Identification and Characterization of Bacteria in the Lungs of Children From 6 Months up to 6 Years Old, With Suspected Infection of the Lungs, in Spain.

Not Applicable

Completed

Conditions: Infections, Streptococcal

Interventions: Other: BAL fluid sampling
Other: Nasopharyngeal swab sampling

Registration Number: NCT02838407

Lead Sponsor: GlaxoSmithKline

Brief Summary: The purpose of this study is to identify and characterise bacteria present in the lower airways of children with suspected chronic LRTIs and for whom bronchoalveolar lavage (BAL) is indicated by the clinician.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 197

Inclusion Criteria

Subjects who the investigator believes that parent(s)/ legally acceptable representatives (LAR[s]) can and will comply with the requirements of the protocol.
A male or female subject aged ≥ 6 months to < 6 years at the time of enrolment.
Subjects meet the case definition of suspected chronic LRTIs where BAL is indicated.
Subject's parent(s)/ LAR(s) agree to the collection of a nasopharyngeal swab from the subject.
Written informed consent obtained from the parent(s)/ LAR(s) of the subject.

Exclusion Criteria

Known cystic fibrosis, immunosuppression, or other severe immunodeficiencies such as agammaglobu-linaemia, T cell deficiency or Human Immunodeficiency Virus/ Acquired Immune Deficiency Syndrome, chemotherapy treatment, etc.
Exacerbation of persistent respiratory symptoms (cough, wheezing, difficulty in breathing, etc.) in the previous 2 weeks.
Antibiotic treatment in the 2 weeks prior to study entry.
Concurrent participation in another study within 30 days prior to study entry or at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
Subjects having previously participated in this study.
Child in care.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Total group	BAL fluid sampling	All enrolled subjects, male or female aged between 6 months included and less than 6 years at the time of enrollment, who visited the hospital with suspected chronic lower respiratory tract infections (LRTIs) and who had an indication for bronchoalveolar lavage (BAL).
Total group	Nasopharyngeal swab sampling	All enrolled subjects, male or female aged between 6 months included and less than 6 years at the time of enrollment, who visited the hospital with suspected chronic lower respiratory tract infections (LRTIs) and who had an indication for bronchoalveolar lavage (BAL).

