Exploring the link between particulate matter pollution and acute respiratory infection risk in children using generalized estimating equations analysis: a robust statistical approach.

BACKGROUND: India is facing a burdensome public health challenge due to air pollution, with a particularly high burden of acute respiratory infections (ARI) among children. To address this issue, our study aims to evaluate the association between exposure to fine particulate matter (PM2.5) and ARI incidence in young children in India. MATERIALS AND METHODS: Our study used PM2.5 data provided by the Atmospheric Composition Analysis Group at Washington University to assess the association between PM2.5 exposure and ARI incidence in 223,375 children sampled from the 2019-2021 Demographic Health Survey in India. We employed the generalized estimating equation and reported odds ratios and 95% confidence intervals for a 10 µg/m3 increase in PM2.5 and quartiles of PM2.5 exposure. RESULTS: Each 10 µg/m3 increase in PM2.5 levels was associated with an increased odds of ARI (OR: 1.23, 95% CI: 1.19-1.27). A change from the first quartile of PM2.5 (2.5-34.4 µg/m3) to the second quartile (34.5-51.5 µg/m3) of PM2.5 was associated with a two-fold change (OR: 2.06, 95% CI: 1.60-2.66) in the odds of developing ARI. Similarly, comparing the first quartile to the fourth quartile of PM2.5 exposure (78.3-128.9 µg/m3) resulted in an over four-fold increase in the odds of ARI (OR: 4.45, 95% CI: 3.37-5.87). CONCLUSION: Mitigation efforts must be continued implementing higher restrictions in India and to bring new interventions to ensure safe levels of air for reducing the burden of disease and mortality associated with air pollution in India.

Nirsevimab Immunization to Prevent Respiratory Syncytial Virus-Associated Lower Respiratory Tract Infections in Infants and Children up to 24 Months of Age.

Respiratory syncytial virus (RSV) infects nearly all infants in their first year of life and is the leading cause of hospitalization for infants younger than 1 year of age in the United States. Historically, the only option for RSV prevention was palivizumab. However, not all infants are eligible for palivizumab, it requires multiple doses per RSV season, and it is costly. In July 2023, the U.S. Food and Drug Administration approved nirsevimab for the prevention of RSV-associated lower respiratory tract infections for all infants. Nirsevimab inhibits RSV from fusing to cellular membranes and thereby neutralizes the virus in the body. Nirsevimab is expected to significantly reduce the health and economic burdens of RSV. This article provides an overview of nirsevimab, potential adverse effects, and implications for nursing practice.

Procalcitonin as a biomarker to guide treatments for patients with lower respiratory tract infections.

INTRODUCTION: Lower respiratory tract infections are amongst the main causes for hospital/intensive care unit admissions and antimicrobial prescriptions. In order to reduce antimicrobial pressure, antibiotic administration could be optimized through procalcitonin-based algorithms. AREAS COVERED: In this review, we discuss the performances of procalcitonin for the diagnosis and the management of community-acquired and ventilator-associated pneumonia. We provide up-to-date evidence and deliver clear messages regarding the purpose of procalcitonin to reduce unnecessary antimicrobial exposure. EXPERT OPINION: Antimicrobial pressure and resulting antimicrobial resistances are a major public health issue as well as a daily struggle in the management of patients with severe infectious diseases, especially in intensive care units where antibiotic exposure is high. Procalcitonin-guided antibiotic administration has proven its efficacy in reducing unnecessary antibiotic use in lower respiratory tract infections without excess in mortality, hospital length of stay or disease relapse. Procalcitonin-guided algorithms should be implemented in wards taking care of patients with severe infections. However, procalcitonin performances are different regarding the setting of the infection (community versus hospital-acquired infections) the antibiotic management (start or termination of antibiotic) as well as patient's condition (immunosuppressed or in shock) and we encourage the physicians to be aware of these limitations.

