**1. Introduction**

Acute bronchiolitis is the most common lower lung disease that causes substantial morbidity and hospitalization in young infants under 6 months of age [1, 2]. In the first year of life, approximately 20–30% of children suffer from acute bronchiolitis that is frequently seen during the winter season, and infants are hospitalized with bronchiolitis [3]. During the epidemic season (late-autumn and winter months), the rate of bronchiolitis requiring hospitalization in all infants smaller than 12 months have been reported as 3% of in the US and Europe [4]. Prematurity and being born during the RSV season are risks factors for hospitalization [5]. A recent study has stated that the rate of hospitalization for bronchiolitis is 5.4% in preterm infants in the first 12 months of life [6]. A few studies particularly focused on the costs of bronchiolitis hospitalization reported that bronchiolitis admissions cost more than 500 million dollars annually and a co-diagnosis of bronchiolitis and pneumonia almost doubles the cost of the hospitalization [7].

Bronchiolitis is a viral disease in the infant period. Respiratory syncytial virus (RSV) is the most common agent that causes 50–80% of the cases. Its peak clinical severity is seen between third and fifth days. Respiratory syncytial virus bronchiolitis is responsible for a short history of low-grade fever, cough, coryza, and difficulty in breathing and feeding. Infants who are under 6 weeks of age might be present with apnea alone without other clinical symptoms [8]. There are several predispositions to developing RSV infection in infants. A few of them are presence of an older sibling, birth in the RSV season, low birth weight, male sex, young age (<6 months), exposure to smoking, young maternal age, and suburban residence. Having congenital heart disease, chronic lung disease, immunodeficiency, cystic fibrosis, Down syndrome, or cerebral palsy increases the severity of RSV bronchiolitis [9]. In the pathogenesis of RSV bronchiolitis, there are a defective inflammatory response and cellular damage related to viral replication. Annually, RSV associated with lower respiratory tract infection in infants and young children leads to around 3.2 million hospitalizations and 59,000 deaths worldwide [10]. To date, there is no modality to prevent RSV infection. RSV vaccines, that named a formalin-inactivated RSV vaccine, have been improved in the mid-1960s. Due to the fact that the vaccines had caused "vaccine enhanced disease", the subunit vaccines schedule were not recommended. Afterward, RSV immune globulin (RespiGamTM) that reduced RSV-mediated hospitalizations had been prophylactically developed for infants with several risks for severe RSV disease. Currently, SynagisTM (palivizumab) is used to decrease RSV related hospitalizations by >55%. SynagisTM is implemented for newborns with a birth age of 35 weeks or less and infants under 6 months in RSV season. Additionally, for under 2 years, children with chronic lung disease treatment and hemodynamically serious congenital heart disease in the last 6 months are proposed to prevent severe RSV infection with the monoclonal antibody. SynagisTM should be given once a month at a dose of 15 mg/kg as long as the risk of RSV infection persists [11]. No matter what virus, the main treatment of bronchiolitis is liquid and oxygen therapy. However, Alansari et al. tested the efficacy of the anti-RSV monoclonal antibody palivizumab in infants <3 months of age with RSV bronchiolitis. Results of clinical trials have shown that intravenous palivizumab did not appear to help young infants with acute RSV-positive bronchiolitis [12]. Not only RSV has been reported as the most common cause of acute bronchiolitis in children younger than 1 year, but also the global annual rate of RSV hospitalization among children <5 years is 4.4 per 1000 lower respiratory tract infection in a systematic review and metaanalysis [8, 9, 13, 14]. History of prematurity is also reported to be a leading cause of mortality in acute bronchiolitis [15]. Due to the fact that the RSV vaccine is not available, prophylaxis with the monoclonal antibodies, palivizumab and motavizumab, has been developed to prevent RSV associated with mortality-morbidity in premature infants [16].

Rhinovirus is the second most common pathogen in acute bronchiolitis. Epidemiologic studies have stated that rhinoviruses-A and -C are to be the more common subtype acute respiratory infections and wheezing illnesses, and have reported that rhinovirus is related to moderate and severe bronchiolitis and in childhood [17]. In COAST cohort study, rhinovirus-A and -C species were associated with a higher risk of moderate-to-severe acute respiratory infection compared with those with rhinovirus-B infection [18]. The prevalence of rhinovirus causing acute lower respiratory infection varies between 17 and 35% among young children. A study from Turkey conducted by Gökçe et al. showed that the respiratory viral agent exhibited seasonal patterns with the number of RSV and rhinovirus cases peaking in the winter season [19]. Data on long-term outcomes report that the rate of recurrent wheezing is significantly higher in rhinovirus infections. Additionally, several cohorts confirmed that rhinovirus causing wheezing illness in early life is a significant predictor of asthma. Teeratakulpisarn et al. showed that the children

**33**

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

diagnose the etiology of acute bronchiolitis.

olitis and to target preventive and monitoring approach.

**2. Pathophysiology and pathogenesis**

associated with rhinoviruses and blood eosinophilia [22].

