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Background: Studies have shown that abnormal temperature at night is a risk factor for respiratory health. However, there is limited evidence on the impact of hot and cold nights on cause-specific diseases such as pneumonia, which is a leading cause of morbidity and mortality in children. Methods: We collected daily data on pneumonia hospitalisations in children under five years from 2011 to 2017 in three low-, middle- and high-income countries (Bangladesh, China, and Australia). The intensity of hot and cold nights was measured by excess temperature. A space–time-stratified case-crossover analysis was used to estimate the association between hot and cold nights and childhood pneumonia hospitalisations. We further estimated the fraction of childhood pneumonia hospitalisations attributable to hot and cold nights. Results: Both hot and cold nights were associated with an increased risk of hospitalisations for childhood pneumonia in low-, middle-, and high-income countries, with a greater disease burden from hot nights. Specifically, the fraction of childhood pneumonia attributable to hot nights was the largest in Australia [21.2%, 95% confidence interval (CI): 11.8%-28.1%], followed by Bangladesh (15.2%, 95% CI: 4.1%–23.8%) and China (2.7%, 95% CI: 0.4%-4.7%). Additionally, the fraction of childhood pneumonia attributable to cold nights was 1.3% (95% CI: 0.4%-2.0%) in Bangladesh and 0.4% (95% CI: 0.1%-0.7%) in China. Conclusion: This multi-country study suggests that hot and cold nights are not only associated with a higher risk of pneumonia hospitalisations in children but also responsible for substantial fraction of hospitalisations, with a greater impact from hot nights.

Background: Pneumonia is a top serious problem for under-five children. Although pneumonia affects children worldwide, the disease's risk and consequences are more widespread in low- and middle-income countries. Objectives: This study aimed to identify predictors of childhood pneumonia among children who visited public Hospitals located in West Shoa Zone, Oromia, Ethiopia. Methods: A case–control study was conducted among 375 (125 cases and 250 controls) to identify predictors of childhood pneumonia among children who visited in nine public health Hospitals from May to July 2022. Binary logistic regression was used to analyze the data. Variables with a p-value less than 0.05 in a multivariable logistic regression were declared statistically significant. Results: Among respondents 42.1% were males and 57.9% were females. Factors such as using water without soap for hand washing before child feeding [AOR: 3.09, 95% CI: 1.59–6.00] and house near the street [AOR: 2.87, 95% CI: 1.54–5.37] were found to be the determinant of under-five pneumonia. Similarly, animal dung as a source of fuel [AOR: 2.26, 95% CI: 1.06–4.79], Child care given by the house worker or home maid [AOR: 3.35, 95% CI: 1.59–7.05], and having acute respiratory tract infection in the last two weeks [AOR: 6.46, 95% CI: 3.32–12.56] were significantly associated with under-five pneumonia. Conclusions: Hand washing with soap before child feeding, cooking with animal manure, and a history of acute respiratory tract infection in the previous two weeks were found as risk factors for childhood pneumonia.

Objectives: The relative scarcity of paediatric COVID-19 disease infers protection from its direct harms. We aim to highlight the potentially severe indirect effects of COVID-19 upon global childhood pneumonia. Study design: This is a discussion piece written from the authors’ perspective. Methods: We use the social determinants of health to describe the indirect impact of COVID-19 upon global childhood pneumonia. Results: The social determinants of health are a range of social, economic, and environmental factors used to explore and explain global health differences and inequalities. Global childhood pneumonia is a significant public health problem with clear linkage to the social determinants of health. COVID-19 is a significant threat to the health and wellbeing of children around the world through its potentially severe effects on all strata of the social determinants of health. Conclusions: The COVID-19 pandemic could undermine years of progress in reducing both global childhood pneumonia incidence and mortality, and most significantly affect vulnerable children living in poverty.

