Effect of Pediatric Lung Ultrasound on Antibiotic Prescriptions in Hospitalized Children and Adolescents With Lower Respiratory Tract Infections.
Phase: NA
Conditions: Lower Resp Tract Infection
Sponsor: American University of Beirut Medical Center

 
1 
August-2024 
Clinical Trial Protocol 
 
Administrative information 
Title 
1- Effect of Pediatric Lung Ultrasound on Antibiotic Prescriptions in Hospitalized Children and 
Adolescents with Lower Respiratory Tract Infections. A Randomized Controlled Trial.  
“PLUS-AP Trial” 
 
Trial registration  
       2a-  Intended registry: ClinicalTrials.gov 
 
       2b- WHO Trial Registration data 
Data category  
Information 
Primary registry and trial identifying number  
ClinicalTrials.gov 
Date of registration in primary registry  
TBD 
Secondary identifying numbers  
- 
Source(s) of monetary or material support  
American University of Beirut Medical Center 
(AUBMC) 
Primary sponsor  
American University of Beirut (AUB) – University 
Research Board (URB)  
AUBMC - Medical Practice Plan (MPP)  
Secondary sponsor(s)  
none 
Contact for public queries  
Ali Ismail: ai18@aub.edu.lb 
Contact for scientific queries  
Ali Ismail: ai18@aub.edu.lb 
Public title  
Lung ultrasound (LUS) effect on antibiotic 
prescriptions in children with lower respiratory 
tract infections (LRTIs). 
Scientific title  
Effect of Pediatric Lung Ultrasound on Antibiotic 
Prescriptions in Hospitalized Children with Lower 
Respiratory Tract Infections. A Randomized 
Controlled Trial. “PLUS-AP Trial” 
Countries of recruitment  
Lebanon 
Health condition(s) or problem(s) studied  
-Antibiotic prescriptions to children and 
adolescents with viral LRTIs 

 
2 
-Differentiation between viral and bacterial LRTIs 
with the help of LUS 
Intervention(s)  
(Lung ultrasound “LUS” + standard treatment) vs. 
(Sham lung ultrasound “SLUS” + standard 
treatment) 
Key inclusion and exclusion criteria  
Age eligibility for study: 3 months -18 years 
Gender eligibility for study: both males and 
females 
Accepts healthy volunteers: no 
Inclusion criteria:  
- Age between 3 months and 17 years old 
inclusive 
-Currently admitted to the pediatric Ward or 
boarding in the Emergency Department within 24 
hours of admission order due to lower 
respiratory tract infections. 
Exclusion criteria:  
-Sickle cell disease (SCD). 
-On chemotherapy or any other 
immunosuppressive therapy except systemic 
corticosteroids use of ≤ 5 days duration. 
-Cystic fibrosis and other chronic lung diseases 
except asthma 
-Pre-existing and/or congenital neurologic, 
metabolic, and cardiac conditions 
-Hospitalized within the previous month  
- Patients with suspected foreign body aspiration 
-Received antibiotic therapy within the previous 
week 
-Patients admitted under PI’s care 
Study type  
Interventional 
Allocation: randomized 
Intervention model: parallel assignment 
Blinding:  
-Patients will be blinded to LUS vs SLUS. 
-Principal Investigator (PI), who will solely be 
doing LUS, will be blinded to CXR findings. Data 
analyst, Dr. Ziad Mahfoud will be blinded to 
patients’ allocation. 
Primary purpose: prevention 
Phase III 
Date of first enrolment  
TBD 
Target sample size  
176 patients (88 in each arm) 
Recruitment status 
Not yet 

 
3 
Primary outcome 
-Antibiotic prescriptions rate upon discharge in 
hospitalized children and adolescents with LRTIs 
on standard care who undergo LUS vs. SLUS  
Secondary outcomes 
-Length of stay (LOS) in the hospital 
-Rate of complications by 4 weeks after 
enrollment: admission to ICU, chest tube 
insertion, mortality 
-Frequency of chest x-ray (CXR) performance by 4 
weeks after enrollment. 
-The rate of antibiotic intake, evaluated 4 weeks 
following enrollment.  
Table 1: WHO Trial Registration data 
Protocol version  
3-  Date and version identifier: first version dated August 26, 2024.  
Issue Date: August 26, 2024 
Protocol Amendment Number: N/A 
Revision Chronology: N/A 
 
Funding 
4-  This protocol has received financial support from the University Research Board (URB) and 
Medical Practice Plan (MPP) at the American University of Beirut (AUB). The grant specifically 
covers the salary of a research fellow and hospital equipment charges. The funding body has no 
role in the design of the study, collection, analysis, interpretation of data, or in writing the 
manuscript.  
Roles and responsibilities 
5- a- Names, affiliations, and roles of protocol contributors: 
Ali Ismail (A.I.), M.D. (PI); Marianne Majdalani (M.M.), M.D. (Study Coordinator); Hawraa Roof 
(H.R.), M.D. (Co-I); Dima Khreis (D.K.), M.D. (Co_I); Maysaa Slika (M.S.), M.D. (Co_I)  M.D. (Co-I); 
Jihane Moukhaiber (J.M.), M.D. (Co-I); Jana Ayyash (J.A.), Medical student at AUB (Co-I); Ziad 
Mahfoud (Z.M.), Biostatistics (Collaborator), Rita Sebaaly (R.S.), Medical student at AUB (Co-I); 
Sana Kalaji (S.K.), Medical student at AUB (Co-I); Mohamad Hassan (M.H.), Medical student at 
AUB (Co-I).  
A.I. leads protocol development, oversees study implementation, data entry, analyses, 
manuscript writing and publication. A.I. will be responsible for data integrity.   
Ali Hijazi, a medical student at Balamand University and independent from the study 
team, will be responsible for the randomization sequence and giving the allocation by 
phone. 

 
4 
All Authors will contribute to study conduct, and manuscript writing. ZM will do the 
statistical analysis.  
 
b- Name and contact information for the trial sponsor: 
Trial Sponsor: AUB funds - URB 
Sponsor’s Reference: award/project 104524 
Contact name: Mazen Al-Shami 
Address: Beirut, AUB 
Telephone: 01/350000 ext.2973 
Email: ma157@aub.edu.lb 
 
c- The funding source did not play a role in the study's design and will not be involved in its 
execution, data analysis, interpretation, or decision to submit results.  
 
d- Committees: 
Trial Steering Committee (TSC): The Trial Steering Committee will consist of the following 
investigators: Ali Ismail (A.I.) – Principal Investigator (PI), Marianne Majdalani (M.M.), Jihan 
Mkhaiber (J.M.), Maysaa Slika (M.S.), Hawraa Raouf (H.R.), Dima Khreis (D.K.), Co-Principal 
Investigators. And Ziad Mahfoud (Z.M.) – collaborator and Co-Principal Investigator. 
The responsibilities of the trial steering committee include the following: 
1. Recruitment of patients and coordination with the principal investigator. 
2. Regularly reviewing the progress of the study (weekly). 
3. If necessary, agreeing upon changes to the protocol and/or investigators brochure to 
ensure the study runs smoothly. 
Data and Safety Monitoring Committee (DSMC). 
The chair of the DSMC is going to be Dr. Mona Nabulsi (Pediatrician, Department of Pediatrics 
and Adolescent Medicine, AUBMC) with two members: Dr. Lama Charafeddine (Neonatologist, 
Department of Pediatrics and Adolescent Medicine, AUBMC), and Dr. Hani Tamim 
(Biostatistician, Clinical Research Institute, AUB). 
 
