CHAPTER I

INTRODUCTION

1.1 Introduction

Bronchiolitis is an acute inflammatory injury of the bronchioles that is usually caused

by a viral infection. Bronchiolitis is one of the most common infectious respiratory conditions
of early childhood and the leading cause of hospitalization for infants and young children in
both developed countries and developing counties, mentioned by Jonathan M. Mansbach,
MD, et al (2012). The most common pathogen associated with severe bronchiolitis is
respiratory syncytial virus (RSV), and the second most common is human rhinovirus.
However, regardless of pathogen, children with bronchiolitis are considered to have
essentially the same disease. Thus, et al (2006) American Academy of Pediatrics bronchiolitis
clinical practice guideline recommends that clinicians limit viral diagnostic testing when
caring for children with bronchiolitis.
Risk factors plays important role in predicting the clinical outcome of patients with
bronchiolitis. As Simoes et al (2003) point out, RSV infection cause the greatest morbidity
and mortality in infants under 6 months of age and in those who possess risk factors such as
prematurity, chronic lung disease, congenital heart disease, crowded living conditions, and
tobacco smoke exposure. Therefore, prompt and early recognition of the likely outcome of the
children with bronchiolitis is clearly important.
Respiratory syncytial virus (RSV) infections are associated with various levels of
respiratory illnesses, from cold-like mild illness to very severe and even life-threatening lower
respiratory infections. It was well known as the leading cause of bronchiolitis, especially
among young children during their first year of life, but many other viruses such as influenza
virus, parainfluenza virus, rhinovirus and human metapneumovirus have been associated with
acute viral bronchiolitis as well. Furthermore, young children with bronchiolitis often are
infected with more than one virus, most often with RSV and either rhinovirus or human
metapneumovirus [Zorc and Hall, 2010]. Including adenovirus, influenza virus, and
parainfluenza virus have also been reported to cause acute bronchiolitis as the sole pathogen
or as coinfection with or without RSV. A recent global estimate showed that the incidence of
RSV-associated acute lower respiratory infection was 33.1 million, with 3.2 million hospital
admissions and 59,600 in-hospital deaths in children younger than 5 years old in 2015 [Shi et
al., 2017].

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 Dangkor Referral Hospital is a hospital located in St. 217, Khva Village, Sangkat
Dangkor, Khan Dangkor, Phnom Penh, Cambodia. Acute bronchiolitis also is one among the
most common medical reasons for admission to the pediatric ward, providing some challenges
regarding the tools for diagnosis and treatment intervention as well. Moreover, information on
detailed clinical, epidemiological features among these children in this setting are limited.

1.2 Objectives of the Study

1.2.1 General of the Study

To determine the epidemiological clinical features, and management among children

who were hospitalized with acute bronchiolitis at dangkor referral hospital in 2022.

1.2.2 Specific of the Study

- To determine demographics variables and geographical areas

- To explore the clinical features of the disease
- To explore the related tests finding in this setting
- To explore the management of diseases
- To explore the duration of hospital stay for this disease in this hospital

1.3 Research Questions

- What age group does effect by disease?

- What sex does affect in diseases?
- Which geographic area effect in disease?
- When does the disease occur?
- Has the patient breastfed?
- Have all patients been vaccinated in accordance with the national program?
- What are the clinical feature of this disease?
- What are the laboratory finding to confirm diagnosis?
- How to management of diseases?
- How duration of hospital stay for this disease?

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 CHAPTER II
LITERATURE REVIEW

2.1 Introduction

Bronchiolitis is an infection of lower respiratory tract that primary effects on small airways
(bronchioles) usually affect is a common cause of illness and hospitalization in infants and young
children.
Bronchiolitis is broadly defined as a clinical syndrome of respiratory distress that occurs in
children <2 years of age and is characterized by upper respiratory symptoms (eg, rhinorrhea) followed
by lower respiratory infection with inflammation, which results in wheezing and/or crackles.
Obliterate bronchiolitis (OB) was first described in 1985 (Epler GR et al. 1985).
Bronchiolitis obliterans-organizing pneumonia (BOOP) was described as a condition distinct
from OB, with different clinical, radiographic, and prognostic features. BOOP is a
histopathology lesion, not a specific diagnosis. Its pathologic hallmark is proliferative
bronchiolitis or bronchiolitis obliterans in association with organizing pneumonia. BOOP and
OB are beyond the scope of this article and are not discussed further.
Bronchiolitis typically occurs with primary infection or reinfection with a viral
pathogen (Edelson PJ. 1985). It occurs principally during the fall and winter (Garcia-Garcia
ML et al. 2007) Bronchiolitis hospitalization has a peak incidence between two and six
months of age and remains a significant cause of respiratory disease during the first five years
of life (Dollner H. 2004)

2.2 Pathophysiology

Bronchioles are small airways (< 2 mm in diameter) and lack cartilage and sub-
mucosal glands. The terminal bronchiole, a 16th-generation airway, is the final conducting
airway that terminates in the respiratory bronchioles. The acinus (the gas exchange unit of the
lung) consists of respiratory bronchioles, the alveolar duct, and alveoli. The bronchiolar lining
consists of surfactant-secreting Clara cells and neuroendocrine cells, which are the source of
bioactive products such as somatostatin, endothelin, and serotonin.
Bronchiolar injury and the consequent interplay between inflammatory and
mesenchymal cells can lead to diverse pathologic and clinical syndromes. The effects of
bronchiolar injury may begin 18 to 24 hours after the infection and include the following:

3
 o Increased mucus secretion Bronchial obstruction and constriction
o Alveolar cell death, mucus debris, viral invasion
o Air trapping Atelectasis
o Reduced ventilation that leads to ventilation-perfusion mismatch
o Labored breathing
Complex immunologic mechanisms play a role in the pathogenesis of bronchiolitis.
Type 1 allergic reactions mediated by immunoglobulin E (IgE) may account for some
clinically significant bronchiolitis. Infants who are breastfed with colostrum rich in
immunoglobulin A (IgA) appear to be relatively protected from bronchiolitis (Dornelles CT et
al 2007).
Necrosis of the respiratory epithelium is one of the earliest lesions in bronchiolitis and
occurs within 24 hours of acquisition of infection. Proliferation of goblet cells results in
excessive mucus production, whereas epithelial regeneration with non-ciliated cells impairs
elimination of secretions. Lymphocytic infiltration may result in sub-mucosal edema.
Cytokines and chemokines, released by infected respiratory epithelial cells, amplify the
immune response by increasing cellular recruitment into infected airways. Interferon and
interleukin (IL)–4, IL-8, and IL-9 are found in high concentrations in respiratory secretions of
infected patients (McNamara PS et al. 2004).
Johnson et al analyzed autopsy findings from children who died of possible RSV
infection between 1925 and 1959 (before modern intensive care) and those from a child with
RSV bronchiolitis who died in a motor vehicle accident. They found that small bronchiole
epithelium was circumferentially infected but basal cells were spared. Both type 1 and type 2
alveolar pneumocytes were also infected. In this study, airway obstruction was due to
epithelial and inflammatory cell debris mixed with fibrin, mucus, and edema fluid but not to
bronchial smooth muscle constriction (Johnson JE et al 2007). Other research revealed that
neutrophil inflammation, but not eosinophil inflammation, is related to the severity of a first
infection in infants (Marguet C. et al. 2008).
The inflammation, edema, and debris result in obstruction of bronchioles, leading to
hyperinflation, increased airway resistance, atelectasis, and ventilation-perfusion
mismatching. Bronchoconstriction has not been described. Infants are affected most often
because of their small airways, high closing volumes, and insufficient collateral ventilation.
Recovery begins with regeneration of bronchiolar epithelium after 3-4 days; however, cilia do
not appear for as long as 2 weeks. Mucus plugs are instead predominantly removed by
macrophages.

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 Infection is spread by direct contact with respiratory secretions. In most temperate
regions within the United States, epidemics last 2-4 months, beginning in October/November
and peaking in January or February. Whereas 93% of cases occur between November and
early April, sporadic cases may occur throughout the year. In tropical/subtropical climates, the
season may be more prolonged and seems to correlate with the rainy season. Attack rates
within families are as high as 45% and are higher in childcare centers. Rates of hospital-
acquired infection can range from 20-47%.
Virtually, all children experience RSV infection within the first 3 years of life, but a
previous infection does not convey complete immunity. Reinfection is common; however,
significant antibody titers from prior infection ameliorate the severity of symptoms
(Henderson FW et al 1979)

2.3 Etiology

Most cases of bronchiolitis result from a viral pathogen, such as RSV, rhinovirus,
human meta-pneumovirus (hMPV), para-influenza virus, adenovirus, coronavirus, influenza
virus or human bocavirus. In one third of hospitalized cases of bronchiolitis, two or more
viruses may be detected, especially when using molecular-based testing. Bronchiolitis is
highly contagious. The virus that causes it is spread from person to person through direct
contact with nasal secretions, airborne droplets, and fomites.
RSV is the most commonly isolated agent in 75% of children younger than 2 years
who are hospitalized for bronchiolitis. RSV is an enveloped RNA virus that belongs to the
Paramyxoviridae family within the Pneumovirus genus. RSV causes 20-40% of all cases and
44% of cases that involve children younger than 2 years. Two RSV subtypes, A and B, have
been identified on the basis of structural variations in the G protein. Subtype A usually causes
the most severe infections. One subtype or the other usually predominates during a given
season; thus, RSV disease has “good” and “bad” years (Fodha I. et al. 2007). Viral shedding
in nasal secretions continues for 6-21 days after symptoms develop. The incubation period is
2-5 days (Hall CB, et al 1976).
Rhinoviruses, the cause of the common cold, may cause bronchiolitis or lower
respiratory tract infection and are frequently detected in dual infections. Cases tend to occur in
the spring and fall seasons. Rhinovirus may lead to a shorter hospitalization than RSV-
associated bronchiolitis (Mansbach JM, et al. 2012).

