Can an anti-inflammatory diet be effective in preventing or treating viral respiratory diseases? A systematic narrative review.

Respiratory Viruses infections (RVI) such as rhinovirus, coronavirus, influenza virus, and adenovirus affect the respiratory and the immune systems. The role of nutrition in the respiratory and immune systems has been studied in some studies, and its importance is undeniable. In addition, one of the key findings in this disease is high inflammation that affects almost all patients. This systematic narrative review aims to answer the question, "Can an anti-inflammatory diet be effective in preventing or treating viral respiratory diseases?" A systematic review search was used for the articles extraction. All studies published in English from 1999 to 2020 investigating dietary inflammatory conditions and RVI were included. Food items with anti-inflammatory properties were selected based on the definition of the dietary inflammatory index (DII). We used Google Scholar, Pub Med, Scopus, Web of Science, Springer, Science Direct, Directory of Open Access Journals, Elsevier, Taylor and Francis, ProQuest, EBSCO, MEDLINE, and SciELO databases for extracting articles. Keywords were restricted by DII. Based on DII, food items/nutrients are involved in inflammation, some of which have anti-inflammatory and some inflammatory properties. Some foods/nutrients, in addition to their anti-inflammatory properties, have antioxidant, antiviral, and immune-enhancing properties. Considering the immune system's involvement, increased inflammation, and involvement of the pulmonary system in RVI and the remarkable role of the anti-inflammatory foods for counteracting them, it is recommended to use a predominantly anti-inflammatory diet along with prevention/control and treatment protocols. An anti-inflammatory diet (based on DII) includes turmeric, ginger, garlic, onions, saffron, dietary vitamin C, vitamin D, zinc, and omega-3 are recommended to reduce infection symptoms and duration.

Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials.

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry for studies listed from database inception to May 1, 2020. Double-blind RCTs of vitamin D3, vitamin D2, or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. Aggregated study-level data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. Using the proportion of participants in each trial who had one or more ARIs, we did a random-effects meta-analysis to obtain pooled odds ratios (ORs) and 95% CIs to estimate the effect of vitamin D supplementation on the risk of having one or more ARIs (primary outcome) compared with placebo. Subgroup analyses were done to estimate whether the effects of vitamin D supplementation on the risk of ARI varied according to baseline 25(OH)D concentration (<25 nmol/L vs 25·0-49·9 nmol/L vs 50·0-74·9 nmol/L vs >75·0 nmol/L), vitamin D dose (daily equivalent of <400 international units [IU] vs 400-1000 IU vs 1001-2000 IU vs >2000 IU), dosing frequency (daily vs weekly vs once per month to once every 3 months), trial duration (≤12 months vs >12 months), age at enrolment (<1·00 years vs 1·00-15·99 years vs 16·00-64·99 years vs ≥65·00 years), and presence versus absence of airway disease (ie, asthma only, COPD only, or unrestricted). Risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool. The study was registered with PROSPERO, CRD42020190633. FINDINGS: We identified 1528 articles, of which 46 RCTs (75 541 participants) were eligible. Data for the primary outcome were obtained for 48 488 (98·1%) of 49 419 participants (aged 0-95 years) in 43 studies. A significantly lower proportion of participants in the vitamin D supplementation group had one or more ARIs (14 332 [61·3%] of 23 364 participants) than in the placebo group (14 217 [62·3%] of 22 802 participants), with an OR of 0·92 (95% CI 0·86-0·99; 37 studies; I2=35·6%, pheterogeneity=0·018). No significant effect of vitamin D supplementation on the risk of having one or more ARIs was observed for any of the subgroups defined by baseline 25(OH)D concentration. However, protective effects of supplementation were observed in trials in which vitamin D was given in a daily dosing regimen (OR 0·78 [95% CI 0·65-0·94]; 19 studies; I2=53·5%, pheterogeneity=0·003), at daily dose equivalents of 400-1000 IU (0·70 [0·55-0·89]; ten studies; I2=31·2%, pheterogeneity=0·16), for a duration of 12 months or less (0·82 [0·72-0·93]; 29 studies; I2=38·1%, pheterogeneity=0·021), and to participants aged 1·00-15·99 years at enrolment (0·71 [0·57-0·90]; 15 studies; I2=46·0%, pheterogeneity=0·027). No significant interaction between allocation to the vitamin D supplementation group versus the placebo group and dose, dose frequency, study duration, or age was observed. In addition, no significant difference in the proportion of participants who had at least one serious adverse event in the vitamin supplementation group compared with the placebo group was observed (0·97 [0·86-1·07]; 36 studies; I2=0·0%, pheterogeneity=0·99). Risk of bias within individual studies was assessed as being low for all but three trials. INTERPRETATION: Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400-1000 IU for up to 12 months, and age at enrolment of 1·00-15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation. FUNDING: None.

