Aap respiratory syncytial virus

Introduction: Respiratory Syncytial Virus RSV is a common cause of lower respiratory tract infections among pediatric patients, especially during the winter months. It is associated with significant morbidity and mortality among young infants, especially those with history of prematurity and cardiac anomalies. We present a case of a 2-year-old previously healthy girl, with RSV bronchiolitis, who developed cardiac arrest secondary to cardiac tamponade.

Case Report: 2-year-old, healthy female, presented with fever and a four-day history of cough and worsening respiratory distress. At home, parents reported perioral cyanosis, post-tussive emesis, decreased oral intake and urine output. She was in respiratory distress with coarse breath sounds.

The remainder of her exam including the cardiac portion was unremarkable. Albuterol trial was not beneficial. She was started on Ceftriaxone, given a bolus and admitted to the pediatric floor. She received an additional bolus of fluids and continued antibiotic therapy.

Within a few hours, her work of breathing increased with further signs of distress. Repeat CXR was negative for any acute change. Medical emergency was called, she quickly developed bradycardia and went into cardiac arrest.

Patient required vasoactive support. Her initial ECG showed low amplitude waves. A 2D Transthoracic Cardiac ECHO that evening revealed a large pericardial effusion with tamponade that required emergent pericardiocentesis at bedside by pediatric interventional radiologist, revealing ml of serous pericardial fluid 9.

On PICU day 2, her vasoactive agents of epinephrine and norepinephrine were maximized and with impending vascular compromise of her distal extremities, she was transferred to an outside hospital for ExtraCorporeal Membrane Oxygenation ECMO.

Patient tolerated this well and ultimately led to her discharge home with minimal neurological deficits.

Discussion: RSV hospitalizations are very common, especially among infants less than 3 months old. Despite RSV's common occurrence, there is very little in the literature about cardiac effusions and tamponade in these patients. Among the two cases reported thus far in literature, both were in infants. We present this case of 2-year-old previously healthy girl with RSV infection leading to pericardial effusion and cardiac tamponade with subsequent cardiac arrest that required ECMO.

This case highlights the need to maintain a high index of suspicion for rare, but life threatening cardiac sequlae in a predominantly respiratory infection.

Recipient s will receive an email with a link to 'Respiratory Syncytial Virus: More than just Bronchiolitis' and will not need an account to access the content. Advertising Disclaimer ». Sign In or Create an Account. Pediatr Rev December ; 35 12 : — Respiratory syncytial virus RSV is the most common respiratory pathogen in infants and young children worldwide.

Although the most effective management of this infection remains supportive care, many patients continue to be managed with therapies that lack the support of scientific evidence. Although the quest for a safe and effective vaccine remains unsuccessful, the more vulnerable patients can be protected with passive prophylaxis. Because of limited clinical benefits and high costs, RSV prophylaxis should be limited to high-risk infants as directed by the most current evidence-based guidelines that, however, are not consistently followed.

The acute phase of this infection is often followed by episodes of wheezing that recur for months or years and usually lead to a physician diagnosis of asthma. The phenotype of post-RSV wheezing is different from atopic asthma, yet it is usually managed using the same pharmacologic therapy with often ineffective results.

Understand the microbiology, epidemiology, pathophysiology, and clinical manifestations of RSV bronchiolitis in infants and children. Know the scientific evidence relevant to prophylactic and therapeutic strategies currently available and recognize the lack of evidence concerning several pharmacologic agents commonly used in the management of bronchiolitis.

Learn the epidemiologic and experimental information suggesting the existence of a link between early-life infection with RSV and the subsequent development of recurrent wheezing and asthma in childhood and adolescence. Human respiratory syncytial virus RSV is a single-stranded RNA virus of the Paramyxoviridae family whose genome includes 10 genes that encode 11 proteins Figure 1.

Two surface proteins, the F fusion protein and the G attachment glycoprotein protein, are the major viral antigens and play a critical role in the virulence of RSV. The G protein mediates RSV attachment to the host cell, after which the F protein enables fusion of the host and viral plasma membranes to permit virus passage into the host cell.

The F protein also promotes the aggregation of multinucleated cells through fusion of their plasma membranes, producing the syncytia for which the virus is named and allows the transmission of virus from cell to cell. RSV has 2 distinct antigenic subtypes, A and B, which are usually present in the communities during seasonal outbreaks.

