Viral Pulmonary Infections
Brian C. Keller
Steven L. Brody
General Principles
Viral respiratory infections account for nearly 50% of all acute respiratory illnesses. Most infections are self-limited.
Approximately 200 antigenically distinct viruses cause multiple clinical syndromes ranging from common cold, pharyngitis, croup (i.e., laryngotracheobronchitis), tracheitis, bronchitis, bronchiolitis, and pneumonia.
This chapter will introduce the major respiratory viruses encountered in clinical practice, assist in differentiating viral and bacterial respiratory infections, and guide antiviral therapy where specific therapy exists (Tables 16-1, 16-2, and 16-3).
Classification in the Normal Host
Upper Respiratory Tract Infections
Rhinosinusitis is an upper respiratory tract infection (URTI) defined as inflammation of the mucosa of the nasal passage and paranasal sinuses lasting up to 4 weeks.
The most common etiology is viral. Bacteria can secondarily infect an inflamed sinus cavity, but this only accounts for 0.5–2% of cases.1
Since management of an acute viral rhinosinusitis (AVRS) is supportive, the main focus for the clinician should be in identifying those cases with acute bacterial rhinosinusitis (ABRS). Viral etiologies include rhinovirus, adenovirus, parainfluenza virus (PIV), influenza virus, human coronavirus (HCoV), and enterovirus.
The most common bacteria associated with ABRS are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.
Significant complications of ABRS are rare and include orbital cellulitis, cavernous sinus thrombosis, osteomyelitis, meningitis, and brain abscess. These complications represent medical emergencies that require hospitalization.
The diagnosis is clinical. Acute rhinosinusitis of any etiology presents with three major symptoms: nasal congestion or blockage, purulent rhinorrhea, and facial pain or pressure.2,3
AVRS symptoms typically peak within 2–3 days of onset, decline gradually thereafter, and disappear within 10–14 days. Any pattern that deviates from the “classical” viral disease progression could suggest bacterial infection.
Three criteria may help distinguish ABRS from AVRS4:
Persistent signs and symptoms lasting for ≥10 days.
Severe symptoms for 3–4 consecutive days at the beginning of illness: high fever (≥39°C) and purulent rhinorrhea or facial pain.
Double-sickening: new onset of fever or increased nasal discharge following a typical viral URTI that lasted 5–6 days and was initially improving.
Imaging studies such as plain radiographs and CT scans are of little diagnostic value in uncomplicated acute rhinosinusitis and are not routinely recommended. An abnormal radiographic finding cannot distinguish a viral from bacterial etiology.5
Cultures obtained by sinus aspiration are not indicated for uncomplicated ABRS. They could be performed if the patient has failed to respond to initial empiric antimicrobial therapy.
TABLE 16-1 COMMON RESPIRATORY VIRUS INFECTIONS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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TABLE 16-2 DIAGNOSTIC STRATEGIES FOR VIRAL RESPIRATORY INFECTIONS | ||||||||||||||||||||||||||||||||||
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TABLE 16-3 TARGETED ANTIVIRAL THERAPIES FOR VIRAL RESPIRATORY PATHOGENS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Management of AVRS is supportive.
Intranasal saline irrigation with either physiologic or hypertonic saline can be beneficial in symptomatic control, although the evidence supporting it is still very weak.4
Topical or systemic decongestants, antihistamines, and mucolytics are frequently used for symptom control. However, there are no significant data to support their use. Topical decongestants should not be used for more than 3 consecutive days to avoid rebound congestion and tachyphylaxis.
Intranasal corticosteroids have been shown to provide a modest relief in symptoms when compared to placebo and should certainly be strongly considered in patients with allergic rhinitis.6
Antibiotics may be beneficial for patients with a clinical diagnosis of ABRS and who have severe/persistent symptoms, temperature ≥39°C, or double-sickening. Amoxicillin-clavulanate is the drug of choice and doxycycline is an alternative. The infectious Disease Society of America (IDSA) recommends against trimethoprim-sulfamethoxazole and macrolides. High-dose amoxicillin-clavulanate is recommended where there is a ≥10% endemic rate of invasive penicillin-non-susceptible S. pneumoniae, severe infection (e.g., temperature ≥39°C, systemic toxicity, threat of suppurative complication), daycare attendance, age <2 or >65, recent hospitalization, antibiotic use during the past month, and immunocompromised state.4
Pharyngitis/tonsillitis
The large majority of cases in adults are viral in etiology and do not require antibiotics. Antibiotics should be used in cases of Group A β-hemolytic streptococcal pharyngitis.