The Interactive Effects between Drought and Air Pollutants on Children's Upper Respiratory Tract Infection: A Time-Series Analysis in Gansu, China.

As a destructive and economic disaster in the world, drought shows an increasing trend under the continuous global climate change and adverse health effects have been reported. The interactive effects between drought and air pollutants, which may also be harmful to respiratory systems, remain to be discussed. We built the generalized additive model (GAM) and distributed lag nonlinear model (DLNM) to estimate the effects of drought and air pollutants on daily upper respiratory infections (URTI) outpatient visits among children under 6 in three cities of Gansu province. The Standardized Precipitation Index (SPI) based on monthly precipitation (SPI-1) was used as an indicator of drought. A non-stratified model was established to explore the interaction effect of SPI-1 and air pollutants. We illustrated the number of daily pediatric URTI outpatient visits increased with the decrease in SPI-1. The interactive effects between air pollutants and the number of daily pediatric URTIs were significant. According to the non-stratified model, we revealed highly polluted and drought environments had the most significant impact on URTI in children. The occurrence of drought and air pollutants increased URTI in children and exhibited a significant interactive effect.

Air pollution and respiratory infections: the past, present, and future.

Air pollution levels across the globe continue to rise despite government regulations. The increase in global air pollution levels drives detrimental human health effects, including 7 million premature deaths every year. Many of these deaths are attributable to increased incidence of respiratory infections. Considering the COVID-19 pandemic, an unprecedented public health crisis that has claimed the lives of over 6.5 million people globally, respiratory infections as a driver of human mortality is a pressing concern. Therefore, it is more important than ever to understand the relationship between air pollution and respiratory infections so that public health measures can be implemented to ameliorate further morbidity and mortality. This article aims to review the current epidemiologic and basic science research on interactions between air pollution exposure and respiratory infections. The first section will present epidemiologic studies organized by pathogen, followed by a review of basic science research investigating the mechanisms of infection, and then conclude with a discussion of areas that require future investigation.

On the triad of air PM pollution, pathogenic bioaerosols, and lower respiratory infection.

Airborne particulate matter (PM) pollution, as a leading environmental health risk, causes millions of premature deaths globally every year. Lower respiratory infection (LRI) is a sensitive response to short-term exposure to outdoor PM pollution. The airborne transmission of etiological agents of LRI, as an important pathway for infection and morbidity, bridges the public health issues of air quality and pathogen infectivity, virulence, resistance, and others. Enormous efforts are underway to identify common pathogens and substances that are etiological agents for LRI and to understand the underlying toxicological and clinical basis of health effects by identifying mechanistic pathways. Seasonal variations and geographical disparities in the survival and infectivity of LRI pathogens are unsolved mysteries. Weather conditions in geographical areas may have a key effect, but also potentially connect LRI with short-term increases in ambient air PM pollution. Statistical associations show that short-term elevations in fine and coarse PM lead to increases in respiratory infections, but the causative agents could be chemical or microbiological and be present individually or in mixtures, and the interactions between chemical and microbiological agents remain undefined. Further investigations on high-resolution monitoring of airborne pathogens in relation to PM pollution for an integrated exposure-response assessment and mechanistic study are warranted. Improving our understanding of the spatiotemporal features of pathogenic bioaerosols and air pollutants and translating scientific evidence into effective policies is vital to reducing the health risks and devastating death toll from PM pollution.

Atmospheric environment and severe acute respiratory infections in Nanjing, China, 2018-2019.

The annual burden of severe acute respiratory infection (SARI) is enormous, and environmental factors may have a vital role in respiratory infections. This study aimed to investigate the potential effects of the atmospheric environment on SARI. A time-series analysis was performed on the relationship between atmospheric environment and 136,989 SARI cases by distributed lag non-linear model. Wind speed, PM10, PM2.5, O3, and CO exhibited differential effects at a range of lag times or exposure ranges. Air pressure, temperature, and diurnal temperature range showed risk effects in the full range. The lag effect of high pollution was stronger, appeared earlier, and lasted longer than that of low pollution. Most environmental factors had a certain non-linear lag relationship with SARI. Low wind speed and high air pollution may be increasing risk factors for SARI.

