Table 1.
Characteristics of Included Studies
| No. | Study (Author, Year) | Study Type | Country | Criteria for Diagnosis of Severe CAP | Sample Size | Age of Patients | Inclusion Criteria | Exclusion Criteria | Biomarkers Studied |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Agnello et al. (2015) | Cross- sectional | Italy | Extent of chest x-ray infiltration (lobar vs segmental consolidation) and presence of pleural effusion | 119 | 1 to 14 y | Radiographically confirmed diagnosis of CAP | If the patient received antibiotics for >48 h before admission, if they were suffering from a chronic respiratory disease, or if they were hospitalized for >48 h | CRP and PCT |
| 2 | Alcoba et al. (2015) | Secondary analysis from a previous cohort study | Switzerland | CAP with bacteremia (positive blood culture) or empyema (positive pleural culture) | 88 | 0 to 16 y | Age, fever (>38°C), cough, increased respiratory rate or distress, and infiltrates on chest radiographs | Children with immunodeficiency, chronic lung or heart diseases, and hospital-acquired pneumonia | Pro-ADM, CRP, WBC, CoPEP, BC |
| 3 | Alcoba et al. (2017) | Cross-sectional | Switzerland | CAP with bacteremia, pleural effusion, or empyema | 142 | 2 mo to 16 y | Age, fever (>38°C), cough, increased respiratory rate or distress, and infiltrates on chest radiographs | Children with immunodeficiency, chronic lung or heart diseases, and hospital-acquired pneumonia | CRP, PCT |
| 4 | Brito et al. (2016) | Cross-sectional | Brazil | Based on the WHO criteria | 25 | 0 to 18 ya | Patients admitted to 3 hospitals in the municipality of Recife, Northeastern Brazil, from June to December 2012 | History of immunodeficiency, suspicion of TB, chronic conditions, children transferred from other hospitals, and use of antibiotic therapy for >3 d at the time of admission | Cytokines e |
| 5 | Don et al. (2007) | Cross- sectional | Italy | Need for hospital treatment and presence of an alveolar infiltration on chest radiograph | 100 | 1 mo to 18 yb | Signs and/or symptoms compatible with respiratory infection (fever >38°C, tachypnea, cough and/or findings of crackles, bronchial breathing or diminished breath sounds on auscultation) and radiological infiltrations consistent with pneumonia | Infants <1 mo of age, presence of severe and chronic diseases, wheezing, and hospital-acquired pneumonia | PCT |
| 6 | Du et al. (2013) | Cross-sectional | China | Presence of pleural effusion, pneumothorax, pneumatocele, or lung abscess | 165 cases and 100 controls | Preschool children (2 to 6 y) | During the period from January 2010 to January 2012, all preschool children with CAP were initially assessed | Children with genetic diseases (including cystic fibrosis), heart disease with hemodynamic repercussions, pulmonary malformations, and neurological disorders | CRP, CoPEP |
| 7 | Esposito et al. (2016) | Cross-sectional | Italy | Followed the criteria indicated for children by the British Thoracic Society | 110 | 0 to 14 y | Children with clinical signs (tachypnea and abnormal breath sounds) that suggested CAP who required hospitalization | Not reported | LIP-2, WBC, CRP, SYN4 |
| 8 | Esposito et. al (2016) | Cross-sectional | Italy | Followed the criteria indicated for children by the British Thoracic Society | 433 | 4 mo to 14 y | Healthy children consecutively hospitalized for clinical signs suggestive of CAP (tachypnea and abnormal breath sounds) and radiological confirmation of CAP | Patients with underlying chronic disease or an antibiotic treatment of any type in the 48 h before admission | CRP, PCT, WBC, N%, MR-proADM, MR-proANP, sTREM-1 |
| 9 | Haugen et al. (2015) | Cross-sectional (secondary analysis from a previous RCT) | Nepal | WHO-defined severe pneumonia | 430 | 2 to 35 mo | Children with severe or nonsevere pneumonia according to WHO definitions attending the study clinic because of cough and/or difficulty breathing | Lack of consent, not planning to live in the area for the next 6 mo, requiring care for very severe disease, severe malnutrition, presence of congenital heart disease, documented tuberculosis, documentation of any oral antibiotic treatment in the past 48 h, children whose symptoms resolved after receiving 2 doses of salbutamol, cough for >14 d, severe anemia or dysentery | CRP, cytokines, chemokines, and growth factorsf |
| 10 | Haugen et al. (2017) | Cross-sectional (secondary analysis from a previous RCT) | Nepal | WHO-defined severe pneumonia | 430 | 2 to 35 mo | Children with severe or nonsevere pneumonia according to WHO definitions attending the study clinic because of cough and/or difficulty breathing | Lack of consent, not planning to live in the area for the next 6 mo, requiring care for very severe disease, severe malnutrition, presence of congenital heart disease, documented tuberculosis, documentation of any oral antibiotic treatment in the past 48 h, children whose symptoms resolved after receiving 2 doses of salbutamol, cough for >14 d, severe anemia or dysentery | Plasma-25(OH)D |
| 11 | Huang et al. (2014) | Secondary analysis from a previous cohort study | Gambia | Cough or difficulty in breathing plus respiratory distress (lower chest wall indrawing or nasal flaring) | 204 cases and 186 controls | 2–59 mo | Children from the Greater Banjul and Basse areas taking part in a study of childhood pneumonia between June 2007 and June 2010 at 5 health facilities in this area | Not reported | LIP-2, CRP, Hap, vWF |
