Pediatric Respiratory Tract Research Articles

Clinical Progress Note: Procalcitonin in the Management of Pediatric Lower Respiratory Tract Infection.

Procalcitonin (PCT) is a biomarker that has shown promise to identify bacterial etiology in acute infections, including bacterial lower respiratory tract infection (LRTI). In 2017, the United States Food and Drug Administration (FDA) approved the use of PCT as a diagnostic aid to guide the decisions around antibiotic therapy in acute LRTI.1 Although most of the data supporting the use of PCT for LRTI stems from adult studies, the high disease burden, predominance of viral etiologies, and frequent diagnostic uncertainty resulting in antibiotic overuse make pediatric LRTI an ideal target for the use of PCT as a diagnostic aid. This review evaluates and summarizes the current evidence regarding the role of PCT in the clinical care of pediatric LRTI, including its use in guiding antibiotic use and prognosticating disease severity.

The alpha-1 subunit of the Na+,K+-ATPase (ATP1A1) is required for macropinocytic entry of respiratory syncytial virus (RSV) in human respiratory epithelial cells.

Human respiratory syncytial virus (RSV) is the leading viral cause of acute pediatric lower respiratory tract infections worldwide, with no available vaccine or effective antiviral drug. To gain insight into virus-host interactions, we performed a genome-wide siRNA screen. The expression of over 20,000 cellular genes was individually knocked down in human airway epithelial A549 cells, followed by infection with RSV expressing green fluorescent protein (GFP). Knockdown of expression of the cellular ATP1A1 protein, which is the major subunit of the Na+,K+-ATPase of the plasma membrane, had one of the strongest inhibitory effects on GFP expression and viral titer. Inhibition was not observed for vesicular stomatitis virus, indicating that it was RSV-specific rather than a general effect. ATP1A1 formed clusters in the plasma membrane very early following RSV infection, which was independent of replication but dependent on the attachment glycoprotein G. RSV also triggered activation of ATP1A1, resulting in signaling by c-Src-kinase activity that transactivated epidermal growth factor receptor (EGFR) by Tyr845 phosphorylation. ATP1A1 signaling and activation of both c-Src and EGFR were found to be required for efficient RSV uptake. Signaling events downstream of EGFR culminated in the formation of macropinosomes. There was extensive uptake of RSV virions into macropinosomes at the beginning of infection, suggesting that this is a major route of RSV uptake, with fusion presumably occurring in the macropinosomes rather than at the plasma membrane. Important findings were validated in primary human small airway epithelial cells (HSAEC). In A549 cells and HSAEC, RSV uptake could be inhibited by the cardiotonic steroid ouabain and the digitoxigenin derivative PST2238 (rostafuroxin) that bind specifically to the ATP1A1 extracellular domain and block RSV-triggered EGFR Tyr845 phosphorylation. In conclusion, we identified ATP1A1 as a host protein essential for macropinocytic entry of RSV into respiratory epithelial cells, and identified PST2238 as a potential anti-RSV drug.

Comparative study of clinical and epidemiological characteristics of major pediatric adenovirus epidemics in southern Taiwan

BackgroundHuman adenoviruses (HAdV) are important pathogens of pediatric respiratory tract infections in Taiwan. There were two major HAdV epidemics in southern Taiwan in 2011 and 2014, respectively.MethodsThe demographic, clinical characteristics, and risk factors for hospitalization of pediatric patients with HAdV infection in the two outbreaks were retrospectively compared. The epidemic was defined as > 7% HAdV detection rate for six consecutive weeks. HAdV infection was defined as positive HAdV isolates from respiratory tract specimens. HAdV genotype was determined by PCR-based hexon gene sequencing.ResultsA total of 1145 pediatric patients were identified (635 cases in 2011; 510 cases in 2014). HAdV genotype 3 and 7 contributed to both epidemics, although the proportion of HAdV3 decreased significantly (64.7% in 2011 to 25.5% in 2014, p < 0.001) and was replaced by other genotypes (type 1, 4, and 6) in the 2014 epidemic. Among the hospitalized patients, there were more patients hospitalized with bronchopneumonia/or pneumonia in the 2011 epidemic (10.6% vs 5.1%, p < 0.001), while more patients hospitalized with acute pharyngitis/pharyngoconjunctival fever (63.9% vs. 38.6%, p < 0.001) in the 2014 epidemic. In both epidemics, hospitalized patients had higher WBC and C-reactive protein (CRP) levels than non-hospitalized patients. Using multivariate regression analysis, underlying disease and elevated CRP levels were independent risk factors for hospitalization in both epidemics.ConclusionThere were significant differences in clinical, viral characteristics and risk factors of hospitalization between the 2011 and 2014 epidemics. Understanding changes in the epidemiological and clinical characteristics of HAdV epidemics is important from a public health perspective.