It remains controversial whether subtype A is more strongly associated with severe disease. Respiratory syncytial virus RSV classification. The closely related Metapneumovirus genus was considered an exclusively avian virus until the discovery of a human strain in RSV is the most frequent cause of bronchiolitis in infants and young children and accounts in the United States alone for approximately , hospitalizations and infant deaths every year.

In summary, RSV is by far the most frequent cause of pediatric bronchiolitis and pneumonia Figure 2. Etiology of acute respiratory infections in children. Therefore, RSV is by far the most frequent cause of pediatric bronchiolitis and pneumonia. Nearly all children are infected at least once by the time they are age 2 years, but peak incidence occurs between ages 2 and 3 months and corresponds to nadir concentrations of protective maternal IgG transferred to the fetus through the placenta.

Seasonal outbreaks occur each year throughout the world, although onset, peak, and duration vary from one year to the next. However, the epidemiology of RSV differs widely across latitudes and meteorologic conditions.

For example, at sites with persistently warm temperatures and high humidity, RSV activity tends to be continuous throughout the year, peaking in summer and early autumn.

In temperate climates, RSV activity is maximal during winter and correlates with lower temperatures. In areas where temperatures remain colder throughout the year, RSV activity again becomes nearly continuous. Thus, RSV activity in communities is affected by both ambient temperature and absolute humidity, perhaps reflecting meteorologic combinations that allow greater stability of RSV in aerosols.

Morbidity and mortality of RSV disease are higher in premature infants and in infants with chronic lung disease eg, bronchopulmonary dysplasia, cystic fibrosis, and interstitial lung diseases or hemodynamically significant congenital heart disease. Because preterm infants miss, in part or completely, the third trimester window during which the placenta expresses Fc receptors mediating the transfer of maternal IgG to the fetus, they are born with reduced humoral protection against infection and reach lower nadir concentrations of maternal IgG.

This is compounded by T-cell—mediated responses that are inefficient because T cells also mature primarily during the last trimester of pregnancy. Development of bronchopulmonary dysplasia or other chronic respiratory conditions amplifies the risk of severe infections by limiting pulmonary functional reserve, distorting airway architecture, and promoting a proinflammatory milieu.

Additional risk factors for severe disease include age younger than 12 weeks, history of prematurity, male sex, crowding, lack of breastfeeding, congenital heart disease, and any immunodeficiency. Despite numerous studies that have explored whether environmental tobacco smoke exposure affects RSV morbidity, definitive evidence of this association is lacking, and its clinical significance remains controversial.

Nevertheless, physicians should inquire about tobacco smoke exposure when assessing infants and children for bronchiolitis and advise caregivers about smoke cessation. Previous infection with RSV does not convey persistent immunity even in the presence of significant antibody titers, although higher titers may attenuate the course of the disease.

Consequently, subsequent infection is common, can recur within the same viral season, and occurs across all age groups. The first episodes of infection typically occur in the first 2 years after birth and tend to be the most severe because of the limited immunologic protection discussed above, smaller airway size, and unique structural and functional features of the developing respiratory tract eg, lack of interalveolar pores and channels and different innervation patterns.

Most subsequent infections remain confined to the upper respiratory tract and run a milder course, although the illness may still progress to an LRTI, especially in elderly and immunodeficient patients, usually characterized by more severe symptoms. The clinical manifestations of RSV pneumonia in immunocompromised patients vary, depending on the extent and severity of the underlying deficit, ranging from substantial morbidity and mortality in the first 3 months after bone marrow transplantation to a usually milder course in patients with AIDS.

Transmission of RSV infection occurs through inoculation of the nasopharyngeal or conjunctival mucosa with respiratory secretions from infected individuals. The virus remains viable on hard surfaces for up to 6 hours, on rubber gloves for 90 minutes, and on skin for 20 minutes. This prolonged survival highlights the need for hand washing and contact precautions as an essential and cost-effective practice to limit the spread of infection, especially in clinic settings.

The incubation period ranges from 2 to 8 days, and immunocompetent individuals can shed the virus for up to 3 weeks, although on average this is limited to approximately 8 days.

