Parental knowledge on the respiratory syncytial virus before the nirsevimab immunization program: Attitudes toward immunization in an autonomous community of Spain.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children and associated with most bronchiolitis- and pneumonia-related hospitalizations. A new preventive monoclonal antibody (MAb), nirsevimab, has been launched in the United States, Luxembourg, and France, and was recently approved to be given in a population-based manner throughout Spain. This study aimed to have a first pre-immunization insight into the Spanish parental knowledge about bronchiolitis, RSV, and nirsevimab immunization. Parents in Murcia with children <2 years of age up to the date of September 1, 2023, were selected to complete a questionnaire. The primary endpoint was the parental knowledge about bronchiolitis, RSV, and nirsevimab. A total of 3,217 responses were analyzed. The majority (95.8%) were aware of bronchiolitis. Meanwhile, 46.6% of the respondents knew about RSV, most of them only after the first child's birth. Information about RSV or bronchiolitis was mainly obtained from family members, with only 4.8% reporting having been informed by Health care Professionals (HCPs). Only 11.2% of respondents were aware of nirsevimab. Nonetheless, these were not entirely satisfied with the information received (score of 3.3 out of 5) and shared that HCPs should be the primary source of information. The present survey then highlights the need for better and more efficient educational strategies directed to all parents/legal guardians. It also sheds some light on the different factors that should be considered to improve awareness of RSV immunization to decrease its burden in Spain and beyond.

Lung ultrasound and procalcitonin, improving antibiotic management and avoiding radiation exposure in pediatric critical patients with bacterial pneumonia: a randomized clinical trial.

BACKGROUND: Pneumonia is a major public health problem with an impact on morbidity and mortality. Its management still represents a challenge. The aim was to determine whether a new diagnostic algorithm combining lung ultrasound (LUS) and procalcitonin (PCT) improved pneumonia management regarding antibiotic use, radiation exposure, and associated costs, in critically ill pediatric patients with suspected bacterial pneumonia (BP). METHODS: Randomized, blinded, comparative effectiveness clinical trial. Children < 18y with suspected BP admitted to the PICU from September 2017 to December 2019, were included. PCT was determined at admission. Patients were randomized into the experimental group (EG) and control group (CG) if LUS or chest X-ray (CXR) were done as the first image test, respectively. Patients were classified: 1.LUS/CXR not suggestive of BP and PCT < 1 ng/mL, no antibiotics were recommended; 2.LUS/CXR suggestive of BP, regardless of the PCT value, antibiotics were recommended; 3.LUS/CXR not suggestive of BP and PCT > 1 ng/mL, antibiotics were recommended. RESULTS: 194 children were enrolled, 113 (58.2%) females, median age of 134 (IQR 39-554) days. 96 randomized into EG and 98 into CG. 1. In 75/194 patients the image test was not suggestive of BP with PCT < 1 ng/ml; 29/52 in the EG and 11/23 in the CG did not receive antibiotics. 2. In 101 patients, the image was suggestive of BP; 34/34 in the EG and 57/67 in the CG received antibiotics. Statistically significant differences between groups were observed when PCT resulted < 1 ng/ml (p = 0.01). 3. In 18 patients the image test was not suggestive of BP but PCT resulted > 1 ng/ml, all of them received antibiotics. A total of 0.035 mSv radiation/patient was eluded. A reduction of 77% CXR/patient was observed. LUS did not significantly increase costs. CONCLUSIONS: Combination of LUS and PCT showed no risk of mistreating BP, avoided radiation and did not increase costs. The algorithm could be a reliable tool for improving pneumonia management. CLINICAL TRIAL REGISTRATION: NCT04217980.

Effects of intrauterine and post-natal exposure to air pollution on children's pneumonia: Key roles in different particulate matters exposure during critical time windows.

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 PM2.5, PM2.5-10, and PM10, 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 PM2.5 exposure and post-natal PM10 exposure were associated with a higher risk of pneumonia. We identified the 2nd trimester, 3rd trimester, and first year as critical windows respectively for PM2.5, PM2.5-10, and PM10 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.