Impact of Education and Peer Comparison on Antibiotic Prescribing for Pediatric Respiratory Tract Infections.

Inappropriate prescribing of broad-spectrum antibiotics is a significant modifiable risk factor for the development of antibiotic resistance. The objective was to improve guideline-concordant care for 3 common acute respiratory tract infections (ARTIs) and to reduce broad-spectrum antibiotic prescribing in ambulatory pediatric patients. Quality measures were developed for 3 ARTIs: viral upper respiratory infection (URI), acute bacterial sinusitis (ABS), and acute otitis media (AOM). Among 22 pediatric clinics, a collaborative of 10 was identified for intervention using baseline data for each ARTI, and 3 plan-do-study-act cycles were planned and completed. Outcomes included guideline-concordant antibiotic utilization and broad-spectrum antibiotic prescribing percentage (BSAP%). Comparison in number of diagnoses for the ARTI measures and total antibiotic prescribing over time served as balancing measures. Collaborative clinics had baseline medians for appropriate or first-line treatment of 70% for URI, 53% for ABS, and 36% for AOM. To reach targets for URI, ABS, and AOM required 6, 14, and 18 months, respectively. At 42 months, performance for all 3 ARTIs remained ≥90%. BSAP% decreased from a baseline of 57% to 34% at 24 months. There was a limited effect from financial incentives but a significant decrease was noted in total antibiotic utilization. Diagnosis shifting may have occurred for URI and ABS while the rates for diagnoses for AOM declined over time. Through education and peer comparison feedback, guideline-concordant care for 3 ARTIs in collaborative clinics improved and remained beyond above targets and was accompanied by reductions in BSAP% and total antibiotic prescribing.

Prevention of Pediatric Respiratory Syncytial Virus Lower Respiratory Tract Illness: Perspectives for the Next Decade.

The landscape of infant bronchiolitis and viral pneumonia may be altered by preventive interventions against respiratory syncytial virus under evaluation today. Pediatric wards in 2018 in developing countries may differ from those attended by future generation pediatricians who may not witness the packed emergency rooms, lack of available beds, or emergency situations that all physicians caring for children with RSV experience every year. In this review, we describe and discuss different prevention strategies under evaluation to protect pediatric patients. Then, we outline a number of potential challenges, benefits, and concerns that may result from successful interventions after licensure.

Reducing Primary Care Attendance Intentions for Pediatric Respiratory Tract Infections.

The aim of this study was to evaluate a theory and evidence-based, parent-targeted online intervention, combining microbiological local syndromic surveillance data, symptom information, and home-care advice, to reduce primary care attendance for self-limiting, low-risk pediatric respiratory tract infections (RTIs). The effect of this novel intervention on primary care attendance intentions was evaluated in an online experimental study. A representative sample of mothers (n = 806) was randomly assigned to receive the intervention material before (intervention) or after (control) answering questions concerning attendance intentions for an RTI illness scenario and mediating factors. Both groups provided feedback on the material. Group comparisons, linear regression, and path analyses were conducted. Intervention participants reported lower attendance intentions compared with control participants (d = 0.69, 95% CI, 0.55-0.83), an effect that remained when controlling for demographic and clinical characteristics (B = -1.62, 95% CI, -1.97 to -1.30). The path model highlighted that the intervention effect (B = -0.33, 95% CI, -0.40 to -0.26) was mostly indirect and mediated by infection and antibiotic knowledge, symptom severity concerns, and social norm perceptions concerning attendance. Information on when to attend was rated as the most important intervention component 227 times, followed by symptoms rated 186 times. Information on circulating viruses was rated as least important 274 times. The intervention was effective in reducing primary care attendance intentions by increasing knowledge, lowering attendance motivation, and reducing the need for additional resources. The contribution of individual intervention components and effects on behavioral outcomes requires further testing.

Primary care clinicians’ views of paediatric respiratory infection surveillance information to inform clinical decision-making: a qualitative study

AimTo investigate primary care clinicians’ views of a prototype locally relevant, real-time viral surveillance system to assist diagnostic decision-making and antibiotic prescribing for paediatric respiratory tract infections (RTI). Clinicians’ perspectives...

