Viral Pneumonia

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Chapter 25 Viral Pneumonia

Ganapathi Iyer Parameswaran, Sanjay Sethi

Despite increasing recognition of the role of viruses in causing pneumonia in adults, either as sole pathogens or as copathogens with bacteria, diagnosis and treatment of viral pneumonias remain difficult clinical problems. Progress has been made in development of precise laboratory tests to diagnose lower respiratory tract infections of viral origin. Wider availability of such tests is likely to spur recognition and give impetus to development of new therapies.

Burden of Disease

Viral Community-Acquired Pneumonia

The proportion of pneumonias in adults that are caused by viruses is difficult to quantify with any precision. This lack of certainty is not surprising, because in approximately 50% of pneumonias, an identifiable pathogen cannot be established by conventional laboratory testing. Molecular techniques such as polymerase chain reaction (PCR) analysis improve this number but are rarely performed in routine clinical care. Difficulties in obtaining adequate specimens for viral cultures or molecular testing add to the problem. However, several recent studies have made efforts to quantify the burden of viral community-acquired pneumonias in adults and are summarized in Table 25-1. Although the proportion of viral pneumonias varies in these studies owing to differences in study populations and rigor of testing for viruses, it is clear that viruses cause a significant proportion of pneumonias. Overall, in immunocompetent adults hospitalized with pneumonia, viruses are the responsible pathogens in 15% to 30% of the cases, either by themselves or as copathogens with bacteria. Lower respiratory secretions such as bronchoalveolar lavage (BAL) fluid, tracheal aspirates, or good-quality induced sputum are preferable as specimens for diagnosis of viral pneumonia. Such specimens are more difficult to obtain, however, and most studies have used nasopharyngeal wash samples or swabs for culture and molecular testing. Presence of established pathogens such as influenza virus in such upper respiratory tract samples in a patient with pneumonia most probably implies that the virus is a sole or copathogen in causation of pneumonia; however, this general rule may not be applicable to other viruses. Presence of such viruses as rhinovirus might imply only upper respiratory infection in a patient with pneumonia due to another pathogen. Findings on studies of viral pneumonias must therefore be interpreted with some caution.

Table 25-1 Summary of Selected Clinical Studies of Viral Pneumonia

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Viral Pneumonia in Immunocompromised Patients

Patients who have undergone hematopoietic stem cell transplantation (HSCT) or solid organ transplantation or who are undergoing intensive chemotherapy for leukemias exhibit a higher incidence of viral upper respiratory infections than that in normal control subjects, as well as more frequent involvement of the lower respiratory tract, more severe pneumonias, and higher rates of death from viral pneumonia. All of the pathogens mentioned in Table 25-1 are represented in these patients. Respiratory syncytial virus (RSV), adenovirus, and parainfluenza virus, which usually cause only mild illness in immunocompetent persons, can cause severe pneumonias with high mortality rates in this high-risk patient population. Extrapulmonary manifestations of influenza infection, such as myocarditis, are not unusual in this population. RSV is the most common viral pathogen of the lower respiratory tract in patients who have undergone hematopoietic stem cell or solid organ transplantation, as reported in many series. Fulminant, disseminated adenoviral infections have been reported in patients with advanced human immunodeficiency virus (HIV) disease. Cytomegalovirus (CMV) infection is a major problem in stem cell and solid organ transplant recipients and probably is the most common viral pneumonia among patients who are not on prophylaxis or preemptive treatment regimens.

Pathogens

Although some variability has been documented in the frequency with which different viral pathogens are diagnosed as the etiologic agent of pneumonia in specific series, the most frequent pathogens are influenza A virus, influenza B virus, and RSV. In addition, parainfluenza viruses 1, 2, and 3 and adenovirus, coronaviruses, and rhinovirus also may cause pneumonia. Human metapneumovirus (hMPV) and, more recently, bocavirus have been recognized as pathogens. Rarer pathogens are CMV, varicella-zoster virus (VZV), herpes simplex virus (HSV), rubeola virus (the measles virus), and hantavirus.

