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Dr Michael J. Epton

Michael Epton

BM BS BMedSci(Hons) MRCP(UK) FRACP PhD

Email michael.epton@cdhb.health.nz

Canterbury Respiratory Research Group
40 Stewart St
Christchurch
New Zealand

Current Roles

  • 2016 - Present
    Adjunct Professor, Departments of Geography, and Communication Disorders, University of Canterbury, Christchurch, New Zealand
  • November 2014 - Present
    Investigator (Christchurch Clinical Studies Trust, New Zealand)
  • February 2010 - Present
    Community Respiratory Physician, Canterbury Initiative, Christchurch, New Zealand
  • January 2009 - Present
    Consultant Physician, Department of Respiratory Medicine, Christchurch Hospital, New Zealand
  • July 2002 - Present
    Director, The Canterbury Respiratory Research Group, Christchurch, New Zealand

Research Interests

  • Asthma, allergy and airway inflammation
  • Air Pollution and airway inflammation
  • COPD
  • Alpha-1 anti-trypsin deficiency
  • Beta agonist pharmacogenetics
  • Exhaled Breath Condensate

Top 10 Publications

  • Darlow BA, Horwood LJ, Woodward LJ, Elliott JM, Troughton RW, Elder MJ, Epton MJ, Stanton JD, Swanney MP, Keenan R, Melzer TR, McKelvey VA, Levin K, Meeks MG, Espiner EA, Cameron VA, Martin J. The New Zealand 1986 very low birth weight cohort as young adults: mapping the road ahead. BMC Pediatr. 2015 Aug 5;15:90
  • Storer M, Curry K, Squire M, Kingham S, Epton M. Breath testing and personal exposure--SIFT-MS detection of breath acetonitrile for exposure monitoring. J Breath Res. 2015 May 26;9(3):036006
  • Frith PA, Thompson PJ, Ratnavadivel R, Chang CL, Bremner P, Day P, Frenzel C, Kurstjens N; Glisten Study Group. Glycopyrronium once-daily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD: the GLISTEN study, a randomised controlled trial. Thorax. 2015 Jun;70(6):519-27.
  • Epton MJ, Stanton JD, McGeoch GR, Shand BI, Swanney MP. The development of a community-based spirometry service in the Canterbury region of New Zealand: observations on new service delivery. NPJ Prim Care Respir Med. 2015 Mar 5;25:15003.
  • Magnussen H, Disse B, Rodriguez-Roisin R, Kirsten A, Watz H, Tetzlaff K, Towse L, Finnigan H, Dahl R, Decramer M, Chanez P, Wouters EF, Calverley PM; WISDOM Investigators. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014 Oct 2;371(14):1285-94
  • Storer M., Salmond J., Dirks K.N., Kingham, S., Epton, M. Mobile selected ion flow tube mass spectrometry (SIFT-MS) devices and their use for pollution exposure monitoring in breath and ambient air-pilot study. Journal of Breath Research 2014;8(3).
  • Maze M.J., Slow S., Cumins A.M., Boon K., Goulter P., Podmore R.G., Anderson T.P., Barratt K., Young S.A., Pithie A.D., Epton M.J., Werno A.M., Chambers S.T., Murdoch D.R. Enhanced detection of Legionnaires' disease by PCR testing of induced sputum and throat swabs. European Respiratory Journal 2014;43(2):644-646.
  • Scott-Thomas A., Epton M., Chambers S. Validating a breath collection and analysis system for the new tuberculosis breath test. Journal of Breath Research 2013;7(3)
  • Sturney S.C., Storer M.K., Shaw G.M., Shaw D.E., Epton M.J. Off-line breath acetone analysis in critical illness. Journal of Breath Research 2013;7(3)
  • Scott-Thomas A., Syhre M., Epton, M., Murdoch D.R., Chambers S.T. Assessment of potential causes of falsely positive Mycobacterium tuberculosis breath test. Tuberculosis 2013;93(3):312-317
  • Dummer J., Storer M., Sturney S., Scott-Thomas A., Chambers S., Swanney M., Epton E. Quantification of hydrogen cyanide (HCN) in breath using selected ion flow tube mass spectrometry - HCN is not a biomarker of Pseudomonas in chronic suppurative lung disease. Journal of Breath Research 2013;7(1). doi:10.1088/1752-7155/7/1/017105

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Publications

Hoskin, T. S., Crowther, J. M., Cheung, J., Epton, M. J., Sly, P. D., Elder, P. A., … Kettle, A. J., & Dickerhof, N. (2019). Oxidative cross-linking of calprotectin occurs in vivo, altering its structure and susceptibility to proteolysis. Redox Biology. Advance online publication. doi: 10.1016/j.redox.2019.101202