 
Introduction  
Background and rationale 
       6a-     Lower Respiratory Tract Infections (LRTIs) are  a substantial global health concern 
associated with a high morbidity and mortality.1 According to Unicef, in 2022 more than 2000 
children under 5 years of age died every month because of pneumonia globally and mostly in the 
developing countries, where pneumonia is the number one cause of death. Immunization against 

 
5 
streptococcus pneumonia and Haemophilus Influenza-type b lead to a significant drop in the 
related mortality.2,3 
Children under the age of 5 years have the highest rate of hospitalization due to pneumonia. 
When multiple pathogens were tested for diagnostic purposes, it was found that 81% of the 
children with pneumonia had at least one pathogen detected. Among these children, viral 
pathogens were identified in 66% of cases, bacterial pathogens were detected in 8% of cases, 
while both viral and bacterial pathogens in 7%.4 
Many, if not most, children with viral LRTIs are receiving incorrect treatment with antibiotics.  
A retrospective study conducted in Canada examined 131 hospitalized children aged 1-24 months 
with bronchiolitis. The findings revealed that approximately 44% of the patients were given 
antibiotics as part of their management.5 
In 2022, a retrospective multicenter study conducted in Pakistan examined 5,926 hospitalized 
children with lower respiratory tract infections. The study revealed that all of the children, 
representing 100% of the cases, were prescribed antibiotics as part of their treatment.6 
The latest guidelines from CDC on the management of community acquired pneumonia 
recommended against using antibiotics in children with viral pneumonia in the absence of 
findings suggestive of bacterial coinfection.7 British Thoracic Society, on the other hand, in 2011 
recommended to treat all children who have pneumonia with antibiotics because they found it 
difficult to reliably differentiate between viral and bacterial pneumonia. They emphasized on the 
need to detect the etiologic organism in those patients and to seek for better diagnostic 
methods.8  
Antibiotic stewardship programs place emphasis on avoiding the unnecessary use of antibiotics 
to reduce the risk of antibiotic resistance, which poses a threat to public health.9 
Comparative studies conducted in pediatric populations show that point of care LUS has a better 
diagnostic accuracy than, physical examination and CXR in diagnosing various respiratory tract 
diseases. These include pneumonia, bronchiolitis, pneumothorax, pulmonary edema, acute chest 
syndrome, pleural effusion, and pulmonary contusion.10 
In recent years, efforts have been made to assess the utility, reliability and efficiency of LUS in 
the proper diagnosis of community acquired pneumonia (CAP) in children.11 A meta-analysis in 
2015 of 8 studies, published by the American Academy of Pediatrics (AAP), showed that LUS had 
a sensitivity of 96% and a specificity of 93% in the diagnosis of pneumonia in children when 
compared to CXR as a reference standard. Indeed, they proposed to use LUS as an alternative 
method to CXR for the evaluation of pneumonia in children.12 Another meta-analysis came out in 
2019 by Heuvelings et al. and included 30 well conducted studies, went further in the evaluation 
of children with suspected pneumonia and suggested that LUS should replace CXR as a first-line 
imaging study.13 

 
6 
Differentiating between viral and bacterial etiology in children with CAP is crucial for initial 
management, and lung ultrasound proves highly beneficial in this regard.10,14–17 In a prospective 
study that was published in Nature Scientific Reports in 2019 and included 147 hospitalized 
children with CAP, Berce et al. stratified patients according to the microbiological results and 
described the differences in LUS findings between bacterial and viral pneumonia. In bacterial 
CAP, the consolidations were more likely to be solitary, larger, and unilateral compared to those 
observed in viral CAPs.14 The combination of epidemiological, clinical, and laboratory data greatly 
enhances the usefulness of lung ultrasound. In 2022 Omran et al. described the effectiveness of 
LUS with and without the neutrophil-to-lymphocyte ratio (NLR) in early detection and 
differentiation of viral and bacterial pneumonia in young children from Egypt. In this prospective 
study LUS exhibited superior sensitivity and specificity in detecting bacterial pneumonia 
compared to CXR. LUS demonstrated sensitivities of 88.2% for bacterial pneumonia and 83.3% 
for viral pneumonia, while CXR showed sensitivities of 70.6% for bacterial pneumonia and a 
lower sensitivity of 33.3% for viral pneumonia. In terms of specificity, LUS had a specificity of 
85.7% for viral pneumonia and 100% for bacterial pneumonia, whereas CXR had specificities of 
78.5% for viral pneumonia and 85.7% for bacterial pneumonia.15 A cluster randomized clinical 
trial that was conducted in adults with LRTIs, showed that doing LUS in addition to procalcitonin 
level, when compared to standard care, resulted in a significant 26% decrease in the likelihood of 
receiving a 28-day antibiotic prescriptions, while maintaining patient safety.18 
The prevalence of bacterial pneumonia among hospitalized patients with lower respiratory tract 
infections (LRTIs) is higher in adults compared to children, with rates of 66% in adults18 and 15% 
in children.4 
Studies in children examining the use of procalcitonin to differentiate between bacterial and 
viral etiologies have yielded inconsistent findings due to the diverse methods employed and 
variations in the reference standards used to determine the cause such as blood culture versus 
polymerase chain reaction testing (PCR).19 
The integration of anatomical and/or physiological information obtained through point of care 
ultrasound with clinical and laboratory data enables the making of timely and 
accurate decisions.20 
There isn’t enough evidence in the literature on the benefit of adding LUS to standard care in 
decreasing the prescription rate of antibiotics upon discharge in hospitalized children with LRTIs. 
We hypothesize that among hospitalized children due to lower respiratory disease, doing a lung 
ultrasound in addition to standard care as compared to simulated Sham LUS (SLUS) with standard 
care is associated with less prescriptions of antibiotics upon discharge while maintaining patient 
safety. Complications of LRTIs (ICU admission, chest tube insertion, mortality, readmission to the 
hospital) can occur in those patients who will not receive a timely etiology treatment, in 
particular antibiotics in the case of bacterial pneumonia. We will repeat LUS 48 hours after 
enrollment or upon discharge whichever comes first, to ensure patients’ safety. Evaluation of the 

 
7 
primary endpoint will be done by assessing the rate of antibiotic prescriptions upon discharge. As 
for the secondary endpoints, we will evaluate patient safety by examining the length of hospital 
stay, complications of LRTIs (ICU admission, chest tube insertion, mortality), and the rate of 
readmission to the hospital and antibiotic intake along with the rate of chest X-rays performed 
within 4 weeks of enrollment. 
LUS offers several benefits, including the absence of ionizing radiation, reduced expenses, the 
potential for subsequent examinations, the ability to track treatment progress, and improved 
patient collaboration. Additionally, this diagnostic method is readily available, portable, rapid, 
user-friendly, and can be promptly employed as a point-of-care approach.20 
 
      6b-     Despite the high evidence on the role of LUS in the management of children with LRTIs, 
it is still not part of the standard care in Lebanon. The standard care includes taking the patient's 
history, physical exam, CXR and laboratory workup. Sham ultrasound can be done safely in the 
control group, where patients will get the standard care. The safety of LUS is well established and 
do not expose patients to any harm or risk.20 
 
Objectives  
7- Specific objectives or hypotheses 
- 
Research Hypothesis: The addition of LUS to standard care in hospitalized children with LRTIs, 
will result in a notable reduction in the rate of antibiotic prescriptions, compared to SLUS and 
standard of care while maintaining patient safety. 
- 
Study objectives:  
o Primary objective: To investigate the effect of adding LUS to standard care on the 
endpoint of antibiotic prescriptions upon discharge in children hospitalized with LRTIs, 
compared to standard care and SLUS. 
o Secondary objectives: To investigate the effect of adding LUS to standard care, as 
compared to standard care with SLUS, on the end points of: 
▪ 
Length of stay in the hospital 
▪ 
Rate of complications by 4 weeks after enrollment: admission to ICU, chest tube 
insertion, mortality 
▪ 
Frequency of CXR performance within 4 weeks of enrollment 
▪ 
Rate of antibiotic intake assessed 4 weeks after enrollment 
▪ 
Rate of hospital readmission within 4 weeks of enrollment.     
 
