Table 2.

Reported effects of probiotics in respiratory tract infections (RTIs) in clinical settings in children, healthy adults, and the elderly

Study design	Subjects	Probiotics used	Main findings: probiotic vs. placebo
Children
R DB PC 7 months [42]	571 healthy children at day care centers (1–6 years)	L. rhamnosus GG in milk (on average, 108 cfu) 3× daily	- Days with respiratory symptoms ↔ - No. of children with RTIs ↓ - Antibiotic treatments ↓ - Days of absence from day care ↓ - Age-adjusted results ↔
R DB PC 7 months [45]	523 healthy children at day care centers (2–6 years)	L. rhamnosus GG in milk (on average, 108 cfu) 3× daily	- Days with respiratory symptoms/month ↔ (subgroup of completed cases:↓) - Respiratory symptom episodes/month ↔ - Antibiotic treatments ↔
[47]			Subgroup of children visiting study physician: - Days with respiratory symptoms/month ↓ - Occurrence of respiratory viruses in the nasopharynx ↔ - RTI symptoms associated with viral findings ↔
R DB PC 3 months [43]	281 healthy children at day care centers (2–6 years)	L. rhamnosus GG (109 cfu) in milk daily	- No. of children with RTIs ↓ - No. of URTIs ↓ - No. of lower RTIs ↔ - No. of RTIs lasting >3 days ↓
R DB PC during hospital stay [44]	742 hospitalized children (≥12 months)	L. rhamnosus GG (109 cfu) in milk administered daily for duration of hospitalization	- Risk for RTIs ↓ - Risk for duration of RTI episodes lasting >3 days ↓ - Duration of hospitalization ↔
R DB PC 57 days (3 days from birth) [46]	94 preterm infants (gestational age >32 + 0 and <36 + 6 weeks)	Prebiotic GOS and polydextrose mixture or L. rhamnosus GG 1 × 109 cfu/day for 1–30 days and 2 × 109 cfu/day for 31 to 60 days stirred in 10 ml of liquid	Prebiotic and L. rhamnosus group: - Incidence of RTIs ↓ - Incidence of HRV-induced episodes ↓ - HRV RNA load during infections ↔ - Duration of HRV RNA shedding ↔ - Duration/severity of HRV infections ↔
R DB PC 6 months [56]	309 otitis-prone children (10 months to 6 years)	Combination of L. rhamnosus GG, L. rhamnosus LC705, B. breve 99, P. freudenreichii JS in capsules 8–9 × 109 cfu/capsule of each strain on 1 capsule daily	- Occurrence of AOM ↔ - Occurrence of recurrent (≥4) RTIs ↓ - Moraxella catarrhalis in the nasopharynx ↑
[59]			- HBoV DNA in the nasopharynx after 3–6 months (studied in 152 children) ↓
R DB PC 10–12 months [57]	72 healthy newborns (<2 months)	Combination of L. rhamnosus GG, B. animalis ssp. lactis Bb12 1010 cfu in capsules supplemented to infant formula once a day	During first 7 months of life: - Incidence of AOM ↓ - Antibiotic treatments ↓ - No. of RTIs ↔ During first 12 months of life: - Incidence of AOM ↔ - No. of recurrent RTIs ↓
R DB PC 3 months [58]	80 healthy children (8–13 years)	Combination of L. acidophilus (min. 109/capsule) and B. bifidum (min. 109/capsule) (strain information not provided) in capsules 2× daily	- Median duration of cold symptoms + school absence ↓ - Risk of fever, cough, rhinorrhea, school absence, and school absence related to common cold ↓
R DB PC 6–7 months [52]	109 healthy newborns (1 month old)	B. animalis ssp. lactis Bb12 (109 cfu/day) in tablet, 2× daily	- No. of RTIs ↓ - Occurrence of AOM ↔ - Symptoms of otitis media ↔
