During the 8-year period, 1380 children (age <19 years) were treated for sepsis. Over the study period, mean adherence to the sepsis bundle of care improved from 73% to 84%. Researchers conducted a chart review to compare process and patient outcomes between 1119 children who received the sepsis bundle of care and 261 who did not. Children who did not receive the bundle had significantly higher in-hospital mortality than those who did receive the bundle (4.2% vs. 1.2%). The QI program resulted in a decrease in mortality without an increase in admissions to the pediatric intensive care unit or an increase in the overall cost of care.

Comment

This is a very nice example of a QI improvement program as it evolved over 8 years. Steady improvement was demonstrated with iterative changes based on front-line provider feedback and measurement, resulting in an impressive benefit to patients. This study demonstrates the power of QI methodology to improve patient outcomes.

- David J. Amrol, MD

David J. Amrol, MD, is an Associate Professor of Clinical Internal Medicine and Director of the Division of Allergy and Immunology at the University of South Carolina School of Medicine in Columbia.

Current asthma guidelines recommend adding a long-acting beta-agonist (LABA) for children whose asthma is not controlled with low- to medium-dose inhaled corticosteroids (ICSs). However, there is evidence that LABAs increase the risk for asthma-related deaths in adults, and it is unclear if concomitant use of an ICS mitigates this risk. The FDA asked the manufacturer to conduct large studies to assess the safety of salmeterol when used with fluticasone in a fixed-dose combination device (Advair Diskus).

In an international trial, 6208 children aged 4 to 11 years with asthma and an exacerbation in the previous year were randomized to salmeterol or placebo plus twice-daily inhaled fluticasone (100 or 250 µg, depending on asthma severity) for 26 weeks. There was no significant difference between the ICS/LABA and ICS monotherapy groups in the primary safety endpoint of a serious asthma-related event (death, intubation, or hospitalization; 27 and 21 children); all events were hospitalizations. There was also no significant difference in the primary efficacy endpoint of asthma exacerbation requiring systemic steroids (265 and 309 children, respectively).

Comment For most children with asthma, a low- to medium-dose ICS is very effective if used properly and consistently. For children who continue to have uncontrolled asthma on an ICS, results from this study and a similar study of adolescents and adults provide reassurance that the addition of a LABA does not lead to increased serious adverse asthma outcomes (NEJM JW Gen Med May 1 2016 and N Engl J Med 2016; 374:1822). A LABA should never be used as monotherapy for asthma and should only be used in fixed-dose combination devices also containing an ICS.

- David J. Amrol, MD

David J. Amrol, MD, is an Associate Professor of Clinical Internal Medicine and Director of the Division of Allergy and Immunology at the University of South Carolina School of Medicine in Columbia.

Editor Disclosures at Time of Publication

Disclosures for David J. Amrol, MD at time of publication

Equity	Abbott; AbbieVie; Express Scripts; Johnson and Johnson; Novartis; Pfizer; United Health
Leadership positions in professional societies	Allergy Society of South Carolina (Past President)

Citation(s):

Stempel DA et al. Safety of adding salmeterol to fluticasone propionate in children with asthma. N Engl J Med 2016 Sep 1; 375:840. (http://dx.doi.org/10.1056/NEJMoa1606356)

Bush A and Frey U.Safety of long-acting beta-agonists in children with asthma. N Engl J Med 2016 Sep 1; 375:889. (http://dx.doi.org/10.1056/NEJMe1608508)