Childhood Pneumonia: What's Unchanged, and What's New?

Childhood pneumonia is still a significant clinical and public health problem. India contributes the highest number of deaths due to pneumonia, accounts for about 20% of global mortality among under five children. Various etiologic agents including bacteria, viruses and atypical organism are responsible for childhood pneumonia. Recent studies suggest that viruses are one of the major causes of childhood pneumonia. Among viruses, respiratory syncytial virus has got great attention and several recent studies are reporting it as an important organism for pneumonia. Lack of exclusive breast feeding during first six months, improper timing of start and content of complimentary feeding, anemia, undernutrition, indoor pollution due to tobacco smoking and use of coal and wood for cooking food and lack of vaccinations are important risk factors. X-ray chest is not routinely performed to diagnose pneumonia while use of lung ultrasound is increasing to detect consolidation, pleural effusion, pneumothorax and pulmonary edema (interstitial syndrome). Role of C-reactive protein (CRP) and procalcitonin is similar, to differentiate between viral and bacterial pneumonia, however duration of antibiotics is better guided by procalcitonin. Newer biomarkers like IL-6, presepsin and triggering receptor expressed on myeloid cells 1 are needed to be evaluated for their use in children. Hypoxia is significantly associated with childhood pneumonia. Therefore, use of pulse oximetry should be encouraged for early detection and prompt treatment of hypoxia to prevent adverse outcomes. Among the available tools for risk of mortality assessment in children due to pneumonia, PREPARE score is the best but external validation will be needed.

Poor accuracy of single serological IgM tests in children with suspected acute Mycoplasma pneumoniae infection in Guangzhou, China.

Introduction. Early and accurate diagnosis of Mycoplasma pneumoniae (MP) infection of children with pneumonia is at the core of treatment in clinical practice.Gap Statement. Serological immunoglobulin M (IgM) tests for MP infection of children in south China have been rarely described.Aim. To assess the diagnostic performance and clinical application of serodiagnosis of MP infection in paediatric pneumonia patients.Methodology. Serum samples from 144 children diagnosed with MP pneumonia were subjected to a particle agglutination (PA)-based IgM assay. Meanwhile, we used an established suspension array as the reference standard method for the detection of MP DNA in bronchoalveolar lavage fluid (BALF) from all patients to assess the reliability of serological assays.Results. When running immunological testing in single serum samples, 80.6 %(79/98) of cases were diagnosed with MP infection, whereas only 55 (56.1 %) cases were positive in MP DNA analysis. Furthermore, single serum tests for IgM during acute MP infection resulted in 85.5 % (47/55) sensitivity and 25.6 % (11/43) specificity. Nevertheless, immunological testing and MP DNA analysis yielded the same results when paired sera were available for MP IgM antibody testing.Conclusion. Paired serological IgM assays are necessary for the determination of an acute MP infection, whereas single serological IgM testing is unreliable. Moreover, even a short interval of two MP serological tests works well.

Factors associated with childhood pneumonia and care seeking practices in Nepal: further analysis of 2019 Nepal Multiple Indicator Cluster Survey.