Effects of Probiotics in Conditions or Infections Similar to COVID-19 on Health Outcomes: An Evidence Analysis Center Scoping Review.

Probiotics have been suggested as a potential intervention for improving outcomes, particularly ventilatory-associated pneumonia, in patients infected with coronavirus disease 2019 (COVID-19). However, with the rapid development of the COVID-19 pandemic, there is little direct evidence available in infected patients. The objective of this scoping review is to examine the availability and nature of literature describing the effect of probiotics in adults with conditions or infections similar to COVID-19 infection on related health outcomes. MEDLINE, Cumulative Index to Nursing & Allied Health Literature, and Cochrane Databases were searched for studies published from 1999 to May 1, 2020, examining the effect of probiotics in conditions applicable to individuals infected with COVID-19, including, but not limited to, other forms of coronavirus, critical illness, and mechanical ventilation. The databases search identified 1925 unique articles, 77 full-text articles were reviewed, and 48 studies were included in this scoping review, including 31 primary studies and 17 systematic reviews. Primary studies examined a range of interventions that varied by probiotic diversity and types, including 8 studies that focused on synbiotics, which include both pre- and probiotics. Several systematic reviews examined the effect of probiotics on ventilator-associated pneumonia and other infections. Although most systematic reviews concluded probiotics may improve these outcomes, most systematic review authors concluded that the evidence was low in quality and high in heterogeneity. In the absence of direct evidence with patients infected with COVID-19, studies in comparable populations are currently the best resource to guide probiotics interventions in conjunction with clinical expertise and multidisciplinary health care planning.

Probiotic nasal spray development by spray drying.

The upper respiratory tract (URT) is the main entrance point for many viral and bacterial pathogens, and URT infections are among the most common infections in the world. Recent evidences by our own group and others imply the importance of lactobacilli as gatekeepers of a healthy URT. However, the benefits of putting health-promoting microbes or potential probiotics, such as these URT lactobacilli, in function of URT disease control and prevention is underestimated, among others because of the absence of adequate formulation modalities. Therefore, this study entails important aspects in probiotic nasal spray development with a novel URT-derived probiotic strain by spray drying. We report quantitative and qualitative analysis of several spray-dried formulations, i.e. powders for reconstitution, based on disaccharide or sugar alcohol combinations with a polymer, including their long-term stability. Four formulations with the highest survival of >109 (Colony Forming Units) CFU/g after 28 weeks were further examined upon reconstitution which confirmed sufficiency of one bottle/dosage form during 7 days and rheological properties of shear-thinning. Tests also demonstrated maintained viability and cell morphology overall upon spraying through a nasal spray bottle in all 4 formulations. Lastly, application suitability in terms of high adherence to Calu-3 cells and antimicrobial activity against common URT pathogens was demonstrated and was not impacted neither by powder production process nor by spraying of reconstituted powder through a nasal spray device.

Respiratory syncytial virus acute respiratory infection-associated hospitalizations in preterm Mexican infants: A cohort study.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of severe acute respiratory infections (ARI) in preterm infants. The incidence of RSV-associated hospitalizations has not been defined in Mexico. OBJECTIVES: To determine the incidence of ARI- and RSV-associated hospitalizations in preterm infants during the first year of life. METHODS: Prospective cohort study of 294 preterm infants followed up through monthly telephone calls and routine outpatient visits. Hospitalized children were identified through daily visits to pediatric wards of participating hospitals and through telephone calls. Respiratory samples were tested for RSV by RT-PCR. RESULTS: Mean gestational age of participating infants was 33 weeks. Ninety-six infants were diagnosed with bronchopulmonary dysplasia (BPD) and 17 with congenital heart disease (CHD); 11 had both conditions. There were 71 hospitalization episodes in 53 infants. Respiratory samples for RSV detection were available in 44 hospitalization episodes, and the result was positive in 16 (36.3%). At least one hospitalization for ARI was recorded in 33 of 96 participants with BPD, in seven of 17 with CHD, and 18 of 192 infants without these diagnoses. Five (71.4%) of CHD infants who required admission also had BPD. RSV-confirmed hospitalization rates were 9.4%, 5.9%, and 2.6% for infants with BPD, CHD, and otherwise healthy preterm infants, respectively. Attributable RSV admission frequencies were estimated to be 13.6%, 16.5%, and 4.1%, respectively. CONCLUSIONS: Mexican preterm infants, particularly those with BPD, have high rates of ARI- and RSVassociated hospitalizations. Specific interventions to reduce the incidence of severe infections in this highrisk group are required.

