Theresa Laguna - Academia.edu (original) (raw)

Papers by Theresa Laguna

Research paper thumbnail of Editorial Commentary : Pseudomonas aeruginosa Eradication: How Do We Measure Success?

Clinical Infectious Diseases, 2015

Research paper thumbnail of Metabolomics analysis identifies novel plasma biomarkers of cystic fibrosis pulmonary exacerbation

Pediatric pulmonology, 2015

Cystic fibrosis (CF) lung disease is characterized by infection, inflammation, lung function decl... more Cystic fibrosis (CF) lung disease is characterized by infection, inflammation, lung function decline, and intermittent pulmonary exacerbations. However, the link between pulmonary exacerbation and lung disease progression remains unclear. Global metabolomic profiling can provide novel mechanistic insight into a disease process in addition to putative biomarkers for future study. Our objective was to investigate how the plasma metabolomic profile changes between CF pulmonary exacerbation and a clinically well state. Plasma samples and lung function data were collected from 25 CF patients during hospitalization for a pulmonary exacerbation and during quarterly outpatient clinic visits. In collaboration with Metabolon, Inc., the metabolomic profiles of matched pair plasma samples, one during exacerbation and one at a clinic visit, were analyzed using gas and liquid chromatography coupled with mass spectrometry. Compounds were identified by comparison to a library of standards. Mixed ef...

Research paper thumbnail of Specific Gravity As A Novel Normalization Method For Urinary Biomarker Measurement In A Cystic Fibrosis Population During Pulmonary Exacerbation

A53. CYSTIC FIBROSIS: CLINICAL PEDIATRIC STUDIES, 2010

Research paper thumbnail of Vitamin D Deficiency Is Associated with Pulmonary Exacerbations in Children with Cystic Fibrosis

Annals of the American Thoracic Society, 2014

Rationale: Recent literature suggests vitamin D has an effect on lung function and on the lung's ... more Rationale: Recent literature suggests vitamin D has an effect on lung function and on the lung's ability to fight infection, both important in the cystic fibrosis (CF) population as predictors of morbidity and mortality.

Research paper thumbnail of Contributors

Berman's Pediatric Decision Making, 2011

Research paper thumbnail of Fifteen-Year-Old Girl With Severe Obstructive Lung Disease, Pansinusitis, and Failure to Thrive

Clinical Pediatrics, 2014

Research paper thumbnail of The arginine decarboxylase pathways of host and pathogen interact to impact inflammatory pathways in the lung

PloS one, 2014

The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both human... more The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both humans and most bacterial pathogens. In humans agmatine is a neurotransmitter with affinities towards α2-adrenoreceptors, serotonin receptors, and may inhibit nitric oxide synthase. In bacteria agmatine serves as a precursor to polyamine synthesis and was recently shown to enhance biofilm development in some strains of the respiratory pathogen Pseudomonas aeruginosa. We determined agmatine is at the center of a competing metabolism in the human lung during airways infections and is influenced by the metabolic phenotypes of the infecting pathogens. Ultra performance liquid chromatography with mass spectrometry detection was used to measure agmatine in human sputum samples from patients with cystic fibrosis, spent supernatant from clinical sputum isolates, and from bronchoalvelolar lavage fluid from mice infected with P. aeruginosa agmatine mutants. Agmatine in human sputum peaks during illness...

Research paper thumbnail of Comparison of quantitative sweat chloride methods after positive newborn screen for cystic fibrosis

Pediatric Pulmonology, 2012

Rapid and reliable confirmatory sweat testing following a positive newborn screen (NBS) for cysti... more Rapid and reliable confirmatory sweat testing following a positive newborn screen (NBS) for cystic fibrosis (CF) is preferred to allow for early diagnosis and to decrease parental anxiety. The Cystic Fibrosis Foundation (CFF) recently recommended a quantity not sufficient (QNS) rate of ≤ 10% in infants <3 months of age referred for quantitative sweat chloride analysis. Two CFF-approved methods are available by which to quantitatively measure chloride concentration in sweat. Our objective was to compare the performance of the Macroduct® sweat collection system (MSCS) with the Gibson and Cooke technique (GCT) in the acquisition of samples for the determination of sweat chloride concentration in infants with a positive Minnesota State NBS for CF. A retrospective database review of infants referred to the core Minnesota CF Center or its affiliate site for confirmatory sweat testing was performed to compare the QNS rates for the two techniques. Associations between birthweight, age at test, race, and QNS rates were examined. Five hundred sixty-eight infants were referred for 616 sweat tests from March 2006 to January 2010. The mean age was 32.8 days at the initial sweat test. The GCT had a significantly higher QNS rate compared to the MSCS (15.4% vs. 2.1%, P < 0.0001). There was no association between age and the probability of QNS. The probability of QNS decreased as birthweight increased (P = 0.02). After adjusting for age, the odds of QNS using the GCT remained 8.34 (95% CI: 3.72-18.71) times that of the MSCS. Non-White infants had a significantly higher likelihood of QNS compared to non-Hispanic White infants (P = 0.0025). Given the performance of the MSCS, the Minnesota CF Center has implemented the MSCS as its method of choice for diagnostic sweat testing in infants following a positive state NBS.