Calvo et al. stated that coinfections do not increase the severity [25].

seen in children previously diagnosed with cardiovascular disease, chronic pulmonary disease, and immunodeficiency. Persistently increased respiratory effort, hypoxemia, apnea, and acute respiratory failure define severe bronchiolitis that requires intensive monitoring and repeated examinations. Risks of severe bronchiolitis generally increase in infants with chronic lung disease, congenital heart disease, anatomic defects of the airways, immunodeficiency, and neurologic disease. It has also been reported that male gender, indigenous status, exposure to tobacco smoke, and poor socioeconomic factors were to be associated with severe bronchiolitis. Various polymerase chain reaction (PCR) techniques provide us to

diagnosed with rhinovirus bronchiolitis could be possessed of recurrent wheezing. However, these symptoms mostly disappeared before the age of 6, and nearly half of the study patients subsequently had asthma [20, 21]. Another study from Italy also showed that recurrent wheezing 36 months after infant bronchiolitis was

Studies have reported that influenza, coronavirus, adenovirus, human bocavirus, human metapneumovirus, and parainfluenza viruses cause acute bronchiolitis as the sole pathogen or as coinfection with a similar seasonal pattern. Miron et al. aimed a study to assess the prevalence of sole and mixed respiratory organisms infection/detection in young children diagnosed with acute bronchiolitis. In this study, 590 respiratory organisms were detected in 423 (91%) children, and the two most commonly detected agents were RSV and rhinovirus [23]. In bronchiolitis, the most common dual infection was between RSV and rhinovirus, and the second was between RSV and human bocavirus. Adenovirus coinfections were also reported as the third most frequent. A study conducted in the United States asserted that dual infections had more ratios of hospitalizations than single infections [24]. Contrary,

The risk of acute bronchiolitis-associated respiratory failure or death is more

The clinical studies for new diagnostic measurements have been brought forth by clinicians in order to predict severe bronchiolitis, because severe bronchiolitis might be associated with morbidity and mortality in infants. It has been found that children with RSV had a more severe initial clinical presentation. Bamberger et al. stated that infants with RSV bronchiolitis, especially young infants, had high clinical severity score on admission when compared to those with other respiratory viruses [26]. In this respect, it has been aimed to evaluate the accuracy of virologic testing for RSV in detecting patients at risk for more severe disease. Hasegawa et al. have reported that the major viruses (RSV-A, RSV-B, rhinovirus, adenovirus, and hMPV) had different temporal patterns in a study which was multicenter-multiyear prospective cohorts of the US infants with severe bronchiolitis. Their data provide guidance for optimal timing of RSV immunoprophylaxis, effective prophylactic (e.g., immunoprophylaxis), and treatment (e.g., antiviral agents) strategies in infants at higher risk for severe bronchiolitis [27]. Another study stated that infants attended daycare, had older siblings, had high parental educational levels, had birth weights of >4 kg, and were born between April and September had a 10-fold higher risk for severe RSV infection than those who had no these factors [28]. These features provide us to differentiate between infants with high risks of RSV bronchi-

Generally, acute bronchiolitis is characterized by upper respiratory symptoms

(e.g., rhinorrhea) followed by lower respiratory infection with inflammation

#### *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*

severity is seen between third and fifth days. Respiratory syncytial virus bronchiolitis is responsible for a short history of low-grade fever, cough, coryza, and difficulty in breathing and feeding. Infants who are under 6 weeks of age might be present with apnea alone without other clinical symptoms [8]. There are several predispositions to developing RSV infection in infants. A few of them are presence of an older sibling, birth in the RSV season, low birth weight, male sex, young age (<6 months), exposure to smoking, young maternal age, and suburban residence. Having congenital heart disease, chronic lung disease, immunodeficiency, cystic fibrosis, Down syndrome, or cerebral palsy increases the severity of RSV bronchiolitis [9]. In the pathogenesis of RSV bronchiolitis, there are a defective inflammatory response and cellular damage related to viral replication. Annually, RSV associated with lower respiratory tract infection in infants and young children leads to around 3.2 million hospitalizations and 59,000 deaths worldwide [10]. To date, there is no modality to prevent RSV infection. RSV vaccines, that named a formalin-inactivated RSV vaccine, have been improved in the mid-1960s. Due to the fact that the vaccines had caused "vaccine enhanced disease", the subunit vaccines schedule were not recommended. Afterward, RSV immune globulin (RespiGamTM) that reduced RSV-mediated hospitalizations had been prophylactically developed for infants with several risks for severe RSV disease. Currently, SynagisTM (palivizumab) is used to decrease RSV related hospitalizations by >55%. SynagisTM is implemented for newborns with a birth age of 35 weeks or less and infants under 6 months in RSV season. Additionally, for under 2 years, children with chronic lung disease treatment and hemodynamically serious congenital heart disease in the last 6 months are proposed to prevent severe RSV infection with the monoclonal antibody. SynagisTM should be given once a month at a dose of 15 mg/kg as long as the risk of RSV infection persists [11]. No matter what virus, the main treatment of bronchiolitis is liquid and oxygen therapy. However, Alansari et al. tested the efficacy of the anti-RSV monoclonal antibody palivizumab in infants <3 months of age with RSV bronchiolitis. Results of clinical trials have shown that intravenous palivizumab did not appear to help young infants with acute RSV-positive bronchiolitis [12]. Not only RSV has been reported as the most common cause of acute bronchiolitis in children younger than 1 year, but also the global annual rate of RSV hospitalization among children <5 years is 4.4 per 1000 lower respiratory tract infection in a systematic review and metaanalysis [8, 9, 13, 14]. History of prematurity is also reported to be a leading cause of mortality in acute bronchiolitis [15]. Due to the fact that the RSV vaccine is not available, prophylaxis with the monoclonal antibodies, palivizumab and motavizumab, has been developed to prevent RSV associated with mortality-morbidity in