5
 Parainfluenza virus causes 10-30% of all bronchiolitis cases. Parainfluenza type 3 is
more likely to cause bronchiolitis than types 1, 2 or 4 which are associated with croup.
Epidemics of bronchiolitis due to parainfluenza virus usually begin earlier in the year and
tend to occur every other year.
Adenovirus accounts for 5-10% of bronchiolitis cases while influenza virus accounts
for 10-20%. Mycoplasma pneumoniae infection accounts for 5-15%, particularly among older
children and adults.
The paramyxovirus hMPV, first identified in the Netherlands in 2001 (van den
Hoogen et al. 2001) has been increasingly implicated as an etiologic agent in bronchiolitis.
(Williams JV et al 2004). Serologic studies indicated that by age 5 years, all Dutch children
had seroconverted and that the virus had been prevalent in the population for at least 50 years
(van den Hoogen BG.2004). In a retrospective examination of nasal washings obtained
between 1976 and 2001 from 2009 children with acute respiratory tract illness, 248 had
identifiable viruses. (Williams JV et al 2004). In 20% of these, hMPV was identified,
accounting for 12% of all viral lower respiratory illness in children younger than 2 years. The
mean age in the hMPV group was 11.6 months, with a male-to-female ratio of 1.8:1. They
most often had illnesses between December and April, and 2% were hospitalized. The virus
was associated with bronchiolitis in 59% of patients.
Subsequent studies showed that hMPV accounts for 5-50% of bronchiolitis cases,
seems to occur later in the bronchiolitis season, occurs with higher fevers, affects somewhat
older children, and causes more wheezing but less requirement for oxygen (possibly because
the children are older and have less atelectasis) (Garcia-Garcia ML, et al.2007). Other studies
found that combined hMPV-RSV infections were strongly associated with severe
bronchiolitis, with a 10-fold increase in pediatric intensive care unit (PICU) admission
(McNamara PS, et al 2007).
Human bocavirus (HBoV), discovered in 2005, is known to cause both upper and
lower respiratory tract infections and type 1 has been implicated in both bronchiolitis and
pertussis-like syndromes. Other HBoV types (2 through 4) are primarily enteric viruses.
HBoV is isolated infrequently as a single agent from children hospitalized with bronchiolitis
leading to speculation that it may be an innocent bystander rather than a true pathogen.
Arnold et al demonstrated that 5.6% of 1474 nasal scrapings collected over a 20-month period
at San Diego Children’s Hospital tested positive for HBoV, mostly from March through May
(Arnold JC, et al 2006).

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2.4 Risk Factors

Risk factors for the development of bronchiolitis include the following (Shaw KN et al
1991)
o Age less than 3 months (two thirds of all infants hospitalized with RSV infection
are younger than 5 months of age)
o Low birth weight, particularly premature infants.
o Gestational age (infants born at <29 weeks of gestation are at a particularly higher
risk for hospitalization from RSV infection)
o Lower socioeconomic group
o Crowded living conditions, childcare center attendance, presence of an older
sibling or a combination of these
o Parental smoking
o Chronic lung disease, particularly broncho-pulmonary dysplasia
o Severe congenital or acquired neurologic disease
o Hemodynamic significant congenital heart disease (CHD) (e.g, with pulmonary
hypertension)
o Congenital or acquired immune deficiency diseases
o Airway anomalies
In a study that collected epidemiologic, clinical, and virologic data to determine the
incidence and predisposing factors for severe bronchiolitis in 310 previously healthy term
infants younger than 12 months who were experiencing their first episode of bronchiolitis,
(Papoff P,et al 2011) the infants with severe disease were found to present with lower birth
weight, younger gestational age, lower postnatal weight, younger postnatal age, and a stronger
likelihood of having been born via cesarean delivery. Elevated C-reactive protein (CRP)
values (>0.8 mg/dL) and pulmonary consolidation on chest radiographs were more common
among infants with severe disease, though no significant differences in epidemiologic
variables were found (Papoff P, et al 2011). Although severe bronchiolitis is uncommon in
infants with these characteristics (ie, previously healthy term infants younger than 12
months), severity is predicted by young age and RSV carriage. Residency at high altitude
(over 2500 meters) may also contribute to severe disease and increased risk of hospitalization.
When severe bronchiolitis is present, it typically develops soon after disease onset (Choudhuri
JA, et al 2006).

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2.5 Epidemiology

2.5.1 United States Statistics

Respiratory infection is observed in 25% of children younger than 12 months and 13%
of children aged 1-2 years (Carlsen KH. Et al. 1983) . Of these 25%, one half has wheezing-
associated respiratory disease. RSV can be cultured from one third of these outpatients and
from 80% of hospitalized children younger than 6 months of age (Denny FW 1986).
Nearly 100% of children experience an RSV infection within 2 RSV seasons, and 1%
are hospitalized (Henderson FW, et al 1979). Among healthy full-term infants, 80% of
hospitalizations due to bronchiolitis occur in the first year, and 50% of hospitalizations occur
in children aged 1-3 months (Glezen WP, et al 1981). Fewer than 5% of hospitalizations occur
in the first 30 days of life, presumably because of trans-placental transfer of maternal antibody
(La Via WV, 1992).
Descriptive analysis of the US National Hospital Discharge Survey data from 1980
through 1996 showed that admissions associated with bronchiolitis totaled 1.65 million. (Shay
DK, et al 1980). In a retrospective analysis of data from the same source for 1997-2006, RSV-
coded hospitalizations accounted for 24% of an estimated 5.5 million lower respiratory tract
infection hospitalizations among children younger than 5 years of age (Stockman LJ, et al
2006). Between 2-3% of all children younger than 12 months of age are hospitalized with a
diagnosis of bronchiolitis, which accounts for between 57,000 and 172,000 hospitalizations
annually (Hall CB, et al 2013). The cost of hospitalization for bronchiolitis in children
younger than 2 years is estimated to be more than $1.7 billion in 2009 (Hasegawa K, et al
2013). While bronchiolitis remains a cause of significant mortality among children in the
developing world, fewer than 100 annual deaths in the United States among young children
are attributable to RSV infection (Byington CL, et al 2015).
In most regions of the United States, the highest RSV activity usually occurs in winter
with peaks from October to February and a relative subsidence only from March to July. An
exception is the subtropical regions of the southeastern United States (eg, Florida) where RSV
is endemic throughout the year (Halstead DC, 1998).
Secondary RSV infections occur in 46% of family members, 98% of other
children attending a childcare center, 42% of hospital staff, and 45% of previously uninfected
hospitalized infants (Henderson FW, et al 1979) Infection is spread through self-inoculation of
nasopharyngeal or ocular mucous membranes after direct contact with respiratory fomites and

8
contaminated environmental surfaces. RSV can survive for several hours on hands and
surfaces; therefore, handwashing and using disposable gloves and gowns may reduce
nosocomial spread (Leclair JM, et al 1987).

2.5.2 International Statistics

Bronchiolitis is a significant cause of respiratory disease worldwide. According to the

World Health Organization bulletin an estimated 150 million new cases occur annually; 11-20
million (7-13%) of these cases are severe enough to require hospital admission. Worldwide,
95% of all cases occur in developing countries (Rudan I, et al 2004).
The frequency of bronchiolitis in developed countries appears to be similar to that in
the United States. Epidemiologic data for underdeveloped countries are incomplete.
Epidemiologic data from underdeveloped countries show that RSV is a predominant viral
cause of acute lower respiratory tract infections and accounts for about 65% of
hospitalizations attributed to viruses (Weber MW, et al 1998).
Despite incomplete data about RSV-associated mortality from developing countries, in
2005, RSV alone was estimated to cause 66,000 to 199,000 deaths among children younger
than 5 years of age (Nair H, et al 2010). Morbidity and mortality are higher in less-developed
countries likely because of poor nutrition and lack of resources for supportive medical care.
In the northern hemisphere, RSV epidemics generally occur annually in winter and
late spring, whereas para-influenza outbreaks usually occur in the fall. Conversely, in the
southern hemisphere, wintertime epidemics occur from May to September.
Descriptive epidemiologic data from a population-based cohort Georgia Air Basin,
Canada reported by Koehoorn et al indicated that from 1999 through 2002, bronchiolitis was
associated with 12,474 inpatient and outpatient physician contacts during the first year of life.
This equates to 134.2 cases per 1000 person-years. In total, 1588 bronchiolitis cases resulted
in hospitalization (17.1 cases per 1000 person-years) (Koehoorn M, et al 2008).

2.5.3 Age-Related Demographics

Although infection with the agents that cause bronchiolitis may occur at any age, the
clinical entity of bronchiolitis includes only infants and young children. About 75% of cases
of bronchiolitis occur in children younger than 1 year and 95% in children younger than 2
years. Incidence peaks in those aged 2-8 months.