Research paper thumbnail of Increased adherence to CFF practice guidelines for pulmonary medications correlates with improved FEV1

Pediatric Pulmonology, 2013

Background: CFF practice guidelines recommend patients age 6 use dornase alfa and hypertonic sali... more Background: CFF practice guidelines recommend patients age 6 use dornase alfa and hypertonic saline daily, and those age 6 colonized with Pseudomonas aeruginosa use inhaled tobramycin and oral azithromycin to improve lung function and reduce pulmonary exacerbations. A decline in FEV1 was noted in our 2008 CF Center Report. We hypothesized that increasing adherence to prescribing guidelines for these pulmonary medications would improve mean FEV1. Methods: This was a quality improvement project completed at a US CF center. CFF practice guidelines were reviewed with the center physicians. Patients were identified that were eligible to receive recommended therapies and it was determined whether they were prescribed the therapies. Baseline FEV1 data was collected. Adherence rates and FEV1 were followed quarterly for 1 year. Providers received a quarterly report card with adherence rates, mean FEV1 compared to colleagues, and a list of eligible patients that were not prescribed recommended therapies. Results: Ninety-two patients were included. At baseline, the overall adherence rate was 59%. Overall adherence increased quarterly (P ¼ < 0.001). Each quarter there was improvement in adherence to prescribing for each medication (P < 0.001). Except in quarter 1, FEV1 increased quarterly (P ¼ 0.092). There was moderate correlation (r ¼ 0.533) between improved adherence and improved FEV1. Conclusions: Educating clinicians about guidelines, providing feedback on adherence to guidelines, and monitoring prescribing patterns improves prescribing adherence. FEV1 showed improvement after months of sustained adherence, trending towards significance. Longer follow-up is necessary to determine if improved prescribing adherence translates into improved FEV1 or slows rate of decline in FEV1. Pediatr Pulmonol. ß

Research paper thumbnail of Urinary desmosine: A biomarker of structural lung injury during CF pulmonary exacerbation

Pediatric Pulmonology, 2012

Rationale-Cystic fibrosis (CF) lung disease is characterized by structural changes and remodeling... more Rationale-Cystic fibrosis (CF) lung disease is characterized by structural changes and remodeling in airway architecture and lung parenchyma. Neutrophilic inflammation and infection lead to injury and breakdown of airway matrix constituents, including elastin. The non-invasive measurement of urinary desmosine (UDes), a breakdown product of elastin, may be reflective of ongoing lung injury and may serve as a biomarker of active short-term damage during pulmonary exacerbation. Our objectives were to measure desmosine in the urine of CF patients hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between desmosine concentration and other markers of clinical improvement, including lung function and inflammatory mediators.

Research paper thumbnail of Epilepsy: An Anticipatory Presentation of Pediatric Wegener's Granulomatosis

Pediatric Neurology, 2010

Wegener&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;a... more Wegener&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s granulomatosis is a necrotizing, granulomatous vasculitis that primarily affects the respiratory tract and kidneys. It is rare in children. Few pediatric and adult case reports described seizures and central nervous system involvement at initial presentation, and none described central nervous system involvement in the absence of respiratory or renal disease. We describe a 17-year-old girl with secondarily generalized seizures and granulomatous lesions in her brain. Although a systemic inflammatory disorder was suspected, she lacked evidence of pulmonary or renal involvement, so her signs were initially labeled as postinfectious encephalitis or variant acute disseminated encephalomyelitis. After 1 year of immunosuppressive therapy, she developed additional signs, leading to histologic confirmation on lung biopsy of Wegener&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s granulomatosis. This case emphasizes the need for close follow-up to monitor the asynchronous development of diagnostic clues when a systemic vasculitis is suspected but cannot be confirmed.