BACKGROUND: Acute Respiratory Infection (ARI) is still a major public health problem in Nepal. The prevalence of ARI among under five children was 2.1% in 2019 and many children from marginalized families suffer disproportionately and many of them die without proper care and treatment. The objective of this study was to identify factors associated with childhood pneumonia and care-seeking practices in Nepal. METHODS: This was a secondary analysis of the Nepal Multiple Indicator Cluster Survey (MICS) 2019, which uses multi-stage Probability Proportional to Size sampling. Data from 6658 children were analyzed using SPSS 22. Chi-square test and logistic regression analysis were conducted with odds ratio and its corresponding 95% confidence interval after adjusting for confounders. RESULTS: Children aged 0 to 23 months had1.5 times higher odds of pneumonia compared to the age group 24 to 59 months (AOR = 1.5, CI 1.0-2.3) and children from rural area had 1.9 times the odds of having pneumonia than urban children (AOR = 1.9, CI 1.2-3.2). Underweight children had 2.3 times greater odds of having pneumonia than normal weight children (AOR = 2.3, CI 1.4-3.9). The odds of having pneumonia were 2.5 higher among children of current smoking mothers compared those with non-smoking mothers (AOR = 2.5, CI 1.1-5.7). Similarly, children from disadvantaged families had 0.6 times protective odds of pneumonia than children from non-disadvantaged families (AOR = 0.6, CI 0.4-1.0). Only one quarter of children received treatment from public facilities. Of those who received treatment, nearly half of the children received inappropriate treatment for pneumonia. One in ten children with pneumonia did not receive any kind of treatment at all. CONCLUSIONS: Pneumonia is still a public health problem in low-income countries. Public health program and treatment services should be targeted to younger children, careful attention should be given to underweight children, and awareness and nutrition related activities should be focused on rural areas. Addressing inequity in access to and utilization of treatment of childhood illnesses should be prioritized.

Pneumonia hospitalizations and mortality in children 3 - 24-month-old in Nigeria from 2013 to 2020: Impact of pneumococcal conjugate vaccine ten valent (PHiD-CV-10).

Pneumococcal conjugate vaccine ten valent (PCV 10) was introduced into Nigeria in three phases. Phase 3 introduction started in August 2016. However, its impact on pneumonia admissions and mortality among vaccinated Nigerian children has not been determined. Data in the period before PCV-10 introduction (3 August 2013-2 August 2016), and after (3 August 2017-2 August 2020) were retrospectively extracted from the medical charts of eligible patients aged 3-24 months with hospitalized radiological pneumonia at the University College Hospital (UCH), Ibadan; National Hospital (NH), Abuja; and Federal Teaching Hospital (FTH), Gombe, allowing for an intervening period of 1 year. Proportions of the patients with hospitalized pneumonia and case fatality rates were determined during both periods. The results were compared using z-test, multiple logistic regression analysis and p < .05 was considered significant. Adjusted pneumonia hospitalization rates between the two periods increased at the NH Abuja (10.7% vs 14.6%); decreased at the UCH, Ibadan (8.7% vs 6.9%); and decreased at the FTH, Gombe (28.5% vs 18.9%). Case fatality rates decreased across all the sites during the post-PCV introduction period: NH Abuja, from 6.6% to 4.4% (p = .106); FTH, Gombe, 11.7% to 7.7% (p = .477); and UCH, Ibadan, 2.0% to 0% (p = .045); but only significant at Ibadan. Overall, proportion of hospitalized pneumonia cases decreased after 3 years of PCV 10 introduction into the National Immunization Programme in Nigeria. The case fatality rate during post-PCV 10 introduction decreased at all the three sites, but this difference was significant at the UCH, Ibadan.

Pneumonia is the commonest killer of Nigerian children aged less than 5 years. Pneumonia vaccine (PCV 10) was introduced into Nigeria Vaccination Program between 2014 and 2016, but up till now the value has not been confirmed. We conducted a retrospective study in which data before and after PCV 10 introduction were compared. The study sites were the University College Hospital (UCH), Ibadan; National Hospital (NH), Abuja; and Federal Teaching Hospital (FTH), Gombe. The data were extracted from the medical charts of eligible patients aged 3­24 months who were admitted for severe pneumonia with evidences on lung radiographs. We found that the proportion of hospitalized pneumonia cases decreased after 3 years of PCV 10 introduction into the National Immunization Program in Nigeria. The death rate during post-PCV 10 introduction decreased at all the three sites, but was only significantly decreased at the UCH, Ibadan.

Health System Considerations for Community-Based Implementation of Automated Respiratory Counters to Identify Childhood Pneumonia in 5 Regions of Ethiopia: A Qualitative Study.