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Bacterial Aetiology Characteristics in BAL Fluid Samples	From Day 0 up to Year 2	S. pneumoniae (S.p.), H. influenzae (H.i.) and M. catarrhalis (M.c.) were confirmed by bacterial identification (B.I.) load higher than (\>) 10\^4 colony forming units per milliliter (cfu/mL), if bacterial species were present alone, or \>10\^5 cfu/mL if presented as co-infection. Analysis was also performed for other bacterial pathogens alone or as co-infection. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses
Number of Subjects With Bacterial Aetiology, Assessed by Culture Growth, From Bronchoalveolar Lavage (BAL) Fluid Samples	From Day 0 up to Year 2	Bacterial aetiology was assessed by culture growth from BAL fluid sample for Steptococcus pneumoniae (S.p.), Haemophilus influenzae (H.i.) and Moraxella catarrhalis (M.c.) , through either qualitative or quantitative bacterial identification (B.I.). The categories assessed were: positive (Pos.), negative (Neg.) and Missing (Mis.). For quantitative bacterial identification, S.p., H.i. and M.c. were confirmed by bacterial identification load higher than (\>) 10\^4 colony forming units per milliliter (cfu/mL), if bacterial species were present alone, or \>10\^5 cfu/mL if present as co-infection. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Number of Subjects With Bacterial Identification >10^4 Cfu/mL in BAL Fluid Samples (S. Pneumoniae and H. Influenzae Results for the "Negative M. Catarrhalis" BAL Fluid Samples Results Category)	From Day 0 up to Year 2	S. pneumoniae, H. influenzae and M. catarrhalis were confirmed by bacterial identification load higher than (\>) 10\^4 colony forming units per milliliter (cfu/mL), if bacterial species were present alone. Bacterial load referred to Negative M. catarrhalis - Negative S. pneumoniae - Negative H. influenzae (N.M.c.-N.S.p.-N.H.i.), Negative M. catarrhalis - Negative S. pneumoniae - Positive H. influenzae (N.M.c.-N.S.p.-P.H.i.), Negative M. catarrhalis - Positive S. pneumoniae - Negative H. influenzae (N.M.c.-P.S.p.-N.H.i.), Negative M. catarrhalis - Positive S. pneumoniae - Positive H. influenzae (N.M.c.-P.S.p.-P..H.i.). Notes: bacterial identification for the N.M.c.-P.S.p.-P.H.i. category was confirmed as a co-infection with a bacterial load \>10\^5 cfu/mL. For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Number of Subjects With Bacterial Identification >10^4 Cfu/mL in BAL Fluid Samples (S. Pneumoniae and H. Influenzae Results for the "Positive M. Catarrhalis" BAL Fluid Samples Results Category)	From Day 0 up to Year 2	S. pneumoniae, H. influenzae and M. catarrhalis were confirmed by bacterial identification load higher than (\>) 10\^4 colony forming units per milliliter (cfu/mL), if bacterial species were present alone and by bacterial load \>10\^5 cfu/mL if presented as co-infection. Categories referred to Positive M. catarrhalis -Negative S. pneumoniae - Negative H. influenzae (P.M.c.-N.S.p.-N.H.i.), Positive M. catarrhalis -Negative S. pneumoniae - Positive H. influenzae (P.M.c.-N.S.p.-P.H.i.), Positive M. catarrhalis - Positive S. pneumoniae - Negative H. influenzae (P.M.c.-P.S.p.-N.H.i.), Positive M. catarrhalis - Positive S. pneumoniae - Positive H. influenzae (P.M.c.-P.S.p.-P.H.i.). Notes: bacterial identification for the P.M.c.-N.S.p.-P.H.i., P.M.c.-P.S.p.-N.H.i. and P.M.c.-P.S.p.-P.H.i. categories was confirmed by a bacterial identification \>10\^5 cfu/mL. For one subject who underwent BAL procedure, no BAL fluid was available for study analyses

