among patients. This perception is affected by the neuro-sensitivity of afferent inputs, baseline levels of pulmonary and body fitness and psychological factors.17 The complexity of sensory inputs and central processing is underscored by the multiple facets of dyspnoea, including the sensation of air hunger, chest tightness, breathlessness and laboured breathing.
Non-Pathological Dyspnoea
Unlike cough, chest pain and hypoxia, dyspnoea can be a normal and even common experience during pregnancy. In small cohort studies, upwards of half of pregnant patients endorse dyspnoea.18 Non-pathological dyspnoea during pregnancy appears related to increased demand on the ventilatory system, with little evidence to support an insufficient mechanical response in normal patients (see Chapter 16, Dyspnoea of Pregnancy). Progesterone stimulates the respiratory centre to increase minute ventilation, which occurs largely via an increase in tidal volume, although one study also identified an increase in the respiratory rate.19 While rates of dyspnoea increase as pregnancy advances, dyspnoea often presents early in pregnancy, long before the onset of mechanical effects from an enlarging uterus.20
Increased minute ventilation is present at rest and with exercise, where pregnant patients demonstrate increased minute ventilation responses at submaximal exercise compared to non-pregnant controls.19 An awareness of this increase is presumed to underlie the non-pathological dyspnoea of pregnancy. Accordingly, limitations in exercise capacity during pregnancy have not been demonstrated, and dyspnoea reports at peak exercise were similar in pregnant vs non-pregnant controls.15 In another study, in spite of increased minute ventilation with graduated exertion, exertional dyspnoea (as captured by the Borg perceived exertion score) was not more prevalent among pregnant women.19 There were also no significant differences in dyspnoea rates among early pregnancy, second trimester and third trimester patients.
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