Biofilm Formations in Pediatric Respiratory Tract Infection Part 2: Mucosal Biofilm Formation by Respiratory Pathogens and Current and Future Therapeutic Strategies to Inhibit Biofilm Formation or Eradicate Established Biofilm.

The purpose of this review is to discuss the unique pathways of biofilm formation utilized by respiratory pathogens and current and future therapeutic strategies to inhibit biofilm formation or eradicate established biofilm in the context of these pathogens. Both nonselective and selective strategies for inhibiting biofilm formation or disrupting established biofilm are discussed. Numerous strategies are being actively pursued to inhibit biofilm formation or eradicate established biofilm in respiratory pathogens. These can be broadly categorized by the stage of biofilm formation (adhesion, extracellular polysaccharide synthesis or structure, EPS, and matrix degradation) that they target and by their selectivity or lack thereof for specific biofilm pathogens. Nonselective inhibitors of adhesion include N-acetylcysteine and artificial surfactants and biosurfactants. Selective inhibitors of adhesion include mannosides that target host-EPS interactions, EPS-targeted antibodies, and other inhibitors of bacterial adhesion. Nonselective inhibitors of EPS synthesis and structure include cyclic di-GMP and cyclic di-AMP-through disruption of glucan-producing exoenzymes. Selective inhibitors of EPS synthesis and structure include antibodies that target proteins essential for biofilm structure (such as DNABII proteins and type IV pilin protein in NTHi) or antibodies that target critical molecules in biofilm formation (such as DNA adenine methyltransferase in Streptococcus pneumoniae). Nonselective agents for EPS or biofilm matrix degradation include peptidoglycan hydrolases that enzymatically degrade bacterial cell wall peptidoglycan and DNase, which degrades extracellular DNA from neutrophils and microorganism-derived DNA. Selective agents for EPS or biofilm matrix degradation include exopolysaccharide-degrading enzymes, such as glycoside hydrolases active against Staphylococcus aureus or exopolysaccharide-degrading enzymes that target Psl and Pel from Pseudomonas aeruginosa. Current strategies toward inhibiting biofilm formation or disrupting established biofilm represent an exciting new approach toward treatment of chronic infectious diseases. Application of these strategies toward treatment of pediatric respiratory tract infections also offers promise of a better understanding of the significance of mucosal biofilm in the pathogenesis of these conditions.

Utility of the Neonatal Calf Model for Testing Vaccines and Intervention Strategies for Use against Human RSV Infection.

Respiratory syncytial virus (RSV) is a significant cause of pediatric respiratory tract infections. It is estimated that two-thirds of infants are infected with RSV during the first year of life and it is one of the leading causes of death in this age group worldwide. Similarly, bovine RSV is a primary viral pathogen in cases of pneumonia in young calves and plays a significant role in bovine respiratory disease complex. Importantly, naturally occurring infection of calves with bovine RSV shares many features in common with human RSV infection. Herein, we update our current understanding of RSV infection in cattle, with particular focus on similarities between the calf and human infection, and the recent reports in which the neonatal calf has been employed for the development and testing of vaccines and therapeutics which may be applied to hRSV infection in humans.

Pidotimod in the treatment of pediatric recurrent respiratory tract infection.

Objective:To observe the clinical efficacy of pidotimod in the treatment of recurrent respiratory tract infection in children.Methods:One hundred thirty-two patients with recurrent respiratory tract infection who received treatment in Tianan City Central Hospital were selected and divided into an observation group and a control group using random number table, 66 in each group. Patients in the control group were given conventional treatment, while patients in the observation group were given conventional treatment and pidotimod treatment; the clinical efficacy of the two therapies was compared. The levels of IgG and IgM were measured after treatment.Results:The vital signs and the content of inflammatory mediator and Th1/Th2 in serum before and after treatment were compared, and the clinical efficacy of the two groups was evaluated. The fever, pulmonary rale, cough and antiadoncus of patients in the observation group disappeared earlier than those in the control group (P<0.05). The onset duration of respiratory tract infection and days of antibiotic application of the observation group were shorter than those of the control group after treatment (P<0.05). The times of infection of the observation group were less than that of the control group (P<0.05). Before treatment, the two groups had no significant difference in the content of inflammatory mediators and Th1/Th2 in the serum (P>0.05). The serum content of tumor necrosis factor (TNF)-α and interleukin (IL)-4 of the two groups one week after treatment was lower than that before treatment, and the content of interferon (IFN)-γ and IFN-γ/IL-4 were higher than that before treatment; moreover the observation group had lower serum content of TFN-α and IL-4 and lower content of IFN-γ and IFN-γ/IL-4 compared to the control group (P<0.05). The overall response rate of the observation group was 92.4%, much higher than 81.8% in the control group (P<0.05).Conclusion:Pidotimod has a remarkable efficacy in the treatment of pediatric recurrent respiratory tract infection because it can effectively inhibit the infection and optimize Th1/Th2 immune function.