Infectious complications after intensive chemotherapy with CLAG-M versus 7+3 for AML and other high-grade myeloid neoplasms.

Contemporary data on infections after intensive chemotherapy for acute myeloid leukemia (AML) are scarce. Cladribine, high-dose cytarabine, G-CSF, and dose-escalated mitoxantrone ("CLAG-M") may result in higher remission rates than standard-dose cytarabine plus anthracycline ("7 + 3") but may result in more infections. We compared moderate to severe infections occurring up to 90 days after the first induction cycle for AML or other high-grade myeloid neoplasms in patients receiving CLAG-M for newly diagnosed (n = 196) or relapsed/refractory disease (n = 131) or 7 + 3 for newly diagnosed disease (n = 115). For newly diagnosed disease, microbiologically documented infections were more frequent after CLAG-M compared to 7 + 3 (adjusted rate ratio, 1.65 [95% CI, 1.06-2.58]; P = 0.03), with a cumulative incidence of 27.8% and 16.5% by day 90, respectively. Patients receiving CLAG-M for relapsed/refractory disease had the highest cumulative incidence of 50.7%. Bacterial bloodstream infections were the most frequent followed by respiratory tract infections. Among 29 patients (7%) who died, infection was a primary or contributing cause of death in 59%. These data indicate that infections continue to cause substantial morbidity in patients treated for AML, especially those treated for relapsed/refractory disease, and are more common with newer, more myelosuppressive regimens such as CLAG-M. Improved strategies for infection prevention are needed.

Application of machine learning approaches to predict the impact of ambient air pollution on outpatient visits for acute respiratory infections.

With a remarkable increase in industrialization among fast-developing countries, air pollution is rising at an alarming rate and has become a public health concern. The study aims to examine the effect of air pollution on patient's hospital visits for respiratory diseases, particularly Acute Respiratory Infections (ARI). Outpatient hospital visits, air pollution and meteorological parameters were collected from March 2018 to October 2021. Eight machine learning algorithms (Random Forest model, K-Nearest Neighbors regression model, Linear regression model, LASSO regression model, Decision Tree Regressor, Support Vector Regression, X.G. Boost and Deep Neural Network with 5-layers) were applied for the analysis of daily air pollutants and outpatient visits for ARI. The evaluation was done by using 5-cross-fold confirmations. The data was randomly divided into test and training data sets at a scale of 1:2, respectively. Results show that among the studied eight machine learning models, the Random Forest model has given the best performance with R2 = 0.606, 0.608 without lag and 1-day lag respectively on ARI patients and R2 = 0.872, 0.871 without lag and 1-day lag respectively on total patients. All eight models did not perform well with the lag effect on the ARI patient dataset but performed better on the total patient dataset. Thus, the study did not find any significant association between ARI patients and ambient air pollution due to the intermittent availability of data during the COVID-19 period. This study gives insight into developing machine learning programs for risk prediction that can be used to predict analytics for several other diseases apart from ARI, such as heart disease and other respiratory diseases.

Short-term exposure to gaseous air pollutants and daily hospitalizations for acute upper and lower respiratory infections among children from 25 cities in China.