Secondary Outcome Measures

Name	Time	Method
C-reactive Protein (CRP) Laboratory Results	From Day 0 to Year 2	Laboratory results for CRP were expressed in milligrams per litre (mg/L).
Bacterial Load Detected (log10 Transformation) by Quantitative Culture From Nasopharyngeal Swab Samples	From Day 0 up to Year 2	Bacterial load was detected by quantitative culture from nasopharyngeal swab samples for S. pneumoniae, H. influenzae and M. catarrhalis and expressed in colony-forming unit/ milliliter (cfu/mL). Quantitative bacterial identification was used to indicate the presence of bacterial pathogen load \>10\^4 cfu/mL if present alone or \> 10\^5 cfu/mL if present as co-infection.
Number of Subjects With Other Bacterial Pathogens Detected by Qualitative Culture From Nasopharyngeal Swab Samples	From Day 0 and up to Year 2	Bacterial pathogens were detected by qualitative culture from nasopharyngeal swab samples and included: Staphylococcus aureus and Stenotrophomonas maltophilia
Number of S. Pneumoniae Unique Isolates With Antimicrobial Susceptibility Response, Among Qualitative Positive Subjects	From Day 0 to Year 2	Antibiotic response of S.pneumoniae was susceptible (Sus), or intermediate (Int), or resistant (Res)(following Clinical and Laboratory Standards Institute \[CLSI\] guidelines \[CLSI, 2015\]) towards the tested antibiotics which included: Penicilin, Amoxicillin/Clavulanate, Erythromycin, Azithromycin, Tetracycline, Levofloxacin, Trimethoprim/Sulfamethoxazole. Samples assessed were BAL fluid (BALF) samples and Nasopharyngeal swab (NPS) samples. For the "Unique isolate definition", please refer to the previous outcome description. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Descriptive Statistics of the Antimicrobial Susceptibility Response of H. Influenzae for Unique Isolates Among Qualitative Positive Subjects, for Penicilin and Erythromycin	From Day 0 to Year 2	Antibiotic response of H. influenzae was tested against antibiotics which included: Penicilin and Erythromycin (following Clinical and Laboratory Standards Institute \[CLSI\] guidelines \[CLSI, 2015\]). Samples assessed were BAL fluid (BALF) samples and Nasopharyngeal swab (NPS) samples. Unique isolate definition: 2 isolates of S.p., H.i. and M.c. were selected per specimen type per subjects. For analyses, the 2 isolates were compared to determine if they were clones vs. different ("unique") pathogen. Isolates were considered "unique" based on the comparison of serotype and antibiotic susceptibility (AS) profile for S.p. and H.i. and on the AS profile alone for M.c.. If the 2 isolates had different serotypes, or the same serotype but a different AS profile, then the 2 isolates were considered "unique", and both isolates were retained in the analyses. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Number of M. Catarrhalis Unique Isolates With Antimicrobial Susceptibility Response From Quantitative Positive Subjects	From Day 0 to Year 2	Antibiotic response of M. catarrhalis was susceptible (Sus.), or intermediate (Int.), or resistant (Res.)(following Clinical and Laboratory Standards Institute \[CLSI\] guidelines \[CLSI, 2015\]) towards the tested antibiotics which included: Amoxicillin/Clavulanate, Erythromycin, Azithromycin, Tetracycline, Levofloxacin, Trimethoprim/Sulfamethoxazole. Samples assessed were BAL fluid (BALF) samples and Nasopharyngeal swab (NPS) samples. For the "Unique isolate definition", please refer to the previous outcome description. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Number of Qualitative Positive Unique Isolates of Subjects With S. Pneumoniae Serogroups and Serotypes From Nasopharyngeal Swab Samples	From Day 0 to Year 2	S. pneumoniae serogoups and serotypes included: 3, 6A, 6B, 7C, 9N, 10A, 11A, 11D, 12B, 12F, 14, 16F, 18C, 18F, 19A, 19C, 19F, 21, 23A, 23B, 31, 35A, 35F, 42, 48, NT (not typeable), Synflorix serotypes (1, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) and Pneumococcal conjugate vaccine (PCV) 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F). Unique isolate definition: 2 isolates of S.p., H.i. and M.c. were selected per specimen type per subjects. For analyses, the 2 isolates were compared to determine if they were clones vs. different ("unique") pathogen. Isolates were considered "unique" based on the comparison of serotype and antibiotic susceptibility (AS) profile for S.p. and H.i. and on the AS profile alone for M.c.. If the 2 isolates had different serotypes, or the same serotype but a different AS profile, then the 2 isolates were considered "unique", and both isolates were retained in the analyses.
