High-dose vitamin D3 supplementation shows no beneficial effects on white blood cell counts, acute phase reactants, or frequency of respiratory infections.

BACKGROUND: Vitamin D has been suggested to influence the immune system, and vitamin D metabolites and the vitamin D receptor (VDR) are generated and expressed in white blood cells (WBC). Moreover, vitamin D status has been associated with incidence and prognosis of some respiratory tract infections (RTI). Therefore, we investigated the effect of vitamin D3 supplementation on WBC, acute phase reactants (APR), and the risk of developing RTIs. METHODS: A double-blinded, randomized, placebo-controlled clinical trial of 307 infertile men with multiple secondary immunological endpoints. The vitamin D3 group (n = 151) initially received 300,000 IU (7,500 µg) cholecalciferol once - followed by 1,400 IU (35 µg) daily for 150 days. The placebo group (n = 156) did not receive active ingredients. RESULTS: At baseline, stratification into clinically relevant groups of vitamin D status (< 25; 25-50; 50-75; >75 nmol/L), showed an inverse association with total leucocyte concentrations (7.0 vs. 6.0 vs. 6.0 vs. 5.5 (109/L); p = 0.007), lymphocytes (2.4 vs. 2.1 vs. 2.0 vs. 2.0 (109/L); p = 0.048), CRP (2.0 vs. 1.7 vs. 1.2 vs. 1.2 (mg/L); p = 0.037), and orosomucoid (0.82 vs. 0.77 vs. 0.76 vs. 0.70 (g/L); p = 0.015). After 150 days, no differences were detected in WBC counts or APRs between the vitamin D3 and the placebo group. However, vitamin D3 treated men had a higher prevalence of self-reported RTIs compared with the placebo group (55% vs. 39%; p = 0.005). CONCLUSIONS: High-dose vitamin D3 supplementation did not alter WBCs or APRs, but a higher prevalence of respiratory infections was observed in the vitamin D3 group. Serum 25(OH)D3 was negatively correlated with most WBCs, indicating that vitamin D status may be linked with inflammation and WBC turnover, but not an important determinant of developing RTIs. TRIAL REGISTRATION: NCT01304927 (ClinicalTrials.gov). Registered February 20, 2011.

Prevalence and determinants of diarrhoea and acute respiratory infections among children aged under five years in West Africa: evidence from demographic and health surveys.

BACKGROUND: Diarrhoea and pneumonia are the leading causes of morbidity and mortality in children aged <5 y (under five) globally. This study sought to investigate the prevalence and determinants of diarrhoea and acute respiratory infections (ARIs) among children under five in West Africa. METHODS: The most recent demographic and health survey (DHS) standard for 13 West African countries was used in the study. We calculated the prevalence of diarrhoea and ARIs (2 wk prior to the survey) and performed multivariable complex logistic regression analysis to identify possible predictors of diarrhoea and ARIs. RESULTS: The weighted prevalence of diarrhoea and ARI was 13.7% and 15.9%, respectively. The prevalence of comorbid diarrhoea and ARI was 4.4%. Children aged <2 y (p<0.001), mothers aged <30 y (p<0.003), mothers without formal education (p<0.001), poor households (p<0.001) and poor nutritional status, wasting (p=0.005) and underweight (p<0.001), were the independent predictors of diarrhoea. The independent predictors of ARIs were children with no childhood vaccinations (p=0.002), use of solid fuel in the household (p=0.007), being underweight (p=0.05) and diarrhoea (p<0.001). CONCLUSIONS: The findings imply the need for holistic public health interventions such as increased vaccination coverage, population-based nutritional programmes and campaigns on the use of cleaner cooking fuel targeted at high-risk subgroups in the population to reduce the burden and adverse effects of diarrhoea and ARIs in the West African region.

Molecular epidemiology and characteristics of respiratory syncytial virus among hospitalized children in Guangzhou, China.