 
                         
Trial design  

 
8 
8-  The PLUS-AP trial is designed as a phase III, randomized, controlled, blinded, single center 
superiority trial with two parallel groups and a primary endpoint of antibiotic prescriptions by the 
day of discharge from the hospital. Randomization will be performed as permuted block 
randomization with a 1:1 allocation. 
 
Methods: Participants, interventions, and outcomes 
Study setting  
9-  Selection of Countries: The study will take place in the capital city of Lebanon Beirut. It is mainly an 
urban area with few rural areas around it. The population is estimated to be around 2.4 million 
people. It represents a diverse population that includes a significant number of refugees and 
displaced people from Syria and Palestine. This adds complexity to the economic, social and 
healthcare systems. The American University of Beirut Medical Center (AUBMC), a tertiary 
prestigious academic institution in the region that provides high-quality medical care, education and 
research, is the only site of our trial. 
 
Eligibility criteria  
10-  Inclusion criteria: Patients eligible for the trial must provide a written informed consent before any 
study procedures and comply with all of the following at randomization: 
o Age between 3 months and 18 years 
o Currently admitted to the Pediatric Ward or boarding in the Emergency Department 
within 24 hours of admission order due to LRTIs. 
- 
Exclusion criteria: 
o Sickle cell disease (SCD). 
o On chemotherapy or any other immunosuppressive therapy, except systemic 
corticosteroids use of ≤ 5 days duration. 
o Cystic fibrosis and other chronic lung diseases except asthma. 
o Pre-existing and/or congenital neurologic, metabolic, and cardiac conditions 
o Hospitalized within the previous month  
o Patients with suspected foreign body aspiration 
o Received antibiotic therapy within the previous week  
o Patients admitted under the PI’s care  
 
Interventions  
11a- Eligible patients will be randomized between LUS and sham LUS (SLUS) groups. The bedside 
LUS will be exclusively performed by the principal investigator (A.I.), who has credentialing in 
LUS with more than 5 years of experience, and will be blinded to CXR results. The LUS or SLUS 

 
9 
will be done at his earliest convenient time, within a maximum of 24 hours of enrollment and 
will be repeated 48 hours after the first ultrasound or before discharge from the hospital 
whichever comes first. The PI will explain to the family the procedure of the LUS before 
conducting it without telling them the results nor whether it is LUS or SLUS. Since the patients 
are seen after being admitted to the hospital, these patients undergo standard care including 
history taking, physical exam, laboratory workup and CXR in the emergency Department (ED) as 
deemed necessary by the primary physician.  
In the LUS group: AI will make sure to have adequate depth of the ultrasound image (at least 
double the distance from skin to the pleural line in order to be able to assess reverberation 
artifacts – A-lines). He will scan each lung in the longitudinal and transverse orientation views in 
the midclavicular line anteriorly, paraspinal line posteriorly, and the mid-axillary line for a total 
of six scanning zones as described by Copetti and Cattarossi.21 The ultrasound findings will be 
assessed and recorded on a data collection form (Appendix III) and will be interpreted 
immediately after finishing LUS and will be communicated to the patient’s attending physician 
who will decide on what changes in the management of patients will take place. 
To perform a proper lung ultrasound, the image depth should be at least twice the distance 
from the skin to the pleural line. A depth of 1 cm is never adequate for this purpose. In the SLUS 
group, we will deliberately use a shallow image (1 cm depth) to mimic LUS without the capability 
to detect lung pathology, while ensuring that the same areas of the chest wall are covered in the 
same amount of time as a complete LUS.              
 
11b- No Criteria for discontinuing or modifying allocated interventions for a given trial 
participant. 
              11c-  Strategies to improve adherence to intervention protocols, and any procedures for 
monitoring adherence are not applicable to our trial because it is a one-time occurrence. 
       11d-  Relevant concomitant care and interventions that are permitted or prohibited during the trial 
- 
All kinds of standard care for children with LRTIs will be allowed in the controlled group except 
doing lung ultrasound. 
 
Outcomes  
12-   
o Primary outcome:  
▪ 
Antibiotic prescriptions rate upon discharge in hospitalized children and 
adolescents with LRTIs who undergo LUS vs. SLUS, both in addition to standard 
care. Patients who will receive antibiotics for ≤ 48 hours before enrolment and 
will stop it after enrolment will be considered not taking antibiotics since this 
short course will not affect the outcome of a bacterial LRTI. 

 
10 
o Secondary outcome:  
▪ 
Length of stay in the hospital 
▪ 
Rate of complications (by 4 weeks after enrollment will be analyzed as single 
outcomes): admission to ICU, chest tube insertion, mortality 
▪ 
Frequency of chest x-ray (CXR) performance by the 4 weeks after enrollment. 
▪ 
The rate of antibiotic intake, evaluated 4 weeks after enrollment. 
▪ 
Rate of readmission to hospital by 4 weeks after enrollment 
 
Participant timeline 
13-   
 
Study Period 
Close-
out 
 
Enrollment 
Allocation 
Post-Enrollment  
Time Point 
0 
1st 24 
hours 
1st 24 hours 
3rd day or 
upon 
discharge 
whicheve
r comes 
1st 
1 
week 
2 
week
s 
3 
week
s 
4 
weeks 
Eligibility 
screen 
x 
 
 
 
 
 
 
 
Informed 
consent 
x 
 
 
 
 
 
 
 
Allocation 
 
x 
 
 
 
 
 
 
LUS 
 
 
x 
x 
 
 
 
 
SLUS 
 
 
x 
x 
 
 
 
 
Phone call 
 
 
 
 
x 
x 
x 
x 
Table 2: Participant timeline 
 
 
Sample Size: 
14-   The sample size was determined based on the primary hypothesis.  
 
