Nirsevimab Effectiveness Against Cases of Respiratory Syncytial Virus Bronchiolitis Hospitalised in Paediatric Intensive Care Units in France, September 2023-January 2024.

In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory syncytial virus (RSV). Using data from a network of paediatric intensive care units (PICUs), we aimed to estimate nirsevimab effectiveness against severe cases of RSV bronchiolitis in France. We conducted a case-control study based on the test-negative design and included 288 infants reported by 20 PICUs. We estimated nirsevimab effectiveness at 75.9% (48.5-88.7) in the main analysis and 80.6% (61.6-90.3) and 80.4% (61.7-89.9) in two sensitivity analyses. These real-world estimates confirmed the efficacy observed in clinical studies.

Acute viral bronchiolitis phenotype in response to glucocorticoid and bronchodilator treatment.

OBJECTIVE: To analyze whether infants admitted to hospital with Acute Viral Bronchiolitis (AVB), who received glucocorticoids and bronchodilators, and who had an atopic phenotype, spent less time in hospital and/or less time on oxygen therapy when compared to those who did not have the phenotype. METHOD: A cross-sectional, retrospective epidemiological study was developed with data from medical records of infants admitted to hospital due to AVB from 2012 to 2019 in a sentinel public hospital. It was verified that the frequency of prescription of glucocorticoids, bronchodilators and antibiotics. Length of stay and oxygen therapy duration were then compared in the group that used glucocorticoids and bronchodilators between those who had a personal or family history of atopy and those who did not. Subsequently, the length of hospital stay was compared among infants who received antibiotic therapy and those who did not. RESULTS: Fifty-eight infants were included. Of these, 62.1 % received an antibiotic, 100 % a bronchodilator and 98.3 % a glucocorticoid. When comparing infants without a family history of atopy, those who received antibiotics had a longer hospital stay (p = 0.01). CONCLUSION: The presence of an atopic phenotype did not interfere with the length of stay and/or oxygen therapy duration of those who received bronchodilators and glucocorticoids. Increased length of stay of infants without a family history of atopy, who used antibiotics without evidence of bacterial co-infection, and the high frequency of prescription of non-recommended drugs call attention to stricter protocol implementation and professional training in AVB diagnosis and care.

Azithromycin therapy in infants hospitalized for respiratory syncytial virus bronchiolitis: Airway matrix metalloproteinase-9 levels and subsequent recurrent wheeze.

BACKGROUND: Early life respiratory syncytial virus (RSV) bronchiolitis is a significant risk factor for childhood asthma. In vitro and in vivo studies suggested that decreasing levels of airway matrix metalloproteinase (MMP)-9 during RSV bronchiolitis may be associated with clinical benefits. OBJECTIVE: To investigate whether azithromycin therapy during severe RSV bronchiolitis reduces upper airway MMP-9 levels, whether upper airway MMP-9 levels correlate with upper airway interleukin IL-8 levels, and whether MMP-9 level reduction is associated with reduced post-RSV recurrent wheeze (RW). METHODS: A total of 200 otherwise healthy 1- to 18-month-old infants hospitalized with RSV bronchiolitis were randomized into a double-blind, placebo-controlled trial of oral azithromycin (10 mg/kg daily for 7 days followed by 5 mg/kg daily for 7 days) or placebo. Infants were followed for 2 to 4 years for the outcome of RW (3 or more wheezing episodes). Nasal lavage samples for MMP-9 levels were obtained at baseline, day 14 (end of the study treatment), and after 6 months. RESULTS: Upper airway MMP-9 levels were highly correlated with IL-8 levels at all 3 time points: randomization, day 14, and 6 months (r = 0.80; P < .0001 for all time points). MMP-9 levels were similar between treatment groups at randomization, were lower on day 14 among children treated with azithromycin (P = .0085), but no longer different after 6 months. MMP-9 levels at baseline and change from baseline to day 14 were not associated with the development of RW (P = .49, .39, respectively). CONCLUSION: Azithromycin therapy in children hospitalized with RSV bronchiolitis had a short-term anti-inflammatory effect in reducing upper airway MMP-9 levels. However, the reduction in MMP-9 levels did not relate to subsequent RW post-RSV. TRIAL REGISTRATION: This study is a secondary analysis of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis-II clinical trial registered at Clinicaltrials.gov (NCT02911935).

