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Asclepius Medical Research and Reviews  •  Vol 2  •  Issue 2  •  2019 4
INTRODUCTION
B
ronchiolitis is defined as a clinical syndrome that occurs
in children 2 years of age that is characterized by upper
respiratory symptoms followed by lower respiratory
tract infection (LRTIs) which in turn results in wheezing
and/or crackles, retractions, and cyanosis as well as other
complications. Its typically caused by a viral infection, among
which, respiratory syncytial virus (RSV) is the most common
cause.[1]
RSVcauses seasonal outbreaks throughout the world.[2]
It appears to be greatest in infants younger than 3 months of age
and in those with risk factors, especially prematurity.[3]
RSV
bronchiolitis is considered to be a more severe illness compared
to that caused by other viruses; infected patients had a longer
length of hospital stay, had more oxygen requirements, and
other comorbidities (atelectasis/condensation and acute otitis
RSV Versus Non-RSV Bronchiolitis at Haykal
Hospital between January 2016 and December 2018
Farah Rida1
, Bassem Abou Merhi1
, Laudy Abi Rida1
, Joelle Azzi2
, Manal Dahrouj1
,
Ghaiss Makkoul3
1
Department of Pediatrics, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon, 2
Department of
Public Health, Faculty of Public Health, Lebanese University, Beirut, Lebanon, 3
Department of Neonatology,
Haykal Hospital, Tripoli, Lebanon
ABSTRACT
Introduction: Bronchiolitis is a clinical syndrome that occurs in children 2 years, characterized by upper respiratory symptoms
followed by lower respiratory tract infection that results in wheezing and/or crackles and other complications. Its typically
caused by a viral infection, among which, respiratory syncytial virus (RSV) is the most common cause. Objective: The aim of
this study is to determine whether RSV is the most common cause of acute bronchiolitis in North Lebanon and to determine
the most common age, season for RSV bronchiolitis, whether it is more prevalent in preterm patients and whether it is a more
serious infection. Our study is the first one conducted in North Lebanon that provides information related to RSV versus
non-RSV bronchiolitis. Materials and Methods: A retrospective study was conducted at Haykal hospital in North Lebanon
over a period of 3 years; a total of 368 medical records of cases younger than 2 years who presented with complaints related to
bronchiolitis, admitted based on clinical presentation, with evidence of an International Classification of Diseases, 10th
 Revision
codes and in whom the RSV nasal swab test was done, were all reviewed. Results: Among 368 cases enrolled in the study,
211 (57.3%) were RSV positive bronchiolitis. RSV was mostly found among younger ages 3 months with P = 0.014. Cases
with RSV bronchiolitis had a longer hospital stay and more oxygen requirement compared to cases with non-RSV bronchiolitis
with P ≤ 0.001 and P = 0.028, respectively. Both RSV and non-RSV bronchiolitis peaked in December and being reported
throughout the whole year P  0.001. Prematurity was the only risk factor studied P = 0.010, but our data did not show
significantly higher rates of hospitalization for RSV versus non-RSV bronchiolitis among preterm infants. City of residence
was associated with more intensive care admissions, increased rates of RSV infection in higher regions (Akkar and Dinieh)
and more crowded cities (Tripoli) compared (P = 0.013). Conclusion: RSV is the most common cause of hospitalization for
bronchiolitis in North Lebanon, it has a more severe course in all parameters, and thus, physicians should emphasize on the use
of palivizumab for the prevention of RSV infections in children at high risk as recommended by guidelines.
Key words: Bronchopulmonary dysplasia, congenital heart disease, respiratory syncytial virus
Address for correspondence:
Bassem Abou Merhi, Department of Pediatrics, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon.
E-mail: bassemaboumerhi@gmail.com
https://doi.org/10.33309/2639-8605.020202 www.asclepiusopen.com
Š 2019 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license.
ORIGINAL ARTICLE
Rida, et al.: RSV versus non RSV bronchiolitis at Haykal hospital
5 Asclepius Medical Research and Reviews  •  Vol 2  •  Issue 2  •  2019
media). These findings suggest that RSV bronchiolitis is a more
severe illness compared to that caused by other viruses.[4]
OBJECTIVES
Primary objective
The aim of this study is to determine whether RSV
bronchiolitis is the most common cause of acute bronchiolitis
in hospitalized children 2 years old in North Lebanon and
to examine RSV and non-RSV bronchiolitis hospitalization
rates from 2016 to 2018 among infants less 2 years.
Secondary objectives
The objectives of the study were to assess the hospitalization
trends for RSV and non-RSV for children 2 years with
or without higher-risk medical conditions, to determine:
At what age in the first 2 years of life, children mostly got
infected with RSV/non-RSV bronchiolitis? (To determine
the age and duration of an RSV/non-RSV bronchiolitis
admission), when during the year does RSV bronchiolitis
mostly occur (Monthly distribution)? If preterm infants are
more susceptible to RSV compared to term babies? The
length of hospitalization for RSV bronchiolitis is longer than
non-RSV bronchiolitis. Which is proportionate to the cost of
hospitalization; thereafter is RSV bronchiolitis a more severe
disease than that caused by other viruses?
MATERIALS AND METHODS
Ethical information’s
This study was done in a manner that ensures the
confidentiality of patients. Data collected were identified and
stored at the principal investigator’s office that was locked as
a measure of security.
Study design
This study is a retrospective study conducted at Haykal
hospital in North Lebanon over a period of 3 years, from
January 1, 2016, to December 31, 2018.
Study population
After board approval, 368 medical records were retrieved
from the hospital’s archive; all of them included cases younger
than 2 years old who presented with a chief complaint related
to bronchiolitis; more specifically based on the ICD10 codes
for those who were treated for bronchiolitis.