Influenza Viruses

The most frequent viral pathogen implicated in causing pneumonia and increased mortality, influenza virus serotypes A and B, especially A, are responsible for outbreaks of respiratory illness each winter. Minor changes in hemagglutinin and neuraminidase proteins of the virus causing “antigenic drift” are responsible for seasonal influenza outbreaks. Although people of all ages are exposed to infection, the consequences of influenza-specific respiratory infection are more severe in certain groups of patients—elderly persons, nursing home residents, infants, those with severe coexisting cardiac and respiratory diseases such as congestive heart failure and chronic obstructive pulmonary disease (COPD), pregnant women, patients with immunosuppression due to hematologic malignancies, and those with HIV disease. Most of the deaths attributable to seasonal influenza occur in these groups. In addition, obesity has been associated with more severe disease and higher mortality in the recent H1N1 pandemic.

Major mutations in hemagglutinin and neuraminidase result in “antigenic shifts” and are responsible for pandemics. The most recently described is the current H1N1 (swine origin) virus pandemic starting in 2009. In contrast with seasonal influenza, the proportion of deaths in younger patients (18 to 65 years) has increased during pandemics. This increased mortality has been attributed to lack of previous exposure to a similar strain of the virus, with corresponding lack of protective antibodies, in patients who were not alive at the time of an earlier outbreak with a similar virus. This pattern has been seen in the current H1N1 pandemic.

Thus, influenza-related pneumonia occurs each year during the fall, winter, and spring seasons as a consequence of infection with circulating seasonal influenza viruses. Distinct from this pattern, pandemic influenza viruses cause pneumonias in explosive outbreaks. Such pandemic viral pneumonias differ from the seasonal disease in several ways: (1) Patients 18 to 65 years of age, especially those in the 20- to 45-year-old age group, are affected more often than in seasonal disease; (2) mortality due to influenza-related pneumonia is increased among adults 20 to 45 years of age; (3) the proportion of primary viral pneumonias is higher than in seasonal disease, in which most influenza-related pneumonias are due to bacteria; (4) viral influenza–related illness occurs outside of the usual influenza season; and (5) special risk factors for severe disease and mortality have been recognized, such as pregnancy and severe obesity. The recent H1N1 pandemic has infected more than 50 million persons in the United States alone, and caused approximately 18,000 deaths worldwide. Severe infections, consisting of pneumonia and acute respiratory distress syndrome (ARDS), typically have been seen in adults, with a median age of 40 years.

The true incidence of pneumonia in influenza respiratory infection is unknown, because most patients with influenza-related illness are evaluated and managed as outpatients without radiographs. Of a group of elderly adults with a high vaccination rate (greater than 90%), 2% to 6% were hospitalized with influenza-related illness; of these, only 5% had radiographically confirmed pneumonia. A significant proportion of such patients will have other illnesses, such as congestive heart failure, that precipitate hospitalization. Pneumonia developing during influenza infection can be one of two types: primary viral pneumonia or postinfluenza bacterial pneumonia. Louria and co-workers, reporting on the 1957-1958 pandemic, described four syndromes of lower respiratory tract illness due to influenza in New York City: (1) influenza illness with physical signs of lower respiratory involvement, but no infiltrates on the chest film; (2) influenza illness followed by bacterial pneumonia; (3) acute, rapidly progressive pneumonia due to influenza virus; and (4) concomitant viral and bacterial pneumonia. The histopathologic changes of influenza-related viral infection of the lower respiratory tract consist of desquamation of tracheobronchial epithelium, alveolar duct dilatation, hyaline membrane covering alveolar surfaces, and hemorrhage and inflammatory infiltrate in the alveolar spaces and interstitium.