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 Age is a significant factor in the severity of infection: The younger the patient is, the
more severe the infection tends to be, as measured by the lowest oxygen saturation. Infants
younger than 6 months are most severely affected, owing to their smaller, more easily
obstructed airways and their decreased ability to clear secretions.
Intrauterine cigarette-smoke exposure may impair in utero airway development or alter
the elastic properties of the lung tissue. Exposure to second-hand cigarette smoke (eg, by a
parent or family member) in the postnatal period compounds the severity of RSV
bronchiolitis in infants.
Although RSV bronchiolitis is clearly a significant disease of the young child,
immunity has been shown to wane over time (Terrosi C, et al 2009), susceptible adults may
be asymptomatic or mildly symptomatic and act as carriers. With the increasing use of
treatment modalities that compromise cellular immunity, RSV infection may be life-
threatening to older children and adults undergoing organ and bone marrow transplantation, as
well as to the elderly. (Falsey AR, et al 1749)

2.5.4 Sex-Related Demographics

Severe bronchiolitis occurs more frequently in males than in females; a pattern similar
to other respiratory viral infections. The exact reason for this difference is unknown. (Weber
MW, et al 1998). Death is 1.5 times more likely in males (Mage DT, et al 2004).

2.5.5 Race-Related Demographics

Race and low socioeconomic status may adversely affect outcome in patients with
acute bronchiolitis. Multiple population-based reports sponsored by the Centers for Disease
Control and Prevention (CDC) indicate no disparity in the rates of hospitalization for RSV
infection between black and white children (Iwane MK, et al 2002). A study by La Via et al.
demonstrated that although more minority children than white children were hospitalized with
RSV infection, nothing indicated that the infections in minority children were more or less
severe than those in white children (La Via et al 1993).
Lower socioeconomic status may increase the likelihood of hospitalization.
Hospitalization rates are higher in Native American, Alaskan, and Hispanic populations, but it
is not clear if this is due to more severe infection or to a lower threshold for admission.

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2.6 Diagnosis

Bronchiolitis is a clinical diagnosis based on a directed history and physical

examination. Bronchiolitis may present with a wide range of symptoms and severity, from a
mild upper respiratory tract infection (URTI) to impending respiratory failure (table2.1).
Bronchiolitis typically presents with a first episode of wheezing before the age of 12 months.
The course begins with a two-to-three-day viral prodrome of fever, cough and rhinorrhea
progressing to tachypnea, wheeze, crackles and a variable degree of respiratory distress. Signs
of respiratory distress may include grunting, nasal flaring, in drawing, retractions or
abdominal breathing. There may or may not be a history of exposure to an individual with a
viral URTI.

Table 2.1 History, symptoms and signs of viral bronchiolitis

Preceding viral upper respiratory tract infection, cough and/or rhinorrhea

Exposure to an individual with viral upper respiratory tract infection
Signs of respiratory illness may also include:
 Tachypnea
 Intercostal and/or subcostal retractions
 Accessory muscle use
 Nasal flaring
 Grunting
 Colour change or apnea
 Wheezing or crackles
 Lower O2 saturations

Physical examination findings of importance include increased respiratory rate, signs

of respiratory distress, and crackles and wheezing on auscultation. Measurement of oxygen
saturation often shows decreased saturation levels. Signs of dehydration may be present if
respiratory distress has been sufficient to interfere with feeding.
While the majority of wheezing infants who present acutely between November and
April most likely have viral bronchiolitis, clinicians should consider a broad differential
diagnosis, especially in patients with atypical presentations such as severe respiratory distress,
no viral URTI symptoms and/or frequent recurrences (Zorc JJ, et al 2011).

11
Table 2.2 Differential diagnosis for wheezing in young children

Viral bronchiolitis

Asthma

Other pulmonary infections (eg, pneumonia)

Laryngotracheomalacia

Foreign body aspiration

Gastroesophageal reflux

Congestive heart failure

Vascular ring

Allergic reaction

Cystic fibrosis

Mediastinal mass

Tracheoesophageal fistula

2.7 Investigations

Diagnostic studies are not indicated for most children with bronchiolitis (Table2.3).
Tests are often unhelpful and can lead to unnecessary admissions, further testing and
ineffective therapies. Evidence-based reviews have not supported the use of diagnostic testing
in typical cases of bronchiolitis (Zorc JJ, et al 2010).

Table 2.3 Role of diagnostic studies in typical cases of bronchiolitis

Type Specific indications

Chest radiograph Only if severity or course suggests alternate diagnosis

Nasopharyngeal swabs Only if required for cohorting admitted patients

Generally, not helpful in diagnosis or monitoring of routine
Complete blood count
cases

Blood gas Only if concerned about potential respiratory failure

Not recommended routinely; may be required based on clinical

Bacterial cultures
findings and a child’s age.

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 2.7.1 Chest Radiograph (CXR)
Chest radiography of infants with bronchiolitis often reveals nonspecific, patchy
hyperinflation and areas of atelectasis (Smyth RL, et al 2006) which may be misinterpreted as
consolidation. This can lead to increased and inappropriate use of antibiotics (Swingler GH, et
al 1998) In infants with typical bronchiolitis, a recent prospective study found CXR findings
inconsistent with bronchiolitis in only two of 265 infants, and in no case did the results
change acute management (Schuh S, et al 2007). While routine CXR is not supported by
current evidence, it should be considered when the diagnosis of bronchiolitis is unclear, the
rate of improvement is not as expected or the severity of disease raises other diagnostic
possibilities such as bacterial pneumonia.

2.7.2 Nasopharyngeal Swabs

Nasopharyngeal swabs for respiratory viruses generally are not helpful from a
diagnostic perspective and do not alter management in most cases. They are not routinely
recommended unless required for infection control (ie, the cohorting of hospitalized patients).
Recently, however, the high rate of co-infection with multiple viruses has called even this
indication into question (Mansbach JM, et al 2012).

2.7.3 Complete Blood Count

Complete blood count has not been found to be useful in predicting serious bacterial
infections (SBI) (Purcell K, et al 2007).

2.7.4 Examination Often Reveals Bacterial Cultures

The incidence of concomitant SBI is believed to be very low, but not insignificant, in
febrile infants with bronchiolitis (Zorc JJ, Hall CB. 2010). Infants in their first two months of
life have the greatest risk of SBI, especially urinary tract infection. Rates vary from 0% to
6.1%. Bacteremia is rare (<1%) in most studies. Meningitis complicating bronchiolitis is also
extremely rare. A study in the office setting of febrile infants with bronchiolitis found no
cases of SBI out of 125 patients with bronchiolitis, compared with 212 of 1933 (11%) in a
febrile group of similar age without bronchiolitis (Luginbuhl LM, et al 2008).

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2.8 Decision for Admission to Hospital

The decision to admit should be based on clinical judgment and consider the infant’s
respiratory status, ability to maintain adequate hydration, risk for progression to severe
disease and the family’s ability to cope (Tables2.4 and Table2.5). Physicians should keep in
mind that the disease tends to worsen over the first 72 h when deciding whether to hospitalize
(Wainwright C. et al 2010). Clinical scores and individual findings on physical examination
cannot be relied on, in isolation to predict outcomes. Severity scoring systems exist; however,
none are widely used and few have demonstrated predictive validity. Respiratory rate,
subcostal retractions and oxygen need may be the most helpful parameters used in the various
bronchiolitis severity scores (Destino L, et al 2012).

Table 2.4 Groups at higher risk for severe disease

 Infants born prematurely (<35 weeks’ gestation)

 <3 months of age at presentation
 Hemodynamically significant cardiopulmonary disease
 Immunodeficiency

Table 2.5 Guidelines for admission may include:

 Signs of severe respiratory distress (eg, indrawing, grunting, RR >70/min)

 Supplemental O2 required to keep saturations >90%
 Dehydration or history of poor fluid intake
 Cyanosis or history of apnea
 Infant at high risk for severe disease
 Family unable to cope

Repeated observations over a period of time are important because there may be
significant temporal variability. Consistent predictors of hospitalization in outpatient
populations (Zorc JJ, Hall CB. 2010) include age (<3 months) and history of prematurity (<35
weeks’ gestation). Another study found that patients with any three of the following four
factors – decreased hydration, accessory muscle score >6 of 9, oxygen saturation<92% and
respiratory rate >60 breaths/min, had a 13-fold increase in hospitalization rate (Parker MJ, et
al 2009). The role of pulse oximetry in clinical decision-making remains controversial. While

14
oxygen saturations of <94% are associated with a more than five-fold increase in likelihood of
admission, (Mansbach JM, et al 2008) it is important to recognize that setting arbitrary
thresholds for oxygen therapy will influence admission rates. This effect was illustrated in a
survey of emergency department physicians that showed a significant increase in the
likelihood of recommending admission by simply reducing saturation from 94% to 92% in
clinical vignettes (Mallory MD, et al 2003).

2.9 Management

Bronchiolitis is a self-limiting disease. Most children have mild disease and can be
managed with supportive care at home. For those requiring admission, supportive care with
assisted feeding, minimal handling, gentle nasal suctioning and oxygen therapy still forms the
mainstay of treatment table2.6.

