Paula Heikkilä

High-flow oxygen therapy is more cost-effective for bronchiolitis than standard treatment-a decision-tree analysis.

We evaluated the cost‐effectiveness of high‐flow nasal cannula (HFNC) to provide additional oxygen for infants with bronchiolitis, compared to standard low‐flow therapy.

Nebulised hypertonic saline inhalations do not shorten hospital stays in infants with bronchiolitis

Viral bronchiolitis is worldwide the most common reason for infants to be admitted to hospital. Currently, no effective drugs are available, and oxygen and feeding supports, if needed, are still the cornerstones of bronchiolitis treatment. Inhaled nebulised hypertonic saline (HS) has been actively studied in infant bronchiolitis during the last 15 years, but no consensus has been reached although 24 randomised or semi-randomised controlled trials including over 3200 patients were done before May 2015 (1). Zhang et al. (1) collected the data of these studies in a meta-analysis and published a systematic review on the effectiveness of HS inhalations in bronchiolitis in the October 2015 issue of Pediatrics. The same authors had previously published three meta-analyses and systematic reviews on the same subject in Cochrane Library in 2008, 2011 and 2013 (2–4). The 2008, 2011 and 2013 meta-analyses showed that infantswithbronchiolitiswhoweretreatedwith3%nebulised HS had a significantly shorter mean length of stay (LOS) in hospital than those treated with normal 0.9% saline inhalations. The mean differences were 0.94 days (95% confidence interval (CI) 1.48 to 0.40) in 2008 (2), 1.16 days (95%CI 1.55 to 0.77) in 2011 (3) and 1.15 days (95%CI 1.49 to 0.82) in 2013 (4) Cochrane reviews. The 2015 systematic review and meta-analysis in Pediatrics included 24 studies and 3207 infants with bronchiolitis. The meta-analysis, which covered 15 studies and 1956 hospitalised patients, showed that treatment with 3% or 5% nebulised HS resulted in a shorter LOS than treatment with normal saline inhalations or with standard care without any inhalations. The mean difference was 0.45 days (95% CI 0.82 to 0.08) (1). Thus, the effect size of nebulised HS inhalations on reducing LOS in infants hospitalised for bronchiolitis was only onethird of the levels shown by the 2011 and 2013 Cochrane reviews (3,4). The difference was only narrowly significant, as the upper limit of the 95% CI was close to zero. The combined HS inhalation group had lower postinhalation clinical scores than the control group during the first days of treatment (1), which was seen also in the earlier Cochrane reviews (2–4). However, the 2015 meta-analysis contained two Chinese studies and one Italian study in which the LOS in hospital was surprisingly long (5–7) and not in line with the other studies reviewed and with our clinical experience. The mean LOS in these three studies was 7.4, 6.4 and 5.6 days in the NS inhalation group, versus 6.0, 4.8 and 4.9, respectively, in the HS inhalation group. In all of the other studies reviewed, the mean LOS was less than 4.5 days in the NS groups and less than 4.2 days in the HS groups (1). The long LOS in these three studies (5–7) may have been due to the severity of bronchiolitis or due to local treatment traditions, but irrespective of the reason, it led to larger differences between the HS and NS groups. We re-analysed the meta-analysis published in Pediatrics (1), by excluding the three studies with a long LOS (5–7) and the two unpublished studies registered at www. clinicaltrials.gov with the codes NCT01488448 and Articles in the series A Different View are edited by William Meadow (wlm1@uchicago.edu). We encourage you to offer your own different view either in response to A Different View you do not fully agree with, or on an unrelated topic. Send your article to Dr. Meadow (wlm1@uchicago.edu).