Research paper thumbnail of Insulin secretion improves in cystic fibrosis following ivacaftor correction of CFTR: a small pilot study

Pediatric Diabetes, 2013

To determine whether the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is invol... more To determine whether the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is involved in human insulin secretion by assessing the metabolic impact of the new CFTR corrector-ivacaftor. This open-label pilot study was conducted in CF patients with the G551D mutation given new prescriptions for ivacaftor. At baseline and 4 wk after daily ivacaftor therapy, intravenous glucose tolerance tests (IVGTT) and oral glucose tolerance tests (OGTT) were performed. Five patients aged 6-52 were studied. After 1 month on ivacaftor, the insulin response to oral glucose improved by 66-178% in all subjects except one with long-standing diabetes. OGTT glucose levels were not lower in the two individuals with diabetes or the two with normal glucose tolerance (NGT), but the glucose tolerance category in the subject with impaired glucose tolerance (IGT) improved to NGT after treatment. In response to intravenous glucose, the only patient whose acute insulin secretion did not improve had newly diagnosed, untreated CFRD. The others improved by 51-346%. Acute insulin secretion was partially restored in two subjects with no measurable acute insulin response at baseline, including the one with IGT and the one with long-standing diabetes. This small pilot study suggests there is a direct role of CFTR in human insulin secretion. Larger, long-term longitudinal studies are necessary to determine whether early initiation of CFTR correction, particularly in young children with CF who have not yet lost considerable β-cell mass, will delay or prevent development of diabetes in this high-risk population.

Research paper thumbnail of Incidental sinusitis in a pediatric intensive care unit*

Pediatric Critical Care Medicine, 2012

Intubation is a risk factor for nosocomial sinusitis in adult intensive care patients. Sinusitis ... more Intubation is a risk factor for nosocomial sinusitis in adult intensive care patients. Sinusitis in intubated adults can be an occult cause of fever. In children, nasal intubation may increase the risk of sinusitis. No pediatric study has determined the frequency of nosocomial sinusitis in the pediatric intensive care unit setting. We hypothesized that within a subset of patients who had head computed tomography imaging 1) the incidental frequency of sinusitis in pediatric intensive care unit patients exceeds the frequency in non-pediatric intensive care unit patients, 2) the frequency of sinusitis is greater in pediatric intensive care unit patients with a tube (nasotracheal, nasogastric, orotracheal, or orogastric) compared to those without a tube, and 3) nasal tubes confer an increased risk for sinusitis over oral tubes. Retrospective chart review. Independent not-for-profit pediatric healthcare system. Pediatric intensive care unit and non-pediatric intensive care unit (inpatients hospitalized on medical-surgical wards) patients referred for head computed tomography. None. Computed tomography images were scored using the Lund-MacKay staging system. Sinusitis was defined as a Lund-MacKay score ≥5. A total of 596 patients were studied, 395 (66.3%) in the pediatric intensive care unit. A total of 154 (44.3%) pediatric intensive care unit vs. 54 (26.9%) non-pediatric intensive care unit patients had sinusitis (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). A total of 102 of 147 (69.4%) pediatric intensive care unit patients with a tube present had sinusitis vs. 73 of 248 (29.4%) patients without a tube present (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). There was no difference in sinusitis based on tube location (p = .472). Of patients with sinusitis, 51.3% (81 of 158) compared to 39.4% (89 of 226) were febrile within 48 hrs of imaging (p = .021). A younger age or the presence of a tube increased the probability of sinusitis (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). A total of 44.3% of our pediatric intensive care unit patients imaged for reasons other than evaluation for sinus disease had evidence of sinusitis, and 51.3% of these had fever. These findings raise the concern that sinusitis in pediatric intensive care unit patients is common and should be considered in the differential diagnosis of fever in pediatric intensive care unit patients.

Research paper thumbnail of Decreased Total Serum Coenzyme-Q10 Concentrations: A Longitudinal Study in Children with Cystic Fibrosis

The Journal of Pediatrics, 2008

To assess total serum levels of coenzyme Q(10) (Co-Q(10)), an important antioxidant, in children ... more To assess total serum levels of coenzyme Q(10) (Co-Q(10)), an important antioxidant, in children with cystic fibrosis (CF) and to investigate an association between Co-Q(10) level and clinical outcome. Co-Q(10) levels were measured annually in a prospective cohort study of 381 children with CF. A total of 1092 serum levels of total Co-Q(10) were obtained by high-performance liquid chromatography and ultraviolet light detection. Associations of Co-Q(10) with demographic variables and clinical outcomes were investigated. Of the 381 initial total serum Co-Q(10) measurements, 188 were in the deficient range. Low Co-Q(10) was significantly more prevalent in patients with pancreatic insufficiency (PI) (55%) compared with patients with pancreatic sufficiency (PS) (3%); 22% of the patients with PI exhibited persistently low Co-Q(10) levels. Low Co-Q(10) levels were significantly associated with Pseudomonas aeruginosa colonization in patients with PI and CF under age 24 months, but not with subsequent lung function or hospitalization rates. Low Co-Q(10) levels were related to other markers of nutritional status, including total lipids, beta-carotene, and alpha-tocopherol. Persistently low total serum Co-Q(10) levels are common in children with CF and PI. A prospective study is indicated to determine whether Co-Q(10) supplementation in CF is beneficial.

