**2. Pathophysiology and pathogenesis**

Generally, acute bronchiolitis is characterized by upper respiratory symptoms (e.g., rhinorrhea) followed by lower respiratory infection with inflammation

which is commenced by a pathogen and leads to epithelial necrosis in the bronchial epithelium. Classical symptoms of bronchiolitis including wheezing, crackles, and bronchospasm consist of partial obstruction in the lumen through the accumulation of degenerated squamous epithelium secretions [29]. Bronchiolar obstruction with edema and accumulation of mucus and cellular debris in the airways can persist for many weeks or months following acute bronchiolitis [30]. The reconstruction process may result in complete recovery. However, it can also be characterized by exaggerated proliferation of granulation tissue. There is an exaggerated inflammatory response mediated by cytokines especially T-helper 1 in the pathogenesis of acute bronchiolitis with a variable cytokine profile, according to the infective virus. Due to the fact that exaggerated proliferation causes narrowing or obliteration of the airway lumen, severe clinical findings can be seen in some cases [31–33].

The mucosal innate immune system procures a strong barrier to respiratory infections. In particular, RSV and/or rhinovirus can trigger/induce the concomitant production of type I (IFNα/β) and type III (IFNλs). A study was designed to investigate the airway type III IFN receptor (IFNLR1/IL10RB) expression during respiratory syncytial virus or human rhinovirus bronchiolitis. The results of this study showed that the association of IFNLR1 with rhinovirus infection could cause more severe bronchiolitis and blood eosinophilia. The type III IFN receptor also dictates an important role in the host immune response during bronchiolitis [34].

#### **2.1 Etiology**

Respiratory syncytial virus is the most common etiologic pathogen in acute bronchiolitis with a rate of 50–80%. Various studies have shown that other viruses, including adenovirus, coronavirus, parainfluenza, influenza, rhinovirus, human bocavirus, and human metapneumovirus, are associated with acute bronchiolitis [35]. Rhinovirus (RV), which is the most common human respiratory pathogens and are responsible for most upper respiratory infections (e.g., the common cold), is the second most commonly associated viral bronchiolitis [36–38]. In recent years, new human respiratory viruses like human metapneumovirus, human bocavirus, and new human coronaviruses have also been reported as possible pathogens causing acute bronchiolitis [38]. Respiratory viruses could occur as coinfection with other respiratory viruses: dual, triple, or more [37, 39, 40]. Today, various viral diagnostic tests provide us to determine the epidemiological differences/clinical characteristics of respiratory viruses. One of the diagnostic methods is multiplex polymerase chain reaction which has been the most commonly used method [41]. Rarely, several atypical infections, for instance, *Bordetella pertussis*, *Mycoplasma pneumonia*, *Simkania negevensis*, and a Chlamydia-like intracellular organism have also shown in bronchiolitis [42–44].

#### **2.2 Diagnosis**

American Academy of Pediatrics Clinical Practice Guidelines has reported the definition of acute bronchiolitis in 2006. According to the guideline, bronchiolitis has been described as the first episode of wheezing in children under 24 months of age who have respiratory findings during the viral infection episode. Tachypnea, nasal flaring, chest retractions, and wheezing and/or rales are clinical characteristic features of acute bronchiolitis. Rhinorrhea, cough, tachypnea, wheezing, rales, and increased respiratory effort manifested as grunting, nasal flaring, and intercostal and/or subcostal retractions are clinical signs and symptoms of bronchiolitis [3]. Early presentations of asthma or wheeze with viral infections may potentially overlap with the diagnosis of bronchiolitis. Chest radiographs and laboratory studies

**35**

bronchiolitis.

*One of the Main Problems of Infants: Bronchiolitis DOI: http://dx.doi.org/10.5772/intechopen.89417*

**2.3 Hospital admission and investigations**

requirement for supplemental oxygen.

**2.4 Assessment**

therapy [45–48].

may be thought of on clinical suspicion after evaluating the differential diagnosis for secondary or comorbid bacterial infection, complications, or other conditions. Viral diagnosis methods that are not routinely suggested for testing, including antigen detection or immunofluorescence of nasal secretion wash or nasal aspiration, rapid antigen tests, and PCR, are only suggested for identifying specific viral agents in children with bronchiolitis if the results will determine discontinuation of palivizumab prophylaxis, initiation, or continuation/discontinuation of antibiotic

Bronchiolitis must be distinguished from a variety of acute and chronic diseases including asthma, pneumonia, airway lesions, congenital lung disease or diaphragmatic hernia, cystic fibrosis, congenital heart disease, sepsis, and severe metabolic acidosis that might present with similar presentation. Atypical clinical findings like lack of preceding upper respiratory tract symptoms, witnessed an episode of choking, and poor growth may be useful to discriminate from acute bronchiolitis. It

should be considered further investigation for the differential diagnosis.

