Cori L Daines

Interests

No activities entered.

Courses

Scholarly Contributions

Chapters

• Daines, C. L. (2021). Cystic Fibrosis. In Conns Current Therapy 2022. Elsevir.
• Daines, C. L. (2021). Indications and Risks of Flexible Bronchoscopy in Children. In Diagnostic and Interventional Bronchoscopy in Children(pp 51-64). Humana Press.
• Phan, H., & Daines, C. L. (2020). Cystic Fibrosis. In Conns Current Therapy 2021(pp 843-847). Elsevir.
• Daines, C. L. (2018). Aspiration Syndromes. In Rudolph's Pediatrics, 23rd ed.
• Daines, C. L. (2017). Aspiration Syndromes. In Rudolph's Pediatrics.
• Daines, C. L. (2020). Cystic Fibrosis. In Conn's Current Therapy 2020.
• Daines, C. L. (2011). Aspiration Syndroms. In Rudolph's Pediatrics(pp 1958-1962). McGraw-Hill.

Journals/Publications

• Daines, C. L., Tullis, E., Costa, S., Linnemann, R. W., Mall, M. A., McKone, E. F., Polineni, D., Quon, B. S., Ringshausen, F. C., Rowe, S. M., Selvadurai, H., Taylor-Cousar, J. L., Withers, N. J., Ahluwalia, N., Moskowitz, S. M., Prieto-Centurion, V., Tan, Y. V., Tian, S., Weinstock, T., , Xuan, F., et al. (2023). Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and at least one allele: 144-week interim results from a 192-week open-label extension study. The European respiratory journal, 62(6).
  More info

  In two pivotal phase 3 trials, up to 24 weeks of treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was efficacious and safe in patients with cystic fibrosis (CF) ≥12 years of age who have at least one allele. The aim of this study is to assess long-term safety and efficacy of ELX/TEZ/IVA in these patients.
• Daines, C. (2022). Childhood Respiratory Conditions: Nonasthma Chronic Lung Disease. FP essentials, 513, 32-38.
  More info

  Bronchopulmonary dysplasia (BPD) is a chronic lung disease that results from impaired lung development or lung injury from ventilatory support. It primarily is seen in infants born prematurely. Approximately 95% of infants with BPD had a low birth weight (ie, less than 1,500 g). This condition affects pulmonary function throughout the life span. Many children with BPD develop asthmalike symptoms with recurrent wheezing beginning in the preschool-aged years. Complications include pulmonary hypertension, tracheomalacia, glottic damage, sleep apnea, and more frequent and/or severe respiratory infections. Measures should be taken to prevent respiratory infections in these patients. Cystic fibrosis (CF) is caused by an autosomal recessive sequence variation in the CF transmembrane conductance regulator () gene that results in mucus accumulation on cell surfaces. Mucus accumulation in the airways causes chronic cough, wheezing, recurrent infections, and progressive loss of lung function. Treatment includes clearance of mucus from the lungs and infection management. Complications and associated conditions include sinusitis, nutritional and gastrointestinal issues, dehydration, pancreatic insufficiency, and CF-related diabetes. All of these should be addressed. Most cases of CF are diagnosed via newborn screening and follow-up sweat tests. New CFTR modulators that improve CFTR protein function offer hope of improved longevity and quality of life for patients with specific sequence variants.
• Ezmigna, D., Brown, M., Daines, C., & Morgan, W. (2022). Bronchoalveolar lavage profiles in uncontrolled wheezy children compared by asthma predictive index. Pediatric pulmonology, 57(1), 293-299.
  More info

  The asthma predictive index (API) predicts later asthma in preschoolers with frequent wheeze. We hypothesized that airway cytology differs between API positive (API+)/negative (API-) children with uncontrolled/recurrent wheezing with dominance of eosinophils in API+ and neutrophils in API- groups respectively. The main objective of this study is to compare bronchoalveolar lavage (BAL) cell profiles in API+/API- children with recurrent wheezing unresponsive to inhaled corticosteroids (ICS).
• Fajac, I., Daines, C., Durieu, I., Goralski, J. L., Heijerman, H., Knoop, C., Majoor, C., Bruinsma, B. G., Moskowitz, S., Prieto-Centurion, V., Van Brunt, K., Zhang, Y., & Quittner, A. (2022). Non-respiratory health-related quality of life in people with cystic fibrosis receiving elexacaftor/tezacaftor/ivacaftor. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society.
  More info

  Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in people with cystic fibrosis (CF) heterozygous for F508del and a minimal function mutation (F/MF) or homozygous for F508del (F/F) in two pivotal Phase 3 trials, significantly improving percentage predicted forced expiratory volume in 1 second, Cystic Fibrosis Questionnaire-Revised, Respiratory Domain (CFQ-R RD) scores, and sweat chloride concentration. Here, we analyzed the 11 non-respiratory domains (non-RDs) of the CFQ-R, which assess general health-related quality of life (i.e., Physical Functioning, Role Functioning, Vitality, Health Perceptions, Emotional Functioning, and Social Functioning) and quality of life impacted by CF (i.e., Body Image, Eating Problems, Treatment Burden, Weight, and Digestive Symptoms), for participants in these two Phase 3 trials. ELX/TEZ/IVA treatment led to higher scores in all CFQ-R non-RDs, with improvements in most domains compared with control treatments. These findings demonstrate that ELX/TEZ/IVA improves a range of CF-specific symptoms and general functioning and well-being.
• Asseri, A. A., Khattab, N., Ezmigna, D., Awadalla, N. J., Daines, C., & Morgan, W. (2021). Diagnostic Accuracy of Nasopharyngeal Swab Cultures in Children Less Than Five Years with Chronic Wet Cough. Children (Basel, Switzerland), 8(12).
  More info

  It is necessary to find a non-invasive and accurate procedure to predict persistent bacterial bronchitis (PBB) causative organisms and guide antibiotic therapy. The study objective was to compare the diagnostic accuracy of nasopharyngeal swab cultures with bronchoalveolar lavage (BAL) cultures in children with PBB.
• Daines, C. L., & Morgan, W. J. (2021). The Future of Highly Effective Modulator Therapy in Cystic Fibrosis. American journal of respiratory and critical care medicine, 203(12), 1453-1455.
• Elborn, J. S., Konstan, M. W., Taylor-Cousar, J. L., Fajac, I., Horsley, A., Sutharsan, S., Aaron, S. D., Daines, C. L., Uluer, A., Downey, D. G., Lucidi, V. V., Ahuja, S., Springman, E., Mershon, J., Grosswald, R., Rowe, S. M., & , E. s. (2021). Empire-CF study: A phase 2 clinical trial of leukotriene A4 hydrolase inhibitor acebilustat in adult subjects with cystic fibrosis. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 20(6), 1026-1034.
  More info

  Cystic fibrosis (CF) is characterized by neutrophilic inflammation in the airways. Leukotriene B4 (LTB) is a neutrophil chemoattractant and has been implicated in CF pathogenesis. Acebilustat, a novel, synthetic, small-molecule leukotriene A4 hydrolase inhibitor, reduces LTB production. We report findings from a randomized placebo-controlled trial of acebilustat in adult subjects with mild-to-moderate lung disease.
• Flume, P. A., Amelina, E., Daines, C. L., Charlton, B., Leadbetter, J., Guasconi, A., & Aitken, M. L. (2021). Efficacy and safety of inhaled dry-powder mannitol in adults with cystic fibrosis: An international, randomized controlled study. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 20(6), 1003-1009.
  More info

  Mannitol is a mucoactive hyperosmotic agent used as add-on therapy in patients with cystic fibrosis (CF), administered twice-daily (BID) via a small, portable, breath-actuated dry-powder inhaler. This study was conducted to provide confirmatory evidence of mannitol's efficacy and safety in adults.
• Griese, M., Costa, S., Linnemann, R. W., Mall, M. A., McKone, E. F., Polineni, D., Quon, B. S., Ringshausen, F. C., Taylor-Cousar, J. L., Withers, N. J., Moskowitz, S. M., & Daines, C. L. (2021). Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor for 24 Weeks or Longer in People with Cystic Fibrosis and One or More Alleles: Interim Results of an Open-Label Phase 3 Clinical Trial. American journal of respiratory and critical care medicine, 203(3), 381-385.
• Leadbetter, J., Guasconi, A., Flume, P. A., Daines, C. L., Charlton, B., Amelina, E., & Aitken, M. L. (2021). Efficacy and safety of inhaled dry-powder mannitol in adults with cystic fibrosis: An international, randomized controlled study.. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. doi:10.1016/j.jcf.2021.02.011
  More info