Pathogenesis of Bacterial Pneumonia in Influenza

The association of influenza lower respiratory infection with bacterial pneumonia is striking. Such influenza-associated bacterial pneumonias, caused by Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus, including methicillin-resistant strains, are more frequent and severe than primary bacterial pneumonias due to the same pathogens. The seasonal incidence of S. pneumoniae infection in a community parallels the incidence of influenza illness. The mechanisms underlying the increased frequency and severity of these influenza-associated bacterial pneumonias are mostly unclear at present, but emerging evidence suggests roles for multiple viral and host factors. Increased apoptosis and desquamation of airway epithelial cells infected with influenza virus exposes multiple surface adhesins for pathogenic bacteria. Influenza viruses expressing PB1-F2, a proapoptotic protein that interferes with mitochondrial function and increases epithelial cell apoptosis, increase susceptibility to S. pneumoniae infection. When infected with viral strains lacking PB1-F2, mice were less susceptible to bacterial pneumonia, compared with those infected with wild-type viral strains. Moreover, influenza infection decreases the efficacy of airway mucociliary clearance, and thus clearance of pathogenic bacteria.

Viral neuraminidase increases bacterial growth and dissemination, and adherence of S. pneumoniae to airway epithelial cells in mouse models. Influenza strains with high neuraminidase activity are associated with higher mortality after bacterial infection. Influenza virus inhibits neutrophil chemotaxis and phagocytic capacity; inhibits, through induction of IFN-γ, macrophage receptor with collagenous structure (MARCO) production by macrophages. MARCO is a scavenger protein involved in macrophage recognition and killing of bacteria. Influenza virus also causes desensitization of Toll-like receptors (TLRs), and this desensitization persists for several weeks.

Primary Influenza-Related Viral Pneumonia

The true incidence of primary influenza pneumonia is unknown, because many patients do not undergo radiography or detailed clinical evaluation. It originally was considered that most of the deaths in the 1918 influenza pandemic were due to primary viral pneumonia. Later analysis of multiple data sources, however, strongly suggested that a majority of deaths (approximately 80%) from influenza-related pneumonia were due to secondary bacterial (postinfluenza) pneumonias, caused primarily by S. pneumoniae and H. influenzae and other gram-negative organisms such as Klebsiella pneumoniae and Escherichia coli. A series of 33 patients with influenza-related pneumonias and deaths from the 1957-1958 pandemic again showed that a majority of deaths were due to bacterial pneumonia. Of 33 patients, 15 had acquired bacterial pneumonia after influenza illness; six had primary viral pneumonia with isolation of influenza virus, but no bacterial pathogen, from lung tissue; and nine had concomitant bacterial and viral pneumonia. In the recent (2009) H1N1 virus pandemic, initial reports suggested that deaths were mostly due to viral pneumonia. Further analysis of autopsy lung specimens showed that in approximately 30% of these deaths, a bacterial pathogen could be identified by molecular studies. However, the proportion of viral pneumonia (approximately 70%) is striking and higher than in previous pandemics. Moreover, S. aureus, especially methicillin-resistant S. aureus (MRSA), was found in a significant proportion of bacterial pneumonias, with high mortality, especially among teenage patients. Therefore, in summary, primary viral as well as secondary bacterial infections, including those due to MRSA, must be considered in every case of influenza-related pneumonia and treated presumptively until full identification of the pathogens involved is obtained.

The typical clinical course of primary viral pneumonia is described as progression of the initial upper respiratory tract symptoms to shortness of breath, increased cough and sputum, and respiratory failure, as compared with secondary bacterial pneumonia, in which a period of improvement after the initial influenza infection is followed by new and worsening respiratory symptoms due to pneumonia. The sputum often is thin and blood-stained in primary viral pneumonia. Radiographs usually show bilateral interstitial or infiltrative opacities, which may mimic the appearance of congestive heart failure.

Respiratory Syncytial Virus

Long considered to be a pathogen of children only, RSV is now recognized as a significant pathogen in elderly and immunocompromised adults. It is the second most common pathogen in most series of viral pneumonias. Similar to the influenza viruses, RSV causes winter outbreaks of respiratory illness. It is estimated that in most populations of nursing home residents, approximately 10% develop RSV respiratory infections each year. Most of these are self-limiting upper respiratory infections; the remaining 10% or so develop pneumonia. Centers for Disease Control and Prevention (CDC) surveillance data suggest that RSV infections are responsible for about 10,000 deaths annually in elderly patients living in the community. In one prospective series of elderly adults, RSV was the responsible pathogen in 11% of patients hospitalized with pneumonia during winter months. Chest radiographs often show bilateral fluffy infiltrates.