Number of Qualitative Positive Unique Isolates of Subjects With H. Influenzae Typing Results From Nasopharyngeal Swab Samples	From Day 0 to Year 2	The H. influenzae typing results include "f " and "NT" (not typeable). Unique isolate definition: 2 isolates of S.p., H.i. and M.c. were selected per specimen type per subjects. For analyses, the 2 isolates were compared to determine if they were clones vs. different ("unique") pathogen. Isolates were considered "unique" based on the comparison of serotype and antibiotic susceptibility (AS) profile for S.p. and H.i. and on the AS profile alone for M.c.. If the 2 isolates had different serotypes, or the same serotype but a different AS profile, then the 2 isolates were considered "unique", and both isolates were retained in the analyses.
Number of S. Pneumoniae Unique Isolates With Antimicrobial Susceptibility Response From Quantitative Positive Subjects	From Day 0 to Year 2	Antibiotic response of S.pneumoniae was susceptible (Sus), or intermediate (Int), or resistant (Res)(following Clinical and Laboratory Standards Institute \[CLSI\] guidelines \[CLSI, 2015\]) towards the tested antibiotics which included: Penicilin, Amoxicillin/Clavulanate, Erythromycin, Azithromycin, Tetracycline, Levofloxacin, Trimethoprim/Sulfamethoxazole. Samples assessed were BAL fluid (BALF) samples and Nasopharyngeal swab (NPS) samples. For the "Unique isolate definition", please refer to the previous outcome description. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Number of M. Catarrhalis Unique Isolates With Antimicrobial Susceptibility Response, Among Qualitative Positive Subjects	From Day 0 to Year 2	Antibiotic response of M. catarrhalis was susceptible (Sus), or intermediate (Int), or resistant (Res)(following Clinical and Laboratory Standards Institute \[CLSI\] guidelines \[CLSI, 2015\]) towards the tested antibiotics which included: Amoxicillin/Clavulanate, Erythromycin, Azithromycin, Tetracycline, Levofloxacin, Trimethoprim/Sulfamethoxazole. Samples assessed were BAL fluid (BALF) samples and Nasopharyngeal swab (NPS) samples. For the "Unique isolate definition", please refer to the previous outcome description. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Descriptive Statistics of the Antimicrobial Susceptibility Response of M. Catarrhalis for Unique Isolates Among Qualitative Positive Subjects, for Penicilin	From Day 0 to Year 2	Antibiotic response of M. catarrhalis was tested against antibiotics which included: Penicilin. Samples assessed were BAL fluid (BALF) samples and Nasopharyngeal swab (NPS) samples. Unique isolate definition: 2 isolates of S.p., H.i. and M.c. were selected per specimen type per subjects. For analyses, the 2 isolates were compared to determine if they were clones vs. different ("unique") pathogen. Isolates were considered "unique" based on the comparison of serotype and antibiotic susceptibility (AS) profile for S.p. and H.i. and on the AS profile alone for M.c.. If the 2 isolates had different serotypes, or the same serotype but a different AS profile, then the 2 isolates were considered "unique", and both isolates were retained in the analyses. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Erythrocyte Sedimentation Rate (ESR) Laboratory Results	From Day 0 to Year 2	Laboratory results for ESR were expressed in millimeters per hour (mm/hr).
Number of Subjects With Bacterial Colonization, Assessed by Culture Growth, From Nasopharyngeal Swab Samples	From Day 0 up to Year 2	Bacterial colonization was assessed by culture growth from nasopharyngeal swab samples for S. pneumoniae, H. influenzae and M. catarrhalis, through either qualitative or quantitative bacterial identification (B.I.). The categories assessed were: positive (Pos.) and negative (Neg.).