Inclusion criteria
Infants and children up to 24 months of age and in whom the
RSV nasal swab test was done that has a sensitivity and a
specificity of 80% and 97% respectively.
Exclusion criteria
We excluded those admitted for bronchiolitis in whom the
RSV swab test was not done and those born at the hospital
in whom the RSV was isolated in the 1st
week suggesting
hospital-acquired infection.
Procedures of data collection and measurements
Data were collected from medical records and entered into a
Microsoft Excel spreadsheet which was designed specifically
for this study. After that, data were transferred into IBM
SPSS, version 22, which was used for data cleaning and
analyses.
Statistical analysis
All statistical analyses were performed using the Statistical
Package of the Social Science (IBM SPSS, version 22.0).
Continuous variables were reported as mean and standard
deviation, while categorical variables were summarized
as frequency and percentage. Categorical variables were
compared using the Chi-square test. The mean of quantitative
variables was compared using the Student’s t-test. All tests
were two-sided and P  0.05 was considered to be statistically
significant.
RESULTS
This is a retrospective study done in a tertiary medical center
in Tripoli-Lebanon. Records of 368 patients admitted to
the hospital for bronchiolitis were collected. Demographic
information was gathered. Age and gender groups: The
mean age of patients was 4.23 months. Of all those
cases, 219 (59.3%) cases were males while 149 (40.4%)
were females with a similar mean of age in both groups
(4.09 months in males vs. 4.44 months in females). The cases
were classified into three groups according to age. The results
are summarized in Figure 1. Those between 1 and 3 months
constituted the largest group.
Month of hospitalization
The cases were classified according to the month of admission
to the hospital; the results are summarized in Figure 2.
December and January had the highest number of admissions
for bronchiolitis.
Length of hospitalization
The cases were classified according to the length of
hospitalization; the results are summarized in Table 1. The
median length of hospitalization for bronchiolitis was 5 days.
Resident region
Our cases were grouped according to their living city or
region, Figure 3 shows that most of our patients were from
the Northern part of Lebanon. The highest ones were Tripoli
and Akkar.
Term versus preterm
The cases were divided between those born at term and
those born prematurely; there was no enough data on those
Rida, et al.: RSV versus non RSV bronchiolitis at Haykal hospital
Asclepius Medical Research and Reviews  •  Vol 2  •  Issue 2  •  2019 6
born prematurely (small number of preterm patients and
no available gestational age) also in a few patients, the
neonatal history was missed in the medical records and we
could not even reach the family. The results are shown in
Figure 4.
Oxygen requirement
The cases were classified if they required or not oxygen
during hospitalization. The results are shown in Figure 5.
ICN/ICU admission
The cases were divided whether they required intensive care
unit admission. The results are shown in Figure 6.
RSV versus non-RSV bronchiolitis
The cases were divided into two groups: The first group
included 158 cases that had non-RSV bronchiolitis, and the
second one included 211 cases that had RSV bronchiolitis.
The results are shown in Figure 7.
Figure 1: Distribution of gender by age groups
Figure 2: Month of hospitalization distribution
Table 1: Length of hospitalization distribution
Length of hospitalization n (%)
Valid answers 368
MeanÂąSD 5.8Âą4.1
Median 5.0
Min-Max 1–44
Rida, et al.: RSV versus non RSV bronchiolitis at Haykal hospital
7 Asclepius Medical Research and Reviews  •  Vol 2  •  Issue 2  •  2019
DISCUSSION
Other studies conducted in Lebanon
Three other studies on RSV were done in Lebanon; one of
them “Respiratory Syncytial Virus: Prevalence and Features
among Hospitalized Lebanese Children “conducted at
Makassed General Hospital, Beirut, Lebanon (MGH) reported
by Assaf-Casals et al. between 2012 and 1014, published
on December 15, 2014, included infants and children from
0–13 years,[5]
the second one “Etiology, Seasonality, and
Clinical Characterization of Viral Respiratory Infections
Among Hospitalized Children in Beirut, Lebanon” also done
at Makassed General Hospital, Beirut, Lebanon (MGH)
published on May 19, 2016, included children 16 years,
and the third one “Bronchiolitis Admissions in a Lebanese
Tertiary Medical Center: A 10 Years’ Experience” done at
AUBMC reported by Zeina Naja, between October 2004
and October 2014 published on May 17, 2019, included
children 5 years.[6]
None of them fit with the definition
of bronchiolitis “the first episode of wheezing in a child
younger than 12–24 months”,[7,8]
also the second study
examined the viral etiology of acute respiratory infection and
their epidemiology and not the severity. Thus, none of the
above studies compared between “RSV bronchiolitis” and
“non RSV bronchiolitis.”