At our institution, the rate of antibiotic prescriptions for hospitalized children with LRTIs is 
approximately 60%. In the PLUS-AP trial, we anticipate that performing Lung Ultrasound (LUS) 

 
11 
will lead to a 25% reduction in the rate of antibiotic prescriptions in the LUS arm. Specifically, 
this means that while 60% of children in the SLUS arm are expected to receive antibiotics, we 
expect that only 35% of children in the LUS arm will be prescribed antibiotics. This reduction is 
expected without the addition of procalcitonin testing. 
The primary study endpoint will be assessed upon discharging the patient from the hospital, 
that’s why a very minimal percentage (5%) is anticipated to have loss to follow-up. To ensure 
adequate statistical power (80%) and a significance level of 5%, we used SPSS to calculate the 
sample size using proportions and the independent samples binomial test. The calculated 
sample size for each arm is 62 patients. Accounting for a potential 5% loss to follow-up, the 
adjusted sample size is 66 patients in each arm. Therefore, a total of 132 patients will be 
required to recruit for the study. The variability in antibiotic prescriptions among the 11 
pediatricians in our institution can be attributed to their differing practices rather than patient-
related factors. When determining the sample size, we have assumed that the clustering occurs 
by physician, resulting in 11 distinct clusters. As there are no similar studies available, the 
specific intra-class correlation coefficient (ICC) is currently unknown. However, limited 
comparable studies have indicated that the ICC typically falls within the range of 0.01 to 
0.07.22,23 For our trial, we have conservatively estimated the ICC to be 0.03. By using the formula 
1 + (M‐1) ICC, where M represents the average cluster size (which is 12 patients per physician, 
calculated as 132 patients divided by 11 physicians), the design effect (DE) was computed to be 
1.33. Consequently, the average cluster sample size is calculated as 132 multiplied by the DE 
(1.33), resulting in 176 patients (or 88 per arm). Table 3 shows different scenarios of sample size 
based on different effect size and different power.  
 
Effect  
Size 
Alpha 
Power 
Loss to  
follow-
up 
Sample  
Size 
(Arm) 
Total 
Sample 
 Size 
Ρ 
k 
Design 
Effect 
Sample  
Size 
(Arm) 
Adjusted 
Sample 
Size  
25% 
0.05 
80% 
5% 
66 
132 
0.03 
11 
1.33 
88 
176 
25% 
0.05 
90% 
5% 
87 
174 
0.03 
11 
1.33 
116 
232 
20% 
0.05 
80% 
5% 
101 
202 
0.03 
11 
1.33 
134 
268 
20% 
0.05 
90% 
5% 
135 
270 
0.03 
11 
1.33 
180 
360 
15% 
0.05 
80% 
5% 
179 
358 
0.03 
11 
1.33 
238 
476 
15% 
0.05 
90% 
5% 
239 
478 
0.03 
11 
1.33 
318 
636 
Table 3: Sample size based on different scenarios of effect size estimates and power 
 
 
Recruitment  
15-  To identify eligible patients for the PLUS-AP Trial, the Principal Investigator (PI) will circulate 
the IRB-approved protocol to all attending physicians who admit patients to the pediatric ward. 
During a divisional meeting, the PI will present the protocol to familiarize colleagues with its 

 
12 
implementation, gather valuable feedback to enhance the study’s execution, and seek their 
agreement to allow the research team to approach eligible patients under their care whenever they 
are admitted. 
During the trial, co-investigators, excluding the PI (who will remain blinded to chest X-ray 
findings), will conduct daily screenings by inquiring with the pediatric ward and emergency room 
teams about any patients admitted with respiratory tract infections (RTIs), including those 
admitted to the pediatric floor or boarding in the emergency room with admission orders. When a 
potentially eligible patient is identified, a member of the clinical care team will first approach the 
parents to inquire if they are willing to be contacted by the research team. If they accept, the 
research team will approach the family to obtain oral consent to access and review the child’s 
medical records. This oral consent will encompass an explanation of the study’s purpose, 
screening procedures, potential risks and benefits, and measures to ensure confidentiality. 
Following oral consent, the research team will review the patient’s EPIC chart to confirm 
eligibility based on inclusion and exclusion criteria. If the patient meets the criteria, the research 
team will provide a detailed explanation of the study to the parents or guardians, obtain written 
informed consent for participation, and request permission to contact them by telephone for 
follow-up or potential future studies. Once a patient is deemed eligible for the study, the PI will 
inform the primary treating physician about the planned enrollment. Following enrollment, the PI 
will provide the physician with the patient’s study allocation, as well as the results of the lung 
ultrasound, including the impression of whether the respiratory tract infection is likely viral or 
bacterial. 
The screening and enrollment process will continue until the target sample size of 176 patients is 
achieved, with an estimated enrollment period of 18 months. This comprehensive process ensures 
efficient identification of eligible participants while maintaining clear communication and 
collaboration with the treating physicians and families. 
 
Methods: Assignment of interventions (for controlled trials) 
 
Allocation:  
Sequence generation  
16. a- Participants will be randomly assigned to either control (SLUS) or experimental (LUS) 
group with a 1:1 allocation as per a computer generated Permuted-Block Randomization  
blocks of size 2 and 4. Ali Hijazi will be responsible for the randomization sequence and giving 
the allocation by phone and will have no role in outcome assessment and data analysis. 
Allocation concealment mechanism  
16. b- Allocation concealment will be ensured, as the randomization code will not be released 
by Ali Hijazi until the patient has been enrolled in the trial. 
Implementation 

 
13 
16. c-  The randomization process will be conducted by the Co-I J.A., who is not involved in 
patient recruitment. She will generate the randomization sequence. Once an eligible patient 
provides consent to participate in the study, the PI will contact J.A. by phone and provide her 
with the patient's ID number. J.A. will record this information and provide the randomization 
allocation in return.  
Blinding (masking)  
17. a- The participants and their parents will be kept unaware of the treatment allocation in 
order to maintain blinding. The PI and the treating physician will not be blinded to the 
allocation. To ensure unbiased data analysis, a research assistant who is not part of the 
research team will input data into separate datasheets on the computer. This will allow the 
researchers (except AI and JA) to analyze the data without having access to information 
regarding the treatment allocation. Consequently, the analyst will remain unaware of the 
study group to which the trial participants have been assigned. Additionally, to maintain 
independence between lung ultrasound (LUS) and chest X-ray (CXR), the PI will also be 
blinded to the CXR findings. This approach aligns with the existing literature, which supports 
LUS as a replacement for CXR in children with lower respiratory tract infections (LRTIs). 
Emergency unblinding  
17. b- Since the PI and treating physicians will not be blinded to the allocation of patients, any 
code breaks will not have an impact on the subsequent management of the patients. As a 
result, there will be no need for exceptional circumstances that would require 
emergency unblinding. 
 
Methods: Data collection, management, and analysis  
 
Data collection methods 
18. a-Outcomes and procedures: 
 
Principal Investigator (PI) Responsibilities and Equipment: 
The PI (A.I.) will perform LUS examination within 24 hours of enrollment using the CX50 
portable ultrasound machine, manufactured by Philips – Bothell, USA. The machine, owned by 
the Department of Pediatrics and Adolescent Medicine, will be equipped with a Linear 
transducer (L:12-3) set to lung presetting. LUS will be conducted exclusively by the PI, who has 
over five years of credentialing experience in LUS.  
 
Scanning Procedure: 

 
14 
Each lung will be scanned in the longitudinal and transverse orientation from the apex to the 
diaphragm along three lines: the midclavicular line (anterior view), the line between the 
paraspinal and scapular lines (posterior view), and the mid-axillary line (lateral view), following 
the methodology described by Copetti and Cattarossi.21 Both upper and lower lung zones will 
be examined in each orientation, as shown in Appendix-I. Lung ultrasound score will be 
calculated based on appendix-III. All captured perspectives will be saved, with each recorded 
video clip lasting 8 seconds. 
 