Bronchiolitis versus bronchopneumonia: navigating antibiotic use within the LRTI spectrum.

Bronchiolitis, a common reason for infant hospitalisation in South Africa (SA), is caused by viral pathogens. Bronchiolitis is typically an illness of mild to moderate severity that occurs in well-nourished children. Hospitalised SA infants frequently have severe disease and/or coexisting medical conditions, and these cases of bronchiolitis may have bacterial co-infection that requires antibiotic therapy. However, the existence of widespread antimicrobial resistance in SA warrants the judicious use of antibiotics. This commentary describes: (i) common clinical pitfalls leading to an incorrect diagnosis of bronchopneumonia; and (ii) considerations for antibiotic therapy in hospitalised infants with bronchiolitis. If antibiotics are prescribed, the indication for their use should be clearly stated, and antibiotic therapy must be stopped promptly if investigations indicate that bacterial co-infection is unlikely. Until more robust data emerge, we recommend a pragmatic management strategy to inform antibiotic use in hospitalised SA infants with bronchiolitis in whom bacterial co-infection is suspected.

For which infants with viral bronchiolitis could it be deemed appropriate to use albuterol, at least on a therapeutic trial basis?

Although there is increasing evidence showing that infants with viral bronchiolitis exhibit a high degree of heterogeneity, a core uncertainty shared by many clinicians is with regard to understanding which patients are most likely to benefit from bronchodilators such as albuterol. Based on our review, we concluded that older infants with rhinovirus (RV) bronchiolitis, especially those with a nasopharyngeal microbiome dominated by Haemophilus influenzae; those affected during nonpeak months or during non-respiratory syncytial virus (RSV) predominant months; those with wheezing at presentation; those with clinical characteristics such as atopic dermatitis or a family history of asthma in a first-degree relative; and those infants infected with RSV genotypes ON1 and BA, have the greatest likelihood of benefiting from albuterol. Presently, this patient profile could serve as the basis for rational albuterol administration in patients with viral bronchiolitis, at least on a therapeutic trial basis, and it could also be the starting point for future targeted randomized clinical trials (RCTs) on the use of albuterol among a subset of infants with bronchiolitis.

For which infants with viral bronchiolitis could it be deemed appropriate to use albuterol, at least on a therapeutic trial basis?

Although there is increasing evidence showing that infants with viral bronchiolitis exhibit a high degree of heterogeneity, a core uncertainty shared by many clinicians is with regard to understanding which patients are most likely to benefit from bronchodilators such as albuterol. Based on our review, we concluded that older infants with rhinovirus (RV) bronchiolitis, espe­cially those with a nasopharyngeal microbiome dominated by Haemophilus influenzae; those affected during nonpeak months or during non-respiratory syncytial virus (RSV) predominant months; those with wheezing at presentation; those with clinical characteristics such as atopic dermatitis or a family history of asthma in a first-degree relative; and those infants infected with RSV genotypes ON1 and BA, have the greatest likelihood of benefiting from albuterol. Presently, this patient profile could serve as the basis for rational albuterol administration in patients with viral bronchiolitis, at least on a therapeutic trial basis, and it could also be the starting point for future targeted randomized clinical trials (RCTs) on the use of albuterol among a subset of infants with bronchiolitis

No disponible

Cost-effectiveness analysis of phenotypic-guided versus guidelines-guided bronchodilator therapy in viral bronchiolitis.

