Pediatric Bronchiolitis

Etiology

RSV is the leading infectious agent in acute bronchiolitis among children, accounting for up to two-thirds of cases. Human metapneumovirus and parainfluenza virus type 3 contribute to nearly half of the remaining cases.

During the COVID-19 pandemic, a small number of SARS-CoV-2–related bronchiolitis cases were reported, alongside a significant decline in RSV bronchiolitis admissions. However, this trend reversed after the pandemic, with RSV again emerging as the predominant cause of bronchiolitis.[2] 

Although RSV is the leading pathogen causing bronchiolitis, other respiratory viruses can also contribute, albeit less frequently. These include adenoviruses, bocaviruses, coronaviruses (such as SARS-CoV-2), enteroviruses, human metapneumovirus, influenza, measles, and rhinoviruses.[3][4] Occasionally, Mycoplasma pneumoniae has been associated with a bronchiolitis-like illness characterized by wheezing.

With the expansion of therapeutic options for respiratory infections, identifying the specific causative agent has become increasingly important. This is particularly vital in critically ill children, as determining the cause can guide targeted treatments and enhance outcomes.

Epidemiology

Bronchiolitis is one of the most common respiratory illnesses affecting infants and young children worldwide, referring to a clinical condition predominantly seen in this age group.[1] This condition is characterized by wheezing, tachypnea, and other common symptoms of viral respiratory tract infections, such as cough, nasal congestion, and rhinorrhea. The condition most often occurs in children between 2 and 6 months of age.

The severity of bronchiolitis varies significantly, from mild wheezing with an increased respiratory rate (commonly referred to as the "happy wheezer") to severe respiratory distress that may progress to respiratory failure, necessitating intubation and mechanical ventilation. Early recognition and timely management are essential to prevent complications and improve outcomes in severe cases.

Bronchiolitis outbreaks occur annually, typically during the fall and winter months in temperate climates, aligning with the circulation of other respiratory viruses. In subtropical and tropical regions, bronchiolitis can occur year-round, with outbreaks more common during the rainy season. In desert climates, cases are usually confined to a narrow window in winter, with minimal or no activity reported throughout the rest of the year.[1][5] Factors such as temperature, humidity, and UV-B radiation are believed to influence the seasonality of the virus. However, further research is needed to better understand the factors driving these patterns worldwide.[5]

Many respiratory viruses have relatively short incubation periods, typically lasting 2 to 3 days. In older children and adults, viral shedding is generally brief, lasting only a few days. However, viral shedding can persist for more than 4 weeks in infants, young children, and immunocompromised individuals.[6] This prolonged viral shedding can complicate infection control efforts and challenge the interpretation of PCR diagnostics. Residual shedding from a recent but inactive infection may be detected, potentially confounding the diagnosis of a new illness.

Various host, environmental, and social factors contribute to an increased risk of severe bronchiolitis in infants and children (see Table below).[7][8][9][10] Recognizing these risk factors is essential for guiding prevention strategies and implementing early interventions to mitigate the severity of the illness.

Table. Risk Factors for Severe Bronchiolitis

Pathophysiology

Most viral pathogens enter the body through the nasopharynx and oral or conjunctival mucosal surfaces. RSV, the most common cause of bronchiolitis, initially replicates in the nasopharynx before spreading to respiratory tract cells lining the terminal bronchioles. RSV primarily infects type I alveolar pneumocytes, with some involvement of type II alveolar pneumocytes, while sparing basal cells. Aspiration of upper respiratory tract secretions and subsequent cell-to-cell spread typically leads to lower respiratory tract involvement within 1 to 3 days of the initial upper respiratory infection.

Infection of the respiratory tract cells lining the terminal bronchioles leads to cellular damage and activates local inflammatory responses. The virus-induced inflammation triggers the release of cytokines and chemokines, resulting in edema, increased mucus production, and the recruitment of additional inflammatory cells to the respiratory tract.[11] 

Dead bronchial epithelial and inflammatory cells slough into the inflamed, mucus-filled airways, further exacerbating small airway obstruction. Infants are particularly prone to airway obstruction due to the small caliber of their airways, which can result in wheezing and air trapping. Atelectasis of the lung parenchyma and resulting hypoxemia further contribute to varying levels of respiratory distress.

The pathology of bronchiolitis involves necrosis of airway epithelial cells, along with proliferation of the bronchiolar epithelium and cellular infiltration of monocytes and T cells affecting both bronchial and pulmonary arterioles. Neutrophilic infiltration can also be observed between the vascular structures and small airways.[12][13] Airway obstruction and air trapping result in increased airway resistance. Additionally, neutrophilia is frequently observed in pediatric cases following bronchoalveolar lavage.[14]

History and Physical

The history and physical examination of infants with bronchiolitis typically reveal a consistent clinical presentation. During the initial days, symptoms include cough, congestion, and rhinorrhea, with or without fever, as viral replication occurs in the upper respiratory tract.

Parents often describe initial cold-like symptoms, which progress to signs such as "breathing funny" or "breathing fast," difficulty feeding, or bluish discoloration of the lips and nailbeds. They may also observe nasal flaring and intercostal retractions as the infant struggles to optimize air entry.

On physical examination, vital signs may show a low-grade fever, increased respiratory rate, and hypoxemia. Respiratory rates exceeding 100 breaths per minute are common and often contribute to feeding difficulties in infants.