BACKGROUND: In Ethiopia, childhood pneumonia is diagnosed in primary healthcare settings by measuring respiratory rate (RR) along with the presence of cough, chest indrawing, difficulty breathing, and fast breathing. Our aim was to identify health system-level lessons from implementing two automated RR counters, Children's Automated Respiration Monitor (ChARM) by Phillips® and Rad-G by Masimo®, to provide considerations for integrating such devices into child health programmes and health systems. This study was part of an initiative called the Acute Respiratory Infection Diagnostic Aids (ARIDA). METHODS: Key informant interviews (KIIs) were conducted with 57 participants (health workers in communities and facilities, trainers of health workers, district management, and key decision-makers) in five regions of Ethiopia. Data were analyzed in ATLAS.ti using thematic content analysis and themes were categorized using the Tanahashi bottleneck analysis. RESULTS: All participants recommended scaling up the ARIDA initiative nationally as part of Integrated Management of Newborn and Childhood Illness (IMNCI) in primary healthcare. Health workers perceived the devices as: time saving, acceptable by parents and children, and facilitating diagnosis and referrals. Health workers perceived an increased demand for services and reduced numbers of sick children not seeking care. Participants recommended increasing the number of devices distributed and health workers trained. Strengthening drug supply chains, improving oxygen gas availability, and strengthening referral networks would maximize perceived benefits. While training improved knowledge, more supportive supervision, integration with current guidelines and more guidance related to community engagement was recommended. CONCLUSION: Automatic RR counters for the decentralized diagnosis of childhood pneumonia could have positive impact on improving the quality of diagnosis and management of pneumonia in children. However, the study has shown that a health system approach is required to ensure all steps along the pneumonia pathway are adequate, including drug and oxygen supply, community engagement, health worker training and support, and referral pathways.

Risk factors for childhood pneumonia at Adama Hospital Medical College, Adama, Ethiopia: a case-control study.

BACKGROUND: Pneumonia is an acute respiratory infection of the lungs. A child dies of pneumonia every 39 s globally. Even though pneumonia affects children worldwide, the risk and repercussions of the disease are more prevalent in poor and middle-income nations. Despite the initiatives by the Ethiopian government, there are still numerous instances and deaths caused by childhood pneumonia. Therefore, this study aimed to identify the risk factors for pneumonia among 2-59 months-old children visiting Adama Hospital Medical College, Adama, Ethiopia. METHODS: An institution-based unmatched case-control study was conducted among 124 cases and 124 controls from January 1, 2021, to March 15, 2021. Cases were selected using a consecutive sampling technique. For each case, the next patient from the same pediatric outpatient room who met the inclusion criteria was taken as a control. Data were collected using a pretested, structured interviewer-administered questionnaire containing sociodemographic, environmental, and nutritional factors, comorbid illnesses, and related care practices. A multiple logistic regression model was fitted. RESULTS: Family size of ≥ 5 compared to < 5 (Adjusted odds ratio (AOR): 3.08, 95% CI: 1.23, 7.71), household monthly income of < 2500 compared to > 5000 birr (AOR: 3.94, 95% CI: 1.06, 14.6), use of charcoal as the main fuel for cooking (AOR: 7.03, 95% CI: 2.38, 20.78), and wood or dung as the main fuel for cooking compared to electricity (AOR: 6.58, 95% CI: 2.07, 20.9), malnutrition compared to no malnutrition (AOR: 4.77, 95% CI: 1.89, 12.06), diarrhea compared to no diarrhea in the past 2 weeks (AOR: 3.3, 95% CI: 1.52, 7.14) and upper respiratory tract infection (URTI) compared to no infection in the past 2 weeks (AOR: 3.29, 95% CI: 1.31, 8.23) were found to be risk factors for pneumonia. CONCLUSION: In this study, risk factors for pneumonia were family size, monthly income, type of energy used for cooking, malnutrition, and diarrhea or URTI in the past 2 weeks. Relatively simple interventions such as cooking with electricity, and other interventions like prevention, early detection and treatment of malnutrition, diarrhea, and URTI, and promotion of family planning are important.

