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Respiratory Viral Infections in High-Risk Patients

Posted on: Wednesday, 15 December 2004, 03:00 CST

Improved diagnostic tests have redefined the role of viruses as causes of acute respiratory disease in high-risk patients. Over the past decade, epidemiologic studies have demonstrated that respiratory viruses are commonly associated with acute exacerbations in adults with asthma, chronic obstructive pulmonary disease, and/ or underlying malignancy (1-4). With the use of polymerase chain reaction (PCR) technology, the most commonly identified viruses and their prevalence in these patient populations have been better defined (5-8). In addition to influenza virus and respiratory syncytial virus (RSV), rhinoviruses, coronaviruses, and parainfluenza viruses are now the most frequently identified viruses in these patients.

In the current issue of the Journal (pp. 1197-1203), Garbino and colleagues report on a retrospective study of respiratory viruses identified in immunocompromised, hospitalized patients with acute respiratory illness (9). During one winter season, a sampling of bronchoalveolar lavage specimens from patients with or without a clinical likelihood of acute respiratory infection were tested by a qualitative real-time (RT-)PCR assay for eleven different respiratory viruses as well as Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila. Of the 148 processed specimens, 29% of those with suspicious clinical symptoms (Group 1) had a virus detected. In a control group without clinical symptoms (Group 2), only 6% tested positive for a respiratory virus. Mycoplasma pneumoniae was found rarely. Rhinoviruses (55%) and RSV (25%) accounted for the majority of the documented infections. Adenoviruses, influenza viruses, coronaviruses, and parainfluenza viruses were far less common. No human metapneumoviruses (hMPVs) were detected in these patients. Dual viral infections were observed in five cases (15%). Human cylomegaloviruses were detected equally in both groups. In a subgroup of lung transplant recipients, respiratory viruses were found in 55% (Group 1) and 4% (Group 2) of patients. Rhinoviruses and RSV accounted for over 80% of the identified viruses. An increase in morbidity, as measured by persistent decrease in FEV^sub 1^ over 3 months, was more common in Group 1 patients. However, there was no difference in mortality between the two groups.

Multiple studies have shown the value of RT-PCR in identifying respiratory viruses in clinical samples (6, 8, 9). As much as a three- to fourfold increase in positive specimens has been found when PCR testing is added to conventional cell culture and/or "standard" serologic methods. Improved detection depends on the patient population studied as well as the culture system employed. The greatest benefit appears to be in detecting rhinoviruses, coronaviruses, and parainfluenza viruses. This has led to a new appreciation for the contribution of these difficult-to-culture respiratory viruses to the etiology of acute respiratory disease in adults.

In transplant recipients, respiratory viruses contribute to mortality and/or prolonged hospitalization (2). In patients with asthma and chronic obstructive pulmonary disease, these viruses account for almost half of the illnesses in hospitalized patients and provide another trigger for acute exacerbations (10, 11). The current study from Switzerland, plus other recent series (2, 3, 10, 12), highlight the clinical impact and cost of these infections. Many patients received unnecessary antibiotics and required extended hospitalization, including mechanical ventilation.

While there have been significant changes in our understanding of the epidemiology and impact of respiratory viral infections in high- risk patients, there have been few advancements in their prevention and treatment. The only approved vaccine for viral infections is for influenzaviruses. Newer RSV vaccines are being developed, but are years away from being approved (13). Prophylaxis for RSV has been shown to be effective in premature infants given a humanized mouse monoclonal antibody, Palivizumab (14).

Only a few approved antivirals are available for respiratory viral infections. Amantadine and rimantadine are useful for influenza type A only. The newer neuraminidase inhibitors, osellamivir and zanamivir, are approved for influenzavirus type A and B. These drugs should be considered for prevention and early treatment when influenzavirus is known to be circulating in the community. Ribavirin is approved for the treatment of RSV infections (15).

Because there are multiple serotypes of rhinoviruses (> 100) causing respiratory infections, it is unlikely that a vaccine will be developed. For the foreseeable future, vaccines for coronaviruses and parainfluenzaviruses are not likely to be clinically available. In addition, there are no antivirals currently approved for prevention and treatment of rhinoviruses, coronaviruses, and parainfluenzaviruses. Several antivirals, such as interferon and pleconaril, are effective against rhinoviruses, but side effects in clinical trials have precluded their approval for general clinical use (16, 17). Serious consideration should be given to reevaluating these antivirals in these high-risk adults. Because timely interventions will be possible with readily available diagnostics, we should refocus our efforts on finding safe and effective antiviral drugs against clinically important viruses, including rhinovirus and RSV, that have now been identified to play a major role in causing acute respiratory illness.

Conflict of Interest Statement: S.B.G. has received consultancy fees from ViroPharma and GlaxoSmithKline in 2001.

References

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2. Whimbey E, Champlin RE, Couch RB, Englund JA, Goodrich JM, Raad I, Przepiorka D, Lewis VA, Mirza N, Yousuf H, et al. Community respiratory virus infections among hospitalized adult bone marrow transplant recipients. Clin Infect Dis 1996;22:778-782.

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12. Marcolini JA, Malik S, Suki D, Whimbey E, Bodey GP. Respiratory disease due to parainfluenza virus in adult leukemia patients. Eur J Clin Microbiol Infect Dis 2003;22:79-84.

13. Kneyber MC, Kimpen JL. Advances in respiratory syncytial virus vaccine development. Curr Opin Investig Drugs 2004;5:163-170.

14. Group TIRS. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 1998;102:531-537.

15. Maggon K, Barik S. New drugs and treatment for respiratory syncytial virus. Rev Med Virol 2004;14:149-168.

16. Hayden FG, Turner RB, Gwaltney JM, Chi-Burris K, Gersten M, Hsyu P, Patick AK, Smith GJ III, Zalman LS. Phase II, randomized, double-blind, placebo-controlled studies of ruprintrivir nasal spray 2-percent suspension for prevention and treatment of experimentally induced rhinovirus colds in healthy volunteers. Antimicrob Agents Chemother 2003;47:3907-3916.

17. Wat D. The common cold: a review of the literature. Eur J Intern Med 2004;15:79-88.

DOI: 10.1164/rccm.2409002

STEPHEN B. GREENBERG, M.D.

Baylor College of Medicine

Houston, Texas

Copyright American Thoracic Society Dec 1, 2004

Source: American Journal of Respiratory and Critical Care Medicine

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