Figures
- FIGURE 1
a) Flow of children with chest-indrawing pneumonia by country: Mozambique (M) and Pakistan (P). b) Flow of children with no fast breathing, no chest indrawing and no fever by country. #: 70 children in Mozambique (27.3% of screened) and 1318 children in Pakistan (81.8% of screened) met the “no chest indrawing” exclusion criterion.
- FIGURE 2
Lung ultrasound examinations consisted of longitudinal and oblique scans obtained of the anterior, lateral and posterior sides of the child's chest.
Tables
- TABLE 1
Study definitions and eligibility criteria
Definitions Fast breathing for age Children 2 to <12 months of age: RR ≥50 breaths per min
Children ≥12 months of age: RR ≥40 breaths per minSevere respiratory distress Grunting, nasal flaring and/or head nodding WHO IMCI general danger signs Lethargy or unconsciousness, convulsions, vomiting everything, inability to drink or breastfeed Eligibility criteria Inclusion criteria Chest-indrawing pneumonia cohort
2 to 23 months of age
Cough <14 days or difficulty breathing
Visible indrawing of the chest wall with or without fast breathing for age
Ability and willingness of child's caregiver to provide informed consent and to be available for follow-up for the planned duration of the study, including accepting a home visit if he/she fails to return for a scheduled study follow-up visit
No pneumonia cohort
2 to 23 months of age
Cough <14 days or difficulty breathing
Ability and willingness of child's caregiver to provide informed consent and to be available for follow-up for the planned duration of the study, including accepting a home visit if he/she fails to return for a scheduled study follow-up visitExclusion criteria Chest-indrawing pneumonia cohort
Resolution of chest indrawing after bronchodilator challenge if wheezing at screening examination
Severe respiratory distress
Arterial SpO2 <90% in room air, as assessed noninvasively by a pulse oximeter
WHO IMCI general danger signs
Stridor when calm
Known or possible tuberculosis (history of a cough ≥14 days)
Any medical or psychosocial condition or circumstance that, in the opinion of the investigators, would interfere with the conduct of the study or for which study participation might jeopardise the child's health
Living outside the study catchment area
No pneumonia cohort
Axillary temperature ≥38°C
Fast breathing for age
Visible indrawing of the chest wall
SpO2 <95% in room air, as assessed noninvasively by a pulse oximeter
WHO IMCI general danger signs
Stridor when calm
Known or possible tuberculosis (history of a cough ≥14 days)
Any medical or psychosocial condition or circumstance that, in the opinion of the investigators, would interfere with the conduct of the study or for which study participation might jeopardise the child's health
Living outside the study catchment areaRR: respiratory rate; WHO: World Health Organization; IMCI: Integrated Management of Childhood Illnesses; SpO2: oxyhaemoglobin saturation.
- TABLE 2
Baseline characteristics of enrolled and analysed children by cohort and country
Chest-indrawing pneumonia cohort No pneumonia cohort Between-cohort comparison p-value Mozambique Pakistan Between-country comparison p-value Mozambique Pakistan Between-country comparison p-value Mozambique Pakistan Subjects n 98 128 20 20 Age months 10.9±6.0 6.8±4.8 <0.01 11.0±6.1 7.6±4.8 0.06 0.91 0.45 <12 months 55 (56.1%) 111 (86.7%) <0.01 12 (60.0%) 15 (75.0%) 0.50 0.94 0.18 Female 39 (39.8%) 34 (26.6%) 0.049 14 (70.0%) 12 (60.0%) 0.74 0.03 <0.01 Temperature °C 37.1±1.1 36.7±0.8 <0.01 36.3±0.6 36.3±0.6 0.72 <0.01 0.02 Fever (≥38°C) n (%) 21 (21.4%) 11 (8.6%) 0.01 0 (0.0%) 0 (0.0%) 0.02 0.36 Respiratory rate breaths per min <12 months 52.5±11.4 53.5±7.9 0.58 39.7±7.1 38.8±4.8 0.72 <0.01 <0.01 ≥12 months 44.3±10.0 47.6±9.6 0.23 34.4±4.2 32.2±4.5 0.41 <0.01 <0.01 Fast breathing 52 (53.1%) 83 (64.8%) 0.10 0 (0.0%) 0 (0.0%) <0.01 <0.01 Oxyhaemoglobin saturation % 97.8±2.6 95.3±2.2 <0.01 96.2±1.5 96.8±1.6 0.23 <0.01 <0.01 <90% n (%) 1 (1.0%) 0 (0.0%) 0.43 0 (0.0%) 0 (0.0%) >0.99 Haemoglobin g·dL−1 10.0±1.3 10.7±1.3 <0.01 10.3±1.0 9.4±1.5 0.04 0.37 <0.01 Positive HIV rapid diagnostic test# 0 (0.0%) 0 (0.0%) >0.99 Positive malaria rapid diagnostic test¶ 1 (1.0%) 0 (0.0%) >0.99 C-reactive protein+ µg·mL−1 38.8±49.8 109.9±199.7 <0.01 18.2±33.9 0.03 Procalcitonin§ ng·mL−1 1.7±7.2 0.2±0.6 0.07 Streptococcus pneumoniaeƒ 84 (86.6%) Bordetella pertussis## 3 (3.1%) 0 (0.0%) >0.99 Chlamydophila pneumophila## 0 (0.0%) 0 (0.0%) Legionella pneumophila## 0 (0.0%) 0 (0.0%) Mycoplasma pneumoniae## 3 (3.1%) 0 (0.0%) >0.99 Nasopharyngeal viral PCR¶¶ Number of viruses detected 1.67±1.04 1.08±0.65 <0.01 1.25±0.55 0.01 Any viruses detected 90 (91.8%) 84 (84.0%) 0.14 19 (95.0%) 0.31 1 virus detected 41 (41.8%) 61 (61.0%) 13 (65.0%) 2 viruses detected 30 (30.6%) 22 (22.0%) 6 (30.0%) ≥3 viruses detected 19 (19.4%) 1 (1.0%) 0 (0.0%) Data are presented as mean±sd or n (%), unless otherwise stated. #: HIV testing only conducted in Mozambique; missing for 55 children with chest-indrawing pneumonia. ¶: malaria testing only conducted in Mozambique; missing for two children with chest-indrawing pneumonia. +: C-reactive protein missing for five children with chest-indrawing pneumonia in Mozambique; in Pakistan, only measured for children with chest-indrawing pneumonia. §: procalcitonin only measured in Mozambique; missing for five children with chest-indrawing pneumonia. ƒ: S. pneumoniae carriage only tested for 97 children with chest-indrawing pneumonia in Mozambique. ##: B. pertussis, C. pneumophila, L. pneumophila and M. pneumoniae carriage only tested in Mozambique; all children with B. pertussis were also positive for S. pneumoniae, and two of the three children with M. pneumoniae were also positive for S. pneumoniae; no children were positive for both B. pertussis and M. pneumoniae. ¶¶: viral carriage in Pakistan only tested in 100 analysed children with chest-indrawing pneumonia.
- TABLE 3
Baseline lung ultrasound pattern by nasopharyngeal carriage in the chest-indrawing pneumonia cohort in Mozambique
Chest-indrawing pneumonia cohort in Mozambique Bacteria but no viruses detected Viruses but no bacteria detected Both bacteria and viruses detected Carriage type comparison p-value Subjects n 8 12 77 Any consolidation 4 (50.0%) 1 (8.3%) 10 (13.0%) 0.03 Peripheral 2 (25.0%) 1 (8.3%) 8 (10.4%) Lobar 2 (25.0%) 1 (8.3%) 2 (2.6%) Present in both lungs 1 (12.5%) 1 (8.3%) 2 (2.6%) Any pleural effusion 0 (0.0%) 0 (0.0%) 0 (0.0%) Any interstitial pattern 4 (50.0%) 4 (33.3%) 16 (20.8%) 0.14 Focal 4 (50.0%) 4 (33.3%) 16 (20.8%) Multifocal 1 (12.5%) 0 (0.0%) 0 (0.0%) Present in both lungs 1 (12.5%) 2 (16.7%) 5 (6.5%) Any obstructive atelectasis 0 (0.0%) 0 (0.0%) 0 (0.0%) Data are presented as n (%) unless otherwise stated. Both bacterial and viral carriage assessed in Mozambique. Pakistan did not have bacterial carriage testing conducted.
- TABLE 4
Baseline lung ultrasound imaging patterns of children by cohort and country
Chest-indrawing pneumonia cohort No pneumonia cohort Between-cohort comparison p-value Mozambique Pakistan Between-country comparison p-value Mozambique Pakistan Between-country comparison p-value Mozambique Pakistan Subjects n 98 128 20 20 Any consolidation 15 (15.3%) 57 (44.5%) <0.01 0 (0.0%) 1 (5.0%) >0.99 0.07 <0.01 Peripheral 11 (11.2%) 51 (39.8%) 0 (0.0%) 1 (5.0%) Lobar 5 (5.1%) 18 (14.1%) 0 (0.0%) 0 (0.0%) Present in both lungs 4 (4.1%) 18 (14.1%) 0 (0.0%) 0 (0.0%) Any pleural effusion 0 (0.0%) 2 (1.6%) 0.51 0 (0.0%) 0 (0.0%) >0.99 Simple 0 (0.0%) 2 (1.6%) 0 (0.0%) 0 (0.0%) Complex 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Present in both lungs 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Any interstitial pattern 24 (24.5%) 80 (62.5%) <0.01 2 (10.0%) 6 (30.0%) 0.24 0.24 0.01 Focal 24 (24.5%) 64 (50.0%) 2 (10.0%) 6 (30.0%) Multifocal 1 (1.0%) 28 (21.9%) 0 (0.0%) 1 (5.0%) Present in both lungs 8 (8.2%) 46 (35.9%) 0 (0.0%) 4 (20.0%) Any obstructive atelectasis 0 (0.0%) 3 (2.3%) 0.26 0 (0.0%) 0 (0.0%) >0.99 Present in both lungs 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Data are presented as n (%) unless otherwise stated.
- TABLE 5
Inter rater reliability among lung ultrasound experts
Chest-indrawing
pneumonia cohort# κNo pneumonia cohort¶ κ Overall pneumonia 0.915 1+ Consolidation 0.915 1+ Pleural effusion 1+ Interstitial pattern 0.901 0.635 Obstructive atelectasis 0.746 Testing of κ only signifies that the level of inter rater reliability differs from what would occur by chance (κ=0). Thus, p-values are not noted for κ results. #: n=226. ¶: n=40. +: based on small counts for one of the two possible categories of inter rater reliability, with two or fewer children in the smaller category.
Supplementary Material
Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.
Supplementary material 00518-2020.SUPPLEMENT