Table 2.6 Treating bronchiolitis:

Recommended Evidence equivocal Not recommended

Salbutamol (Ventolin;
Epinephrine nebulization GlaxoSmithKline, USA)
Nasal suctioning Corticosteroids
Oxygen
3% hypertonic saline nebulization Antibiotics
Hydration
Combined epinephrine and Antivirals
dexamethasone Cool mist therapies or therapy
with saline aerosol

2.9.1 Therapies Recommence Base on Evidences

[Link] Oxygen

Supplemental oxygen therapy is a mainstay of treatment in hospital. Oxygen should be

administered if saturations fall below 90% and used to maintain saturations at ≥90%. To
minimize handling, oxygen is usually administered via nasal cannula, face mask or a head
box. A recent alternative is humidified high-flow nasal cannula therapy (Mayfield S, et al
2014) which may be better tolerated and potentially decrease the need for mechanical

15
ventilation (McKiernan C, et al. 2012). At this point, there is insufficient evidence to
determine effectiveness (Beggs S, et al 2014). There are, however, ongoing studies
investigating this question, which will likely help to guide practice in the near future.

[Link] Hydration

Some degree of fluid supplementation is required in 30% of hospitalized patients with

bronchiolitis (Kennedy N, Flanagan N. 2005).
Frequent feeds should be encouraged and breastfeeding supported; both may be
facilitated by providing supplemental oxygen. Infants with a respiratory rate >60 breaths/min,
particularly those with nasal congestion, may have an increased risk of aspiration and may not
be safe to feed orally. When supplemental fluids are required, a recent randomized trial found
nasogastric (NG) and intravenous (IV) routes to be equally effective, with no difference in
length of hospital stay (Oakley E, et al, 2013). NG insertion may require fewer attempts and
have a higher success rate than IV placement. If NG bolus feeds are not tolerated, slow
continuous feeds are an option. If the IV route is used, isotonic fluids (0.9% NaCl/5%
dextrose) are preferred for maintenance, with regular monitoring of serum Na because of the
risk of hypernatremia (Wang J, 2014).

2.9.2 Therapies for Which Evidence is Equivocal

[Link] Epinephrine

Some studies have shown that epinephrine nebulization may be effective for reducing
hospital admissions, and one trial showed that combined treatment with epinephrine and
steroids reduced admissions (Plint AC, et al. 2009). However, the evidence remains
insufficient to support routine use of epinephrine in the emergency department. It may be
reasonable to administer a dose of epinephrine and carefully monitor clinical response;
however, unless there is clear evidence of improvement, continued use is not appropriate. A
systematic review of 19 studies evaluating the use of epinephrine in bronchiolitis shows no
effect on length of hospital stay and there is insufficient evidence to support its routine use in
admitted patients (Hartling L, et al. 2011).

[Link] Nasal Suctioning

16
 As for many long-standing and commonly used therapies for children, there is scant
evidence supporting the use of nasal suctioning in the management of bronchiolitis. While it
appears that suctioning mucus out of blocked nares would be a harmless procedure, one recent
study has suggested that deep suctioning and long intervals between suctioning are associated
with increased length of stay. This suggests that if suctioning is performed, it should be done
superficially and reasonably frequently (Mussman GM, et al 2013).

[Link] Hypertonic Saline Nebulization

The value of nebulized 3% hypertonic saline is being strongly debated and definitive
recommendations will likely require further accumulation of evidence. It is hypothesized that
hypertonic saline increases mucociliary clearance and rehydrates airway surface liquid, and
there is evidence of reduced clinical severity scores in both inpatient and outpatient
populations with no reports of significant adverse events (Zhang L, et al 2013). A Cochrane
review of 11 trials found that nebulized hypertonic saline was associated with a reduced
length of stay of one day in settings where the admission was longer than three days. The
optimal treatment regimen remains unclear. The most commonly used regimen in most trials
has been 3% saline with or without added bronchodilator by jet nebulizer three times daily,
with an interval of 8 hours between treatments. Further studies since the Cochrane review
have shown mixed results (Wu S, et al, 2014). Nebulized 3% saline may be helpful in the
inpatient setting; this treatment appears primarily to benefit patients with a longer length of
stay. Evidence does not currently support its routine use in the outpatient setting.

[Link] Combination Epinephrine and Dexamethasone

One publication from the Pediatric Emergency Research Canada group found an
unexpected synergism between the administrations of nebulized epinephrine with oral
dexamethasone. The combination appeared to result in a reduced hospitalization rate, with a
number needed to treat of 11. However, these results were rendered non-significant when
adjusted for multiple comparisons (Plint AC, et al. 2009). More research is needed to assess
the role of combination therapies. Pending better definition of its risks and benefits, this
combination is not recommended for the therapy of otherwise healthy children with bronchiolitis.
2.9.3 Therapies Not Recommenced Based On Evidence

17
 [Link] Salbutamol (Ventolin, GlaxoSmithKline, USA)

Children with bronchiolitis present with a wheeze that is clinically similar to that
observed with asthma. However, the pathophysiology of bronchiolitis is such that the airways
are obstructed (Zorc JJ 2010) rather than constricted. Furthermore, infants appear to have
inadequate β-agonist lung receptor sites and immature bronchiolar smooth muscles (Anil AB,
et al. 2010) While studies have shown small improvements in clinical scores, bronchodilators
have not been shown to improve O2 saturation, do not reduce admission rates and do not
shorten the duration of stay in hospital (Gadomski AM 2014). When the diagnosis of
bronchiolitis is clear, a trial of salbutamol is not currently recommended (American Academy
of Pediatrics, 2006).

[Link] Corticosteroids

Corticosteroids, such as dexamethasone, prednisone or inhaled glucocorticoids, are not

associated with a clinically significant improvement in disease, as measured by reduction in
clinical scores, rates of hospitalization and length of hospital stay (American Academy of
Pediatrics, 2006). Furthermore, any small benefit that corticosteroids may offer must be
weighed against the risks of steroid treatment. Corticosteroids are not recommended for
routine use in bronchiolitis.

[Link] Antibiotics

Many children with acute bronchiolitis are prescribed an antibiotic. However, bacterial
infection in otherwise healthy children with bronchiolitis is exceedingly rare. Research on the
role of antibiotics in bronchiolitis is limited and has, to date, failed to identify any benefit.
Further research is needed to develop criteria for identifying the minority of patients at high
risk for secondary bacterial infection. Currently, antibiotics should not be used except in cases
in which there is clear, documented evidence of a secondary bacterial infection (Spurling GK,
et al 2011).

[Link] Antivirals

Antiviral therapies, such as ribavirin, are expensive, cumbersome to administer,

provide limited benefit and are potentially toxic to care providers and, thus, are not
recommended for the routine treatment of bronchiolitis in otherwise healthy children. In
patients with or at risk for particularly severe disease, antivirals could be considered, but this

18
decision should be made on an individual basis in consultation with appropriate subspecialists
(American Academy of Pediatrics, 2006).

[Link] Chest Physiotherapy

Nine clinical trials comparing physiotherapy with no treatment were reviewed (Roqué
i Figuls M, et al 2012). Neither vibration and percussion nor passive expiratory techniques
were shown to improve clinical scores or to reduce hospital stay or duration of symptoms.
Chest physiotherapy is not recommended for the treatment of bronchiolitis (American
Academy of Pediatrics 2006).

[Link] Cool Mist Therapies or Aerosol Therapy with Isotonic Saline

Cool mist and other aerosol therapies have been used for some time to manage
bronchiolitis, with scant evidence supporting their efficacy. A recent Cochrane review
concluded that there is no evidence supporting or refuting the use of cool mist and other
aerosols for managing bronchiolitis (Umoren R 2011).
Other therapies used for critically ill infants with severe bronchiolitis, such as
helium/oxygen, nasal continuous positive airway pressure, mechanical ventilatory support and
surfactant, are beyond the scope of this statement (Essouri S, et al. 2011).

2.10 Monitoring in Hospital

Patients with bronchiolitis should be cared for in an environment with ready access to
suction equipment and supplemental oxygen that can be delivered at measurable rates. Close
attention must be devoted to infection control processes. Respiratory contact isolation may
reduce nosocomial transmission, but there is conflicting evidence regarding the benefits of
cohorting patients (Hall CB, et al. 2009).
The most important component of monitoring infants admitted with bronchiolitis is
regular and repeated clinical assessments by staff with appropriate expertise in the respiratory
assessment of young children. Monitoring should include assessment and documentation of
respiratory rate, work of breathing, oxygen saturation, findings on auscultation and general
condition, including feeding and hydration status. Scoring tools have been developed in an
attempt to standardize assessments and facilitate communication among caregivers. However,

