Nebulised hypertonic saline solution for acute bronchiolitis in infants.

BACKGROUND: Airway oedema (swelling) and mucus plugging are the principal pathological features in infants with acute viral bronchiolitis. Nebulised hypertonic saline solution (≥ 3%) may reduce these pathological changes and decrease airway obstruction. This is an update of a review first published in 2008, and updated in 2010, 2013, and 2017. OBJECTIVES: To assess the effects of nebulised hypertonic (≥ 3%) saline solution in infants with acute bronchiolitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily, Embase, CINAHL, LILACS, and Web of Science on 13 January 2022. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 13 January 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs using nebulised hypertonic saline alone or in conjunction with bronchodilators as an active intervention and nebulised 0.9% saline or standard treatment as a comparator in children under 24 months with acute bronchiolitis. The primary outcome for inpatient trials was length of hospital stay, and the primary outcome for outpatients or emergency department (ED) trials was rate of hospitalisation. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction, and assessment of risk of bias in included studies. We conducted random-effects model meta-analyses using Review Manager 5. We used mean difference (MD), risk ratio (RR), and their 95% confidence intervals (CI) as effect size metrics. MAIN RESULTS: We included six new trials (N = 1010) in this update, bringing the total number of included trials to 34, involving 5205 infants with acute bronchiolitis, of whom 2727 infants received hypertonic saline. Eleven trials await classification due to insufficient data for eligibility assessment. All included trials were randomised, parallel-group, controlled trials, of which 30 were double-blinded. Twelve trials were conducted in Asia, five in North America, one in South America, seven in Europe, and nine in Mediterranean and Middle East regions. The concentration of hypertonic saline was defined as 3% in all but six trials, in which 5% to 7% saline was used. Nine trials had no funding, and five trials were funded by sources from government or academic agencies. The remaining 20 trials did not provide funding sources. Hospitalised infants treated with nebulised hypertonic saline may have a shorter mean length of hospital stay compared to those treated with nebulised normal (0.9%) saline or standard care (mean difference (MD) -0.40 days, 95% confidence interval (CI) -0.69 to -0.11; 21 trials, 2479 infants; low-certainty evidence). Infants who received hypertonic saline may also have lower postinhalation clinical scores than infants who received normal saline in the first three days of treatment (day 1: MD -0.64, 95% CI -1.08 to -0.21; 10 trials (1 outpatient, 1 ED, 8 inpatient trials), 893 infants; day 2: MD -1.07, 95% CI -1.60 to -0.53; 10 trials (1 outpatient, 1 ED, 8 inpatient trials), 907 infants; day 3: MD -0.89, 95% CI -1.44 to -0.34; 10 trials (1 outpatient, 9 inpatient trials), 785 infants; low-certainty evidence). Nebulised hypertonic saline may reduce the risk of hospitalisation by 13% compared with nebulised normal saline amongst infants who were outpatients and those treated in the ED (risk ratio (RR) 0.87, 95% CI 0.78 to 0.97; 8 trials, 1760 infants; low-certainty evidence). However, hypertonic saline may not reduce the risk of readmission to hospital up to 28 days after discharge (RR 0.83, 95% CI 0.55 to 1.25; 6 trials, 1084 infants; low-certainty evidence). We are uncertain whether infants who received hypertonic saline have a lower number of days to resolution of wheezing compared to those who received normal saline (MD -1.16 days, 95% CI -1.43 to -0.89; 2 trials, 205 infants; very low-certainty evidence), cough (MD -0.87 days, 95% CI -1.31 to -0.44; 3 trials, 363 infants; very low-certainty evidence), and pulmonary moist crackles (MD -1.30 days, 95% CI -2.28 to -0.32; 2 trials, 205 infants; very low-certainty evidence). Twenty-seven trials presented safety data: 14 trials (1624 infants; 767 treated with hypertonic saline, of which 735 (96%) co-administered with bronchodilators) did not report any adverse events, and 13 trials (2792 infants; 1479 treated with hypertonic saline, of which 416 (28%) co-administered with bronchodilators and 1063 (72%) hypertonic saline alone) reported at least one adverse event such as worsening cough, agitation, bronchospasm, bradycardia, desaturation, vomiting and diarrhoea, most of which were mild and resolved spontaneously (low-certainty evidence). AUTHORS' CONCLUSIONS: Nebulised hypertonic saline may modestly reduce length of stay amongst infants hospitalised with acute bronchiolitis and may slightly improve clinical severity score. Treatment with nebulised hypertonic saline may also reduce the risk of hospitalisation amongst outpatients and ED patients. Nebulised hypertonic saline seems to be a safe treatment in infants with bronchiolitis with only minor and spontaneously resolved adverse events, especially when administered in conjunction with a bronchodilator. The certainty of the evidence was low to very low for all outcomes, mainly due to inconsistency and risk of bias.

