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Diagnosis and Treatment of Rhinovirus Respiratory Infections^*

^* From the South Texas Veterans Health Care System (Dr. Anzueto), Audie L. Murphy Memorial Veterans Hospital Division, San Antonio, TX; and the Department of Medicine (Dr. Niederman), Winthrop University Hospital, State University of New York at Stony Brook, Mineola, NY.

Correspondence to: Antonio Anzueto, MD, Audie L. Murphy Memorial Veterans Hospital, Pulmonary Diseases Section (111E), 7400 Merton Minter Blvd, San Antonio, TX 78284; e-mail: ANZUETO{at}UTHSCSA.EDU

	Abstract

TOP Abstract Introduction Diagnosis of VRI Role of Picornaviruses in... HRVs Complications of VRIs VRIs in Children VRIs in Adults Management of VRIs Symptomatic Treatment of VRIs Antiviral Agents Conclusion References

 
Acute upper viral respiratory infection (VRI) is the number one cause of illness for which patients seek medical care in the United States. Rhinoviruses, members of the family Picornaviridae, are the causative pathogens in more than half of VRIs, and they are associated with acute exacerbations of respiratory disease, including asthma, sinusitis, otitis media, and COPD. Owing to the lack of commercial availability of rapid and cost-effective laboratory tests to confirm the presence of VRI, the diagnosis is most commonly made empirically, based on patient history and physical examination. Currently, no antiviral agents that are active against picornaviruses are available for clinical use. Antimicrobial agents, frequently prescribed for VRIs, are not active against viruses, and their inappropriate and widespread use has contributed to an increase in antimicrobial resistance among bacteria commonly involved in respiratory tract infections. Several newer antiviral agents are being evaluated for treatment of VRIs. Although a variety of mechanisms and agents have been tested, few have shown significant clinical benefit in human trials. The most advanced antiviral agent in clinical trials is pleconaril, a novel viral capsid–binding inhibitor with potent and highly specific in vitro activity against the majority of serotypes of rhinoviruses and enteroviruses. Clinical trials of pleconaril for the treatment of VRIs have been conducted, and the role of pleconaril in patients with chronic lung disease is being evaluated.

Key Words: antiviral agents • asthma • COPD • otitis media • pleconaril • rhinoviruses • sinusitis • viral respiratory infection

	Introduction

TOP Abstract Introduction Diagnosis of VRI Role of Picornaviruses in... HRVs Complications of VRIs VRIs in Children VRIs in Adults Management of VRIs Symptomatic Treatment of VRIs Antiviral Agents Conclusion References

 
Acute upper respiratory tract infection (URI), is the most widespread type of acute infection in humans.¹ Viral respiratory infections (VRIs) are cited as the most frequent reason for visits to clinicians.² Although VRIs have been considered to be generally self-limited illnesses, their impact on society, quality of life, and productivity is, in fact, significant.³

Epidemiologic data vary, but most experts agree that annually in the United States, VRIs account for a minimum of approximately 20 million absences from work and 22 million absences from school.^{3 4} In 1998, there were an estimated 84 million ambulatory office visits for acute respiratory infections, 76 million of which (90%) were managed by primary care physicians.⁵ Depending on the survey conducted, schoolchildren average five to eight colds per year.^{3 4 6} The frequency of VRIs among children declines over time, although a higher incidence may be found among children who attend day-care centers.^{3 6} Adults average two to four colds per year, presumably because immunity develops against organisms associated with respiratory infections.^{3 6 7}

The search for a "cure" for VRIs has been ongoing for centuries. In the United States each year, consumers seeking relief from cold symptoms spend $2 billion³ to $3 billion⁷ on selections from > 2,800 over-the-counter products, which include antihistamines, analgesics, antitussives, and anti-inflammatory agents that are marketed to treat cold symptoms.^{3 8}

VRIs and their related sequelae are among the most frequent illnesses for which antimicrobial agents are prescribed in the United States.² A viral etiology is suspected in more than half of all colds and URIs.² Despite their lack of activity against viruses, antibiotics are the mainstay of therapy for VRIs in adults⁹ and children.¹⁰ These practices have contributed to the widespread emergence of antimicrobial-resistant pathogens.²

	Diagnosis of VRI

TOP Abstract Introduction Diagnosis of VRI Role of Picornaviruses in... HRVs Complications of VRIs VRIs in Children VRIs in Adults Management of VRIs Symptomatic Treatment of VRIs Antiviral Agents Conclusion References