Rhinovirus is the second most common pathogen in acute bronchiolitis. Epidemiologic studies have stated that rhinoviruses-A and -C are to be the more common subtype acute respiratory infections and wheezing illnesses, and have reported that rhinovirus is related to moderate and severe bronchiolitis and in childhood [17]. In COAST cohort study, rhinovirus-A and -C species were associated with a higher risk of moderate-to-severe acute respiratory infection compared with those with rhinovirus-B infection [18]. The prevalence of rhinovirus causing acute lower respiratory infection varies between 17 and 35% among young children. A study from Turkey conducted by Gökçe et al. showed that the respiratory viral agent exhibited seasonal patterns with the number of RSV and rhinovirus cases peaking in the winter season [19]. Data on long-term outcomes report that the rate of recurrent wheezing is significantly higher in rhinovirus infections. Additionally, several cohorts confirmed that rhinovirus causing wheezing illness in early life is a significant predictor of asthma. Teeratakulpisarn et al. showed that the children

**32**

premature infants [16].

diagnosed with rhinovirus bronchiolitis could be possessed of recurrent wheezing. However, these symptoms mostly disappeared before the age of 6, and nearly half of the study patients subsequently had asthma [20, 21]. Another study from Italy also showed that recurrent wheezing 36 months after infant bronchiolitis was associated with rhinoviruses and blood eosinophilia [22].

Studies have reported that influenza, coronavirus, adenovirus, human bocavirus, human metapneumovirus, and parainfluenza viruses cause acute bronchiolitis as the sole pathogen or as coinfection with a similar seasonal pattern. Miron et al. aimed a study to assess the prevalence of sole and mixed respiratory organisms infection/detection in young children diagnosed with acute bronchiolitis. In this study, 590 respiratory organisms were detected in 423 (91%) children, and the two most commonly detected agents were RSV and rhinovirus [23]. In bronchiolitis, the most common dual infection was between RSV and rhinovirus, and the second was between RSV and human bocavirus. Adenovirus coinfections were also reported as the third most frequent. A study conducted in the United States asserted that dual infections had more ratios of hospitalizations than single infections [24]. Contrary, Calvo et al. stated that coinfections do not increase the severity [25].

The risk of acute bronchiolitis-associated respiratory failure or death is more seen in children previously diagnosed with cardiovascular disease, chronic pulmonary disease, and immunodeficiency. Persistently increased respiratory effort, hypoxemia, apnea, and acute respiratory failure define severe bronchiolitis that requires intensive monitoring and repeated examinations. Risks of severe bronchiolitis generally increase in infants with chronic lung disease, congenital heart disease, anatomic defects of the airways, immunodeficiency, and neurologic disease. It has also been reported that male gender, indigenous status, exposure to tobacco smoke, and poor socioeconomic factors were to be associated with severe bronchiolitis. Various polymerase chain reaction (PCR) techniques provide us to diagnose the etiology of acute bronchiolitis.

The clinical studies for new diagnostic measurements have been brought forth by clinicians in order to predict severe bronchiolitis, because severe bronchiolitis might be associated with morbidity and mortality in infants. It has been found that children with RSV had a more severe initial clinical presentation. Bamberger et al. stated that infants with RSV bronchiolitis, especially young infants, had high clinical severity score on admission when compared to those with other respiratory viruses [26]. In this respect, it has been aimed to evaluate the accuracy of virologic testing for RSV in detecting patients at risk for more severe disease. Hasegawa et al. have reported that the major viruses (RSV-A, RSV-B, rhinovirus, adenovirus, and hMPV) had different temporal patterns in a study which was multicenter-multiyear prospective cohorts of the US infants with severe bronchiolitis. Their data provide guidance for optimal timing of RSV immunoprophylaxis, effective prophylactic (e.g., immunoprophylaxis), and treatment (e.g., antiviral agents) strategies in infants at higher risk for severe bronchiolitis [27]. Another study stated that infants attended daycare, had older siblings, had high parental educational levels, had birth weights of >4 kg, and were born between April and September had a 10-fold higher risk for severe RSV infection than those who had no these factors [28]. These features provide us to differentiate between infants with high risks of RSV bronchiolitis and to target preventive and monitoring approach.