Beverage Containing Dispersible Yeast ß-Glucan Decreases Cold/Flu Symptomatic Days After Intense Exercise: A Randomized Controlled Trial.

In this double-blind, randomized, placebo-controlled parallel study, we examined the effect of dairy-based beverages (250 mL/day) containing 250 mg of dispersible baker's yeast ß-glucan (Wellmune) compared to a macronutrient- and calorie-matched control on upper respiratory tract infection (URTI) in marathon runners. Healthy adults running in the 2017 Austin Marathon consumed either ß-glucan (N = 132) or control (N = 225) for the 45 days prior to, day of, and 45 days after the marathon (91 days total). Participants completed a daily online survey assessing compliance, training status, and URTI symptoms. URTI occurrence and severity were evaluated using the Jackson Index and confirmed by the study physician. No significant differences in average duration and number of URTI episodes were found between ß-glucan and control. However, those who completed the study per protocol on the ß-glucan beverage reported significantly fewer URTI symptomatic days (3.43 ± 6.44 days, max 27 days) compared to those on control beverage (3.84 ± 6.84 days, max 49 days). Total URTI severity was significantly lower for ß-glucan (4.52 ± 1.61) compared to control (5.60 ± 2.23). Specifically, lower (p < .05) severity ratings for nasal discharge and sore throat were reported for ß-glucan compared to control. Average missed postmarathon workout days due to URTI were significantly less for ß-glucan (0.09 ± 0.38 days, max 2 days) compared to control (0.36 ± 1.40 days, max 10 days). Overall, consumption of dairy-based beverages containing dispersible yeast ß-glucan decreased URTI symptomatic days, severity of specific URTI symptoms, and missed postmarathon workout days due to URTI, without affecting duration and number of URTI episodes.

Cost-effectiveness analysis of a multi-dimensional intervention to reduce inappropriate antibiotic prescribing for children with upper respiratory tract infections in China.

BACKGROUND: We developed a multifaceted intervention to reduce antibiotic prescription rate for children with upper respiratory tract infections (URTIs) among primary care doctors in township hospitals in China. The intervention achieved a 29% (95% CI 16-42) absolute risk reduction in antibiotic prescribing. This study was to assess the cost-effectiveness of our intervention at reducing antibiotic prescribing in rural primary care facilities as measured by the intervention's effect on the antibiotic prescription rates for childhood URTIs. METHODS: We took a healthcare provider perspective, measuring costs of consultation (time cost of doctor), prescription monitoring process and peer-review meetings (time cost of participants) and medication costs. Costs on provider side were collected through a bespoke questionnaire from all 25 township hospitals in December 2016, while medication costs were collected prospectively in the trial. Incremental cost-effectiveness ratios were calculated by dividing the mean difference in cost of the two trial arms by the mean difference in antibiotic prescribing rate. RESULTS: This showed an incremental cost of $0.03 per percentage point reduction in antibiotic prescribing. In addition to this incremental cost, the cost of implementing the intervention, including training and materials delivered by township hospitals, was $390.65 (SD $145.68) per healthcare facility. CONCLUSIONS: This study shows that a multifaceted intervention programme, when embedded into routine practice, is very cost-effective at reducing antibiotic prescribing in primary care facilities and has the potential of scale up in similar resource limited settings.

Probiotics for Modification of the Incidence or Severity of Respiratory Tract Infections.