OBJECTIVES: Although recent evidence suggests that management of viral bronchiolitis requires something other than guidelines-guided therapy, there is a lack of evidence supporting the economic benefits of phenotypic-guided bronchodilator therapy for treating this disease. The aim of the present study was to compare the cost-effectiveness of phenotypic-guided versus guidelines-guided bronchodilator therapy in infants with viral bronchiolitis. METHODS: A decision analysis model was developed to compare the cost-effectiveness of phenotypic-guided versus guidelines-guided bronchodilator therapy in infants with viral bronchiolitis. Phenotypic-guided bronchodilator therapy was defined as the administration of albuterol in infants exhibiting a profile of increased likelihood of response to bronchodilators. The effectiveness parameters and costs of the model were obtained from systematic reviews of the literature with meta-analyses and electronic medical records. The main outcome was the avoidance of hospital admission after initial care in the emergency department. RESULTS: Compared to guidelines-guided strategy, treating patients with viral bronchiolitis with the phenotypic-guided bronchodilator therapy strategy was associated with lower total costs (US$250.99; 95% uncertainty interval [UI]: US$184.37 to $336.51 vs. US$263.46; 95% UI: US$189.81 to $349.19 average cost per patient) and a higher probability of avoidance of hospital admission (0.7902; 95% UI: 0.7315-0.8356 vs. 0.7638; 95% UI: 0.7062-0.8201), thus leading to dominance. Results were robust to deterministic and probabilistic sensitivity analyses. CONCLUSIONS: Compared to guidelines-guided strategy, treating infants with viral bronchiolitis using the phenotypic-guided bronchodilator therapy strategy is a more cost-effective strategy, because it involves a lower probability of hospital admission at lower total treatment costs.

The traditional use of southern African medicinal plants in the treatment of viral respiratory diseases: A review of the ethnobotany and scientific evaluations.

ETHNOPHARMACOLOGICAL RELEVANCE: Viral respiratory infections are amongst the most common infections globally, with most of the world's population contracting at least one infection annually. Numerous plant species are used in traditional southern African healing systems to treat these diseases and to alleviate the symptoms. Despite this, the therapeutic potential of these plants against viral respiratory diseases remains poorly explored. AIM OF THE STUDY: The aim of this study was to document the southern African plant species used in traditional medicine to treat viral respiratory infections. We also examined the extent of scientific evaluations of southern African plant species against the respiratory-infective viruses, with the aim of stimulating interest in this area and focusing on future studies. MATERIALS AND METHODS: We undertook an extensive review of ethnobotanical books, reviews and primary scientific studies to identify southern African plants which are used in traditional southern African medicine to treat viral respiratory diseases. This information was used to identify gaps in the current research that require further study. RESULTS: Two hundred and fifty-seven southern African plant species were identified as traditional therapies for viral respiratory diseases. Surprisingly, only one of those species (as well as twenty-one other species not recorded for these purposes) has been evaluated for the ability to block respiratory virus production. Furthermore, most of these studies screened against a single viral strain and none of those studies examined the mechanism of action of the plant preparations. CONCLUSIONS: Despite well documented records of the use of southern African plants to treat respiratory viral diseases, the field is poorly explored. Nearly all of the plant species used in traditional healing systems to treat these diseases are yet to be tested. Substantial further work is required to verify the efficacy of these traditional medicines.

Rational use of mucoactive medications to treat pediatric airway disease.

Many airway diseases in children, notably bronchiolitis, cystic fibrosis (CF), non-CF bronchiectasis including primary ciliary dyskinesia, pneumonia, and severe asthma are associated with retention of airway secretions. Medications to improve secretions clearance, the mucoactive medications, are employed to treat these diseases with varying degrees of success. This manuscript reviews evidence for the use of these medications and future directions of study.

Conditions of vulnerability to the inadequate treatment of bronchiolitis.