BACKGROUND: Human respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection and hospitalization, especially in children. Highly mutagenic nature and antigenic diversity enable the RSV to successfully survive in human population. We conducted a molecular epidemiological study during 2017-2021 to investigate the prevalence and genetic characteristics of RSV. METHODS: A total of 6499 nasopharyngeal (NP) swabs were collected from hospitalized children at Department of Pediatrics, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, China. All NP swab specimens were preliminary screened for common respiratory viruses and then tested for RSV using specific PCR assays. Partial G genes of RSV were amplified for phylogenetic analysis and genetic characterization. RESULTS: The overall detection rate for common respiratory viruses was 16.12% (1048/6499). Among those, 405 specimens (6.20%, 405/6499) were found positive for RSV. The monthly distribution of RSV and other respiratory viruses was variable, and the highest incidence was recorded in Autumn and Winter. Based on the sequencing of hypervariable region of G gene, 93 RSV sequences were sub-grouped into RSV-A (56, 60.2%) and RSV-B (37, 39.8%). There was no coinfection of RSV-A and RSV-B in the tested samples. Phylogenetic analysis revealed that RSV-A and RSV-B strains belonged to ON1 and BA9 genotypes respectively, indicating predominance of these genotypes in Guangzhou. Several substitutions were observed which may likely change the antigenicity and pathogenicity of RSV. Multiple glycosylation sites were noticed, demonstrating high selection pressure on these genotypes. CONCLUSION: This study illustrated useful information about epidemiology, genetic characteristics, and circulating genotypes of RSV in Guangzhou China. Regular monitoring of the circulating strains of RSV in different parts of China could assist in the development of more effective vaccines and preventive measures.

Association between serum copper-zinc ratio and respiratory tract infection in children and adolescents.

BACKGROUND: The aim of this study was to explore the association between serum copper-zinc (Cu-Zn) ratio and the risk of respiratory tract infection in children and adolescents. METHODS: This cross-sectional study collected the data of 1695 participants who aged 6-17 years with follow-up data on respiratory tract infection in 2011-2012, 2013-2014 and 2015-2016 cycles from the National Health and Nutrition Examination Survey (NHANES) database. Univariate logistic regression analysis was applied to explore the covariates. Each covariate was adjusted in multivariate logistic regression analysis to explore the correlation between serum Cu-Zn ratio and respiratory tract infection. Subgroup analysis was performed to stratify the data according to age, gender and BMI. Restricted cubic spline (RCS) curve was plotted to identify the association between serum Cu-Zn ratio and respiratory tract infection. RESULTS: The results of RCS curve depicted that the risk of respiratory tract infection was increased as the elevation of the serum Cu-Zn ratio. After adjusting for confounders, risk of respiratory tract infection in children and adolescents was elevated with the increase of serum copper-zinc ratio (OR = 1.38, 95%CI: 1.19-1.60). Compared with people with serum copper-zinc ratio <1.25, subjects who had serum copper-zinc ratio >1.52 was associated with increased risk of respiratory tract infection in children and adolescents (OR = 1.88, 95%CI: 1.19-2.98). Subgroup analysis demonstrated that the risk of respiratory tract infection was elevated as the increase of serum copper-zinc ratio in participants <12 years (OR = 1.65, 95%CI: 1.28-2.12), ≥12 years (OR = 1.27, 95%CI: 1.03-1.57), males (OR = 1.63, 95%CI: 1.29-2.06), females (OR = 1.26, 95%CI: 1.01-1.57), underweight and normal (OR = 1.35, 95%CI: 1.11-1.65), and overweight and obese participants (OR = 1.44, 95%CI: 1.15-1.80). CONCLUSION: Higher serum Cu-Zn ratio was associated with increased risk of respiratory tract infection in children and adolescents, which suggests the importance of Zn supplement and the balance of serum Cu-Zn ratio in children and adolescents.

Moderate Dose Bovine Colostrum Supplementation in Prevention of Upper Respiratory Tract Infections in Medical University Students: A Randomized, Triple Blind, Placebo-Controlled Trial.