Bacterial Load Detected (log10 Transformation) by Quantitative Molecular Techniques (Polymerase Chain Reaction) From BAL Fluid Samples	From Day 0 up to Year 2	Bacterial load was detected by quantitative molecular techniques (PCR) from BAL fluid samples for S. pneumoniae, H. influenzae and M. catarrhalis and expressed in colony-forming unit/milliliter (cfu/mL). Quantitative bacterial identification was used to indicate the presence of bacterial pathogen load \>10\^4 cfu/mL if present alone or \> 10\^5 cfu/mL if present as co-infection. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Number of H. Influenzae Unique Isolates With Antimicrobial Susceptibility Response From Quantitative Positive Subjects	From Day 0 to Year 2	Antibiotic response of H.ifluenzae was susceptible (Sus), or intermediate (Int), or resistant (Res)(following Clinical and Laboratory Standards Institute \[CLSI\] guidelines \[CLSI, 2015\])towards the tested antibiotics which included: Amoxicillin/Clavulanate, Azithromycin, Tetracycline, Levofloxacin, Trimethoprim/Sulfamethoxazole. Samples assessed were BAL fluid (BALF) samples and Nasopharyngeal swab (NPS) samples. For the "Unique isolate definition", please refer to the previous outcomes description. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Number of H. Influenzae and M. Catarrhalis Unique Isolates With Antimicrobial Susceptibility Positive Response From Quantitative Positive Subjects, for Beta-lactamase	From Day 0 to Year 2	Antimicrobial response of H. influenzae and M. catarrhalis was tested for Beta-lactamase (following Clinical and Laboratory Standards Institute \[CLSI\] guidelines \[CLSI, 2015\]). Samples assessed were BAL fluid (BALF) samples and Nasopharyngeal swab (NPS) samples. Unique isolate definition: 2 isolates of S.p., H.i. and M.c. were selected per specimen type per subjects. For analyses, the 2 isolates were compared to determine if they were clones vs. different ("unique") pathogen. Isolates were considered "unique" based on the comparison of serotype and antibiotic susceptibility (AS) profile for S.p. and H.i. and on the AS profile alone for M.c.. If the 2 isolates had different serotypes, or the same serotype but a different AS profile, then the 2 isolates were considered "unique", and both isolates were retained in the analyses. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Subject Gender	From Day 0 to Year 2	Demographic characteristics included gender: female and male.
Number of Subjects Presenting General Medical History Characteristics	From Day 0 to Year 2	General medical history characteristics included: any pre-existing conditions, congenital chromosomal abnormality, prematurity (less than 37 weeks) neonatal problems, chronic renal failure, immune system disorder (including auto-immune), atopic dermatitis, clinician-confirmed eczema, asthma and other.
Mean Gestational Age of Subjects	From Day 0 to Year 2	General medical history included mean gestational age.
Number of Subjects With Laboratory Results	From Day 0 to Year 2	Laboratory results included blood sample results available, white blood Cell (WBC) count analysed, WBC reference range, Clinically relevant to the suspected chronic lower respiratory tract infection (LRTI) in the child if out of the range of WBC \[LRTI-WBC\], CRP (C-reactive protein) reference range, CRP groups, Clinically relevant to the suspected chronic LRTI in the child if out of the range of CRP \[LRTI-CRP\], ESR (Erythrocyte sedimentation rate) analysed, ESR reference range and Clinically relevant to the suspected chronic LRTI in the child if out of the range of ESR \[LRTI-ESR\].
Bacterial Load Detected (log10 Transformation) by Quantitative Culture Growth, From BAL Fluid Samples	From Day 0 up to Year 2	Bacterial load was detected by quantitative culture growth from BAL fluid samples for S. pneumoniae, H. influenzae and M. catarrhalis and expressed in colony-forming unit/ milliliter (cfu/mL). Quantitative bacterial identification was used to indicate the presence of bacterial pathogen load \>10\^4 cfu/mL if present alone or \> 10\^5 cfu/mL if present as co-infection. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Number of Subjects With Other Bacterial Pathogens Detected by Qualitative Culture, From BAL Fluid Samples	From Day 0 up to Year 2	Bacterial pathogens were detected by qualitative culture from BAL fluid samples and included: Staphylococcus aureus, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Pseudomonas putida. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Bacterial Load Detected (log10 Transformation) by Molecular Techniques (PCR) From Nasopharyngeal Swab Samples	From Day 0 and up to Year 2	Bacterial load was detected by quantitative molecular techniques from nasopharyngeal swab samples for S. pneumoniae, H. influenzae and M. catarrhalis and expressed in colony-forming unit/milliliter (cfu/mL). Quantitative bacterial identification was used to indicate the presence of bacterial pathogen load \>10\^4 cfu/mL if present alone or \> 10\^5 cfu/mL if present as co-infection.