However, viral shedding from immunocompromised individuals can continue for several months because intracellular replication is not effectively contained by specific cell-mediated immunity. RSV infection starts in the nasopharyngeal epithelium but then spreads rapidly by intercellular transmission through the lower airways, reaching the terminal bronchioles, where the replication of this virus is most efficient. Direct pathologic consequences of lytic viral replication include sloughing of necrotic epithelial cells, which exposes the dense subepithelial network of nociceptive nerve fibers, forming the afferent limb for the cough reflex.

The initial influx of polymorphonuclear neutrophils into the airways is rapidly replaced by predominantly lymphomononuclear infiltration of peribronchiolar tissues and increased microvascular permeability, leading to submucosal edema and swelling. Mucous secretions increase in quantity and viscosity and tend to pool because of the loss of ciliated epithelium, resulting in widespread mucous plugging. This constellation of acute inflammatory changes that form the immediate response to exponential viral replication in the bronchioles leads to airway obstruction and air trapping, producing the classic clinical triad of polyphonic wheezing, patchy atelectasis, and bilateral hyperinflation.

However, disease severity and duration are primarily a function of the immune response mounted by the host. Innate immune mechanisms provide the respiratory tract with a first barrier against the establishment of a productive infection.

Subsequently, specific humoral and cell-mediated immunity play a critical role in clearing the infection and attenuating its course.

Although this response does not result in complete protection against subsequent infection, it decreases their severity. In infants, higher titers of maternally derived RSV-neutralizing antibody are associated with a much lower risk of hospitalization due to RSV, and this protective effect can be replaced or enhanced in high-risk infants by passive prophylaxis.

Cytotoxic T lymphocytes are central in the control of active infection and viral clearance, which explains why immunocompromised individuals with deficient cell-mediated immunity experience more severe and prolonged RSV disease and shed the virus much longer. Typically, the infection starts with signs and symptoms of mucosal inflammation and irritation of the upper respiratory tract congestion, rhinorrhea, and sneezing.

In the next few days, the clinical status evolves with involvement of the lower respiratory tract manifested by cough and increased work of breathing with use of accessory respiratory muscles to overcome the increased resistance of obstructed airways.

As noted above, many of the clinical manifestations of airway obstruction are driven by the immune response against the virus rather than by viral replication and direct cytotoxicity. Therefore, wheezing and other typical signs of bronchiolitis may be reduced or even absent in immunosuppressed patients and be replaced by rapidly evolving parenchymal infiltrates that can lead to acute respiratory distress syndrome. Inspection reveals respiratory distress ranging from minimal to profound respiratory failure associated with a variable degree of nasal flaring and intercostal retractions.

Auscultation reflects the vibration of conducting airways generated by turbulent airflow and is remarkable for a prolonged expiratory phase, diffuse polyphonic wheezing, and coarse crackles rales scattered throughout the lung fields. Pulse oxymetry and arterial blood gas analysis detect moderate to severe hypoxemia derived primarily from the perfusion of respiratory units that are poorly ventilated because of mucous plugging ventilation-perfusion mismatch.

Progressive carbon dioxide retention and respiratory acidosis signal the development of respiratory muscle fatigue and evolving respiratory failure that require ventilatory assistance. Infants are usually more severely affected and may also develop lethargy, fever, poor feeding, and otitis media, whereas older children typically manifest symptoms of the upper respiratory tract but may also develop tracheobronchitis.

When present, apnea usually is an early event that precedes lower respiratory tract signs and symptoms, suggesting the involvement of reflex neural activity triggered in the upper airways. The highest incidence of apnea occurs in premature infants and in infants younger than 1 month, probably because of the relative immaturity of ventilatory control.

In most cases, however, apnea is self-limited and does not recur with subsequent infections. The diagnosis of acute bronchiolitis should be based exclusively on the history and physical examination findings and does not require radiographic or laboratory studies. The specific cause can be confirmed by antigen detection tests, currently being replaced by more sensitive polymerase chain reaction—based assays.

Arguably, this step in not essential because, especially during the epidemic peak and in the first year after birth, RSV is responsible for most cases of bronchiolitis and other pathogens are much less common. However, confirming the viral origin strengthens the rationale for withholding therapies known to be ineffective and provides prognostic clues concerning complications, such as recurrent wheezing and asthma, based on robust epidemiologic data.

Correct etiologic diagnosis is also important to rule out rare conditions that could be worsened by the management commonly used for bronchiolitis. In cases of suspected cardiac disease, chest radiography will reveal cardiomegaly, suggesting a different diagnosis and therapy, and thereby might avoid significant complications or even death.