Overall results
Our study is the first one done in North Lebanon in a tertiary
medical center: “Haykal hospital.” It is a retrospective,
Figure 3: Living region or city distributions
Figure 4: Term versus preterm distribution Figure 5: Oxygen requirement distribution
Rida, et al.: RSV versus non RSV bronchiolitis at Haykal hospital
Asclepius Medical Research and Reviews  •  Vol 2  •  Issue 2  •  2019 8
comparative study that includes all cases admitted for
bronchiolitis (up to 24 months) over a period of 3 years
(January 2016 to December 2018), and compared between
RSV positive versus RSV negative bronchiolitis. Our
study yielded to a total of 368 patients. About 57.3% were
RSV positive bronchiolitis; this value was higher than the
one reported by Assaf-Casals et al. at another tertiary care
center (MGH) in Beirut (22.1%),[5]
and to those published in
neighboring countries: About 16.9% in Turkey[9]
and 22.9%
in Egypt.[10]
However, our results were almost similar to the
one reported by Zeina Naja at AUBMC in Beirut (61%).[6]
The seasonality patterns for RSV and non-RSV bronchiolitis
hospitalizations were almost the same; both subgroups
peaked in December, which coincides with the one described
by Assaf-Casals et al.[5]
while the study described by Zeina
Naja[6]
showed that RSV hospitalizations were most common
during the first 3 months of the year, in accordance with the
previous studies conducted in Turkey[9]
and Jordan.[11]
We
reported RSV cases throughout the whole year with RSV
being a lot more common than non-RSV in the months of
June and July. Thus, in North Lebanon, the RSV outbreak
season seems to start near October, peaks in December,
continues throughout the winter, spring, and summer season
and does not end at all. Which somehow again coincides with
the one described by Assaf-Casals et al.[5]
that reported RSV
cases throughout the whole year except in August. A variety
of risk factors and demographic features were associated
with a higher likelihood of acquiring RSV bronchiolitis. Our
study revealed male predominance in both subgroups (RSV
and non-RSV), which is expected, since male infants are
suspected to have decreased pulmonary function compared
to female infants[12]
). A result that came in accordance with
a recent US multicenter prospective cohort study of 1836
pediatric patients with bronchiolitis where 60% of the patients
were males,[13]
and in the one reported by Zeina Naja.[6]
In our
study, RSV bronchiolitis peaked in the age group between 1
and 3 months and was more common than non-RSV in the age
group of 1 month while non-RSV bronchiolitis peaked in
the age group between 4 and 12 months. This repartition was
different from the one reported by Zeina Naja[6]
that showed
an older mean age at the admission of 7 months for both
RSV and non-RSV subgroups. Although prematurity is a risk
factor for RSV bronchiolitis, as mentioned in literature, “RSV
has the potential to cause severe LRTI in certain high-risk
groups: Young, premature infants with chronic lung disease
or congenital heart disease (CHD), patients with significant
asthma, and patients who are immunocompromised;”[3]
our
data did not show significantly higher rates of hospitalization
for RSV and non-RSV bronchiolitis among preterm infants
similar to the ones reported byAssaf-Casals et al.[5]
and Zeina
Naja[6]
(NodataontheotherriskfactorsforRSVbronchiolitis).
In agreement with previous studies, we found that RSV
infections led to a longer hospital course compared to non-
RSV (mean days of hospitalization 6.6 vs. 4.8, respectively)
and that the patients in the RSV group required more oxygen
during their hospitalization and more ICN/ICU admissions;
a result that is expected since RSV bronchiolitis is a more
severe illness compared to that caused by other viruses.[4]
Thus, physicians should emphasize on the use of palivizumab
which is a humanized monoclonal antibody against the RSV
F-Glycoprotein, licensed for the prevention of serious RSV
lower respiratory tract disease in children at high risk of
RSV disease;[14]
among them: Bronchopulmonary dysplasia
(BPD), prematurity without BPD  28 weeks.[15]
The role of
breastfeeding in protecting against RSV bronchiolitis and
preventing hospitalization and death has been very well-
established.[16]
Thus, again all mothers should be encouraged
to breastfeed for at least 6 months to prevent LRTIs according
to the 2014 American Academy of Pediatrics guidelines for
the management of bronchiolitis,[17]
and all families should
be warned about the consequences of the second-hand smoke
exposure that was associated with an increase in the severity
of RSV infection by several studies.[18]
But unfortunately,
there were no data on the availability of breastfeeding or
on the exposure to a second-hand smoke to support these
findings. In our study, inhaled bronchodilators, inhaled, and
Figure 6: ICN/ICU distribution
Figure 7: RSV versus non-RSV distribution
Rida, et al.: RSV versus non RSV bronchiolitis at Haykal hospital
9 Asclepius Medical Research and Reviews  •  Vol 2  •  Issue 2  •  2019
systematic corticosteroids and antibiotics were frequently
used in the management of RSV and non-RSV bronchiolitis.
However, due to the retrospective nature of our study, it was
difficult to assess whether the usage of those therapies was
warranted. Regardless of that, based on guidelines, physicians
should not regularly prescribe bronchodilators, antibiotics,
and/or corticosteroids to children with bronchiolitis.[17]
City
of residence was associated with more ICN admission, with
higher rates of RSV infection in higher regions (Akkar and
Dinieh), and more crowded cities (Tripoli). However, this
result is biased, because this study enrolled patients from
only one tertiary care center in North Lebanon (Albert
Haykal Hospital) and not multiple ones (P = 0.013). This
result may lead to the fact that in one side, these mentioned
regions (Akkar and Dinieh) are poor in facilities: Absence of
electricity during many hours of the day and night, limitation
in the ways of warmth in Winter, limitation in the number
of hospitals or medical centers and even a total absence of
hospitals in Dinieh. Moreover, on the other side, an important
number of families belong to the poor socio-economic status
in these regions. Do not these regions need to be more
supervised by our Ministry?! Doesn’t the population there
deserve all the appropriate facilities for their children?
Study limitations and perspectives
It is a retrospective study that limited our ability to collect
data on the following: The exact gestational age of the child,
also in some records the neonatal history is missing, and we
could not reach the family to know it. No data on other risk
factors for RSV (CHD, immunocompromised, smoking, etc.).
No data on the availability of breastfeeding or on second-
hand smoking exposure. In some records, we could not find
if the child required oxygen. We did not find data on the use
of palivizumab in high-risk patients. Some of the non-RSV
bronchiolitis might have had RSV since they were tested with
the RSV antigen swab test, and not with the polymerase chain
reaction diagnostic technologies. The cases of bronchiolitis in
whom the RSV swab test was not done, were missed. This
study was done in North Lebanon; it enrolled patients from
only one tertiary care center in Lebanon and not multiple ones.