Number of Qualitative Positive Unique Isolates of Subjects With S. Pneumoniae Serogroups and Serotypes in BAL Fluid Samples	From Day 0 to Year 2	Two isolates of S.p., H.i. and M.c. were selected per specimen type per subjects. For analyses, the 2 isolates were compared to determine if they were clones vs. different ("unique") pathogen. Isolates were considered "unique" based on the comparison of serotype and antibiotic susceptibility (AS) profile for S.p. and H.i. and on the AS profile alone for M.c.. If the 2 isolates had different serotypes, or the same serotype but a different AS profile, then the 2 isolates were considered "unique", and both isolates were retained in the analyses. S.p. serogoups and serotypes isolates included: 3, 6B, 7C, 10A, 11A, 11D, 12F, 14, 15B, 16F, 18C, 18F, 19A, 19F, 21, 22F, 23A, 23B, 31, 35F, 42, 48, NT (not typeable), Synflorix serotypes (1, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) and Pneumococcal conjugate vaccine (PCV) 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F). Note: For one subject who underwent BAL procedure, no BALF was available for study analyses.
Number of Qualitative Positive Unique Isolates of Subjects With H. Influenzae Typing Results From BAL Fluid Samples	From Day 0 to Year 2	The H. influenzae typing results included "f" and "NT" (not typeable). Unique isolate definition: 2 isolates of S.p., H.i. and M.c. were selected per specimen type per subjects. For analyses, the 2 isolates were compared to determine if they were clones vs. different ("unique") pathogen. Isolates were considered "unique" based on the comparison of serotype and antibiotic susceptibility (AS) profile for S.p. and H.i. and on the AS profile alone for M.c.. If the 2 isolates had different serotypes, or the same serotype but a different AS profile, then the 2 isolates were considered "unique", and both isolates were retained in the analyses. Note: For one subject who underwent BAL procedure, no BALF was available for study analyses.
Number of H. Influenzae Unique Isolates With Antimicrobial Susceptibility Response, Among Qualitative Positive Subjects	From Day 0 to Year 2	Antibiotic response of H.ifluenzae was susceptible (Sus), or intermediate (Int), or resistant (Res)(following Clinical and Laboratory Standards Institute \[CLSI\] guidelines \[CLSI, 2015\]) towards the tested antibiotics which included: Amoxicillin/Clavulanate, Azithromycin, Tetracycline, Levofloxacin, Trimethoprim/Sulfamethoxazole. Samples assessed were BAL fluid (BALF) samples and Nasopharyngeal swab (NPS) samples. For the "Unique isolate definition", please refer to the previous outcomes description. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Number of H. Influenzae or M. Catarrhalis Unique Isolates With Antimicrobial Susceptibility Positive Response Among Qualitative Positive Siubjects for Beta-lactamase	From Day 0 to Year 2	Antimicrobial response of H. influenzae and M. catarrhalis was tested for Beta-lactamase (following Clinical and Laboratory Standards Institute \[CLSI\] guidelines \[CLSI, 2015\]). Samples assessed were BAL fluid (BALF) samples and Nasopharyngeal swab (NPS) samples. Unique isolate definition: 2 isolates of S.p., H.i. and M.c. were selected per specimen type per subjects. For analyses, the 2 isolates were compared to determine if they were clones vs. different ("unique") pathogen. Isolates were considered "unique" based on the comparison of serotype and antibiotic susceptibility (AS) profile for S.p. and H.i. and on the AS profile alone for M.c.. If the 2 isolates had different serotypes, or the same serotype but a different AS profile, then the 2 isolates were considered "unique", and both isolates were retained in the analyses. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Mean Age of Subjects	From Day 0 to Year 2	Demographic characteristics included age, which was expressed in months.