Other laboratory and imaging studies also add little information, although it is advisable to determine the complete and differential blood cell counts and C-reactive protein level to assess the risk of bacterial superinfection in febrile children, as well as electrolyte serum concentrations to monitor hydration status and electrolyte imbalance. If chest radiography is performed, findings typically include bilateral hyperinflation, patchy atelectasis, and peribronchial thickening, but patients with severe lower respiratory tract involvement have radiologic features more consistent with pneumonia and areas of interstitial parenchymal infiltration Figure 3.

Clinical manifestations of respiratory syncytial virus RSV. Chest radiography performed in a child with RSV bronchiolitis revealed bilateral hyperinflation from air trapping, patchy atelectasis from airway plugging, and peribronchial thickening from lymphomonocytic infiltration. Patients with severe disease may also have features more consistent with pneumonia, with areas of interstitial parenchymal infiltration. Most infants with RSV infection develop a mild, self-limited illness, which is usually managed in outpatient settings but still requires close follow-up with special attention to respiratory distress, oxygen requirement, and hydration.

Those infants with difficulty feeding, pronounced respiratory distress, or need for supplemental oxygen require hospital admission for more aggressive management and monitoring. Regardless of the setting in which the patient is treated, the mainstay of therapy remains supportive care, which includes respiratory support combined with appropriate fluid and nutrition management Figure 4.

Evidence-based management of bronchiolitis. Passive prophylaxis is a safe and effective way of protecting infants at risk for severe respiratory syncytial virus RSV disease but is not cost-efficient. Once the infection is established, the mainstay of current therapy remains supportive care because no solid scientific evidence supporting the use of any conventional or experimental pharmacologic agent currently exists. For the future, promising antiviral molecules and new-generation humanized monoclonal antibodies are being investigated, and structural biology may overcome the challenges that have so far prevented the development of a safe and effective RSV vaccine.

Nasal obstruction is a common problem in young infants who are obligate nose breathers and often improves significantly after nasal toilet with saline drops and a suction bulb. Chest physiotherapy is often provided in an effort to mobilize secretions and reexpand atelectatic segments, but a recent Cochrane systematic review found no evidence to support its use, which, combined with the unnecessarily increased hospitalization costs, should discourage this practice.

Infants with hypoxemia refractory to supplemental oxygen, persistent respiratory distress, or evolving respiratory failure require either noninvasive support with nasal continuous positive airway pressure or endotracheal intubation. Positive pressure mechanical ventilation has been used for decades in the management of infants with severe RSV bronchiolitis and is probably one of the most important factors that lead to the progressive decrease in mortality.

A few infants with particularly severe disease may require escalation of mechanical ventilation to high-frequency oscillatory ventilation or extracorporeal membrane oxygenation. Infants hospitalized with RSV bronchiolitis often have decreased nutritional intake due to respiratory distress and tachypnea with increased insensible losses and will need fluid and nutritional support.

Continued oral feeding in the presence of significant tachypnea and respiratory distress is known to increase the risk of aspiration. Indeed, aspiration has been revealed with the use of barium contrast in a significant proportion of infants hospitalized with RSV bronchiolitis. Thus, in patients who are unable to tolerate oral feeds, adequate fluid intake and nutrition should be maintained by placement of a nasogastric or orogastric feeding tube or with parenteral fluids when enteral nutrition is deemed unsafe.

Despite relentless attempts to identify pharmacologic strategies to improve the clinical course and outcomes of this infection, the most effective management remains limited to the supportive care measures discussed above.

There is no solid scientific evidence supporting the use of any pharmacologic agent currently available. Albuterol does not provide consistent benefit in the treatment of RSV infection and should not be administered to infants and children diagnosed as having bronchiolitis. A brief trial with objective evaluation of the response may be warranted, but this therapy should be discontinued if no improvement occurs because of the significant adverse effects, including tachycardia, tremor, hypokalemia, and hyperglycemia.

These adverse effects can be amplified and become life-threatening in patients with underlying lung or heart disease, also due to the interaction with other commonly used therapies eg, diuretics. Epinephrine does not provide consistent benefit in the inpatient setting, and although some studies suggest that it may produce a modest improvement in the outpatient setting, it is not deemed safe for use at home or other settings where cardiorespiratory monitoring is not available.