OBJECTIVE: To analyze clinical and demographic variables possibly associated with the prescriptions of non-recommended but routinely used therapies for infants with acute viral bronchiolitis. METHODS: A cross-sectional study included hospitalized infants with bronchiolitis caused by the respiratory syncytial virus. Those with other associated infections and/or morbidities were excluded. The data were collected from medical records. RESULTS: Among 120 cases, 90% used inhaled beta-agonists, 72.5% corticosteroids, 40% antibiotics, and 66.7% inhaled hypertonic saline solution. The use of bronchodilators did not present an independent association with another variable. More frequent use of corticosteroids was associated with low oximetry, longer hospitalization time, and age>3 months. Antibiotic therapy was associated with the presence of fever, longer hospitalization, and age>3 months. Inhaled hypertonic saline solution was associated with longer hospitalization time. CONCLUSIONS: Non-recommended prescriptions were frequent. Corticosteroid and antibiotic therapy were associated with signs of severity, as expected, but interestingly, they were more frequently used in infants above 3m, which suggested less safety in the diagnosis of viral bronchiolitis in these patients. The use of bronchodilators was even more worrying since they were indiscriminately used, without association with another variable related to the severity or characteristics of the host. The use of the inhaled hypertonic solution, although not associated with severity, seems to have implied a longer hospitalization time. The identification of these conditions of greater vulnerability to the prescription of inappropriate therapies contributes to the implantation of protocols for the bronchiolitis treatment, for continuing education and for analysis of the effectiveness of the strategies employed.

Predictors for the prescription of albuterol in infants hospitalized for viral bronchiolitis.

INTRODUCTION AND OBJECTIVES: Despite the recommendation against routine use of inhaled bronchodilators in infants with viral bronchiolitis given in the main clinical practice guidelines (CPGs) on viral bronchiolitis, albuterol is widely prescribed to patients with this disease. The aim of this study was to identify predictors of prescription of albuterol in a population of infants hospitalized for viral bronchiolitis. MATERIAL AND METHODS: An analytical cross-sectional study performed during the period from March 2014 to August 2015, in a random sample of patients <2 years old hospitalized in the Fundacion Hospital La Misericordia, a hospital located in Bogota, Colombia. After reviewing the electronic medical records, we collected demographic, clinical, and disease-related information, including prescription of albuterol at any time during the course of hospitalization as the outcome variable. RESULTS: For a total of 1365 study participants, 1042 (76.3%) were prescribed with albuterol therapy. After controlling for potential confounders, it was found that age (OR 1.11; CI 95% 1.08-1.15; p<0.001), and a prolonged length of stay (LOS) (OR 1.93; CI 95% 1.44-2.60; p<0.001) were independent predictors of prescription of albuterol in our sample of patients. By contrast, albuterol prescription was less likely in the post-guideline assessment period (OR 0.41; CI 95% 0.31-0.54; p<0.001), and in infants with RSV isolation (OR 0.71; CI 95% 0.52-0.97; p=0.035). CONCLUSIONS: Albuterol was highly prescribed in our population of inpatients with the disease. The independent predictors of prescription of albuterol in our sample of patients were age, implementation of a CPG on viral bronchiolitis, RSV isolation, and LOS.

Conditions of vulnerability to the inadequate treatment of bronchiolitis

SUMMARY OBJECTIVE To analyze clinical and demographic variables possibly associated with the prescriptions of non-recommended but routinely used therapies for infants with acute viral bronchiolitis. METHODS A cross-sectional study included hospitalized infants with bronchiolitis caused by the respiratory syncytial virus. Those with other associated infections and/or morbidities were excluded. The data were collected from medical records. RESULTS Among 120 cases, 90% used inhaled beta-agonists, 72.5% corticosteroids, 40% antibiotics, and 66.7% inhaled hypertonic saline solution. The use of bronchodilators did not present an independent association with another variable. More frequent use of corticosteroids was associated with low oximetry, longer hospitalization time, and age>3 months. Antibiotic therapy was associated with the presence of fever, longer hospitalization, and age>3 months. Inhaled hypertonic saline solution was associated with longer hospitalization time. CONCLUSIONS Non-recommended prescriptions were frequent. Corticosteroid and antibiotic therapy were associated with signs of severity, as expected, but interestingly, they were more frequently used in infants above 3m, which suggested less safety in the diagnosis of viral bronchiolitis in these patients. The use of bronchodilators was even more worrying since they were indiscriminately used, without association with another variable related to the severity or characteristics of the host. The use of the inhaled hypertonic solution, although not associated with severity, seems to have implied a longer hospitalization time. The identification of these conditions of greater vulnerability to the prescription of inappropriate therapies contributes to the implantation of protocols for the bronchiolitis treatment, for continuing education and for analysis of the effectiveness of the strategies employed.