Costs of bronchoalveolar lavage-directed therapy in the first 5 years of life for children with cystic fibrosis.

OBJECTIVES: To determine whether bronchoalveolar lavage (BAL)-directed therapy for infants and young children with cystic fibrosis (CF), rather than standard therapy, was justified on the grounds of a decrease in average costs and whether the use of BAL reduced treatment costs associated with hospital admissions. STUDY DESIGN: Costs were assessed in a randomized controlled trial conducted in Australia and New Zealand on infants diagnosed with CF after newborn screening and assigned to receive either BAL-directed or standard therapy until they reached 5 years of age. A health care funder perspective was adopted. Resource use measurement was based on standardized data collection forms administered for patients across all sites. Unit costs were obtained primarily from government schedules. RESULTS: Mean costs per child during the study period were Australian dollars (AUD)92 860 in BAL-directed therapy group and AUD90 958 in standard therapy group (mean difference AUD1902, 95% CI AUD-27 782 to 31 586, P = .90). Mean hospital costs per child during the study period were AUD57 302 in the BAL-directed therapy group and AUD66 590 in the standard therapy group (mean difference AUD-9288; 95% CI AUD-35 252 to 16 676, P = .48). CONCLUSIONS: BAL-directed therapy did not result in either lower mean hospital admission costs or mean costs overall compared with managing patients with CF by a standard protocol based upon clinical features and oropharyngeal culture results alone. Following on our previous findings that BAL-directed treatment offers no clinical advantage over standard therapy at age 5 years, flexible bronchoscopy with BAL cannot be recommended for the routine management of preschool children with CF on the basis of overall cost savings.

Nebulised hypertonic saline solution for acute bronchiolitis in infants.

BACKGROUND: Airway oedema and mucus plugging are the predominant pathological features in infants with acute viral bronchiolitis. Nebulised hypertonic saline solution may reduce these pathological changes and decrease airway obstruction. OBJECTIVES: To assess the effects of nebulised hypertonic (≥ 3%) saline solution in infants with acute viral bronchiolitis. SEARCH METHODS: We searched CENTRAL 2013, Issue 4, OLDMEDLINE (1951 to 1965), MEDLINE (1966 to April week 4, 2013), EMBASE (1974 to May 2013), LILACS (1985 to May 2013) and Web of Science (1955 to May 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs using nebulised hypertonic saline alone or in conjunction with bronchodilators as an active intervention and nebulised 0.9% saline as a comparator in infants up to 24 months of age with acute bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction and assessment of risk of bias in included studies. We conducted meta-analyses using the Cochrane statistical package RevMan 5.2. We used the random-effects model for meta-analyses. We used mean difference (MD) and risk ratio (RR) as effect size metrics. MAIN RESULTS: We included 11 trials involving 1090 infants with mild to moderate acute viral bronchiolitis (500 inpatients, five trials; 65 outpatients, one trial; and 525 emergency department patients, four trials). All but one of the included trials were of high quality with a low risk of bias. A total of 560 patients received hypertonic saline (3% saline n = 503; 5% saline n = 57). Patients treated with nebulised 3% saline had a significantly shorter mean length of hospital stay compared to those treated with nebulised 0.9% saline (MD -1.15 days, 95% confidence interval (CI) -1.49 to -0.82, P < 0.00001). The hypertonic saline group also had a significantly lower post-inhalation clinical score than the 0.9% saline group in the first three days of treatment (day 1: MD -0.88, 95% CI -1.36 to -0.39, P = 0.0004; day 2: MD -1.32, 95% CI -2.00 to -0.64, P = 0.001; day 3: MD -1.51, 95% CI -1.88 to -1.14, P < 0.00001). The effects of improving clinical score were observed in both outpatients and inpatients. Four emergency department-based trials did not show any significant short-term effects (30 to 120 minutes) of up to three doses of nebulised 3% saline in improving clinical score and oxygen saturation. No significant adverse events related to hypertonic saline inhalation were reported. AUTHORS' CONCLUSIONS: Current evidence suggests nebulised 3% saline may significantly reduce the length of hospital stay among infants hospitalised with non-severe acute viral bronchiolitis and improve the clinical severity score in both outpatient and inpatient populations.