  Mannitol is a mucoactive hyperosmotic agent used as add-on therapy in patients with cystic fibrosis (CF), administered twice-daily (BID) via a small, portable, breath-actuated dry-powder inhaler. This study was conducted to provide confirmatory evidence of mannitol's efficacy and safety in adults..This multicenter, double-blind, randomized, parallel-group, controlled clinical trial recruited adults (aged ≥18 years) with CF, and forced expiratory volume in 1 second (FEV1) 40-90% predicted. Subjects received either mannitol 400 mg or mannitol 50 mg (control), BID via dry-powder inhaler for 26 weeks. Primary endpoint: FEV1 averaged over the 26-week treatment period..Of 423 subjects randomized (209 or 214 receiving mannitol 400 mg BID or control, respectively), 373 (88.2%) completed the study, with a similar proportion completing in the two groups. For FEV1 averaged over 26 weeks, mannitol 400 mg BID was statistically superior to control (adjusted mean difference 54 mL [95% CI 8, 100 mL]; p = 0.020). This was supported by sensitivity analyses of the primary endpoint, and by observed improvements in secondary pulmonary function endpoints (eg, absolute adjusted mean difference in percent predicted FEV1 averaged over 26 weeks 1.21% [0.07%, 2.36%]; p = 0.037). Adverse events were mainly mild or moderate in severity, with treatment-related adverse events in 15.5 and 12.2% of subjects receiving mannitol 400 mg BID and control, respectively..In adults with CF, mannitol 400 mg BID inhaled as a dry-powder statistically significantly improved lung function (FEV1) compared with control, with this improvement supported by sensitivity analyses and secondary pulmonary function endpoints. Mannitol had a good overall safety and tolerability profile. ClinicalTrials.gov: NCT02134353.
• Morgan, W. J., & Daines, C. L. (2021). The Future of Highly Effective Modulator Therapy in Cystic Fibrosis.. American journal of respiratory and critical care medicine, 203(12), 1453-1455. doi:10.1164/rccm.202104-0850ed
• Wang, C., Savage, J., Quittner, A. L., Moskowitz, S. M., Majoor, C., Knoop, C., Heijerman, H. G., Goralski, J., Fajac, I., Durieu, I., Daines, C. L., Brunt, K. V., & Booth, J. (2021). S65 Impact of elexacaftor/tezacaftor/ivacaftor triple combination therapy on health-related quality of life in people with cystic fibrosis heterozygous for F508del and a minimal function mutation (F/MF): results from a Phase 3 clinical study. Thorax. doi:10.1136/thorax-2020-btsabstracts.70
• Wang, C., Savage, J., Quittner, A. L., Moskowitz, S. M., Majoor, C., Knoop, C., Heijerman, H. G., Goralski, J., Fajac, I., Durieu, I., Daines, C. L., Brunt, K. V., & Booth, J. (2021). S66 Impact of elexacaftor/tezacaftor/ivacaftor triple combination therapy on health-related quality of life in people with cystic fibrosis homozygous for F508del (F/F): results from a Phase 3 clinical study. Thorax. doi:10.1136/thorax-2020-btsabstracts.71
• Zemanick, E. T., Zanni, R. L., Yang, Y., Withers, N., Wilson, J. W., Weersink, E. J., Morrissey, B., Morrison, N., Moller, A., Moffett, K., Millar, S. J., Milla, C., Middleton, P. G., Messore, B., Merkus, P., Mehdi, N., Meer, R. V., Mcwilliams, B., Mcnamara, J., , Mckone, E. F., et al. (2021). Long-term safety and efficacy of tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years or older who are homozygous or heterozygous for Phe508del CFTR (EXTEND): an open-label extension study.. The Lancet. Respiratory medicine, 9(7), 733-746. doi:10.1016/s2213-2600(20)30510-5
  More info

  Tezacaftor-ivacaftor is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator shown to be efficacious and generally safe and well tolerated over 8-24 weeks in phase 3 clinical studies in participants aged 12 years or older with cystic fibrosis homozygous for the Phe508del CFTR mutation (F/F; study 661-106 [EVOLVE]) or heterozygous for the Phe508del CFTR mutation and a residual function mutation (F/RF; study 661-108 [EXPAND]). Longer-term (>24 weeks) safety and efficacy of tezacaftor-ivacaftor has not been assessed in clinical studies. Here, we present results of study 661-110 (EXTEND), a 96-week open-label extension study that assessed long-term safety, tolerability, and efficacy of tezacaftor-ivacaftor in participants aged 12 years or older with cystic fibrosis who were homozygous or heterozygous for the Phe508del CFTR mutation..Study 661-110 was a 96-week, phase 3, multicentre, open-label study at 170 clinical research sites in Australia, Europe, Israel, and North America. Participants were aged 12 years or older, had cystic fibrosis, were homozygous or heterozygous for Phe508del CFTR, and completed one of six parent studies of tezacaftor-ivacaftor: studies 661-103, 661-106, 661-107, 661-108, 661-109, and 661-111. Participants received oral tezacaftor 100 mg once daily and oral ivacaftor 150 mg once every 12 h for up to 96 weeks. The primary endpoint was safety and tolerability. Secondary endpoints were changes in lung function, nutritional parameters, and respiratory symptom scores; pulmonary exacerbations; and pharmacokinetic parameters. A post-hoc analysis assessed the rate of lung function decline in F/F participants who received up to 120 weeks of tezacaftor-ivacaftor in studies 661-106 (F/F) and/or 661-110 compared with a matched cohort of CFTR modulator-untreated historical F/F controls from the Cystic Fibrosis Foundation Patient Registry. Primary safety analyses were done in all participants from all six parent studies who received at least one dose of study drug during this study. This study was registered at ClinicalTrials.gov (NCT02565914)..Between Aug 31, 2015, to May 31, 2019, 1044 participants were enrolled in study 661-110 from the six parent studies of whom 1042 participants received at least one dose of study drug and were included in the safety set. 995 (95%) participants had at least one TEAE; 22 (2%) had TEAEs leading to discontinuation; and 351 (34%) had serious TEAEs. No deaths occurred during the treatment-emergent period; after the treatment-emergent period, two deaths occurred, which were both deemed unrelated to study drug. F/F (106/110; n=459) and F/RF (108/110; n=226) participants beginning tezacaftor-ivacaftor in study 661-110 had improvements in efficacy endpoints consistent with parent studies; improvements in lung function and nutritional parameters and reductions in pulmonary exacerbations observed in the tezacaftor-ivacaftor groups in the parent studies were generally maintained in study 661-110 for an additional 96 weeks. Pharmacokinetic parameters were also similar to those in the parent studies. The annualised rate of lung function decline was 61·5% (95% CI 35·8 to 86·1) lower in tezacaftor-ivacaftor-treated F/F participants versus untreated matched historical controls..Tezacaftor-ivacaftor was generally safe, well tolerated, and efficacious for up to 120 weeks, and the safety profile of tezacaftor-ivacaftor in study 661-110 was consistent with cystic fibrosis manifestations and with the safety profiles of the parent studies. The rate of lung function decline was significantly reduced in F/F participants, consistent with cystic fibrosis disease modification. Our results support the clinical benefit of long-term tezacaftor-ivacaftor treatment for people aged 12 years or older with cystic fibrosis with F/F or F/RF genotypes..Vertex Pharmaceuticals Incorporated.
• Devereux, G., Wrolstad, D., Bourke, S. J., Daines, C. L., Doe, S., Dougherty, R., Franco, R., Innes, A., Kopp, B. T., Lascano, J., Layish, D., MacGregor, G., Murray, L., Peckham, D., Lucidi, V., Lovie, E., Robertson, J., Fraser-Pitt, D. J., & O'Neil, D. A. (2020). Oral cysteamine as an adjunct treatment in cystic fibrosis pulmonary exacerbations: An exploratory randomized clinical trial. PloS one, 15(12), e0242945.
  More info

  Emerging data suggests a possible role for cysteamine as an adjunct treatment for pulmonary exacerbations of cystic fibrosis (CF) that continue to be a major clinical challenge. There are no studies investigating the use of cysteamine in pulmonary exacerbations of CF. This exploratory randomized clinical trial was conducted to answer the question: In future pivotal trials of cysteamine as an adjunct treatment in pulmonary exacerbations of CF, which candidate cysteamine dosing regimens should be tested and which are the most appropriate, clinically meaningful outcome measures to employ as endpoints?
• Hoppe, J. E., Guimbellot, J., Martiniano, S. L., Toprak, D., Davis, C., Daines, C. L., Muhlebach, M. S., Esther, C. R., & Dellon, E. P. (2020). Highlights from the 2019 North American Cystic Fibrosis Conference. Pediatric pulmonology, 55(9), 2225-2232.
  More info