CONCLUSION
Our study showed that more than half of cases with
bronchiolitis were RSV positive thus; it showed that RSV is
the most common cause of bronchiolitis among hospitalized
infants and children up to 24 months. Both RSV and non-
RSV bronchiolitis were more common in boys with the
younger cases being more affected by RSV bronchiolitis.
It also showed that RSV is associated with a more severe
course compared to non-RSV bronchiolitis, because RSV
cases had a longer hospital stay, required more oxygen during
their stay, and the ICN/ICU admissions were more common
in the RSV group.
Recommendations
For sure, all mothers should be encouraged to breastfeed for
at least 6 months to prevent LRTIs. All families should be
warned about the consequences of the second-hand smoke
exposure that was associated with an increase in the severity
of RSV infection. Parent’s education for preventive hygiene
measures is easy and worth to perform, to limit the virus’s
transmission. All parents should be aware that a minor cold
to them may cause life-threatening illness in a young infant
or a high-risk child. Physicians should emphasize on the
use of palivizumab for the prevention of serious RSV lower
respiratory tract disease in children at high risk of RSV
disease as recommended by guidelines. Regions in the North
Lebanon with the low facilities (Akkar and Dinieh) were
the ones with a prevalent number of ICN/ICU admissions
with higher rates of RSV bronchiolitis. Our ministry should
reconsider to assure all the appropriate needs for this
population.
REFERENCES
1.	 American Academy of Pediatrics Subcommittee on Diagnosis
and Management of Bronchiolitis. Diagnosis and management
of bronchiolitis. Pediatrics 2006;118:1774-93.
2.	 HallCB,WeinbergGA,IwaneMK,BlumkinAK,Edwards KM,
Staat MA, et al. The burden of respiratory syncytial virus
infection in young children. N Engl J Med 2009;360:588-98.
3.	 Langley GF, Anderson LJ. Epidemiology and prevention of
respiratory syncytial virus infections among infants and young
children. Pediatr Infect Dis J 2011;30:510-7.
4.	 García CG, Bhore R, Soriano-Fallas A, Trost M, Chason R,
Ramilo O, et al. Risk factors in children hospitalized
with RSV bronchiolitis versus non-RSV bronchiolitis.
Pediatrics 2010;126:e1453-60.
5.	 Assaf-Casals A, Ghanem S, Rajab M. Respiratory syncytial
virus: Prevalence and features among hospitalized Lebanese
children. Br J Med Res 2014;6:77-87.
6.	 Naja Z, Fayad D, Khafaja S, Chamseddine S, Dbaibo G,
Hanna-Wakim R. Bronchiolitis admissions in a Lebanese
tertiary medical center: A 10 years’ experience. Front Pediatr
2019;7:189.
7.	 Wainwright C, Altamirano L, Cheney M, Cheney J, Barber S,
Price D, et al. A multicenter, randomized, double-blind,
controlled trial of nebulized epinephrine in infants with acute
bronchiolitis. N Engl J Med 2003;349:27-35.
8.	 Plint AC, Johnson DW, Patel H, Wiebe N, Correll R, Brant R,
et al. Epinephrine and dexamethasone in children with
bronchiolitis. N Engl J Med 2009;360:2079-89.
9.	 Turkish Neonatal Society.The seasonal variations of respiratory
syncytial virus infections in Turkey: A 2-year epidemiological
study. Turk J Pediatr 2012;54:216-22.
10.	 El Kholy AA, Mostafa NA, El-Sherbini SA, Ali AA, Ismail RI,
Magdy RI, et al. Morbidity and outcome of severe respiratory
syncytial virus infection. Pediatr Int 2013;55:283-8.
11.	 Halasa N, Williams J, Faouri S, Shehabi A, Vermund SH,
Wang L, et al. Natural history and epidemiology of respiratory
syncytial virus infection in the Middle East: Hospital
surveillance for children under age two in Jordan. Vaccine
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Asclepius Medical Research and Reviews  •  Vol 2  •  Issue 2  •  2019 10
2015;33:6479-87.
12.	 Jones M, Castile R, Davis S, Kisling J, Filbrun D, Flucke R,
et al. Forced expiratory flows and volumes in infants.
Normative data and lung growth. Am J Respir Crit Care Med
2000;161:353-9.
13.	 Hasegawa K, Mansbach JM, Teach SJ, Fisher ES, Hershey D,
Koh JY, et al. Multicenter study of viral etiology and relapse
in hospitalized children with bronchiolitis. Pediatr Infect Dis J
2014;33:809-13.
14.	 SYNAGIS-palivizumab Injection, Solution. Available from:
https://www.dailymed.nlm.nih.gov/dailymed/drugInfo.
cfm?setid=8e35c4c8-bf56-458f-a73c-8f5733829788. [Last
accessed on 2019 Nov 09 ].
15.	 Shay DK, Holman RC, Newman RD, Liu LL, Stout JW,
Anderson LJ. Bronchiolitis-associated hospitalizations
among US children, 1980-1996. JAMA 1999;282:1440-6.
16.	 Shi T, Balsells E, Wastnedge E, Singleton R, Rasmussen ZA,
Zar HJ, et al. Risk factors for respiratory syncytial virus
associated with acute lower respiratory infection in children
under five years: Systematic review and meta-analysis. J Glob
Health 2015;5:020416.
17.	 Ralston SL, Lieberthal AS, Meissner HC, Alverson BK,
Baley JE, Gadomski AM, et al. Clinical practice guideline:
The diagnosis, management, and prevention of bronchiolitis.