Colostrum supplementation has been confirmed to protect from upper respiratory tract infections (URTIs) in athletes. Our trial was designed to find out whether other young adults who have potentially been exposed to increased risk of developing URTIs can also benefit. Homogenous population of medical (MED) students (at risk) and health science (HSci) peers were supplemented with a relatively low dose (0.5-1.0 g/day) of bovine colostrum (COL) or placebo (PBO) over 45 days and then once again over 7 days starting at day 87. The trial lasted 107 days. Subjects were monitored solely by them filling out online daily questionnaires containing questions about frequency and severity of URTIs symptoms, well-being, and potential gastrointestinal side-effects. A significant level of protection from URTIs was observed as expressed by dropping frequency of symptomatic days in COL vs. PBO group among MED vs. HSci students. The same effect was also recorded for severity of symptoms, as well as general well-being perception. Overall, it can be concluded that although young healthy people seem to have sufficient defenses from URTIs, COL supplementation can provide significant support in such protection among those at higher infectious risk because of exposure to a heavy workload and increased contact with infectious agents.

Understanding and managing respiratory infections in children and young adults with neurological impairment.

INTRODUCTION: Patients with neurocognitive impairment (NI) have multiple medical needs, with respiratory problems leading to an important reduction in quality of life and life expectancy. We aimed to explain that the origin of chronic respiratory symptoms in patients with NI is multifactorial. AREAS COVERED: In people with NI there is a high prevalence of swallowing dysfunction and hypersalivation inducing aspiration; cough efficacy is decreased resulting in chronic lung infection; sleep-disordered breathing is frequent and muscle mass is abnormal due to malnutrition. Technical investigations are not always specific and sensitive enough to better diagnose the causes of the respiratory symptoms; moreover, they can sometimes be difficult to perform in this vulnerable patient population. We provide a clinical pathway to adopt to identify, prevent, and treat respiratory complications in children and young adults with NI. A holistic approach in discussion with all care providers and the parents is highly recommended. EXPERT OPINION: The care for people with NI and chronic respiratory problems is challenging. The interplay between several causative factors may be difficult to entangle. Well-performed clinical research in this field is largely missing and should be encouraged. Only then, evidence-based clinical care will become possible for this vulnerable patient group.

Vitamin D supplementation and lower respiratory tract infection in infants: a nested case-control study.

PURPOSE: To assess the association between vitamin D (VD) supplementation and the risk of lower respiratory tract infection (LRTI) among infants. METHODS: This is a nested case-control study from an ongoing prospective birth cohort in Wuhan from 2013. Cases were subjects free of neonatal pneumonia but later developed LRTI during infancy, who were matched with five randomly selected controls by infant sex, birth year, and birth season. We included 190 cases and 950 controls in the final analysis. The primary outcome was the first LRTI incident and the exposure was VD supplementation from birth to the index endpoint. The association between VD supplementation and LRTI risk was assessed using the Cox proportional-hazards regression model. RESULTS: Infants taking supplements had a 59% relative reduction in the hazard ratio of LRTI (HR = 0.41; 95% CI 0.26, 0.64) compared to those not supplemented. There was a linear relationship between LRTI risk and VD supplementation within range of 0-603 IU/day: for each 100 IU per day increment in VD supplementation, infants experienced a 21% lower risk of developing LRTI (adjusted HR: 0.79; 95% CI 0.71, 0.89). The linear relationship was stably observed in the sensitivity analyses as well. CONCLUSIONS: VD supplementation was associated with the reduced risk of LRTI throughout infancy, and the optimal supplementation dose for infants may be beyond the current recommendation.

Tea consumption and risk of lower respiratory tract infections: a two-sample mendelian randomization study.

BACKGROUND: Observational studies have reported the association between tea consumption and the risk of lower respiratory tract infections (LRTIs). However, a consensus has yet to be reached, and whether the observed association is driven by confounding factors or reverse causality remains unclear. METHOD: A two-sample Mendelian randomization (MR) analysis was conducted to determine whether genetically predicted tea intake is causally associated with the risk of common LRTI subtypes. Genome-wide association study (GWAS) from UK Biobank was used to identify single-nucleotide polymorphisms (SNPs) associated with an extra cup of tea intake each day. The summary statistics for acute bronchitis, acute bronchiolitis, bronchiectasis, pneumonia, and influenza and pneumonia were derived from the FinnGen project. RESULTS: We found that genetically predicted an extra daily cup of tea intake was causally associated with the decreased risk of bronchiectasis [odds ratio (OR) = 0.61, 95% confidence interval (CI) = 0.47-0.78, P < 0.001], pneumonia (OR = 0.90, 95% CI = 0.85-0.96, P = 0.002), influenza and pneumonia (OR = 0.91, 95% CI = 0.85-0.97, P = 0.002), but not with acute bronchitis (OR = 0.91, 95% CI = 0.82-1.01, P = 0.067) and acute bronchiolitis (OR = 0.79, 95% CI = 0.60-1.05, P = 0.100). Sensitivity analyses showed that no heterogeneity and pleiotropy could bias the results. CONCLUSIONS: Our findings provided new evidence that genetically predicted an extra daily cup of tea intake may causally associated with a decreased risk of bronchiectasis, pneumonia, and influenza and pneumonia.