  This review briefly summarizes presentations in several major topic areas at the conference: pathophysiology and basic science of cystic fibrosis lung disease, clinical trials, clinical quality improvement, microbiology and treatment of infection, and transition, advanced lung disease and transplant, mental health and psychosocial concerns. The review is intended to highlight several areas and is not a comprehensive summary of the conference. Citations from the conference are by the first author and abstract number or symposium number, as designated in the supplement.
• Wang, C., Savage, J., Quittner, A. L., Moskowitz, S. M., Majoor, C., Knoop, C., Heijerman, H. G., Goralski, J., Fajac, I., Durieu, I., Daines, C. L., Brunt, K. V., & Booth, J. (2020). P221 Impact of elexacaftor/tezacaftor/ivacaftor triple combination therapy on health-related quality of life in people with cystic fibrosis heterozygous for F508del and a minimal function mutation: results from a Phase 3 clinical study. Journal of Cystic Fibrosis, 19, S118-S119. doi:10.1016/s1569-1993(20)30555-5
• Wang, C., Savage, J., Quittner, A. L., Moskowitz, S. M., Majoor, C., Knoop, C., Heijerman, H. G., Goralski, J., Fajac, I., Durieu, I., Daines, C. L., Brunt, K. V., & Booth, J. (2020). WS19.6 Impact of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) triple combination therapy on health-related quality of life (HRQoL) in people with cystic fibrosis (pwCF) homozygous for F508del (F/F): results from a Phase 3 clinical study. Journal of Cystic Fibrosis, 19, S32. doi:10.1016/s1569-1993(20)30268-x
• Asseri, A. A., Zeng, Y., & Daines, C. L. (2019). Acute pulmonary embolism in a child with ANCA-negative Idiopathic Pulmonary Capillaritis. Saudi medical journal, 40(6), 610-613.
  More info

  Diffuse alveolar hemorrhage is an uncommon and often fatal condition in children that is characterized by distinct histopathological etiologies. Herein, we discuss the case of an 11-year-old girl who presented with acute worsening of hypoxia and left-sided chest pain. The patient had lung biopsy-proven idiopathic pulmonary capillaritis and was being treated with prednisolone every alternate day, azathioprine, and hydroxychloroquine. A contrast-computed tomography (CT) scan of the chest showed an acute left lower-lobe pulmonary embolism. Negative results were obtained on a test for thrombophilia. In children, pulmonary embolism with anti-neutrophil cytoplasmic antibody-negative idiopathic pulmonary capillaritis is a rare clinical condition. The exact cause of thrombus formation in this case is unknown; however, obesity, immobility, and chronic systemic corticosteroid therapy probably played a role.
• Balakrishnan, K., Sidell, D. R., Bauman, N. M., Bellia-Munzon, G. F., Boesch, R. P., Bromwich, M., Cofer, S. A., Daines, C., de Alarcon, A., Garabedian, N., Hart, C. K., Ida, J. B., Leboulanger, N., Manning, P. B., Mehta, D. K., Monnier, P., Myer, C. M., Prager, J. D., Preciado, D., , Propst, E. J., et al. (2019). Outcome measures for pediatric laryngotracheal reconstruction: International consensus statement. The Laryngoscope, 129(1), 244-255.
  More info

  Develop multidisciplinary and international consensus on patient, disease, procedural, and perioperative factors, as well as key outcome measures and complications, to be reported for pediatric airway reconstruction studies.
• Flume, P. A., Daines, C. L., Kissner, D. G., Zhang, Y., Xuan, F., Withers, N., Welter, J., Welter, J. J., Waltz, D., Walker, S., Wachter, E. D., Vermeulen, F., Verhulst, S., Tullis, E., Teneback, C. C., Taylor-cousar, J. L., Sosnay, P. R., Simard, C., Scher, H., , Rubenstein, R. C., et al. (2019). Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial.. Lancet (London, England), 394(10212), 1940-1948. doi:10.1016/s0140-6736(19)32597-8
  More info

  Cystic fibrosis transmembrane conductance regulator (CFTR) modulators correct the basic defect caused by CFTR mutations. Improvements in health outcomes have been achieved with the combination of a CFTR corrector and potentiator in people with cystic fibrosis homozygous for the F508del mutation. The addition of elexacaftor (VX-445), a next-generation CFTR corrector, to tezacaftor plus ivacaftor further improved F508del-CFTR function and clinical outcomes in a phase 2 study in people with cystic fibrosis homozygous for the F508del mutation..This phase 3, multicentre, randomised, double-blind, active-controlled trial of elexacaftor in combination with tezacaftor plus ivacaftor was done at 44 sites in four countries. Eligible participants were those with cystic fibrosis homozygous for the F508del mutation, aged 12 years or older with stable disease, and with a percentage predicted forced expiratory volume in 1 s (ppFEV1) of 40-90%, inclusive. After a 4-week tezacaftor plus ivacaftor run-in period, participants were randomly assigned (1:1) to 4 weeks of elexacaftor 200 mg orally once daily plus tezacaftor 100 mg orally once daily plus ivacaftor 150 mg orally every 12 h versus tezacaftor 100 mg orally once daily plus ivacaftor 150 mg orally every 12 h alone. The primary outcome was the absolute change from baseline (measured at the end of the tezacaftor plus ivacaftor run-in) in ppFEV1 at week 4. Key secondary outcomes were absolute change in sweat chloride and Cystic Fibrosis Questionnaire-Revised respiratory domain (CFQ-R RD) score. This study is registered with ClinicalTrials.gov, NCT03525548..Between Aug 3 and Dec 28, 2018, 113 participants were enrolled. Following the run-in, 107 participants were randomly assigned (55 in the elexacaftor plus tezacaftor plus ivacaftor group and 52 in the tezacaftor plus ivacaftor group) and completed the 4-week treatment period. The elexacaftor plus tezacaftor plus ivacaftor group had improvements in the primary outcome of ppFEV1 (least squares mean [LSM] treatment difference of 10·0 percentage points [95% CI 7·4 to 12·6], p
• Franco, R., Innes, A., Lascano, J., Murray, L., Lovie, E., Fraser-pitt, D., O'neil, D., Robertson, J. M., Volpi, S., Smith, T., Robertson, J., Peckham, D., O'neil, D., Murray, L., Mcgregor, G., Lucidi, V., Lovie, E., Layish, D., Lascano, J., , Kopp, B. T., et al. (2019). WS12-6 Evaluating appropriate PROMs in CARE-CF-1 trial: Lynovex® (cysteamine) an oral adjunct to SOC interventions in cystic fibrosis infectious exacebations. Journal of Cystic Fibrosis, 18, S23-S24. doi:10.1016/s1569-1993(19)30191-2
• Hobart, C. B., Daines, C. L., & Phan, H. (2019). Developing Future Clinical Pharmacy Leaders in the Interprofessional Care of Children with Special Health Care Needs and Medical Complexity (CSHCN-CMC) in a Pediatric Pulmonary Center. Children (Basel, Switzerland), 6(12).
  More info

  The health care needs of children with special health care needs and medical complexity (CSHCN-CMC) are multifaceted and often require the expertise of various disciplines. The medication-related needs of this population can be further complicated with off-label medication use, polypharmacy, and vulnerability to medication errors. Although clinical pharmacists are increasingly becoming a common part of inpatient, pediatric interprofessional patient care teams, their presence remains lacking in the outpatient or ambulatory care realm. Pediatric clinical pharmacists in the ambulatory care setting have the potential to help optimize medication use and safety through collaborative efforts as part of the interprofessional team. Since the late 1960s, Pediatric Pulmonary Centers (PPCs) provide training programs designed to develop interprofessional leaders who will improve the health status of CSHCN-CMC, specifically those with chronic respiratory and sleep-related conditions. The addition of pharmacists not only provides a more comprehensive care model for CSHCN-CMC, it creates an avenue to encourage the career paths of pediatric pharmacists in the ambulatory care setting. Here, we describe the addition of clinical pharmacy as part of an interprofessional patient care team and the development and implementation of a maternal child health (MCH) pharmacy discipline training model designed to mentor future pharmacist leaders in the care of CSHCN-CMC.
• Liou, T. G., Adler, F. R., Argel, N., Asfour, F., Brown, P. S., Chatfield, B. A., Daines, C. L., Durham, D., Francis, J. A., Glover, B., Heynekamp, T., Hoidal, J. R., Jensen, J. L., Keogh, R., Kopecky, C. M., Lechtzin, N., Li, Y., Lysinger, J., Molina, O., , Nakamura, C., et al. (2019). Prospective multicenter randomized patient recruitment and sample collection to enable future measurements of sputum biomarkers of inflammation in an observational study of cystic fibrosis. BMC medical research methodology, 19(1), 88.
  More info

  Biomarkers of inflammation predictive of cystic fibrosis (CF) disease outcomes would increase the power of clinical trials and contribute to better personalization of clinical assessments. A representative patient cohort would improve searching for believable, generalizable, reproducible and accurate biomarkers.
• Martiniano, S. L., Daines, C. L., Dellon, E. P., Esther, C. R., Muhlebach, M. S., Ong, T., Rabinowitz, E. C., Toprak, D., & Zemanick, E. T. (2019). Highlights from the 2018 North American cystic fibrosis conference. Pediatric pulmonology, 54(7), 941-948.
  More info