Background: Low blood oxygen saturation (SpO2), or hypoxaemia, is an indicator of severe illness in children. Pulse oximetry is a globally accepted, non-invasive method to identify hypoxaemia, but rarely available outside higher-level facilities in resource-constrained countries. This study aims to evaluate the performance of different types of pulse oximeters amongst frontline health workers in Cambodia, Ethiopia, South Sudan, and Uganda. Methods: Five pulse oximeters (POx) which passed laboratory testing, out of an initial 32 potential pulse oximeters, were evaluated by frontline health workers for performance, defined as agreement between the SpO2 measurements of the test device and the reference standard. The study protocol is registered with the Australia New Zealand Clinical Trials Registry (Ref: ACTRrn12615000348550). Findings: Two finger-tip pulse oximeters (Contec and Devon), two handheld pulse oximeters (Lifebox and Utech), and one phone pulse oximeter (Masimo) passed the laboratory testing. They were evaluated for performance on 1,313 children under five years old by 207 frontline health workers between February and May 2015. Phone and handheld pulse oximeters had greater overall agreement with the reference standard (56%; 95% CI 0.52 - 0.60 to 68%; 95% CI 0.65 - 0.71) than the finger-tip POx (31%; 95% CI 0.26 to 0.36 and 47%; 95% CI 0.42 to 0.52). Fingertip POx performance was substantially lower in the 0–2 month olds; having just 17% and 25% agreement. The finger-tip devices more often underreported SpO2 readings (mean difference -7.9%; 95%CI -8.6,-7.2 and -3.9%; 95%CI -4.4,-3.4), and therefore over diagnosed hypoxaemia in the children assessed. Interpretation: While the Masimo phone pulse oximeter performed best, all handheld POx with age-specific probes performed well in the hands of frontline health workers, further highlighting their suitability as a screening tool of severe illness. The poor performance of the fingertip POx suggests they should not be used in children under five by frontline health workers. It is essential that POx are performance tested on children in routine settings (in vivo), not only in laboratories or controlled settings (in vitro), before being introduced at scale. Funding: Bill & Melinda Gates Foundation [OPP1054367].

Background: Increasing evidence has linked childhood pneumonia with early exposure to ambient air pollution. However, the impact of exposure to air pollutants before birth is unclear. Objective: To further clarify whether exposure to a particular pollutant during preconceptional and prenatal periods, may pose a higher risk of developing childhood pneumonia. Methods: This case-control cohort study consisted of 1510 children aged 0–14 years in Changsha, China between 2017 and 2019. Data of children's history of pneumonia and blood biomarkers were obtained from the XiangYa Hospital records. Each child's exposure to air pollutants, including nitrogen dioxide (NO2), sulfur dioxide (SO2), and particulate matter with an aerodynamic diameter ≤ 10 µm (PM10), was calculated using data from ten air pollution monitoring stations. A multivariate logistic regression model was used to quantify the relationship between childhood pneumonia and exposure to ambient air pollution during the preconceptional and prenatal periods. Results: Childhood pneumonia was significantly associated with preconceptional and prenatal exposure to the industrial-related air pollutant, SO2, for 1 year before conception, for 3 months before conception and for the entire pregnancy, with ORs(95% CI)= 4.01(3.17–5.07), 4.06(3.29–5.00) and 6.51(4.82–8.79). Also, children who were sick with pneumonia had higher white blood cell and neutrophil counts, and children with low eosinophil count or hemoglobin are likely to get pneumonia. Sensitivity analysis showed that boys, and children in high temperature area were susceptible to the effect of both preconceptional and prenatal exposure to industrial SO2. Conclusion: Preconceptional and prenatal exposure to industrial-related air pollution plays a significant role in the incidence and progression of childhood pneumonia, supporting the hypothesis of “(pre-)fetal origin of childhood pneumonia”.

The long-term effects of ambient PM2.5 and chemical constituents on childhood pneumonia were still unknown. A cross-sectional study was conducted in 30,315 children in the China Children, Homes, Health (CCHH) project, involving 205 preschools in six cities in China, to investigate the long-term effects of PM2.5 constituents on lifetime-ever diagnosed pneumonia. Information on the lifetime-ever pneumonia and demographics were collected by validated questionnaires. The lifetime annual average ambient PM2.5, ozone and five main PM2.5 constituents, including SO42−, NO3−, NH4+, organic matter (OM) and black carbon (BC), were estimated according to preschool addresses by a combination of satellite remote sensing, chemical transport modeling and ground-based monitors. The prevalence of lifetime-ever diagnosed pneumonia was 34.5% across six cities and differed significantly among cities (p = 0.004). The two-level logistic regression models showed that the adjusted odds ratio for PM2.5 (per 10 µg/m3) and its constituents (per 1 µg/m3)-SO42−, NO3−, NH4+, and OM were 1.12 (95% CI:1.07–1.18), 1.02 (1.00–1.04), 1.06 (1.04–1.09), 1.05 (1.03–1.07) and 1.09 (1.06–1.12), respectively. Children in urban area, aged

Objectives: This study aimed to investigate the disparities in pneumonia-specific under-five mortality rates (U5MRs) among and within three geographic regions in Mainland China from 1996 to 2015. Methods: Data were obtained from the national Under-Five Child Mortality Surveillance System and grouped into 2-year periods. The Cochran–Armitage trend test and Cochran–Mantel–Haenszel test were used to assess trends and differences in the pneumonia-specific U5MRs among and within geographic regions. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated. Results: The pneumonia-specific U5MR decreased by 90.6%, 89.0%, and 83.5% in East, Middle, and West China, respectively, with a larger decrease in rural areas. The pneumonia-specific U5MR was highest in West China, and was 7.2 (95% CI 5.9–8.7) times higher than that in East China in 2014–2015. In 2014–2015, the RRs were 1.7 (95% CI 1.2–2.5), 1.6 (95% CI 1.1–2.1), and 3.4 (95% CI 2.8–4.0) between rural and urban areas in East, Middle, and West China, respectively. Conclusions: Pneumonia-specific U5MRs decreased from 1996 to 2015 across China, particularly in rural areas. However, disparities remained among and within geographic regions. Additional strategies and interventions should be introduced in West China, especially the rural areas, to further reduce the pneumonia-specific U5MR.