Pediatrics 2014;134:e1474-502.
18.	 Bradley JP, Bacharier LB, Bonfiglio J, Schechtman KB,
Strunk R, Storch G, et al. Severity of respiratory syncytial
virus bronchiolitis is affected by cigarette smoke exposure and
atopy. Pediatrics 2005;115:e7-14.
How to cite this article: Rida F, Merhi BA, Rida LA,
Azzi J, Dahrouj M, Makkoul G. RSV Versus Non-RSV
Bronchiolitis at Haykal Hospital between January 2016
and December 2018. Asclepius Med Res Rev
2019;2(2):4-10.

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RSV Versus Non-RSV Bronchiolitis at Haykal Hospital between January 2016 and December 2018

  • 1. Asclepius Medical Research and Reviews  •  Vol 2  •  Issue 2  •  2019 4 INTRODUCTION B ronchiolitis is defined as a clinical syndrome that occurs in children 2 years of age that is characterized by upper respiratory symptoms followed by lower respiratory tract infection (LRTIs) which in turn results in wheezing and/or crackles, retractions, and cyanosis as well as other complications. Its typically caused by a viral infection, among which, respiratory syncytial virus (RSV) is the most common cause.[1] RSVcauses seasonal outbreaks throughout the world.[2] It appears to be greatest in infants younger than 3 months of age and in those with risk factors, especially prematurity.[3] RSV bronchiolitis is considered to be a more severe illness compared to that caused by other viruses; infected patients had a longer length of hospital stay, had more oxygen requirements, and other comorbidities (atelectasis/condensation and acute otitis RSV Versus Non-RSV Bronchiolitis at Haykal Hospital between January 2016 and December 2018 Farah Rida1 , Bassem Abou Merhi1 , Laudy Abi Rida1 , Joelle Azzi2 , Manal Dahrouj1 , Ghaiss Makkoul3 1 Department of Pediatrics, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon, 2 Department of Public Health, Faculty of Public Health, Lebanese University, Beirut, Lebanon, 3 Department of Neonatology, Haykal Hospital, Tripoli, Lebanon ABSTRACT Introduction: Bronchiolitis is a clinical syndrome that occurs in children 2 years, characterized by upper respiratory symptoms followed by lower respiratory tract infection that results in wheezing and/or crackles and other complications. Its typically caused by a viral infection, among which, respiratory syncytial virus (RSV) is the most common cause. Objective: The aim of this study is to determine whether RSV is the most common cause of acute bronchiolitis in North Lebanon and to determine the most common age, season for RSV bronchiolitis, whether it is more prevalent in preterm patients and whether it is a more serious infection. Our study is the first one conducted in North Lebanon that provides information related to RSV versus non-RSV bronchiolitis. Materials and Methods: A retrospective study was conducted at Haykal hospital in North Lebanon over a period of 3 years; a total of 368 medical records of cases younger than 2 years who presented with complaints related to bronchiolitis, admitted based on clinical presentation, with evidence of an International Classification of Diseases, 10th  Revision codes and in whom the RSV nasal swab test was done, were all reviewed. Results: Among 368 cases enrolled in the study, 211 (57.3%) were RSV positive bronchiolitis. RSV was mostly found among younger ages 3 months with P = 0.014. Cases with RSV bronchiolitis had a longer hospital stay and more oxygen requirement compared to cases with non-RSV bronchiolitis with P ≤ 0.001 and P = 0.028, respectively. Both RSV and non-RSV bronchiolitis peaked in December and being reported throughout the whole year P 0.001. Prematurity was the only risk factor studied P = 0.010, but our data did not show significantly higher rates of hospitalization for RSV versus non-RSV bronchiolitis among preterm infants. City of residence was associated with more intensive care admissions, increased rates of RSV infection in higher regions (Akkar and Dinieh) and more crowded cities (Tripoli) compared (P = 0.013). Conclusion: RSV is the most common cause of hospitalization for bronchiolitis in North Lebanon, it has a more severe course in all parameters, and thus, physicians should emphasize on the use of palivizumab for the prevention of RSV infections in children at high risk as recommended by guidelines. Key words: Bronchopulmonary dysplasia, congenital heart disease, respiratory syncytial virus Address for correspondence: Bassem Abou Merhi, Department of Pediatrics, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon. E-mail: bassemaboumerhi@gmail.com https://doi.org/10.33309/2639-8605.020202 www.asclepiusopen.com Š 2019 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license. ORIGINAL ARTICLE
  • 2. Rida, et al.: RSV versus non RSV bronchiolitis at Haykal hospital 5 Asclepius Medical Research and Reviews  •  Vol 2  •  Issue 2  •  2019 media). These findings suggest that RSV bronchiolitis is a more severe illness compared to that caused by other viruses.[4] OBJECTIVES Primary objective The aim of this study is to determine whether RSV bronchiolitis is the most common cause of acute bronchiolitis in hospitalized children 2 years old in North Lebanon and to examine RSV and non-RSV bronchiolitis hospitalization rates from 2016 to 2018 among infants less 2 years. Secondary objectives The objectives of the study were to assess the hospitalization trends for RSV and non-RSV for children 2 years with or without higher-risk medical conditions, to determine: At what age in the first 2 years of life, children mostly got infected with RSV/non-RSV bronchiolitis? (To determine the age and duration of an RSV/non-RSV bronchiolitis admission), when during the year does RSV bronchiolitis mostly occur (Monthly distribution)? If preterm infants are more susceptible to RSV compared to term babies? The length of hospitalization for RSV bronchiolitis is longer than non-RSV bronchiolitis. Which is proportionate to the cost of hospitalization; thereafter is RSV bronchiolitis a more severe disease than that caused by other viruses? MATERIALS AND METHODS Ethical information’s