Slow, S., Epton, M., Storer, M., Thiessen, R., Lim, S., Wong, J., Chin, P., Tovaranonte, P., Pearson, J., Chambers, S. T., Murdoch, D. R., and VIDCAPS Group, including Jardine, D., & Pithie, A. (2018). Effect of adjunctive single high-dose vitamin D3 on outcome of community-acquired pneumonia in hospitalised adults: The VIDCAPS randomised controlled trial. Scientific Reports, 8(1), 13829. doi: 10.1038/s41598-018-32162-2

Pattemore, P. K., Silvers, K. M., Frampton, C. M., Wickens, K., Ingham, T., Fishwick, D., Crane, J., Town, G. I., Epton, M. J., on behalf of the New Zealand Asthma and Allergy Cohort Study Group, including Lampshire, P., Leadbitter, P., Nicholson, A., & Siebers, R. (2018). Hair nicotine at 15 months old, tobacco exposure and wheeze or asthma from 15 months to 6 years old. Pediatric Pulmonology, 53(4), 443-451. doi: 10.1002/ppul.23903

Yang, J., Epton, M., Darlow, B., Horwood, J., Martin, J., & Swanney, M. P. (2018). Effects of very low birth weight and bronchopulmonary dysplasia on adult pulmonary function. American Journal of Respiratory & Critical Care Medicine, 197, A2325. [Full Paper]

McEvoy, R. D., Antic, N. A., Heeley, E., Luo, Y., Ou, Q., Zhang, X., … for the SAVE Investigators and Coordinators, including Epton, M. J., Brockway, B., Cowan, J., Taylor, D. R., Palmay, R., Ferrier, K., & Neill, A. (2016). CPAP for prevention of cardiovascular events in obstructive sleep apnea. New England Journal of Medicine, 375(10), 919-932. doi: 10.1056/NEJMoa1606599

Journal - Research Article

Hoskin, T. S., Crowther, J. M., Cheung, J., Epton, M. J., Sly, P. D., Elder, P. A., … Kettle, A. J., & Dickerhof, N. (2019). Oxidative cross-linking of calprotectin occurs in vivo, altering its structure and susceptibility to proteolysis. Redox Biology. Advance online publication. doi: 10.1016/j.redox.2019.101202

Slow, S., Epton, M., Storer, M., Thiessen, R., Lim, S., Wong, J., Chin, P., Tovaranonte, P., Pearson, J., Chambers, S. T., Murdoch, D. R., and VIDCAPS Group, including Jardine, D., & Pithie, A. (2018). Effect of adjunctive single high-dose vitamin D3 on outcome of community-acquired pneumonia in hospitalised adults: The VIDCAPS randomised controlled trial. Scientific Reports, 8(1), 13829. doi: 10.1038/s41598-018-32162-2

Pattemore, P. K., Silvers, K. M., Frampton, C. M., Wickens, K., Ingham, T., Fishwick, D., Crane, J., Town, G. I., Epton, M. J., on behalf of the New Zealand Asthma and Allergy Cohort Study Group, including Lampshire, P., Leadbitter, P., Nicholson, A., & Siebers, R. (2018). Hair nicotine at 15 months old, tobacco exposure and wheeze or asthma from 15 months to 6 years old. Pediatric Pulmonology, 53(4), 443-451. doi: 10.1002/ppul.23903

McEvoy, R. D., Antic, N. A., Heeley, E., Luo, Y., Ou, Q., Zhang, X., … for the SAVE Investigators and Coordinators, including Epton, M. J., Brockway, B., Cowan, J., Taylor, D. R., Palmay, R., Ferrier, K., & Neill, A. (2016). CPAP for prevention of cardiovascular events in obstructive sleep apnea. New England Journal of Medicine, 375(10), 919-932. doi: 10.1056/NEJMoa1606599

Scott-Thomas, A., Syhre, M., Epton, M., Murdoch, D. R., & Chambers, S. T. (2013). Assessment of potential causes of falsely positive Mycobacterium tuberculosis breath test. Tuberculosis, 93(3), 312-317. doi: 10.1016/j.tube.2013.01.005

Storer, M., Dummer, J., Sturney, S., & Epton, M. (2013). Validating SIFT-MS analysis of volatiles in breath. Current Analytical Chemistry, 9(4), 576-583. doi: 10.2174/15734110113099990022

Dummer, J., Storer, M., Sturney, S., Scott-Thomas, A., Chambers, S., Swanney, M., & Epton, M. (2013). Quantification of hydrogen cyanide (HCN) in breath using selected ion flow tube mass spectrometry: HCN is not a biomarker of Pseudomonas in chronic suppurative lung disease. Journal of Breath Research, 7(1), 017105. doi: 10.1088/1752-7155/7/1/017105