RESUMO OBJETIVOS Analisar variáveis clínicas e demográficas possivelmente associadas às prescrições de terapêuticas não recomendadas, porém rotineiramente utilizadas, para lactentes com bronquiolite viral aguda. MÉTODOS Estudo transversal incluiu lactentes hospitalizados com bronquiolite por vírus sincicial respiratório. Excluídos aqueles com outras infecções e/ou morbidades. Dados coletados de prontuários. RESULTADOS Analisados 120 casos, para os quais foram prescritos: beta-agonistas inalatórios a 90%; corticosteroides a 72,5%, antibióticos a 40% e solução salina hipertônica inalatória a 66,7%. O uso de broncodilatadores não apresentou associação independente com outra variável. Maior uso de corticosteroide associou-se à baixa oximetria, maior tempo de internação e idade >3 meses. Antibioticoterapia associou-se à presença de febre, maior tempo de internação e idade >3 meses. Solução salina hipertônica inalatória associou-se a maior tempo de internação. CONCLUSÕES A frequência das prescrições não recomendadas foi elevada. Corticosteroide e antibioticoterapia foram associados a sinais de gravidade, como esperado, porém, interessantemente, foram mais utilizados nos lactentes com idade acima de 3 meses, o que sugeriu menor segurança no diagnóstico de bronquiolite viral nesses pacientes. O uso de broncodilatadores foi ainda mais preocupante, uma vez que foram indiscriminadamente utilizados, sem associação com outra variável, seja relacionada à gravidade, seja a características do hospedeiro. O uso de solução hipertônica inalatória, apesar de não associado à gravidade, parece ter implicado maior tempo de internação. A identificação dessas condições de maior vulnerabilidade à prescrição de terapêuticas inadequadas contribui para a implantação de protocolos para o tratamento da BVA, para educação continuada e para posteriores comparações e análises de eficácia das estratégias empregadas.

Evaluating the Placebo Status of Nebulized Normal Saline in Patients With Acute Viral Bronchiolitis: A Systematic Review and Meta-analysis.

Importance: In therapeutic trials for acute viral bronchiolitis, consistent clinical improvement in groups that received nebulized normal saline (NS) as placebo raises the question of whether nebulized NS acts as a treatment rather than a placebo. Objective: To measure the short-term association of nebulized NS with physiologic measures of respiratory status in children with bronchiolitis by analyzing the changes in these measures between the use of nebulized NS and the use of other placebos and the changes before and after nebulized NS treatment. Data Sources: MEDLINE and Scopus were searched through March 2019, as were bibliographies of included studies and relevant systematic reviews, for randomized clinical trials evaluating nebulized therapies in bronchiolitis. Study Selection: Randomized clinical trials comparing children 2 years or younger with bronchiolitis who were treated with nebulized NS were included. Studies enrolling a treatment group receiving an alternative placebo were included for comparison of NS with other placebos. Data Extraction and Synthesis: Data abstraction was performed per PRISMA guidelines. Fixed- and random-effects, variance-weighted meta-analytic models were used. Main Outcomes and Measures: Pooled estimates of the association with respiratory scores, respiratory rates, and oxygen saturation within 60 minutes of treatment were generated for nebulized NS vs another placebo and for change before and after receiving nebulized NS. Results: A total of 29 studies including 1583 patients were included. Standardized mean differences in respiratory scores for nebulized NS vs other placebo (3 studies) favored nebulized NS by -0.9 points (95% CI, -1.2 to -0.6 points) at 60 minutes after treatment (P < .001). There were no differences in respiratory rate or oxygen saturation comparing nebulized NS with other placebo. The standardized mean difference in respiratory score (25 studies) after nebulized NS was -0.7 (95% CI, -0.7 to -0.6; I2 = 62%). The weighted mean difference in respiratory scores using a consistent scale (13 studies) after nebulized NS was -1.6 points (95% CI, -1.9 to -1.3 points; I2 = 72%). The weighted mean difference in respiratory rate (17 studies) after nebulized NS was -5.5 breaths per minute (95% CI, -6.3 to -4.6 breaths per minute; I2 = 24%). The weighted mean difference in oxygen saturation (23 studies) after nebulized NS was -0.4% (95% CI, -0.6% to -0.2%; I2 = 79%). Conclusions and Relevance: Nebulized NS may be an active treatment for acute viral bronchiolitis. Further evaluation should occur to establish whether it is a true placebo.