Clinical Evaluation and Categorization: 
The PI will evaluate patients’ clinical findings, including their medical history, physical 
examination results, and laboratory data to determine the clinical etiology of respiratory 
symptoms. Patients will be categorized as either having infectious (e.g. patients with fever, 
cough, positive rapid antigen test or PCR for respiratory infection) or non-infectious etiologies 
(e.g. patients with a history of chest trauma or asthma), as detailed in Appendix-II A and B. 
Subsequently, the PI will conduct lung ultrasound scans, and integrate lung ultrasound findings 
with clinical and laboratory data to suggest an etiology diagnosis targeting a better therapeutic 
decision.20 
 
Infectious Etiology: 
For suspected infectious etiologies, patients will be further assessed as clinically stable or 
unstable (Appendix-II A). Clinically stable conditions are defined by hemodynamic stability 
without dependence on inotropic and vasopressor support, and not classified under severe 
pediatric acute respiratory distress syndrome (PARDS) or severe possible PARDS according to 
the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines with SF 
ratio > 150 and/or PF ratio > 100.24 Patients who are clinically unstable will be excluded from 
the study as they will receive treatment in the pediatric intensive care unit and likely be 
administered antibiotics for potential bacterial infection. For patients who will be clinically 
stable and have a potential lower respiratory tract infection, the initial step in LUS involves 
checking for the presence of B-lines.  
If B-lines are absent and there is no consolidation, the condition will be considered as an upper 
respiratory tract infection (URTI).25,26  
Bilateral B-lines:  
When bilateral B-lines are observed, with or without consolidation smaller than 1 cm, this will 
be considered viral changes. The diagnosis that will be suggested to the treating physician will 
be either bronchiolitis (for those under 2 years of age) or viral bronchitis (for those over 2 years 
of age).10,14,27,28  
 Although a consolidation size of ≥1 cm on LUS typically indicates bacterial pneumonia, a 
diagnosis of viral pneumonia will still be considered in patients who also exhibit bilateral B-
lines.14,15 In those patients, the next step is to assess for signs of ill appearance or complicated 
pneumonia (simple or complex pleural effusion, abscess). If such signs are present, bacterial 
pneumonia will be considered. If these signs are absent, viral pneumonia will be considered, 

 
15 
and a repeat LUS within 48 hours will be advised if clinically indicated. If the follow-up 
ultrasound shows worsening, bacterial pneumonia will be considered; if there is no change or 
improvement without antibiotics, this will be considered as viral pneumonia.  
Unilateral B-lines:  
In cases where B-lines are focal and unilateral with a consolidation ≥1 cm, with or without 
pleural effusion, and accompanied by a dynamic air bronchogram, bacterial pneumonia will 
be considered.29 If the bronchogram is static or absent (hepatization), the etiology may be  
bacterial pneumonia or atelectasis.10,15,29,30 When B-lines are focal and unilateral without 
consolidation, or if accompanied by a consolidation smaller than 1 cm, this will be considered 
as mild viral infection in most cases, or early bacterial infection. In such cases, a repeat 
ultrasound within 48 hours will be advised. If the findings show progression to bilateral B-lines, 
or show improvement without antibiotics, viral etiology will be considered. Conversely, if the 
findings show consolidation of 1 cm or larger, this will be considered as bacterial pneumonia. 
Clinically unstable patients and those diagnosed with bacterial pneumonia, superimposed 
bacterial pneumonia, or complicated pneumonia will be ultimately considered for antibiotic 
treatment. 
 
Non-infectious etiology:  
Patients with suspected non-infectious etiology (Appendix-II B) can present with a range of 
conditions, such as atelectasis, contusion, cardiogenic edema, pulmonary embolism, chronic 
lung disease, or lung mass. Our trial will only include patients with LRTIs. Asthma exacerbation 
can be infection-induced or allergen-induced, thus our trial will include patients with asthma 
exacerbation. For patients presenting with clinical signs indicative of asthma—such as a past 
medical history of asthma, acute onset of shortness of breath, and wheezing observed during 
physical examination—ultrasound findings can be diverse. These may range from normal 
appearances to the presence of consolidation of any size, B-lines, or pleural effusion.31 If the 
consolidation is less than 1 cm, the etiology diagnosis will be considered as asthma 
exacerbation. This will also be considered in the case of consolidation equal to or larger than 
1 cm, with or without static air bronchograms, though a repeat ultrasound within 48 hours will 
be advised if clinically indicated. Should the repeat ultrasound show that the consolidation is 
improving without antibiotic treatment, the diagnosis of asthma exacerbation will be 
considered. Conversely, if LUS findings show worsening, it will be considered as possible 
superimposed infection. Regarding pleural effusion in patients with a clinical diagnosis of 
asthma exacerbation, a large or moderate effusion will be considered as bacterial infection. In 
the case of a small pleural effusion and clinical findings of asthma, a follow-up lung ultrasound 
within 48 hours will be advised. If the effusion is unchanged or improving without antibiotics, 
asthma exacerbation will be considered. However, if the effusion worsens, then superimposed 
bacterial pneumonia will be considered.  
 
Communication and Documentation: 

 
16 
Etiology diagnosis will be communicated to the treating physician to guide treatment 
decisions. Clinical findings, ultrasound findings and etiology diagnosis will be recorded on a 
data collection form (Appendix-III). Following the patient's discharge, outcome forms will be 
filled out, with follow-up phone calls at 1, 2, 3, and 4 weeks post-enrollment to collect data on 
length of stay, PICU admissions, chest tube insertions, mortality, antibiotic intake, and 
readmission rates, as well as the type and duration of antibiotics used and the number of CXRs 
performed during the study period (Appendix-IV).the outcome forms will be filled, along with 
phone calls at 1, 2, 3 and 4 weeks after enrollment (Appendix-IV).  
 
b- After a participant is enrolled or randomized, the study site will make all reasonable 
attempts to ensure that the participant is followed throughout the entire study duration. The 
anticipated rate of loss-to-follow-up is expected to be no more than 5%. The staff at the study 
site have the responsibility of creating and implementing local standard operating procedures 
to achieve this level of follow-up. 
 
 
Data management  
 
19- LUS will be performed twice on each patient during their hospital stay to monitor the 
progression or regression of LRTI and to screen for signs of complicated pneumonia. Ultrasound 
findings and etiology diagnoses will be recorded on a data collection form immediately after 
each LUS exam (see Appendix-III). Socio-demographic data, including age, gender, 
daycare/school attendance, comorbidities, parental highest level of education, number of 
siblings, parental smoking habits, and history of breastfeeding, will be directly collected from 
patients' families. 
Primary and secondary outcomes forms will be completed after the patient's discharge from the 
hospital and during follow-up phone calls at 1 week, 2 weeks, 3 weeks, and 4 weeks post-
enrollment (see Appendix-IV). All data retrieved from Appendices III and IV will be entered into 
REDCap, a web-based application designed specifically for data capture in research studies. This 
platform ensures secure and reliable data management, facilitating real-time data entry 
validation and comprehensive data analysis capabilities.  
Access to redcap will be password protected, with access restricted to the team of the study. 
 
The integrity of data analysis will be further ensured by the biostatistician collaborator(Z.M.), 
who will conduct the statistical analysis using data files exported from REDCap, with coded 
allocations ("A" for SLUS and "B" for LUS arms). 
All informed consent, data collection forms, and outcomes forms will be stored in locked 
cabinets in the principal investigator’s (AI) office, with restricted access limited to authorized 
personnel. Electronic data will be securely stored on the principal investigator's computer, 
which is password-protected. 

