BACKGROUND: Probiotics are live micro-organisms that may give a beneficial physiological effect when administered in adequate amounts. Some trials show that probiotic strains can prevent respiratory infections. Even though our previously published review showed the benefits of probiotics for acute upper respiratory tract infections (URTIs), several new studies have been published. This is an update of a review first published in 2011 and updated in 2015.
OBJECTIVES: To assess the effectiveness and safety of probiotics (any specified strain or dose), compared with placebo or no treatment, in the prevention of acute URTIs in people of all ages, at risk of acute URTIs.
SEARCH METHODS: We searched CENTRAL (2022, Issue 6), MEDLINE (1950 to May week 2, 2022), Embase (1974 to 10 May 2022), Web of Science (1900 to 10 May 2022), the Chinese Biomedical Literature Database, which includes the China Biological Medicine Database (from 1978 to 10 May 2022), the Chinese Medicine Popular Science Literature Database (from 2000 to 10 May 2022), and the Master's Degree Dissertation of Beijing Union Medical College Database (from 1981 to 10 May 2022). We searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov for completed and ongoing trials on 10 May 2022.
SELECTION CRITERIA: We included individual randomised controlled trials (RCTs) and cluster-RCTs comparing probiotics with placebo or no treatment to prevent acute URTIs. The participants were children, adults, or the elderly in the community, care facilities, schools, or hospitals. Our main outcomes were the number of participants diagnosed with URTIs (at least one event and at least three events), the incidence rate (number of cases/person year) of acute URTIs, and the mean duration of an episode of URTIs. Our secondary outcomes were the number of participants who were absent from childcare centre, school, or work due to acute URTIs; the number of participants who used prescribed antibiotics for acute URTIs; and the number of participants who experienced at least one adverse event from probiotics. We excluded studies if they did not specify acute respiratory infections as 'upper'; studies with more than 50% of participants vaccinated against influenza or other acute URTIs within the last 12 months; and studies with significantly different proportions of vaccinated participants between the probiotics arm and the placebo or no treatment arm.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of trials and extracted data using standard Cochrane methodological procedures. We analysed both intention-to-treat and per-protocol data and used a random-effects model. We expressed results as risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, both with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS: We included 23 individual RCTs and one cluster-RCT. As one of the individual RCTs did not report outcomes in a usable way, we could only meta-analyse data from 23 trials, involving a total of 6950 participants including children (aged from one month to 11 years old), adults (mean age 37.3), and older people (mean age 84.6 years). One trial reported 22.5% flu-vaccine participants within the last 12 months, and 25.4% flu-vaccine participants during the intervention. Probiotics were more likely to be given with milk-based food in children; administered in powder form in adults; and given with milk-based food or in capsules in the elderly. Most of the studies used one or two strains (e.g. Lactobacillus plantarum HEAL9, Lactobacillus paracasei (8700:2 or N1115)) and 109 or 1011 colony-forming units (CFU)/day of probiotics for more than three months. We found that probiotics may reduce the number of participants diagnosed with URTIs (at least one event) (RR 0.76, 95% CI 0.67 to 0.87; P < 0.001; 16 studies, 4798 participants; low-certainty evidence); likely reduce the number of participants diagnosed with URTIs (at least three events) (RR 0.59, 95% CI 0.38 to 0.91; P = 0.02; 4 studies, 763 participants; moderate-certainty evidence); may reduce the incidence rate (number of cases/person year) of URTIs (rate ratio 0.82, 95% CI 0.73 to 0.92, P = 0.001; 12 studies, 4364 participants; low-certainty evidence); may reduce the mean duration of an episode of acute URTIs (MD -1.22 days, 95% CI -2.12 to -0.33; P = 0.007; 6 studies, 2406 participants; low-certainty evidence); likely reduce the number of participants who used prescribed antibiotics for acute URTIs (RR 0.58, 95% CI 0.42 to 0.81; P = 0.001; 6 studies, 1548 participants; moderate-certainty evidence); and may not increase the number of participants who experienced at least one adverse event (RR 1.02, 95% CI 0.90 to 1.15; P = 0.79; 8 studies, 2456 participants; low-certainty evidence). Evidence showing a decrease in the number of people absent from childcare centre, school, or work due to acute URTIs with probiotics is very uncertain (RR 0.14, 95% CI 0.03 to 0.59; 1 study, 80 participants; very low-certainty evidence). Adverse events from probiotics were minor, and most commonly gastrointestinal symptoms, such as vomiting, flatulence, diarrhoea, and bowel pain. AUTHORS' CONCLUSIONS: Overall, we found that probiotics were better than placebo or no treatment in preventing acute URTIs.