  The 32nd annual North American Cystic Fibrosis Conference was held in Denver, CO on Oct. 18 to 20, 2018. This review highlights presentations in several topic areas, including the pathophysiology and basic science of cystic fibrosis lung disease, clinical trials, clinical care, and quality improvement. Citations from the conference are by first author and abstract or symposium number, as designated in the previously published supplement.
• Wheatley, C. M., Baker, S. E., Daines, C. M., Phan, H., Martinez, M. G., Morgan, W. J., & Snyder, E. M. (2019). Influence of the Vibralung Acoustical Percussor on pulmonary function and sputum expectoration in individuals with cystic fibrosis. Therapeutic advances in respiratory disease, 12, 1753466618770997.
  More info

  The Vibralung Acoustical Percussor is a new airway clearance therapy (ACT) utilizing intrapulmonary sound waves in addition to positive expiratory pressure (PEP). We evaluated the safety of the Vibralung and collected preliminary data on its ability to mediate sputum expectoration in individuals with cystic fibrosis (CF).
• Boesch, R. P., Balakrishnan, K., Acra, S., Benscoter, D. T., Cofer, S. A., Collaco, J. M., Dahl, J. P., Daines, C. L., DeAlarcon, A., DeBoer, E. M., Deterding, R. R., Friedlander, J. A., Gold, B. D., Grothe, R. M., Hart, C. K., Kazachkov, M., Lefton-Greif, M. A., Miller, C. K., Moore, P. E., , Pentiuk, S., et al. (2018). Structure and Functions of Pediatric Aerodigestive Programs: A Consensus Statement. Pediatrics, 141(3).
  More info

  Aerodigestive programs provide coordinated interdisciplinary care to pediatric patients with complex congenital or acquired conditions affecting breathing, swallowing, and growth. Although there has been a proliferation of programs, as well as national meetings, interest groups and early research activity, there is, as of yet, no consensus definition of an aerodigestive patient, standardized structure, and functions of an aerodigestive program or a blueprint for research prioritization. The Delphi method was used by a multidisciplinary and multi-institutional panel of aerodigestive providers to obtain consensus on 4 broad content areas related to aerodigestive care: (1) definition of an aerodigestive patient, (2) essential construct and functions of an aerodigestive program, (3) identification of aerodigestive research priorities, and (4) evaluation and recognition of aerodigestive programs and future directions. After 3 iterations of survey, consensus was obtained by either a supermajority of 75% or stability in median ranking on 33 of 36 items. This included a standard definition of an aerodigestive patient, level of participation of specific pediatric disciplines in a program, essential components of the care cycle and functions of the program, feeding and swallowing assessment and therapy, procedural scope and volume, research priorities and outcome measures, certification, coding, and funding. We propose the first consensus definition of the aerodigestive care model with specific recommendations regarding associated personnel, infrastructure, research, and outcome measures. We hope that this may provide an initial framework to further standardize care, develop clinical guidelines, and improve outcomes for aerodigestive patients.
• Keating, D., Marigowda, G., Burr, L., Daines, C., Mall, M. A., McKone, E. F., Ramsey, B. W., Rowe, S. M., Sass, L. A., Tullis, E., McKee, C. M., Moskowitz, S. M., Robertson, S., Savage, J., Simard, C., Van Goor, F., Waltz, D., Xuan, F., Young, T., , Taylor-Cousar, J. L., et al. (2018). VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. The New England journal of medicine, 379(17), 1612-1620.
  More info

  VX-445 is a next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector designed to restore Phe508del CFTR protein function in patients with cystic fibrosis when administered with tezacaftor and ivacaftor (VX-445-tezacaftor-ivacaftor).
• Martiniano, S. L., Toprak, D., Ong, T., Zemanick, E. T., Daines, C. L., Muhlebach, M. S., Esther, C. R., & Dellon, E. P. (2018). Highlights from the 2017 North American Cystic Fibrosis Conference. Pediatric pulmonology, 53(7), 979-986.
  More info

  The 31st annual North American Cystic Fibrosis Conference (NACFC) was held in Indianapolis, IN on November 2-4, 2017. Abstracts of presentations from the conference were published in a supplement to Pediatric Pulmonology [2017; Pediatr Pulmonol Suppl. 52: S1-S776]. The current review summarizes several major topic areas addressed at the conference: the pathophysiology and basic science of cystic fibrosis (CF) lung disease, clinical trials, clinical management issues, and quality improvement (QI). In this review, we describe emerging concepts in several areas of CF research and care.
• Sagel, S. D., Khan, U., Jain, R., Graff, G., Daines, C. L., Dunitz, J. M., Borowitz, D., Orenstein, D. M., Abdulhamid, I., Noe, J., Clancy, J. P., Slovis, B., Rock, M. J., McCoy, K. S., Strausbaugh, S., Livingston, F. R., Papas, K. A., & Shaffer, M. L. (2018). Effects of an Antioxidant-enriched Multivitamin in Cystic Fibrosis. A Randomized, Controlled, Multicenter Clinical Trial. American journal of respiratory and critical care medicine, 198(5), 639-647.
  More info

  Cystic fibrosis (CF) is characterized by dietary antioxidant deficiencies, which may contribute to an oxidant-antioxidant imbalance and oxidative stress.
• Wheatley, C. M., Baker, S. E., Daines, C. L., Phan, H., Martinez, M. G., Morgan, W. J., & Snyder, E. M. (2018). Influence of the Vibralung Acoustical Percussor on pulmonary function and sputum expectoration in individuals with cystic fibrosis.. Ther Adv Respir Dis., 12, 1-15. doi:10.1177/1753466618770997
• Rowe, S. M., Daines, C., Ringshausen, F. C., Kerem, E., Wilson, J., Tullis, E., Nair, N., Simard, C., Han, L., Ingenito, E. P., McKee, C., Lekstrom-Himes, J., & Davies, J. C. (2017). Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis. The New England journal of medicine, 377(21), 2024-2035.
  More info

  Cystic fibrosis is an autosomal recessive disease caused by mutations in the CFTR gene that lead to progressive respiratory decline. Some mutant CFTR proteins show residual function and respond to the CFTR potentiator ivacaftor in vitro, whereas ivacaftor alone does not restore activity to Phe508del mutant CFTR.
• Sanders, D. B., Solomon, G. M., Beckett, V. V., West, N. E., Daines, C. L., Heltshe, S. L., VanDevanter, D. R., Spahr, J. E., Gibson, R. L., Nick, J. A., Marshall, B. C., Flume, P. A., Goss, C. H., & , S. S. (2017). Standardized Treatment of Pulmonary Exacerbations (STOP) study: Observations at the initiation of intravenous antibiotics for cystic fibrosis pulmonary exacerbations. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 16(5), 592-599.
  More info

  The Standardized Treatment of Pulmonary Exacerbations (STOP) program has the intent of defining best practices in the treatment of pulmonary exacerbations (PEx) in patients with cystic fibrosis (CF). The objective of this analysis was to describe the clinical presentations of patients admitted for intravenous (IV) antibiotics and enrolled in a prospective observational PEx study as well as to understand physician treatment goals at the start of the intervention.
• VanDevanter, D. R., Heltshe, S. L., Spahr, J., Beckett, V. V., Daines, C. L., Dasenbrook, E. C., Gibson, R. L., Jain, R., Sanders, D. B., Goss, C. H., Flume, P. A., & , S. S. (2017). Rationalizing endpoints for prospective studies of pulmonary exacerbation treatment response in cystic fibrosis. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 16(5), 607-615.
  More info

  Given the variability in pulmonary exacerbation (PEx) management within and between Cystic Fibrosis (CF) Care Centers, it is possible that some approaches may be superior to others. A challenge with comparing different PEx management approaches is lack of a community consensus with respect to treatment-response metrics. In this analysis, we assess the feasibility of using different response metrics in prospective randomized studies comparing PEx treatment protocols.
• Zemanick, E. T., Daines, C. L., Dellon, E. P., Esther, C. R., Kinghorn, B., Ong, T., & Muhlebach, M. S. (2017). Highlights from the 2016 North American Cystic Fibrosis Conference. Pediatric pulmonology, 52(8), 1103-1110.
  More info