 
Symptoms of viral URI most commonly include rhinorrhea, nasal congestion, and sore throat. Other common symptoms are nonproductive cough, sneezing, facial pressure, and headache, and less commonly malaise, myalgias, and low-grade fever.² Because these symptoms may be present with a bacterial URI, it has been a challenge for clinicians to differentiate viral from bacterial causes. Now that agents specifically targeted to respiratory viruses have been developed and may become available, it has become more important to distinguish the causative organism as viral or bacterial, so that the patient can be given appropriate treatment. It is hoped that the additional benefit of more accurate diagnosis will reduce the widespread use of antimicrobial agents for the treatment of viral URIs and thereby stem the increasing rates of bacterial resistance to current antimicrobial agents.

A complete physical examination for VRI includes a thorough inspection of the pharynx, nasal cavity, ears, and sinuses. In patients who are symptomatic for VRI, an examination of the nasal cavity may reveal postnasal discharge and erythema around the nose and mucous membranes, although normal variations in color may make erythema difficult to distinguish. Proteinaceous exudates and increased mucus secretion may give the nasal mucous membranes a glassy appearance.¹¹

Clinicians often treat patients with respiratory viruses empirically, owing to a lack of on-site laboratory testing capabilities for viruses. The serology assays require paired specimens and are not useful for timely diagnosis. Virus isolation performed with cell cultures is the "gold standard," but the sensitivity is variable.¹² Furthermore, cultures take 3 to 7 days to yield results, require specific technical expertise, are labor-intensive, expensive, and have a high percentages of false-positive and false-negative results.² The direct testing of patient specimens with simplified antigen assays has become more common and has been developed for detection of a variety of viruses. The development of molecular assays for the direct detection of viruses has been actively growing in recent years. The first commercial assays were based on hybridization with DNA probe technology to detect specific ribosomal RNA (Gen-Probe; San Diego, CA). This system uses single-stranded DNA probes to detect complementary ribosomal RNA sequences of the targeted virus. Application techniques such as direct antigen identification, reverse transcriptase polymerase chain reaction (RT-PCR), and ligase chain assays provide increased sensitivity because of the extensive amplification of the target nuclei assay that can be done. Commercial amplification systems for clinical laboratory use in viral detection have been approved by the US Food and Drug Administration. At present, however, the spectrum of validated assays is limited, and the performance of these assays is technically complex and requires well-trained and knowledgeable personnel. Although they are not readily available for clinical use, cultures, serology, and RT-PCR assays can be used to identify picornaviruses.¹² More rapid techniques, including optimized microplate in situ cellular enzyme-linked immunosorbent assays, are in development and have been used successfully to test for influenza viruses. These tests have been found to be as reliable as plaque-reduction assays for detecting the presence of influenza.¹³

Bacteria also may be the causative agents in infections of the pharynx, ears, and sinuses, and they typically present clinically as localized infections. Pharyngeal pain, dysphagia, and exudates in the pharynx raise suspicion of bacterial infection (in particular, with group A ß-hemolytic streptococcus), which is confirmed by rapid antigen detection tests and microbiological testing.^{1 11} A bright red, bulging, opaque tympanic membrane and the presence of fluid in the middle ear are characteristic findings in patients with otitis media.¹ Bacterial sinusitis, which frequently presents with symptoms of URIs, is most often secondary to a viral infection and typically follows a cold or periods of allergic rhinitis.¹⁴

	Role of Picornaviruses in VRI

TOP Abstract Introduction Diagnosis of VRI Role of Picornaviruses in... HRVs Complications of VRIs VRIs in Children VRIs in Adults Management of VRIs Symptomatic Treatment of VRIs Antiviral Agents Conclusion References

 
The family of picornaviruses is the most common source of human viral infections in the world.² Named for their small size (approximately 30 nm) and RNA genomes, picornaviruses are ubiquitous and include human rhinoviruses (HRVs), enteroviruses, and hepatoviruses.⁸ Variations of capsid proteins containing the viral genome produce > 100 distinct HRV serotypes.¹⁵ Nearly 70 serotypes of enteroviruses exist, including polioviruses and coxsackieviruses.¹⁶

	HRVs

TOP Abstract Introduction Diagnosis of VRI Role of Picornaviruses in... HRVs Complications of VRIs VRIs in Children VRIs in Adults Management of VRIs Symptomatic Treatment of VRIs Antiviral Agents Conclusion References

 
Ever since their identification from cell and organ cultures in the 1950s,⁶ HRVs have been used to study the pathogenesis of colds.¹⁴ A number of studies have confirmed rhinoviruses as being the most common cause of VRIs. In studies conducted by Arruda and colleagues,¹⁷ rhinovirus was found in 80% of patients tested who had URIs and colds over the fall season (ie, September through October). Other studies¹² have confirmed a high prevalence of rhinovirus in VRIs, with seasonal peaks in the fall and early spring (ie, March and April).