19
there is insufficient evidence of impact on patient outcomes to recommend using any specific
tool (Liu LL, et al, 2004).
The use of electronic monitoring of vital signs and oxygen saturation should not be
considered to be a substitute for regular clinical assessments by experienced personnel.
Furthermore, there is growing evidence to suggest that continuous monitoring may prolong
length of stay, particularly if staff react to normal transient dips in oxygen saturation or
changes in heart and respiratory rates with interventions such as restarting oxygen therapy
(Schroeder AR 2004). The accuracy of pulse oximetry is relatively poor, particularly at
saturations <90 % (Ross PA 2014).
The primary rationale for cardiac and respiratory monitoring is to detect episodes of
apnea requiring intervention. The incidence of apnea in RSV bronchiolitis may be lower than
previously believed. In a large study involving 691 infants <6 months of age, only 2.7% had
documented apnea, and all had risk criteria of either a previous apneic episode or young age
(<1 month or <48 weeks post-conception in premature infants). Continuous electronic cardiac
and respiratory monitoring may be useful for high-risk patients in the acute phase of illness
but are not necessary for the vast majority of patients with bronchiolitis (Willwerth BM 2006).
Determining oxygen saturation can aid in decisions about escalating or weaning
oxygen therapy. However, the issue of continuous versus intermittent monitoring of oxygen
saturation is controversial. Continuous monitoring may be more sensitive for identifying
patients who are deteriorating and need escalation of treatment. At the same time, many
healthy infants exhibit typical transient O 2 saturation dips and length of stay may be
prolonged if oxygen therapy is based on arbitrary saturation targets. Several clinical trials
currently underway are attempting to determine best practices in this area. Until clear
evidence is available, a reasonable approach is to adjust the intensity of oxygen saturation
monitoring according to the patient’s clinical status. Continuous saturation monitoring is
appropriate for high-risk patients early in the course of disease, while intermittent monitoring
is most appropriate for lower-risk patients and for all patients once they are feeding well,
weaning from supplemental oxygen and showing improvement in work of breathing (Hunt
CE, et al. 1999; Poets A. et al. 2009).
Readiness for discharge from hospital should be based on clinical judgment and
consider the family’s ability to recognize and respond to signs of deterioration. In general,
patients may be safely discharged from hospital once they are improving clinically and meet
criteria listed in Table2.7.
Table 2.7 Discharge from hospital

20
 Tachypnea and work of breathing improved

Maintain O2 saturations >90% without supplemental oxygen OR stable for home oxygen
therapy

Adequate oral feeding

Education provided and appropriate follow-up arranged

2.11 Patient Education

Education should be provided regarding the following:

 Importance of RSV prophylaxis for high-risk patients
 Importance of avoiding RSV exposure in the first 2-3 months of life
 Natural history of bronchiolitis
Instructions to be provided at discharge should include the following:
 Positioning
 Maintenance of oral hydration
 Temperature control
 Use of prescribed medications
 Avoidance of exposure to tobacco smoke or other irritants
 Methods for limiting transmission (eg, hand washing and avoiding childcare
centers while ill)
 Criteria for return to the ED

2.12 Complications

Complication with bronchiolitis, as with any disease, various complications are

possible, including those caused by therapy. In most cases, the disease is mild and self-
limited. However, in infants who are immunosuppressed and those with preexisting heart or
lung disease, RSV bronchiolitis can result in any of the following (Thomas JA, et al 1997).
 Acute respiratory distress syndrome (ARDS)
 Bronchiolitis Obliterans

21
  Congestive heart failure
 Secondary infection
 Myocarditis
 Arrhythmias
 Chronic lung disease
A possible association with asthma has been reported (Hyvarinen MK, et al 2007)
RSV infections have been associated with the development of asthma later in life, with an
odds ratio of 4.3 in children aged 11 years or younger. However, because virtually all children
encounter an RSV infection during the first 2-3 years of life, this association may reflect a
multifactorial etiology or a genetic predisposition. A genetic predisposition to wheeze after
severe RSV bronchiolitis has been suggested (McNamara PS, et al, 2004). Other studies
suggest that human meta-pneumovirus (hMPV) or rhinovirus-associated bronchiolitis or co-
infection with RSV and hMPV increase the likelihood of developing asthma in later years
(Garcia-Garcia ML, et al, 2007).
A genetic predisposition to severe bronchiolitis and to subsequent development of
asthma is supported by findings of polymorphisms in genes involved in allergy, inflammatory
response and innate immunity (Bucasas KL, et al, 2013). In fact, a Danish study of twins
found that severe bronchiolitis may be an indicator of a genetic predisposition to asthma and
without this disposition, asthma is less likely to develop even if the infant had developed
bronchiolitis (Thomsen SF, et al, 2009).
As many as 1% of previously healthy children and 3% of development impaired in
children with bronchiolitis experience neurologic complications. These include seizures,
encephalopathy with hypotonia, irritability, and abnormal tone. The long-term prognosis for
these children is still unknown (Sweetman LL 2005).

2.13 Prognosis

According to the WHO 2015 Global Health Observatory data repository, acute
lower respiratory infection in children younger than 5 years of age remains a leading cause of
childhood mortality in the world. In 2015, acute respiratory tract infection accounted for an
estimated 1.84 million deaths worldwide; 85% of these deaths occurred in Africa followed by
8% in Southeast Asia (World Health Organization 2015).

22
 Bronchiolitis is an infectious, self-limited disease. Therapy is based on supportive
care, oxygenation, hydration, and fever control. With early recognition and treatment,
prognosis is usually very good. Most children with bronchiolitis, regardless of severity,
recover without sequelae. The course of disease is usually 7-10 days, but a few remain ill for
weeks. Some infants who recover from acute bronchiolitis have an increased frequency of
recurrent wheezing.
Hospitalization is required in 2-3% of bronchiolitis cases among infants younger
than 12 months of age. Annually, RSV bronchiolitis accounts for about 57,000-172,000
hospitalizations. In a prospective, population-based surveillance of acute respiratory
infections, RSV accounted for 20% of hospitalizations, 18% of ED visits, and 15% clinic
visits in winter (Hall CB, et al. 2009). Hospitalization is significantly more likely at altitudes
above 2500 meters.
Overall, the mortality in children hospitalized for bronchiolitis in different series
ranges from 0.2% to 7%. This large variability is based on investigations of different cohorts
with different risk factors and different points in time relative to modern intensive care.
Morbidity and mortality from RSV mostly occur in children younger than 2 years. Other
high-risk infants and children include premature infants younger than 6 months, infants and
children with underlying pulmonary or cardiac disease, and those an immune deficiency
(Holman RC, et al. 2003).
Studies in pediatric ICUs (PICUs) of children with RSV bronchiolitis without
comorbidities show a 2-3% death rate, regardless of whether the children had CHD with
pulmonary hypertension (Wang EE 1995). In a cohort study from 1999-2007 in the United
Kingdom, RSV bronchiolitis-related mortality was 1.7% with higher risk of death associated
with preexisting conditions, especially cardiac anomalies (Thorburn K 2009).
Although significant morbidity is unusual, multiple small studies suggest that children
who have been hospitalized with RSV bronchiolitis have a higher incidence of reactive airway
disease and more abnormalities in pulmonary function than children never hospitalized for
RSV (Goetghebuer T, et al 2004). These abnormalities may persist for as long as 5 years,
eventually normalizing. Conflicting small studies have failed to prove whether early treatment
of acute RSV bronchiolitis with ribavirin reduces the persistence of pulmonary dysfunction
(Krilov LR, et al 1997).
Although bronchiolitis has been identified as a risk factor for asthma, this does not
necessarily imply causation. Children already predisposed to asthma may be more likely to
wheeze when exposed to RSV or other respiratory infections or allergic stimuli. On the other

23
hand, it is postulated that RSV infection may predispose an individual to later bronchospasm
by selective promotion of specific subsets of helper T cells.
Multiple studies have shown that children, including febrile infants younger than 8
weeks, with confirmed RSV infection have a lower risk of serious bacterial infections or
secondary bacterial super-infection than controls (eg, 0% vs 2.7% for bacteremia, and 2% vs.
14% for urinary tract infection). The risk of concurrent bacterial infections is low (Titus MO,
Wright SW, 2003).

2.14 Prevention

RSV is transmitted via direct contact with secretions of infected patients. Droplets and
fomites play a less important role. Meticulous attention to hand washing between patient
contacts should reduce the likelihood of hospital staff acquiring RSV infection from patients
and of spreading infection by carrying RSV on their hands (Hall CB, et al 1976).
Attempts to develop a safe and effective RSV vaccine have thus far been unsuccessful.
A 1967 study of a formalin-inactivated RSV vaccine resulted in a 15-fold increase in
hospitalization and mortality when immunized patients were subsequently re-infected; an
adequate explanation for this exaggerated pulmonary response has not been elucidated
(Englund J.2005). Efforts to develop an RSV vaccine continue (Remot A, et al, 2012). A live-
attenuated intranasal administered RSV vaccine is being developed. Another approach being
studied involves maternal immunization against RSV during pregnancy, with the hope of
providing neutralizing antibodies that cross the placenta to protect the infant (Glenn GM, et
al. 2016).
Active prophylaxis using RSV immunoglobulin intravenously (RSV-IGIV) at high
doses was shown to prevent RSV in high-risk patients (Groothuis JR, et al 1993). However, a
more convenient RSV-specific humanized mouse IgG1 monoclonal antibody preparation,
palivizumab, was subsequently developed and FDA-approved in 1998 for prophylaxis for
infants at high risk for RSV infection. Palivizumab is administered intramuscularly (IM) at a
dose of 15 mg/kg every month for a maximum of 5 doses during the RSV season (ie, from
October through February in most U.S. regions).
In a multi-institutional, randomized, placebo-controlled study of 1502 high-risk
preterm infants in 139 centers in the United States and Canada during the 1996-1997 RSV
season, rate of hospitalization was reduced by 5.8% (10.6% in placebo vs. 4.8% in