 
17 
Physical data collection forms will be destroyed 10 years after the publication of the study's 
findings. Data cleaning will be addressed through: 
- Requesting missing information during the phone calls after discharge, 
- Removing data points that are missing at random if they constitute less than 5% of the 
data, otherwise using imputation methods (mean or median), 
- Performing sensitivity analysis to assess the impact of missing data, 
- Documenting all data cleaning procedures thoroughly. 
This protocol ensures meticulous management and preservation of data integrity throughout 
the study. 
 
 
 
Statistical methods 
 
20a- Demographic and clinical characteristics variables will be summarized using means and 
standard deviations for numeric variables, and frequency distribution for the categorical 
variables. Those characteristics will be checked visually for any sizable imbalances. The primary 
analysis will include comparing the primary outcome, the rate of antibiotic prescriptions, 
between the two study arms using the Chi-square test and the univariate logistic regression will 
be used to obtain the unadjusted odds ratio (OR) and the 95% confidence interval (CI). In 
addition, adjusted standard error for cluster effect and relative risk (RR) and relative risk 
reduction (RRR) will be computed with 95% CI. For the secondary analysis, we will adjust the 
primary analysis based on the imbalances in the demographic variables using multivariate 
logistic regression and obtain OR and 95% CI. Length of stay in the hospital and frequency of CXR 
performance by 4 weeks after enrollment are numeric secondary variables. Those will be 
compared using t-test and univariate and multivariate linear regression. We will report the 
unadjusted and the adjusted mean differences (slopes) and 95% CI. Rate of chest tube insertion, 
mortality rate, rate of antibiotic intake and rate of readmission to the hospital both evaluated 
four weeks following enrollment are categorical secondary outcomes and will be analyzed using 
the Chi-square test and the univariate and multivariate logistic regression to obtain the 
unadjusted and adjusted OR and the 95% CI. The analysis will be conducted using the latest 
version of SPSS. Two-sided p-values with an alpha level of ≤ 0.05 will be used for all tests. The 
analyses will be conducted by a professional academic statistician who will be blinded to the 
study groups. Table 4 summarizes the statistical tests for each outcome. 
 
 
Variable 
Type 
unadjusted  (95% CI) 
Adjusted  (95% CI) 
RR (95% 
CI) 
RRR (95% 
CI) 

 
18 
Rate of antibiotic 
prescriptions 
upon discharge 
Categorical 
✔                      OR 
✔                SE    
OR 
✔ 
✔ 
Length of Stay 
Numeric 
✔                      β₁ 
✔                      β₁ 
 
 
Frequency of CXR 
Numeric 
✔                      β₁ 
✔                      β₁ 
 
 
Rate of chest tube  
insertion  
Categorical 
✔                      OR 
✔                      OR 
 
 
Mortality rate  
Categorical 
✔                      OR 
✔                      OR 
 
 
Rate of antibiotic 
intake and rate of 
readmission to the 
hospital both 
evaluated 4 weeks  
following enrollment  
Categorical 
✔                      OR 
✔                      OR 
 
 
Table 4: summary of statistical tests for each outcome 
 
20b- We are not going to conduct a subgroup analysis. 
 
20c- We will perform intention-to-treat analysis to examine the effectiveness of LUS usage 
compared to SLUS. The potential impact of missing data on the results will be evaluated through 
measuring means or medians.  
 
Methods: Monitoring  
 
Data monitoring  
21- a- A Data and Safety Monitoring Committee (DSMC) will be formed, operating independently 
from the study organizers. Throughout the recruitment phase of the study, the DSMC will 
receive one interim analysis, which will be treated as confidential. Additionally, the committee 
may request any other analyses as deemed necessary. The main function of the DSMC is to 
regularly assess the accumulating data and make decisions regarding potential modifications or 
discontinuation of the trial. The DSMC will communicate the results of its evaluations to the trial 
steering committee. 
The chair of the DSMC is going to be Dr. Mona Nabulsi (Pediatrician, Department of Pediatrics 
and Adolescent Medicine, AUBMC) with two members: Dr. Lama Charafeddine (Neonatologist, 
Department of Pediatrics and Adolescent Medicine, AUBMC), and Dr. Hani Tamim 
(Biostatistician, Clinical Research Institute, AUB). All members are at the professorial rank. The 
charter will be appended to the protocol (Appendix V).  

 
19 
 
21b- An interim analysis will be conducted on the primary endpoint once during the trial, once 
50% of the patients have been randomized and completed the 4-week follow-up. The analysis 
will be carried out by the Collaborator (Z.M.), who will be unaware of the patients’ allocation. 
The statistician will provide a report to DSMC. The DSMC will have full access to unblinded data 
and will hold a joint meeting with the steering committee to discuss the results of the interim 
analysis. The steering committee will make the decision regarding the continuation of the trial. 
For the interim analysis, the Peto approach will be utilized, employing symmetric stopping 
boundaries at a significance level of P < 0.01.  
Harms  
22- Lung ultrasonography is a radiation-free imaging technique, making it a safe choice for children. 
There will be no harm induced to patients from the intervention itself. We will still capture 
solicited and unsolicited adverse events and report it to IRB. As for the potential complications 
of LRTIs (ICU admission, chest tube, mortality, readmission to the hospital) that can occur in 
both study arms, this can occur in those patients who will not receive a timely etiology 
treatment, in particular antibiotics in the case of bacterial pneumonia. Complications of 
mismanagement of LRTIs and the rate of antibiotic intake and rate of CXR performed by 4 weeks 
after enrollment will be assessed as secondary endpoints.   
Recognizing the potential for false negatives with lung ultrasound, it's important to highlight 
that all patients will receive the standard of care, which includes cessation of antibiotics when 
clinical judgment and diagnostic findings, such as CXR and lab results, indicate a viral infection. 
This practice is consistent with our institution's approach, even in the vulnerable 3 to 6 months 
age group. The literature supports LUS as having superior sensitivity compared to CXR, 
minimizing the risk associated with false negatives. Additionally, the ongoing observation of 
admitted patients and repeated ultrasound before discharge provide further safeguards. These 
measures ensure that any necessary adjustments to treatment can be made timely based on the 
treating physician's continuous assessment. 
 
Auditing  
23- The investigators will handle the data in accordance with standard confidentiality regulations. 
Direct access to source documents will be granted for monitoring, audits, and inspections. IRB 
will conduct audits on an annual basis. Moreover, the study protocol will be published before 
starting the recruitment of participants. 
 
Ethics and dissemination  
 

 
20 
Research ethics approval  
24-  The institutional review board (IRB) at AUB will review and approve the protocol and informed 
consent forms and the supplementary appendices. This review ensures that the documents meet 
scientific standards and comply with relevant regulations concerning research and the protection of 
human subjects. Once the initial review and approval are complete, the IRBs will continue to 
periodically review the consent process and protocol-related issues, such as recruitment and the 
criteria for including or excluding participants. These reviews will occur at least once every year. 
Additionally, the PI will provide safety and progress reports to the IRBs at least once a year as part of 
continuing review. 
 
Protocol amendments  
25- If any changes to the protocol could affect how the study is conducted, the potential benefits for 
patients, or patient safety, including modifications to study objectives, design, patient 
population, sample sizes, study procedures, or significant administrative aspects, a formal 
amendment to the protocol will be necessary. This amendment must be submitted to the IRB 
for approval before it can be implemented. On the other hand, administrative changes to the 
protocol refer to minor corrections or clarifications that do not impact the study's conduct. The 
IRB will be informed of any administrative changes that occur. 
 