Though bronchiolitis is usually a self-limiting entity, several infants have severe bronchiolitis and should be safely managed at hospital. Severity score of bronchiolitis is described with several clinical parameters including wheezing, retraction, respiratory rate, and general situation (Wang respiratory score) [49]. However, the severity score has not been shown to be useful in a clinical setting. Therefore, the scoring system is not generally used in hospitalization decision. If the infants have any of features, such as apnea, difficulty in feeding, severe respiratory distress with accessory muscle use or grunting, respiratory rate greater than 60/min, diagnostic uncertainty, and cyanosis/hemoglobin saturation < 92%, they are should be referred for hospital admission. Infants with specific risk factors, such as poor socioeconomic circumstances, a history of prematurity, congenital heart disease, or chronic lung disease, also need to be hospitalized. Around 1–5% of infants might need pediatric intensive care support in bronchiolitis [50]. If infants under 6 months of age or with comorbidities, they are more likely to require intensive care unit admission. After hospitalization, the infants with severe respiratory distress, exhaustion, failure to maintain hemoglobin saturation above 92–94% with supplemental oxygen or with recurrent apnea should be followed-up in intensive care units. Since the diagnosis of acute bronchiolitis is done clinically, infants with bronchiolitis require no further investigations. During the hospitalization, hemoglobin saturation should be measured using pulse oximetry to determine the

Initially, the management of bronchiolitis is assessed by clinical features. Persistently increased respiratory effort, hypoxemia, apnea, and acute respiratory failure show severe bronchiolitis. Therefore, basic airway management and emergency endotracheal intubation should be considered in a child with deterioration and respiratory failure. In nonsevere bronchiolitis, supportive care including adequate hydration and relief of nasal congestion/obstruction are the mainstays of management for infants with bronchiolitis. Disease progression should also be monitored. Although bronchodilators (inhaled or oral), glucocorticoids, nebulized hypertonic saline, or leukotriene inhibitors have been used in some situations, randomized trials do not recommend pharmacologic interventions in nonsevere

#### *One of the Main Problems of Infants: Bronchiolitis DOI: http://dx.doi.org/10.5772/intechopen.89417*

*Update on Critical Issues on Infant and Neonatal Care*

which is commenced by a pathogen and leads to epithelial necrosis in the bronchial epithelium. Classical symptoms of bronchiolitis including wheezing, crackles, and bronchospasm consist of partial obstruction in the lumen through the accumulation of degenerated squamous epithelium secretions [29]. Bronchiolar obstruction with edema and accumulation of mucus and cellular debris in the airways can persist for many weeks or months following acute bronchiolitis [30]. The reconstruction process may result in complete recovery. However, it can also be characterized by exaggerated proliferation of granulation tissue. There is an exaggerated inflammatory response mediated by cytokines especially T-helper 1 in the pathogenesis of acute bronchiolitis with a variable cytokine profile, according to the infective virus. Due to the fact that exaggerated proliferation causes narrowing or obliteration of the airway lumen, severe clinical findings can be seen in some cases [31–33]. The mucosal innate immune system procures a strong barrier to respiratory infections. In particular, RSV and/or rhinovirus can trigger/induce the concomitant production of type I (IFNα/β) and type III (IFNλs). A study was designed to investigate the airway type III IFN receptor (IFNLR1/IL10RB) expression during respiratory syncytial virus or human rhinovirus bronchiolitis. The results of this study showed that the association of IFNLR1 with rhinovirus infection could cause more severe bronchiolitis and blood eosinophilia. The type III IFN receptor also dictates an important role in the host immune response during bronchiolitis [34].

Respiratory syncytial virus is the most common etiologic pathogen in acute bronchiolitis with a rate of 50–80%. Various studies have shown that other viruses, including adenovirus, coronavirus, parainfluenza, influenza, rhinovirus, human bocavirus, and human metapneumovirus, are associated with acute bronchiolitis [35]. Rhinovirus (RV), which is the most common human respiratory pathogens and are responsible for most upper respiratory infections (e.g., the common cold), is the second most commonly associated viral bronchiolitis [36–38]. In recent years, new human respiratory viruses like human metapneumovirus, human bocavirus, and new human coronaviruses have also been reported as possible pathogens causing acute bronchiolitis [38]. Respiratory viruses could occur as coinfection with other respiratory viruses: dual, triple, or more [37, 39, 40]. Today, various viral diagnostic tests provide us to determine the epidemiological differences/clinical characteristics of respiratory viruses. One of the diagnostic methods is multiplex polymerase chain reaction which has been the most commonly used method [41]. Rarely, several atypical infections, for instance, *Bordetella pertussis*, *Mycoplasma pneumonia*, *Simkania negevensis*, and a Chlamydia-like intracellular organism have also shown in bronchi-

American Academy of Pediatrics Clinical Practice Guidelines has reported the definition of acute bronchiolitis in 2006. According to the guideline, bronchiolitis has been described as the first episode of wheezing in children under 24 months of age who have respiratory findings during the viral infection episode. Tachypnea, nasal flaring, chest retractions, and wheezing and/or rales are clinical characteristic features of acute bronchiolitis. Rhinorrhea, cough, tachypnea, wheezing, rales, and increased respiratory effort manifested as grunting, nasal flaring, and intercostal and/or subcostal retractions are clinical signs and symptoms of bronchiolitis [3]. Early presentations of asthma or wheeze with viral infections may potentially overlap with the diagnosis of bronchiolitis. Chest radiographs and laboratory studies

**34**

**2.1 Etiology**

olitis [42–44].

