Acute Lower Respiratory Infections In Children Research Articles

Prevalence of Parainfluenza Viruses in Seoul, 2021 - 2022.

Parainfluenza virus (PIV) is a significant etiological agent of acute lower respiratory tract infections (ALRIs) in infants and young children. The present study has been conducted to investigate the prevalence of recently identified respiratory viruses. In total, 543 oropharyngeal or nasopharyngeal swab samples collected from hospitalized patients with acute respiratory symptoms (ARS) between January and December 2021 (5,653 females and 4,950 males) were tested for respiratory viruses using RT-PCR. At least one respiratory virus was detected by RT-PCR in 119 out of 175 samples (68%). The most frequently detected virus was human rhinovirus (HRV) (34, 6.5%), followed by human parainfluenza viruses (HPIVs) (19, 3.6%), human bocavirus (HBoV) (8, 1.5%), human adenovirus (HAdV) (7, 1.3%), and human respiratory syncytial virus (HRSV) (4, 0.8%). HPIV-3 accounted for 3.6% (19/175) of all viral pathogens and was the second most frequently detected viral pathogen in our study. HPIV-3 infections peaked in the fall (November) of 2021. Phylogenetic analysis of the coding region of the viral protein HA revealed that all 35 (100%) of 35 HPIV-infected patients were infected with HPIV-3. HPIV was an important causative pathogen associated with ALRI in children hospitalized in Korea in the late fall of 2021, as the social distancing rules for COVID-19 were relaxed. These findings highlight the im-portance of HPIV as a cause of ALRI.

Short-term effects of air pollution on hospitalization for acute lower respiratory infections in children: a time-series analysis study from Lanzhou, China

BackgroundShort-term exposure to air pollution is associated with acute lower respiratory infections (ALRI) in children. We investigated the relationship between hospitalization for ALRI in children and air pollutant concentrations from January 1, 2014 to December 31, 2020 in Lanzhou City.MethodsWe collected data on air pollutant concentrations and children’s hospitalization data during the study period. A time series regression analysis was used to assess the short-term effects of air pollutants on ALRI in children, and subgroup analyses and sensitivity analyses were performed.ResultsA total of 51,206 children with ALRI were studied, including 40,126 cases of pneumonia and 11,080 cases of bronchiolitis. The results of the study revealed that PM2.5, PM10, SO2 and NO2 were significantly associated with hospitalization for ALRI in children aged 0–14 years. For each 10 µg/m3 increase in air pollutant concentration in lag0-7, the relative risk of ALRI hospitalization in children due to PM2.5, PM10, SO2 and NO2 increased by 1.089 (95%CI:1.075, 1.103), 1.018 (95%CI:1.014, 1.021), 1.186 (95%CI:1.154. 1.219) and 1.149 (95%CI:1.130, 1.168), respectively.ConclusionsPM2.5, PM10, SO2 and NO2 short-term exposures were positively associated with ALRI, pneumonia and bronchiolitis hospitalizations in Lanzhou, China. Local governments should make efforts to improve urban ambient air quality conditions to reduce hospitalization rates for childhood respiratory diseases.

Sono-Elastography: An Ultrasound Quantitative Non-Invasive Measurement to Guide Bacterial Pneumonia Diagnosis in Children.

Lung ultrasound (LUS) is, at present, a standard technique for the diagnosis of acute lower respiratory tract infections (ALRTI) and other lung pathologies. Its protocolised use has replaced chest radiography and has led to a drastic reduction in radiation exposure in children. Despite its undeniable usefulness, there are situations in which certain quantitative measurements could provide additional data to differentiate the etiology of some pulmonary processes and thus adapt the treatment. Our research group hypothesises that several lung processes such pneumonia may lead to altered lung tissue stiffness, which could be quantified with new diagnostic tests such as lung sono-elastography (SE). An exhaustive review of the literature has been carried out, concluding that the role of SE for the study of pulmonary processes is currently scarce and poorly studied, particularly in pediatrics. The aim of this review is to provide an overview of the technical aspects of SE and to explore its potential usefulness as a non-invasive diagnostic technique for ALRTI in children by implementing an institutional image acquisition protocol.

Clinical epidemiology and disease burden of bronchiolitis in hospitalized children in China: a national cross-sectional study.