Research paper thumbnail of The applicability of urinary creatinine as a method of specimen normalization in the cystic fibrosis population

Journal of Cystic Fibrosis, 2010

Background-Urine specimens are commonly used in biomarker research. Urinary creatinine (UCr) is o... more Background-Urine specimens are commonly used in biomarker research. Urinary creatinine (UCr) is often used to adjust for urine analyte concentration. We aim to explore the applicability of UCr as a normalization method in a cystic fibrosis (CF) population during hospitalization.

Research paper thumbnail of Managing diabetes in cystic fibrosis

Diabetes, Obesity and Metabolism, 2010

Cystic fibrosis related diabetes (CFRD) is the most common co-morbidity in persons with cystic fi... more Cystic fibrosis related diabetes (CFRD) is the most common co-morbidity in persons with cystic fibrosis (CF). As the life expectancy of persons with CF continues to increase, the need to proactively diagnose and aggressively treat CFRD and its potential complications has become more apparent. CFRD negatively impacts lung function, growth and mortality, making its diagnosis and management crucial in a population already at high risk for early mortality. Compared to type 1 and type 2 diabetes, CFRD is a unique entity, requiring a thorough understanding of its unique pathophysiology to facilitate the creation and utilization of an effective medical treatment plan. The physiology of CFRD is complex, likely consisting of a combination of insulin deficiency, insulin resistance and a genetic predisposition towards the development of diabetes. However, the hallmark of CFRD is insulin deficiency, necessitating the use of exogenous insulin as the mainstay of therapy. Insulin administration, in combination with a multidisciplinary team of health professionals with expertise in the care of patients with CF and CFRD, is the cornerstone of the care for these patients. The goals of treatment of the CFRD population are to reverse protein catabolism, maintain a healthy weight, and reduce acute and chronic diabetes complications. Creating a partnership between the treatment team and the patient is the ideal way to accomplish these goals and is essential for successful diabetes care.

Research paper thumbnail of Impaired Fasting Glucose in Cystic Fibrosis

Diabetes Care, 2010

OBJECTIVE -While glucose tolerance abnormalities are common in cystic fibrosis (CF), impaired fas... more OBJECTIVE -While glucose tolerance abnormalities are common in cystic fibrosis (CF), impaired fasting glucose (IFG) has scarcely been explored. No studies have examined the relation between IFG and clinical status.

Research paper thumbnail of Recent trends in cystic fibrosis-related diabetes

Current Opinion in Endocrinology, Diabetes and Obesity, 2010

To provide an updated literature review highlighting important aspects of cystic fibrosis-related... more To provide an updated literature review highlighting important aspects of cystic fibrosis-related diabetes (CFRD) including epidemiology, pathogenesis, complications, screening, and management. Although CFRD continues to be associated with increased rates of mortality in the cystic fibrosis (CF) population, this has improved over the past several years, and the previous sex difference is no longer present. Recent studies support that CFRD is primarily caused by insulin deficiency due to loss of beta cells, which may occur via a number of mechanisms including oxidative stress. Aggressive screening programs with oral-glucose tolerance testing and early treatment with insulin for patients with CFRD with or without fasting hyperglycemia have led to improvements in nutritional states and lung function. Oral agents do not appear to be effective in CFRD. CFRD is the most common comorbidity in the CF population and is associated with microvascular complications and protein catabolism leading to worse health outcomes. Recognition of glycemic abnormalities through aggressive screening has led to improvements in nutritional status, pulmonary function, and mortality rates.

Research paper thumbnail of Sputum Desmosine During Hospital Admission for Pulmonary Exacerbation in Cystic Fibrosis

CHEST Journal, 2009

Background: Cystic fibrosis (CF) lung disease is characterized by structural changes in the airwa... more Background: Cystic fibrosis (CF) lung disease is characterized by structural changes in the airways and parenchyma. No sputum biomarker exists to measure the degree of active structural destruction during pulmonary exacerbation in patients with CF. The noninvasive measurement of desmosine, a breakdown product of elastin, may reflect ongoing lung injury and serve as a biomarker of short-term damage. Our objectives were to measure desmosine in the sputum of patients with CF hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between desmosine levels and other markers of clinical improvement, including lung function and inflammatory mediators, following hospitalization. Methods: Sputum and blood samples collected and lung function measurements were made at multiple time points during hospitalization. We used a repeated measures model, adjusted for age and time between measurements, to compare log-transformed sputum desmosine levels across multiple time points and to correlate those levels with related variables.

Research paper thumbnail of Challenges in translating plasma proteomics from bench to bedside: update from the NHLBI Clinical Proteomics Programs

AJP: Lung Cellular and Molecular Physiology, 2008

The emerging scientific field of proteomics encompasses the identification, characterization and ... more The emerging scientific field of proteomics encompasses the identification, characterization and quantification of the protein content or proteome of whole cells, tissues or body fluids. The potential for proteomic technologies to identify and quantify novel proteins in the plasma that can function as biomarkers of the presence or severity of clinical disease states holds great promise for clinical use.