Pneumonia in the first 2 years of life, and asthma in preschool-age children.

BACKGROUND: The relationship between viral bronchiolitis in early infancy and subsequent wheezing and asthma has been well established. The aim of the present cross-sectional study was to test the hypothesis that pneumonia severe enough to require hospitalization during the first 2 years of life could also be associated with asthma or asthma-like symptoms in pre-school children. METHODS: Structured interviews were conducted with parents of children who were classified as exposed (n= 36) or non-exposed (n= 84), based on whether they were hospitalized with radiologically confirmed pneumonia during the first 2 years of life. The main outcomes were ever physician-diagnosed asthma, asthma-like symptoms and use of anti-asthmatic medications during the last 2 months and during the last 12 months. RESULTS: The prevalence of ever physician-diagnosed asthma was higher in the exposed group compared with the non-exposed group (41.6% vs 22.6%, P= 0.01), with an adjusted prevalence ratio of 2.03 (95% confidence interval: 1.10-3.62). The exposed group had a trend toward a higher prevalence of asthma-like symptoms and use of anti-asthmatic medications during the last 2 months and during the last 12 months. CONCLUSIONS: Radiologically confirmed pneumonia in the first 2 years of life may be associated with asthma or asthma-like symptoms in pre-school children.

Quality-of-life in children and adolescents with cystic fibrosis managed in both regional outreach and cystic fibrosis center settings in Queensland.

OBJECTIVES: To assess the health-related quality-of-life (HRQOL) of children/adolescents with cystic fibrosis (CF) and compare HRQOL in children managed by cystic fibrosis outreach service (CFOS) with those treated in a cystic fibrosis center (CFC). To compare HRQOL of children with CF in Queensland with previously published HRQOL data from the United States and examine the relationship between HRQOL scores and pulmonary function. STUDY DESIGN: Participants were children/adolescents with CF and their parents managed by the Royal Children's Hospital Queensland at a CFC or CFOS. Two HRQOL surveys were used: PedsQL and Cystic Fibrosis Questionnaire (CFQ). RESULTS: There were 91 CFC and 71 CFOS participants with similar demographics. PedsQL total summary score was statistically higher in CFOS, P=.05. There was no significant difference in CFQ scores between groups. Queensland parents reported lower HRQOL for their children compared with US parents (P<.01) despite similar pulmonary function. Declining pulmonary function correlated with worse CFQ scores in adolescents, P<.05. CONCLUSIONS: Children living in regional Queensland reported as good as or slightly better HRQOL compared with children attending a CFC. Parent proxy HRQOL scores were generally low suggesting a reduced perception of HRQOL by parents for their children.

A clinical pathway for bronchiolitis is effective in reducing readmission rates.

OBJECTIVE: To examine the use of a clinical pathway in the management of infants hospitalized with acute viral bronchiolitis. STUDY DESIGN: A clinical pathway with specific management and discharge criteria for the care of infants with bronchiolitis was developed from pathways used in tertiary care pediatric institutions in Australia. Two hundred and twenty-nine infants admitted to hospital with acute viral bronchiolitis and prospectively managed using a pathway protocol were compared with a retrospective analysis of 207 infants managed without a pathway in 3 regional and 1 tertiary care hospital. RESULTS: Readmission to hospital was significantly lower in the pathway group (P = .001), as was administration of supplemental fluids (P = .001) and use of steroids (P = .005). There were no differences between groups in demographic factors or clinical severity. The pathway had no overall effect on length of stay or time in oxygen. CONCLUSIONS: A clinical pathway specifying local practice guidelines and discharge criteria can reduce the risk of readmission to hospital, the use of inappropriate therapies, and help with discharge planning.