Bronchiolitis is a common acute lower respiratory tract infection (ALRTI) and the most frequent cause of hospitalization of infants and young children with ALRTI. Respiratory syncytial virus is the main pathogen that leads to severe bronchiolitis. The disease burden is relatively high. To date, few descriptions of the clinical epidemiology and disease burden of children hospitalized for bronchiolitis are available. This study reports the general clinical epidemiological characteristics and disease burden of bronchiolitis in hospitalized children in China. This study included the face sheet of discharge medical records collected from 27 tertiary children's hospitals from January 2016 to December 2020 that were aggregated into the FUTang Update medical REcords (FUTURE) database. The sociodemographic variables, length of stay (LOS) and disease burden of children with bronchiolitis were analyzed and compared using appropriate statistical tests. In total, 42,928 children aged 0-3years were hospitalized due to bronchiolitis from January 2016 to December 2020, accounting for 1.5% of the total number of hospitalized children of the same age in the database during the period and 5.31% of the hospitalizations for ALRTI. The male to female ratio was 2.01:1. Meanwhile, more boys than girls were observed in different regions, age groups, years, and residences. The 1-2year age group had the greatest number of hospitalizations for bronchiolitis, while the 29days-6months group had the largest proportion of the total inpatients and inpatients with ALRTI in the same age group. In terms of region, the hospitalization rate of bronchiolitis was the highest in East China. Overall, the number of hospitalizations from 2017 to 2020 showed a decreasing trend from that in 2016. Seasonally, the peak hospitalizations for bronchiolitis occurred in winter. Hospitalization rates in North China in autumn and winter were higher than those in South China, while hospitalization rates in South China were higher in spring and summer. Approximately, half of the patients with bronchiolitis had no complications. Among the complications, myocardial injury, abnormal liver function and diarrhea were more common. The median LOS was 6days [interquartile range (IQR) = 5-8], and the median hospitalization cost was 758 United States dollars (IQR = 601.96-1029.53). Bronchiolitis is a common respiratory disease in infants and young children in China, and it accounts for a higher proportion of both total hospitalizations and hospitalizations due to ALRTI in children. Among them, children aged 29days-2years are the main hospitalized population, and the hospitalization rate of boys is significantly higher than that of girls. The peak season for bronchiolitis is winter. Bronchiolitis causes few complications and has a low mortality rate, but the burden of this disease is heavy.

Short-term effects and economic burden of air pollutants on acute lower respiratory tract infections in children in Southwest China: a time-series study

BackgroundThere are few studies on the effects of air pollutants on acute lower respiratory tract infections (ALRI) in children. Here, we investigated the relationship of fine particulate matter (PM2.5), inhalable particulate matter (PM10), sulfur dioxide (SO2), and nitrogen dioxide (NO2) with the daily number of hospitalizations for ALRI in children in Sichuan Province, China, and to estimate the economic burden of disease due to exposure to air pollutants.MethodsWe collected records of 192,079 cases of childhood ALRI hospitalization between January 1, 2017 and December 31, 2018 from nine municipal/prefecture medical institutions as well as the simultaneous meteorological and air pollution data from 183 monitoring sites in Sichuan Province. A time series-generalized additive model was used to analyze exposure responses and lagged effects while assessing the economic burden caused by air pollutant exposure after controlling for long-term trends, seasonality, day of the week, and meteorological factors.ResultsOur single-pollutant model shows that for each 10 μg/m3 increase in air pollutant concentration (1 μg/m3 for SO2), the effect estimates of PM2.5, PM10, SO2, and NO2 for pneumonia reached their maximum at lag4, lag010, lag010, and lag07, respectively, with relative risk (RR) values of 1.0064 (95% CI, 1.0004–1.0124), 1.0168(95% CI 1.0089–1.0248), 1.0278 (95% CI 1.0157–1.0400), and 1.0378 (95% CI, 1.0072–1.0692). By contrast, the effect estimates of PM2.5, PM10, SO2, and NO2 for bronchitis all reached their maximum at lag010, with RRs of 1.0133 (95% CI 1.0025–1.0242), 1.0161(95% CI 1.0085–1.0238), 1.0135 (95% CI 1.0025–1.0247), and 1.1133(95% CI 1.0739–1.1541). In addition, children aged 5–14 years were more vulnerable to air pollutants than those aged 0–4 years (p < 0.05). According to the World Health Organization’s air quality guidelines, the number of ALRI hospitalizations attributed to PM2.5, PM10, and NO2 pollution during the study period was 7551, 10,151, and 7575, respectively, while the incurring economic burden was CNY 2847.06, 3827.27, and 2855.91 million.ConclusionThis study shows that in Sichuan Province, elevated daily average concentrations of four air pollutants lead to increases in numbers of childhood ALRI hospitalizations and cause a serious economic burden.