Wheezing, asthma, and respiratory infections (RTI) are among the most common causes of morbidity in children and their economic and social burden could be significantly reduced by specific prevention strategies. Epidemiological studies suggest that lower levels of some nutrients are associated with higher prevalence of these conditions, but the possible protective effect of early supplementation with these nutrients has not yet been established. Aim of our review is to synthetize the available scientific evidence on the role of supplementation with pre- and probiotics, vitamin D, fish and poly-unsaturated fatty acids (PUFA), vitamin A, C, and E, given during the first year of life, in the prevention of wheezing, asthma and RTI. We searched studies published on this topic in the PubMed database between January 2000 and September 2021. As for pre- and probiotics, most of the studies showed that an early supplementation had no protective effect toward the development of asthma and wheezing, while conflicting results were reported on their role in the reduction of RTI. As for vitamin D, the available data suggest that early and regular (on a daily or weekly base) supplementation of vitamin D during infancy could have a role in the prevention of RTI, while most studies showed no effect in the prevention of wheezing or asthma. Finally, early introduction of fish in the diet in most studies has proved protective toward wheezing and asthma development.
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.
ObjectivesTo assess the overall effect of vitamin D supplementation on risk of acute respiratory infection (ARI), and to identify factors modifying this effect.
DesignWe conducted a systematic review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ARI prevention using a random effects model. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen.
Data SourcesMEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard RCT Number (ISRCTN) registry from inception to May 2020.
Eligibility Criteria for Selecting StudiesDouble-blind RCTs of supplementation with vitamin D or calcidiol, of any duration, were eligible if they were approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome.
ResultsWe identified 40 eligible RCTs (total 30,956 participants, aged 0 to 95 years). Data were obtained for 29,841 (96.5%) of 30,909 participants in 39 studies. For the primary comparison of vitamin D supplementation vs. placebo, the intervention reduced risk of ARI overall (Odds Ratio [OR] 0.89, 95% CI 0.81 to 0.98; P for heterogeneity 0.009). No statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration. However, protective effects were seen for trials in which vitamin D was given using a daily dosing regimen (OR 0.75, 95% CI 0.61 to 0.93); at daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89); and for a duration of [≤]12 months (OR 0.82, 95% CI 0.72 to 0.94). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0.94, 95% CI 0.81 to 1.08). Risk of bias within individual studies was assessed as being low for all but two trials. A funnel plot showed asymmetry, suggesting that small trials showing non-protective effects of vitamin D may have been omitted from the meta-analysis.
ConclusionsVitamin D supplementation was safe and reduced risk of ARI, despite evidence of significant heterogeneity across trials. The overall effect size may have been over-estimated due to publication bias. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not known and requires investigation.
Systematic Review RegistrationCRD42020190633
O_TEXTBOXSummary Box
What is already known on this subject?O_LIA previous individual participant data meta-analysis from 10,933 participants in 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infection (ARI) demonstrated an overall protective effect (number needed to treat to prevent one ARI [NNT]=33).Sub-group analysis revealed most benefit in those with the lowest vitamin D status at baseline and not receiving bolus doses.
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What this study addsO_LIWe updated this meta-analysis with trial-level data from an additional 14 placebo-controlled RCTs published since December 2015 (i.e. new total of 39 studies with 29,841 participants).
C_LIO_LIAn overall protective effect of vitamin D supplementation against ARI was seen (NNT=36).