HRV Pathogenesis and Transmission
Following inoculation into the nasal cavity, HRVs are transported to the posterior nasopharynx, primarily by ciliated epithelial cells. In the nasopharynx, they gain entry into the host cell following attachment to intercellular adhesion molecule (ICAM)–1, a rhinovirus receptor found in the nasal epithelium and adenoids. The resulting viral infection stimulates the parasympathetic nervous system and activates several inflammatory pathways. The host response to the virus is believed to be the major cause of cold symptoms.^{3 4 18} As the cold progresses, the virus moves more anteriorly in the nares.¹⁸ The prominent symptoms of rhinorrhea and nasal obstruction result from increased vascular permeability, with leakage of serum into the nasal mucosa and nasal secretions. Cold symptoms also are caused by neurogenic reflexes triggered by the infection.^{3 18} The inflammatory mediators interleukin (IL)-1, IL-6, IL-8 have been found in the nasal secretions of symptomatic subjects and are responsible for symptoms.^{3 18}

Although there is some controversy about the principal mode of transmission of HRV, direct contact appears to be the most efficient means of transmission.³ HRV infections also have been documented to be spread as large-particle and small-particle aerosols, but, regardless of the route of transmission, the initiation of infection occurs when contact is made between the virus and nasal mucosa.³ Typically, HRV transmission occurs in the home with a child attending day care or a school-age child as the most frequent introducer of the infection.^{1 3 15} Infection is spread from hand-to-hand contact with contaminated nasal secretions, usually from child to mother. Self-inoculation from eye-rubbing or nose-picking also spreads infection.^{2 18}

Symptoms occur within 16 h of inoculation and peak from 24 to 48 h postinoculation.¹⁹ The virus can be recovered 24 h after nasal inoculation, and shedding peaks on days 2 to 3.¹⁹ Viral shedding persists after the resolution of symptoms, and the virus may be cultured from 10 to 20% of subjects 2 to 3 weeks after infection.³ Arruda and colleagues¹⁷ found the median duration of a cold caused by HRV to be 9.5 to 11 days. In certain populations such as the elderly, however, Nicholson and coworkers²⁰ found the median duration to be 16 days. Sore throat is usually the first sign of infection. Other prominent symptoms initially experienced by patients are rhinorrhea and nasal congestion.¹⁷ Facial or sinus pressure, headache, and cough are also common. In adults, fever is uncommon, although low-grade fevers may occur. Nasal symptom severity is greatest on presentation (ie, 1 to 5 days after symptoms appear). Nonproductive cough can persist for a week, and it may be more protracted in smokers.²

	Complications of VRIs

TOP Abstract Introduction Diagnosis of VRI Role of Picornaviruses in... HRVs Complications of VRIs VRIs in Children VRIs in Adults Management of VRIs Symptomatic Treatment of VRIs Antiviral Agents Conclusion References

 
HRVs are important causes of upper and lower VRIs (Table 1 ) and affect all age groups. Complications of HRV infection are not uncommon, and they include otitis media, sinusitis, acute exacerbations of asthma and COPD, and exacerbations of cystic fibrosis.¹⁵

	VRIs in Children

TOP Abstract Introduction Diagnosis of VRI Role of Picornaviruses in... HRVs Complications of VRIs VRIs in Children VRIs in Adults Management of VRIs Symptomatic Treatment of VRIs Antiviral Agents Conclusion References

 
Respiratory syncytial virus is often thought of as the principal infectious pathogen for URIs in infants and young children, and there is increasing evidence that HRV also causes significant lower respiratory tract disease in this population.¹⁵ HRV spreads through the airway and infects the epithelial lining of the lower respiratory tract, ultimately precipitating exacerbations of asthma or cystic fibrosis.⁷ In studies of pediatric community-acquired pneumonia and acute respiratory hospitalizations, mixed infections with bacteria and rhinovirus were found in 10 to 11% of patients. Rhinovirus coinfection was associated with a worsening of clinical status.¹⁵