Understanding the rural-urban disparity in acute respiratory infection symptoms among under-five children in Sub-Saharan Africa: a multivariate decomposition analysis.

BACKGROUND: Acute Respiratory Infections (ARIs) account for more than 6% of the worldwide disease burden in children under the age of five, with the majority occurring in Sub-Saharan Africa. Rural children are more vulnerable to and disproportionately affected by ARIs. As a result, we examined the rural-urban disparity in the prevalence of ARI symptoms and associated factors among children under the age of five in Sub-Saharan Africa. METHODS: We used the most recent Demographic and Health Survey (DHS) data from 36 countries in Sub-Saharan Africa. The study included 199,130 weighted samples in total. To identify variables associated with ARIs symptoms, a multilevel binary logistic regression model was fitted. The Adjusted Odds Ratio (AOR) with a 95% CI was used to determine the statistical significance and strength of the association. To explain the rural-urban disparity in ARI prevalence, a logit-based multivariate decomposition analysis was used. RESULTS: Being female, ever breastfeeding, belonging to a poorer, better wealth status, and having better maternal educational status were significantly associated with lower odds of ARIs among under-five children. Whereas, small size or large size at birth, not taking vitamin A supplementation, being severely underweight, having diarrhea, didn't have media exposure, never had the vaccination, being aged 36-47 months, and being aged 48-59 months were significantly associated with higher odds of ARIs among under-five children. The multivariate decomposition analysis revealed that the difference in characteristics (endowment) across residences explained 64.7% of the overall rural-urban difference in the prevalence of ARIs, while the difference in the effect of characteristics (change in coefficient) explained 35.3%. CONCLUSION: This study found that rural children were highly affected by ARIs in SSA. To reduce the excess ARIs in rural children, public health interventions aimed at impoverished households, home births, and unvaccinated and malnourished children are crucial.

Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT).

OBJECTIVE: To determine the effect of population level implementation of a test-and-treat approach to correction of suboptimal vitamin D status (25-hydroxyvitamin D (25(OH)D) <75 nmol/L) on risk of all cause acute respiratory tract infection and covid 19. DESIGN: Phase 3 open label randomised controlled trial. SETTING: United Kingdom. PARTICIPANTS: 6200 people aged ≥16 years who were not taking vitamin D supplements at baseline. INTERVENTIONS: Offer of a postal finger prick test of blood 25(OH)D concentration with provision of a six month supply of lower dose vitamin D (800 IU/day, n=1550) or higher dose vitamin D (3200 IU/day, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, compared with no offer of testing or supplementation (n=3100). Follow-up was for six months. MAIN OUTCOME MEASURES: The primary outcome was the proportion of participants with at least one swab test or doctor confirmed acute respiratory tract infection of any cause. A secondary outcome was the proportion of participants with swab test confirmed covid-19. Logistic regression was used to calculate odds ratios and associated 95% confidence intervals. The primary analysis was conducted by intention to treat. RESULTS: Of 3100 participants offered a vitamin D test, 2958 (95.4%) accepted and 2674 (86.3%) had 25(OH)D concentrations <75 nmol/L and received vitamin D supplements (n=1328 lower dose, n=1346 higher dose). Compared with 136/2949 (4.6%) participants in the no offer group, at least one acute respiratory tract infection of any cause occurred in 87/1515 (5.7%) in the lower dose group (odds ratio 1.26, 95% confidence interval 0.96 to 1.66) and 76/1515 (5.0%) in the higher dose group (1.09, 0.82 to 1.46). Compared with 78/2949 (2.6%) participants in the no offer group, 55/1515 (3.6%) developed covid-19 in the lower dose group (1.39, 0.98 to 1.97) and 45/1515 (3.0%) in the higher dose group (1.13, 0.78 to 1.63). CONCLUSIONS: Among people aged 16 years and older with a high baseline prevalence of suboptimal vitamin D status, implementation of a population level test-and-treat approach to vitamin D supplementation was not associated with a reduction in risk of all cause acute respiratory tract infection or covid-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04579640.

