Gregg E Dinse1, Christine G Parks2, Helen C S Meier3, Caroll A Co4, Edward K L Chan5, Todd A Jusko6, James Yeh7, Frederick W Miller8. 1. Public Health Sciences, Social & Scientific Systems Inc., Durham, NC, USA. Electronic address: gdinse@s-3.com. 2. Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. Electronic address: parks1@niehs.nih.gov. 3. Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI, USA. Electronic address: meierh2@uwm.edu. 4. Public Health Sciences, Social & Scientific Systems Inc., Durham, NC, USA. Electronic address: cco@s-3.com. 5. University of Florida Health Science Center, Gainesville, FL, USA. Electronic address: echan@dental.ufl.edu. 6. Departments of Public Health Sciences and Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. Electronic address: todd_jusko@urmc.rochester.edu. 7. Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA,. Electronic address: jamesyeh87@gmail.com. 8. Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. Electronic address: millerf@mail.nih.gov.
Abstract
BACKGROUND: Clinical reports link specific medications with the development of antinuclear antibodies (ANA), but population-based evidence is limited. OBJECTIVE: The present study investigated associations between prescription medication use and ANA in a representative sample of the adult noninstitutionalized US population, first focusing on medications previously related to ANA and then considering all medications reported in the National Health and Nutrition Examination Survey (NHANES). METHODS: Based on NHANES data (1999-2004) for 3608 adults (ages ≥18 years), we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess associations between recent medication use and ANA (overall and in sex and age subgroups), adjusted for potential confounders and the survey sampling design. RESULTS: We found no evidence that most medications previously associated with ANA in specific individuals were risk factors for ANA in the general population, although statistical power was limited for some medications. Overall, ANA were less prevalent in adults who recently used any prescription medications compared with those who did not (OR = 0.73; CI = 0.57,0.93), and likewise several classes of medications were inversely associated with ANA, including hormones (OR = 0.73; CI = 0.55,0.98), thiazide diuretics (OR = 0.43; CI = 0.24,0.79), sulfonylureas (OR = 0.41; CI = 0.19,0.89), and selective serotonin reuptake inhibitor antidepressants (OR = 0.65; CI = 0.42,0.98). Positive associations with ANA were seen for loop diuretics (OR = 1.72; CI = 1.03,2.88) in all adults, and for benzodiazepines (OR = 2.11; CI = 1.09,4.10) and bronchodilators (OR = 1.83; CI = 1.00,3.38) in older (ages ≥60) adults. Estrogens were positively associated with ANA in older women (OR = 1.80; CI = 1.00,3.23) but inversely associated with ANA in younger (ages 18-59) women (OR = 0.43; CI = 0.20,0.93). Regarding individual medications, ANA were positively associated with ciprofloxacin (OR = 4.23; CI = 1.21,14.8), furosemide (OR = 1.79; CI = 1.09,2.93), and omeprazole (OR = 2.05; CI = 1.03,4.10) in all adults, and with salmeterol (OR = 3.76; CI = 1.66,8.52), tolterodine (OR = 6.64; CI = 1.45,30.5), and triamterene (OR = 3.10; CI = 1.08,8.88) in older adults. Also, in younger adults, hydrochlorothiazide was inversely associated with ANA (OR = 0.44; CI = 0.20,0.98). CONCLUSIONS: Our findings in the general population do not confirm most clinically reported positive associations between specific medications and ANA in some individuals. However, novel positive ANA associations with other medications, as well as unexplained inverse associations with certain classes of medications and overall medication use, deserve further research to clarify the possible roles of medications as risk and protective factors in the development of autoantibodies and autoimmune disease.