Detection of respiratory syncytial virus & Mycoplasma pneumoniae in paediatric lower respiratory tract infections.

Background & objectives:Respiratory syncytial virus (RSV) and Mycoplasma pneumoniae are considered common cause of lower respiratory tract infections (LRTIs) in children. The present study was conducted to detect M. pneumoniae and RSV in paediatric LRTIs employing serology, polymerase chain reaction (PCR) and reverse transcriptase PCR (RT-PCR) analysis.Methods:Seventy five children aged one month to five years with acute LRTIs were investigated for M. pneumoniae antibodies and RSV antigen using immunochromatographic test, RT-PCR for RSV and M. pneumoniae by PCR on nasopharyngeal aspirates.Results:RSV infection was observed in 33 (44%) and M. pneumoniae was positive in 26 (35%) children. No significant difference in infection was noted between male and female children. Clinical and radiological features among RSV and M. pneumoniae positive and negative cases were similar. Considering RT-PCR for RSV as gold standard, RSV antigen immunochromatography was 90.90 per cent sensitive and 100 per cent specific.Interpretation & conclusions:Our study showed the presence of RSV and M. pneumoniae infection in 44 and 35 per cent children, respectively with community-acquired LRTIs and aged less than five years.

Drug Prescription Pattern in Paediatric Respiratory Tract Infections

Drug Prescription Pattern in Paediatric Respiratory Tract Infections

The Qualitative Evaluation Of Antibiotics Used In Pediatric Respiratory Tract Infection Treatments At A Primary Hospital In Surabaya

Respiratory Tract Infections (RTIs) commonly occur as an infection in children. A considerable amount of antibiotics consumption is used to treat RTIs in many hospitals. Unwise antibiotic treatments in RTIs will increase bacterial resistance and treatment cost. This study aimed to investigate the quality or appropriateness of antibiotics use in RTI treatments in pediatric inpatients. A retrospective analysis of antibiotics consumption data was conducted through inpatient medical records for three months in 2017 at a primary hospital in Surabaya, Indonesia. The qualitative assessment was performed using a modified Gyssens algorithm based on the National Guideline and other relevant international standards of antibiotics applications in RTI treatment. The medical records of a total of 87 pediatric inpatients aged 0-14 y.o. were included in this study. The most common diagnosis was tonsillopharyngitis (32.18%), and the average length of hospital stay was 4.84 days. Antibiotics used in the treatments were from the class of -lactams and cephalosporins, all of which were applied in empirical therapy. According to the analysis, the antibiotic treatments were not appropriate. The most inappropriate use of antibiotics was in the form of wrong choice of drug choice (95.40%), followed by the sub-optimal duration of antibiotics (4.60%). The RTI treatment in pediatrics has to avoid any inappropriate uses of antibiotics, which can be achieved through the evaluation of institutional policy against the local guideline, antibiogram, or any relevant international guidelines.

738. Role of Respiratory Syncytial Virus and Mycoplasma pneumoniae in Pediatric Community-Acquired Lower Respiratory Tract Infections