24
palivizumab group, P< 0.001) (Palivizumab,1998). Infants receiving palivizumab had reduced
hospital length of stay, days on oxygen, and ICU admissions. Adverse effects were
uncommon. Romero summarized 4 outcome studies encompassing over 16,000 children after
the use of palivizumab; all showed high effectiveness in reducing RSV admissions (Romero
JR. 2003).
A 2005 study of PICU admissions for bronchiolitis did not demonstrate a decrease in
admissions or need for ventilation before and after palivizumab was licensed. In this study,
83% of the infants admitted to the ICU did not meet AAP criteria for RSV prophylaxis (Prais
D 2005). Stevens and Hall summarized the controversies regarding the use of palivizumab for
children born at 32-35 weeks’ gestation. They concluding that if these infants do not have
chronic lung disease and are younger than 6 months at the start of the RSV season, they may
benefit from RSV prophylaxis if at least 2 of the following are observed: daycare attendance,
school-aged siblings, passive smoke exposure, airway abnormalities or neuromuscular disease
(Stevens TP 2004).
Since palivizumab was licensed for RSV immune-prophylaxis, the recommendations
for its use have become more restrictive as additional information became available regarding
the epidemiology of RSV hospitalizations and the limited benefit of prophylaxis in selected
patient populations. AAP guidance regarding palivizumab use is stratified according to risk
and can be summarized as follows:
 Preterm infants born before 29 weeks of gestation, without chronic lung disease of
prematurity or congenital heart disease and less than 12 months of age at the start
of RSV season; those born on or after 29 weeks of gestation should NOT receive
prophylaxis as their rate of hospitalization for bronchiolitis is not different from
full0term infants.
 Preterm infants born before completing 32 weeks of gestation with chronic lung
disease of prematurity and requirement for supplemental oxygen for the first 28
days of life.
 Infants born with a cyanotic congenital heart disease. Palivizumab is NOT
recommended routinely for infants with cyanotic congenital heart diseases there is
no significant reduction in rate of hospitalization for RSV.
 For children older than 12 months of age, palivizumab is recommended only for
when there is chronic lung disease requiring supplemental oxygen or diuretic or
glucocorticoid therapy.

25
 Prevention of serious RSV infection by giving palivizumab may reduce the incidence
of subsequent wheezing (Simoes EA, et al 2007).
Unfortunately, although the use of palivizumab is possibly cost-effective, the cost per
individual patient is still high (approximately $5000), which means that the availability of this
agent is limited to high-risk patients (Wegner S, et al 2004).

26
 CHAPTER III
RESEARCH METHODOLOGY

3.1 Study Design

This is a retrospective study of acute bronchiolitis.

3.2 Study Period

All data that selected from patient’s documents with diagnosis acute bronchiolitis from
January 1st to December 31st, 2022.

3.3 Study Population

All children age <5 years old registered for acute bronchiolitis in Dangkor Referral
Hospital.

3.4 Sample Size

Number of children were hospitalized total acute bronchiolitis profiles had 94 cases.

3.5 Inclusion Criteria

- Children diagnosed with acute bronchiolitis in a medical file.

- Aged under 5 years old.
- Complete patient’s profiles

3.6 Exclusion Criteria

- Incomplete patient’s profiles

- The age of children over 5 years old.

27
3.7 Equipment and Instrument

- Patient’s documents in the hospital

- Computer for data management, data entry and data analysis
- Check list

3.8 Data Collection

- Age of the patient

- Sex of the patient
- Patient's place of residence
- Month of illness
- Breastfeeding
- Vaccinated in accordance with the national program
- Clinical feature
- Investigation for diagnosis
- Management
- Hospitalization

3.9 Data Management

3.9.1 Data Entry

The data started to record in to the computer with the Microsoft Excel. It’s the special
program for data entry that’s can prevent from error while entry. All 94 cases had completed
entry by taking a few days for these whole data.

3.9.2 Data Analysis

This processing is the good steps for analyzing by using Microsoft Excel. Those data
are transcript in to the tables or figures related to our objectives.

3.10 Ethics

All personal information of the patient is not disclosed to the public. All patient
outcomes are results that do not identify the patient. The identities of patients are known only
to the researchers and their leaders. This study did not affect patients or their guardians.

28
 CHAPTER IV
RESULTS

By collecting data from patient files kept in the pediatric department of Dangkor
Referral Hospital, all data has been to classify and identify important data related topics for a
full year from January 1st to December 31st, 2022, with a total of 94 cases. For the results to
show the following table and graphics:

4.1 Sex of Children

60
56 (59.57%)

50

38 (40.43%)
40

30

20

10

0
Male Female

Figure 4.1 Distribution by Sex of Children

Out of these 94 cases, 56 cases (59.57%) were male and 38 cases (40.43%) were
female. Sex ratio for male to female was 1.47:1.

4.2 Age of Children

The median age of children at the time of admission for care and treatment was 8
months old, range from 14 days of age (haft months) to 50 months, IQR: 3 -15 months. Age <
6months old was 34 cases (36.17%); aged 6-11 months was 27 cases (28.72%); aged 12-23
months was 16 cases (17.02%); aged 24-35 months was 9 cases (9.57%) and aged ≥36 months
was 8 cases (8.51%). Table4.1. below 77 cases of 94 cases (81.91%) were at age under 24
months old.

29
Table 4.1 Distribution by Age groups

Age groups Number of cases Percentage

<6 months 34 36.17%

6 months to 11 months 27 28.72%

12 months to 23 months 16 17.02%

24 months to 35 months 9 9.57%

36 months to <60 months 8 8.51%

Total 94 100.00%

4.3 Geographical Distribution

70
61 (64.89%)
60

50

40

30
24 (25.53%)
20

9 (9.57%)
10

0
Dangkor District Other Districts Other Provinces

Figure 4.2 Distribution by Geographical

Most of children were from dangkor district that accounted for 61 cases (64.89), 24
cases (25.53%) from other districts and 9 cases (9.57%) from other provinces.

30
4.4 Distribution of Cases Admission by Months

For the month of the disease, in this result to show that in January there were 9 cases
(9.57%), in February there were 2 cases (2.13%), in March there were 4 cases (4.26%), in
April there were 7 cases (7.45%), in May there were 11 cases (11.69%), in June there were 3
cases (3.19%), in July there were 5 cases (5.32%), in August there were 12 cases (12.77%), in
September there were 17 cases (18.09%), in October there were 10 cases (10.64%), in
November there were 6 cases (6.38%) and in December there were 8 cases (8.51%).
The median number of cases admitted was 7.8 cases per month, range from 2 cases to
17 cases.

Table 4.2 Distribution of cases admitted by months

Months Number of cases Percentage

January 9 9.57%

February 2 2.13%

March 4 4.26%

April 7 7.45%

May 11 11.69%

Jun 3 3.19%

July 5 5.32%

August 12 12.77%

September 17 18.09%

October 10 10.64%

November 6 6.38%

December 8 8.51%

Total 94 100.00%

4.5 Breast Feeding Distribution

31
 50
45 (47.87%)
45
39 (41.49%)
40
35
30
25
20
15
10 (10.64%)
10
5
0
Breast Feeding Breast Milk Breast Mixed

Figure 4.3 Distribution by Breast feeding

The children had breast feeding has 39 cases (41.49%), the children that breast milk
has 45 cases (47.87%) and 10 cases (10.64%) of children’s document that breast mixed.

4.6 Patient Vaccination

60 57 (60.64%)

50

40
35 (37.23%)

30

20

10
2 (2.13%)
0
Completed Vaccination Incomplete Vaccination No Information

Figure 4.4 Distribution by Patient Vaccination

The children had completed vaccination has 35 cases (37.23%), the children had
incomplete vaccination has 57 cases (60.64%) and 2 cases (2.13%) no information.
4.7 Clinical Presentations

32
 4.7.1 Fever

70
63 (67.02%)
60

50

40
31 (32.98%)
30

20

10

0
Fever No Fever

Figure 4.5 Characteristics of fever

Among all children admitted, 63 cases (67.02%) were presented with fever and 31
cases (32.98%) presented without fever. However, in the history taken, there were reported
that had fever during this disease.

4.7.2 Cough

100
90 89 (94.68%)

80
70
60
50
40
30
20
10
5 (5.32%)
0
Cough No Cough

Figure 4.6 Characteristics of cough

On this result to found that the children had presented with cough 89 cases (94.68%)
and 5 cases (5.32%) had no caugh.

33
 4.7.3 Rhinorrhea

80 78 (82.98%)

70

60

50

40

30

20 16 (17.02%)

10

0
Rhinorrhea No Rhinorrhea

Figure 4.7 Characteristics of Rhinorrhea

On the figure above to shows that the children had presented with rhinorrhea 78 cases
(82.98%) and 16 cases (17.02%) did not has rhinorrhea.

4.7.4 Tachypnea (fast breathing)

80 76 (80.85%)
70

60

50

40

30
18 (19.15%)
20

10

0
Fast Breathing No Fast Breathing

Figure 4.8 Characteristics of breathing

In this study to defined as fast breathing for respiratory rate of ≥60/mn for infants
aged <2 months; ≥50/mn for children aged 2 months up to 12 months, and ≥40/mn for
children aged 12 months up to <60 months.