R DB PC 3 months [53]	201 healthy infants (4–10 months)	L. reuteri SD 112 (107 cfu/g) or B. animalis ssp. lactis Bb12 (107 cfu/g) in milk formula daily	L. reuteri vs. B. Bb12/control: - No. of days with fever, clinic visits, child care absences, and antibiotic prescriptions ↓ Both bacteria: - Rate and duration of RTIs ↔
R DB PC 5 months [50]	251 healthy school children (3–12 years)	L. casei DN 114001 2× daily in fermented yoghurt	- Incidence and duration (days) of RTI ↔ - Duration of lower RTIs ↓ - Incidence of lower RTI and fatigue ↓
CR DB PC 3 months [78]	638 healthy children (3–6 years)	L. casei DN 114001 (1 × 108 cfu/g ) in fermented dairy yoghurt drink: 1× bottle daily	- Incidence rate for CIDs ↓ - Incidence rate for URTIs ↓ - Missed day care/school or parental missed work ↔
R DB C 6 months [55]	494 healthy children (1–6 years)	L. casei CRL431(5 × 108 cfu/day) or L. reuteri DSM17938 (5 × 108 cfu/day) in milk (low or regular calcium)	- Incidence of acute RTIs ↔ - No. of RTI episodes ↔ - Duration of acute RTIs↔
R DB PC 6 months [51]	215 healthy infants (6 months)	L. fermentum CECT5716 (2 × 108 cfu/day) + GOS in formula daily	- Incidence ratio of URTIs ↓ - Incidence ratio of upper and lower RTIs↓
DBRC 3–7 months [49]	986 children (<5 years)	L. casei rhamnosus: 2 sachets (2× 108 cfu) daily or L. rhamnosus T cell-1: 3 tablets (1 × 1010 cfu) daily or combination of 12 bacteria (7× Lactobacilli, 3× Bifidobacteria, 1× Streptococcus, 1× Enterococcus 5 capsules daily (109 cfu/strain) 5 days a week	L. casei rhamnosus: - Incidence of bacterial infections ↓ - Doctor-diagnosed viral infection in 3 months ↓ - Doctor-diagnosed RTI in 3 and 7 months ↓ L. rhamnosus T cell-1: - Incidence of bacterial infections in 7 months ↓ Combination: - No. of RTIs ↔
Adults
R DB PC 1 month + 5 months follow-up (intramuscular anti-influenza vaccine) [61]	50 healthy adults (22–56 years)	L. fermentum CECT5716 in capsule (1010 cfu/day): 2 weeks before and 2 weeks after vaccination	- No. of RTIs ↓ - Antigen-specific IgA ↑
R DB PC C-O 1 month [67]	20 healthy elite male distance runners	L. fermentum VR1003 (1.3 × 1010 cfu/day), 3× capsules 2× daily	- Incidence of RTIs ↔ - No. of days with respiratory symptoms ↓ - Severity of symptoms ↔
R DB PC 11 weeks [68]	99 competitive cyclists (26–45 years)	L. fermentum PCC® (minimum 109 cfu/day) in capsules: 1× daily	- URTI illness load ↔ - Self-reported symptoms of lower RTI ↔ (↓ in men)
R DB PC 4 months [73]	1,000 shift workers (18–65 years)	L. casei DN 114001 (1010 cfu/g) in yoghurt drink, 2× 100-g bottle daily	- Cumulated number of CIDs ↓ - Proportion of volunteers experiencing at least 1 CID ↓ -No. of CIDs in the subgroup of smokers ↓ - Leukocyte, neutrophil, and natural killer cell counts and activity ↑
R DB PC 1 month [71]	47 healthy men in French commando training	L. casei DN 114001 in milk, 3× 100 ml/day during training	- Incidence of RTIs ↔ - Proportion of rhinopharyngitis ↑ - Symptoms of infection ↔
R DB PC 3 months [70]	141 marathon runners (22–69 years)	L. rhamnosus GG in milk 2× bottles daily (4 × 1010 cfu) or capsules 2× daily (1010 cfu)	- No. of RTI episodes (during training or 2 weeks after marathon) ↔ - No. of healthy days ↔
R DB PC 4 months [72]	66 healthy training adults (18–35 years)	L. salivarius(2 × 1010 cfu) powder in water daily for 16 weeks	- No. of RTI episodes ↔ - Severity and duration of URTI symptoms ↔