Red propolis supplementation does not decrease acute respiratory events in stunted preschool children: A paired nonrandomized clinical trial.

BACKGROUND & AIMS: This study aimed to evaluate the efficacy of "red propolis" supplementation in the frequency of acute respiratory infections incidence in stunted preschool children. We hypothesized that the "red" propolis supplementation is effective in the reduce frequency of acute respiratory complications in stunted children. METHODS: This is a non-randomized, pair-matched clinical trial with 70 children, ranging from 1 to 5 years old, followed for 1 year, which were paired into two groups according to age, sex, and stunting classification. The children were in the day hospital regimen of CREN and received 5 meals/day and an additional 8 ml of honey or honey with "red propolis" in a 3% dilution. The children had access to nutritional, psychological, dental, and physician care. Respiratory complications were recorded in a pre-existing protocol of the institution by the same pediatrician, who was blind for the children's allocation. Anthropometric measurements and biochemical tests such as hemogram, IGF-1, and immunoglobulin E, G, M were conducted. RESULTS: The most prevalent symptoms were coughing, runny nose, nasal congestion and wheezing. The use of "red propolis" did not decrease the frequency of infections between the control and propolis groups, respectively (2 [1-7] vs 3 [1-7], p = 0.10), which was within the estimated by the Pan American Health Organization. There were no differences between groups in anthropometric and biochemical parameters. CONCLUSION: Supplementation with "red propolis" did not reduce the number of infections in stunted children over 1 year. Possibly, the dilution percentage (3%) may have been insufficient to allow effective action. The protocol of published in the Brazilian Registry of Clinical Trials (http://www.ensaiosclinicos.gov.br/rg/RBR-4n7j6h).

Primary care experience on Stimunex® gocce in children with recurrent respiratory infections: a real-world study during the COVID-19 pandemic era.

BACKGROUND: Respiratory infections (RI) significantly burden society, mainly when there are recurrent respiratory infections (RRI). Thus, there is a need to prevent RI in clinical practice. In this regard, the modulation of the immune system and resolution of the inflammatory cascade could represent an ideal way to prevent RI. Stimunex® gocce, a multicomponent food supplement, contains Sambucus nigra extract, ß-glucan, Zinc, and Vitamin D3. This study investigated its ability to prevent RRI in children using a real-world setting: the pediatric primary care. MATERIALS AND METHODS: Two hundred and ninety-eight children with RRI were enrolled in the current study. The food supplement was randomly prescribed to 160 children with RRI daily for 4 months (Active group); the remaining 138 children with RRI were treated only with standard therapy for RI (Control group). The number and duration of RI, parental perception of symptom severity and treatment efficacy, use of medications, and school and working absence were evaluated. RESULTS: Children treated with Stimunex® gocce had significantly less RI than the Control group, both concerning upper and lower RI (p˂0.001 and 0.003, respectively) during the follow-up period. Moreover, children in the Active group experienced shorter RI duration during the treatment and follow-up phases (p˂0.001 for both). In addition, parents of treated children perceived less severe symptoms and better treatment efficacy during the first and follow-up phases (p˂0.001 for all). The food supplement was well tolerated and there was no adverse event. CONCLUSIONS: The current real-world study demonstrated that Stimunex® gocce supplementation in children with RRI might safely prevent RI episodes and reduce RI duration. These outcomes should be highlighted as obtained during the COVID-19 pandemic era, characterized by a dramatic reduction of RI.

Bayesian multilevel analysis of determinants of acute respiratory infection in children under the age of five years in Ethiopia.