34
 4.7.5 Chest Indrawing (Tirage)

50 49 (52.13%)
45 (47.87%)
45
40
35
30
25
20
15
10
5
0
Chest Indrawing No Chest Indrawing

Figure 4.9 Result of chest indrawing finding

On this study to observe that the children had chest indrawing has 49 cases (52.13%)
and the children without chest indrawing has 45 cases (47.87%).

4.7.6 Wheezing

89 (94.68%)
90

80

70

60

50

40

30

20

10 5 (5.32%)

0
Wheezing No Wheezing

Figure 4.10 Result of wheezing finding

According to this study to show that the children had wheezing has 89 cases (94.68%)
and the children without wheezing has 5 cases (5.32%).

35
4.8 Chest X-Ray Performed

80 79 (84.04%)

70

60

50

40

30

20
15 (15.96%)
10

0
Chest X-Ray done No Chest X-Ray

Figure 4.11 Cases received CXR

Among all children admitted, 15 cases (15.96%) were received Chest X-Ray performed
and 79 cases (84.04%) no required to Chest X-Ray.

4.8.1 Chest X-Ray Result Findings

12
11 (73.33%)

10

4 (26.67%)
4

0
Abnormal Finding Normal

Figure 4.12 Result of CXR finding

Among 15 cases with CX-Ray performed, 11 cases (73.33%) presented with abnormal
finding suggestive for a favor of bronchiolitis, such as infiltrates and or atelectasis, and other
4 cases (26.67%) presented with normal image findings.

36
4.9 Blood Tests
90
81 (86.17%)
80

70

60

50

40

30

20
13 (13.83%)
10

0
Blood Tests No Blood Tests

Figure 4.13 Cases received blood testing

Routine blood test for CBC and CRP was done in 81 cases (86.17%). The result of
CBC was mostly presented with normal range of white blood cells and or leucopenia in some
cases. No blood culture test was requested in this setting.
The results of CRP, revealed value ranging from zero mg/L to 48 mg/L, in which 0
mg/L presented for 41 cases (50.62%), with value from >0mg/L to 10mg/L for 28 cases
(34.57%), and value >10mg/L for 12 cases (14.81%).

Table 4.3 Results of CRP

CRP Number of cases Percentage

0 mg/L 41 50.62%

>0mg/L to 10mg/L 28 34.57%

>10mg/L 12 14.81%

Total 81 100.00%

37
4.10 Diagnosis at Admission

In this table below to show that the children admission to diagnose with acute
bronchiolitis has 58 cases (%), and many other diagnoses as described in this table.

Table 4.4 Distribution by initial diagnosis at the time of admission

Item Initial diagnosis Number of cases Percentage

1 Acute Bronchiolitis 45 47.87%

2 Pharyngitis 11 11.71%

3 Pneumonia 9 9.57%

4 Asthma 7 7.45%

5 Bronchitis 5 5.32%

6 Broncho-pneumonia 4 4.26%

7 Rhinopharyngitis 3 3.19%

8 Neonatal infection 3 3.19%

9 Acute gastroenteritis (GEA) 2 2.13%

10 Beri Beri 2 2.13%

11 Dengue infection? 1 1.06%

12 Diarrhea 1 1.06%

13 Stomatitis 1 1.06%

Total 94 100.00%

38
4.11 Diagnosis at Discharge

For final diagnosis at discharge with acute bronchiolitis has 90 cases (95.74%), final
diagnosis with acute bronchiolitis with pharyngitis has 3 cases (3.19%) and final diagnosis
with acute bronchiolitis with laryngitis has 1 case (1.06%).

Table 4.5 Distribution by diagnosis at discharge

Item Final diagnosis Number of cases Percentage

1 Acute Bronchiolitis 90 95.74%

2 Acute Bronchiolitis with pharyngitis 3 3.19%

3 Acute Bronchiolitis with laryngitis 1 1.06%

Total 94 100.00%

12 Treatment

4.12.1 Antibiotic Use

80
75 (79.79%)
70

60

50

40

30

20 19 (20.21%)

10

0
Antibiotic Used Antibiotic Not Used

Figure 4.14 Antibiotic use

Among all children admitted, 19 cases (20.21%) received any kind of antibiotics
during this admission, and other 75 cases (79.79%) did not received antibiotics.

39
 4.12.2 Nebulization Use

Most of patients received adjunct medicines to treatment and care during admission.
Hypertonic saline was used in 70.21% of cases, berodual inhaler was used in 62.77%,
salbutamol inhaler was used in 47.87% .

Table 4.6 Types of nebulization used

Item Type of Inhalation’s drugs Number of cases Percentage

1 Hypertonic Saline 66 70.21%

2 Berodual Inhaler 59 62.77%

3 Salbutamol (Ventolin respirator solution) 45 47.87%

4.13 Length of Hospital Stay

The most of children stay in hospital was 4 days. The length of hospital stay less than
7 days was 82 cases (87.23%) and ≥7 days was 12 cases (12.77%).

Table 4.7 List of length of hospital stay by number of days

Duration of hospital stay in day Number of cases Percentage

1 day 3 3.19%

2 days 12 12.77%

3 days 18 19.15%

4 days 24 25.53%

5 days 14 14.89%

6 days 11 11.70%

7 days 4 4.26%

8 days 4 4.26%

40
 9 days 2 2.13%

10 days 1 1.06%

11 days 1 1.06%

Total 94 100.00%

4.14 Treatment Outcomes

Among all children, 93 cases (98.94%) were discharged with competed cure or
improvement and 1 case (1.06%) were referred to Kantha Bopha based on family request.

Table 4.8 Main Outcomes

Outcomes Number of cases Percentage

Cured (discharged) 93 98.94%

Referred 1 1.06%

94 100.00%

41
 CHAPTER V
DISCUSSION

Based on this study conducted to found some interesting information to discuss in

comparison with the other studies as below.

5.1 Comparison of Sex

Out of these 94 children admitted with the final diagnosis as acute bronchiolitis, 56
cases (59.57%) were male and 38 cases (40.43%) were female. So male was predominance
over female with male to female ratio 1.47:1.
The male predominance in this study was in line with many studies carried out in other
developing countries, with male to female ratio ranging from 1.05:1 to 2.19:1 and in the
proportion from 51.14% in a study in the Philippines by Fumihiko Ueno et al. (2019) up to
68.66% in a study of Vietnam by Lien Anh Ha Do, et al. (2019) as shows in the table below.
Contrary to male predominance, a study in Thailand conducted by Puneyavee
Aikphaibul et al. (2020) in a retrospective medical record review among children under 5
years old hospitalized with acute bronchiolitis showed that male was less predominant and
accounted for only 45.43%, for both severe and not severe presentations.

Table 5.1 Comparison of sex of children

Male to
Male Female
Author (year) Number Female
N (%) N (%)
Ratio
Our study 56 38
94 1.47:1
(Cambodia, 2022) (59.57%) (40.43%)

Lien Anh Ha Do, et al. 138 63

201 2.19:1
(Vietnam, 2019) (68.66%) (31.34%)

A Hindupur, et al. 75 71
146 1.06:1
(India, 2018) (51.37%) (48.86%)

Fumihiko Ueno, et al. 202 193

395 1.05:1
(Philippines, 2019) (51.14%) (48.86%)

Puneyavee A, et al. 194 233

427 0.83:1
(Thailand, 2020) (45.43%) (54.57%)

42
5.2 Comparison of Age

Age-specific incidence is important for targeting future prevention and control

strategies. In this result to found that the highest rate was 36.17% were among children aged
below 6 months, the second was children aged 6-11 months for 28.72%, the third was
children aged 12-23 months for 17.02%, and the last group was children aged ≥24 months old
for 18.09%. So, finding the highest rates among children aged <24 months were accounted for
81.91% that was consistent with previous other studies in developing countries (table5.3).
As compared with a study in the Vietnam [Lien Anh Ha Do, et al. 2019] which was
classified age of children in 5 groups, the children aged below 6 months has 24.38%, the
second was children aged 6-11 months for 21.39%, the third was children aged 12-23 months
for 28.36%, the four was children aged 24-35 months for 15.92% and the last group was
children aged ≥36 months old for 9.95%.
A study in the Philippines [Fumohiko Ueno et al. 2019] which was classified age of
patients in 5 groups as well and presented that the majority of children was in aged 12-23
months for 35.19%, the second was aged ≥36months for 20.51%.
However, another retrospective study conducted at the King Chulalongkorn Memorial
Hospital, children age <6month was almost the same of our result for 31.62%, the majority
presented in aged 12-23 moths for 34.66%, but age ≥24 months was only 11.48% [Puneyavee
A. et al. 2020].

Table 5.2 Comparison of specific age groups in 5 categories

<6 6-11 12-23 24-35 ≥ 36

Author (year) Number
months months months months months

34 27 16
Our study 9 8
94 (36.17% (28.72% (17.02%
(Cambodia, 2022) (9.57%) (8.51%)
) ) )
Lien Anh Ha Do, et 49 43 57 32
20
al. 201 (24.38% (21.39% (28.36% (15.92%
(9.95%)
(Vietnam, 2019) ) ) ) )
60 55 139 60 81
Fumihiko Ueno, et al.
395 (15.19% (13.92% (35.19% (15.19% (20.51%
(Philippines, 2019)
) ) ) ) )
135 95 148
Puneyavee A, et al. 49
427 (31.62% (22.25% (34.66%
(Thailand, 2020) (11.48%)
) ) )

43
 The epidemiological incidence stratified by two groups, in this study was in consistent
with others 3 studies presented the highest proportion in children aged <24 months ranging
from 64.30% to 88.52% as shows in table below.