The impact of viral bronchiolitis phenotyping: Is it time to consider phenotype-specific responses to individualize pharmacological management?

Although recent guidelines recommend a minimalist approach to bronchiolitis, there are several issues with this posture. First, there are concerns about the definition of the disease, the quality of the guidelines, the method of administration of bronchodilators, and the availability of tools to evaluate the response to therapies. Second, for decades it has been assumed that all cases of viral bronchiolitis are the same, but recent evidence has shown that this is not the case. Distinct bronchiolitis phenotypes have been described, with heterogeneity in clinical presentation, molecular immune signatures and clinically relevant outcomes such as respiratory failure and recurrent wheezing. New research is critically needed to refine viral bronchiolitis phenotyping at the molecular and clinical levels as well as to define phenotype-specific responses to different therapeutic options.

Azithromycin is the answer in paediatric respiratory medicine, but what was the question?

The first clinical indication of non-antibiotic benefits of macrolides was in the Far East, in adults with diffuse panbronchiolitis. This condition is characterised by chronic airway infection, often with Pseudomonas aeruginosa, airway inflammation, bronchiectasis and a high mortality. Low dose erythromycin, and subsequently other macrolides, led in many cases to complete remission of the condition, and abrogated the neutrophilic airway inflammation characteristic of the disease. This dramatic finding sparked a flurry of interest in the many hundreds of macrolides in nature, especially their anti-inflammatory and immunomodulatory effects. The biggest subsequent trials of azithromycin were in cystic fibrosis, which has obvious similarities to diffuse panbronchiolitis. There were unquestionable improvements in lung function and pulmonary exacerbations, but compared to diffuse panbronchiolitis, the results were disappointing. Case reports, case series and some randomised controlled trials followed in other conditions. Three trials of azithromycin in preschool wheeze gave contradictory results; a trial in pauci-inflammatory adult asthma, and a trial in non-cystic fibrosis bronchiectasis both showed a significant reduction in exacerbations, but none matched the dramatic results in diffuse panbronchiolitis. There is clearly a huge risk of antibacterial resistance if macrolides are used widely and uncritically in the community. In summary, Azithromycin is not the answer to anything in paediatric respiratory medicine; the paediatric respiratory community needs to refocus on the dramatic benefits of macrolides in diffuse panbronchiolitis, use modern - omics technologies to determine the endotypes of inflammatory diseases and discover in nature or synthesise designer macrolides to replicate the diffuse panbronchiolitis results. We must now find out how to do better!

Efficacy of Prednisolone in bronchiolitis with and without family history of atopy.

OBJECTIVE: To determine decrease in respiratory distress and hospital stay in bronchiolitis patients with and without family history of atopy when treated with prednisolone. METHODS: The multi-centre quasi-experimental study was conducted in three hospitals of Sialkot, Pakistan, from October 2017 to March 2018, and comprised patients of bronchiolitis who were divided into 2 groups on the basis of presence or absence of family history of atopy. Half of the patients in each group received oral prednisolone 2mg/kg/day for three consecutive days along with supportive care, and the remaining half received only supportive care. Patients were monitored at 12 and 24 hours for clinical response using Modified Respiratory distress Assessment Instrument score. Length of hospital stay was monitored upto 72 hours. SPSS 20 was used for data analysis. RESULTS: Of the 212 patients, 72(34%) were in the atopic group and 140(66%) in the non-atopic group. In atopic group, there was a significant respiratory distress difference observed between steroid and non-steroid subgroups at 24 hours (p=0.001) and all (100%) patients in the steroid subgroup got discharged at 24 hours, while only 8(22%) were discharged in the non-steroid subgroup. In non-atopic group, no significant improvement in corresponding terms was observed (p>0.05). CONCLUSIONS: Oral prednisolone in bronchiolitis was found to be only effective in patients with family history of atopy.