Human Metapneumovirus

Since being described as a cause of respiratory illness in children in 2001, hMPV is now recognized to cause pneumonias in adults, especially elderly patients with cardiopulmonary diseases. A prospective study, using reverse transcriptase PCR testing of nasopharyngeal samples, found evidence of hMPV infection in 4% of 193 adults hospitalized with pneumonia during an influenza season. Evidence of hMPV infection was present, by PCR analysis of nasopharyngeal aspirate and/or paired serologic samples, in 4% of adults visiting an emergency department in Canada with pneumonia or exacerbation of COPD.

Parainfluenza Viruses 1, 2, and 3

Parainfluenza viruses 1, 2, and 3 cause upper respiratory infections as well as pneumonia in elderly adults, especially nursing home residents. A study in Sweden found serologic evidence for recent parainfluenza virus infection in approximately 10% of community-acquired pneumonias in elderly persons.

Coronaviruses

Several coronavirus strains cause the common cold during winter months. Pneumonia has been described in elderly persons and immunocompromised patients; the frequency of such infections is not known. In 2002, a novel strain, SARS-CoV, spread around the globe, causing an acute pneumonia and ARDS.

Rhinovirus

The most frequent cause of the common cold was thought to be not a pathogen in the lower respiratory tract. However, the advent of molecular methods such as real-time PCR analysis has demonstrated that in many patients, especially in those with chronic respiratory diseases such as COPD or immunosuppression, rhinovirus is present in the lower airways during pneumonia. The role of rhinovirus as a sole pathogen in causation of pneumonia is still a matter of debate and research.

Varicella-Zoster Virus

Pneumonia associated with chickenpox in adults is a well-recognized complication and continues to occur each year in the United States. When chickenpox occurs in adults, the incidence of pneumonia as a complication is increased by approximately 25-fold over that in children. Except in rare instances, such pneumonia is associated with the rash typical of the disease. A study of military recruits revealed that radiographic lung abnormalities are much more common than signs and symptoms of pneumonia—that is, most lung involvement is subclinical. Mortality rates for severe pneumonia leading to respiratory failure have decreased over the last few decades owing to improvements in ventilatory support and prompt therapy with acyclovir.

Clinical Features

Viral pneumonias in general have the same clinical symptoms (cough, shortness of breath, increased sputum, and chest pain) and signs (radiographic consolidation, fever, tachycardia, tachypnea, reduced arterial oxygen saturation) as those of bacterial pneumonias. Some clinical features occur more often in viral pneumonias than in bacterial pneumonias, although this distinction is not precise enough for a diagnosis to be made on clinical evaluation without further testing, except in rare situations. Patients with viral pneumonias tend to be older and frailer, with other comorbid conditions such as cardiac failure and COPD; have less chest pain, tachycardia, and fever; and show lower levels of leukocytosis than in the characteristic clinical picture in bacterial pneumonias. Features such as rhinitis, conjunctivitis, and pharyngitis or a typical rash for varicella or measles can point to a viral etiology for pneumonia. Gastrointestinal complaints often accompany influenza-related infections. RSV infections are more likely to be associated with wheezing than influenza virus infections. Chest radiographs show lobar infiltrates or basal atelectasis–like patterns, and infiltrates often are bilateral; these features are not specific enough, however, to allow clinical differentiation between viral and bacterial pneumonia. Varicella pneumonia often causes nodular lung lesions on chest films, although interstitial infiltrates also are described. The difficulties in differentiating between viral and bacterial pneumonias on clinical features alone are illustrated by a study that compared findings on the chest radiograph in children with community-acquired pneumonia. In children with alveolar infiltrates, 71% had a bacterial cause; in those with proven bacterial pneumonia, 72% had alveolar infiltrates; and in those who had only interstitial infiltrates, approximately 50% had a bacterial cause. CT scans show a variety of appearances—ground glass opacities, nodules, and lobular and segmental infiltrates.