BACKGROUND: Acute respiratory tract infection (ARI) is one of the leading causes of illness and mortality in children under the age of five worldwide. Pneumonia, which is caused by a respiratory tract infection, kills about 1.9 million children under the age of 5 years around the world. The majority of these deaths occur in underdeveloped countries. According to the 2016 Ethiopia Demographic and Health Survey (EDHS), the prevalence rate of ARI in Ethiopia was 7%. Prevalence is defined as the number of infectious diseases present at a given period in relation to the total number of children under the age of five who have been exposed to ARI. The goal of this study was to determine the risk factors for acute respiratory infection among children under the age of five in Ethiopia. METHODS: To provide representative samples of the population, a community-based cross-sectional sampling scheme was designed. Bayesian multilevel approach was employed to assess factors associated with the prevalence of ARI among children under age five in Ethiopia. The data was collected from 10,641 children under the age of 5 years out of which 9918 children were considered in this study. RESULTS: The ARI prevalence rate in children under the age of 5 years was assessed to be 8.4%, somewhat higher than the country's anticipated prevalence rate. Children whose mothers did not have a high level of education had the highest prevalence of ARI. The key health, environmental, and nutritional factors influencing the proportion of children with ARI differed by area. Tigray (15.3%) and Oromia (14.4%) had the highest prevalence of ARI, while Benishangul Gumuz had the lowest prevalence (2.6%). The use of vitamin A was investigated, and the results revealed that roughly 43.1% of those who received vitamin A had the lowest prevalence of ARI (7.7%) as compared to those who did not receive vitamin A. Diarrhea affected 11.1% of children under the age of five, with the highest frequency of ARI (24.6%) and the highest prevalence of ARI reported in children whose drinking water source was unprotected/unimproved (9.4%). CONCLUSIONS: The prevalence of ARI among children under the age of 5 years was found to be strongly affected by the child's age, household wealth index, mother's educational level, vitamin A supplement, history of diarrhea, maternal work, stunting, and drinking water source. The study also found that the incidence of ARI varies significantly between and within Ethiopian areas. When intending to improve the health status of Ethiopian children, those predictive variables should be taken into consideration.

Current opinion on the role of vitamin D supplementation in respiratory infections and asthma/COPD exacerbations: A need to establish publication guidelines for overcoming the unpublished data.

BACKGROUND & AIMS: The role of prophylactic vitamin D supplementation in prevention and treatment of respiratory infections and other related pathologies has been extensively explored with conflicting results. The aim of this systematic review and meta-analysis was to evaluate the prophylactic and therapeutic effects of vitamin D administration on respiratory infections. METHODS: A systematic search was performed and randomized controlled trials (RCTs) of vitamin D supplementation and a total of 65 RCTs involving 50,554 participants were included. RESULTS: The overall incidence of respiratory infections in terms of count data (OR: 0.87; 95%CI [0.80-0.95]; p = 0.0028; I2 = 43%) and event rate (IRR: 0.81; 95%CI [0.70-0.95]; p = 0.010; I2 = 79%) was significantly reduced in the intervention group. However, no effect of vitamin D on duration or upper respiratory tract infection severity was observed following the overall analysis. Subgroup analyses revealed more details regarding the protective effect of particular dose ranges, administration frequencies and trial durations on different disease types. CONCLUSIONS: Despite between-study heterogeneity was high for most outcomes and publication bias may have led to an effect size overestimation of incidence count data, vitamin D supplementation could be beneficial in improving resistance to overall respiratory infections, particularly when administered on a daily basis.

Association between ivy leaves dry extract EA 575 prescriptions and antibiotic use, sick leave duration, and repeated infections in adult patients.