C_LIO_LIA funnel plot revealed evidence of publication bias, which could have led to an over-estimate of the protective effect.
C_LIO_LINo statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration.
C_LIO_LIStrongest protective effects were associated with administration of daily doses of 400-1000 IU vitamin D for [≤]12 months (NNT=8).
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C_TEXTBOX
La otitis media (OM) tiene numerosas presentaciones en niños. Junto con las terapias médicas convencionales dirigidas a prevenir y / o tratar OM, se puede ofrecer un número creciente de opciones de tratamiento de medicina complementaria y alternativa (CAM). Dado que el OM es común en los niños, los padres pueden preguntar a los profesionales de la salud acerca de las posibles terapias de CAM. Muchos médicos sienten que su conocimiento es limitado con respecto a estas terapias, y que desean alguna información. Por lo tanto, se realizó una revisión de la literatura de las terapias CAM para el OM, teniendo en cuenta que muchos de estos tratamientos, su validez y eficacia y no han sido científicamente demostrados.Nos realizamos una búsqueda en MEDLINE (acceso a través de PubMed) Se consideraron las siguientes opciones de CAM para el tratamiento de la OM en niños: Se incluyeron ensayos controlados aleatorios, estudios prospectivos / retrospectivos y estudios de casos. La acupuntura, la homeopatía, la fitoterapia, la osteopatía, la quiropráctica, el xilitol, el vendaje de oídos, el suplemento de vitamina D y los probióticos sistémicos y tópicos.Revisamos cada tratamiento y describimos el nivel de evidencia científica de las publicaciones relevantes. CAM son generalmente conservadoras, y no incluyen fármacos o cirugía. Un tratamiento potencial de OM, ya que hay pruebas de apoyo limitadas. Se necesitan más estudios para evaluar el valor potencial de las terapias CAM para OM.
Antecedentes: La otitis media aguda (OMA) es la infección bacteriana más común entre los niños pequeños en los Estados Unidos. Hay limitaciones y preocupaciones sobre su tratamiento con antibióticos y cirugía y medidas preventivas tan eficaces son atractivas. Una posible medida preventiva es el xilitol, un sustituto natural del azúcar que reduce el riesgo de caries dental. El xilitol puede reducir la adherencia de Streptococcus pneumoniae (S pneumoniae) y Haemophilus influenzae (H influenzae) a las células nasofaríngeas in vitro. Esta es una actualización de una revisión publicada por primera vez en 2011. OBJETIVOS: Evaluar la eficacia y la seguridad del xilitol para prevenir la OMA en niños menores de 12 años. Métodos de búsqueda: Se realizaron búsquedas en CENTRAL (edición 12, 2015), MEDLINE (1950 a enero 2016), Embase (1974 a enero 2016), CINAHL (1981 a enero 2016), LILACS (1982 a enero 2016) Web of Science 2011 a enero de 2016) y International Pharmaceutical Abstracts (2000 a enero de 2016). CRITERIOS DE SELECCIÓN: Ensayos controlados aleatorios (ECA) o cuasi-ECA de niños menores de 12 años de edad en los que se comparó la suplementación con xilitol con placebo o sin tratamiento para prevenir la OMA. Dos revisores seleccionaron de forma independiente los ensayos de los resultados de la búsqueda, evaluaron y evaluaron la calidad del estudio y extrajeron los datos pertinentes para su inclusión en la revisión. Nos pusimos en contacto con los autores de los ensayos para solicitar los datos que faltan. Hemos anotado datos sobre cualquier evento adverso de xilitol. Se extrajeron los datos sobre resultados relevantes y se estimó el tamaño del efecto calculando la razón de riesgo (RR), la diferencia de riesgo (RD) y los intervalos de confianza (IC) del 95% asociados. Se identificaron cinco ensayos clínicos en los que participaron 3405 niños. Para esta