Serum procalcitonin levels are being increasingly used to guide decisions regarding the need for antibacterial therapy. A very low level may indicate a low likelihood of bacterial infection in lower respiratory infections. This association, however, does not imply that the cause is viral. To establish a viral cause, another diagnostic method (culture or PCR assay) is still necessary.

Diagnosis

The accuracy of clinical features in predicting a viral infection depends on the pretest probability of viral respiratory infection in a given population. In one series of 258 patients seeking emergency or urgent care for acute respiratory symptoms during influenza season, clinical judgment had sensitivity and specificity of 29% and 92%, respectively, in diagnosing influenza; the figures improved to 67% and 96% if patients presented within 48 hours of symptom onset. Patients with viral pneumonia, however, often do not have accompanying upper respiratory symptoms, and the symptoms and signs overlap with those of bacterial pneumonia.

Attempts at precise definition of the roles and frequency of these viruses in causing pneumonia have been hampered by difficulties in viral culture, and by a nihilistic attitude among medical professionals stemming from lack of effective therapy against many of these viruses. Precise diagnosis of viral causes for pneumonia has multiple benefits: (1) Public health measures against spread of highly infective viruses such as influenza viruses and RSV can be better coordinated. (2) Attempts at development of effective therapies can be supported with increasing recognition of the etiologic roles of these viruses. (3) Unnecessary antibiotic therapy can be curtailed. (4) Infection control and prophylaxis measures can be implemented in hospitals and nursing homes.

A variety of clinical specimens are suitable for diagnosis of viral pneumonia. These include, in order of preference, lung tissue and BAL fluid, nasopharyngeal wash sample, nasopharyngeal swabs, and sputum. BAL often is avoided because of its invasive nature but nevertheless is desirable in immunocompromised and critically ill patients, in whom a specific diagnosis is necessary and co-infections are common. Diagnosis of viral infection in a patient with pneumonia can be attempted by one or more of four methods, as summarized in Table 25-2.

Table 25-2 Commonly Used Methods for Diagnosis of Viral Lower Respiratory Infection

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Culture of virus from clinical specimens, using tissue culture cells, remains the standard diagnostic modality. However, it is labor-intensive, requires expertise in culture techniques and recognition of the effects of virus on cells, and is not always available except in large laboratories. Sending specimens out to reference laboratories is problematic, because many viruses tolerate such transportation poorly. Moreover, some viruses such as rhinovirus, hMPV, and some coronaviruses grow poorly in tissue cultures, and the results of viral culture take several days to become available. With all of these caveats, if a suitable specimen is available, culture should be attempted on samples obtained in patients suspected to have viral pneumonia. Shell vial cultures, especially when combined with immunofluorescent antibody staining of cells, has higher sensitivity than that of tube culture.

Serologic testing had been a mainstay in retrospective diagnosis of viral infections and remains an important epidemiologic tool. However, owing to the requirement for paired samples separated by 4 weeks to demonstrate a significant increase in IgG titers, serologic studies are now rarely used in clinical diagnosis of viral pneumonia.

Antigen detection can be performed in most respiratory secretions using direct fluorescent antibody (DFA) and enzymatic immunoassay (EIA) tests. DFA testing, performed by treating samples with a virus-specific antibody tagged with a fluorophore and a fluorescence microscope, often is used in conjunction with shell vial culture of viruses from respiratory secretions. EIAs are available for detection of influenza A virus in kit form (Rapid Influenza Diagnosis Test [RIDT]). Although highly specific (90% to 95%), these rapid tests have lower sensitivity (approximately 70%) compared with viral culture and molecular methods, especially when the viral load is low. A rapid antigen detection test is available for RSV; its sensitivity is very low compared with that of culture—only about 10%.