OBJECTIVES: The present study aimed to analyze the association between the prescription of ivy leaf dry extract EA 575 (licensed under the trade name Prospan® in Germany) and the incidence of antibiotic use, incident bacterial complications, and days of sick leave in adult patients with cold diseases. METHODS: This retrospective cohort study was based on the IQVIA Disease Analyzer database and included adult patients from 1032 general practices in Germany with a documentation of common cold between 2017 and 2020 (index date) and prescription of either EA 575 or an antibiotic drug within 3 days after index date. 1:1 propensity score matching based on age, sex, index month, physician, health insurance status, and the Charlson Comorbidity Index was carried out. Univariable regression models were used to investigate the association between EA 575 prescription and defined outcomes. RESULTS: Data of 7034 patients treated with EA 575 and 7034 matched patients receiving an antibiotic were available. EA 575 prescription was associated with significantly lower odds of an antibiotic prescription in the time periods of 4-30 days (OR: 0.83; 95% CI: 0.72-0.96) and 31-365 days (OR: 0.44; 95% CI: 0.40-0.48) after the index date. EA 575 prescription was significantly associated with a lower rate of sick leave of more than 7 days (33.0% vs. 37.7%, OR: 0.81; 95% CI: 0.73-0.90) in patients with any sick leave, as well as with lower odds of a new cough diagnosis (OR: 0.91, 95% CI: 0.85-0.98) when compared to antibiotic prescription. CONCLUSION: Our study provides further evidence that the use of phytopharmaceuticals, in particular ivy leaf dry extract EA 575, could contribute to a reduction in the number of inappropriate antibiotic prescriptions for respiratory infection with cough symptoms.

Nutrient supplementation for prevention of viral respiratory tract infections in healthy subjects: A systematic review and meta-analysis.

It remains uncertain as to whether nutrient supplementation for the general population considered healthy could be useful in the prevention of RTIs, such as COVID-19. In this systematic review and meta-analysis, the evidence was evaluated for primary prevention of any viral respiratory tract infection (RTI) such as SARS-CoV-2, through supplementation of nutrients with a recognized role in immune function: multiple micronutrients, vitamin A, folic acid, vitamin B12, C, D, E, beta-carotene, zinc, iron and long-chain polyunsaturated fatty acids. The search produced 15,163 records of which 93 papers (based on 115 studies) met the inclusion criteria, resulting in 199,055 subjects (191,636 children and 7,419 adults) from 37 countries. Sixty-three studies were included in the meta-analyses, which was performed for children and adults separately. By stratifying the meta-analysis by world regions, only studies performed in Asia showed a significant but heterogeneous protective effect of zinc supplementation on RTIs (RR 0.86, 95% CI 0.7-0.96, I2  = 79.1%, p = .000). Vitamin D supplementation in adults significantly decreased the incidence of RTI (RR 0.89, 95% CI 0.79-0.99, p = .272), particularly in North America (RR 0.82 95% CI 0.68-0.97), but not in Europe or Oceania. Supplementation of nutrients in the general population has either no or at most a very limited effect on prevention of RTIs. Zinc supplementation appears protective for children in Asia, whilst vitamin D may protect adults in the USA and Canada. In 10/115 (8.7%) studies post-hoc analyses based on stratification for nutritional status was performed. In only one study zinc supplementation was found to be more effective in children with low zinc serum as compared to children with normal zinc serum levels.

Vitamin D, respiratory infections, and chronic disease: Review of meta-analyses and randomized clinical trials.

BACKGROUND: Observational studies have suggested associations of vitamin D deficiency (VDD) with respiratory tract infections, impaired bone health, and myriad chronic diseases. OBJECTIVE: To assess potential causal relationships between vitamin D supplementation and a reduced risk of these conditions, a review of the evidence across available meta-analyses of randomized control trials (RCTs) and RCTs was performed. METHOD: PubMed, Embase, Cochrane Library, and Web of Science were searched from their inception to March 2021. We included only RCTs and meta-analyses of RCTs focusing on the association between vitamin D and respiratory disease, bone health, cardiovascular disease (CVD), diabetes mellitus, and cancer. RESULTS: A total of 107 RCTs and 62 meta-analysis of RCTs were included. Although most RCTs did not support benefits of vitamin D supplementation, suggestive evidence for benefit was found in populations at greater risk of VDD and for acute respiratory infections, fractures in institutionalized older adults, type 2 diabetes among patients with prediabetes, and cancer mortality. In contrast, no compelling evidence for benefit was found for other respiratory conditions, fractures in community-dwelling adults, falls, cancer incidence, or CVD. CONCLUSIONS: Current evidence from RCTs and meta-analyses of RCTs is inconsistent regarding the effects of vitamin D supplementation on respiratory infections and chronic diseases. Individuals most likely to benefit are those with baseline VDD or with selected high-risk conditions. Public health initiatives are needed to eliminate VDD globally, and future research will be enhanced by a 'precision prevention' approach to identify those most likely to benefit from vitamin D supplementation.

