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.

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.

Time frame: From Day 0 up to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling results available.

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

Time frame: From Day 0 up to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling results available.

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.

Time frame: From Day 0 up to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with negative M.catarrhalis BAL Fluid samples results available.

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

Time frame: From Day 0 up to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with positive M.catarrhalis BAL Fluid samples results available.

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.

Time frame: From Day 0 and up to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with nasopharyngeal swab sampling results available for the outcome measure.

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.

Time frame: From Day 0 up to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with nasopharyngeal swab sampling results available for the outcome measure.

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.

Time frame: From Day 0 up to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling results available for the outcome measure.

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.

Time frame: From Day 0 up to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling results available for the outcome measure.

Laboratory results for CRP were expressed in milligrams per litre (mg/L).

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the H. influenzae unique isolates from qualitative positive subjects who were included in the ATP cohort.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the H. influenzae unique isolates from quantitative positive subjects who were included in the ATP cohort.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the M. catarrhalis unique isolates from qualitative positive subjects who were included in the ATP cohort.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the M. catarrhalis unique isolates from quantitative positive subjects who were included in the ATP cohort.

Laboratory results for ESR were expressed in millimeters per hour (mm/hr).

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

Demographic characteristics included age, which was expressed in months.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

General medical history included mean gestational age.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

Demographic characteristics included height which was expressed in centimeters (cm).

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

Demographic characteristics included weight which was expressed in kilograms (kg).

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the H. influenzae or M. catarrhalis unique isolates from quantitative positive subjects who were included in the ATP cohort.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the H. influenzae and M. catarrhalis unique isolates from qualitative positive subjects who were included in the ATP cohort.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the H. influenzae unique isolates from qualitative positive subjects who were included in the ATP cohort.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the H. influenzae unique isolates from quantitative positive subjects who were included in the ATP cohort.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the M. catarrhalis unique isolates from qualitative positive subjects who were included in the ATP cohort.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the M. catarrhalis unique isolates from quantitative positive subjects who were included in the ATP cohort.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable unique isolates of subjects for H. influenzae, who complied with the protocol and with BAL fluid sampling results available.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable unique isolates of subjects for H. influenzae, who complied with the protocol and with nasopharyngeal swab sampling results available.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable unique isolates of subjects for S. pneumoniae, who complied with the protocol and with nasopharyngeal swab sampling results available.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable unique isolates of subjects for S. pneumoniae, who complied with the protocol and with BAL fluid sampling results available.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the S. pneumoniae unique isolates from qualitative positive subjects who were included in the ATP cohort.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the S. pneumoniae unique isolates from quantitative positive subjects who were included in the ATP cohort.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

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.).

Time frame: From Day 0 up to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with nasopharyngeal swab sampling results available.

Demographic characteristics included body mass index (BMI) whose z-scores were measures of relative weight adjusted for child age and sex.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

Clinical characteristics included affections/pre-conditions, affection episodes, number of children living in a household, children in day-care centres, exposure to cigarette smoke.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

Flu vaccination history included vaccination, Flu vaccine doses (1-5), medical history source validated or not.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

Haemophilus influenzae type b vaccination history included vaccination, Haemophilus influenzae type b vaccine doses (1-4), medical history source validated or not.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

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 \[LRTI-ESR\].

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

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.

Time frame: From Day 0 up to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling results available.

Bacterial pathogens were detected by qualitative culture from nasopharyngeal swab samples and included: Staphylococcus aureus and Stenotrophomonas maltophilia

Time frame: From Day 0 and up to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with nasopharyngeal swab sampling results available.

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.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

Radiological results included x-ray, result normality, relationship of abnormality to BAL sampling.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

Demographic characteristics included gender: female and male.

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.

Laboratory results for WBC were expressed in 10\^9 cells per liter (10\^9 cells/L).

Time frame: From Day 0 to Year 2

Population: The analysis was performed on the According to protocol (ATP) cohort, which included all evaluable subjects, who complied with the protocol and with BAL fluid sampling and/ or nasopharyngeal swab sampling results available.