Molecular methods depend on detection of virus-specific genetic material. Reverse transcriptase PCR (RT-PCR), nucleic acid sequence–based amplification (NASBA), and real-time RT-PCR methods have been used. These methods have sensitivity (97% to 99%) and specificity (90% to 95%) similar to and often better than viral culture. Real-time PCR results are available the same day and can distinguish between strains such as H1N1 and H3N2. Commercially available tests using multiple primers, allowing testing for a panel of viruses, are becoming more common in large laboratories. The x-TAG RVP assay, approved by the U.S. Food and Drug Administration (FDA), tests for 12 viruses commonly implicated in respiratory illness. Even broader tests, using panviral gene microarrays, are being used as research tools and may soon be available for clinical use.

Patients suspected on clinical grounds to have influenza pneumonia should be tested for influenza using RIDT. If the result of this test is negative, viral culture of respiratory secretions (nasopharyngeal swab or wash sample, BAL fluid, endotracheal aspirate) should be performed. If available, a nucleic acid amplification test such as PCR assay should be performed on these specimens. In patients suspected to have other (or unknown) viral pneumonias, viral culture and, if available, a multiplex viral PCR assay are indicated.

Treatment

With pneumonias caused by the aforementioned viruses, effective treatment is available for those due to influenza A and B viruses, VZV, and possibly RSV. Available antiviral drugs are (1) adamantanes (amantadine and rimantadine); (2) neuraminidase inhibitors (oseltamivir, zanamivir, and, provided by the CDC on a case-by-case basis, peramivir); (3) ribavarin; and (4) acyclovir and its derivatives valganciclovir and famciclovir.

The adamantanes—amantadine and rimantadine—are no longer recommended for treatment of influenza owing to widespread resistance of the virus strains and should not be used in treatment of viral pneumonias. Of the neuraminidase inhibitors, oseltamivir is available orally only; zanamivir as an inhaled powder; and peramivir as an intravenous formulation. Ribavirin is available in oral formulation and as a liquid for aerosol administration and has been used intravenously in small series of patients.

The neuraminidase inhibitors are effective in reducing duration of symptoms for outpatients with influenza-related upper respiratory infection, when started within 48 hours of onset of symptoms. Efficacy against influenza pneumonia is unclear. A large Canadian study of adults hospitalized with seasonal influenza–related infections showed reduction in mortality and hospital stay when oseltamivir was started even later than 48 hours. The CDC currently recommends neuraminidase inhibitor treatment for all adults with severe influenza-related illness. It seems reasonable, therefore, to use one of these agents for any patient suspected to have influenza-related pneumonia, whatever the duration of symptoms, while etiologic investigations are under way. This approach also means that any patient with possible viral pneumonia during seasonal influenza season or during an influenza pandemic should receive oseltamivir while appropriate studies are undertaken to identify the specific etiologic agent of pneumonia.

Zanamivir is an alternative to oseltamivir. It is available only as an inhalant. Zanamivir can provoke wheezing and clog nebulizers (the CDC advises against using this agent in a nebulizer) and probably should be avoided in patients with respiratory compromise. Increasing resistance to oseltamivir is being reported in influenza A virus. These strains remain sensitive to zanamivir and peramivir. Oseltamivir is less active against influenza B virus than against influenza A virus; zanamivir is preferred if influenza B virus is known to be the etiologic agent, in the absence of contraindications to its use. The incidence of resistance to oseltamivir in the United States remains low, as reported by the CDC (less than 1% for H1N1 and H3N2) in April 2011 (http://www.cdc.gov/flu/weekly/).

In patients who do not respond to or who deteriorate while on oseltamivir, and if drug resistance is suspected, intravenous peramivir is available from the CDC. A recent uncontrolled case series shows promising results in such patients with use of intravenous peramivir. Drug sensitivity testing for cultured viral strains is available in reference laboratories and at the CDC.