BackgroundRespiratory syncytial virus (RSV) infection is a major cause of serious lower respiratory disease in infancy and early childhood and Mycoplasma pneumoniae (M. pneumoniae) is a common cause of respiratory tract infections in all age groups. This study was conducted to determine the role of RSV and M. pneumoniae and in pediatric lower respiratory tract infections employing serological tests, polymerase chain reaction (PCR) and reverse transcriptase PCR analysis.MethodsIn this prospective study, 75 children aged 1 month to 5 years with acute lower respiratory tract infections (LRTIs) were investigated. Paired serum samples were obtained on admission and after 4–6 weeks to assay for M. pneumonia antibodies. Nasopharyngeal aspirates were obtained for the detection of RSV antigen by using the immunochromatographic test, reverse transcriptase-polymerase chain reaction (RT-PCR) for RSV and M. pneumoniae by PCR.ResultsRSV infection was positive in 20(60.60%) children aged <1 year and 13 (39.40%) aged 2–5 years, the difference being statistically insignificant (P = 0.360). M. pneumoniae infection was documented in a 15(57.6%) children aged <1 year age and 11(42.4%) in age 2–5 years which was statistically significant(P = 0.026). Clinical and radiological features among RSV and M. pnemoniae positive and negative cases were comparable. Thirty (40%) children were positive for RSV antigen and by RT-PCR and 3(12%) only by RT-PCR. Serological evidence of M pneumoniae infection was documented in 24(32%) children. M. pnemoniae PCR was positive in 8 (10.66%) patients. Together, serology and PCR detected M. pneumoniae in 26(34.66%) children. Considering RT-PCR as a diagnostic standard, the sensitivity of RSV antigen by immunochromatography was 90.90%, specificity 100%, positive predictive value 100% and a negative predictive value of 93.3%.The sensitivity of M. pneumoniae serology was 75%, specificity 73.3%, positive predictive value 25% and a negative predictive value of 96% considering PCR as a diagnostic standard,.ConclusionOur data underline the role of RSV and M. pneumoniae as the major cause of community-acquired lower respiratory tract infections in children aged <5 years.Disclosures All authors: No reported disclosures.

170. Characterization of Appropriate Antibiotic Prescribing for Pediatric Respiratory Tract Infections: Setting the Stage for Stewardship

BackgroundInappropriate antibiotic use includes prescribing for antibiotic inappropriate diagnoses and use of broad-spectrum instead of narrow-spectrum therapies and contributes to adverse events and antibiotic resistance. To guide the design and implementation of antibiotic stewardship interventions in a network of pediatric clinics, we sought to characterize appropriate antibiotic prescribing for children diagnosed with uncomplicated respiratory infections.MethodsRetrospective cohort study of visits by children to one of 31 primary care or six urgent care clinics in a university healthcare system between January 1, 2016 and December 31, 2017. Two outcomes were used to characterize antibiotic prescribing: (1) percentage of antibiotic inappropriate diagnoses (bronchitis, bronchiolitis, upper respiratory infection) that were prescribed an antibiotic; (2) percentage of visits with a diagnosis for acute otitis media (AOM), sinusitis, or pharyngitis prescribed first-line recommended antibiotics (amoxicillin or penicillin). Children with a documented penicillin allergy or antibiotic prescriptions in the previous 30 days were excluded. Chi-square tests were used to compare prescribing between settings.ResultsAmong 117,279 total visits examined, 16,760 (14%) were for antibiotic inappropriate diagnoses, 5,912 (5%) for AOM, 844 (1%) for sinusitis and 4,912 (4%) for pharyngitis. Only 3% (95% CI: 2.9–3.4) of antibiotic inappropriate diagnoses were prescribed antibiotics. The percent of visits for AOM, sinusitis, and pharyngitis prescribed first-line antibiotics ranged from 27% (95% CI: 21–33) for sinusitis in urgent care to 91% (95% CI: 90–92) for pharyngitis in urgent care (figure). Differences in appropriate prescribing by setting were observed for AOM (P < 0.01) and sinusitis (P < 0.01).ConclusionIn this network of pediatric practices, we found minimal evidence of unnecessary antibiotic use for respiratory infections but substantial underuse of first-line therapy for sinusitis, especially in urgent care settings. Stewardship interventions designed to reinforce existing practices for antibiotic-inappropriate conditions and promote greater use of appropriate first-line therapies are planned for this setting. Disclosures All authors: No reported disclosures.

Clinical efficacy of Golden Lotus granules combined with ribavirin in the treatment of pediatric acute upper respiratory tract infection and its effect on serum inflammatory markers