Research paper thumbnail of Editorial Commentary : Pseudomonas aeruginosa Eradication: How Do We Measure Success?

Clinical Infectious Diseases, 2015

Research paper thumbnail of Metabolomics analysis identifies novel plasma biomarkers of cystic fibrosis pulmonary exacerbation

Pediatric pulmonology, 2015

Cystic fibrosis (CF) lung disease is characterized by infection, inflammation, lung function decl... more Cystic fibrosis (CF) lung disease is characterized by infection, inflammation, lung function decline, and intermittent pulmonary exacerbations. However, the link between pulmonary exacerbation and lung disease progression remains unclear. Global metabolomic profiling can provide novel mechanistic insight into a disease process in addition to putative biomarkers for future study. Our objective was to investigate how the plasma metabolomic profile changes between CF pulmonary exacerbation and a clinically well state. Plasma samples and lung function data were collected from 25 CF patients during hospitalization for a pulmonary exacerbation and during quarterly outpatient clinic visits. In collaboration with Metabolon, Inc., the metabolomic profiles of matched pair plasma samples, one during exacerbation and one at a clinic visit, were analyzed using gas and liquid chromatography coupled with mass spectrometry. Compounds were identified by comparison to a library of standards. Mixed ef...

Research paper thumbnail of Specific Gravity As A Novel Normalization Method For Urinary Biomarker Measurement In A Cystic Fibrosis Population During Pulmonary Exacerbation

A53. CYSTIC FIBROSIS: CLINICAL PEDIATRIC STUDIES, 2010

Research paper thumbnail of Vitamin D Deficiency Is Associated with Pulmonary Exacerbations in Children with Cystic Fibrosis

Annals of the American Thoracic Society, 2014

Rationale: Recent literature suggests vitamin D has an effect on lung function and on the lung's ... more Rationale: Recent literature suggests vitamin D has an effect on lung function and on the lung's ability to fight infection, both important in the cystic fibrosis (CF) population as predictors of morbidity and mortality.

Research paper thumbnail of Contributors

Berman's Pediatric Decision Making, 2011

Research paper thumbnail of Fifteen-Year-Old Girl With Severe Obstructive Lung Disease, Pansinusitis, and Failure to Thrive

Clinical Pediatrics, 2014

Research paper thumbnail of The arginine decarboxylase pathways of host and pathogen interact to impact inflammatory pathways in the lung

PloS one, 2014

The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both human... more The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both humans and most bacterial pathogens. In humans agmatine is a neurotransmitter with affinities towards α2-adrenoreceptors, serotonin receptors, and may inhibit nitric oxide synthase. In bacteria agmatine serves as a precursor to polyamine synthesis and was recently shown to enhance biofilm development in some strains of the respiratory pathogen Pseudomonas aeruginosa. We determined agmatine is at the center of a competing metabolism in the human lung during airways infections and is influenced by the metabolic phenotypes of the infecting pathogens. Ultra performance liquid chromatography with mass spectrometry detection was used to measure agmatine in human sputum samples from patients with cystic fibrosis, spent supernatant from clinical sputum isolates, and from bronchoalvelolar lavage fluid from mice infected with P. aeruginosa agmatine mutants. Agmatine in human sputum peaks during illness...

Research paper thumbnail of Comparison of quantitative sweat chloride methods after positive newborn screen for cystic fibrosis

Pediatric Pulmonology, 2012

Rapid and reliable confirmatory sweat testing following a positive newborn screen (NBS) for cysti... more Rapid and reliable confirmatory sweat testing following a positive newborn screen (NBS) for cystic fibrosis (CF) is preferred to allow for early diagnosis and to decrease parental anxiety. The Cystic Fibrosis Foundation (CFF) recently recommended a quantity not sufficient (QNS) rate of ≤ 10% in infants &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;3 months of age referred for quantitative sweat chloride analysis. Two CFF-approved methods are available by which to quantitatively measure chloride concentration in sweat. Our objective was to compare the performance of the Macroduct® sweat collection system (MSCS) with the Gibson and Cooke technique (GCT) in the acquisition of samples for the determination of sweat chloride concentration in infants with a positive Minnesota State NBS for CF. A retrospective database review of infants referred to the core Minnesota CF Center or its affiliate site for confirmatory sweat testing was performed to compare the QNS rates for the two techniques. Associations between birthweight, age at test, race, and QNS rates were examined. Five hundred sixty-eight infants were referred for 616 sweat tests from March 2006 to January 2010. The mean age was 32.8 days at the initial sweat test. The GCT had a significantly higher QNS rate compared to the MSCS (15.4% vs. 2.1%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). There was no association between age and the probability of QNS. The probability of QNS decreased as birthweight increased (P = 0.02). After adjusting for age, the odds of QNS using the GCT remained 8.34 (95% CI: 3.72-18.71) times that of the MSCS. Non-White infants had a significantly higher likelihood of QNS compared to non-Hispanic White infants (P = 0.0025). Given the performance of the MSCS, the Minnesota CF Center has implemented the MSCS as its method of choice for diagnostic sweat testing in infants following a positive state NBS.