Oral or parenteral adrenergic agonists have no advantages over nebulized ones but have much stronger adverse effects that contraindicate their use in any obstructive airway disease, including bronchiolitis. Finally, there is no evidence supporting the use of anticholinergic agents, such as atropine or any of its synthetic derivatives, which may also have significant untoward effects by predisposing patients to more extensive mucous plugging.

It has also been reported to reduce length of hospital stay and provide symptomatic relief in patients with bronchiolitis, but its use remains controversial.

In particular, it is not effective in reducing hospitalization when used in emergency settings. Therefore, on the basis of current evidence, the administration of hypertonic saline for bronchiolitis should be limited to hospitalized infant and children. Neither systemic nor inhaled corticosteroids have consistent benefit in the treatment of acute RSV disease or in the prevention of post-RSV wheezing. In particular, a systematic review of 13 trials of corticosteroid therapy in 1, children with viral wheezing ages 0 to 30 months concluded that this therapy lacks any significant clinical benefit compared with placebo and is not indicated for this patient group.

The findings of this meta-analysis have been complemented by a number of more recent individual studies that have reached more or less the same conclusions. Another area of concern derives from safety considerations. In fact, viral bronchiolitis typically occurs during the first year after birth and coincides with a critical phase of rapid lung growth. The safety of corticosteroids during this developmental window is virtually unknown, and corticosteroids are not approved by the Food and Drug Administration FDA for use in the treatment of bronchiolitis or asthma in the first year after birth.

Therefore, on the basis of current and extensive scientific evidence, corticosteroids are not recommended for routine use in the treatment of acute bronchiolitis. It has been argued that virus-induced wheezing in infants and young children could be the early manifestation of persistent asthma and therefore warrant the use of corticosteroids for the secondary prevention and control of asthma.

However, in general young children without an atopic phenotype who wheeze in response to viral infections show a poor response to corticosteroids, and even children who will ultimately develop chronic asthma are usually unresponsive to this therapy when they develop virus-induced wheezing during their first years after birth.

The only antiviral agent ever licensed by the FDA for the therapy of severe RSV infections is ribavirin, a synthetic nucleoside analog with broad in vitro virustatic activity. Unfortunately, by the time the infection manifests clinically in vivo, most of the viral load has already been cleared, and the disease process is driven primarily by inflammatory mechanisms largely independent from viral replication.

After some initial encouraging data from industry-sponsored studies, a series of randomized trials were unable to demonstrate any short- or long-term improvement in the clinical course of bronchiolitis, leading to a rapid decline and virtual disappearance of ribavirin use in this setting.

Therefore, inhaled ribavirin is no longer recommended for routine treatment of RSV infection, although it may be considered in select immunocompromised individuals, who can continue to shed virus for several months because replication is not limited by host defenses. Antibiotics should be used in patients with bronchiolitis only when specific evidence of coexistent bacterial infection is present.

Such coinfections are uncommon, perhaps with the exception of bacterial otitis media that can be managed with oral antibiotics no differently than in the absence of bronchiolitis.

A variety of other experimental therapeutic interventions has been tested, but none have been approved by, or even submitted to, the FDA, and currently the evidence supporting clinical use of any of them is largely insufficient. Starting with aerosol-delivered drugs, DNAse does not provide consistent benefit in the treatment of RSV infection, and although neutrophils, the primary source of extracellular DNA, are indeed recruited in the airways during the early stage of the infection, they are not predominant in RSV-infected airways as they are in cystic fibrosis, which remains the only accepted indication for this therapy.

Surfactant and Heliox may provide some benefit in the treatment of this infection, but again the available data are far from conclusive. Concerning oral drugs, antileukotrienes used during the acute phase of RSV bronchiolitis improve postbronchiolitis respiratory symptoms, especially in younger patients with high urinary leukotriene E 4 levels.

However, a large, multicenter, randomized, double blind, placebo-controlled DBPC trial with montelukast did not find statistically significant clinical improvement. We have elected to not include in this review the extensive pipeline of antiviral compounds currently being developed because they are not likely to become available for clinical use in the foreseeable future.

Disinfection with alcohol-based rubs and hand washing with alcohol-based rubs or soap and water are highly effective in reducing the spread of RSV, and it is invaluable in preventing nosocomial infections. The use of gloves and gowns can help in limiting transmission, but the use of masks is controversial because RSV is mostly transmitted by direct contact with infected secretions and rarely by aerosolization.