  The 30th annual North American Cystic Fibrosis Conference (NACFC) was held in Orlando, FL, on October 27-29, 2016. Abstracts were published in a supplement to Pediatric Pulmonology. This review summarizes several major topic areas addressed at the conference: the pathophysiology of cystic fibrosis (CF) lung disease, clinical trials, clinical management issues, and quality improvement. We sought to provide an overview of emerging concepts in several areas of CF research and care, rather than a comprehensive review of the conference. Citations from the conference are by first author and abstract number or symposium number, as designated in the supplement.
• Daines, C. L., & Morgan, W. J. (2016). Planning the future of newborn screening for cystic fibrosis. Pediatric pulmonology, 51(9), 883-5.
• Fitzpatrick, A. M., Jackson, D. J., Mauger, D. T., Boehmer, S. J., Phipatanakul, W., Sheehan, W. J., Moy, J. N., Paul, I. M., Bacharier, L. B., Cabana, M. D., Covar, R., Holguin, F., Lemanske, R. F., Martinez, F. D., Pongracic, J. A., Beigelman, A., Baxi, S. N., Benson, M., Blake, K., , Chmiel, J. F., et al. (2016). Individualized therapy for persistent asthma in young children. The Journal of allergy and clinical immunology, 138(6), 1608-1618.e12.
  More info

  Phenotypic presentations in young children with asthma are varied and might contribute to differential responses to asthma controller medications.
• Seckeler, M. D., Zahedieh, S., Seckeler, M. D., Scherer, K., Klewer, S. E., Daines, C. L., Barber, B. J., & Andrews, J. (2016). Regional and Racial Variation in Hospitalization Costs in Patients with Duchenne Muscular Dystrophy. Pediatrics, 140, 28-28. doi:10.1542/peds.140.1_meetingabstract.28
  More info

  Advances in management for Duchenne muscular dystrophy (DMD) have improved survival. The purpose of this study was to describe hospital outcomes and costs for DMD patients and to identify regional and racial variation. Retrospective review of University Health System Consortium Clinical Data Base/Resource Manager, a …
• Sheehan, W. J., Mauger, D. T., Paul, I. M., Moy, J. N., Boehmer, S. J., Szefler, S. J., Fitzpatrick, A. M., Jackson, D. J., Bacharier, L. B., Cabana, M. D., Covar, R., Holguin, F., Lemanske, R. F., Martinez, F. D., Pongracic, J. A., Beigelman, A., Baxi, S. N., Benson, M., Blake, K., , Chmiel, J. F., et al. (2016). Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma. The New England journal of medicine, 375(7), 619-30.
  More info

  Studies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking.
• Zemanick, E. T., Ong, T., Daines, C. L., Dellon, E. P., Muhlebach, M. S., & Esther, C. R. (2016). Highlights from the 2015 North American Cystic Fibrosis Conference. Pediatric pulmonology, 51(6), 650-7.
  More info

  The 29th Annual North American Cystic Fibrosis Conference was held in Phoenix, Arizona on October 8-10, 2015. Abstracts were published in a supplement to Pediatric Pulmonology.(1) In this review, we summarize presentations in several of the topic areas addressed at the conference. Our goal is to provide an overview of presentations with relevance to emerging or changing concepts in several areas rather than a comprehensive review. Citations from the conference are by first author and abstract number or symposium number, as designated in the supplement. Pediatr Pulmonol. 2016;51:650-657. © 2016 Wiley Periodicals, Inc.
• Faro, A., Wood, R. E., Schechter, M. S., Leong, A. B., Wittkugel, E., Abode, K., Chmiel, J. F., Daines, C., Davis, S., Eber, E., Huddleston, C., Kilbaugh, T., Kurland, G., Midulla, F., Molter, D., Montgomery, G. S., Retsch-Bogart, G., Rutter, M. J., Visner, G., , Walczak, S. A., et al. (2015). Official American Thoracic Society technical standards: flexible airway endoscopy in children. American journal of respiratory and critical care medicine, 191(9), 1066-80.
  More info

  Flexible airway endoscopy (FAE) is an accepted and frequently performed procedure in the evaluation of children with known or suspected airway and lung parenchymal disorders. However, published technical standards on how to perform FAE in children are lacking.
• Powers, S. W., Stark, L. J., Chamberlin, L. A., Filigno, S. S., Sullivan, S. M., Lemanek, K. L., Butcher, J. L., Driscoll, K. A., Daines, C. L., Brody, A. S., Schindler, T., Konstan, M. W., McCoy, K. S., Nasr, S. Z., Castile, R. G., Acton, J. D., Wooldridge, J. L., Ksenich, R. A., Szczesniak, R. D., , Rausch, J. R., et al. (2015). Behavioral and nutritional treatment for preschool-aged children with cystic fibrosis: a randomized clinical trial. JAMA pediatrics, 169(5), e150636.
  More info

  Evidence-based treatments that achieve optimal energy intake and improve growth in preschool-aged children with cystic fibrosis (CF) are a critical need.
• Schechter, M. S., Trueman, D., Farquharson, R., Higuchi, K., & Daines, C. L. (2015). Inhaled aztreonam lysine versus inhaled tobramycin in cystic fibrosis. An economic evaluation. Annals of the American Thoracic Society, 12(7), 1030-1038.
• Schechter, M. S., Trueman, D., Farquharson, R., Higuchi, K., & Daines, C. L. (2015). Inhaled aztreonam lysine versus inhaled tobramycin in cystic fibrosis. An economic evaluation. Annals of the American Thoracic Society, 12(7), 1030-8.
  More info

  Pseudomonas aeruginosa infection is a significant cause of morbidity and mortality in patients with cystic fibrosis and is associated with a high economic burden. A recently published comparator trial demonstrated that outcomes in patients with cystic fibrosis with chronic P. aeruginosa infections switched from tobramycin solution for inhalation to aztreonam lysine for inhalation were better than those of patients who continued on tobramycin.
• Soler, X., Searing, D. A., Santiago, M. T., Morgan, W. J., Knox, K. S., Goodwin, J. L., Ezmigna, D. R., Daines, M. O., Berry, C. E., Zheng, G., Zagaja, V., Yasin, R., Xu, B., Wu, N., Wu, E. Y., Wolf, D., Wise, R. A., Williams, J., Wences, J. A., , Welter, J., et al. (2015). Effect of a soy isoflavone supplement on lung function and clinical outcomes in patients with poorly controlled asthma: a randomized clinical trial.. JAMA, 313(20), 2033-43. doi:10.1001/jama.2015.5024
  More info

  Soy isoflavone supplements are used to treat several chronic diseases, although the data supporting their use are limited. Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control..To determine whether a soy isoflavone supplement improves asthma control in adolescent and adult patients with poorly controlled disease..Multicenter, randomized, double-blind, placebo-controlled trial conducted between May 2010 and August 2012 at 19 adult and pediatric pulmonary and allergy centers in the American Lung Association Asthma Clinical Research Centers network. Three hundred eighty-six adults and children aged 12 years or older with symptomatic asthma while taking a controller medicine and low dietary soy intake were randomized, and 345 (89%) completed spirometry at week 24..Participants were randomly assigned to receive soy isoflavone supplement containing 100 mg of total isoflavones (n=193) or matching placebo (n=193) in 2 divided doses administered daily for 24 weeks..The primary outcome measure was change in forced expiratory volume in the first second (FEV1) at 24 weeks. Secondary outcome measures were symptoms, episodes of poor asthma control, Asthma Control Test score (range, 5-25; higher scores indicate better control), and systemic and airway biomarkers of inflammation..Mean changes in prebronchodilator FEV1 over 24 weeks were 0.03 L (95% CI, -0.01 to 0.08 L) in the placebo group and 0.01 L (95% CI, -0.07 to 0.07 L) in the soy isoflavone group, which were not significantly different (P = .36). Mean changes in symptom scores on the Asthma Control Test (placebo, 1.98 [95% CI, 1.42-2.54] vs soy isoflavones, 2.20 [95% CI, 1.53-2.87]; positive values indicate a reduction in symptoms), number of episodes of poor asthma control (placebo, 3.3 [95% CI, 2.7-4.1] vs soy isoflavones, 3.0 [95% CI, 2.4-3.7]), and changes in exhaled nitric oxide (placebo, -3.48 ppb [95% CI, -5.99 to -0.97 ppb] vs soy isoflavones, 1.39 ppb [95% CI, -1.73 to 4.51 ppb]) did not significantly improve more with the soy isoflavone supplement than with placebo. Mean plasma genistein level increased from 4.87 ng/mL to 37.67 ng/mL (P < .001) in participants receiving the supplement..Among adults and children aged 12 years or older with poorly controlled asthma while taking a controller medication, use of a soy isoflavone supplement, compared with placebo, did not result in improved lung function or clinical outcomes. These findings suggest that this supplement should not be used for patients with poorly controlled asthma..clinicaltrials.gov Identifier: NCT01052116.
• Daines, C., VanDeVanter, D., Khan, U., Emerson, J., Heltshe, S., McNamara, S., Anstead, M., Langkamp, M., Doring, G., Ratjen, F., Ramsey, B., Gibson, R. L., Morgan, W., Rosenfeld, M., & , E. I. (2014). Serology as a diagnostic tool for predicting initialPseudomonas aeruginosa acquisition in children with cystic fibrosis. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 13(5), 542-9.
  More info