Background: Despite mounting evidence linked pneumonia with air pollution, it is unclear what main pollutant(s) exposure in which critical window(s) play a key role in pneumonia., Objective: To examine effects of intrauterine and post-natal exposure to air pollution on children's doctor-diagnosed pneumonia (DDP)., Methods: A combination of cross-sectional and retrospective cohort study was conducted at Changsha, China during 2019-2020. Personal exposure to outdoor air pollutants at each child's home address was estimated using inverse distance weighted (IDW) method based on data from 10 air quality monitoring stations. Associations between personal air pollution exposure and DDP were evaluated., Results: Children's DDP was associated with intrauterine and post-natal exposure to PM 2.5 , PM 2.5-10 , and PM 10 , adjusted ORs (95% CI) of 1.17 (1.04-1.30), 1.09 (1.01-1.17), and 1.07 (1.00-1.14) for IQR increase in intrauterine exposure and 1.12 (1.02-1.22), 1.13 (1.06-1.21), and 1.28 (1.16-1.41) for post-natal exposure. Intrauterine PM 2.5 exposure and post-natal PM 10 exposure were associated with a higher risk of pneumonia. We identified the 2nd trimester, 3rd trimester, and first year as critical windows respectively for PM 2.5 , PM 2.5-10 , and PM 10 exposure. Daytime exposure to traffic-related air pollution especially during early life increased DDP., Conclusion: Intrauterine and post-natal exposure to particulate matters played a dominant role in children's DDP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Increasing evidence have associated pneumonia with early exposure to ambient air pollution. However, the role of indoor environmental factors exposure in early life on childhood pneumonia remains unclear., Objective: To examine the association between indoor environmental factors exposure during different timing windows and childhood pneumonia, and to identify the key indoor factor(s) in different critical window(s)., Methods: A retrospective cohort study of 8689 pre-schoolers was performed in Changsha, China during 2019-2020. Our questionnaire survey was designed to collect information on pre-schooler's outcome and residential environmental exposure containing indoor pollution and allergens during 1 year before pregnancy, pregnancy, first year, and past year. The associations were further estimated stratified by personal exposure level of outdoor NO 2 , CO, temperature (T) and different covariates. Associations were assessed by multiple logistic regression model in terms of odds ratio (OR) of 95% confidence interval (CI)., Results: Pre-schooler's pneumonia was significantly related with exposure of new furniture, redecoration, mold/damp stains, and mold or damp clothing or bedding exposure during the four periods, with the strongest associations observed during 1 year before pregnancy based on multi-window model, with ORs (95% CI) of 1.27 (1.12-1.44), 1.26 (1.09-1.46), 1.34 (1.14-1.57), and 1.28 (1.05-1.56) respectively. Environmental tobacco smoke (ETS) including both parental and grandparental smoking were significantly related with increased risk of pre-schooler's pneumonia, and ETS played a more important role in early life, with ORs (95% CI) of 1.17 (1.01-1.36) and 1.19 (1.02-1.39) in pregnancy and first year. Indoor plants particularly nonflowering plants significantly elevated pneumonia risk but only in past year, with ORs (95% CI) of 1.17 (1.05-1.30) and 1.14 (1.03-1.26). Higher pneumonia risk was observed for renovation exposure in pre-birth compared to post-birth, while mold/dampness exerted an accumulative effect with the highest risk for exposure during both pre- and post-birth. Living near traffic road and exposure to high level of traffic-related air pollution and high temperature significantly increased pneumonia risk. Sensitivity analysis found that some sub-groups were more susceptible to pneumonia risk of home environment exposure., Conclusion: Early life exposure to indoor environmental factors plays an important role in pneumonia development, supporting the hypothesis of "Preconceptional and Fetal Origin of Childhood Pneumonia" and "Developmental Origins of Health and Pneumonia"., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The imbalance of helper T (Th) 17 and regulatory T (Treg) cells plays an important role in the pathogenesis of pneumonia. This study aims to investigate the role and mechanism of long non-coding RNA growth arrest-specific 5 (GAS5) in the differentiation of Th17 cells and Tregs in childhood pneumonia. Expression of GAS5, miR-217, signal transducer and activator of transcription-5 (STAT5), receptor-related orphan receptor γt (RORγt), and transcription factor Forkhead box P3 (Foxp3) were examined by qRT-PCR and western blot. The percentage of Th17 cells and Tregs in CD4 + T cells were measured by flow cytometry. The interaction between miR-217 and GAS5 or STAT5 was analyzed by luciferase reporter