TY - JOUR
T1 - Prospective multicenter randomized patient recruitment and sample collection to enable future measurements of sputum biomarkers of inflammation in an observational study of cystic fibrosis
AU - Liou, Theodore G.
AU - Adler, Frederick R.
AU - Argel, Natalia
AU - Asfour, Fadi
AU - Brown, Perry S.
AU - Chatfield, Barbara A.
AU - Daines, Cori L.
AU - Durham, Dixie
AU - Francis, Jessica A.
AU - Glover, Barbara
AU - Heynekamp, Theresa
AU - Hoidal, John R.
AU - Jensen, Judy L.
AU - Keogh, Ruth
AU - Kopecky, Carol M.
AU - Lechtzin, Noah
AU - Li, Yanping
AU - Lysinger, Jerimiah
AU - Molina, Osmara
AU - Nakamura, Craig
AU - Packer, Kristyn A.
AU - Poch, Katie R.
AU - Quittner, Alexandra L.
AU - Radford, Peggy
AU - Redway, Abby J.
AU - Sagel, Scott D.
AU - Sprandel, Shawna
AU - Taylor-Cousar, Jennifer L.
AU - Vroom, Jane B.
AU - Yoshikawa, Ryan
AU - Clancy, John P.
AU - Elborn, J. Stuart
AU - Olivier, Kenneth N.
AU - Cox, David R.
N1 - Funding Information:
TGL, JAF, JLJ, YL, KAP and JBV received other support from the CFF (CC132-16 AD, LIOU14Y0, LIOU14P0) and the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) (R01 HL125520) and received support during the current study for performing clinical trials from Abbvie, Gilead, Nivalis, Novartis, Proteostasis, Inc., Savara and Vertex. FRA received additional other support from the NHLBI/NIH (R01 HL125520), the National Science Foundation (EMSW21-RTG) and the Margolis Foundation of Utah. PSB received other support from the CFF (Center and TDC grants) and the NHLBI/ NIH (U01 HL114623) and received support for a clinical trial from Alcresta. BAC received other support from the CFF (C112–12, C112-TDC09Y, 10063SUB, 41,339,154.s132P010379SUB) and received support for clinical trials from Genentech, Novartis and Vertex. CLD received other support from the CFF (C004–11, C004-TDC09Y, DAINES11Y3) and from the Health Resources and Services Administration (T72MC00012). TH received other support from the CFF (PACE, Center Grant) and received support for clinical trials from Celtaxsys and Vertex. JRH received other support from the NHLBI/NIH (HHSN268200900018C) and the Veterans Administration Healthcare System (I01 BX001533). JL received other support from the CFF (C017-11AF). CN received other support from the CFF (C138–12). PR received other support from the CFF (C003–12, C003-TDC09Y). SDS received other support from the CFF (AQUADEK12K1, SAGEL11CS0, GOAL13K2, NICK13A0, SAGEL14K1, NICK15R0) and the NHLBI/NIH (U54 HL096458) and the NCATS/NIH (Colorado CTSA Grant Number UL1 TR002535). JLT-C received other support from the CFF (TDC) and the NHLBI/NIH (HL103801) and received support for clinical trials from Vertex. KNO is funded by the intramural research program of the NHLBI, NIH.
Funding Information:
This project was supported by the CF Foundation (CFF) (LIOU13A0, LIOU14Y4), the National Center for Advancing Translational Science at the National Institutes of Health (NCATS/NIH 8UL1TR000105 [formerly UL1RR025764]), the Ben B and Iris M Margolis Foundation of Utah and the Claudia Ruth Goodrich Stevens Endowment Fund. Neither the sponsors of the project nor any of the sources of other support for the authors had a direct role in the development and conduct of the study. None of the sponsors of clinical trials mentioned in the competing interests section participated in any way with this trial. Prior to submission, the CF Foundation reviewed the manuscript for appropriate use of the CFFPR to protect health information.