Research paper thumbnail of Increased adherence to CFF practice guidelines for pulmonary medications correlates with improved FEV1

Pediatric Pulmonology, 2013

Background: CFF practice guidelines recommend patients age 6 use dornase alfa and hypertonic sali... more Background: CFF practice guidelines recommend patients age 6 use dornase alfa and hypertonic saline daily, and those age 6 colonized with Pseudomonas aeruginosa use inhaled tobramycin and oral azithromycin to improve lung function and reduce pulmonary exacerbations. A decline in FEV1 was noted in our 2008 CF Center Report. We hypothesized that increasing adherence to prescribing guidelines for these pulmonary medications would improve mean FEV1. Methods: This was a quality improvement project completed at a US CF center. CFF practice guidelines were reviewed with the center physicians. Patients were identified that were eligible to receive recommended therapies and it was determined whether they were prescribed the therapies. Baseline FEV1 data was collected. Adherence rates and FEV1 were followed quarterly for 1 year. Providers received a quarterly report card with adherence rates, mean FEV1 compared to colleagues, and a list of eligible patients that were not prescribed recommended therapies. Results: Ninety-two patients were included. At baseline, the overall adherence rate was 59%. Overall adherence increased quarterly (P ¼ < 0.001). Each quarter there was improvement in adherence to prescribing for each medication (P < 0.001). Except in quarter 1, FEV1 increased quarterly (P ¼ 0.092). There was moderate correlation (r ¼ 0.533) between improved adherence and improved FEV1. Conclusions: Educating clinicians about guidelines, providing feedback on adherence to guidelines, and monitoring prescribing patterns improves prescribing adherence. FEV1 showed improvement after months of sustained adherence, trending towards significance. Longer follow-up is necessary to determine if improved prescribing adherence translates into improved FEV1 or slows rate of decline in FEV1. Pediatr Pulmonol. ß

Research paper thumbnail of Urinary desmosine: A biomarker of structural lung injury during CF pulmonary exacerbation

Pediatric Pulmonology, 2012

Rationale-Cystic fibrosis (CF) lung disease is characterized by structural changes and remodeling... more Rationale-Cystic fibrosis (CF) lung disease is characterized by structural changes and remodeling in airway architecture and lung parenchyma. Neutrophilic inflammation and infection lead to injury and breakdown of airway matrix constituents, including elastin. The non-invasive measurement of urinary desmosine (UDes), a breakdown product of elastin, may be reflective of ongoing lung injury and may serve as a biomarker of active short-term damage during pulmonary exacerbation. Our objectives were to measure desmosine in the urine of CF patients hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between desmosine concentration and other markers of clinical improvement, including lung function and inflammatory mediators.

Research paper thumbnail of Epilepsy: An Anticipatory Presentation of Pediatric Wegener's Granulomatosis

Pediatric Neurology, 2010

Wegener&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;a... more Wegener&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s granulomatosis is a necrotizing, granulomatous vasculitis that primarily affects the respiratory tract and kidneys. It is rare in children. Few pediatric and adult case reports described seizures and central nervous system involvement at initial presentation, and none described central nervous system involvement in the absence of respiratory or renal disease. We describe a 17-year-old girl with secondarily generalized seizures and granulomatous lesions in her brain. Although a systemic inflammatory disorder was suspected, she lacked evidence of pulmonary or renal involvement, so her signs were initially labeled as postinfectious encephalitis or variant acute disseminated encephalomyelitis. After 1 year of immunosuppressive therapy, she developed additional signs, leading to histologic confirmation on lung biopsy of Wegener&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s granulomatosis. This case emphasizes the need for close follow-up to monitor the asynchronous development of diagnostic clues when a systemic vasculitis is suspected but cannot be confirmed.

Research paper thumbnail of Insulin secretion improves in cystic fibrosis following ivacaftor correction of CFTR: a small pilot study

