Bronchiolitis therapies and misadventures.

Viral bronchiolitis, which is most commonly caused by an infection with the respiratory syncytial virus (RSV), can lead to respiratory difficulties in young children which may require hospitalization. Despite years of research and medical trials, the mainstay of bronchiolitis treatment remains supportive only. This review provides an overview of the history of different treatments for bronchiolitis, including those that failed, as well as new therapies that are under study. Future studies for the treatment of bronchiolitis should consider different age-groups, important subgroups (i.e., those with a prior history of wheezing, those with a family history of asthma and those with non-RSV viral etiologies) whose response to treatment may differ from that of the composite group.

Neutrophil Extracellular Traps Do Not Induce Injury and Inflammation in Well-Differentiated RSV-Infected Airway Epithelium.

Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) causes a major burden of disease. The host response in RSV-LRTI is characterized by airway epithelial injury, inflammation and neutrophil influx, with the formation of neutrophil extracellular traps (NETs). However, the precise role of NETs in the pathophysiology of RSV-LRTI remains to be elucidated. Here, we used well-differentiated human airway epithelial cultures (HAE) of a pediatric and adult donor to study whether NETs cause airway epithelial injury and inflammation in the setting of RSV infection. The exposure of uninfected and RSV-infected HAE cultures to NETs, as produced by stimulation of neutrophils by a low dose of phorbol 12-myristate 13-acetate (PMA), did not induce or aggravate cell injury or inflammation. RSV infection of HAE cultures caused release of pro-inflammatory cytokines such as IL-6 and RANTES in both adult and pediatric cultures, but the differential gene expression for regulated cell death differed between culture donors. In this in vitro airway epithelial model, NETs in the setting of RSV infection did not cause or aggravate epithelial injury or inflammation.

Use of dornase alfa in the paediatric intensive care unit: current literature and a national cross-sectional survey.

OBJECTIVES: Airway mucus obstruction is a major challenge in children admitted to the paediatric intensive care unit (PICU). We aimed to evaluate the evidence and contemporary use of the mucolytic medication dornase alfa for non-cystic fibrosis conditions in the PICU. METHODS: (1) We performed a systematic review with searches in PubMed, EMBASE, and the Cochrane Library. Study selection: for quality assessment and data synthesis, we included only randomised controlled trials (RCTs) that compared dornase alfa to standard care or placebo in critically-ill paediatric patients (<18 years of age) in the PICU. However, non-randomised controlled studies and case series are also discussed. Data extraction: data were extracted independently by multiple reviewers using data extraction forms. The primary outcome was duration of mechanical ventilation. Data synthesis: The GRADE approach was used for quality assessment. No meta-analysis could be performed. (2) A national cross-sectional survey among all seven PICUs in the Netherlands was also performed. RESULTS: The systematic review yielded only one RCT, comparing dornase alfa with normal saline in children after cardiac surgery. In this study, dornase alfa led to a reduction in duration of mechanical ventilation by approximately 1 day (36% reduction). In addition, we found nine retrospective observational and case studies. The survey revealed high current use of dornase alfa in Dutch PICUs: 42% of the respondents reported prescribing dornase alfa at least once every week. Only 4% of the respondents reported having access to a local PICU dornase alfa protocol. CONCLUSIONS: The off-label use of dornase alfa in the PICU is frequent without strong evidence or local protocols, highlighting the need for further research on the effectiveness of this mucolytic agent.

Body Weight Changes after Deep Brain Stimulation for Obsessive-Compulsive Disorder or Depression.

BACKGROUND: In 2010, we published an often-cited case report describing smoking cessation and substantial weight loss after deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) in an obese patient. To test whether this single observation was also observed in the treated population at large, the weight changes of a larger cohort of patients who underwent DBS for OCD or major depressive disorder (MDD) were studied. RESULTS: Data were available for 46 patients (30 OCD and 16 MDD patients; mean age 46.2 years, SD 10.9) with an average baseline body mass index (BMI) of 28.0 (SD 7.3), 26 of whom (57%) were overweight (n = 11), obese (n = 12), or morbidly obese (n = 3). Mean follow-up was 3.8 years (range 10 months to 8.7 years, SD 2.3), after which the average BMI was 28.1 (SD 7.0), not significantly different from baseline. The average BMI of the 15 patients with (morbid) obesity at baseline decreased from 36.8 to 34.6 (ns), while the average BMI of the 31 normal or "only" overweight patients at baseline increased from 23.8 to 25.0 (ns). CONCLUSION: There was no significant change in body weight on group level after DBS for either OCD or MDD.

Incidence of polyneuropathy in Utrecht, the Netherlands.

OBJECTIVE: Ascertain the incidence of cryptogenic axonal polyneuropathy (CAP) and how this relates to the overall incidence of polyneuropathy. METHODS: Electronic diagnostic registries of all hospital-based neurologic practices in the province of Utrecht (population 1,224,852 = 7.4% of the Dutch population) were consulted in 2010 to identify incident cases with polyneuropathy. Medical files were reviewed to specify the final diagnosis. Age-adjusted incidence rates for the Netherlands were calculated using national age-specific population figures. RESULTS: The overall incidence of polyneuropathy was 77.0/100,000 person-years (95% confidence interval 71.1-82.8) in persons aged 18 years and older. Diabetic polyneuropathy (32%), CAP (26%), toxic polyneuropathy (14%), and immune-mediated polyneuropathy (9%) were the most frequent diagnoses. The incidence of CAP was 31.6/100,000 person-years (95% confidence interval 27.0-36.3) in persons aged 40 years and older. The incidence of polyneuropathy increased with age, as well as the proportion of patients diagnosed with CAP: 12% (40-49 years), 20% (50-59 years), 28% (60-69 years), 32% (70-79 years), and 35% (≥80 years) (χ(2) test, p = 0.005). CONCLUSIONS: The chance of establishing an etiologic diagnosis in patients presenting with a polyneuropathy decreases with age. Given the aging population, polyneuropathy in general and CAP in particular will pose a growing health care problem.