Table 5.3 Comparison of specific age groups in two categories

Author (year) Number <24 months ≥ 24 months

Our study 77 17
121
(Cambodia, 2022) (81.91%) (18.09%)

Lien Anh Ha Do, et al. 149 52

201
(Vietnam, 2019) (74.13%) (25.87%)

Fumihiko Ueno, et al. 254 141

395
(Philippines, 2019) (64.30%) (35.70%)

Puneyavee A, et al. 378 49

427
(Thailand, 2020) (88.52%) (11.48%)

5.3 Comparison of Common Clinical Manifestations

Regarding the common clinical manifestations, this study to observed that there 6
signs and symptoms were recorded in the medical records, such as fever, cough, rhinorrhea,
respiratory rate looking for fast breathing, chest indrawing and wheezing and/or rhonchi.
Cough and wheezing presented the same rate of 94.68% in this study, rhinorrhea for 82.98%,
fast breathing was 80.85%, fever for 67.02% and chest indrawing for 52.13%. Similarly, a
study in India by Sandesh Kini, et al (2019) showed that children with cough for 92.95%, but
wheezing was only 51.17%, rhinorrhea was the second range for 85.90% and fever and chest
indrawing were the same as our findings. A study in Vietnam by Lien Anh Ha Do, et al
(2019) presented that chest indrawing and wheezing are the most common signs for their
study population with the rate of 96.02% and 95.52% respectively (but the author did not
mention the exact number of cough). Another study in the Philippines by Fumihiko Ueno, et
al (2019), the authors just presented 4 common clinical finding (fever for 24.05%, fast
breathing for 76.96%, chest indrawing for 17.72% and wheezing for 28.86%). A study in
Thailand by Puneyavee A, et al (2020) showed that cough was the first common for 94.38%
and second was rhinorrhea for 76.11% and chest indrawing for 74.24%, fever for 53.63%, fast
breathing for 49.65%, but wheezing was only 36.53%.

44
Table 5.4 Comparison of clinical features

Lien Anh Ha Fumihiko Puneyave

Our study Sandesh
Do, et al. Ueno, et al. e A, et al.
Common Clinical (Cambodia, Kini, et al.
(Vietnam, (Philippines, (Thailand,
Features 2022) (India, 2019)
2019) 2019) 2020)
N=94 N=383
N=201 N=395 N=427

95
63 264 112 229
Fever (24.05%)
(67.02%) (68.93%) (55.72%) (53.63%)

89 356 403
Cough - -
(94.68%) (92.95%) (94.38%)

78 329 181 325

Rhinorrhea -
(82.98%) (85.90%) (90.05%) (76.11%)

Dyspnea 76 253 166 304 212

(fast breathing) (80.85%) (66.06%) (82.59%) (76.96%) (49.65%)

Chest Indrawing 49 203 193 70 317

(Tirage) (52.13%) (53.00%) (96.02%) (17.72%) (74.24%)

89 196 192 114 156

Wheezing
(94.68%) (51.17%) (95.52%) (28.86%) (36.53%)

5.4 Comparison of Treatment

In this study to compared only two management categories for discussion, the use of
antibiotics and bronchodilators. We know that management for children with acute viral
bronchiolitis mainly consists of good supportive care, and most do not require specific
measure. Clinical practice in the acute management varies widely even between centers in one
country. In this study to collect only two main categories of treatment in the reporting form,
are antibiotics use and bronchodilators.
In this study to found that antibiotics has been used only in 20.21% that was less than
other studies that ranged from 38.17% in Thailand and up to 84.08% in Vietnam. However,
no surprising, most studies did not show evidence to support the use of antibiotics. Usually,
bacteremia is uncommon in children with RSV infection, unless they have nosocomial RSV
infection, cyanotic congenital heart diseases and other high risk children.

45
 Inhaled bronchodilators are widely used in the treatment of infants with acute viral
bronchiolitis. In this study berodual inhaler was used up to 62.77%. Berodual is a fixed
combination of the anticholinergic agent and the beta2-adrenaergic antagonist fenoterol
hydrobromide.
In this study hypertonic saline was used up to 70.21%, but there were not mentioned in
the studies that we reviewed. Airway edema and mucus plugging are the predominant
pathological features in acute viral bronchiolitis. Most clinicians believe that hypertonic saline
decrease airway edema, improve mucociliary clearance, and thus decrease airway obstruction.

Table 5.5 Comparison of treatment used

Antibiotics Bronchodilators
Author (year) Number Others
used used

Our study 19 59 Hypertonic Saline

94
(Cambodia, 2022) (20.21%) (62.77%) (70.21%)

Lien Anh Ha Do, et

169 168 Corticosteroids
al. 201
(84.08%) (83.58%) (4.48%)
(Vietnam, 2019)

Inhaled steroids
Zeina Naja et al. 108 155 (9.28%)
194
(Lebanon, 2019) (55.67%) (79.90%) Systemic steroids
(17.01%)

Invasive mechanical
Puneyavee A, et al. 163 376
427 ventilation for
(Thailand, 2020) (38.17%) (88.06%)
43 (10.07%)

5.5 Comparison of Length of Hospital Stay

The median duration of hospital stay was 4 days, IQR: 3-6 days; range: 1-11 days. The
length of hospital stays less than 7 days was 104 (86%) and ≥7 days was 17(14%). Our
finding was similar to many studies in the developing countries.

46
Table 5.6 Comparison of length of hospital stay

Author (year) Number Median Others

Our study
94 4 days ≥7days: 12.77%
(Cambodia, 2022)

Lien Anh Ha Do, et al.

201 6 days ≥7days: 38%
(Vietnam, 2019)

Zeina Naja et al.

194 mean: 7.4 (6.7SD) -
(Lebanon, 2019)

Puneyavee A, et al.
427 5 days -
(Thailand, 2020)

5.6 Comparison of Treatment Outcomes

The outcome of this study was similar the study in Vietnam by Lien Anh Ha Do, et al
(2019) and Thailand by Puneyavee A, et al (2020) with no death due to this disease. Other
studies were presented with death 1.03% in a study in Lebanon by Zeina Naja et al (2019).

Table 5.7 Comparison of treatment outcomes (death)

Author (year) Number Death Cured Referred

Our study 0 93 1
94
(Cambodia, 2022) (0.0%) (98.94%) (1.06%)

Lien Anh Ha Do, et al. 0 201

201 -
(Vietnam, 2019) (0.0%) (100%)

Zeina Naja et al. 2 192

194 -
(Lebanon, 2019) (1.03%) (98.97%)

Puneyavee A, et al.
427 0 427
-
(Thailand, 2020) (0.0%) (100%)

47
 CHAPTER VI
CONCLUSION AND RECOMMENDATION

6.1 Conclusion

This study documented the incidence with epidemiological aspects of acute

bronchiolitis hospitalized in a provincial hospital of Cambodia and presented the relevant
common clinical features, treatment, and outcomes.
On this studies to found that the incidence was likely predominance among male
children has 59.57%. Finding the overall incidence was strongly associated with younger age
among children under 24 months that was consistent across many different studies in
developing countries. The median age in our study was 8 months old, and that incidence was
highest among children aged <6 months. The majority of cases live in dangkor district, while
the highest incidence period is September, the rainy season.
The clinical feature include: fever, cough, rhinorrhea, dyspnea, chest indrawing and
wheezing. For the blood test for CBC and CRP was done in 81 cases (86.17%). The result of
CBC was mostly presented with normal range of white blood cells and or leucopenia in some
cases. No blood culture test was requested in this setting. The results of CRP, revealed value
ranging from zero mg/L to 48 mg/L, in which 0 mg/L presented for 50.62%, with value from
>0mg/L to 10mg/L for 34.57%, and value >10mg/L for 14.81%.
Among all children admitted, 20.21% received any kind of antibiotics during this
admission, and most of children received adjunct medicines to treatment and care during
admission. Hypertonic saline was used in 70.21% of cases, berodual inhaler was used in
62.77%, salbutamol inhaler was used in 47.87% .
The length of hospital stay, the most of children stay in hospital was 4 days. The
length of hospital stay less than 7 days was 87.23% and ≥7 days was 12.77%. According to
this result to show that among all children, 98.94% were discharged with competed cure or
improvement and 1.06% were referred to Kantha Bopha based on family request.

48
6.2 Recommendations

-Our finding is in agreement with the results of several studies with most of common
clinical manifestation, in which reported that RSV was the main causes of acute viral
bronchiolitis in infants admitted to hospitals. Although in our study did not test for this
microorganism, but clinical manifestations and epidemiological information may support this
diagnosis.
-Frequent and meticulous hand washing is one the best and applicable means to
prevent the disease since it is transmitted mainly by contact with infected respiratory
secretion.
-Limitation of exposure to crowded places is also an effective preventive practice
which is the same to elimination of passive exposure to cigarette smoke.
-Furthermore, other respiratory tract vaccination is also regarded as one of the
effective prevention for acute bronchiolitis.
-Should encourage our patient for continue breast feeding at least six months to two
years old of baby for prevent lower and upper respiratory disease and other diseases.
-Absence of bacteriological and or serological tests are also a weak point that we could
not evaluate the true positive of diagnosis among these populations.

49