Symptoms strongly suggestive of a viral etiology include rhinorrhea, cough, oral ulcers, and hoarseness.7
The modified Centor criteria can be used to estimate the probability of streptococcal pharyngitis. One point each is given for the following: temperature >38°C, absence of cough, anterior cervical lymphadenopathy, and tonsillar swelling or exudate. The modification adds one point for age 3–14 and subtracts one point for age ≥45; age 15–44 has no effect on the score. The risk of streptococcal infection with ≤0 points is 1–2.5%; 1 point, 5–10%; 2 points, 11–17%; 3 points, 28–35%; and ≥4 points, 21–53%. 8,9,10,11
Regardless, the IDSA recommends rapid strep testing whenever there is consideration of streptococcal pharyngitis, as clinical features alone may cause under- and overdiagnosis.7
Negative rapid strep tests should be confirmed with throat culture in children and adolescents due to a higher risk of developing acute rheumatic fever in these age groups. In adults, however, a backup culture is unnecessary because the pretest probability of rapid antigen detection testing is low to begin with.7
Common viral etiologies include rhinovirus, HCoV, adenovirus, herpes simplex virus (HSV), PIV, and influenza virus. Epstein–Barr virus (EBV), coxsackievirus, and acute HIV have also been identified.
Diagnostic testing of viral pharyngitis should be restricted to cases where symptoms fail to resolve within 1–2 weeks or for surveillance cultures during endemic virus outbreaks.
Treatment is mostly supportive with hydration, antipyretics, and analgesia. Topical anesthetics and lozenges alleviate throat pain.
Lower Respiratory Tract Infections
Bronchitis
Bronchitis is classified as acute, which is essentially always infectious, or chronic.
Chronic bronchitis is a nonspecific clinical term with several meanings and is usually not due to infection.
In the general context of chronic obstructive pulmonary disease (COPD), it is defined as cough with sputum production for 3 months in each of the 2 prior years without other explanation—it may or may not be associated with demonstrable airflow obstruction on pulmonary function testing.
In an even broader context chronic bronchitis can imply a productive cough for >8–12 weeks. Chronic cough is discussed in detail in Chapter 8.
Acute bronchitis is a self-limited infection with cough as the predominant symptom usually lasting up to 3 weeks but can be as long as 6 weeks.12 Significant rhinorrhea, fever, dyspnea, tachypnea, or hypoxemia suggests an alternative diagnosis.
Ninety percent cases of acute bronchitis are viral in nature, most commonly PIV, influenza, adenovirus, HCoV, human metapneumovirus (hMPV), PIV, respiratory syncytial virus (RSV), and rhinovirus.13 When caused by bacteria, mostly the organisms are M. pneumoniae, C. pneumoniae, and B. pertussis. Superinfection with typical respiratory pathogens (i.e., S. pneumoniae, H. influenzae, and M. catarrhalis) is known to occur but are presumed to be very unusual.
Treatment is supportive with antitussives, expectorants, inhaled bronchodilators, and alternative therapies, despite a paucity of data to support their use.
Routine use of antibiotics is discouraged.14,15,16,17 Likewise, there is limited value in treating smokers without COPD with antibiotics. An important exception is when B. pertussis is known or suspected in order to limit spread, particularly to unvaccinated infants. In this case, the treatment of choice is azithromycin. Unless started early, antibiotic treatment has little impact on the course of pertussis in typical, previously vaccinated adolescents and adults.12
Inhaled bronchodilators may be beneficial in patients who have airflow restriction and wheeze.18
Bronchiolitis is an almost exclusively viral infection of the bronchioles and typically occurs in <2-year-old infants though it has been reported in adults.
Differentiated from bronchitis by respiratory symptoms, such as tachypnea and wheezing.
RSV is the most common etiology, but other viruses include rhinovirus, hMPV, and the more recently discovered human bocavirus (HBoV).