Scott-Thomas, A., Epton, M., & Chambers, S. (2013). Validating a breath collection and analysis system for the new tuberculosis breath test. Journal of Breath Research, 7(3), 037108. doi: 10.1088/1752-7155/7/3/037108

Silvers, K. M., Frampton, C. M., Wickens, K., Pattemore, P. K., Ingham, T., Fishwick, D., Crane, J., Town, G. I., Epton, M. J., on behalf of the New Zealand Asthma and Allergy Cohort Study Group, including Duignan, M., Irvine, V., Lampshire, P., Leadbitter, P., & Siebers, R. (2012). Breastfeeding protects against current asthma up to 6 years of age. Journal of Pediatrics, 160(6), 991-996. doi: 10.1016/j.jpeds.2011.11.055

Crane, J., Lampshire, P., Wickens, K., Epton, M., Siebers, R., Ingham, T., Pattemore, P., Town, I., and the Year Six New Zealand Asthma and Allergy Cohort Study Group, (NZAACS6) . (2012). Asthma, atopy and exhaled nitric oxide in a cohort of 6-yr-old New Zealand children. Pediatric Allergy & Immunology, 23(1), 59-64. doi: 10.1111/j.1399-3038.2011.01227.x

Chambers, S. T., Scott-Thomas, A., & Epton, M. (2012). Developments in novel breath tests for bacterial and fungal pulmonary infection. Current Opinion in Pulmonary Medicine, 18(3), 228-232. doi: 10.1097/MCP.0b013e328351f98b

Thomson, C. D., Wickens, K., Miller, J., Ingham, T., Lampshire, P., Epton, M. J., Town, G. I., Pattemore, P., Crane, J., and the Year Six New Zealand Asthma and Allergy Cohort Study Group, (NZAACS6) including Siebers, R. (2012). Selenium status and allergic disease in a cohort of New Zealand Children. Clinical & Experimental Allergy, 42(4), 560-567. doi: 10.1111/j.1365-2222.2011.03924.x

Tanpowpong, P., Ingham, T. R., Lampshire, P. K., Kirchberg, F. F., Epton, M. J., Crane, J., … and the New Zealand Asthma and Allergy Cohort Study Group, including Pattemore, P., Siebers, R., & Wickens, K. (2012). Coeliac disease and gluten avoidance in New Zealand children. Archives of Disease in Childhood, 97, 12-16. doi: 10.1136/archdischild-2011-300248

Wickens, K., Beasley, R., Town, I., Epton, M., Pattemore, P., Ingham, T., Crane, J., and the New Zealand Asthma and Allergy Cohort Study Group, including Duignan, M., Irvine, V., Lampshire, P., Leadbitter, P., & Siebers, R. (2011). The effects of early and late paracetamol exposure on asthma and atopy: A birth cohort. Clinical & Experimental Allergy, 41(3), 399-406. doi: 10.1111/j.1365-2222.2010.03610.x

Camargo, Jr, C. A., Ingham, T., Wickens, K., Thadhani, R., Silvers, K. M., Epton, M. J., Town, G. I., Pattemore, P. K., … Crane, J., and the New Zealand Asthma and Allergy Cohort Study Group, including Duignan, M., Irvine, V., Lampshire, P., Leadbitter, P., & Siebers, R. (2011). Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma. Pediatrics, 127(1), e180-e187. doi: 10.1542/peds.2010-0442

Bhandari, S., Chambers, S., Pearson, J., Syhre, M., Epton, M., & Scott-Thomas, A. (2011). Determining the limits and confounders for the 2-pentyl furan breath test by gas chromatography/mass spectrometry. Journal of Chromatography B, 879(26), 2815-2820. doi: 10.1016/j.jchromb.2011.08.010

Storer, M. K., Dummer, J. F., Cook, J., McEwan, M., & Epton, M. J. (2011). Increased concentrations of breath haloamines are not detectable in airways inflammation using SIFT-MS. Journal of Breath Research, 5(3). doi: 10.1088/1752-7155/5/3/037105

Young, R. P., Hopkins, R. J., Whittington, C. F., Hay, B. A., Epton, M. J., & Gamble, G. D. (2011). Individual and cumulative effects of GWAS susceptibility loci in lung cancer: Associations after sub-phenotyping for COPD. PLoS ONE, 6(2), e16476. doi: 10.1371/journal.pone.0016476