To examine the short-term association between gaseous air pollutants (CO, NO2, SO2, and O3) and all-cause respiratory disease, acute upper respiratory infections (AURIs) as well as acute lower respiratory infections (ALRIs) among children, we conducted the study from 25 major cities in China. Hospitalization records of children aged 0-18 years due to all-cause respiratory diseases (889,926), AURIs (97,858), and ALRIs (642,154) from 2016 to 2019 were extracted. Concentrations of CO, NO2, SO2, and O3 were averaged across monitoring stations. Generalized additive models were used to estimate the associations between gaseous air pollutants and daily hospitalizations for all-cause respiratory disease, AURIs, and ALRIs. The meta-analysis was used to combine the city-specific estimates. A 10 mg/m3 increase in CO at lag01, and a 10 µg/m3 increase in NO2, SO2, and O3 at lag01 were associated with 1.65% (95%CI, 0.41-2.91), 0.54% (95%CI, 0.30-0.79), 0.60% (95%CI, 0.22-0.99), and 0.23% (95%CI, 0.06-0.39) increase of hospitalizations due to all-cause respiratory disease, respectively. For the disease subtype, O3 only had adverse effects on AURIs, CO and SO2 mainly on ALRIs, and NO2 on both AURIs and ALRIs. Children aged 4-6years were more vulnerable to the effects of CO and NO2, but those aged <1year were more susceptible to SO2 and O3. Besides, the O3 effect was stronger in the warm season than in the cold season. The study indicated that short-term exposure to CO, NO2, SO2, and O3 was associated with increased hospitalization for pediatric respiratory disease, and the association may vary by position of the respiratory tract, age, and season.

Long-Term PM2.5 Exposure Is Associated with Symptoms of Acute Respiratory Infections among Children under Five Years of Age in Kenya, 2014.

Introduction: Short-term exposures to air pollutants such as particulate matter (PM) have been associated with increased risk for symptoms of acute respiratory infections (ARIs). Less well understood is how long-term exposures to fine PM (PM2.5) might increase risk of ARIs and their symptoms. This research uses georeferenced Demographic Health Survey (DHS) data from Kenya (2014) along with a remote sensing based raster of PM2.5 concentrations to test associations between PM2.5 exposure and ARI symptoms in children for up to 12 monthly lags. Methods: Predicted PM2.5 concentrations were extracted from raster of monthly averages for latitude/longitude locations of survey clusters. These data and other environmental and demographic data were used in a logistic regression model of ARI symptoms within a distributed lag nonlinear modeling framework (DLNM) to test lag associations of PM2.5 exposure with binary presence/absence of ARI symptoms in the previous two weeks. Results: Out of 7036 children under five for whom data were available, 46.8% reported ARI symptoms in the previous two weeks. Exposure to PM2.5 within the same month and as an average for the previous 12 months was 18.31 and 22.1 µg/m3, respectively, far in excess of guidelines set by the World Health Organization. One-year average PM2.5 exposure was higher for children who experienced ARI symptoms compared with children who did not (22.4 vs. 21.8 µg/m3, p < 0.0001.) Logistic regression models using the DLNM framework indicated that while PM exposure was not significantly associated with ARI symptoms for early lags, exposure to high concentrations of PM2.5 (90th percentile) was associated with elevated odds for ARI symptoms along a gradient of lag exposure time even when controlling for age, sex, types of cooking fuels, and precipitation. Conclusions: Long-term exposure to high concentrations of PM2.5 may increase risk for acute respiratory problems in small children. However, more work should be carried out to increase capacity to accurately measure air pollutants in emerging economies such as Kenya.