Treatment is primarily supportive with supplemental oxygen. Continuous positive airway pressure and high-flow nasal cannula therapy may provide effective ventilatory support and decrease the need for intubation.21,22
Several studies have evaluated the effectiveness of inhaled bronchodilators (epinephrine and albuterol), systemic corticosteroids, inhaled hypertonic saline, and heliox. None of these therapies demonstrated a consistent benefit on mortality or length of hospitalization.23
Pneumonia24
Fifty percent to 70% of childhood pneumonia and up to 30% of adult pneumonia cases have been attributed to a viral etiology. Likely organisms include RSV, rhinovirus, influenza virus, hMPV, PIV, HBoV, and adenovirus.
Symptoms typically include fever, tachypnea, tachycardia, and clinical findings of lung involvement on examination. Other symptoms may include cough, rhinorrhea, sinus congestion, chills, and myalgias.
Physical examination and CXR may demonstrate consolidation due to alveolar or interstitial infiltrates in a lobar or multilobar distribution.
Viral pneumonia may be complicated by secondary bacterial pneumonia or concurrent viral and bacterial infection.
No specific clinical findings clearly differentiate viral from bacterial pneumonia. A high fever (>38.5°C), high respiratory rate, lobar consolidation on chest radiography and significantly elevated levels of C-reactive protein (CRP), white blood cell (WBC) count, and procalcitonin (PCT) suggest bacterial etiology.
Mild cases improve with supportive management on an outpatient basis, while severe cases may necessitate admission to an intensive care unit (ICU), respiratory support with mechanical ventilation or other aggressive measures.
Empiric antibiotics should be given in cases of severe pneumonia while awaiting culture results. Once confirmatory diagnostic testing is completed, therapy should be narrowed to target the pathogen.25
Specific antiviral therapies are discussed in more detail below.
Systemic corticosteroid use for viral pneumonia is controversial and effects may vary depending on the particular viral etiology.
Respiratory Virus Infections in Chronic Airways Disease
Viral lower respiratory tract infections in infants have been linked to later development of asthma in childhood, especially RSV and rhinovirus.
Viral respiratory infections can lead to exacerbations of asthma and COPD and more severe respiratory infections and prolonged disease courses in these patients.
RSV, influenza virus, rhinovirus, and parainfluenza are common culprits.
Patients with acute COPD exacerbation are more likely to have viruses detected in airway samples than those with stable COPD.
Influenza vaccinations of patients with asthma/COPD are recommended and may decrease the risk of exacerbations in some patients.
Respiratory Virus Infections in Special Adult Populations
Pregnancy26
Susceptibility to virus infections is unchanged during pregnancy. However, the severity of viral respiratory infections can be worse in pregnancy, especially during the second and third trimesters.
Treatment is supportive with hydration, antipyretics, oxygen, blood pressure, and ventilatory support. Specific antiviral therapy should be used if available.
Antipyretics help to prevent fetal tachycardia and congenital abnormalities related to high maternal fevers.
Acyclovir is classified as category B but is recommended only for cases of serious infection and not for routine use in pregnancy.
Ribavirin is a teratogen and is contraindicated in pregnancy.
Controlled data on the safety of many other antiviral compounds in pregnancy are lacking. Most (oseltamivir, zanamivir, ganciclovir, cidofovir) are classified as category C by the U.S. Food and Drug Administration (FDA) and should be used only when the benefits of therapy outweigh the risks.
Killed or inactivated vaccines have been shown to be safe in pregnancy, especially during seasonal outbreaks when benefits outweigh small risks. All pregnant females should be offered influenza vaccination.
Immunocompromised
Solid organ transplant recipients are at increased risk for developing cytomegalovirus (CMV), HSV-1, EBV, and varicella zoster virus (VZV), and more recently hMPV respiratory infections, especially in setting of prolonged respiratory failure in the ICU.
Adenovirus has also been documented in transplant recipients and may occur as a result of reactivation of latent virus.
Prevention
Vaccination, when available, remains the best means of preventing viral respiratory illness, but few vaccines are available.
Influenza vaccine
Vaccine strains may change yearly, so influenza vaccines must be administered annually.
Influenza virus vaccines are manufactured as an inactivated (killed virus) vaccine injection or as a live attenuated vaccine nasal spray.
High-dose influenza vaccination may be considered in adults ≥65 years old, though this is not expressly recommended by Centers for Disease Control (CDC) Advisory Committee on Immunization Practices.27
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