Pulse oximetry typically shows varying degrees of hypoxemia due to mucous plugging and atelectasis, resulting in a ventilation-perfusion mismatch.[15] Cyanosis of the lips and nail beds may also be observed. Key physical findings include grunting, nasal flaring, intercostal retractions, and belly breathing. Diffuse inspiratory and expiratory wheezes across all lung fields are characteristic of viral bronchiolitis. A tired, pale-appearing infant with poor air entry is a concerning sign of impending respiratory collapse, requiring urgent intubation and ventilation.

Evaluation

Bronchiolitis is primarily diagnosed clinically. Diagnosis and assessment of illness severity should be based on a comprehensive history of the present illness and the patient's clinical signs. Oxygen saturation levels can help determine the need for supplemental oxygen and hospitalization. An important clinical indicator of the severity of an infant's illness is their ability to breastfeed or bottle-feed. Observing feeding behavior is crucial; if the infant experiences coughing, difficulty breathing, or sputtering during feeding, hospitalization for intravenous fluids should be considered.

Infants with tachypnea exceeding 60 breaths per minute or oxygen saturation levels below 92% should be considered for hospitalization and supplemental oxygen. Patients with severe respiratory compromise may benefit from a trial of aerosolized albuterol.[16] In cases of clinical fatigue or severe hypoxemia, endotracheal intubation and mechanical ventilation should be strongly considered.

Laboratory investigations for patients with bronchiolitis should include viral identification when possible. Rapid diagnostic assays, such as nucleic acid amplification testing, immunofluorescence, and enzyme immunoassay techniques, are commercially available to detect viral RNA or antigens in nasopharyngeal or other respiratory specimens. These results can help clinicians tailor the patient's workup and management. In addition to guiding treatment, this information is crucial for decisions regarding room placement, isolation, and grouping of hospitalized patients. Chest x-rays are generally not recommended, as they often show nonspecific findings such as lung hyperinflation, interstitial markings, and peribronchial thickening, which are typically not diagnostic.

Treatment / Management

The management of bronchiolitis is primarily supportive, and it usually focuses on ensuring hydration, performing upper airway suctioning as needed, and monitoring for signs of respiratory failure or the need for intubation and mechanical ventilation. Infants with oxygen saturation levels below 92% in room air should receive supplemental oxygen, and continuous pulse oximetry monitoring is recommended for hospitalized patients.

Antipyretics should be administered if a fever develops. Although bronchodilators are not universally effective, a trial of aerosolized albuterol may be considered, especially for infants with severe respiratory compromise.[16] Glucocorticoids and racemic epinephrine have not shown efficacy and are not recommended. Antibiotics should be reserved for cases with clear evidence of a superimposed infection in addition to bronchiolitis.

If an infant tests positive for influenza, oseltamivir (Tamiflu™) is recommended, particularly if administered within the first 48 hours of symptom onset. Early initiation of this antiviral improves its effectiveness and may positively impact the course of the illness. Similarly, if SARS-CoV-2 is identified, treatment with nirmatrelvir-ritonavir (Paxlovid™) can be considered. Prevention is preferred over treatment, and new tools are now available to help prevent bronchiolitis. Palivizumab (Synagis™)—a monoclonal antibody targeting the F protein of RSV—was previously recommended for high-risk infants during their first year. This product was administered monthly via intramuscular injection during RSV season but was unavailable for otherwise healthy infants in their first 3 months of life—a group that experiences a substantial burden of RSV disease cases.

Fortunately, 2 options are now available for RSV prevention—vaccination of pregnant individuals with an RSV vaccine (Abrysvo™) or administering the newer monoclonal antibody nirsevimab (Beyfortus™) to infants during their first RSV season if the birth parent did not receive an RSV vaccine.[17] The availability of these products may vary, so clinicians should consult local guidelines for administration in case of limited supplies.

Vaccines are available for influenza and SARS-CoV-2, which, although contributing significantly to the overall burden of respiratory disease, account for only a small proportion of bronchiolitis cases. Nonetheless, the American Academy of Pediatrics and other healthcare organizations recommend age-appropriate vaccination for all infants and children to prevent these infections. For infants too young for vaccination, vaccinating household members and close contacts is essential to minimize the risk of disease transmission.

Differential Diagnosis

The differential diagnoses of bronchiolitis include:

• Gastroesophageal reflux
• Aspiration pneumonia
• Foreign body aspiration into the lower airway
• Congenital malformations, such as vascular rings or slings
• Acute exacerbation of asthma
• Acute anaphylaxis

Prognosis

The prognosis of bronchiolitis is generally favorable, with most infants recovering within 5 to 7 days. Although some studies suggest an increased risk of asthma following bronchiolitis, only a small percentage of affected children develop asthma. A history of recurrent wheezing and a positive family history of asthma, allergies, or atopic dermatitis may increase the likelihood of asthma development in these patients in the future.[18]

Complications

Complications from bronchiolitis are uncommon but can be severe, particularly in infants who are premature or have underlying pulmonary, cardiac, or immunocompromised conditions. Even healthy infants may experience acute or chronic complications, although most recover without incident.[19][20][21][22][23]

Acute complications of bronchiolitis include:

• Aspiration
• Respiratory failure
• Apnea
• Secondary bacterial infections
• Death

Chronic complications of bronchiolitis include:

• Recurrent episodes of wheezing
• Bronchiolitis obliterans