There is increasing interest in probiotics for therapy and prevention of infectious diseases. There are no published trials of probiotics as therapy for respiratory tract infections (RTIs) in children or adults. There is low quality, inconsistent evidence for the efficacy of probiotics for prevention of RTIs or ventilator-associated pneumonia or for modification of the severity of RTIs.

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data.

Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.Systematic review registration PROSPERO CRD42014013953.

Comparison of the Effect of Two Kinds of Iranian Honey and Diphenhydramine on Nocturnal Cough and the Sleep Quality in Coughing Children and Their Parents.

Coughing in a child induced by upper respiratory tract infections (URTIs) can be a problem, both for the child and its parents. Current studies show a lack of proven efficacy for over-the counter (OTC) medications, but promising data support the use of honey for children. The aim of this study was to compare the effects of two kinds of Iranian honey with diphenhydramine (DPH) on nocturnal pediatric coughs and the sleep quality of children and their parents. This was a clinical trial (registered in IRCT; No.: 28.20.7932, 15 October 2013). The study consisted of 87 patients. All the parents completed a standard previously validated questionnaire. The children were randomly assigned to one of three treatment groups: Group 1, Honey type 1 (Kimia Company, Iran) (n = 42), Group 2, Honey type 2 (Shahde-Golha, Iran) (n = 25), and Group 3, DPH (n = 20). Each group received double doses of the respective treatments on two successive nights. A second survey was then administered via a telephone interview in which the parents were asked the same questions. The mean scores for all aspects of coughs were significantly decreased in each group before and after the treatment. All three treatments improved the cough and sleep scores. Honey type 1 was superior to DPH in improving all aspects of coughs, except the frequency, and Honey type 2 was more effective than DPH in improving all aspects of coughs, except the sleep quality of the child. There was no significant difference between Honey type 1 and 2 in any aspects of cough relief in the present study. The results suggest that honey may provide better cough relief than DPH in children and improve the sleep quality of children and their parents.

[Is procalcitonin measurement useful in managing respiratory tract infections?] / Procalcitoninebepaling nuttig bij luchtweginfecties?

Better use of current antibiotics is warranted to curb increasing antimicrobial resistance rates. Procalcitonin guidance can safely reduce antibiotic usage when used to initiate or discontinue antibiotics in adult patients with a respiratory tract infection. However, the claimed reductions in antibiotic usage are mainly achieved in patients with acute bronchitis and exacerbations of COPD, conditions for which guidelines already discourage antibiotic treatment. Sequential procalcitonin measurements can also reduce the treatment duration of community-acquired pneumonia from 10-12 to 5-7 days, which is, however, already the recommended treatment duration for in- and outpatients under the current Dutch guidelines. Investigating why physicians do not follow these guidelines might therefore be more helpful than introducing new laboratory tests such as that for procalcitonin. Determination of the aetiology of community-acquired pneumonia is an important clinical problem. Host gene expression pattern assays are promising for diagnosis of the aetiology of acute respiratory illness. This might be helpful to guide antibiotic therapy.

Use of probiotics in pediatric infectious diseases.

We summarize current evidence and recommendations for the use of probiotics in childhood infectious diseases. Probiotics may be of benefit in treating acute infectious diarrhea and reducing antibiotic-associated diarrhea. Potential benefits of probiotic on prevention of traveler's diarrhea,Clostridium difficile-associated diarrhea, side effects of triple therapy in Helicobacter pylori eradication, necrotizing enterocolitis, acute diarrhea, acute respiratory infections and recurrent urinary tract infections remain unclear. More studies are needed to investigate optimal strain, dosage, bioavailability of drops and tablets, duration of treatment and safety. Probiotics and recombinant probiotic strain represent a promising source of molecules for the development of novel anti-infectious therapy.

Effect of zinc added to a daily small-quantity lipid-based nutrient supplement on diarrhoea, malaria, fever and respiratory infections in young children in rural Burkina Faso: a cluster-randomised trial.