Clinical conditions and risk factors, in predicting risk of Respiratory Syncytial Virus (RSV)-ALRTIs in children

Background: Acute Lower Respiratory Tract Infections (ALRTIs) are an important cause of morbidity and mortality in infant and young children in Africa. The World Health Organization (WHO) in 2015 reported that about four million children aged less than five years die annually and 1.9 million of these deaths result from complications of ALRTIs, mainly pneumonia. This study therefore aims to investigate prevalence of Respiratory Syncytial Virus (RSV) infection and the associated risk factors of ALRTI among under-five children in Lagos, South-West Nigeria. Methods: This is a cross-sectional study among 200 children in Lagos, South-West Nigeria, with Respiratory Syncytial Virus (RSV) infection using Reverse transcription PCR (RT-PCR). A structured questionnaire was self-administered to collect attributes that might directly or indirectly associate with the risks of acquisition of RSV infection. Data was analyzed by both descriptive and inferential statistics using SPSS. Results: A total of 200 participants were recruited, Respiratory Syncytial Virus (RSV) infection was detected in Forty-five (22.5%) using Reverse transcription PCR (RT-PCR). Acute lower respiration tract infections (ALRTIs) were most predominant in age group 25-60 months (35%). One hundred eight (64%) had pneumonia while 72 (36%) had bronchiolitis. Furthermore, exclusive breastfeeding, family history of atopy, history of nasal instrumentation and attended creche were significant risk factors for RSV-ALRTIs. Conclusion: Infants with a family history of atopy are at increased risk of severe RSV infection, and longer hospital stay. Also, there was a significant association between RSV infection and History of nasal instrumentation as well as not been exclusively breastfed.

Burden of respiratory syncytial virus-associated lower respiratory infections in children in Spain from 2012 to 2018

BackgroundRespiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection (ALRI) leading to infant hospitalization, morbidity and postnatal mortality in children younger than 5 years of age worldwide. The aim of this study was to collect data on hospitalizations for RSV-related ALRI in children in Spain from 2012 to 2018.MethodsWe used the discharge reports from the Minimum Basic Data Set (MBDS) to retrospectively analyze hospital discharge data in children ≤ 14 years of age with a diagnosis of acute lower respiratory tract infection, based on the ICD-9-CM and ICD-10-CM diagnosis codes, from 2012 to 2018.ResultsA total of 190,474 children, 58.1% boys and 41.9% girls, were admitted for lower respiratory tract infections in Spain, including 118,731 cases of bronchiolitis, 53,972 cases of bronchitis, 3710 cases of RSV-positive pneumonia, and 14,061 cases of RSV infections. Of these, 92,426 children (48.5%) had laboratory-confirmed RSV infection. The mean case fatality rate was almost 6 times higher for pneumonia (0.6%) than for bronchiolitis (0.1%) or bronchitis (0.1%). A significant linear increase in the mean annual hospitalization rate for pneumonia of almost 15% per year was found, with no changes in the trend over the study period.ConclusionsRSV-related respiratory infections remain a leading cause of infant hospitalization in Spain. Effective antiviral treatments and preventive vaccines are urgently needed for the management of RSV infection in children, especially for those aged 6 to 12 months.

Acute Lower Respiratory Infection Profile in Children at Tertiary Hospital Bandung: Is There a Difference Before and During COVID-19 Pandemic?

This study aims to analyze differences of the prevalence and characteristics of acute lower respiratory infection (ALRI) in children at tertiary hospital before and during COVID-19 pandemic. This was an observational analytic study with cross-sectional design involving pediatric patients based on the time of the study which was in 1 year-prepandemic (A) and 1 year-pandemic period (B). For period A inpatient data were retrieved from medical records and period B used pediatric ALRI registry. The ALRI characteristics were analyzed with significance if P < .05. Prevalence in periods A and B were 5.8% (534/9252) and 4.9% (409/8283), respectively. The characteristics of ALRI for clinical, comorbidities, laboratory findings (NLR, TLC), and chest radiograph showed significant differences (P < .05). ALRI as manifestation of confirmed COVID-19 were identified in 16 (4.9%) cases. Prevalence of ALRI in children during COVID-19 pandemic is lower compared to before. There are differences in the characteristics of ALRI in pediatrics.

Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis

SummaryBackgroundHuman parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global burden of hPIV in childhood ALRI. We aimed to estimate the global and regional hPIV-associated and hPIV-attributable ALRI incidence, hospital admissions, and mortality for children younger than 5 years and stratified by 0–5 months, 6–11 months, and 12–59 months of age.MethodsWe did a systematic review of hPIV-associated ALRI burden studies published between Jan 1, 1995, and Dec 31, 2020, found in MEDLINE, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Global Health Library, three Chinese databases, and Google search, and also identified a further 41 high-quality unpublished studies through an international research network. We included studies reporting community incidence of ALRI with laboratory-confirmed hPIV; hospital admission rates of ALRI or ALRI with hypoxaemia in children with laboratory-confirmed hPIV; proportions of patients with ALRI admitted to hospital with laboratory-confirmed hPIV; or in-hospital case–fatality ratios (hCFRs) of ALRI with laboratory-confirmed hPIV. We used a modified Newcastle-Ottawa Scale to assess risk of bias. We analysed incidence, hospital admission rates, and hCFRs of hPIV-associated ALRI using a generalised linear mixed model. Adjustment was made to account for the non-detection of hPIV-4. We estimated hPIV-associated ALRI cases, hospital admissions, and in-hospital deaths using adjusted incidence, hospital admission rates, and hCFRs. We estimated the overall hPIV-associated ALRI mortality (both in-hospital and out-hospital mortality) on the basis of the number of in-hospital deaths and care-seeking for child pneumonia. We estimated hPIV-attributable ALRI burden by accounting for attributable fractions for hPIV in laboratory-confirmed hPIV cases and deaths. Sensitivity analyses were done to validate the estimates of overall hPIV-associated ALRI mortality and hPIV-attributable ALRI mortality. The systematic review protocol was registered on PROSPERO (CRD42019148570).Findings203 studies were identified, including 162 hPIV-associated ALRI burden studies and a further 41 high-quality unpublished studies. Globally in 2018, an estimated 18·8 million (uncertainty range 12·8–28·9) ALRI cases, 725 000 (433 000–1 260 000) ALRI hospital admissions, and 34 400 (16 400–73 800) ALRI deaths were attributable to hPIVs among children younger than 5 years. The age-stratified and region-stratified analyses suggested that about 61% (35% for infants aged 0–5 months and 26% for 6–11 months) of the hospital admissions and 66% (42% for infants aged 0–5 months and 24% for 6–11 months) of the in-hospital deaths were in infants, and 70% of the in-hospital deaths were in low-income and lower-middle-income countries. Between 73% and 100% (varying by outcome) of the data had a low risk in study design; the proportion was 46–65% for the adjustment for health-care use, 59–77% for patient groups excluded, 54–93% for case definition, 42–93% for sampling strategy, and 67–77% for test methods. Heterogeneity in estimates was found between studies for each outcome.InterpretationWe report the first global burden estimates of hPIV-associated and hPIV-attributable ALRI in young children. Globally, approximately 13% of ALRI cases, 4–14% of ALRI hospital admissions, and 4% of childhood ALRI mortality were attributable to hPIV. These numbers indicate a potentially notable burden of hPIV in ALRI morbidity and mortality in young children. These estimates should encourage and inform investment to accelerate the development of targeted interventions.FundingBill & Melinda Gates Foundation.

Inhibition of Autophagy Does Not Affect Innate Cytokine Production in Human Lung Epithelial Cells During Respiratory Syncytial Virus Infection.

Human respiratory syncytial virus (RSV) is one of the major causes of childhood acute lower respiratory tract infection worldwide. Autophagy is an intracellular pathway involved in nutrient recycling. Recently, autophagy has been reported to play a role in regulating host cytokine response to several viruses, including vesicular stomatitis virus and human immunodeficiency virus. Previous in vivo studies using mouse model has shown that inhibition of autophagy reduces RSV-induced cytokine production. However, the role of autophagy in modulating RSV-induced cytokine response in human cells has not been reported. We investigated the role of autophagy in regulating the production of the cytokines C-X-C motif ligand 8 (CXCL8) and C-C motif ligand 5 (CCL5), in RSV-infected human bronchial epithelium BEAS-2B cells. Fluorescent microscopic analysis showed that RSV infection induced autophagosome formation in BEAS-2B cells. This autophagy inducing ability of RSV was further confirmed by flow cytometry. The effects of pharmacological inhibition of autophagy by SAR405 or chloroquine on cell death and cytokine release were quantified using lactate dehydrogenase assay and enzyme-linked immunosorbent assay (ELISA), respectively. We found that SAR405 or chloroquine did not cause cell death. Importantly, ELISA analysis showed that pharmacological inhibition of autophagy by SAR405 or chloroquine did not affect the productions of both CXCL5 and CXCL8. In contrast to the previous studies using mouse model, our data suggest that pharmacological inhibition of autophagy may not be a suitable strategy in controlling RSV-induced airway inflammation.