HRVs have an important role in precipitating asthma attacks. Johnston and colleagues²¹ reported that among children 9 to 11 years of age, common cold viruses were present in 80 to 85% of asthma exacerbations. HRVs were the most common viral pathogen in this group, being detected in 66% of the viral isolates. Other studies show that HRV infection (detected by RT-PCR or culture) is associated with high rates of wheezing and asthma-related emergency department or hospital admissions.¹⁵ These data suggest that HRV infection may promote asthma exacerbations and other lower respiratory tract disorders through the augmentation of local inflammatory processes. Picornaviruses in children with cystic fibrosis were detected by RT-PCR in 43% of nasopharyngeal specimens in epidemiologic studies reported by Collinson and colleagues.²² Decreases in airflow persisted for at least 3 weeks following the onset of URI. Pulmonary function testing measured decreases in FEV₁ of 16.5% on days 1 through 4 after onset, and of 10.3% on days 21 through 24 after the onset of symptoms. Frequent colds resulted in additional deterioration of pulmonary function over time and predisposed infected patients to further pulmonary bacterial infections.

	VRIs in Adults

TOP Abstract Introduction Diagnosis of VRI Role of Picornaviruses in... HRVs Complications of VRIs VRIs in Children VRIs in Adults Management of VRIs Symptomatic Treatment of VRIs Antiviral Agents Conclusion References

 
HRV infection is characterized by a wide range of clinical respiratory manifestations in adults that cause considerable morbidity and, on rare occasions, mortality, particularly in the elderly.¹⁵ HRV infection may induce airway hyperreactivity, but the mechanisms by which this occurs are not well-defined. Bronchoconstriction, activation of inflammatory cells, the release of immunologic mediators, increased airway response to tachykinins, and the induction of IgE class switching all may play some role in lower respiratory tract changes.¹⁵

In older studies^{2 15} that examined the relationship between viral exposure and lower respiratory tract disease, HRV infection was associated with 40 to 43% of the exacerbations experienced by patients with chronic bronchitis. Wiselka and colleagues²³ reported that patients with chronic bronchitis appeared to be more susceptible to respiratory virus infections and recovered more slowly, compared with asthma patients.

The most common pathogen associated with asthma exacerbations is HRV.^{24 25} In a 2-year adult asthma study,²⁶ colds were documented in 71% of exacerbations, and peak expiratory flow rates deteriorated during 27% of respiratory illnesses. In cases for which an infectious etiology was identified, HRV infections accounted for 57% of asthma exacerbations, and 23% of those infections were followed by peak expiratory flow rate deterioration (ie, a reduction of 50 L/min in mean peak expiratory flow rate).²⁶

Outbreaks of HRV among elderly persons in the community and in nursing homes are important causes of respiratory illness. Nicholson and colleagues²⁰ reported that chronic illness increased the likelihood of HRV-associated lower respiratory tract illness by 40% and that smoking increased the risk by 47%. In this study, almost six HRV infections were reported for every influenza infection, suggesting that the burden of HRVs in the elderly exceeds that of influenza. Those with underlying pulmonary disease including COPD had more prolonged and more severe illness than those without lung disease.

In a report by Wald and colleagues²⁷ on HRV outbreaks among nursing home residents, 66% of the study population had lower respiratory tract symptoms and 52% developed new abnormalities on lung auscultation. Those persons with COPD had more prolonged and severe disease following HRV infection, with symptoms lasting for approximately 7.4 days.

Greenberg and colleagues²⁸ reported that patients with COPD are more likely to develop significant lower respiratory tract symptoms from colds caused by viral respiratory pathogens. Longitudinal surveillance studies conducted to assess the impact of viral respiratory tract pathogens on morbidity and mortality in older adults with COPD showed similar rates of infection among control subjects and COPD cohorts; however, there was a twofold increase in acute respiratory tract illness among study subjects with underlying moderate-to-severe lung disease, suggesting that COPD patients may be more vulnerable to VRIs and may utilize more health-care resources.