  Pseudomonas aeruginosa (Pa) serology could potentially be a useful adjunct to respiratory culture methods for the detection of initial or early Pa infection in patients with cystic fibrosis (CF).
• Hiranrattana, A., & Daines, C. L. (2014). Pediatric dysphagia and aspiration: Evaluation, management strategies, and outcomes. Annals of the American Thoracic Society, 11(10), 1634-1635. doi:10.1513/annalsats.201409-435ot
• Nevin, M. A., Daines, C. L., Redding, G. J., Ren, C. L., Ratjen, F. A., Shah, A. V., Hiranrattana, A., Alexiou, S., Bansal, M., Pizarro-Gamboa, M. E., & Panitch, H. B. (2014). ATS core curriculum 2014: part IV. Pediatric pulmonary medicine. Annals of the American Thoracic Society, 11(10), 1633-9.
• Wheatley, C. M., Morgan, W. J., Cassuto, N. A., Foxx-Lupo, W. T., Daines, C. L., Morgan, M. A., Phan, H., & Snyder, E. M. (2013). Exhaled breath condensate detects baseline reductions in chloride and increases in response to albuterol in cystic fibrosis patients. Clinical medicine insights. Circulatory, respiratory and pulmonary medicine, 7, 79-90.
  More info

  Impaired ion regulation and dehydration is the primary pathophysiology in cystic fibrosis (CF) lung disease. A potential application of exhaled breath condensate (EBC) collection is to assess airway surface liquid ionic composition at baseline and in response to pharmacological therapy in CF. Our aims were to determine if EBC could detect differences in ion regulation between CF and healthy and measure the effect of the albuterol on EBC ions in these populations. Baseline EBC Cl(-), DLCO and SpO2 were lower in CF (n = 16) compared to healthy participants (n = 16). EBC Cl(-) increased in CF subjects, while there was no change in DLCO or membrane conductance, but a decrease in pulmonary-capillary blood volume in both groups following albuterol. This resulted in an improvement in diffusion at the alveolar-capillary unit, and removal of the baseline difference in SpO2 by 90-minutes in CF subjects. These results demonstrate that EBC detects differences in ion regulation between healthy and CF individuals, and that albuterol mediates increases in Cl(-) in CF, suggesting that the benefits of albuterol extend beyond simple bronchodilation.
• Daines, C., & Morgan, W. (2011). The importance of imaging in cystic fibrosis. American journal of respiratory and critical care medicine, 184(7), 751-2.
• Traylor, B. R., Wheatley, C. M., Skrentny, T. T., Foxx-Lupo, W. T., Phan, H., Patanwala, A. E., Morgan, W. J., Daines, C. L., Sprissler, R., & Snyder, E. M. (2011). Influence of genetic variation of the β2-adrenergic receptor on lung diffusion in patients with cystic fibrosis. Pulmonary pharmacology & therapeutics, 24(5), 610-6.
  More info

  Cystic fibrosis (CF) is a disease that adversely affects the lung resulting in a reduction in lung diffusion. Stimulation of the β(2)-adrenergic receptors mediates mucociliary clearance and bronchodilation. We sought to determine the influence of an inhaled β-agonist on the diffusing capacity of the lungs for carbon monoxide (DLCO), alveolar-capillary membrane conductance (D(M)), pulmonary capillary blood volume (Vc), and peripheral oxygen saturation (SaO(2)) in subjects with CF, when compared to matched healthy subjects, according to genetic variation of the β(2)-adrenergic receptor (ADRB2).
• Wheatley, C. M., Foxx-Lupo, W. T., Cassuto, N. A., Wong, E. C., Daines, C. L., Morgan, W. J., & Snyder, E. M. (2011). Impaired lung diffusing capacity for nitric oxide and alveolar-capillary membrane conductance results in oxygen desaturation during exercise in patients with cystic fibrosis. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 10(1), 45-53.
  More info

  Exercise has been shown to be beneficial for patients with cystic fibrosis (CF), but for some CF patients there is a risk of desaturation, although the predicting factors are not conclusive or reliable. We sought to determine the relationship between the diffusion capacity of the lungs for nitric oxide and carbon monoxide (DLNO and DLCO) and the components of DLCO: alveolar-capillary membrane conductance (D(M)), and pulmonary capillary blood volume (V(C)) on peripheral oxygen saturation (SaO(2)) at rest and during exercise in CF.
• Zuckerman, J. B., Zeitlin, P. L., Young, J., Wooldridge, J. L., Woo, M. S., Wilmott, R. W., Willey-courand, D. B., Weiner, D. J., Wall, M., Walker, P., Traplena, L., Towle, D., Smith, J., Schellhase, D., Schechter, M. S., Schaeffer, D., Schaberg, A. E., Rubenstein, R. C., Rock, M. G., , Robles, A., et al. (2011). Denufosol tetrasodium in patients with cystic fibrosis and normal to mildly impaired lung function.. American journal of respiratory and critical care medicine, 183(5), 627-34. doi:10.1164/rccm.201008-1267oc
  More info

  Intervention for cystic fibrosis lung disease early in its course has the potential to delay or prevent progressive changes that lead to irreversible airflow obstruction. Denufosol is a novel ion channel regulator designed to correct the ion transport defect and increase the overall mucociliary clearance in cystic fibrosis lung disease by increasing chloride secretion, inhibiting sodium absorption, and increasing ciliary beat frequency in the airway epithelium independently of cystic fibrosis transmembrane conductance regulator genotype..To evaluate the efficacy and safety of denufosol in patients with cystic fibrosis who had normal to mildly impaired lung function characteristic of early cystic fibrosis..A total of 352 patients greater than or equal to 5 years old with cystic fibrosis who had FEV(1) greater than or equal to 75% of predicted normal were randomized to receive inhaled denufosol, 60 mg, or placebo three times daily in a Phase 3, randomized, double-blind, placebo-controlled, 24-week trial..Main outcome measures included change in FEV(1) from baseline to Week 24 endpoint and adverse events. Mean change from baseline to Week 24 endpoint in FEV(1) (primary efficacy endpoint) was 0.048 L for denufosol (n = 178) and 0.003 L for placebo (n = 174; P = 0.047). No significant differences between groups were observed for secondary endpoints including exacerbation rate and other measures of lung function. Denufosol was well tolerated with adverse event and growth profiles similar to placebo..Denufosol improved lung function relative to placebo in cystic fibrosis patients with normal to mildly impaired lung function. Clinical trial registered with www.clinicaltrials.gov (NCT00357279).
• Daines, C. L., Wood, R. E., & Boesch, R. P. (2008). Foreign body aspiration: an important etiology of respiratory symptoms in children. The Journal of allergy and clinical immunology, 121(5), 1297-8.
• Daines, M. O., Chen, W., Tabata, Y., Walker, B. A., Gibson, A. M., Masino, J. A., Warrier, M. R., Daines, C. L., Wenzel, S. E., & Hershey, G. K. (2007). Allergen-dependent solubilization of IL-13 receptor alpha2 reveals a novel mechanism to regulate allergy. The Journal of allergy and clinical immunology, 119(2), 375-83.
  More info

  Allergic sensitization affects half of western populations and often precedes the development of allergic disorders including asthma. Despite the critical role of allergens in the pathogenesis of these disorders, little is known about how allergens modulate the immune response. IL-13 receptor alpha2 (IL-13Ralpha2) is a decoy receptor for IL-13.
• Boesch, R. P., Daines, C., Willging, J. P., Kaul, A., Cohen, A. P., Wood, R. E., & Amin, R. S. (2006). Advances in the diagnosis and management of chronic pulmonary aspiration in children. The European respiratory journal, 28(4), 847-61.
  More info

  Chronic pulmonary aspiration (CPA) in children is an important cause of recurrent pneumonia, progressive lung injury, respiratory disability and death. It is sporadic, intermittent and variable, and often occurs in children with complicated underlying medical conditions and syndromes that produce symptoms indistinguishable from CPA. For most types of aspiration there is no gold-standard diagnostic test. The diagnosis of CPA is currently made clinically with some supporting diagnostic evaluations, but often not until significant lung injury has been sustained. Despite multiple diagnostic techniques, the diagnosis or exclusion of CPA in children is challenging. This is of particular concern given the outcome of unrecognised progressive lung injury and the invasiveness of definitive therapies. Although new techniques have been introduced since the 1990s and significant advances in the understanding of dysphagia and gastro-oesophageal reflux have been made, characterisation of the aspirating child remains elusive.
• Gibson, R. L., Retsch-Bogart, G. Z., Oermann, C., Milla, C., Pilewski, J., Daines, C., Ahrens, R., Leon, K., Cohen, M., McNamara, S., Callahan, T. L., Markus, R., & Burns, J. L. (2006). Microbiology, safety, and pharmacokinetics of aztreonam lysinate for inhalation in patients with cystic fibrosis. Pediatric pulmonology, 41(7), 656-65.
  More info