Effect of preconceptional, prenatal and postnatal exposure to home environmental factors on childhood pneumonia: A key role in early life exposure.

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 NO2, 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".

The indirect effects of COVID-19 upon global 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.

Chest radiography in children aged 2-59 months enrolled in the Innovative Treatments in Pneumonia (ITIP) project in Lilongwe Malawi: a secondary analysis.

BACKGROUND: Pneumonia is the leading infectious cause of death in children aged under 5 years in low- and middle-income countries (LMICs). World Health Organization (WHO) pneumonia diagnosis guidelines rely on non-specific clinical features. We explore chest radiography (CXR) findings among select children in the Innovative Treatments in Pneumonia (ITIP) project in Malawi in relation to clinical outcomes. METHODS: When clinically indicated, CXRs were obtained from ITIP-enrolled children aged 2 to 59 months with community-acquired pneumonia hospitalized with treatment failure or relapse. ITIP1 (fast-breathing pneumonia) and ITIP2 (chest-indrawing pneumonia) trials enrolled children with non-severe pneumonia while ITIP3 enrolled children excluded from ITIP1 and ITIP2 with severe pneumonia and/or selected comorbidities. A panel of trained pediatricians classified the CXRs using the standardized WHO CXR research methodology. We analyzed the relationship between CXR classifications, enrollee characteristics, and outcomes. RESULTS: Between March 2016 and June 2018, of 114 CXRs obtained, 83 met analysis criteria with 62.7% (52/83) classified as having significant pathology per WHO standardized interpretation. ITIP3 (92.3%; 12/13) children had a higher proportion of CXRs with significant pathology compared to ITIP1 (57.1%, 12/21) and ITIP2 (57.1%, 28/49) (p-value = 0.008). The predominant pathological CXR reading was "other infiltrates only" in ITIP1 (83.3%, 10/12) and ITIP2 (71.4%, 20/28), while in ITIP3 it was "primary endpoint pneumonia"(66.7%, 8/12,; p-value = 0.008). The percent of CXRs with significant pathology among children clinically cured (60.6%, 40/66) vs those not clinically cured (70.6%, 12/17) at Day 14 was not significantly different (p-value = 0.58). CONCLUSIONS: In this secondary analysis we observed that ITIP3 children with severe pneumonia and/or selected comorbidities had a higher frequency of CXRs with significant pathology, although these radiographic findings had limited relationship to Day 14 outcomes. The proportion of CXRs with "primary endpoint pneumonia" was low. These findings add to existing data that additional diagnostics and prognostics are important for improving the care of children with pneumonia in LMICs. TRIAL REGISTRATION: ITIP1, ITIP2, and ITIP3 were registered with ClinicalTrials.gov ( NCT02760420 , NCT02678195 , and NCT02960919 , respectively).

Experiences From an Implementation Model of ARI Diagnostic Device in Pneumonia Case Management Among Under-5 Children in Peripheral Healthcare Centers in India.

OBJECTIVES: To address pneumonia, a major killer of under-5 children in India, a multimodal pulse oximeter was implemented in Health and Wellness Centers. Given the evidence of pulse oximetry in effective pneumonia management and taking into account the inadequate skills of front-line healthcare workers in case management, the device was introduced to help them readily diagnose and treat a child and to examine usability of the device. DESIGN: The implementation was integrated with the routine OPD of primary health centers for 15 months after healthcare workers were provided with an abridged IMNCI training. Monthly facility data was collected to examine case management with the diagnostic device. Feedback on usefulness of the device was obtained. SETTING: Health and Wellness Centers (19) of 7 states were selected in consultation with state National Health Mission based on patient footfall. PARTICIPANTS: Under-5 children presenting with ARI symptoms at the OPD. RESULTS: Of 4846 children, 0.1% were diagnosed with severe pneumonia and 23% were diagnosed with pneumonia. As per device readings, correct referrals were made of 77.6% of cases of severe pneumonia, and 81% of pneumonia cases were correctly given antibiotics. The Pulse oximeter was highly acceptable among health workers as it helped in timely classification and treatment of pneumonia. It had no maintenance issue and battery was long-lasting. CONCLUSION: Pulse oximeter implementation was doable and acceptable among health workers. Together with IMNCI training, PO in primary care settings is a feasible approach to provide equitable care to under-5 children.