R DB PC 3 months [63]	479 healthy adults (18–67 years)	Combination of L. gasseri PA16/8 (4 × 107 cfu/tablet), B. longum SP07/3 (5 × 106 cfu/tablet), B. bifidum MF20/5 (5 × 106 cfu/tablet), vitamins, minerals, 1 tablet daily	- Duration of RTI episode ↓ - Severity of RTI symptoms ↔ - Duration of fever ↓
R DB PC 3–5 months [64]			- Number of RTI episodes ↔ - Duration of RTI episodes ↓ - Severity of RTI symptoms ↔
R DB PC 3–5.5 months [62]	477 healthy adults (23–49 years)		- Viral-induced incidence and duration of RTI ↔ - Days with fever ↓ - Duration of RTIs ↔
R DB PC over 150 days [65]	460 physically active adults (18 to 60 years)	B. animalis ssp. lactis Bl-04 2 × 109 cfu in sachet per day or L. acidophilus NCFM + B. animalis ssp. lactis Bi-07 5 × 109 cfu in sachet per day	Both bacteria groups: - 0.7 + 0.9 month delay in the median time to an illness episode - Duration of RTIs ↔ Only B. animalis: - Risk of URTI episode ↓
R DB PC 1 month [69]	30 rugby union players	Combination of L. gasseri (2.6 × 109 cfu), B. bifidum (0.2 × 109 cfu), and B. longum (0.2 × 109 cfu) 1× capsule daily	- Incidence of URTI ↔ - Incidence of any symptoms ↓ - Severity of symptoms ↔
R DB PC 3 months [66]	198 healthy college students (18–25 years)	Combination of L. rhamnosus GG + B. animalis ssp. lactis Bb12, 1× powder/stick (2 × 109 cfu) daily	- Median duration of URTI ↓ - Severity of URTI ↓ - No. of missed work days ↔ - Missed school days ↓
Elderly
R C (pilot) 3 weeks [74]	260 healthy elderly (>60 years)	L. casei DN 114001 in fermented yoghurt drink	- Incidence of RTI ↔ - Duration of RTI ↓
R DB PC 3 months [75]	1,072 elderly (≤70 years)	L. casei DN 114001 (≤1010 cfu/g) in yoghurt drink, 2 × 100 g daily	- Cumulative number or severity of CID ↔ - Average duration per episode of CID ↓ - Cumulative duration of CID ↓ - Average duration per episode of URTI ↓ - Cumulative duration of URTI ↓
R DB PC 5 months [76]	154 elderly (74–92 years)	L. casei Shirota (4 × 1010 cfu) in milk 1 × 80 ml daily	- No. of persons diagnosed with acute URTIs ↔ - No. of acute URTI events ↔ - Severity of URTIs ↔ - No. of acute URTI events/total days of observation ↔ - Mean duration of URTI per infection event ↓
R DB PC 176 days [77]	737 healthy people aged >65 years in nursing homes	L. casei Shirota (>6.5 × 109 live bacteria/bottle) in milk, 2× daily	- Duration of RTIs ↔ - No. of participants with RTI symptoms ↔ - Influenza vaccination immune response ↔
R DB PC 5 months [60]	265 institutionalized elderly (>65 years)	Combination of L. rhamnosus GG, L. rhamnosus LC705, B. breve 99, P. freudenreichii JS (8-9 × 109 cfu/capsule of each strain), 2× daily	- No. of RTIs ↔ - Duration of RTI episodes ↓ - Duration of RTI symptoms ↔

Abbreviations for columns:

Study design and duration: R DB PC = randomized double-blind placebo-controlled; CR = cluster-randomized; C-O = cross-over

Probiotics used: L = Lactobacillus; B = Bifidobacterium; P = Propionibacterium; cfu = colony-forming units; GOS = galactooligosaccharides

Main findings: probiotic vs. placebo: RTI = respiratory tract infection; URTI = upper respiratory tract infection, AOM = acute otitis media; CID = common infectious disease; Ig = immunoglobulin; HBoV = human bocavirus; HRV = human rhinovirus

↑ = significant increase; ↓ = significant decrease; ↔ = no significant effect