Consent or assent  
26- a- All members of the research team will receive training on the process of obtaining informed 
consent from parents who are 18 years old, as well as assent from participants aged 7 to 17 
years. The team member will ensure that participants and their parents are fully introduced to 
and comprehensively informed about the research study. Written consent and assent will be 
obtained from them. Signed consent forms will be provided to all parents involved in the trial, 
and these forms will be available in both English and Arabic languages. 
 
b- Written consent and assent will be obtained from parents and their children, allowing their 
participation in the current study, as well as granting permission to be contacted by telephone 
for further follow-up if necessary or for future relevant studies. 
 
Confidentiality  
27- We aim to maintain the highest standards of confidentiality and security for the data collected 
in this study. 
Access to the REDCap project will be  restricted to authorized personnel only. Users will require 
login credentials and will be assigned roles based on their need to access specific data. All data 

 
21 
collected will be stored on Redcap’s secure servers, ensuring compliance with institutional and 
federal regulations for data protection and confidentiality. All research team members will 
undergo training on data security and confidentiality practices to ensure they understand their 
responsibilities in protecting participant information. Additionally, the data will be stored in a 
password-protected folder on the desktops of the Principal Investigator, Dr. Ali Ismail. 
All informed consent and data collection forms will be securely stored in locked cabinets located 
in the principal investigator's (AI) office. Access to these cabinets will be restricted to the 
principal investigator and research assistant. All data collection forms will be destroyed after a 
period of 10 years from the publication of the study's findings. 
 
Declaration of interests  
28- The principal investigator (AI) will have no conflict of interest for the overall trial. 
 
Access to data  
29- The final dataset, which will be password protected, will be accessible only to the Principal 
Investigator (AI). In order to maintain confidentiality, any data shared with other members of 
the project team will be stripped of any identifying participant information. 
 
Ancillary and post-trial care  
30- Ultrasound does not cause any harm or risk on our study patients’ health. That’s why patients 
that will be enrolled into the study will not be candidates to be covered by insurance or 
indemnity for harm.  
 
Dissemination policy  
31- a- Maintaining the scientific integrity of the project is crucial, and therefore the data will be 
analyzed and reported on a study-wide basis. The Steering Committee will provide guidance on 
the timing and venues for presenting such endpoint data. The planned duration of the PLUS-AP 
project is 1.5 years till the randomization of the last participant, but it may end earlier or later 
depending on circumstances. We will strive to minimize the time between the completion of 
data collection and the release of study results. It is anticipated that it will take approximately 6-
12 months to compile the final results paper for submission to an appropriate journal. The study 
results will be shared with participating physicians, referring physicians, patients, as well as 
through poster presentation and oral presentation at meetings. 
b- The final authority over the content of manuscripts submitted for publication will be given to 
individuals who meet the authorship criteria defined by the International Committee of Medical 

 
22 
Journal Editors.32 Professional medical writers will not be engaged or hired for the purpose of 
manuscript development. 
 
c- Within a maximum of 3 years after collecting the post-randomization data, when an external 
team requests access to data, they usually submit a research question along with an analysis 
plan. The Trial Steering Committee reviews this submission and either approves it or requests 
clarifications. Upon approval, the external team has the option to work independently of the 
trial TSC or collaborate with them. 
 
Appendices  
 
Informed consent materials  
32- Appendix VI 
 
Biological specimens  
Not Applicable 
 
References: 
1. Troeger, C. et al. Estimates of the global, regional, and national morbidity, mortality, and aetiologies 
of lower respiratory tract infections in 195 countries: a systematic analysis for the Global Burden of 
Disease Study 2015. Lancet Infect. Dis. 17, 1133–1161 (2017). 
2. Obonyo, C. O. & Lau, J. Efficacy of Haemophilus influenzae type b vaccination of children: a meta-
analysis. Eur. J. Clin. Microbiol. Infect. Dis. 25, 90–97 (2006). 
3. Pavia, M., Bianco, A., Nobile, C. G. A., Marinelli, P. & Angelillo, I. F. Efficacy of Pneumococcal 
Vaccination in Children Younger Than 24 Months: A Meta-Analysis. Pediatrics 123, e1103–e1110 
(2009). 
4. Jain, S. et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Children. N. Engl. 
J. Med. 372, 835–845 (2015). 

 
23 
5. Lopez, A. A., Aslanova, R., Bridger, N. & Chafe, R. Antibiotic Use for Inpatient Bronchiolitis: Did 
National Guidelines Impact Practice at a Pediatric Hospital? Hosp. Pediatr. 10, 147–152 (2020). 
6. Mustafa, Z. U. et al. Antibiotic use among hospitalized children with lower respiratory tract infections: 
a multicenter, retrospective study from Punjab, Pakistan. Expert Rev. Anti Infect. Ther. 20, 131–136 
(2022). 
7. Bradley, J. S. et al. The Management of Community-Acquired Pneumonia in Infants and Children 
Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society 
and the Infectious Diseases Society of America. Clin. Infect. Dis. 53, e25–e76 (2011). 
8. Harris, M. et al. British Thoracic Society guidelines for the management of community acquired 
pneumonia in children: update 2011. Thorax 66, ii1–ii23 (2011). 
9. Gerber, J. S. et al. Antibiotic Stewardship in Pediatrics. Pediatrics 147, e2020040295 (2021). 
10. 
Kharasch, S., Duggan, N. M., Cohen, A. R. & Shokoohi, H. Lung Ultrasound in Children with 
Respiratory Tract Infections: Viral, Bacterial or COVID-19? A Narrative Review. Open Access Emerg. 
Med. Volume 12, 275–285 (2020). 
11. 
Caiulo, V. A. et al. Lung ultrasound characteristics of community-acquired pneumonia in 
hospitalized children: Ultrasound Characteristics of Pneumonia in Children. Pediatr. Pulmonol. 48, 
280–287 (2013). 
12. 
Pereda, M. A. et al. Lung Ultrasound for the Diagnosis of Pneumonia in Children: A Meta-
analysis. Pediatrics 135, 714–722 (2015). 
13. 
Heuvelings, C. C. et al. Chest ultrasound for the diagnosis of paediatric pulmonary diseases: a 
systematic review and meta-analysis of diagnostic test accuracy. Br. Med. Bull. 129, 35–51 (2019). 