OBJECTIVE: Preventive zinc supplementation in the form of tablets or syrup reduces the incidence of diarrhoea and acute lower respiratory tract infections (RTI), but its effect on malaria is inconsistent. When zinc is administered with other micronutrients or foods, its effect is also uncertain. We assessed the effects of different amounts and sources of zinc on the frequency of diarrhoea, malaria, fever and RTI in young children. DESIGN, SETTING AND POPULATIONS: This community-based, double-blind, placebo-controlled, cluster-randomised trial of 2435 children 9 months of age was carried out between April 2010 and July 2012 in rural southwestern Burkina Faso. INTERVENTIONS: Participants were randomly assigned at the concession level to receive daily 1 of 4 interventions for 9 months: (1) 20 g small-quantity lipid-based nutrient supplement (SQ-LNS) without zinc and placebo tablet, (2) 20 g SQ-LNS with 5 mg zinc and placebo tablet, (3) 20 g SQ-LNS with 10 mg zinc and placebo tablet or (4) 20 g SQ-LNS without zinc and 5 mg zinc tablet. Participants were visited weekly in their homes for morbidity surveillance for 9 months, and those with uncomplicated diarrhoea and malaria received treatment from the study field workers in the community. MAIN OUTCOMES: Incidence and longitudinal prevalence of diarrhoea, malaria, fever, and lower and upper RTI by intervention group. RESULTS: The incidence of diarrhoea, malaria and fever was 1.10 (±1.03 SD), 0.61 (±0.66 SD) and 1.49 (±1.12 SD) episodes per 100 child-days at risk, respectively, and did not differ by intervention group (p=0.589, p=0.856 and p=0.830, respectively). The longitudinal prevalence of acute lower RTI (0.1%; 95% IC 0.1-0.2%) and of upper RTI (7.8%; 95% IC 7.1-8.4%) did not differ among groups (p=0.234 and p=0.501, respectively). CONCLUSIONS: Inclusion of 5 or 10 mg zinc in SQ-LNS and provision of 5 mg zinc dispersible tablet along with SQ-LNS had no impact on the incidence of diarrhoea, malaria and fever or the longitudinal prevalence of RTI compared with SQ-LNS without zinc in this population. TRIAL REGISTRATION NUMBER: NCT00944281.

A is for aphorisms - feed a fever, starve a cold? Or could it be starve a fever, feed a cold?

The recommendations for management of fever have changed throughout the course of history, as has the very concept of fever. It has changed from something viewed as a diagnosis in its own right to a sign of something to be measured and as a trigger for a diagnostic trail to be made.

Zinc supplementation in young children: A review of the literature focusing on diarrhoea prevention and treatment.

BACKGROUND & AIMS: It is estimated that zinc deficiency is responsible for 4.4% of childhood deaths in Africa, Asia, and Latin America. This review examines the impact of zinc supplementation, administered prophylactically or therapeutically, on diarrhoea. METHODS: Relevant published articles were identified through systematic searches of electronic databases. Bibliographies of retrieved articles were examined. RESULTS: A total of 38 studies were included in this review, 29 studies examined the effect of prophylactic zinc and nine studies examined the effects of therapeutic use of zinc for treatment of diarrhoea in children under five years. CONCLUSION: Prophylactic zinc has been shown to be effective in decreasing both prevalence and incidence of diarrhoea, reducing respiratory infections and improving growth in children with impaired nutritional status. There is less conclusive evidence of reduction in diarrhoea duration or diarrhoea severity. While prophylactic zinc decreases mortality due to diarrhoea and pneumonia, it has not been shown to affect overall mortality. Therapeutic use of zinc for the treatment of diarrhoea in children has been shown to reduce diarrhoea incidence, stool frequency and diarrhoea duration as well as respiratory infections in zinc deficient children. However, stool output is only reduced in children with cholera. Less conclusive evidence exists for therapeutic zinc reducing mortality due to diarrhoea and respiratory infections. Specific definitions of diarrhoea severity, respiratory infection in further studies as well as examination of prophylactic zinc effectiveness in diarrhoea duration and severity effectiveness of therapeutic zinc in reducing mortality due to diarrhoea and respiratory infections are warranted.

Effectiveness of probiotics on the duration of illness in healthy children and adults who develop common acute respiratory infectious conditions: a systematic review and meta-analysis.