Funding Information:
DRC is an Honorary Fellow at Nuffield College. His pioneering work in Statistics includes introduction of the current methods of logistic regression [57] and proportional hazards models [58]. He was awarded the Guy Medal in both Silver and Gold from the Royal Statistical Society, the Kettering Prize and Gold Medal for Cancer Research, the Copley Medal from the Royal Society, and he recently won the first International Prize in Statistics awarded jointly by the American Statistical Association, the International Biometric Society, the Institute of Mathematical Statistics, the International Statistical Institute, and the Royal Statistical Society. His lifelong experience improving the design of experiments [31, 32] was instrumental in the design of the current study. RK received her DPhil under the supervision of DRC from the University of Oxford. She is now Associate Professor in the Department of Medical Statistics at the London School of Hygiene and Tropical Medicine, is funded by a Medical Research Council Methodology Fellowship, and teaches Master’s level courses in medical statistics. She helped the study greatly by participating in the teaching video (Additional files 1, 2 and 3) with DRC and with our initial study design. Our non-MWCFC collaborators brought skills and experience not found in the MWCFC. NL is Director of the Adult CF Program and Associate Professor in the Department of Medicine, Division of Pulmonary and Critical Care Medicine at the Johns Hopkins University. He has published in the area of assessment of pain in patients with CF [45] and brings that expertise to our study. ALQ is a behavioral scientist and clinical psychologist at the Miami Children’s Research Institute. She was awarded the inaugural Mattingly Leadership in Mental Health Care Award in 2016 by the US CF Foundation, and she contributed her expertise on quantitative measurements of depression, anxiety and quality of life [59] to the study. The study benefited greatly from guidance by the external advisory committee. JPC is Professor and Research Director for the Division of Pulmonary Medicine, Department of Pediatrics, at the U of Cincinnati and has been a member or leader of multiple research organizations within the CF Foundation, the European CF Society and the National Institutes of Health in the US (NIH). KNO is Senior Clinician and Chief of the Pulmonary Branch of the National Heart, Lung and Blood Institute (NHLBI) of the NIH and leader of the Chronic Airway Infection Laboratory at the NHLBI. He has led multiple studies of bronchiectasis and infections, especially nontuberculous Mycobacteria. JSE is Faculty Pro-Vice Chancellor of the School of Medicine, Dentistry and Biomedical Sciences and Faculty in the Institute for Health Sciences and the Centre for Experimental Medicine, Queen's University Belfast, UK. He was President of the European CF Society for 8 years and Trustee, Chair or Member of the Medical Advisory Committee of the CF Trust in the UK since 2002. He received knighthood in 2012 for his work in health care in Northern Ireland. He has been author and driving force for many studies that have improved knowledge and care of patients with CF. The authors from the Mountain West CF Consortium have been meeting and working collaboratively for over 20 years including a recent publication [52]. The long-standing close relationships between these individuals and teams enhanced the ability to design and perform this complex multicenter study.
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/4/26
Y1 - 2019/4/26
N2 - Background: 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. Methods: We recruited patients from Mountain West CF Consortium (MWCFC) care centers for prospective observational study of sputum biomarkers of inflammation. After informed consent, centers enrolled randomly selected patients with CF who were clinically stable sputum producers, 12 years of age and older, without previous organ transplantation. Results: From December 8, 2014 through January 16, 2016, we enrolled 114 patients (53 male) with CF with continuing data collection. Baseline characteristics included mean age 27 years (SD = 12), 80% predicted forced expiratory volume in 1 s (SD = 23%), 1.0 prior year pulmonary exacerbations (SD = 1.2), home elevation 328 m (SD = 112) above sea level. Compared with other patients in the US CF Foundation Patient Registry (CFFPR) in 2014, MWCFC patients had similar distribution of sex, age, lung function, weight and rates of exacerbations, diabetes, pancreatic insufficiency, CF-related arthropathy and airway infections including methicillin-sensitive or -resistant Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia complex, fungal and non-tuberculous Mycobacteria infections. They received CF-specific treatments at similar frequencies. Conclusions: Randomly-selected, sputum-producing patients within the MWCFC represent sputum-producing patients in the CFFPR. They have similar characteristics, lung function and frequencies of pulmonary exacerbations, microbial infections and use of CF-specific treatments. These findings will plausibly make future interpretations of quantitative measurements of inflammatory biomarkers generalizable to sputum-producing patients in the CFFPR.
AB - Background: 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. Methods: We recruited patients from Mountain West CF Consortium (MWCFC) care centers for prospective observational study of sputum biomarkers of inflammation. After informed consent, centers enrolled randomly selected patients with CF who were clinically stable sputum producers, 12 years of age and older, without previous organ transplantation. Results: From December 8, 2014 through January 16, 2016, we enrolled 114 patients (53 male) with CF with continuing data collection. Baseline characteristics included mean age 27 years (SD = 12), 80% predicted forced expiratory volume in 1 s (SD = 23%), 1.0 prior year pulmonary exacerbations (SD = 1.2), home elevation 328 m (SD = 112) above sea level. Compared with other patients in the US CF Foundation Patient Registry (CFFPR) in 2014, MWCFC patients had similar distribution of sex, age, lung function, weight and rates of exacerbations, diabetes, pancreatic insufficiency, CF-related arthropathy and airway infections including methicillin-sensitive or -resistant Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia complex, fungal and non-tuberculous Mycobacteria infections. They received CF-specific treatments at similar frequencies. Conclusions: Randomly-selected, sputum-producing patients within the MWCFC represent sputum-producing patients in the CFFPR. They have similar characteristics, lung function and frequencies of pulmonary exacerbations, microbial infections and use of CF-specific treatments. These findings will plausibly make future interpretations of quantitative measurements of inflammatory biomarkers generalizable to sputum-producing patients in the CFFPR.
KW - Calprotectin
KW - Cystic Fibrosis Foundation patient registry
KW - Cystic fibrosis
KW - HMGB-1
KW - Neutrophil elastase
KW - Randomized observational trial
KW - Sputum inflammation
KW - Study design
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U2 - 10.1186/s12874-019-0705-0
DO - 10.1186/s12874-019-0705-0
M3 - Article
C2 - 31027503
AN - SCOPUS:85064983869
SN - 1471-2288
VL - 19
JO - BMC medical research methodology
JF - BMC medical research methodology
IS - 1
M1 - 88
ER -