assay. Downregulated GAS5 expression and Treg cell percentage, and upregulated Th17 cell percentage were observed in pneumonia patients when compared with the healthy controls. Furthermore, GAS5 overexpression corrected the imbalanced Th17/Treg in peripheral blood CD4 + T cells derived from pneumonia patients, and this effect was reversed by miR-217 mimic and STAT5 silencing. Mechanistically, GAS5 acted as a sponge of miR-217 to reduce binding of miR-217 to its target STAT5, leading to upregulation of STAT5 expression. Taken together, GAS5 corrects the Treg/Th17 imbalance by targeting the miR-217/STAT5 axis in childhood pneumonia., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Pneumonia is a significant contributor to mortality and morbidity in children aged <5 years, and it is also one of the leading causes of hospitalisation for children in this age group. This study assessed the association between climate variability, patient characteristics (i.e. age, sex, weight, parental education, socio-economic status) and length of stay (LOS) in hospital for childhood pneumonia and its economic impact on rural Bangladesh., Study Design: An ecological study design was used., Methods: Data on daily hospitalisation for pneumonia in children aged <5 years (including patient characteristics) and daily climate data (temperature and relative humidity) between 1st January 2012 and 31st December 2016 were obtained from the Matlab Hospital (the International Centre for Diarrhoeal Disease Research, Bangladesh) and the Bangladesh Meteorological Department, respectively. A generalised linear model with Poisson link was used to quantify the association between climate factors, patient characteristics and LOS in hospital., Results: The study showed that average temperature, temperature variation and humidity variation were positively associated with the LOS in hospital for pneumonia. A 1°C rise in average temperature and temperature variation during hospital stay increased the LOS in hospital by 1% (relative risk [RR]: 1.010, 95% confidence interval [CI]: 1.001-1.018) and 9.3% (RR: 1.093, 95% CI: 1.051-1.138), respectively. A 1% increase in humidity variation increased the LOS in hospital for pneumonia by 2.2% (RR: 1.022, 95% CI: 1.004-1.039). In terms of economic impact, for every 1° C temperature variation during the period of hospital stay, there is an addition of 0.81 USD/day/patient as a result of direct costs and 1.8 USD/day/patient for total costs. Annually, this results in an additional 443 USD for direct and 985 USD for total costs., Conclusions: Climate variation appears to significantly contribute to the LOS in hospital for childhood pneumonia. These findings may help policymakers to develop effective disease management and prevention strategies., (Copyright © 2020 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Previous investigations in adult smokers from the COPDGene Study have shown that early-life respiratory disease is associated with reduced lung function, COPD, and airway thickening. Using 5-year follow-up data, we assessed disease progression in subjects who had experienced early-life respiratory disease. We hypothesized that there are alternative pathways to reaching reduced FEV 1 and that subjects who had childhood pneumonia, childhood asthma, or asthma-COPD overlap (ACO) would have less lung function decline than subjects without these conditions., Methods: Subjects returning for 5-year follow-up were assessed. Childhood pneumonia was defined by self-reported pneumonia at < 16 years. Childhood asthma was defined as self-reported asthma diagnosed by a health professional at < 16 years. ACO was defined as subjects with COPD who self-reported asthma diagnosed by a health-professional at ≤ 40 years. Smokers with and those without these early-life respiratory diseases were compared on measures of disease progression., Results: Follow-up data from 4,915 subjects were examined, including 407 subjects who had childhood pneumonia, 323 subjects who had childhood asthma, and 242 subjects with ACO. History of childhood asthma or ACO was associated with an increased exacerbation frequency (childhood asthma, P < .001; ACO, P = .006) and odds of severe exacerbations (childhood asthma, OR, 1.41; ACO, OR, 1.42). History of childhood pneumonia was associated with increased exacerbations in subjects with COPD (absolute difference [β], 0.17; P = .04). None of these early-life respiratory diseases were associated with an increased rate of lung function decline or progression on CT scans., Conclusions: Subjects who had early-life asthma are at increased risk of developing COPD and of having more active disease with more frequent and severe respiratory exacerbations without an increased rate of lung function decline over a 5-year period., Trial Registry: ClinicalTrials.gov; No. NCT00608764; https://clinicaltrials.gov., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)