Spatial modeling of mortality from acute lower respiratory infections in children under 5 years of age in 2000-2017: a global study.

BackgroundOver the past few decades, various goals have been defined to reduce the mortality of children caused by acute lower respiratory infections (ALRIs) worldwide. However, few spatial studies to date have reported on ALRI deaths.PurposeWe aimed to assess the spatial modeling of mortality from ALRI in children under 5 years of age during 2000–2017 using a global data.MethodsThe data on the mortality of children under 5 years old caused by ALRI were initially obtained from the official website of the World Health Organization. The income status of their home countries was also gathered from the Country Income Groups (World Bank Classification) website and divided into 5 categories. After that, in the ArcGIS 10.6 environment, a database was created and the statistical tests and related maps were extracted. The Global Moran’s I statistic, Getis-Ord Gi statistic, and geographically weighted regression were used for the analyses. In this study, higher z scores indicated the hot spots, while lower z scores indicated the cold spots.ResultsIn 2000–2017, child mortality showed a downward trend from 17.6 per 100,000 children to 8.1 and had a clustered pattern. Hot spots were concentrated in Asia in 2000 but shifted toward African countries by 2017. A cold spot that formed in Europe in 2007 showed an ascending trend by 2017. Based on the results of geographically weighted regression test, the regions identified as the hot spots of mortality from ALRI in children under 5 years old were among the middle-income countries (R2=0.01, adjusted R2=8.77).ConclusionWhile the total number of child deaths in 2000–2017 has decreased, the number of hot spots has increased among countries. This study also concluded that, during the study period, Central and Western Africa countries became the main new hot spots of deaths from ALRI.

Effect of improved cookstove intervention on childhood acute lower respiratory infection in Northwest Ethiopia: a cluster-randomized controlled trial

BackgroundHousehold air pollution exposure is linked with over 3.5 million premature deaths every year, ranking highest among environmental risk factors globally. Children are uniquely vulnerable and sensitive to the damaging health effects of household air pollution which includes childhood acute lower respiratory infection (ALRI). The use of improved cookstoves has been widely encouraged to reduce these health burdens. It is, however, unclear as to whether it is possible to prevent household air pollution-related disease burdens with biomass-fuelled improved cookstove intervention and the evidence regarding its child health effect still attracts wide debate. Therefore, we investigated the child health effect of improved baking stove intervention compared with the continuation of the open burning traditional baking stove.MethodsA cluster-randomized controlled trial was conducted to assess the health effect of improved baking stove intervention. A total of 100 clusters were randomly allocated to both arms at a 1:1 ratio, and a total of four follow-up visits were carried out within 1 year immediately after the delivery of the intervention to all households allocated into the intervention arm. Data were analyzed in SPSS-22, and the intervention effect was estimated using a Generalized Estimating Equations modeling approach among the intention-to-treat population.ResultsA total of 5508 children were enrolled in the study across 100 randomly selected clusters in both arms, among which data were obtained from a total of 5333 participants for at least one follow-up visit which establishes the intention-to-treat population dataset. The intervention was not found to have a statistically significant effect on the longitudinal childhood ALRI with an estimated odds ratio of 0.95 (95% CI: 0.89–1.02). Nevertheless, the longitudinal change in childhood ALRI was significantly associated with age, baseline childhood ALRI, location of cooking quarter, secondary stove type and frequency of baking event measured at baseline.ConclusionsWe found no evidence that an intervention comprising biomass-fuelled improved baking stove reduced the risk of childhood ALRI compared with the continuation of an open burning traditional baking stove. Therefore, effective cooking solutions are needed to avert the adverse health effect of household air pollution, particularly, childhood ALRI.Trial registrationThe trial was registered on August 2, 2018 at clinical trials.gov registry database (registration identifier number: NCT03612362).

Nonsevere Acute Respiratory Syndrome Human Coronaviruses in Children Hospitalized with Acute Lower Respiratory Infection.