actualización de 2016, identificamos un nuevo ensayo para su inclusión. Este ensayo fue revisado sistemáticamente pero debido a varias fuentes de heterogeneidad, no se incluyó en el metanálisis. Los cuatro ensayos restantes fueron de calidad metodológica adecuada. En tres ECA que incluyeron un total de 1826 niños finlandeses sanos que asisten a guarderías, existen pruebas de calidad moderada de que el xilitol (en cualquier forma) puede reducir el riesgo de OMA del 30% al 22% en comparación con el grupo control (RR 0,75; % CI 0,65 a 0,88). Entre las razones de los abandonos, no hubo diferencias significativas en el malestar abdominal y la erupción entre el xilitol y los grupos de control. El xilitol no fue eficaz en la reducción de la OMA entre los niños sanos durante una infección respiratoria (RR 1,13, IC del 95%: 0,83 a 1,53, evidencia de calidad moderada) o entre los niños sanos con tendencia a la otitis (RR 0,90; IC del 95%: 0,67 a 1,21; evidencia). Existen pruebas de calidad moderada que demuestran que la administración profiláctica de xilitol entre niños sanos que asisten a guarderías puede reducir la ocurrencia de OMA. No hay pruebas concluyentes con respecto a la eficacia del xilitol en la prevención de la OMA entre los niños con infección respiratoria, o entre los niños propensos a la otitis. El metanálisis fue limitado debido a que los datos provienen de un pequeño número de estudios, y la mayoría eran del mismo grupo de investigación.
ANTECEDENTES Y OBJETIVOS: La mayoría de los osteópatas son entrenados en la atención pediátrica, y el tratamiento de manipulación osteopática (OMT) está disponible para muchas enfermedades pediátricas. El objetivo de esta revisión sistemática fue evaluar críticamente la eficacia de la OMT para el tratamiento de afecciones pediátricas.
MÉTODOS: Se realizaron búsquedas en bases de datos de once de sus respectivos inicios se a noviembre de 2012. Sólo se incluyeron ensayos clínicos aleatorios (ECA) que, si se prueban OMT en contra de cualquier tipo de control en los pacientes pediátricos. La calidad del estudio se evaluó críticamente utilizando los criterios Cochrane.
RESULTADOS: Diecisiete ensayos cumplieron los criterios de inclusión. Cinco ECA fueron de alta calidad metodológica. De ellos, 1 favorecieron OMT, mientras que el 4 reveló ningún efecto en comparación con varias intervenciones de control. Repeticiones por investigadores independientes estaban disponibles para sólo 2 condiciones, y ambos no pudieron confirmar los resultados de los estudios anteriores. Siete ECA sugirieron que OMT lleva a una reducción significativamente mayor en los síntomas del asma, la obstrucción congénita del conducto nasolagrimal (después del tratamiento), ganancia diaria de peso y la duración de la estancia hospitalaria, micción disfuncional, cólico infantil, otitis media, o la asimetría postural en comparación con varios controles intervenciones. Siete ECA se indica que la OM no tuvo ningún efecto sobre los síntomas de asma, parálisis cerebral, escoliosis idiopática, la apnea obstructiva, la otitis media, o trastornos temporomandibulares en comparación con diversas intervenciones de control. Tres ECA no se realizaron comparaciones entre grupos. La mayoría de los ECA incluidos no informó las tasas de incidencia de efectos adversos.
CONCLUSIONES: La evidencia de la efectividad de la OMT para las condiciones pediátricos sigue sin comprobarse debido a la escasez y la baja calidad metodológica de los estudios primarios.
OBJETIVO: Revisar sistemáticamente la eficacia de la administración de Lactobacillus rhamnosus GG (LGG) para la prevención de las infecciones respiratorias en los niños.
DISEÑO: revisión sistemática y meta-análisis.
FUENTES DE DATOS: bases de datos electrónicas y registros de ensayos.