  Aztreonam lysinate for inhalation (AI) is a novel monobactam formulation being investigated for pulmonary Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF).
• Piazza-Waggoner, C., Ferguson, K. S., Daines, C., Acton, J. D., & Powers, S. W. (2006). Case study: providing evidence-based behavioral and nutrition treatment to a toddler with cystic fibrosis and multiple food allergies via telehealth. Pediatric pulmonology, 41(10), 1001-4.
  More info

  Barriers to successful outcome for cystic fibrosis (CF) therapies can include distance from a CF care center, co-morbid conditions that require individualized alterations to the prescribed treatment, and patient-provider interactions, among others. We present the case of a 21-month-old female with CF for whom modifications of an efficacious behavioral and nutrition treatment were made due to food allergies and distance from the CF care center. She was classified as at-risk nutritionally. Following treatment a significant increase in energy intake (calories) was observed in addition to her meeting weight and height growth rates for a child of this age and gender who is growing normally at the 50th percentile.
• Piazza-waggoner, C., Driscoll, K. A., Powers, S. W., Piazza-waggoner, C., Jones, J. S., Driscoll, K. A., Daines, C. L., & Acton, J. D. (2006). 315 Two-year outcomes of behavior and nutrition treatment for young children with Cystic Fibrosis. Journal of Cystic Fibrosis, 5, S74. doi:10.1016/s1569-1993(06)80286-9
  More info

  Aims: To evaluate whether changes in energy intake and growth velocity due to behavior and nutrition treatment (BEH) for young children with CF were maintained at 2-yr follow-up (f-up). Methods: Two-yr f-up data for 9 subjects who completed an 8-week BEH intervention, which included nutrition counseling and parental child behavior management training. For f-up assessments three 24-hour recall diet diaries and height (ht) & weight (wt) were obtained. Average daily energy intake and growth velocity (ht&wt) were outcome variables. Velocity was benchmarked against expected velocities for a same age child without CF at the 50th percentile (US 2000 Center for Disease Control growth charts). Results: The average daily energy intake was 2,589±519 kcal/day at the 2-yr f-up. This compares favorably to data from post-treatment (2151±301 kcal/day). Pretreatment intake was 1,381±198kcal/day. Subjects exceeded the goal of 120% RDA/day for energy intake at 2-yr f-up. The average wt velocity was 4.94/2-yr (Median: 4.6). Seven of 9 subjects were above benchmark. The average ht velocity was 15.8/2-yr (Median: 15.7). All subjects were above benchmark. Conclusions: Upon returning to standard care, young children with CF who received BEH continue to maintain clinically significant increases in energy intake, and demonstrate patterns of normal growth at 2-yr post-treatment. Findings suggest this intervention is durable and families are able to continue to implement skills and knowledge acquired during treatment. Supported by US National Institutes of Health. 8. Nutrition
• Powers, S. W., Piazza-Waggoner, C., Jones, J. S., Ferguson, K. S., Daines, C., & Acton, J. D. (2006). Examining clinical trial results with single-subject analysis: an example involving behavioral and nutrition treatment for young children with cystic fibrosis. Journal of pediatric psychology, 31(6), 574-81.
  More info

  To examine the process of change in a clinical trial of behavioral and nutrition treatment for children age 18-48 months with cystic fibrosis (CF) using single-subject analysis.
• Daines, C. L. (2005). Chapter 112 – Disorders of the Bronchi. Pediatrics, 799-803. doi:10.1016/b978-0-323-01199-0.50117-1
• Deterding, R., Retsch-Bogart, G., Milgram, L., Gibson, R., Daines, C., Zeitlin, P. L., Milla, C., Marshall, B., Lavange, L., Engels, J., Mathews, D., Gorden, J., Schaberg, A., Williams, J., Ramsey, B., & , C. F. (2005). Safety and tolerability of denufosol tetrasodium inhalation solution, a novel P2Y2 receptor agonist: results of a phase 1/phase 2 multicenter study in mild to moderate cystic fibrosis. Pediatric pulmonology, 39(4), 339-48.
  More info

  Denufosol tetrasodium (INS37217) is a selective P2Y(2) agonist that stimulates ciliary beat frequency and Cl(-) secretion in normal and cystic fibrosis (CF) airway epithelia, and is being investigated as an inhaled treatment for CF. The Cl(-) secretory response is mediated via a non-CFTR pathway, and the driving force for Cl(-) secretion is enhanced by the effect of P2Y(2) activation to also inhibit epithelial Na(+) transport. Denufosol is metabolically more stable and better tolerated, and may enhance mucociliary clearance for a longer period of time than previously investigated P2Y(2) agonists. The goal of this phase 1/phase 2 study was to assess the safety and tolerability of single and repeated doses of aerosolized denufosol in subjects with CF. The study was a double-blind, placebo-controlled, multicenter comparison of ascending single doses of denufosol (10, 20, 40, and 60 mg, administered by inhalation via the Pari LC Star nebulizer) vs. placebo (normal saline), followed by a comparison of twice-daily administration of the maximum tolerated dose (MTD) of denufosol or placebo for 5 days. Thirty-seven adult (18 years of age or older) and 24 pediatric (5-17 years of age) subjects with CF were evaluated in five cohorts. Subjects were randomized in a 3:1 ratio to receive either denufosol or placebo within each cohort. The percent of subjects experiencing adverse events was similar between the denufosol and placebo groups. The most common adverse event in subjects receiving denufosol was chest tightness in adult subjects (39%) and cough in pediatric subjects (56%). Three (7%) subjects receiving denufosol and one (7%) subject receiving placebo experienced a serious adverse event. Forced expiratory volume in 1 sec (FEV(1)) profiles following dosing were similar across treatment groups, with some acute, reversible decline seen in both groups, most notably in subjects with lower lung function at baseline. In conclusion, doses up to 60 mg of denufosol inhalation solution were well-tolerated in most subjects. Some intolerability was noted among subjects with lower baseline lung function. Based on the results of this phase 1/phase 2 study, the Therapeutics Development Network (TDN) of the Cystic Fibrosis Foundation (CFF) and Inspire Pharmaceuticals, Inc., recently completed a multicenter, 28-day, phase 2 safety and efficacy clinical trial of denufosol inhalation solution in CF subjects with mild lung disease.
• Moss, R. B., Mayer-Hamblett, N., Wagener, J., Daines, C., Hale, K., Ahrens, R., Gibson, R. L., Anderson, P., Retsch-Bogart, G., Nasr, S. Z., Noth, I., Waltz, D., Zeitlin, P., Ramsey, B., & Starko, K. (2005). Randomized, double-blind, placebo-controlled, dose-escalating study of aerosolized interferon gamma-1b in patients with mild to moderate cystic fibrosis lung disease. Pediatric pulmonology, 39(3), 209-18.
  More info

  Interferon gamma-1b (IFN-gamma1b) is a pleiotropic cytokine with immunomodulatory activities that could decrease bacterial burden, inflammation, and obstruction in patients with CF. Patients with CF (> or =12 years old, FEV1 > or =40% predicted) were randomly assigned to sequential dose cohorts inhaling 500 microg IFN-gamma1b, 1,000 microg IFN-gamma1b, or placebo by Respirgard II nebulizer thrice weekly for 12 weeks. Sputum bacterial density and spirometry were measured. Safety, antibiotic use, hospitalization, and sputum neutrophils, elastase, DNA, IL-8, and myeloperoxidase were also evaluated. Sixty-six patients (mean age, 24 years, with mean baseline FEV1 of 74 +/- 20 (SD) percent predicted) were studied. One patient had bronchospasm after the first dose of IFN-gamma1b; the overall withdrawal rate was 15% (5 in the placebo group, 2 in the 500-microg IFN-gamma1b group, and 3 in the 1,000 microg IFN-gamma1b group). The 500-microg IFN-gamma1b dose was well-tolerated, but the 1,000-mug dose cohort, who had a higher baseline bacterial density than placebo patients (mean difference, 1.2 log(10) CFU/g sputum, 95% confidence interval (CI), 0.1,2.8, P=0.04), had 24% more hospitalizations for exacerbation than placebo patients (95% CI, 2,45%, P=0.05). There was a 0.12-l difference between the 500-microg IFN-gamma1b and placebo groups with respect to the 12-week change in FEV1 (active group minus placebo group, 95% CI, -0.03,0.26, P=0.11), as compared to a 0.01-l difference between the 1,000-microg IFN-gamma1b and placebo groups (95% CI, -0.16,0.17, P=0.96). No effects of IFN-gamma1b were seen in sputum bacterial density or inflammatory biomarkers at 12 weeks. Aerosolized IFN-gamma1b did not improve pulmonary function, reduce sputum bacterial density, or affect inflammatory sputum markers in patients with mild-moderate lung disease.
• Powers, S. W., Jones, J. S., Ferguson, K. S., Piazza-Waggoner, C., Daines, C., & Acton, J. D. (2005). Randomized clinical trial of behavioral and nutrition treatment to improve energy intake and growth in toddlers and preschoolers with cystic fibrosis. Pediatrics, 116(6), 1442-50.
  More info