This study was done in a manner that ensures the confidentiality of patients. Data collected were identified and stored at the principal investigator’s office that was locked as a measure of security. Study design This study is a retrospective study conducted at Haykal hospital in North Lebanon over a period of 3 years, from January 1, 2016, to December 31, 2018. Study population After board approval, 368 medical records were retrieved from the hospital’s archive; all of them included cases younger than 2 years old who presented with a chief complaint related to bronchiolitis; more specifically based on the ICD10 codes for those who were treated for bronchiolitis. Inclusion criteria Infants and children up to 24 months of age and in whom the RSV nasal swab test was done that has a sensitivity and a specificity of 80% and 97% respectively. Exclusion criteria We excluded those admitted for bronchiolitis in whom the RSV swab test was not done and those born at the hospital in whom the RSV was isolated in the 1st week suggesting hospital-acquired infection. Procedures of data collection and measurements Data were collected from medical records and entered into a Microsoft Excel spreadsheet which was designed specifically for this study. After that, data were transferred into IBM SPSS, version 22, which was used for data cleaning and analyses. Statistical analysis All statistical analyses were performed using the Statistical Package of the Social Science (IBM SPSS, version 22.0). Continuous variables were reported as mean and standard deviation, while categorical variables were summarized as frequency and percentage. Categorical variables were compared using the Chi-square test. The mean of quantitative variables was compared using the Student’s t-test. All tests were two-sided and P 0.05 was considered to be statistically significant. RESULTS This is a retrospective study done in a tertiary medical center in Tripoli-Lebanon. Records of 368 patients admitted to the hospital for bronchiolitis were collected. Demographic information was gathered. Age and gender groups: The mean age of patients was 4.23 months. Of all those cases, 219 (59.3%) cases were males while 149 (40.4%) were females with a similar mean of age in both groups (4.09 months in males vs. 4.44 months in females). The cases were classified into three groups according to age. The results are summarized in Figure 1. Those between 1 and 3 months constituted the largest group. Month of hospitalization The cases were classified according to the month of admission to the hospital; the results are summarized in Figure 2. December and January had the highest number of admissions for bronchiolitis. Length of hospitalization The cases were classified according to the length of hospitalization; the results are summarized in Table 1. The median length of hospitalization for bronchiolitis was 5 days. Resident region Our cases were grouped according to their living city or region, Figure 3 shows that most of our patients were from the Northern part of Lebanon. The highest ones were Tripoli and Akkar. Term versus preterm The cases were divided between those born at term and those born prematurely; there was no enough data on those
  • 3. Rida, et al.: RSV versus non RSV bronchiolitis at Haykal hospital Asclepius Medical Research and Reviews  •  Vol 2  •  Issue 2  •  2019 6 born prematurely (small number of preterm patients and no available gestational age) also in a few patients, the neonatal history was missed in the medical records and we could not even reach the family. The results are shown in Figure 4. Oxygen requirement The cases were classified if they required or not oxygen during hospitalization. The results are shown in Figure 5. ICN/ICU admission The cases were divided whether they required intensive care unit admission. The results are shown in Figure 6. RSV versus non-RSV bronchiolitis The cases were divided into two groups: The first group included 158 cases that had non-RSV bronchiolitis, and the second one included 211 cases that had RSV bronchiolitis. The results are shown in Figure 7. Figure 1: Distribution of gender by age groups Figure 2: Month of hospitalization distribution Table 1: Length of hospitalization distribution Length of hospitalization n (%) Valid answers 368 MeanÂąSD 5.8Âą4.1 Median 5.0 Min-Max 1–44
  • 4. Rida, et al.: RSV versus non RSV bronchiolitis at Haykal hospital 7 Asclepius Medical Research and Reviews  •  Vol 2  •  Issue 2  •  2019 DISCUSSION Other studies conducted in Lebanon Three other studies on RSV were done in Lebanon; one of them “Respiratory Syncytial Virus: Prevalence and Features among Hospitalized Lebanese Children “conducted at Makassed General Hospital, Beirut, Lebanon (MGH) reported by Assaf-Casals et al. between 2012 and 1014, published on December 15, 2014, included infants and children from 0–13 years,[5] the second one “Etiology, Seasonality, and Clinical Characterization of Viral Respiratory Infections Among Hospitalized Children in Beirut, Lebanon” also done at Makassed General Hospital, Beirut, Lebanon (MGH) published on May 19, 2016, included children 16 years, and the third one “Bronchiolitis Admissions in a Lebanese Tertiary Medical Center: A 10 Years’ Experience” done at AUBMC reported by Zeina Naja, between October 2004 and October 2014 published on May 17, 2019, included children 5 years.[6] None of them fit with the definition of bronchiolitis “the first episode of wheezing in a child younger than 12–24 months”,[7,8] also the second study examined the viral etiology of acute respiratory infection and their epidemiology and not the severity. Thus, none of the above studies compared between “RSV bronchiolitis” and “non RSV bronchiolitis.” Overall results Our study is the first one done in North Lebanon in a tertiary medical center: “Haykal hospital.” It is a retrospective, Figure 3: Living region or city distributions Figure 4: Term versus preterm distribution Figure 5: Oxygen requirement distribution