URIs are occasionally accompanied by secondary bacterial infections of the sinuses (0.5 to 2.0% of cases),¹⁴ complicating the diagnosis between acute bacterial sinusitis and primary viral rhinosinusitis. HRV infections may cause inflammation and a subsequent cascade of host defense mechanisms in the paranasal sinuses.¹⁴ The actual pathogenic mechanisms by which viruses cause disease in the sinuses are unknown. Distinguishing bacterial, viral, or bacterial-viral sinusitis is clinically difficult,¹⁴ consequently sinusitis is most often treated empirically as a bacterial infection.²⁹ Sinus puncture and aspiration for specimen collection are required to definitively determine pathogen etiology, but this procedure is not performed routinely in the primary care setting.¹⁴

	Management of VRIs

TOP Abstract Introduction Diagnosis of VRI Role of Picornaviruses in... HRVs Complications of VRIs VRIs in Children VRIs in Adults Management of VRIs Symptomatic Treatment of VRIs Antiviral Agents Conclusion References

 
Symptoms of VRIs, as reported by patients, are variable.¹¹ The etiology of suspected bacterial and viral organisms in respiratory tract infections is most often established based on clinical signs and symptoms. The identification of viral pathogens is difficult because of a lack of rapid diagnostic tests that give results in a clinically useful time frame. Therefore, clinicians often give antibiotics inappropriately for the treatment of viral infections.^{9 10}

	Symptomatic Treatment of VRIs

TOP Abstract Introduction Diagnosis of VRI Role of Picornaviruses in... HRVs Complications of VRIs VRIs in Children VRIs in Adults Management of VRIs Symptomatic Treatment of VRIs Antiviral Agents Conclusion References

 
First-generation antihistamines, decongestants, and antitussives provide some patients with symptomatic relief of their VRI-associated complaints. However, there is little objective evidence to support the use of second-generation antihistamines, corticosteroids, zinc, or echinacea as treatment for VRIs (Table 2 ).^{2 3}

	Antiviral Agents

TOP Abstract Introduction Diagnosis of VRI Role of Picornaviruses in... HRVs Complications of VRIs VRIs in Children VRIs in Adults Management of VRIs Symptomatic Treatment of VRIs Antiviral Agents Conclusion References

 
A wide variety of agents and mechanisms have been under investigation for the treatment and prophylaxis of picornavirus infections (Table 3 ). New compounds are strategically and rationally designed for antiviral activity. Approaches include targeting viral cell susceptibility, viral attachment and receptor blockade, viral uncoating, viral RNA replication, and viral protein synthesis.³⁰ Unlike amantadine, zanamivir, the neuraminidase inhibitors, and other antiviral chemotherapies that have demonstrated excellent activity against influenza viruses, most of the investigational compounds for HRV have failed to show benefit in human clinical trials.^{31 32} The reasons for failure include lack of bioavailability, adverse events, intolerance, and limited potency.³¹

Intranasal interferon-2 has prophylactic activity against natural HRV infections, but it has not been shown to have benefit in treatment. The side effects of nasal irritation and bleeding have limited its use.³⁰ Early treatment with interferon in experimental HRV infection reduced viral titers and the frequency of middle ear pressure abnormalities. Peak symptoms were modestly altered. Combinations of intranasal antiviral and anti-inflammatory drugs are under investigation and may serve to reduce VRI complications that include sinusitis and otitis media.^{24 25}

Viral Attachment/Binding
Ninety percent of HRVs use ICAM-1 to attach to the cell-surface receptor on the host cell to initiate infection. Soluble ICAM-1 binds to receptor binding sites on the virus, preventing viral attachment to ICAM-1 on the cell surface.³¹ Although soluble ICAM-1 has undergone several randomized clinical trials,³³ the compound showed marginal efficacy, and development has been halted.

Viral Uncoating
Viral capsid-binding compounds block viral uncoating and attachment to host-cell receptors. For the 90% of HRVs that bind ICAM-1, these compounds change the spatial conformation of the virus and prevent attachment to ICAM-1.^{30 31} Several compounds that showed promising activity in experimental picornavirus infections have been studied, but they had significant limitations (eg, dosing, delivery, tolerance, solubility, bioavailability, and safety) for use in treating respiratory infections. Preclinical work continues on analogs of these agents.³²

Pleconaril, or {3-[3,5-dimethyl-4-[(3-methyl-5-isoxazolyl)-propyl]-phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole}, is an orally bioavailable, antiviral agent for the treatment of picornaviral infections.^{30 34} In clinical trials, pleconaril demonstrated significant reductions in VRI symptom severity and duration for individuals with naturally occurring colds. Pleconaril is the first anti-picornavirus compound to be submitted for US Food and Drug Administration review.

In vitro, pleconaril integrates into the cavity or pockets of the viral capsid to inhibit viral capsid uncoating, thus blocking attachment to host-cell receptors and inhibiting viral replication (Fig 1 ).³⁵ It has potent, broad-spectrum activity against HRVs and enteroviruses and is highly bioavailable by an oral route of administration.³⁰ Oral administration studies³¹ in animals have demonstrated tissue penetration where viral replication was likely to occur, as well as tissue concentration levels several times higher than plasma concentrations.