RESULTADOS: Cuatro ECA con 1805 participantes cumplieron los criterios de inclusión. En comparación con el placebo, la administración LGG se asoció con una menor incidencia de otitis media aguda (cuatro ECA, n = 1805, RR 0.76, 95% CI 0,64-0,91 modelo, efectos fijos, NNT 17; IC del 95%: 11 a 46), un menor riesgo de infecciones del tracto respiratorio superior (un ECA, n = 281, RR 0.62, IC 95% 0,50 a 0,78; NNT 4; IC del 95%: 3-8) y tratamientos con antibióticos (cuatro ECA, n = 1805, RR 0.80, 95% IC 0,71-0,91, modelo de efectos fijos). No hubo diferencia significativa entre la LGG y los grupos de control en el riesgo de infecciones respiratorias en general y la incidencia de las infecciones respiratorias inferiores. Sin embargo, el análisis de subgrupos de los dos estudios sobre niños mayores de 1 año mostró una reducción significativa en el riesgo de infecciones respiratorias en general (dos ECA, n = 794, RR 0.73, IC 95% 0,57 hasta 0,92, modelo de efectos aleatorios, NNT 8, 95% CI 5-14). Los efectos adversos fueron similares en ambos grupos. No se informaron eventos adversos graves.
Conclusión: La administración de Lactobacillus rhamnosus GG en comparación con placebo tiene el potencial de reducir la incidencia de otitis media aguda, las infecciones respiratorias superiores y el uso de antibióticos en los niños.
OBJETIVO: Evaluar la evidencia de cualquier tipo de intervención de la homeopatía pruebas terapéuticas o preventivas de enfermedades infantiles y la adolescencia.
MÉTODOS: búsquedas sistemáticas de la literatura se llevaron a cabo hasta enero de 2006 en MEDLINE, EMBASE, AMED, CINAHL, Cochrane Central, Biblioteca Homeopática Británica, ClinicalTrials.gov, y el National Research Register del Reino Unido. Se revisaron las bibliografías de las publicaciones más relevantes. Los estudios fueron seleccionados de acuerdo a la inclusión predefinidos y los criterios de exclusión. Todos los estudios doble ciego, controlados con placebo, los ensayos clínicos aleatorios de cualquier intervención homeopática para prevenir o tratar enfermedades infantiles y la adolescencia se incluyeron. De acuerdo con la clasificación de la Organización Mundial de la Salud, el rango de edad definido para la inclusión fue de 0 a 19 años. Selección de los estudios, la extracción de datos y la evaluación de la calidad metodológica se realizaron de forma independiente por 2 evaluadores.
RESULTADOS: Un total de 326 artículos fueron identificados, de los cuales 91 fueron recuperados para su evaluación detallada. Dieciséis ensayos que evaluaron diferentes condiciones 9 se incluyeron en el estudio. Con la excepción del trastorno de déficit de atención y la diarrea aguda infantil (cada prueba en 3 ensayos), ninguna condición se evaluó en más de 2 doble ciego ensayos clínicos aleatorios. La evidencia para el trastorno de déficit de atención y la diarrea infantil aguda es mixta, mostrando resultados tanto positivos como negativos para sus respectivas medidas de resultado principales. Para la infección de vegetación adenoidea, el asma y las vías respiratorias superiores cada uno, 2 estudios disponibles que sugieren que no hay diferencia en comparación con el placebo. Para 4 condiciones, sólo los ensayos individuales se encuentran disponibles.
CONCLUSIÓN: La evidencia de ensayos clínicos rigurosos de cualquier tipo de intervención de la homeopatía pruebas terapéuticas o preventivas de enfermedades infantiles y la adolescencia no es lo suficientemente convincente como para las recomendaciones en cualquier condición.
Probiotics are live micro-organisms that may give a beneficial physiological effect when administered in adequate amounts. Some trials show that probiotic strains can prevent respiratory infections. Even though our previously published review showed the benefits of probiotics for acute upper respiratory tract infections (URTIs), several new studies have been published. This is an update of a review first published in 2011 and updated in 2015.
OBJECTIVES:
To assess the effectiveness and safety of probiotics (any specified strain or dose), compared with placebo or no treatment, in the prevention of acute URTIs in people of all ages, at risk of acute URTIs.