BACKGROUND: Clinical reports link specific medications with the development of antinuclear antibodies (ANA), but population-based evidence is limited. OBJECTIVE: The present study investigated associations between prescription medication use and ANA in a representative sample of the adult noninstitutionalized US population, first focusing on medications previously related to ANA and then considering all medications reported in the National Health and Nutrition Examination Survey (NHANES). METHODS: Based on NHANES data (1999-2004) for 3608 adults (ages ≥18 years), we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess associations between recent medication use and ANA (overall and in sex and age subgroups), adjusted for potential confounders and the survey sampling design. RESULTS: We found no evidence that most medications previously associated with ANA in specific individuals were risk factors for ANA in the general population, although statistical power was limited for some medications. Overall, ANA were less prevalent in adults who recently used any prescription medications compared with those who did not (OR = 0.73; CI = 0.57,0.93), and likewise several classes of medications were inversely associated with ANA, including hormones (OR = 0.73; CI = 0.55,0.98), thiazide diuretics (OR = 0.43; CI = 0.24,0.79), sulfonylureas (OR = 0.41; CI = 0.19,0.89), and selective serotonin reuptake inhibitor antidepressants (OR = 0.65; CI = 0.42,0.98). Positive associations with ANA were seen for loop diuretics (OR = 1.72; CI = 1.03,2.88) in all adults, and for benzodiazepines (OR = 2.11; CI = 1.09,4.10) and bronchodilators (OR = 1.83; CI = 1.00,3.38) in older (ages ≥60) adults. Estrogens were positively associated with ANA in older women (OR = 1.80; CI = 1.00,3.23) but inversely associated with ANA in younger (ages 18-59) women (OR = 0.43; CI = 0.20,0.93). Regarding individual medications, ANA were positively associated with ciprofloxacin (OR = 4.23; CI = 1.21,14.8), furosemide (OR = 1.79; CI = 1.09,2.93), and omeprazole (OR = 2.05; CI = 1.03,4.10) in all adults, and with salmeterol (OR = 3.76; CI = 1.66,8.52), tolterodine (OR = 6.64; CI = 1.45,30.5), and triamterene (OR = 3.10; CI = 1.08,8.88) in older adults. Also, in younger adults, hydrochlorothiazide was inversely associated with ANA (OR = 0.44; CI = 0.20,0.98). CONCLUSIONS: Our findings in the general population do not confirm most clinically reported positive associations between specific medications and ANA in some individuals. However, novel positive ANA associations with other medications, as well as unexplained inverse associations with certain classes of medications and overall medication use, deserve further research to clarify the possible roles of medications as risk and protective factors in the development of autoantibodies and autoimmune disease.
Authors: Frederick W Miller; K Michael Pollard; Christine G Parks; Dori R Germolec; Patrick S C Leung; Carlo Selmi; Michael C Humble; Noel R Rose Journal: J Autoimmun Date: 2012-07-06 Impact factor: 7.094
Authors: Takeshi Tanaka; Jenna M Doe; Sarah A Horstmann; Shama Ahmad; Aftab Ahmad; Sung-Joon Min; Paul R Reynolds; Saritha Suram; Jeanette Gaydos; Ellen L Burnham; R William Vandivier Journal: J Biol Chem Date: 2014-02-25 Impact factor: 5.157
Authors: Luciana S Branco-de-Almeida; Mikihito Kajiya; Cristina R Cardoso; Marcelo J B Silva; Kouji Ohta; Pedro L Rosalen; Gilson C N Franco; Xiaozhe Han; Martin A Taubman; Toshihisa Kawai Journal: FEMS Immunol Med Microbiol Date: 2011-06-16
Authors: Minoru Satoh; Edward K L Chan; Lindsey A Ho; Kathryn M Rose; Christine G Parks; Richard D Cohn; Todd A Jusko; Nigel J Walker; Dori R Germolec; Irene Z Whitt; Patrick W Crockett; Brad A Pauley; Jason Y F Chan; Steven J Ross; Linda S Birnbaum; Darryl C Zeldin; Frederick W Miller Journal: Arthritis Rheum Date: 2012-07
Authors: W Marieke Schoonen; Sara L Thomas; Emily C Somers; Liam Smeeth; Joseph Kim; Stephen Evans; Andrew J Hall Journal: Br J Clin Pharmacol Date: 2010-10 Impact factor: 4.335
Authors: Gregg E Dinse; Todd A Jusko; Irene Z Whitt; Caroll A Co; Christine G Parks; Minoru Satoh; Edward K L Chan; Kathryn M Rose; Nigel J Walker; Linda S Birnbaum; Darryl C Zeldin; Clarice R Weinberg; Frederick W Miller Journal: Environ Health Perspect Date: 2015-08-07 Impact factor: 9.031
Authors: Henry P Parkman; Mark L Van Natta; Ashima Makol; Madhusudan Grover; Richard W McCallum; Zubair Malik; Kenneth L Koch; Irene Sarosiek; Braden Kuo; Robert J Shulman; Gianrico Farrugia; Laura Miriel; James Tonascia; Frank Hamilton; Pankaj J Pasricha; Thomas L Abell Journal: Neurogastroenterol Motil Date: 2021-10-01 Impact factor: 3.960
Authors: Helen C S Meier; Dale P Sandler; Jesse Wilkerson; Frederick W Miller; Gregg E Dinse; Christine G Parks Journal: Front Immunol Date: 2022-01-28 Impact factor: 7.561
Authors: María José García; Juan Carlos Rodríguez-Duque; Marta Pascual; Coral Rivas; Beatriz Castro; Sandra Raso; Marcos López-Hoyos; María Teresa Arias-Loste; Montserrat Rivero Journal: Therap Adv Gastroenterol Date: 2022-03-02 Impact factor: 4.409