 
24 
14. 
Berce, V., Tomazin, M., Gorenjak, M., Berce, T. & Lovrenčič, B. The Usefulness of Lung 
Ultrasound for the Aetiological Diagnosis of Community-Acquired Pneumonia in Children. Sci. Rep. 9, 
17957 (2019). 
15. 
Omran, A. et al. Lung Ultrasound and Neutrophil Lymphocyte Ratio in Early Diagnosis and 
Differentiation between Viral and Bacterial Pneumonia in Young Children. Children 9, 1457 (2022). 
16. 
Tsung, J. W., Kessler, D. O. & Shah, V. P. Prospective application of clinician-performed lung 
ultrasonography during the 2009 H1N1 influenza A pandemic: distinguishing viral from bacterial 
pneumonia. Crit. Ultrasound J. 4, 16 (2012). 
17. 
Guitart, C. et al. An algorithm combining procalcitonin and lung ultrasound improves the 
diagnosis of bacterial pneumonia in critically ill children: The PROLUSP study, a randomized clinical 
trial. Pediatr. Pulmonol. 57, 711–723 (2022). 
18. 
Lhopitallier, L. et al. Procalcitonin and lung ultrasonography point-of-care testing to determine 
antibiotic prescription in patients with lower respiratory tract infection in primary care: pragmatic 
cluster randomised trial. BMJ n2132 (2021) doi:10.1136/bmj.n2132. 
19. 
Shah, S. S., Florin, T. A. & Ambroggio, L. Procalcitonin in Childhood Pneumonia. J. Pediatr. Infect. 
Dis. Soc. 7, 54–55 (2018). 
20. 
Singh, Y. et al. International evidence-based guidelines on Point of Care Ultrasound (POCUS) for 
critically ill neonates and children issued by the POCUS Working Group of the European Society of 
Paediatric and Neonatal Intensive Care (ESPNIC). Crit. Care 24, 65 (2020). 
21. 
Copetti, R. & Cattarossi, L. Ultrasound diagnosis of pneumonia in children. Radiol. Med. (Torino) 
113, 190–198 (2008). 

 
25 
22. 
Van Duijn, P. J. & Bonten, M. J. Antibiotic rotation strategies to reduce antimicrobial resistance 
in Gram-negative bacteria in European intensive care units: study protocol for a cluster-randomized 
crossover controlled trial. Trials 15, 277 (2014). 
23. 
Arnold, S. H. et al. Reducing Antibiotic Prescriptions for Urinary Tract Infection in Nursing Homes 
Using a Complex Tailored Intervention Targeting Nursing Home Staff: Protocol for a Cluster 
Randomized Controlled Trial. JMIR Res. Protoc. 9, e17710 (2020). 
24. 
Emeriaud, G. et al. Executive Summary of the Second International Guidelines for the Diagnosis 
and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2). Pediatr. Crit. Care 
Med. 24, 143–168 (2023). 
25. 
Chichra, A., Makaryus, M., Chaudhri, P. & Narasimhan, M. Ultrasound for the Pulmonary 
Consultant. Clin. Med. Insights Circ. Respir. Pulm. Med. 10, 1–9 (2016). 
26.         Lichtenstein, D. A. & Mezière, G. A. Relevance of Lung Ultrasound in the Diagnosis of Acute 
Respiratory Failure*: The BLUE Protocol. Chest 134, 117–125 (2008). 
27. 
International Liaison Committee on Lung Ultrasound (ILC-LUS) for the International Consensus 
Conference on Lung Ultrasound (ICC-LUS) et al. International evidence-based recommendations for 
point-of-care lung ultrasound. Intensive Care Med. 38, 577–591 (2012). 
28. 
Biagi, C. et al. Lung ultrasound for the diagnosis of pneumonia in children with acute 
bronchiolitis. BMC Pulm. Med. 18, 191 (2018). 
29.        Lichtenstein, D., Mezière, G. & Seitz, J. The Dynamic Air Bronchogram. Chest 135, 1421–1425 
(2009). 
30. 
Acosta, C. M., Belaunzarán, A. & Gonorazky, S. Accuracy of Transthoracic Lung Ultrasound for 
Diagnosing Anesthesia-induced Atelectasis in Children. Perioper. Med. 

 
26 
31. 
Dankoff, S., Li, P., Shapiro, A. J., Varshney, T. & Dubrovsky, A. S. Point of care lung ultrasound of 
children with acute asthma exacerbations in the pediatric ED. Am. J. Emerg. Med. 35, 615–622 
(2017). 
32. 
Zimba, O. & Gasparyan, A. Y. Scientific authorship: a primer for researchers. Reumatologia 58, 
345–349 (2020). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix I: Illustration of Pediatric Lung Ultrasound Approaches 

 
27 
 
Illustration of Pediatric Lung Ultrasound Approaches 
In red: Anterior Approach: Midclavicular lines  
In blue: Lateral Approach: Midaxillary lines 
In black: Posterior Approach: the Vertical lines extending between the paraspinal and scapular lines. 
Reference: (21) 
 

 
28 
 
 
 
 
 
 
 
 

 
29 
 
 
 
 
 
 

 
30 
 
 
 
 
Appendix III: Data Collection Form (PLUS-AP trial) 
1- Demographics:  
Age:  
  
  
Gender:   
  
Location:                    
Daycare/School:   
  
Comorbidities:             Parents highest level of education:  
  
                        Number of 
siblings: 
 
  
Parental smoking:  
   
  
  History of breastfeeding:    
2- Vital signs:  Temp:              HR:                  RR:                 BP:                         SpO2:  
On oxygen supplementation?  Yes / No              if Yes, Specify: __________________ 
3- Respiratory Symptoms:  
• Respiratory distress   • Cough   
                • Fever  
• Chest pain  
  
 • Pleuritic Chest pain  • Blunt trauma  
• Penetrating Trauma  • Other:   
4- Lab Results:  
 
 
5-Views:  
Right Anterior Thorax:  □ Adequate                         □ Limited                           □ Not obtained  
Right Lateral Thorax:     □ Adequate                         □ Limited                           □ Not obtained  
Right Posterior Thorax: □ Adequate                         □ Limited                           □ Not obtained  
Left Anterior Thorax:     □ Adequate                         □ Limited                           □ Not obtained  
Letf Lateral Thorax:        □ Adequate                         □ Limited                           □ Not obtained  
Left Posterior Thorax:    □ Adequate                         □ Limited                           □ Not obtained  
 

 
31 
 
 
 
 
 
 
 
 
 
 
 Lung Ultrasound Score:  
 
 
 
 
6- LUS Findings: 
Right Lung Sliding: 
• Present 
• Absent 
 
• Indeterminate 
Right Lung Point: 
 
 

 
32 
• Absent 
 
       • Present 
 
   • Indeterminate 
Left Lung Sliding: 
• Present 
 
• Absent 
 
• Indeterminate 
Left Lung Point: 
• Absent 
 
• Present 
 
• Indeterminate 
Right B-Lines: 
• Absent 
 
• Focal  
• Bilateral 
       • Anterior          • Lateral               • Posterior 
Right Consolidation:  
• Absent 
 
• <1 cm (Ant, Lat, Post) • ≥1 cm  (Ant, Lat, Post) • Air bronchograms 
Right Pleural Effusion: 
• Absent 
 
• Simple 
 
• Complex 
• Mild             • Moderate           • Severe      
Left B-Lines:   
• Absent 
 
• Focal  
• Bilateral 
       • Anterior          • Lateral               • Posterior 
Left Consolidation: 
• Absent 
 
• <1 cm (Ant, Lat, Post) • ≥1 cm  (Ant, Lat, Post) • Air bronchograms 
Left Pleural Effusion: 
• Absent 
 
• Simple 
 
• Complex 
• Mild             • Moderate           • Severe      
Comments:  
7- LUS Etiology Diagnosis: 
• URTI • Viral Infection (Bronchiolitis/Bronchitis) 
• Viral Pneumonia     • Bacterial Pneumonia 
• Superimposed bacterial pneumonia     •Complicated pneumonia (effusion, abscess) 
• Asthma 
• Mild Early Infection 
 
• Other:  
8-Duration of Ultrasound: 
 
Time started: 
 
 
Time completed: 
9-Recommendation:  
 

 
33