View larger version (114K): [in this window] [in a new window] [Download PPT slide]   Figure 1. The mechanism of action of pleconaril is shown. Pleconaril integrates into the cavity or pockets of the viral capsid of the picornavirus to inhibit viral capsid uncoating, thereby blocking attachment to host-cell receptors and inhibiting viral replication. This figure was adapted from Rotbart.40 The pleconaril molecular structure was used courtesy of ViroPharma Inc (Exton, PA).

In a recent randomized, double-blind, placebo-controlled trial³⁹ comparing pleconaril, 400 mg tid for 5 days, with placebo in 1,044 patients, HRV-positive patients who were treated with pleconaril showed similar reductions in symptoms as those seen in other studies, but symptom severity was lower in the pleconaril group each day, beginning on the first full day of dosing. Compared with placebo, there was a significant reduction in the median viral titers in nasal mucus on days 3 and 6 in the pleconaril-treated patients. Adverse event rates were similar between the pleconaril and placebo groups. Headache, diarrhea, and nausea were reported most commonly.³⁹

RNA Inhibitors
Enviroxime was an antiviral agent with potent in vitro activity targeting viral replication inhibition of HRVs and enteroviruses through the inhibition of the 3A-coding region of viral RNA. Clinical development was halted on this agent because of intolerance to oral dosing and limited antiviral activity after intranasal administration to humans. Derivatives of this compound are currently under investigation.^{24 25 32}

Viral Protein Synthesis
A virally encoded enzyme, 3C protease, cleaves viral proteins from precursor polyproteins and is essential for the viral replication and assembly of the virion. A number of low-molecular-weight drug candidates have been synthesized to inhibit the 3C protease and show promise of antiviral activity.^{24 25} The most advanced candidate is AG7088, which shows excellent in vitro activity against the picornaviruses and is well-tolerated.³¹ The intranasal compound is now being reformulated to optimize the active ingredient delivery to the nasal cavity. Phase II trials will begin in the near future.³¹

	Conclusion

TOP Abstract Introduction Diagnosis of VRI Role of Picornaviruses in... HRVs Complications of VRIs VRIs in Children VRIs in Adults Management of VRIs Symptomatic Treatment of VRIs Antiviral Agents Conclusion References

 
An understanding of the impact of picornaviruses on respiratory illnesses has expanded with the advent of new techniques for viral detection. Picornaviruses are ubiquitous respiratory pathogens and the most common cause of VRIs. Picornaviruses can result in significant illness and exacerbations of upper and lower respiratory disease in both children and adults.

Patients who are infected with viral and bacterial respiratory tract pathogens often present with similar symptoms. The determination of the etiologic agent in respiratory tract infections is important for the selection of an appropriate treatment regimen. Antimicrobial agents are extremely effective in eradicating susceptible bacterial pathogens, but the inappropriate use of antimicrobial agents for the treatment of viral infections has contributed to the widespread emergence of resistant organisms. Over-the-counter remedies provide limited symptomatic relief, and, until recently, few medications have been available to treat viral infections.

HRVs are common sources of VRIs and cause significant morbidity in patients with lower respiratory tract illnesses, particularly in the elderly and those with chronic illnesses and pulmonary disease. Pleconaril is a safe and effective antiviral agent for the treatment of adult VRIs caused by picornaviruses. It is one of the few antiviral therapies that have been well-tolerated, and it has demonstrated excellent antiviral activity and selectivity for the picornaviruses in pivotal clinical trials. Pleconaril may reduce the disease burden associated with VRI in patients with airway disease. Future studies should specifically assess the role of pleconaril in the prevention and treatment of VRIs in high-risk patients with chronic lung disease or asthma.

	Footnotes

 
Abbreviations: HRV = human rhinovirus; ICAM = intercellular adhesion molecule; IL = interleukin; RT-PCR = reverse transcriptase polymerase chain reaction; URI = upper respiratory tract infection; VRI = viral respiratory infection

Received for publication December 28, 2001. Accepted for publication September 20, 2002.

	References

TOP Abstract Introduction Diagnosis of VRI Role of Picornaviruses in... HRVs Complications of VRIs VRIs in Children VRIs in Adults Management of VRIs Symptomatic Treatment of VRIs Antiviral Agents Conclusion References

 

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