Recent systematic reviews have reported a positive, although modest, effect of probiotics in terms of preventing common cold symptoms. In this systematic review, the effect of probiotics, specifically Lactobacillus and Bifidobacterium strains, on the duration of acute respiratory infections in otherwise healthy children and adults was evaluated. To identify relevant trials, eight databases, including MEDLINE, Embase, the Cochrane Database of Systematic Reviews (CDSR), the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Science Citation Index (SCI) and OAISTER, were searched from inception to 20 July 2012. Details regarding unpublished studies/databases were also obtained from probiotic manufacturers. Study selection, data extraction and quality assessment were carried out by two reviewers. Risk of bias was assessed using criteria adapted from those published by the Centre for Reviews and Dissemination. In this review, twenty randomised controlled trials (RCT) were included, of which twelve were considered to have a low risk of bias. Meta-analysis revealed significantly fewer numbers of days of illness per person (standardised mean difference (SMD) - 0·31 (95% CI - 0·41, - 0·11), I²= 3%), shorter illness episodes by almost a day (weighted mean difference - 0·77 (95% CI - 1·50, - 0·04), I²= 80%) (without an increase in the number of illness episodes), and fewer numbers of days absent from day care/school/work (SMD - 0·17 (95% CI - 0·31, - 0·03), I²= 67%) in participants who received a probiotic intervention than in those who had taken a placebo. Reasons for heterogeneity between the studies were explored in subgroup analysis, but could not be explained, suggesting that the effect sizes found may differ between the population groups. This systematic review provides evidence from a number of good-quality RCT that probiotics reduce the duration of illness in otherwise healthy children and adults.

Follow-up formula consumption in 3- to 4-year-olds and respiratory infections: an RCT.

OBJECTIVE: Children are vulnerable to diet inadequacies, which may affect immune function. Our objective was to determine if a follow-up formula (FUF) containing DHA, the prebiotics PDX and GOS, and yeast ß-glucan affects incidence of respiratory infections and diarrheal disease in healthy children. METHODS: In a double-blind, randomized, controlled, prospective trial, 3-4 year old children were fed 3 servings per day of either a FUF with 25 mg DHA, 1.2 g PDX/GOS, and 8.7 mg yeast ß-glucan per serving or an unfortified, cow's milk-based beverage (control) for 28 weeks. Fecal and blood samples were collected to assess immune markers and iron/zinc status. Incidence of acute respiratory infections (ARI), diarrheal disease, and antibiotic treatment were obtained from medical records. RESULTS: The FUF group had fewer episodes and shorter duration of ARI (mean days [SE]; control = 4.3 [0.2]; FUF = 3.5 [0.2]; P = .007), less antibiotic use (n [%]; control = 21 [14%]; FUF = 8 [5%]; P = .01), and fewer missed days of day care due to illness. No diarrheal disease was diagnosed in either group. The FUF group had higher interleukin-10 and white blood cell count at the end of the study. There were no differences in hemoglobin, serum ferritin and zinc, or fecal secretory immunoglobulin A. CONCLUSIONS: Daily consumption of a FUF was associated with fewer episodes and shorter duration of ARI, as well as less antibiotic use. The children who consumed the FUF had increased interleukin-10 and white blood cells, suggesting an antiinflammatory mechanism and/or an increase of effector immune cells.

Definitions and outcomes of nutritional interventions in children with respiratory infections: the approach of the COMMENT initiative.

BACKGROUND/AIMS: This study is aimed at assessing definitions and outcomes used to measure the effects of nutrition in the prevention and treatment of respiratory tract infections in childhood. METHODS: We reviewed clinical trials studying the impact of nutritional interventions on upper and lower respiratory tract infections (URTI and LRTI), focusing on definitions and key outcomes. RESULTS: Fifty trials were included (46 on prevention and 4 on treatment). The definitions of respiratory infections were highly heterogeneous. In 15 of the trials, URTI or LRTI were diagnosed by a pediatrician. In 30 trials, definitions were based on symptoms reported by family members or field-workers only. Five trials did not provide any specific definition. Incidence was the most common outcome measure reported in the trials on prevention, and duration and illness severity were the most common in the treatment trials. CONCLUSIONS: The results showed a major heterogeneity with the use of a wide array of different definitions and clinical end points. To overcome these limitations, outcome measures might be differentiated into two categories: 'direct outcomes' in which respiratory infections are diagnosed and monitored by physicians according to rigorous definitions and 'indirect outcomes' (e.g. chest X-ray, antibiotic prescription and hospitalizations) to assess the burden of respiratory illnesses. Agreement on standard definitions and end points is needed to drive future trials.