Hypertonic saline inhalations in bronchiolitis-A cumulative meta-analysis

We undertook a cumulative meta‐analysis for the efficacy of hypertonic saline (HS) compared to normal saline (NS) inhalations or no inhalations as controls in bronchiolitis. We performed literature searches from PubMed, Scopus, and by hand search until 20 June 2017. We accepted published randomized controlled trials of HS inhalations in children with bronchiolitis aged <24 months. We evaluated the differences between treatment group with HS and control group without HS inhalations for the length‐of‐stay in hospital (LOS) by cumulative mean difference (MD) and in hospitalization rate by cumulative risk ratio (RR). We identified 18 studies including 2102 children treated in hospital, and the cumulative MD in LOS was −0.471 days (95% confidence interval [CI] −0.765 to −0.177, Higgins heterogeneity test [I2] 72.9%). The cumulative MD reduced in more recently published papers. In studies with the upper age limit of 12 months, the cumulative MD was −0.408 days (95%CI −0.733 to −0.083) without any important heterogeneity (I2u2009=u20090%). If only studies with a very low risk of bias were included, the cumulative MD was 0.034 (95%CI −0.361 to 0.293) without any important heterogeneity (I2u2009=u20090%). We identified eight studies including 1834 children in the outpatient setting, and the cumulative risk ratio for hospitalization was 0.771 (95%CI 0.619‐0.959, I2 55.8%). In conclusion, HS inhalations offered only limited clinical benefits, though the differences between HS and control groups were statistically significant. The heterogeneity between the studies was substantial. Further studies are warranted with consistent definitions of bronchiolitis and comparable research frames.

Low age, low birthweight and congenital heart disease are risk factors for intensive care in infants with bronchiolitis

This study evaluated the incidence and risk factors for intensive care and respiratory support in infant bronchiolitis.

National high-flow nasal cannula and bronchiolitis survey highlights need for further research and evidence-based guidelines

High‐flow nasal cannula (HFNC) therapy provides noninvasive respiratory support for infant bronchiolitis and its use has increased following good clinical experiences. This national study describes HFNC use in Finland during a severe respiratory syncytial virus (RSV) epidemic.

Randomised controlled studies are needed to evaluate the use of high-flow nasal cannula therapy in bronchiolitis.