LncRNA GAS5 participates in childhood pneumonia by inhibiting cell apoptosis and promoting SHIP-1 expression via downregulating miR-155.

BACKGROUND: LncRNA GAS5 and miR-155 are reported to play opposite roles in lung inflammatory responses. Lung inflammation participates in childhood pneumonia, indicating the involvement of GAS5 and miR-155 in pneumonia. The study aimed to analyze the potential interaction between GAS5 and miR-155 in childhood pneumonia. METHODS: GAS5 and miR-155 levels in plasma samples from pneumonia patients and controls were detected using RT-qPCR. The role of GAS5 in miR-155 RNA gene methylation in human bronchial epithelial cells (HBEpCs) was analyzed by methylation analysis. Flow cytometry and RT-qPCR were applied to analyze cell apoptosis and SHIP-1 expression, respectively. RESULTS: GAS5 was downregulated in pneumonia, and miR-155 was upregulated in pneumonia. GAS5 and miR-155 were inversely correlated. GAS5 overexpression decreased miR-155 expression in HBEpCs, while miR-155 overexpression showed no significant effects on GAS5 expression. In addition, GAS5 suppressed LPS-induced HBEpC apoptosis, promoted SHIP-1 expression, and reduced the enhancing effect of miR-155 on cell apoptosis and SHIP-1 expression. CONCLUSIONS: GAS5 may participate in childhood pneumonia by inhibiting cell apoptosis and promoting SHIP-1 expression via downregulating miR-155.

Weather Variability, Socioeconomic Factors, and Pneumonia in Children Under Five-Years Old - Bangladesh, 2012-2016.

WHAT IS ALREADY KNOWN ON THIS TOPIC?: Different socioecological factors were associated with childhood pneumonia in Bangladesh. However, previous studies did not assess spatial patterns, and socioecological factors and spatial variation have the potential to improve the accuracy and predictive ability of existing models. WHAT IS ADDED BY THIS REPORT?: The spatial random effects were present at the district level and were heterogeneous. Average temperature, temperature variation, and population density may influence the spatial pattern of childhood pneumonia in Bangladesh. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: The study results will help policymakers and health managers to identify the vulnerable districts, plan further investigations, help to improve proper resource allocation, and improve health interventions.

Performance of five pulse oximeters to detect hypoxaemia as an indicator of severe illness in children under five by frontline health workers in low resource settings - A prospective, multicentre, single-blinded, trial in Cambodia, Ethiopia, South Sudan, and Uganda.

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].

Experiences with use of a pulse oximeter multimodal device in outpatient management of children with Acute Respiratory Infection during Covid pandemic.

BACKGROUND: While Covid-19 infection rate in children is low, respiratory symptoms are a common mode of presentation which calls for better management of such symptoms. However, ARI case managemnet in primary health settings settings has challenges as health workers lack skills to count respiratory rate and check chest indrawing. To address this multimodal pulse oximeters have been introduced in health and wellness centres of seven states to ease the work of front line health workers. A study was undertaken to understand the usability of the multimodal pulse oximeter during Covid times. METHODS: A qualitative study was conducted with the aid of indepth interviews among a convenience sample of eleven health care workers from ten health and wellness centres. Interviews were conducted and recorded over phone, after obtaining consent. Transcribed interviews were coded and analysed on a qualitative analysis software. Content analysis was conducted. RESULTS: Total children screened during covid lockdown period (April 1-May 31) is 571, those diagnosed with pneumonia and severe pneumonia is 68 and 2. Health care workers were satisfied with pulse oximeter as it helped in timely diagnosis and treatment, and offered protection from possible infection as it mitigated the need for physical contact. CONCLUSION: The multimodal pulse oximeter is well accepted among providers as it is easy to use aiding in timely management of ARI in children. It has an added protection as it's use reduces the need for physical contact. It can be adopted in other HWC and primary health facilities.