Background:The nonzoonotic (nonsevere acute respiratory syndrome (SARS)/Middle East respiratory syndrome) human coronaviruses (HCoVs) are usually considered as the causative agent for acute respiratory infection. We studied the characteristics and outcome of children with non-SARS HCoV acute lower respiratory infection (ALRI).Methods:This was a cross-sectional study from a tertiary care teaching hospital in eastern India.Results:Of 137 samples tested positive for respiratory viruses, 13 were due to HCoV (7 boys, median age: 2 years). Cough was the most common symptom, followed by breathing difficulty and fever. An underlying comorbid condition present in 38.4%. Co-infection with other viruses was seen in 69% of cases. Chest radiograph was abnormal in 69.3% of children. Antibiotics were administered in 53.8%. The median length of hospitalization was 5 d, irrespective of underlying disease. There was no mortality.Conclusions:HCoV is an uncommon but increasingly recognized cause of ALRI in hospitalized children. No severe illness was found in children with underlying comorbidities. This study underscores the importance of HCoV in causation of childhood ALRI, necessitating a surveillance system in India.

The impact of cytokine levels in young South African children with and without HIV-associated acute lower respiratory infections.

Altered host immune responses are considered to play a key role in the pathogenesis of acute lower respiratory infections (ALRI). The existing literature on cytokine responses in ALRI is largely focussed on adults from developed countries and there are few reports describing the role of cytokines in childhood ALRI, particularly in African or human immunodeficiency virus (HIV)-infected populations. To measure systemic cytokine levels in blood plasma from young South African children with and without ALRI and with and without HIV to determine associations between cytokine responses and disease status and respiratory viral identification. Blood plasma samples were collected from 106 hospitalized ALRI cases and 54 non-ALRI controls less than 2 years of age. HIV status was determined. Blood plasma concentrations of 19 cytokines, 7 chemokines, and 4 growth factors (epidermal growth factor, fibroblast growth factor-basic, hepatocyte growth factor, and vascular endothelial) were measured using The Human Cytokine 30-Plex Panel. Common respiratory viruses were identified by PCR. Mean cytokine concentrations for G-CSF, interferon (IFN)-γ, interleukin (IL)-5, and MCP-1 were significantly higher in ALRI cases than in nonrespiratory controls. Within the ALRI cases, several cytokines were higher in children with a virus compared with children without a virus. Mean cytokine concentrations for IFN-α, IFN-γ, IL-4, IL-5, IL-13, tumour necrosis factor-α, and MIP-1α were significantly lower in HIV-infected cases than in HIV-uninfected cases, while IP-10 and monokine induced by interferon-γ were significantly higher in HIV-infected cases than in HIV-uninfected cases. Certain cytokines are likely to play an important role in the host immune response to ALRI. HIV-infected children have impaired inflammatory responses to respiratory infections compared with HIV-uninfected children.

A hierarchical model for estimating the exposure-response curve by combining multiple studies of acute lower respiratory infections in children and household fine particulate matter air pollution.

We present hierarchical models for estimating long-term exposure concentrations and estimating a common exposure-response curve. The exposure concentration model combines temporally sparse, clustered longitudinal observations to estimate household-specific long-term average concentrations. The exposure-response model provides a flexible, semiparametric estimate of the exposure-response relationship while accommodating heterogeneous clustered data from multiple studies. We apply these models to three studies of fine particulate matter (PM2.5) and ALRIs in children in Nepal: a case-control study in Bhaktapur, a stepped-wedge trial in Sarlahi, and a parallel trial in Sarlahi. For each study, we estimate household-level long-term PM2.5 concentrations. We apply the exposure-response model separately to each study and jointly to the pooled data. The estimated long-term PM2.5 concentrations were lower for households using electric and gas fuel sources compared with households using biomass fuel. The exposure-response curve shows an estimated ALRI odds ratio of 3.39 (95% credible interval = 1.89, 6.10) comparing PM2.5 concentrations of 50 and 150 μg/m3 and a flattening of the curve for higher concentrations. These flexible models can accommodate additional studies and be applied to other exposures and outcomes. The studies from Nepal provides evidence of a nonlinear exposure-response curve that flattens at higher concentrations.