Synergistic effect of Mahaenggamseok-tang in the treatment of pediatric patients with lower respiratory tract infections: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Infants are often hospitalized because of lower respiratory tract infections, and overuse of antibiotics to treat such infections has led to severe problems. Herbal medicines may be more effective and safer than antibiotics. Mahaenggamseok-tang is a common herbal medicine in Asia, but the evidence for its effectiveness in lower respiratory tract infection treatment is insufficient. This review assesses the efficacy of Mahaenggamseok-tang in treating lower respiratory tract infections. METHODS: The study used Chinese, English, and Korean databases, as well as one Japanese database. All included studies were randomized controlled trials comparing Mahaenggamseok-tang with medication to treat lower respiratory tract infections. Studies using Mahaenggamseok-tang plus Western medicine were also included. Standardized mean difference (SMD), risk ratio (RR) with 95% confidence interval (CI), and risk of bias were analyzed using Review Manager 5.4 software. The GRADEpro website was used to assess the reviews. RESULTS: Seventeen randomized controlled trials with a total of 1993 participants were included in the meta-analysis. All studies compared the Mahaenggamseok-tang plus Western medicine group to the Western medicine only group. Meta-analysis showed that Mahaenggamseok-tang affected total effective rate (risk ratio: 1.20, 95% confidence interval [CI]: 1.10-1.31, P < .001), cough disappearance time (SMD: -1.62, 95% CI: -2.30 to -0.95, P < .001), fever disappearance time (SMD: -2.04, 95% CI: -2.87 to -1.21, P < .001), abnormal lung sound disappearance time (SMD: -1.68, 95% CI: -2.43 to -0.93, P < .001), Creactive protein (SMD: -3.18, 95% CI: -4.36 to -1.99, P < .001), procalcitonin (SMD: -5.04, 95% CI: -9.20 to -0.88, P < .05), tumor necrosis factor-α (SMD: -0.84, 95% CI: -1.46 to -0.23, P < .01), IgE (SMD: -2.69, 95% CI: -2.91 to -2.47, P < .001), and adverse events (risk ratio: 0.44, 95% CI: 0.29-0.68, P < .001), but not interleukin-6 (SMD: -1.59, 95% CI: -3.48 to 0.30, P>.05). DISCUSSION: Mahaenggamseok-tang plus Western medicine is more effective and safer than Western medicine alone for treating lower respiratory tract infections. However, the included randomized controlled trials were not randomized well; therefore, better randomized randomized controlled trials are needed to make significant recommendations.PROSPERO registration number: CRD42020165698.

Outdoor particulate matter exposure and upper respiratory tract infections in children and adolescents: A systematic review and meta-analysis.

BACKGROUND: While the relationship between outdoor particulate matter (PM) and lower respiratory tract infections in children and adolescents is accepted, we know little about the impacts of outdoor PM on the risk of developing or aggravating upper respiratory tract infections (URTIs). METHODS: We aimed to review the literature examining the relationship between outdoor PM exposure and URTIs in children and adolescents. A systematic search of EMBASE, MEDLINE, PubMed, Scopus, CINAHL and Web of Science databases was undertaken on April 3, 2020 and October 27, 2021. Comparable short-term studies of time-series or case-crossover designs were pooled in meta-analyses using random-effects models, while the remainder of studies were combined in a narrative analysis. Quality, risk of bias and level of evidence for health effects were appraised using a combination of emerging frameworks in environmental health. RESULTS: Out of 1366 articles identified, 34 were included in the systematic review and 16 of these were included in meta-analyses. Both PM2.5 and PM10 levels were associated with hospital presentations for URTIs (PM2.5: RR = 1.010, 95%CI = 1.007-1.014; PM10: RR = 1.016, 95%CI = 1.011-1.021) in the meta-analyses. Narrative analysis found unequivocally that total suspended particulates were associated with URTIs, but mixed results were found for PM2.5 and PM10 in both younger and older children. CONCLUSION: This study found some evidence of associations between PM and URTIs in children and adolescents, the relationship strength increased with PM10. However, the number of studies was limited and heterogeneity was considerable, thus there is a need for further studies, especially studies assessing long-term exposure and comparing sources.

Association between satellite-detected tropospheric nitrogen dioxide and acute respiratory infections in children under age five in Senegal: spatio-temporal analysis.