  • 5. Rida, et al.: RSV versus non RSV bronchiolitis at Haykal hospital Asclepius Medical Research and Reviews  •  Vol 2  •  Issue 2  •  2019 8 comparative study that includes all cases admitted for bronchiolitis (up to 24 months) over a period of 3 years (January 2016 to December 2018), and compared between RSV positive versus RSV negative bronchiolitis. Our study yielded to a total of 368 patients. About 57.3% were RSV positive bronchiolitis; this value was higher than the one reported by Assaf-Casals et al. at another tertiary care center (MGH) in Beirut (22.1%),[5] and to those published in neighboring countries: About 16.9% in Turkey[9] and 22.9% in Egypt.[10] However, our results were almost similar to the one reported by Zeina Naja at AUBMC in Beirut (61%).[6] The seasonality patterns for RSV and non-RSV bronchiolitis hospitalizations were almost the same; both subgroups peaked in December, which coincides with the one described by Assaf-Casals et al.[5] while the study described by Zeina Naja[6] showed that RSV hospitalizations were most common during the first 3 months of the year, in accordance with the previous studies conducted in Turkey[9] and Jordan.[11] We reported RSV cases throughout the whole year with RSV being a lot more common than non-RSV in the months of June and July. Thus, in North Lebanon, the RSV outbreak season seems to start near October, peaks in December, continues throughout the winter, spring, and summer season and does not end at all. Which somehow again coincides with the one described by Assaf-Casals et al.[5] that reported RSV cases throughout the whole year except in August. A variety of risk factors and demographic features were associated with a higher likelihood of acquiring RSV bronchiolitis. Our study revealed male predominance in both subgroups (RSV and non-RSV), which is expected, since male infants are suspected to have decreased pulmonary function compared to female infants[12] ). A result that came in accordance with a recent US multicenter prospective cohort study of 1836 pediatric patients with bronchiolitis where 60% of the patients were males,[13] and in the one reported by Zeina Naja.[6] In our study, RSV bronchiolitis peaked in the age group between 1 and 3 months and was more common than non-RSV in the age group of 1 month while non-RSV bronchiolitis peaked in the age group between 4 and 12 months. This repartition was different from the one reported by Zeina Naja[6] that showed an older mean age at the admission of 7 months for both RSV and non-RSV subgroups. Although prematurity is a risk factor for RSV bronchiolitis, as mentioned in literature, “RSV has the potential to cause severe LRTI in certain high-risk groups: Young, premature infants with chronic lung disease or congenital heart disease (CHD), patients with significant asthma, and patients who are immunocompromised;”[3] our data did not show significantly higher rates of hospitalization for RSV and non-RSV bronchiolitis among preterm infants similar to the ones reported byAssaf-Casals et al.[5] and Zeina Naja[6] (NodataontheotherriskfactorsforRSVbronchiolitis). In agreement with previous studies, we found that RSV infections led to a longer hospital course compared to non- RSV (mean days of hospitalization 6.6 vs. 4.8, respectively) and that the patients in the RSV group required more oxygen during their hospitalization and more ICN/ICU admissions; a result that is expected since RSV bronchiolitis is a more severe illness compared to that caused by other viruses.[4] Thus, physicians should emphasize on the use of palivizumab which is a humanized monoclonal antibody against the RSV F-Glycoprotein, licensed for the prevention of serious RSV lower respiratory tract disease in children at high risk of RSV disease;[14] among them: Bronchopulmonary dysplasia (BPD), prematurity without BPD 28 weeks.[15] The role of breastfeeding in protecting against RSV bronchiolitis and preventing hospitalization and death has been very well- established.[16] Thus, again all mothers should be encouraged to breastfeed for at least 6 months to prevent LRTIs according to the 2014 American Academy of Pediatrics guidelines for the management of bronchiolitis,[17] and all families should be warned about the consequences of the second-hand smoke exposure that was associated with an increase in the severity of RSV infection by several studies.[18] But unfortunately, there were no data on the availability of breastfeeding or on the exposure to a second-hand smoke to support these findings. In our study, inhaled bronchodilators, inhaled, and Figure 6: ICN/ICU distribution Figure 7: RSV versus non-RSV distribution
  • 6. Rida, et al.: RSV versus non RSV bronchiolitis at Haykal hospital 9 Asclepius Medical Research and Reviews  •  Vol 2  •  Issue 2  •  2019 systematic corticosteroids and antibiotics were frequently used in the management of RSV and non-RSV bronchiolitis. However, due to the retrospective nature of our study, it was difficult to assess whether the usage of those therapies was warranted. Regardless of that, based on guidelines, physicians should not regularly prescribe bronchodilators, antibiotics, and/or corticosteroids to children with bronchiolitis.[17] City of residence was associated with more ICN admission, with higher rates of RSV infection in higher regions (Akkar and Dinieh), and more crowded cities (Tripoli). However, this result is biased, because this study enrolled patients from only one tertiary care center in North Lebanon (Albert Haykal Hospital) and not multiple ones (P = 0.013). This result may lead to the fact that in one side, these mentioned regions (Akkar and Dinieh) are poor in facilities: Absence of electricity during many hours of the day and night, limitation in the ways of warmth in Winter, limitation in the number of hospitals or medical centers and even a total absence of hospitals in Dinieh. Moreover, on the other side, an important number of families belong to the poor socio-economic status in these regions. Do not these regions need to be more supervised by our Ministry?! Doesn’t the population there deserve all the appropriate facilities