Ribavirin is active against RSV. However, efficacy in RSV-related lower respiratory infections in adults is unproved. Limited evidence for efficacy comes from small case series of patients with immunocompromised states such as hematopoietic stem cell transplantation and patients undergoing chemotherapy for leukemia. Its use in adults critically ill with pneumonia and proven RSV infection should be considered carefully, with involvement of a physician who has some experience in using ribavirin in such situations. Ribavirin aerosol often is combined with intravenous immunoglobulin to treat severe RSV infections in immunocompromised patients. In addition, testing and, during the wait for results, initial treatment for bacterial pneumonias should be added. Ribavirin can cause hemolytic anemia. Aerosol use introduces hospital staffing problems, because this agent is teratogenic in animal experiments, and accidental exposure of women of reproductive age must be avoided. In VZV pneumonia, antiviral treatment with intravenous acyclovir should be given.

In every patient with suspected influenza-related lower respiratory infection, bacterial pneumonia due to S. pneumoniae, H. influenzae, or S. aureus including MRSA is a major consideration. Bacterial cultures should be performed, and antibiotics effective against these pathogens should be prescribed.

Controversies and Pitfalls

Probably the major reason for underdiagnosis of viral pneumonia is an inappropriately low level of clinical suspicion and corresponding lack of laboratory testing. During influenza season or a pandemic outbreak, the clinical management plan for every patient with pneumonia should include consideration of viral pneumonia. Similarly, any pneumonia in an immunosuppressed patient or elderly nursing home resident should raise suspicion for a viral cause. In patients with suspected influenza-related pneumonia, bacterial infection, especially due to S. pneumoniae, H. influenzae, or S. aureus including MRSA, should be a consideration in laboratory testing and initial treatment, because it is not possible to distinguish between viral and bacterial pneumonia with certainty on clinical examination alone.

Diagnosing viral lower respiratory infections using upper respiratory samples such as nasopharyngeal washings inevitably raises the question of whether the identified virus is involved in the lower respiratory infection. This remains an area to be explored. Pending further data, clinical judgment of whether the virus detected from upper respiratory samples might be responsible for pneumonia is necessary. When serious pathogens such as influenza virus are detected in a patient with pneumonia, the prudent approach is to assume that the patient has a viral and possibly a secondary bacterial pneumonia and treat accordingly. The situation is much less clear cut for less well-established lower respiratory tract pathogens such as hMPV, bocavirus, and rhinovirus. Recent evidence shows that high viral load in nasopharyngeal samples, as determined using quantitative PCR assay, correlates with an increased chance that the lower respiratory disease is due to the virus. Such tests are not commonly available.

Although good evidence supports the efficacy of antiviral drugs in treatment of influenza-related pneumonia, treatment of RSV infections in adults with ribavirin is controversial. There are no high-quality, controlled trials of ribavirin in adults to date. Based on small uncontrolled case series, expert opinion favors use of ribavirin and intravenous immunoglobulin in hematopoietic stem cell transplant recipients with RSV-related lower respiratory infections. Although it may be reasonable to extend this approach to patients with other serious immunocompromising conditions such as solid organ transplantation and prolonged steroid therapy, ribavirin use in elderly patients with no identified immunocompromising conditions is based on anecdotal reports and has to be approached on a case-by-case basis with advice from a physician who is experienced in treatment of RSV infections.

Conclusions

Advances in molecular methods of diagnosis have increased awareness and recognition of the role of viruses in causing pneumonia in immunocompetent as well as immunosuppressed adults. The list of viruses capable of causing such pneumonias is increasing. Although current therapeutic options are mostly limited to influenza infection, increasing recognition of viral pneumonias and underlying pathogenetic mechanisms would spur research and development of more effective and varied therapies.

Suggested Readings

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Bautista E, Chotpitayasunondh T, Gao Z, et al. Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med. 2010;362:1708–1719.

Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006;42:518–524.

Falsey AR, Hennessey PA, Formica MA, et al. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med. 2005;352:1749–1759.

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McGeer A, Green KA, Plevneshi A, et al. Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis. 2007;45:1568–1575.

Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, et al. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med. 2009;361:680–689.

Rello J, Pop-Vicas A. Clinical review: primary influenza viral pneumonia. Crit Care. 2009;13:235.

Shah JN, Chemaly RF. Management of RSV infections in adult recipients of hematopoietic stem cell transplantation. Blood. 2011;117:2755–2763.

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