BACKGROUND: There is growing evidence to suggest that exposure to a high concentration of nitrogen dioxide (NO2) can lead to a higher incidence of Acute Respiratory Infections (ARIs) in children; however, such an association remains understudied in Sub-Saharan Africa due to the limited availability of exposure data. This study explored this association by using the satellite-detected tropospheric NO2 concentrations measured by Sentinel-5 Precursor and ARI symptoms in children under age five collected in the Demographic and Health Survey (DHS) in Senegal. METHODS: We matched the daily tropospheric NO2 exposure with the individual ARI symptoms according to the DHS survey clusters spatially and temporally and conducted a logistic regression analysis to estimate the association of exposure to NO2 with ARI symptoms in two preceding weeks. RESULTS: We observed a positive association between exposure to continuous levels of NO2 and ARI symptoms after adjusting for confounders (OR 1.27 per 10 mol/m2, 95% CI: 1.06 - 1.52). When the association was further examined by quartile exposure categories, the 4th quartile category was positively associated with symptoms of ARI after adjusting for confounders (OR 1.71, 95% CI: 1.08-2.69). This suggests that exposure to certain high levels of NO2 is associated with the increased risk of children having symptoms of ARI in Senegal. CONCLUSIONS: This study highlights the need for increased research on the effects of ambient NO2 exposure in Africa as well as the need for more robust, ground-based air monitoring in the region. For a country like Senegal, where more than 90% of the population lives in areas that do not meet the national air quality standards, it is urgently required to implement air pollution prevention efforts to protect children from the health hazards of air pollution.

Associations between air pollutants and risk of respiratory infection: patient-based bacterial culture in sputum.

Air pollution is a crucial risk factor for respiratory infection. However, the relationships between air pollution and respiratory infection based on pathogen detection are scarcely explored in the available literature. We detected respiratory infections through patient-based bacterial culture in sputum, obtained hourly data of all six pollutants (PM2.5, PM10, SO2, NO, CO, and O3) from four air quality monitoring stations, and assessed the relationships of air pollutants and respiratory bacterial infection and multi-drug-resistant bacteria. Air pollution remains a challenge for Mianyang, China, especially PM2.5 and PM10, and there are seasonal differences; pollution is the heaviest in winter and the lowest in summer. A total of 4237 pathogenic bacteria were detected, and the positive rate of multi-drug-resistant bacteria was 0.38%. Similar seasonal differences were found with respect to respiratory infection. In a single-pollutant model, all pollutants were significantly associated with respiratory bacterial infection, but only O3 was significantly associated with multi-drug-resistant bacteria. In multi-pollutant models (adjusted for one pollutant), the relationships of air pollutants with respiratory bacterial infection remained significant, while PM2.5, PM10, and O3 were significantly associated with the risk of infection with multi-drug-resistant bacteria. When adjusted for other five pollutants, only O3 was significantly associated with respiratory bacterial infection and the risk of infection with multi-drug-resistant bacteria, showing that O3 is an independent risk factor for respiratory bacterial infection and infection with multi-drug-resistant bacteria. In summary, this study highlights the adverse effects of air pollution on respiratory infection and the risk of infection with multi-drug-resistant bacteria, which may provide a basis for the formulation of environmental policy to prevent respiratory infections.

Excessive Vitamin A Supplementation Increased the Incidence of Acute Respiratory Tract Infections: A Systematic Review and Meta-Analysis.

(1) Background: vitamin A deficiency (VAD) is highly prevalent in children living in poor conditions. It has been suggested that vitamin A supplementation (VAS) may reduce the risk of acute respiratory tract infections (ARTI). Our study provides updates on the effects of oral VAS (alone) in children on ARTI and further explores the effect on interesting subgroups. (2) Methods: eight databases were systematically searched from their inception until 5 July 2021. The assessments of inclusion criteria, extraction of data, and data synthesis were carried out independently by two reviewers. (3) Results: a total of 26 randomized trials involving 50,944 participants fulfilled the inclusion criteria. There was no significant association of VAS with the incidence of ARTI compared with the placebo (RR 1.03, 95% CI 0.92 to 1.15). Subgroup analyses showed that VAS higher than WHO recommendations increased the incidence of ARTI by 13% (RR 1.13, 95% CI 1.07 to 1.20), and in the high-dose intervention group, the incidence rate among well-nourished children rose by 66% (RR 1.66, 95% CI 1.30 to 2.11). (4) Conclusions: no more beneficial effects were seen with VAS in children in the prevention or recovery of acute respiratory infections. Excessive VAS may increase the incidence of ARTI in children with normal nutritional status.