**2.2 Diagnosis**

may be thought of on clinical suspicion after evaluating the differential diagnosis for secondary or comorbid bacterial infection, complications, or other conditions.

Viral diagnosis methods that are not routinely suggested for testing, including antigen detection or immunofluorescence of nasal secretion wash or nasal aspiration, rapid antigen tests, and PCR, are only suggested for identifying specific viral agents in children with bronchiolitis if the results will determine discontinuation of palivizumab prophylaxis, initiation, or continuation/discontinuation of antibiotic therapy [45–48].

Bronchiolitis must be distinguished from a variety of acute and chronic diseases including asthma, pneumonia, airway lesions, congenital lung disease or diaphragmatic hernia, cystic fibrosis, congenital heart disease, sepsis, and severe metabolic acidosis that might present with similar presentation. Atypical clinical findings like lack of preceding upper respiratory tract symptoms, witnessed an episode of choking, and poor growth may be useful to discriminate from acute bronchiolitis. It should be considered further investigation for the differential diagnosis.

### **2.3 Hospital admission and investigations**

Though bronchiolitis is usually a self-limiting entity, several infants have severe bronchiolitis and should be safely managed at hospital. Severity score of bronchiolitis is described with several clinical parameters including wheezing, retraction, respiratory rate, and general situation (Wang respiratory score) [49]. However, the severity score has not been shown to be useful in a clinical setting. Therefore, the scoring system is not generally used in hospitalization decision. If the infants have any of features, such as apnea, difficulty in feeding, severe respiratory distress with accessory muscle use or grunting, respiratory rate greater than 60/min, diagnostic uncertainty, and cyanosis/hemoglobin saturation < 92%, they are should be referred for hospital admission. Infants with specific risk factors, such as poor socioeconomic circumstances, a history of prematurity, congenital heart disease, or chronic lung disease, also need to be hospitalized. Around 1–5% of infants might need pediatric intensive care support in bronchiolitis [50]. If infants under 6 months of age or with comorbidities, they are more likely to require intensive care unit admission. After hospitalization, the infants with severe respiratory distress, exhaustion, failure to maintain hemoglobin saturation above 92–94% with supplemental oxygen or with recurrent apnea should be followed-up in intensive care units. Since the diagnosis of acute bronchiolitis is done clinically, infants with bronchiolitis require no further investigations. During the hospitalization, hemoglobin saturation should be measured using pulse oximetry to determine the requirement for supplemental oxygen.

#### **2.4 Assessment**

Initially, the management of bronchiolitis is assessed by clinical features. Persistently increased respiratory effort, hypoxemia, apnea, and acute respiratory failure show severe bronchiolitis. Therefore, basic airway management and emergency endotracheal intubation should be considered in a child with deterioration and respiratory failure. In nonsevere bronchiolitis, supportive care including adequate hydration and relief of nasal congestion/obstruction are the mainstays of management for infants with bronchiolitis. Disease progression should also be monitored. Although bronchodilators (inhaled or oral), glucocorticoids, nebulized hypertonic saline, or leukotriene inhibitors have been used in some situations, randomized trials do not recommend pharmacologic interventions in nonsevere bronchiolitis.

Fluid support is absolutely necessary for infants with any level bronchiolitis. Because bronchiolitis causes difficulty in maintaining adequate hydration and children with bronchiolitis may also decrease intake the fluid due to tachypnea and respiratory distress. Related to clinical features, fluid replacement treatment may have been provided by parenteral or small frequent feedings or orogastric or nasogastric feedings in children who can tolerate enteral feedings strategies.

The second most important support treatment is oxygen supplementation by nasal cannula, face mask, or head box to provide the SpO2 > 90–92% for infants. If there is insufficient oxygen therapy during support treatment, it means that a progression to respiratory failure. In order to reduce the work of breathing, improve gas exchange, and avoid the need for endotracheal intubation, heated humidified highflow nasal cannula (HFNC, also called high-flow warm humidified oxygen) therapy and/or continuous positive airway pressure (CPAP) are recently used mostly.

## **2.5 Clinical course**

Bronchiolitis, which is a self-limited disease, often resolves without complications. Generally, the respiratory status improves over 2–5 days in bronchiolitis. Standard strategies include hand hygiene to reduce the risk of bronchiolitis to minimize the transmission of infectious agents. Additionally, avoiding passive exposure to cigarette smoke and contact with individuals with respiratory tract infections might reduce the risk of bronchiolitis.
