Role of multi-strain probiotics in preventing severity and frequency of recurrent respiratory tract infections in children

Respiratory tract infections (RTIs) are among the most common infections in the pediatric population throughout the globe. In developing countries like Pakistan, RTIs (especially pneumonia) are among the leading cause of mortality in children below five years of age [1]. Globally around 20% of all deaths in children below five years of age are secondary to acute respiratory infections, mostly pneumonia [2]. Pneumonia is the leading cause of death in children with worldwide deaths reported up to 740,180 children under the age of 5 in 2019. Most of these deaths were reported in developing countries from South Asia and sub-Saharan Africa [3]. As per WHO data, pneumonia cause 11.5% of deaths in children below five years of age in Pakistan and is the leading cause of death after the neonatal age period during which prematurity and birth asphyxia are the leading causes [4].

Recurrent respiratory tract infections (RRTIs) are common in children, especially in infants and young children, primarily due to their naïve immune system that is not sensitized to environmental pathogens. Studies show that 25% of infants and 6% of children below six years experience RRTIs [5, 6]. RTIs are also one of the leading causes of inadvertent antibiotic administration, thereby increasing their resistance [7]. Due to the high burden of RRTIs, studies have been done on alternative strategies for their prevention in children. Some studies have shown that probiotics and vitamin C supplementation decrease the duration and frequency of RRTIs [8, 9], while others found no beneficial effect of both these strategies [10, 11].

Probiotics are live microorganisms, when administered in adequate amount confer a health benefit on the host [10]. Although gut probiotics are thought to adhere to the mucosal lining, thereby preventing infective organisms from adherence to mucosa and causing disease, their mechanism in preventing respiratory tract infections is not known. It is supposed that probiotics act by modulating the immune system [12], but this hypothesis was also nullified by Garaiova et al. who found no significant change in cytokines [13].

Respiratory tract infections are common in Pakistan and other developing countries, primarily due to malnutrition, poor vaccination coverage, poor sanitation, large joint families and many other issues. Unfortunately, no proper strategies are developed and no research is done in this part of the world on the factors to decrease RRTIs. Clinical research using probiotic formulations has shown that it improves GI and immunological functioning in young infants and children. Unfortunately, no significant data is available (especially from low-middle-income countries) on whether these formulations are effective in preventing RRTIs and decreasing their severity or not. Therefore, we conducted this study on the local population to find out whether this simple strategy of using probiotics is effective in decreasing the severity and frequency of RRTIs or not. If found effective this may be incorporated into the national health system and policymakers be notified to start mass usage of probiotics for high-risk children.

Out of 70 children, 39 (i.e. 55.71%) were male and 31 (i.e. 44.29%) female with male to female ratio of 1.2:1. Most of the children were below 12 months of age (i.e. 41.43%) and overall around 75% of the children were below 5 years of the age, Table 1.

The most common presenting complaints among the patients with recurrent respiratory tract infections were fever, which was present in 72.86% of the patients, followed by cough (68.57%), wheezes (45.71%) and nasal discharge/sneezing (32.86%), respectively. Other common presenting complaints were earache/ear discharge (27.14%), sore throat (25.71%), respiratory distress (12.86%) and headache (8.57%). Table 2.

The most common RRTI was Infectious rhinitis which was diagnosed in 30% of the children, followed by otitis media (24%) and pharyngitis/tonsillitis (21%), Fig. 1. After giving probiotics for 2 weeks, we followed these patients for the next 6 months. There was a significant decrease in RRTIs at 6 months after the use of probiotics. The most significant decrease (p-value less than 0.05) was found in recurrent infectious rhinitis (17.14% percentage decrease) followed by recurrent otitis media and recurrent bronchiolitis. Table 3 shows the frequency and percentage of RRTIs before and after 6 months of probiotics, along with the percentage decrease in RRTIs.

In recent years, the effect of probiotics on immune function has been a hot topic in many diseases. Studies have shown that microbiome given in the form of probiotics (whether pharmaceutical or natural foods) causes immunomodulation that leads to decreased episodes of gut and respiratory tract infections [17, 18]. In the gut, probiotics play a safeguarding role by improving intestinal barrier functionaries along with immune-modulatory functioning by generating and modulating helper T cells [19]. However, their effectiveness in the prevention of respiratory tract infections is not much studied. Studies done in pediatric and geriatric patients show that when probiotics are given in combination, fewer incidences of respiratory tract infections were observed as compared to placebo [19, 20].

In this study, we observed that when patients with RRTIs were given probiotics containing a combination of stains for two weeks, there was a significant decrease in RRTIs over the next six months. All RRTIs episodes decreased over the next six months but the most significant decrease was found in recurrent infectious rhinitis, recurrent otitis media and recurrent bronchiolitis. A randomized controlled trial (RCT) based systemic review done by de Araujo et al. showed that all those children who were given probiotics and followed over 6–7 months showed a decrease in new disease episodes, decrease in disease symptoms and duration of disease episodes as compared to placebo-controlled patients. The drawback of this systemic review is that it includes all RCTs from developed countries [21]. Another study by Li et al. also showed that children who received multi-strain probiotics for two months had lesser episodes of RTIs and the need for antibiotics was also decreased as compared to the control group [22].

The duration for which probiotics should be given to assess their effects is not variably studied. Some authors have given probiotics for longer durations while some for just a few days. In our study, we gave probiotics for two weeks and assessed whether it is effective in decreasing the severity and frequency of RRTIs over the next six months. Skovbjerg et al. gave probiotics for ten days only and found a decrease in respiratory disease symptoms, while Rautava et al. gave probiotics till 11 to 12 months of life and found decreased episodes of acute otitis media in the first year of life [23, 24]. Similarly, Li et al. gave multi-strain probiotics for two months and found that these children had lesser episodes of RTIs [22].

In our study, we gave a combination of probiotics that is lactobacillus and bifidobacterium and found that these are effective enough to decrease the episodes and severity of many of the RRTIs. Taipale et al. gave Bifidobacterium subspecies lactis in infants and found that it decreased the episodes of RTIs in infants [25]. Rutava et al. found that giving lactobacillus and bifidobacterium-containing probiotics to the infants before first two months of life, decreases the incidence of RRTIs and the need for antibiotics usage over the next 6–7 months of life [24]. A study done by Hojsak et al. on hospitalized Croatian children found that those who received lactobacillus probiotic-containing milk were less likely to suffer from RTI than the placebo group [26].

The results of our study indicate that the administration of probiotics may be useful in reducing recurrent respiratory tract infections among children. This six months trial has demonstrated that there was a significant decline in respiratory symptoms among study participants. The study also observed a significant decrease in respiratory diseases during the follow-up. Further large-scale, well-designed, randomized, multicenter trials are required to validate the current findings and determine the effectiveness of different strains of probiotics.