Asthma symptoms and respiratory infections in Malaysian students-associations with ethnicity and chemical exposure at home and school.

Little is known on respiratory effects of indoor chemicals in the tropics. We investigated associations between asthma and respiratory infections in Malaysian students and chemical exposure at home and at school. Moreover, we investigated differences in home environment between the three main ethnic groups in Malaysia (Malay, Chinese, Indian). Totally, 462 students from 8 junior high schools in Johor Bahru participated (96% participation rate). The students answered a questionnaire on health and home environment. Climate, carbon dioxide (CO2), volatile organic compounds (VOC), formaldehyde and nitrogen dioxide (NO2) were measured inside and outside the schools. Multilevel logistic regression was applied to study associations between exposure and health. Totally 4.8% were smokers, 10.3% had wheeze, 9.3% current asthma, and had 18.8% any respiratory infection in the past 3 months. Malay students had more dampness or mould (p < 0.001), more environmental tobacco smoke (ETS) (p < 0.001) and more cats (p < 0.001) at home as compared to Chinese or Indian students. Wheeze was associated with ethnicity (p = 0.02; lower in Indian), atopy (p = 0.002), current smoking (p = 0.02) and recent indoor painting at home (p = 0.03). Current asthma was associated with ethnicity (p = 0.001; lower in Chinese) and para-dichlorobenzene in classroom air (p = 0.008). Respiratory infections were related to atopy (p = 0.002), ethylbenzene (p = 0.02) and para-dichlorobenzene (p = 0.01) in classroom air. Para-dichlorobenzene is used in Asia against insects. In conclusion, chemical emissions from recent indoor painting at home can increase the risk of wheeze. In schools, para-dichlorobenzene can increase the risk of current asthma and respiratory infections while ethylbenzene can increase the risk of respiratory infections.

The risk of respiratory tract infections and interstitial lung disease with interleukin 12/23 and interleukin 23 antagonists in patients with autoimmune diseases: A systematic review and meta-analysis.

BACKGROUND: Respiratory tract infections (RTIs) and interstitial lung disease (ILD) secondary to interleukin (IL) 12/23 or IL-23 antagonists have been reported in autoimmune diseases. OBJECTIVE: To assess the risk of RTIs and noninfectious ILD with these drugs. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials. Risk of RTIs and noninfectious ILD was compared to placebo by Mantel-Haenszel risk difference. We divided RTIs into upper RTIs (URTI), viral URTIs, and lower RTIs (LRTIs) including infectious pneumonia. Noninfectious ILD included ILD, eosinophilic pneumonia, and pneumonitis. RESULTS: We identified 54 randomized controlled trials including 10,907 patients with 6 IL-12/23 or IL-23 antagonists and 5175 patients with placebo. These drugs significantly increased the risk of RTIs (Mantel-Haenszel risk difference, 0.019; 95% confidence interval, 0.005-0.033; P = .007), which was attributed to URTIs, but not viral URTIs or LRTIs. There was no significant difference in infectious pneumonia and noninfectious ILD between 2 groups. LIMITATIONS: Because of the rarity of infectious pneumonia and ILD, sensitivity analysis was required. CONCLUSIONS: The use of IL-12/23 or IL-23 antagonists for autoimmune diseases increased the risk of URTIs, but not viral URTIs, LRTIs, and noninfectious ILD.

The airways microbiome of individuals with asthma treated with high and low doses of inhaled corticosteroids.