Prevalence and risk factors of acute lower respiratory infection among children living in biomass fuel using households: a community-based cross-sectional study in Northwest Ethiopia

BackgroundChildhood acute lower respiratory infection in the form of pneumonia is recognized as the single largest cause of childhood death globally accounting for 16% of the overall deaths. Some studies also reported a higher prevalence of childhood acute respiratory infection in Ethiopia, which ranges from 16% up to 33.5%. Concerning the risk factors, there are limited community-based studies in Ethiopia in general, and in the current study region in particular. Therefore, the present study was conducted to investigate the prevalence of childhood acute respiratory infection and associated factors in Northwest Ethiopia.MethodsAs part of the wider stove trial project, a cross-sectional study was conducted in May 2018 among a total of 5830 children aged less than 4 years old in randomly selected clusters. Binary logistic regression was applied to identify factors linked with childhood acute lower respiratory infection and adjusted odds ratios were used as measures of effect with a 95% confidence interval.ResultsA total of 5830 children were included in the study within 100 clusters. Out of which 51.7% were male and 48.3% female. The prevalence of childhood lower acute respiratory infection was 19.2% (95% CI: 18.2–20.2) and found to decrease among children living in homes with chimney, eaves space and improved cookstove than children living in households with no chimney, eaves space and improved cookstove with estimated AOR of 0.60 (95% CI: 0.51–0.70), 0.70 (95% CI: 0.60–0.84) and 0.43 (95% CI: 0.28–0.67) respectively. It was also associated with other cooking-related factors such as cow dung fuel use [AOR = 1.54 (95% CI: 1.02–2.33)], child spending time near stove during cooking [AOR = 1.41 (95% CI: 1.06–1.88), presence of extra indoor burning events [AOR = 2.19 (95% CI: 1.41–3.40)] and with frequent cooking of meals [AOR = 1.55 (95% CI: 1.13–2.13)].ConclusionHigh prevalence of childhood acute lower respiratory infection was demonstrated by this study and it was found to be associated with household ventilation, cooking technology, and behavioral factors. Therefore, we recommend a transition in household ventilation, cooking technologies as well as in child handling and in the peculiar local extra indoor burning practices.

IL-33 and ST2 as predictors of disease severity in children with viral acute lower respiratory infection

BackgroundMechanisms influencing severity of acute lower respiratory infection (ALRI) in children are not established. We aimed to assess the role of inflammatory markers and respiratory viruses in ALRI severity. MethodsConcentrations of interleukin(IL)-33, soluble suppression of tumorigenicity (sST)2, IL-1ß, tumor necrosis factor α, IL-4, IL-6 and IL- 8 and types of respiratory viruses were evaluated in children at the first and fifth days after hospital admission. Disease severity was defined as need for mechanical ventilation. ResultsSeventy-nine children <5 years-old were included; 33(41.8%) received mechanical ventilation. No associations between virus type, viral load or co-detections and severity of disease were observed. Detection of IL-33 and sST2 in nasopharyngeal aspirates (NPA) on admission were associated with higher risk for mechanical ventilation (RR = 2.89 and RR = 4.57, respectively). IL-6 and IL-8 concentrations were higher on Day 5 in mechanically ventilated children. IL-6 NPA concentrations decreased from Day 1 to Day 5 in children who did not receive mechanical ventilation. Increase in sST2 NPA concentrations from Day 1 to Day 5 was associated with longer hospital length of stay (p < 0.01). ConclusionsAn exacerbated local activation of the IL-33/ST2 axis and persistently high sST2 concentrations over time were associated with severity of viral ALRI in children.

Duration of solid fuel cookstove use is associated with increased risk of acute lower respiratory infection among children under six months in rural central India

IntroductionIndia has a higher number of deaths due to acute lower respiratory infections (ALRIs) in children <5 years than any other country. The underlying cause of half of ALRI deaths is household air pollution from burning of solid fuels, according to the World Health Organization. If there is a direct association between duration of exposure and increased ALRI risk, a potential strategy might be to limit the child’s exposure to burning solid fuel.Methods and materialsChildren born to pregnant women participating in the Global Network for Women and Children's Health Maternal and Newborn Health Registry near Nagpur, India were followed every two weeks from birth to six months to diagnose ALRI. The number of hours per day that the child’s mother spent in front of a burning solid fuel cookstove was recorded. Children of mothers using only clean cookstoves were classified as having zero hours of exposure. Odds Ratios with 95% confidence intervals were obtained from Generalized Estimating Equations logistic models that assessed the relationship of exposure to solid fuels with risk of ≥1 ALRI, adjusted for sex of the child, household smoking, wealth, maternal age, birth weight and parity.ResultsBetween August 2013 and March 2014, 302 of 1,586 children (19%) had ≥1 episode of ALRI. Results from the multivariable analysis indicate that the odds of ALRI significantly increased from 1.2 (95% CI: 0.7–2.2) for <1 hour of exposure to 2.1 (95% CI: 1.4–3.3) for >3 hours of exposure to solid fuel cookstoves compared with no exposure (p<0.01). Additionally, decreasing wealth [middle: 1.2 (0.9, 1.6); poor: 1.4 (1.2–1.7); p<0.001] was associated with ALRIs.ConclusionsOur study findings indicate that increasing the time mothers spend cooking near solid fuel cookstoves while children are in the house may be associated with development of ≥1 ALRI in children <6 months.