  To conduct a randomized clinical trial comparing a behavioral and nutrition intervention (BEH) with a usual care control condition (CTL) for children (ages 18 months to 4 years) with cystic fibrosis (CF) and pancreatic insufficiency. This trial was designed to (1) evaluate a randomized comparison of BEH with CTL over 8 weeks, (2) provide a replication of the impact of BEH by inviting the CTL group to receive BEH after 8 weeks, and (3) examine the maintenance of BEH at 3- and 12-month follow-up.
• White, D. R., Giambra, B. K., Hopkin, R. J., Daines, C. L., & Rutter, M. J. (2005). Aspiration in children with CHARGE syndrome. International journal of pediatric otorhinolaryngology, 69(9), 1205-9.
  More info

  Patients with Coloboma, Heart defect, choanal Atresia, Retarded development, Genitorenal and Ear abnormalities (CHARGE) syndrome have been reported to be at high risk for aspiration and swallowing difficulties. Aspiration has been implicated as the most common cause of mortality in these patients. To date, however, aspiration and swallowing disorders in CHARGE patients have not been independently studied.
• Ordoñez, C. L., Henig, N. R., Mayer-Hamblett, N., Accurso, F. J., Burns, J. L., Chmiel, J. F., Daines, C. L., Gibson, R. L., McNamara, S., Retsch-Bogart, G. Z., Zeitlin, P. L., & Aitken, M. L. (2003). Inflammatory and microbiologic markers in induced sputum after intravenous antibiotics in cystic fibrosis. American journal of respiratory and critical care medicine, 168(12), 1471-5.
  More info

  Induced sputum has been used to study airway inflammation. We sought to determine whether markers of infection and inflammation in induced sputum were a useful and safe outcome measure in cystic fibrosis. We hypothesized that bacterial density and inflammatory content of induced sputum would decrease after antibiotic therapy. Induced sputum was assayed for bacterial density, cell count, and differential and inflammatory markers before and after treatment with intravenous antibiotics. Fifty-five of the 72 subjects enrolled (mean age +/- SD 18.2 +/- 7.9 years) completed the study. FEV1 increased by an average 0.3 +/- 0.3 L (10.4 +/- 8.7% predicted FEV1), p

Proceedings Publications

• Morgan, W. J., Morgan, W. J., Ezmigna, D. R., Daines, C. L., & Brown, M. A. (2012). Comparing Bronchoalveolar Lavage Cell Profiles In Uncontrolled Wheezy Children With Negative And Positive Asthma Predictive Indices. In A105. EVALUATION OF PEDIATRIC LUNG DISEASES.
• Morgan, W. J., Wong, E. C., Wheatley, C. M., Snyder, E. M., Morgan, W. J., Martinez, F. D., Lau, S., Gilbertson, D., Daines, C. L., & Cassuto, N. A. (2012). CT-Derived Pulmonary Vascular Volume And Lung Structure And Function In Humans. In A65. LUNG IMAGING: PHYSIOLOGY AND TECHNOLOGY.
• Trueman, D., Schechter, M. S., Higuchi, K., Farquharson, R., & Daines, C. L. (2012). An Economic Evaluation Of Aztreonam Lysine For Inhalation And Tobramycin For Inhalation, In An Intermittent Aerosolised Antibiotic Regime, Among Cystic Fibrosis Patients With Chronic Pulmonary Pseudomonas Aeruginosa Infection. In A40. THE ECONOMIC BURDEN OF RESPIRATORY DISEASE AND COST-EFFECTIVENESS OF TREATMENTS.
• Morgan, W. J., Wong, E. C., Wheatley, C. M., Snyder, E. M., Pett, R. G., Morgan, W. J., Morgan, M. A., Foxx-lupo, W. T., & Daines, C. L. (2011). Influence Of Genetic Variation Of The Alpha-Subunit Of Enac On Lung Diffusion In Patients With Cystic Fibrosis. In A23. ADULT CYSTIC FIBROSIS: ADVANCES IN TREATMENT AND UNDERSTANDING OF MECHANISMS OF DISEASE.
• Morgan, W. J., Wheatley, C. M., Snyder, E. M., Phan, H., Morgan, W. J., Molina, O., Foxx-lupo, W. T., Daines, C. L., & Cassuto, N. A. (2010). Influence Of An Inhaled ²-Agonist On Exhaled Na+, K+, And Cl- In Patients With Cystic Fibrosis. In A53. CYSTIC FIBROSIS: CLINICAL PEDIATRIC STUDIES.
• Morgan, W. J., Wheatley, C. M., Traylor, B. R., Snyder, E. M., Skrentny, T., Phan, H., Morgan, W. J., Foxx-lupo, W. T., Daines, C. L., & Cassuto, N. A. (2010). Influence Of An Inhaled B-agonist On Alveolar-Capillary Membrane Conductance And Oxygen Saturation In Patients With Cystic Fibrosis. In A53. CYSTIC FIBROSIS: CLINICAL PEDIATRIC STUDIES.
• Morgan, W. J., Wong, E. C., Wheatley, C. M., Traylor, B. R., Snyder, E. M., Morgan, W. J., Foxx-lupo, W. T., Daines, C. L., & Cassuto, N. A. (2010). Red Blood Cell Transit Time Is Lower During Exercise In Patients with Cystic Fibrosis Compared To Healthy Subjects. In C109. REVISITING EXERCISE FOR CHILDREN AND ADULTS.

Poster Presentations

• Phan, H., Sawicki, G. S., Quittner, A. L., Daines, C. L., Nasr, S. Z., Butcher, J. L., Psoter, K., & Riekert, K. A. (2018, Oct). Medication beliefs among adolescent and adult patients prescribed cystic fibrosis transmembrane protein regulator (CFTR) modulators.. 2018 North American Cystic Fibrosis Conference. Denver, CO: Cystic Fibrosis Foundation.
  More info

  Phan H, Sawicki GS, Quittner AL, Daines CL, Nasr SZ, Butcher JL, Psoter K, Riekert KA. Medication beliefs among adolescent and adult patients prescribed cystic fibrosis transmembrane protein regulator (CFTR) modulators. Pediatr Pulmonol. 2018;53: 425.
• Repholz, A., Matthias, K. R., Sivinski, J., Lew, D., Tien, Q., Daines, C. L., & Phan, H. (2017, November). Extended Infusion of Beta-Lactams in the Treatment of Acute Pulmonary Exacerbations in Cystic Fibrosis: A Pilot Evaluation of Safety and Efficiacy Outcomes. 2017 North American Cystic Fibrosis Conference. Indianapolis, IN: Cystic Fibrosis Foundation.
• Daines, C. L. (2016, October). Depression and Anxiety Associate with Pain and Dyspnea but not FEV1 in the Mountain West. North American Cystic Fibrosis Conference.
• Daines, C. L. (2016, October). Effects of an Antioxidant-Enriched Multivitamin Supplement on Inflammation and Oxidative Stress in CF. North American Cystic Fibrosis Conference.
• Daines, C. L. (2016, October). Mountain West CF Consortium Sputum Biomarkers Study. North American Cystic Fibrosis Conference.
• Daines, C. L. (2016, October). Personalizing Cystic Fibrosis: A Longitudinal Analysis of the Microbiome From CF Patients. North American Cystic Fibrosis Conference.
• Daines, C. L. (2016, October). Redesigning Clinic Workflow to Improve Outpatient Cystic Fibrosis Care. North American Cystic Fibrosis Conference.
• Zahedieh, S., Seckeler, M., Andrews, J., Klewer, S. E., Scherer, K., Daines, C. L., & Barber, B. J. (2015, Fall). Regional and Racial Variation in Hospitalization Costs in Patients with Duchenne Muscular Dystrophy. American Academy of Pediatrics National Conference and Exhibition. Washington, DC: AAP.

Others

• Phan, H., Cruz, V., Drake, G., McGuire, M. T., Werchan, B., Settle, P., Werchan, A., Campion, J. M., & Daines, C. L. (2016, October). Redesigning clinic workflow to improve outpatient cystic fibrosis care (published abstract and invited project platform presentation). Pediatric Pulmonology.
  More info

  Published Abstract for Platform Presentation, North American Cystic Fibrosis Conference