Number of Subjects With Body Mass Index (BMI) Characteristics	From Day 0 to Year 2	Demographic characteristics included body mass index (BMI) whose z-scores were measures of relative weight adjusted for child age and sex.
Number of Subjects With Pneumococcal Vaccination History Characteristics	From Day 0 to Year 2	Pneumococcal vaccination history characteristics included vaccination, pneumococcal vaccines received (Prevnar only, Prevnar 13 only, Synflorix only, Mix of vaccines), Prevnar only doses (1-4), Prevnar 13 only doses (1-4), Synflorix only doses (4), medical history source validated or not.
White Blood Cells (WBC) Laboratory Results	From Day 0 to Year 2	Laboratory results for WBC were expressed in 10\^9 cells per liter (10\^9 cells/L).
Descriptive Statistics of the Antimicrobial Susceptibility Response of H.Influenzae for Unique Isolates Among Quantitative Positive Subjects, for Penicilin and Erythromycin	From Day 0 to Year 2	Antibiotic response of H.ifluenzae was tested against antibiotics which included: Penicilin and Erythromycin (following Clinical and Laboratory Standards Institute \[CLSI\] guidelines \[CLSI, 2015\]). Samples assessed were BAL fluid (BALF) samples and Nasopharyngeal swab (NPS) samples. Unique isolate definition: 2 isolates of S.p., H.i. and M.c. were selected per specimen type per subjects. For analyses, the 2 isolates were compared to determine if they were clones vs. different ("unique") pathogen. Isolates were considered "unique" based on the comparison of serotype and antibiotic susceptibility (AS) profile for S.p. and H.i. and on the AS profile alone for M.c.. If the 2 isolates had different serotypes, or the same serotype but a different AS profile, then the 2 isolates were considered "unique", and both isolates were retained in the analyses. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Number of Subjects With Flu Vaccination History Characteristics	From Day 0 to Year 2	Flu vaccination history included vaccination, Flu vaccine doses (1-5), medical history source validated or not.
Number of Subjects With Antibiotics and Other Medications Administered	From Day 0 to Year 2	Medication history referred to antibiotics administered in the past 6 months, drug names, antibiotic information source, other medications administered during the past 6 months, information source.
Number of Subjects With Clinical Characteristics	From Day 0 to Year 2	Clinical characteristics included affections/pre-conditions, affection episodes, number of children living in a household, children in day-care centres, exposure to cigarette smoke.
Number of Subjects With Radiological Results	From Day 0 to Year 2	Radiological results included x-ray, result normality, relationship of abnormality to BAL sampling.
Descriptive Statistics of the Antimicrobial Susceptibility Response of M. Catarrhalis for Unique Isolates Among Quantitative Positive Subjects, for Penicilin	From Day 0 to Year 2	Antibiotic response of M. catarrhalis was tested against antibiotics which included: Penicilin (following Clinical and Laboratory Standards Institute \[CLSI\] guidelines \[CLSI, 2015\]). Samples assessed were BAL fluid (BALF) samples and Nasopharyngeal swab (NPS) samples. Unique isolate definition: 2 isolates of S.p., H.i. and M.c. were selected per specimen type per subjects. For analyses, the 2 isolates were compared to determine if they were clones vs. different ("unique") pathogen. Isolates were considered "unique" based on the comparison of serotype and antibiotic susceptibility (AS) profile for S.p. and H.i. and on the AS profile alone for M.c.. If the 2 isolates had different serotypes, or the same serotype but a different AS profile, then the 2 isolates were considered "unique", and both isolates were retained in the analyses. Note: For one subject who underwent BAL procedure, no BAL fluid was available for study analyses.
Mean Weight of Subjects	From Day 0 to Year 2	Demographic characteristics included weight which was expressed in kilograms (kg).
Mean Height of Subjects	From Day 0 to Year 2	Demographic characteristics included height which was expressed in centimeters (cm).
Number of Subjects With Haemophilus Influenzae Type b Vaccination History Characteristics	From Day 0 to Year 2	Haemophilus influenzae type b vaccination history included vaccination, Haemophilus influenzae type b vaccine doses (1-4), medical history source validated or not.