Safety of corticosteroids in young children with acute respiratory conditions: a systematic review and meta-analysis.

OBJECTIVE: Adverse events (AEs) associated with short-term corticosteroid use for respiratory conditions in young children. DESIGN: Systematic review of primary studies. DATA SOURCES: Medline, Cochrane CENTRAL, Embase and regulatory agencies were searched September 2014; search was updated in 2017. ELIGIBILITY CRITERIA: Children <6 years with acute respiratory condition, given inhaled (high-dose) or systemic corticosteroids up to 14 days. DATA EXTRACTION AND SYNTHESIS: One reviewer extracted with another reviewer verifying data. Study selection and methodological quality (McHarm scale) involved duplicate independent reviews. We extracted AEs reported by study authors and used a categorisation model by organ systems. Meta-analyses used Peto ORs (pORs) and DerSimonian Laird inverse variance method utilising Mantel-Haenszel Q statistic, with 95% CI. Subgroup analyses were conducted for respiratory condition and dose. RESULTS: Eighty-five studies (11 505 children) were included; 68 were randomised trials. Methodological quality was poor overall due to lack of assessment and inadequate reporting of AEs. Meta-analysis (six studies; n=1373) found fewer cases of vomiting comparing oral dexamethasone with prednisone (pOR 0.29, 95% CI 0.17 to 0.48; I2=0%). The mean difference in change-from-baseline height after one year between inhaled corticosteroid and placebo was 0.10 cm (two studies, n=268; 95% CI -0.47 to 0.67). Results from five studies with heterogeneous interventions, comparators and measurements were not pooled; one study found a smaller mean change in height z-score with recurrent high-dose inhaled fluticasone over one year. No significant differences were found comparing systemic or inhaled corticosteroid with placebo, or between corticosteroids, for other AEs; CIs around estimates were often wide, due to small samples and few events. CONCLUSIONS: Evidence suggests that short-term high-dose inhaled or systemic corticosteroids use is not associated with an increase in AEs across organ systems. Uncertainties remain, particularly for recurrent use and growth outcomes, due to low study quality, poor reporting and imprecision.

Long term follow-up of Palivizumab administration in children born at 29-32 weeks of gestation.

BACKGROUND: Severe respiratory syncytial virus (RSV) bronchiolitis requiring hospitalization induces long term immunological and respiratory abnormalities. The long-term immunomodulation effect of Palivizumab (RSV monoclonal antibody) prophylaxis and its impact on the development of asthma remain controversial. Our aim was to evaluate airway hyper-reactivity, systemic inflammatory markers, allergic parameters and respiratory morbidity, 5-7 years following Palivizumab administration to children born at 29-32 weeks of gestation (WGA). METHODS: Children born at 29-32 WGA were evaluated at age 5-7 years. Methacholine challenge test (MCT), serum inflammatory cytokines, fractional exhaled nitric oxide (FeNO), blood tests for eosinophil count, IgE and assessment of respiratory morbidity by questionnaire were compared between those born before Palivizumab prophylaxis was extended to 29-32 WGA and those who received Palivizumab prophylaxis. RESULTS: Of 42 children recruited, 27 received Palivizumab and 15 did not. The mean gestational age and weight were lower in the Palivizumab group. Similar values of spirometry, MCT, FeNO and allergic parameters were observed in the two groups. The Palivizumab group had higher IL4, IL5 and IL13 (Th2 cytokines), IL6, IL17α, and G-CSF (Th17 activation), and lower IL12 and higher INF-γ (Th1 cytokines). CONCLUSION: Compared to children who did not receive immunoprophylaxis, among children who received Palivizumab, no beneficial effects on long-term respiratory morbidity, airway reactivity or allergic parameters were observed, and levels of Th2 and Th17 cytokines implicated in the pathogenesis of asthma were higher. These findings cast doubt on the potential long-term beneficial effect of Palivizumab on asthma inception.