Pediatric Diabetes, 2013

To determine whether the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is invol... more To determine whether the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is involved in human insulin secretion by assessing the metabolic impact of the new CFTR corrector-ivacaftor. This open-label pilot study was conducted in CF patients with the G551D mutation given new prescriptions for ivacaftor. At baseline and 4 wk after daily ivacaftor therapy, intravenous glucose tolerance tests (IVGTT) and oral glucose tolerance tests (OGTT) were performed. Five patients aged 6-52 were studied. After 1 month on ivacaftor, the insulin response to oral glucose improved by 66-178% in all subjects except one with long-standing diabetes. OGTT glucose levels were not lower in the two individuals with diabetes or the two with normal glucose tolerance (NGT), but the glucose tolerance category in the subject with impaired glucose tolerance (IGT) improved to NGT after treatment. In response to intravenous glucose, the only patient whose acute insulin secretion did not improve had newly diagnosed, untreated CFRD. The others improved by 51-346%. Acute insulin secretion was partially restored in two subjects with no measurable acute insulin response at baseline, including the one with IGT and the one with long-standing diabetes. This small pilot study suggests there is a direct role of CFTR in human insulin secretion. Larger, long-term longitudinal studies are necessary to determine whether early initiation of CFTR correction, particularly in young children with CF who have not yet lost considerable β-cell mass, will delay or prevent development of diabetes in this high-risk population.

Research paper thumbnail of Incidental sinusitis in a pediatric intensive care unit*

Pediatric Critical Care Medicine, 2012

Intubation is a risk factor for nosocomial sinusitis in adult intensive care patients. Sinusitis ... more Intubation is a risk factor for nosocomial sinusitis in adult intensive care patients. Sinusitis in intubated adults can be an occult cause of fever. In children, nasal intubation may increase the risk of sinusitis. No pediatric study has determined the frequency of nosocomial sinusitis in the pediatric intensive care unit setting. We hypothesized that within a subset of patients who had head computed tomography imaging 1) the incidental frequency of sinusitis in pediatric intensive care unit patients exceeds the frequency in non-pediatric intensive care unit patients, 2) the frequency of sinusitis is greater in pediatric intensive care unit patients with a tube (nasotracheal, nasogastric, orotracheal, or orogastric) compared to those without a tube, and 3) nasal tubes confer an increased risk for sinusitis over oral tubes. Retrospective chart review. Independent not-for-profit pediatric healthcare system. Pediatric intensive care unit and non-pediatric intensive care unit (inpatients hospitalized on medical-surgical wards) patients referred for head computed tomography. None. Computed tomography images were scored using the Lund-MacKay staging system. Sinusitis was defined as a Lund-MacKay score ≥5. A total of 596 patients were studied, 395 (66.3%) in the pediatric intensive care unit. A total of 154 (44.3%) pediatric intensive care unit vs. 54 (26.9%) non-pediatric intensive care unit patients had sinusitis (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). A total of 102 of 147 (69.4%) pediatric intensive care unit patients with a tube present had sinusitis vs. 73 of 248 (29.4%) patients without a tube present (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). There was no difference in sinusitis based on tube location (p = .472). Of patients with sinusitis, 51.3% (81 of 158) compared to 39.4% (89 of 226) were febrile within 48 hrs of imaging (p = .021). A younger age or the presence of a tube increased the probability of sinusitis (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). A total of 44.3% of our pediatric intensive care unit patients imaged for reasons other than evaluation for sinus disease had evidence of sinusitis, and 51.3% of these had fever. These findings raise the concern that sinusitis in pediatric intensive care unit patients is common and should be considered in the differential diagnosis of fever in pediatric intensive care unit patients.

Research paper thumbnail of Decreased Total Serum Coenzyme-Q10 Concentrations: A Longitudinal Study in Children with Cystic Fibrosis

The Journal of Pediatrics, 2008

To assess total serum levels of coenzyme Q(10) (Co-Q(10)), an important antioxidant, in children ... more To assess total serum levels of coenzyme Q(10) (Co-Q(10)), an important antioxidant, in children with cystic fibrosis (CF) and to investigate an association between Co-Q(10) level and clinical outcome. Co-Q(10) levels were measured annually in a prospective cohort study of 381 children with CF. A total of 1092 serum levels of total Co-Q(10) were obtained by high-performance liquid chromatography and ultraviolet light detection. Associations of Co-Q(10) with demographic variables and clinical outcomes were investigated. Of the 381 initial total serum Co-Q(10) measurements, 188 were in the deficient range. Low Co-Q(10) was significantly more prevalent in patients with pancreatic insufficiency (PI) (55%) compared with patients with pancreatic sufficiency (PS) (3%); 22% of the patients with PI exhibited persistently low Co-Q(10) levels. Low Co-Q(10) levels were significantly associated with Pseudomonas aeruginosa colonization in patients with PI and CF under age 24 months, but not with subsequent lung function or hospitalization rates. Low Co-Q(10) levels were related to other markers of nutritional status, including total lipids, beta-carotene, and alpha-tocopherol. Persistently low total serum Co-Q(10) levels are common in children with CF and PI. A prospective study is indicated to determine whether Co-Q(10) supplementation in CF is beneficial.