BACKGROUND: Inhaled corticosteroids (ICS) are the mainstay of asthma treatment, but evidence suggests a link between ICS usage and increased rates of respiratory infections. We assessed the composition of the asthmatic airways microbiome in asthma patients taking low and high dose ICS and the stability of the microbiome over a 2 week period. METHODS: We prospectively recruited 55 individuals with asthma. Of these, 22 were on low-dose ICS and 33 on high-dose ICS (16 on budesonide, 17 on fluticasone propionate). Sputum from each subject underwent DNA extraction, amplification and 16S rRNA gene sequencing of the bacterial component of the microbiome. 19 subjects returned for further sputum induction after 24 h and 2 weeks. RESULTS: A total of 5,615,037 sequencing reads revealed 167 bacterial taxa in the asthmatic airway samples, with the most abundant being Streptococcus spp. No significant differences in sputum bacterial load or overall community composition were seen between the low- and high-dose ICS groups. However, Streptococcus spp. showed significantly higher relative abundance in subjects taking low-dose ICS (p = 0.002). Haemophilus parainfluenzae was significantly more abundant in subjects on high-dose fluticasone propionate than those on high-dose budesonide (p = 0.047). There were no statistically significant changes in microbiota composition over a 2-week period. DISCUSSION: Whilst no significant differences were observed between the low- and high-dose ICS groups, increased abundance of the potential pathogen H. parainfluenzae was observed in patients taking high-dose fluticasone propionate compared to those taking high-dose budesonide. The microbiota were stable over fourteen days, providing novel evidence of the established community of bacteria in the asthmatic airways. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02671773.

Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial.

Importance: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced disease severity in moderate to severe atopic dermatitis (AD) in 2 phase 3 monotherapy studies. Objective: To assess the efficacy and safety of 4 mg and 2 mg of baricitinib in combination with background topical corticosteroid (TCS) therapy in adults with moderate to severe AD who previously had an inadequate response to TCS therapy. Design, Setting, and Participants: This double-blind, placebo-controlled, phase 3 randomized clinical trial, BREEZE-AD7 (Study of Baricitinib [LY3009104] in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis) was conducted from November 16, 2018, to August 22, 2019, at 68 centers across 10 countries in Asia, Australia, Europe, and South America. Patients 18 years or older with moderate to severe AD and an inadequate response to TCSs were included. After completing the study, patients were followed up for up to 4 weeks or enrolled in a long-term extension study. Interventions: Patients were randomly assigned (1:1:1) to receive 2 mg of baricitinib once daily (n = 109), 4 mg of baricitinib once daily (n = 111), or placebo (n = 109) for 16 weeks. The use of low-to-moderate potency TCSs was allowed. Main Outcomes and Measures: The primary end point was the proportion of patients achieving a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear), with a 2-point or greater improvement from baseline at week 16. Results: Among 329 patients (mean [SD] age, 33.8 [12.4] years; 216 [66%] male), at week 16, a vIGA-AD score of 0 (clear) or 1 (almost clear) was achieved by 34 patients (31%) receiving 4 mg of baricitinib and 26 (24%) receiving 2 mg of baricitinib compared with 16 (15%) receiving placebo (odds ratio vs placebo, 2.8 [95% CI, 1.4-5.6]; P = .004 for the 4-mg group; 1.9 [95% CI, 0.9-3.9]; P = .08 for the 2-mg group). Treatment-emergent adverse events were reported in 64 of 111 patients (58%) in the 4-mg group, 61 of 109 patients (56%) in the 2-mg group, and 41 of 108 patients (38%) in the placebo group. Serious adverse events were reported in 4 patients (4%) in the 4-mg group, 2 (2%) in the 2-mg group, and 4 (4%) in the placebo group. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and folliculitis. Conclusions and Relevance: A dose of 4 mg of baricitinib in combination with background TCS therapy significantly improved the signs and symptoms of moderate to severe AD, with a safety profile consistent with previous studies of baricitinib in AD. Trial Registration: ClinicalTrials.gov Identifier: NCT03733301.