目的 探讨金莲花颗粒联合利巴韦林治疗小儿急性上呼吸道感染的疗效及其对血清炎症标记物的影响。 方法 选取2014年1月至2016年12月安吉县中医医院急性上呼吸道感染的患儿116例，采用随机数字表法分为观察组和对照组，每组58例。两组患儿均给予支持治疗，对照组给予利巴韦林颗粒，观察组在对照组的基础上给予金莲花颗粒。两组疗程均为1周。比较两组治疗疗效，临床症状积分，血清C反应蛋白(CRP)和肿瘤坏死因子因子α(TNF-α)水平的变化，并建立ROC曲线，分析CRP和TNF-α的曲线下面积(AUC)，敏感性和特异性。 结果 观察组的临床总有效率为94.8%，显著高于对照组的77.5%，差异有统计学意义(χ2＝9.854，P<0.05)；治疗后观察组咳嗽、发热和咽喉肿痛积分均显著低于对照组，差异均有统计学意义(t＝－30.698、－29.786、－33.377，均P<0.01)，其血清CRP和TNF-α水平均均显著低于对照组，差异有统计学意义(t＝－11.3528、－17.4182，均P<0.01)；ROC曲线分析可知TNF-α的AUC、敏感度和特异度最高，分别为0.820、85.8%和80.0%。 结论 金莲花颗粒联合利巴韦林治疗小儿急性上呼吸道感染的临床疗效明确，其作用机制可能与下调CRP和TNF-α的水平有关，其中TNF-α对小儿支气管肺炎具有较高的诊断价值。

Application of chromatographic assay and reverse transcriptase polymerase chain reaction for detection of respiratory syncytial virus in pediatric community-acquired lower respiratory tract infections

Application of chromatographic assay and reverse transcriptase polymerase chain reaction for detection of respiratory syncytial virus in pediatric community-acquired lower respiratory tract infections

Developmental Regulation of Effector and Resident Memory T Cell Generation during Pediatric Viral Respiratory Tract Infection.

Viral respiratory tract infections (VRTI) remain a leading cause of morbidity and mortality among infants and young children. In mice, optimal protection to VRTI is mediated by recruitment of effector T cells to the lungs and respiratory tract, and subsequent establishment of tissue resident memory T cells (Trm), which provide long-term protection. These critical processes of T cell recruitment to the respiratory tract, their role in disease pathogenesis, and establishment of local protective immunity remain undefined in pediatric VRTI. In this study, we investigated T cell responses in the upper respiratory tract (URT) and lower respiratory tract (LRT) of infants and young children with VRTI, revealing developmental regulation of T cell differentiation and Trm generation in situ. We show a direct concurrence between T cell responses in the URT and LRT, including a preponderance of effector CD8+ T cells that was associated with disease severity. During infant VRTI, there was an accumulation of terminally differentiated effector cells (effector memory RA+ T cells) in the URT and LRT with reduced Trm in the early neonatal period, and decreased effector memory RA+ T cell and increased Trm formation with age during the early years of childhood. Moreover, human infant T cells exhibit increased expression of the transcription factor T-bet compared with adult T cells, suggesting a mechanism for preferential generation of effector over Trm. The developmental regulation of respiratory T cell responses as revealed in the present study is important for diagnosing, monitoring, and treating VRTI in the critical early life stages.

Judicious Use of Antibiotics and Radiologic Imaging in Diagnosis and Management of Pediatric Upper Respiratory Tract Infections

AbstractA considerable amount of effort has been put into the reduction of the overuse of antibiotics and reduction in radiographic studies in the pediatric population. Infections within the ear, nose, and throat and in cervical regions are a frequent source of antibiotic use in children. Quality improvement projects creating clear care pathways have been important to delineate which imaging may be most helpful.

Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence.

Purpose of reviewTo provide an overview of the mechanistic and clinical evidence for the use of nonspecific immunomodulators in paediatric respiratory tract infection (RTI) and wheezing/asthma prophylaxis.Recent findingsNonspecific immunomodulators have a long history of empirical use for the prevention of RTIs in vulnerable populations, such as children. The past decade has seen an increase in both the number and quality of studies providing mechanistic and clinical evidence for the prophylactic potential of nonspecific immunomodulators against both respiratory infections and wheezing/asthma in the paediatric population. Orally administered immunomodulators result in the mounting of innate and adaptive immune responses to infection in the respiratory mucosa and anti-inflammatory effects in proinflammatory environments. Clinical data reflect these mechanistic effects in reductions in the recurrence of respiratory infections and wheezing events in high-risk paediatric populations. A new generation of clinical studies is currently underway with the power to position the nonspecific bacterial lysate immunomodulator OM-85 as a potential antiasthma prophylactic.SummaryAn established mechanistic and clinical role for prophylaxis against paediatric respiratory infections by nonspecific immunomodulators exists. Clinical trials underway promise to provide high-quality data to establish whether a similar role exists in wheezing/asthma prevention.