Quality Improvement to Reduce High-Flow Nasal Cannula Overuse in Children With Bronchiolitis.

BACKGROUND: High-flow nasal cannula oxygen therapy (HFNC) is increasingly used to treat bronchiolitis. However, HFNC has not reduced time on supplemental oxygen, length of stay (LOS), or ICU admission. Our objective was to reduce HFNC use in children admitted for bronchiolitis from 41% to 20% over 2 years. METHODS: Using quality improvement methods, our multidisciplinary team formulated key drivers, including standardization of HFNC use, effective communication, knowledgeable staff, engaged providers and families, data transparency, and high-value care focus. Interventions included: (1) standardized HFNC initiation criteria, (2) staff education, (3) real-time feedback to providers, (4) a script for providers to use with families about expectations during admission, (5) team huddle for patients admitted on HFNC to discuss necessity, and (6) distribution of a bronchiolitis toolkit. We used statistical process control charts to track the percentage of children with bronchiolitis who received HFNC. Data were compared with a comparison institution not actively involved in quality improvement work around HFNC use to ensure improvements were not secondary to the COVID-19 pandemic alone. RESULTS: Over 10 months of interventions, we saw a decrease in HFNC use for patients admitted with bronchiolitis from 41% to 22%, which was sustained for >12 months. There was no change in HFNC use at the comparison institution. The overall mean LOS for children with bronchiolitis decreased from 60 to 45 hours. CONCLUSIONS: We successfully reduced HFNC use in children with bronchiolitis, improving delivery of high-value and evidence-based care. This reduction was associated with a 25% decrease in LOS.

Opposing effects of collagen I and vitronectin on fibronectin fibril structure and function.

Extracellular matrix fibronectin fibrils serve as passive structural supports for the organization of cells into tissues, yet can also actively stimulate a variety of cell and tissue functions, including cell proliferation. Factors that control and coordinate the functional activities of fibronectin fibrils are not known. Here, we compared effects of cell adhesion to vitronectin versus type I collagen on the assembly of and response to, extracellular matrix fibronectin fibrils. The amount of insoluble fibronectin matrix fibrils assembled by fibronectin-null mouse embryonic fibroblasts adherent to collagen- or vitronectin-coated substrates was not significantly different 20 h after fibronectin addition. However, the fibronectin matrix produced by vitronectin-adherent cells was ~10-fold less effective at enhancing cell proliferation than that of collagen-adherent cells. Increasing insoluble fibronectin levels with the fibronectin fragment, anastellin did not increase cell proliferation. Rather, native fibronectin fibrils polymerized by collagen- and vitronectin-adherent cells exhibited conformational differences in the growth-promoting, III-1 region of fibronectin, with collagen-adherent cells producing fibronectin fibrils in a more extended conformation. Fibronectin matrix assembly on either substrate was mediated by α5ß1 integrins. However, on vitronectin-adherent cells, α5ß1 integrins functioned in a lower activation state, characterized by reduced 9EG7 binding and decreased talin association. The inhibitory effect of vitronectin on fibronectin-mediated cell proliferation was localized to the cell-binding domain, but was not a general property of αvß3 integrin-binding substrates. These data suggest that adhesion to vitronectin allows for the uncoupling of fibronectin fibril formation from downstream signaling events by reducing α5ß1 integrin activation and fibronectin fibril extension.

Identification of the heparin-binding determinants within fibronectin repeat III1: role in cell spreading and growth.

Fibronectins are high molecular mass glycoproteins that circulate as soluble molecules in the blood, and are also found in an insoluble, multimeric form in extracellular matrices throughout the body. Soluble fibronectins are polymerized into insoluble extracellular matrix (ECM) fibrils via a cell-dependent process. Recent studies indicate that the interaction of cells with the ECM form of fibronectin promotes actin organization and cell contractility, increases cell growth and migration, and enhances the tensile strength of artificial tissue constructs; ligation of integrins alone is insufficient to trigger these responses. Evidence suggests that the effect of ECM fibronectin on cell function is mediated in part by a matricryptic heparin-binding site within the first III1 repeat (FNIII1). In this study, we localized the heparin-binding activity of FNIII1 to a cluster of basic amino acids, Arg613, Trp614, Arg615, and Lys617. Site-directed mutagenesis of a recombinant fibronectin construct engineered to mimic the ECM form of fibronectin demonstrates that these residues are also critical for stimulating cell spreading and increasing cell proliferation. Cell proliferation has been tightly correlated with cell area. Using integrin- and heparin-binding fibronectin mutants, we found a positive correlation between cell spreading and growth when cells were submaximally spread on ECM protein-coated surfaces at the time of treatment. However, cells maximally spread on vitronectin or fibronectin still responded to the fibronectin matrix mimetic with an increase in growth, indicating that an absolute change in cell area is not required for the increase in cell proliferation induced by the matricryptic site of FNIII1.

Fibronectin matrix polymerization increases tensile strength of model tissue.

The composition and organization of the extracellular matrix (ECM) contribute to the mechanical properties of tissues. The polymerization of fibronectin into the ECM increases actin organization and regulates the composition of the ECM. In this study, we examined the ability of cell-dependent fibronectin matrix polymerization to affect the tensile properties of an established tissue model. Our data indicate that fibronectin polymerization increases the ultimate strength and toughness, but not the stiffness, of collagen biogels. A fragment of fibronectin that stimulates mechanical tension generation by cells, but is not incorporated into ECM fibrils, did not increase the tensile properties, suggesting that changes in actin organization in the absence of fibronectin fibril formation are not sufficient to increase tensile strength. The actin cytoskeleton was needed to initiate the fibronectin-induced increases in the mechanical properties. However, once fibronectin-treated collagen biogels were fully contracted, the actin cytoskeleton no longer contributed to the tensile strength. These data indicate that fibronectin polymerization plays a significant role in determining the mechanical strength of collagen biogels and suggest a novel mechanism by which fibronectin can be used to enhance the mechanical performance of artificial tissue constructs.