| 12 | Korkmaz et al. (2018) | Cross-sectional | Turkey | Patients were classified into severity groups according to the respiratory clinical scorec | 66 | 3 to 181 mo | Presence of fever, respiratory symptoms, and at least 1 abnormality on physical examination or chest radiograph according to the WHO definition | Congenital heart disease, neuromuscular disease, immunodeficiency, or any chronic disease (cystic fibrosis, asthma, bronchopulmonary dysplasia, tuberculosis, etc.) | Pro-ADM, IL-1β, CRP, WBC, NC, LC |
| 13 | Ning et al. (2016) | Cross-sectional | China | Defined by the extent of consolidation on chest x-ray and presence of pleural effusion | 174 cases and 33 controls | 3 mo to 12.4 y (cases) 8 mo to 9.8 y (controls) | Presence of signs and symptoms of pneumonia and pulmonary consolidation on chest radiography in a previously healthy child caused by an infection that was acquired outside the hospital | Children who had received antibiotic treatments for >48 h before admission or those suffering from an underlying chronic respiratory disease | N%, NC, WBC, ESR, CRP, PCT, M%, PA |
| 14 | Ramakrishna et al. (2015) | Cross-sectional | Malawi | WHO-defined severe and very severe pneumonia | 233 | 2 mo to 14 y | Children with severe or very severe pneumonia who had serum lactate concentration measured at the time of admission | Children who had clinical features consistent with the WHO criteria for pneumonia but found to have other diagnoses characterized by respiratory distress | Lactate |
| 15 | Saghafian-Hedengren et al. (2017) | Cohort | India | WHO-defined severe pneumonia | 196 | 1 mo to 12 y | Patients with pneumonia based on WHO criteria of tachypnea with cough or difficulty breathing | Children with chronic conditions, illness duration >1 wk, use of antibiotics for >24 h at presentation, previous hospitalization within the preceding 30 d, and children whose symptoms resolved after receiving a single dose of salbutamol | Cytokines, chemokines, and growth factorsg |
| 16 | Sanchez et al. (2012) | Cohort | Spain | Presence of pleural effusion, cavitation, lung abscess or necrosis, air escape, massive atelectasis, or signs of systemic infection (sepsis) | 50 | 1.9 mo to 13.6 y | Patients assessed between January and October 2009 in the ES and hospitalized with CAP as the main diagnosis, with blood work completed on admission | Children with immunocompromising or chronical medical condition, patients with complicated CAP at the time of admission, and those receiving antibiotic treatment for a previous diagnosis of CAP | Pro-ADM, CRP |
| 17 | Wrotek et al. (2014) | Cross-sectional | Poland | Clinical and laboratory indicatorsd | 227 cases and 119 controls | 8 d to 18 y (cases) 7 d to 18 y (controls) | Children who were diagnosed with pneumonia up to 48 hours after hospital admission with radiologic confirmation of CAP and hsCRP levels within the normal range | Previously diagnosed proliferative disease, hsCRP levels above normal, diabetes mellitus and organ insufficiency, medical interventions, musculoskeletal defects, and lack of full information on the CAP course | su-PAR |
Abbreviations: BC, band cell; CAP, community-acquired pneumonia; CoPEP, copeptin; CRP, C-reactive protein; ES, emergency service; ESR, erythrocyte sedimentation rate; Hap, haptoglobin; hsCRP, high sensitive C-reactive protein; IFN, interferon; IL, interleukin; LC, lymphocyte count; LIP-2, lipocallin-2; hsCRP, high sensitive C-reactive protein; MR-proADM, midregional proadenomedullin; MR-proANP, midregional proatrial natriuretic peptide; N%, percentage of neutrophils; NC, neutrophil count; PCT, procalcitonin; Plasma-25(OH)D, plasma 25-hydroxy vitamin D; Pro-ADM, proadenomedullin; RCT, randomized controlled trial; sTREM-1, soluble triggering receptor expressed on myeloid cells-1; su-PAR, soluble urokinase plasminogen activator receptor; SYN4, syndecan-4; vWF, von Willembrand factor; TNF, tumor necrosis factor; WBC, white blood cell count; WHO, World Health Organization.
aThe article does not specify the age group, but as it followed WHO criteria, we assumed this range.
bWhich age cuts were used was not detailed, only that children <1 month were excluded, so we assumed this range.
cThe respiratory clinical score includes 4 clinical parameters: respiratory rate, retractions, dyspnea, and auscultation. Patients were classified into 3 severity groups according to this classification; low (1–3 points), moderate (4–6 points), and high (7–12 points) severity.
dClinical indicators: fever, time to defervescence, heart and breath rate, saturation, and length of antibiotic treatment and hospitalization. Laboratory indicators: CRP, procalcitonin, white blood cell count, and sodium.
eCytokines studied: IL-8, IL-1β, IL- 6, IL-10, TNF, IL-12p70, IL-17A, IL-2, IL-4, IL-5, and IFN-γ.
fCytokines, chemokines, and growth factors studied: IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17A, bFGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1 MIP-1α, MIP-1β, RANTES, TNF-α, PDGF-BB, and VEGF.
gCytokines, chemokines, and growth factors studied: IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-15, IL-17, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, CCL17, CCL22, GM-CSF, and IL-1RA.