2316. RSV Mortality: 19 Years’ Experience in a Pediatric Hospital in Argentina

BackgroundRespiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection (ALRI) in children. We aimed to describe the clinical–epidemiological pattern and risk factors for mortality associated with RSV infection.MethodsProspective, cross-sectional study of ALRI in children admitted to a Children’s Hospital among 2000–2018. Viral diagnosis was made by fluorescent antibody techniques or real-time PCR. We compared clinical–epidemiological characteristics of RSV infection in nonfatal vs. fatal cases. Multiple logistic regression was used to identify independent predictors of mortality.ResultsFrom a total 16,018 patients with ALRI, 13,545(84.6%) were tested for respiratory viruses, 6047 (45%) were positive: RSV 81.1% (4,907), influenza 7.5% (456), parainfluenza 6.9% (419) and adenovirus 4.4% (265). RSV had a seasonal epidemic pattern coinciding with months of lowest average temperature. RSV mortality rate: 1.7% (83/4,855). Fatal cases had a higher proportion of: prematurity (P < 0.01), perinatal respiratory history (P < 0.01), malnourishment (P < 0.01), congenital heart disease (P < 0.01), chronic neurological disease (P < 0.01) and pneumonia as clinical presentation (<0.01). No significant difference between gender was observed. The annual mortality rate distribution was not stable over the study period with the highest mortality in the year 2002. Most deaths occurred among children who had complications: respiratory distress (80.7%), sepsis (31.3%) and atelectasis (13.2%). Independent predictors of RSV mortality were: moderate to severe malnourishment OR 3.64 (95% CI 1.96–6.74)P < 0.01, chronic neurological disease OR 3.99 (95% CI 2.04–7.79) P < 0.01, congenital heart disease OR 4.10 (95% CI 2.36–7.15)P < 0.01 and age under 6 months OR 1.96 (95% CI 1.23–3.11)P < 0.01.ConclusionRSV showed an epidemic seasonal pattern. Malnourishment, chronic neurological disease, congenital heart disease, age under 6 months and pneumonia were the independent risk factors for RSV mortality.Disclosures All authors: No reported disclosures.

Vitamin D status and vitamin D receptor gene polymorphism in Saudi children with acute lower respiratory tract infection.

There is a significant association exists between vitamin D deficiencies, low respiratory tract infections, and certain types of VDR gene polymorphism. Various studies are being conducted to prove any such link between the different clinical conditions due to disturbed vitamin D regulation and VDR gene polymorphisms. The present study analyzed the presence of vitamin D receptor (VDR) gene polymorphisms (ApaI and TaqI) in Saudi pediatric patient suffering from acute lower respiratory tract infection (ALRTI) cases. Fifty children (50) with ALRTI admitted at King Saud University Medical City, Riyadh/Saudi Arabia were included in addition to seventy-three (73) apparently healthy children who were considered as the control group. Genomic DNA from whole blood was extracted and subjected to polymerase chain reaction (PCR) targeting TaqI and ApaI VDR polymorphisms. RFLP-PCR genotyping was performed to determine the allelic frequency within the VDR gene. In the whole sample, the allelic frequency of ApaI polymorphism in the VDR gene was 58.5%, 17.9%, and 23.6% for AA, Aa, and aa respectively (p = 0.11), while it was 48%, 19%, and 33% for TT, Tt, and tt respectively (p = 0.33) with regards to the frequency of TaqI polymorphism in the VDR gene. VDR ApaI Aa and aa genotypes and VDR TaqI Tt and tt genotypes were not associated with increased risk of ALRTI in children (OR 0.87, 95% CI 0.33-2.28, p = 0.77; OR 0.56, 95% CI 0.23-1.4, p = 0.21; OR 1.15, 95% CI 0.44-2.99, p = 0.77; OR 0.73, 95% CI 0.32-1.68, p = 0.46 respectively). To conclude, neither vitamin D status nor VDR gene polymorphisms such as ApaI and TaqI is associated with increased susceptibility to ALRTI. Linkage disequilibrium was not detected between ApaI and TaqI VDR gene polymorphisms as in the case of serum vitamin D status in ALRTI patients versus apparent healthy children.