Bronchiolitis is the most common infection in infancy that leads to hospitalisation. In a recent two-year study from Finland, 3.7% of all infants under six months of age were admitted to the emergency room for bronchiolitis each year. The majority (70%) were hospitalised, and 6% of those needed intensive care (1). Oxygen and feeding support, if needed, are the cornerstones of bronchiolitis treatment, but the different drugs that have been studied have been ineffective. Administering a warmed, moistened mixture of oxygen and air using a high-flow nasal cannula (HFNC) is a promising new approach for treating infant bronchiolitis. In experimental studies, HFNC treatment has led to beneficial physiological effects on infant bronchiolitis (2–4), and the clinical experiences of using HFNC in neonatology have been good (5). High-flow nasal cannula therapy works by delivering a larger volume of air and oxygen into the nasal passages than standard low-flow oxygen therapy, using a higher flow of humidified and heated gas. Physiological studies have reported that this high flow resulted in more efficient delivery of oxygen to the terminal airways, resulting in reduced work of breathing and improved gas exchange in infant bronchiolitis (2,3). The end-expiratory lung volume and oxygen saturation were reported to be higher, the respiratory rate was lower and less supplementary oxygen was needed when the 8 L/min flow rate was compared to the 2 L/min flow rate in 13 infants (2). Another study of 14 infants showed that the work of breathing, as estimated by diaphragmatic electrical activity and oesophageal pressure, decreased after starting HFNC treatment with a 2 L/kg/ min flow rate (3). Meanwhile, a study of 19 infants reported that nasopharyngeal pressure increased linearly with flow rates up to 6 L/min and that bronchiolitis severity scores improved significantly at this level (6). In this issue of the journal, Milani et al. (7) report the results of their prospective observational study on the use of HFNC therapy in moderate-to-severe infant bronchiolitis treated on the paediatric ward, comparing their results with standard low-flow oxygen administration. The study included 36 infants aged 1.2–5.0 months who needed oxygen support when they were treated on a paediatric ward. The allocation of the patients into the HFNC and standard low-flow treatment groups depended on the availability of the HFNC device. The assessment of the flow rate in the HFNC treatment group was rather complex (L/min = 8 mL/kg*respiratory rate*0.3), but, on the other hand, it was based on the respiratory effort needed. The outcome measures were respiratory rate, the doctors’ clinical assessment of respiratory effort and the ability to feed, which was assessed by nurses who recorded the infants’ milk intake during bottle-feeding or weighed the infants before and after breastfeeding. The improvements in respiratory rate and effort, and the ability to feed, were significantly faster in the infants treated with HFNC than in the controls (7). The median duration of oxygen support was 4 days (interquartile, IQ 3–5 days) in the HFNC group versus 6 days (IQ 5–7 days) in the standard low-flow oxygen group, and the median lengths of hospital stays were 6 days (IQ 5–7 days) versus 9 days (IQ 8–10 days), respectively. Two patients in each group needed to be admitted to the paediatric intensive care unit (PICU). An open, randomised, pilot study of 19 infants treated for bronchiolitis on the paediatric ward that compared HFNC and head-box oxygen supports (8) found that oxygen saturation was higher in the HFNC group at eight and 12 hours, but not at 24 hours onwards. The improvement in respiratory effort was not reported. The total time spent receiving oxygen support and the length of hospital stay did not differ between the groups (8). So far, that study has been the only randomised controlled trial on the effectiveness of HFNC therapy in infant bronchiolitis, but only eight infants were treated with HFNC. As the authors stated, the study did not have significant power to find more differences between the HFNC and control groups. High-flow nasal cannula therapy decreased the need for intensive care in an Australian cohort of 61 infants aged less than 12 months, who were treated for bronchiolitis on a paediatric ward using a 2 L/kg/min flow rate (9). The need for intensive care was 13% in the HFNC group, compared with 31% in the 33 retrospectively collected, matched controls treated with standard low-flow oxygen therapy. In the HFNC group, the responders could be identified from the nonresponders within 60 minutes of treatment, by the decreases in their heart rate and respiratory rate (9). Three retrospective studies evaluated HFNC therapy in infants treated for bronchiolitis in the PICU. In two studies,

The cost-effectiveness of hypertonic saline inhalations for infant bronchiolitis: a decision analysis

BackgroundThis study evaluated the cost-effectiveness of hypertonic saline (HS) inhalations for infant bronchiolitis, compared to normal saline inhalations or standard treatment without inhalations as controls.MethodsThe decision tree in the decision analysis was used to calculate the expected costs. Actual cost data were obtained from our retrospective case-control study on bronchiolitis treatment. The effectiveness of treatment, based on the hospitalization rate of those admitted to the emergency department and the length of stay (LOS) of those who were hospitalized, was collected from previous studies. For the effectiveness estimations, we made a meta-analysis summarizing the results of the meta-analysis of the Cochrane review in 2013 and the results of 10 studies published after it.ResultsThe mean hospitalization rate was 24.7% in the HS inhalation group and 32.6% in the control group [risk ratio: 0.80, 95% confidence interval (CI) 0.67–0.96] and the mean LOS was 3.736 (HS group) and 4.292 (controls) days (mean difference: − 0.55xa0days, 95% CI − 0.96 to − 0.15), respectively. The expected costs per patient, when both inpatients and outpatients were included, were €816 (

The change in management of bronchiolitis in the intensive care unit between 2000 and 2015

1111) in the HS inhalation group and €962 (

Using high-flow nasal cannulas for infants with bronchiolitis admitted to paediatric wards is safe and feasible

1310) in the control group. The expected costs per hospitalization, when only inpatients were included, were €2600 (

National allergy programme had little impact on parent-reported food allergies in children aged 6-7 years

3540) in the HS inhalation group and €2890 (