SEARCH METHODS:
We searched CENTRAL (2022, Issue 6), MEDLINE (1950 to May week 2, 2022), Embase (1974 to 10 May 2022), Web of Science (1900 to 10 May 2022), the Chinese Biomedical Literature Database, which includes the China Biological Medicine Database (from 1978 to 10 May 2022), the Chinese Medicine Popular Science Literature Database (from 2000 to 10 May 2022), and the Master's Degree Dissertation of Beijing Union Medical College Database (from 1981 to 10 May 2022). We searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov for completed and ongoing trials on 10 May 2022.
SELECTION CRITERIA:
We included individual randomised controlled trials (RCTs) and cluster-RCTs comparing probiotics with placebo or no treatment to prevent acute URTIs. The participants were children, adults, or the elderly in the community, care facilities, schools, or hospitals. Our main outcomes were the number of participants diagnosed with URTIs (at least one event and at least three events), the incidence rate (number of cases/person year) of acute URTIs, and the mean duration of an episode of URTIs. Our secondary outcomes were the number of participants who were absent from childcare centre, school, or work due to acute URTIs; the number of participants who used prescribed antibiotics for acute URTIs; and the number of participants who experienced at least one adverse event from probiotics. We excluded studies if they did not specify acute respiratory infections as 'upper'; studies with more than 50% of participants vaccinated against influenza or other acute URTIs within the last 12 months; and studies with significantly different proportions of vaccinated participants between the probiotics arm and the placebo or no treatment arm.
DATA COLLECTION AND ANALYSIS:
Two review authors independently assessed the eligibility of trials and extracted data using standard Cochrane methodological procedures. We analysed both intention-to-treat and per-protocol data and used a random-effects model. We expressed results as risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, both with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS:
We included 23 individual RCTs and one cluster-RCT. As one of the individual RCTs did not report outcomes in a usable way, we could only meta-analyse data from 23 trials, involving a total of 6950 participants including children (aged from one month to 11 years old), adults (mean age 37.3), and older people (mean age 84.6 years). One trial reported 22.5% flu-vaccine participants within the last 12 months, and 25.4% flu-vaccine participants during the intervention. Probiotics were more likely to be given with milk-based food in children; administered in powder form in adults; and given with milk-based food or in capsules in the elderly. Most of the studies used one or two strains (e.g. Lactobacillus plantarum HEAL9, Lactobacillus paracasei (8700:2 or N1115)) and 109 or 1011 colony-forming units (CFU)/day of probiotics for more than three months. We found that probiotics may reduce the number of participants diagnosed with URTIs (at least one event) (RR 0.76, 95% CI 0.67 to 0.87; P < 0.001; 16 studies, 4798 participants; low-certainty evidence); likely reduce the number of participants diagnosed with URTIs (at least three events) (RR 0.59, 95% CI 0.38 to 0.91; P = 0.02; 4 studies, 763 participants; moderate-certainty evidence); may reduce the incidence rate (number of cases/person year) of URTIs (rate ratio 0.82, 95% CI 0.73 to 0.92, P = 0.001; 12 studies, 4364 participants; low-certainty evidence); may reduce the mean duration of an episode of acute URTIs (MD -1.22 days, 95% CI -2.12 to -0.33; P = 0.007; 6 studies, 2406 participants; low-certainty evidence); likely reduce the number of participants who used prescribed antibiotics for acute URTIs (RR 0.58, 95% CI 0.42 to 0.81; P = 0.001; 6 studies, 1548 participants; moderate-certainty evidence); and may not increase the number of participants who experienced at least one adverse event (RR 1.02, 95% CI 0.90 to 1.15; P = 0.79; 8 studies, 2456 participants; low-certainty evidence). Evidence showing a decrease in the number of people absent from childcare centre, school, or work due to acute URTIs with probiotics is very uncertain (RR 0.14, 95% CI 0.03 to 0.59; 1 study, 80 participants; very low-certainty evidence). Adverse events from probiotics were minor, and most commonly gastrointestinal symptoms, such as vomiting, flatulence, diarrhoea, and bowel pain.
AUTHORS' CONCLUSIONS:
Overall, we found that probiotics were better than placebo or no treatment in preventing acute URTIs.