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.

Dietary Supplementation with Biobran/MGN-3 Increases Innate Resistance and Reduces the Incidence of Influenza-like Illnesses in Elderly Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Clinical Trial.

Influenza-like illness (ILI) remains a major cause of severe mortality and morbidity in the elderly. Aging is associated with a decreased ability to sense pathogens and mount effective innate and adaptive immune responses, thus mandating the development of protective nutraceuticals. Biobran/MGN-3, an arabinoxylan from rice bran, has potent anti-aging and immunomodulatory effects, suggesting that it may be effective against ILI. The objective of the current study was to investigate the effect of Biobran/MGN-3 on ILI incidence, natural killer (NK) cell activity, and the expressions of RIG-1 (retinoic acid-inducible gene 1), MDA5 (melanoma differentiation-associated protein 5), and their downstream signaling genes ISG-15 (interferon-stimulated genes 15) and MX1 (myxovirus (influenza) resistance 1, interferon-inducible). A double-blind, placebo-controlled clinical trial included eighty healthy older adults over 55 years old, 40 males and 40 females, who received either a placebo or Biobran/MGN-3 (500 mg/day) for 3 months during known ILI seasonality (peak incidence) in Egypt. The incidence of ILI was confirmed clinically according to the WHO case definition criteria. Hematological, hepatic, and renal parameters were assessed in all subjects, while the activity of NK and NKT (natural killer T) cells was assessed in six randomly chosen subjects in each group by the degranulation assay. The effect of Biobran/MGN-3 on RIG-1 and MDA5, as well as downstream ISG15 and MX1, was assessed in BEAS-2B pulmonary epithelial cells using flow cytometry. The incidence rate and incidence density of ILI in the Biobran/MGN-3 group were 5.0% and 0.57 cases per 1000 person-days, respectively, compared to 22.5% and 2.95 cases per 1000 person-days in the placebo group. Furthermore, Biobran/MGN-3 ingestion significantly enhanced NK activity compared to the basal levels and to the placebo group. In addition, Biobran/MGN-3 significantly upregulated the expression levels of RIG-1, MDA5, ISG15, and MX1 in the human pulmonary epithelial BEAS-2B cell lines. No side effects were observed. Taken together, Biobran/MGN-3 supplementation enhanced the innate immune response of elderly subjects by upregulating the NK activity associated with reduction of ILI incidence. It also upregulated the intracellular RIG-1, MDA5, ISG15, and MX1 expression in pulmonary epithelial tissue cultures. Biobran/MGN-3 could be a novel agent with prophylactic effects against a wide spectrum of respiratory viral infections that warrants further investigation.

Probiotics with vitamin C for the prevention of upper respiratory tract symptoms in children aged 3-10 years: randomised controlled trial.

In a double-blind, randomised, parallel-group, placebo-controlled study, healthy school children aged 3-10 years received a probiotic based supplement daily for 6 months to assess the impact on the incidence and duration of upper respiratory tract infection (URTI) symptoms. The intervention comprised Lab4 probiotic (Lactobacillus acidophilus CUL21 and CUL60, Bifidobacterium bifidum CUL20 and Bifidobacterium animalis subsp. lactis CUL34) at 12.5 billion cfu/day plus 50 mg vitamin C or a matching placebo. 171 children were included in the analysis (85 in placebo and 86 in active group). Incidence of coughing was 16% (P=0.0300) significantly lower in the children receiving the active intervention compared to the placebo. No significant differences in the incidence rate of other URTI symptoms were observed. There was significantly lower risk of experiencing five different URTI related symptoms in one day favouring the active group (Risk ratio: 0.31, 95% confidence interval: 0.12, 0.81, P=0.0163). Absenteeism from school and the use of antibiotics was also significantly reduced for those in the active group (-16%, P=0.0060 and -27%, P=0.0203, respectively). Our findings indicate that six months daily supplementation with the Lab4 probiotic and vitamin C combination reduces the incidence of coughing, absenteeism and antibiotic usage in 3 to 10 year old children.