for their children? Study limitations and perspectives It is a retrospective study that limited our ability to collect data on the following: The exact gestational age of the child, also in some records the neonatal history is missing, and we could not reach the family to know it. No data on other risk factors for RSV (CHD, immunocompromised, smoking, etc.). No data on the availability of breastfeeding or on second- hand smoking exposure. In some records, we could not find if the child required oxygen. We did not find data on the use of palivizumab in high-risk patients. Some of the non-RSV bronchiolitis might have had RSV since they were tested with the RSV antigen swab test, and not with the polymerase chain reaction diagnostic technologies. The cases of bronchiolitis in whom the RSV swab test was not done, were missed. This study was done in North Lebanon; it enrolled patients from only one tertiary care center in Lebanon and not multiple ones. CONCLUSION Our study showed that more than half of cases with bronchiolitis were RSV positive thus; it showed that RSV is the most common cause of bronchiolitis among hospitalized infants and children up to 24 months. Both RSV and non- RSV bronchiolitis were more common in boys with the younger cases being more affected by RSV bronchiolitis. It also showed that RSV is associated with a more severe course compared to non-RSV bronchiolitis, because RSV cases had a longer hospital stay, required more oxygen during their stay, and the ICN/ICU admissions were more common in the RSV group. Recommendations For sure, all mothers should be encouraged to breastfeed for at least 6 months to prevent LRTIs. All families should be warned about the consequences of the second-hand smoke exposure that was associated with an increase in the severity of RSV infection. Parent’s education for preventive hygiene measures is easy and worth to perform, to limit the virus’s transmission. All parents should be aware that a minor cold to them may cause life-threatening illness in a young infant or a high-risk child. Physicians should emphasize on the use of palivizumab for the prevention of serious RSV lower respiratory tract disease in children at high risk of RSV disease as recommended by guidelines. Regions in the North Lebanon with the low facilities (Akkar and Dinieh) were the ones with a prevalent number of ICN/ICU admissions with higher rates of RSV bronchiolitis. Our ministry should reconsider to assure all the appropriate needs for this population. REFERENCES 1. American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics 2006;118:1774-93. 2. HallCB,WeinbergGA,IwaneMK,BlumkinAK,Edwards KM, Staat MA, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med 2009;360:588-98. 3. Langley GF, Anderson LJ. Epidemiology and prevention of respiratory syncytial virus infections among infants and young children. Pediatr Infect Dis J 2011;30:510-7. 4. GarcĂ­a CG, Bhore R, Soriano-Fallas A, Trost M, Chason R, Ramilo O, et al. Risk factors in children hospitalized with RSV bronchiolitis versus non-RSV bronchiolitis. Pediatrics 2010;126:e1453-60. 5. Assaf-Casals A, Ghanem S, Rajab M. Respiratory syncytial virus: Prevalence and features among hospitalized Lebanese children. Br J Med Res 2014;6:77-87. 6. Naja Z, Fayad D, Khafaja S, Chamseddine S, Dbaibo G, Hanna-Wakim R. Bronchiolitis admissions in a Lebanese tertiary medical center: A 10 years’ experience. Front Pediatr 2019;7:189. 7. Wainwright C, Altamirano L, Cheney M, Cheney J, Barber S, Price D, et al. A multicenter, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis. N Engl J Med 2003;349:27-35. 8. Plint AC, Johnson DW, Patel H, Wiebe N, Correll R, Brant R, et al. Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med 2009;360:2079-89. 9. Turkish Neonatal Society.The seasonal variations of respiratory syncytial virus infections in Turkey: A 2-year epidemiological study. Turk J Pediatr 2012;54:216-22. 10. El Kholy AA, Mostafa NA, El-Sherbini SA, Ali AA, Ismail RI, Magdy RI, et al. Morbidity and outcome of severe respiratory syncytial virus infection. Pediatr Int 2013;55:283-8. 11. Halasa N, Williams J, Faouri S, Shehabi A, Vermund SH, Wang L, et al. Natural history and epidemiology of respiratory syncytial virus infection in the Middle East: Hospital surveillance for children under age two in Jordan. Vaccine
  • 7. Rida, et al.: RSV versus non RSV bronchiolitis at Haykal hospital Asclepius Medical Research and Reviews  •  Vol 2  •  Issue 2  •  2019 10 2015;33:6479-87. 12. Jones M, Castile R, Davis S, Kisling J, Filbrun D, Flucke R, et al. Forced expiratory flows and volumes in infants. Normative data and lung growth. Am J Respir Crit Care Med 2000;161:353-9. 13. Hasegawa K, Mansbach JM, Teach SJ, Fisher ES, Hershey D, Koh JY, et al. Multicenter study of viral etiology and relapse in hospitalized children with bronchiolitis. Pediatr Infect Dis J 2014;33:809-13. 14. SYNAGIS-palivizumab Injection, Solution. Available from: https://www.dailymed.nlm.nih.gov/dailymed/drugInfo. cfm?setid=8e35c4c8-bf56-458f-a73c-8f5733829788. [Last accessed on 2019 Nov 09 ]. 15. Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ. Bronchiolitis-associated hospitalizations among US children, 1980-1996. JAMA 1999;282:1440-6. 16. Shi T, Balsells E, Wastnedge E, Singleton R, Rasmussen ZA, Zar HJ, et al. Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: Systematic review and meta-analysis. J Glob Health 2015;5:020416. 17. Ralston SL, Lieberthal AS, Meissner HC, Alverson BK, Baley JE, Gadomski AM, et al. Clinical practice guideline: The diagnosis, management, and prevention of bronchiolitis. Pediatrics 2014;134:e1474-502. 18. Bradley JP, Bacharier LB, Bonfiglio J, Schechtman KB, Strunk R, Storch G, et al. Severity of respiratory syncytial virus bronchiolitis is affected by cigarette smoke exposure and atopy. Pediatrics 2005;115:e7-14. How to cite this article: Rida F, Merhi BA, Rida LA, Azzi J, Dahrouj M, Makkoul G. RSV Versus Non-RSV Bronchiolitis at Haykal Hospital between January 2016 and December 2018. Asclepius Med Res Rev 2019;2(2):4-10.