Long non-coding RNA GAS5 regulates Th17/Treg imbalance in childhood pneumonia by targeting miR-217/STAT5.

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.

Preconceptional and prenatal exposure to diurnal temperature variation increases the risk of childhood pneumonia.

BACKGROUND: Pneumonia is the leading cause of death and hospitalization among young children worldwide, but its risk factors remain unclear. OBJECTIVE: To evaluate the effect of maternal exposure to diurnal temperature variation (DTV) during preconceptional and prenatal periods on childhood pneumonia. METHODS: A retrospective cohort study by case-control design was conducted for pneumonia (N = 699) and normal (N = 811) children under age of 14 who were enrolled in XiangYa Hospital, Changsha, China from May 2017 to April 2019. Demographic data including gender, age, birth season, gestational age, parity, mode of delivery, and parental atopy were collected from the electronic medical records in the hospital system. We obtained the data of daily DTV in Changsha during 2003-2019 from China Meteorological Administration. Maternal exposure to DTV during preconceptional and prenatal periods was respectively calculated by the average of daily DTV during one year and three months before conception and entire pregnancy as well as the three trimesters. The association between maternal exposure to outdoor DTV and childhood pneumonia was analyzed by multiple logic regression model. RESULTS: We found that childhood pneumonia was significantly associated with exposure to an increase in DTV during one year before conception and entire pregnancy, with ORs (95 % CI) = 2.53 (1.56-4.10) and 1.85 (1.24-2.76). We further identified a significant risk of pneumonia of DTV exposure during the first and second trimester of pregnancy. Sensitivity analysis showed that boys were more susceptible to the effect of prenatal exposure to outdoor DTV during pregnancy particularly in the first two trimesters compared to girls. CONCLUSIONS: Preconceptional and prenatal exposure to DTV plays an important role in development of childhood pneumonia, especially during the first and second trimesters of pregnancy.

LncRNA RP11-248E9.5 and RP11-456D7.1 are Valuable for the Diagnosis of Childhood Pneumonia.

BACKGROUND: Pneumonia is a common infection of the lung parenchyma in children, and early and accurate diagnosis of childhood pneumonia (CP) is important for implementing appropriate preventive and treatment strategies. This study aimed to evaluate the diagnostic value of the combination of long non-coding RNA (lncRNA) RP11-248E9.5, RP11-456D7.1, c-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in CP. PATIENTS AND METHODS: A total of 50 healthy children (HC) and 100 CP patients were enrolled. The serum expression of RP11-248e9.5 and RP11-456d7.1 was detected by qRT-PCR. The white blood cell (WBC), hemoglobin (HB), platelet (PLT), neutrophil, and lymphocyte were analyzed by automated hematology analyzer. The serum levels of CRP and procalcitonin (PCT) were analyzed by automatic biochemical analyzer. The receiver operating characteristic (ROC) curves were applied to evaluate the diagnostic value in CP. RESULTS: The NLR and PLR, expression of RP11-248E9.5 and RP11-456D7.1, and serum levels of CRP and PCT were significantly higher in the CP group than those in the HC group. Both RP11-248E9.5 (AUC, 0.86; sensitivity, 84%; specificity, 78%) and RP11-456D7.1 (AUC, 0.89; sensitivity, 79%; specificity, 92%) exhibited certain diagnostic value in CP. The diagnostic values of PCT, CRP, NLR and PLR in CP were limited by low sensitivity (≤ 71%). The combination of multiple indicators improved the diagnostic value. The combination of RP11-248E9.5, RP11-456D7.1, CRP, NLR, and PLR had the best diagnostic value in CP (AUC, 0.992; Sensitivity, 0.97; Specificity, 0.99). CONCLUSION: The combination of RP11-248E9.5, RP11-456D7.1, CRP, NLR, and PLR was a potential diagnostic strategy for CP.