Research paper thumbnail of The applicability of urinary creatinine as a method of specimen normalization in the cystic fibrosis population

Journal of Cystic Fibrosis, 2010

Background-Urine specimens are commonly used in biomarker research. Urinary creatinine (UCr) is o... more Background-Urine specimens are commonly used in biomarker research. Urinary creatinine (UCr) is often used to adjust for urine analyte concentration. We aim to explore the applicability of UCr as a normalization method in a cystic fibrosis (CF) population during hospitalization.

Research paper thumbnail of Managing diabetes in cystic fibrosis

Diabetes, Obesity and Metabolism, 2010

Cystic fibrosis related diabetes (CFRD) is the most common co-morbidity in persons with cystic fi... more Cystic fibrosis related diabetes (CFRD) is the most common co-morbidity in persons with cystic fibrosis (CF). As the life expectancy of persons with CF continues to increase, the need to proactively diagnose and aggressively treat CFRD and its potential complications has become more apparent. CFRD negatively impacts lung function, growth and mortality, making its diagnosis and management crucial in a population already at high risk for early mortality. Compared to type 1 and type 2 diabetes, CFRD is a unique entity, requiring a thorough understanding of its unique pathophysiology to facilitate the creation and utilization of an effective medical treatment plan. The physiology of CFRD is complex, likely consisting of a combination of insulin deficiency, insulin resistance and a genetic predisposition towards the development of diabetes. However, the hallmark of CFRD is insulin deficiency, necessitating the use of exogenous insulin as the mainstay of therapy. Insulin administration, in combination with a multidisciplinary team of health professionals with expertise in the care of patients with CF and CFRD, is the cornerstone of the care for these patients. The goals of treatment of the CFRD population are to reverse protein catabolism, maintain a healthy weight, and reduce acute and chronic diabetes complications. Creating a partnership between the treatment team and the patient is the ideal way to accomplish these goals and is essential for successful diabetes care.

Research paper thumbnail of Impaired Fasting Glucose in Cystic Fibrosis

Diabetes Care, 2010

OBJECTIVE -While glucose tolerance abnormalities are common in cystic fibrosis (CF), impaired fas... more OBJECTIVE -While glucose tolerance abnormalities are common in cystic fibrosis (CF), impaired fasting glucose (IFG) has scarcely been explored. No studies have examined the relation between IFG and clinical status.

Research paper thumbnail of Recent trends in cystic fibrosis-related diabetes

Current Opinion in Endocrinology, Diabetes and Obesity, 2010

To provide an updated literature review highlighting important aspects of cystic fibrosis-related... more To provide an updated literature review highlighting important aspects of cystic fibrosis-related diabetes (CFRD) including epidemiology, pathogenesis, complications, screening, and management. Although CFRD continues to be associated with increased rates of mortality in the cystic fibrosis (CF) population, this has improved over the past several years, and the previous sex difference is no longer present. Recent studies support that CFRD is primarily caused by insulin deficiency due to loss of beta cells, which may occur via a number of mechanisms including oxidative stress. Aggressive screening programs with oral-glucose tolerance testing and early treatment with insulin for patients with CFRD with or without fasting hyperglycemia have led to improvements in nutritional states and lung function. Oral agents do not appear to be effective in CFRD. CFRD is the most common comorbidity in the CF population and is associated with microvascular complications and protein catabolism leading to worse health outcomes. Recognition of glycemic abnormalities through aggressive screening has led to improvements in nutritional status, pulmonary function, and mortality rates.

Research paper thumbnail of Sputum Desmosine During Hospital Admission for Pulmonary Exacerbation in Cystic Fibrosis

CHEST Journal, 2009

Background: Cystic fibrosis (CF) lung disease is characterized by structural changes in the airwa... more Background: Cystic fibrosis (CF) lung disease is characterized by structural changes in the airways and parenchyma. No sputum biomarker exists to measure the degree of active structural destruction during pulmonary exacerbation in patients with CF. The noninvasive measurement of desmosine, a breakdown product of elastin, may reflect ongoing lung injury and serve as a biomarker of short-term damage. Our objectives were to measure desmosine in the sputum of patients with CF hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between desmosine levels and other markers of clinical improvement, including lung function and inflammatory mediators, following hospitalization. Methods: Sputum and blood samples collected and lung function measurements were made at multiple time points during hospitalization. We used a repeated measures model, adjusted for age and time between measurements, to compare log-transformed sputum desmosine levels across multiple time points and to correlate those levels with related variables.

Research paper thumbnail of Challenges in translating plasma proteomics from bench to bedside: update from the NHLBI Clinical Proteomics Programs

AJP: Lung Cellular and Molecular Physiology, 2008

The emerging scientific field of proteomics encompasses the identification, characterization and ... more The emerging scientific field of proteomics encompasses the identification, characterization and quantification of the protein content or proteome of whole cells, tissues or body fluids. The potential for proteomic technologies to identify and quantify novel proteins in the plasma that can function as biomarkers of the presence or severity of clinical disease states holds great promise for clinical use.