Dummer, J., Storer, M., Swanney, M., McEwan, M., Scott-Thomas, A., Bhandari, S., Chambers, S., … Epton, M. (2011). Analysis of biogenic volatile organic compounds in human health and disease. Trends in Analytical Chemistry, 30(7), 960-967. doi: 10.1016/j.trac.2011.03.011

Fukuda, K., Hider, P. N., Epton, M. J., Jennings, L. C., & Kingham, S. (2011). Including viral infection data supports an association between particulate pollution and respiratory admissions. Australian & New Zealand Journal of Public Health, 35(2), 163-169. doi: 10.1111/j.1753-6405.2010.00620.x

Storer, M., Dummer, J., Lunt, H., Scotter, J., McCartin, F., Cook, J., Swanney, M., … Epton, M. (2011). Measurement of breath acetone concentrations by selected ion flow tube mass spectrometry in type 2 diabetes. Journal of Breath Research, 5, 046011. doi: 10.1088/1752-7155/5/4/046011

Hu, W.-P., Langford, V. S., McEwan, M. J., Milligan, D. B., Storer, M. K., Dummer, J., & Epton, M. J. (2010). Monitoring chloramines and bromamines in a humid environment using selected ion flow tube mass spectrometry. Rapid Communications in Mass Spectrometry, 24(12), 1744-1748. doi: 10.1002/rcm.4570

Young, R. P., Whittington, C. F., Hopkins, R. J., Hay, B. A., Epton, M. J., Black, P. N., & Gamble, G. D. (2010). Chromosome 4q31 locus in COPD is also associated with lung cancer. European Respiratory Journal, 36(6), 1375-1382. doi: 10.1183/09031936.00033310

Scott-Thomas, A. J., Syhre, M., Pattemore, P. K., Epton, M., Laing, R., Pearson, J., & Chambers, S. T. (2010). 2-Aminoacetophenone as a potential breath biomarker for Pseudomonas aeruginosa in the cystic fibrosis lung. BMC Pulmonary Medicine, 10, 56. doi: 10.1186/1471-2466-10-56

Camargo, Jr, C. A., Ingham, T., Wickens, K., Thadhani, R. I., Silvers, K. M., Epton, M. J., Town, G. I., … Crane, J., and the New Zealand Asthma and Allergy Cohort Study Group, including Leadbitter, P., Pattemore, P., & Siebers, R. (2010). Vitamin D status of newborns in New Zealand. British Journal of Nutrition, 104(7), 1051-1057. doi: 10.1017/S0007114510001674

Dummer, J. F., . . ., Frampton, C. M., Scotter, J. M., Prisk, G., & Epton, M. J. (2010). Accurate, reproducible measurement of acetone concentration in breath using selected ion flow tube-mass spectrometry. Journal of Breath Research, 4, 046001. doi: 10.1088/1752-7155/4/4/046001

Young, R. P., Hopkins, R. J., Hay, B. A., Epton, M. J., Mills, G. D., Black, P. N., … Gamble, G. D. (2009). Lung cancer susceptibility model based on age, family history and genetic variants. PLoS ONE, 4(4), e5302. doi: 10.1371/journal.pone.0005302

Chambers, S. T., Syhre, M., Murdoch, D. R., McCartin, F. J., & Epton, M. J. (2009). Detection of 2-Pentylfuran in the breath of patients with Aspergillus fumigatus. Medical Mycology, 47(5), 468-476. doi: 10.1080/13693780802475212

Silvers, K. M., Frampton, C. M., Wickens, K., Epton, M. J., Pattemore, P. K., Ingham, T., … Crane, J., Town, G. I., and the New Zealand Asthma and Allergy Cohort Study Group, including Duignan, M., Irvine, V., Lampshire, P., Leadbitter, P., & Siebers, R. (2009). Breastfeeding protects against adverse respiratory outcomes at 15 months of age. Maternal & Child Nutrition, 5(3), 243-250. doi: 10.1111/j.1740-8709.2008.00169.x

Dummer, J. F., Epton, M. J., Cowan, J. O., Cook, J. M., Condliffe, R., Landhuis, C. E., Smith, A. D., & Taylor, D. R. (2009). Predicting corticosteroid response in chronic obstructive pulmonary disease using exhaled nitric oxide. American Journal of Respiratory & Critical Care Medicine, 180(9), 846-852. doi: 10.1164/rccm.200905-0685OC

Young, R. P., Hopkins, R. J., Hay, B. A., Epton, M. J., Mills, G. D., Black, P. N., … Gamble, G. D. (2009). A gene-based risk score for lung cancer susceptibility in smokers and ex-smokers. Postgraduate Medical Journal, 85(1008), 515-524. doi: 10.1136/pgmj.2008.077107

Laugesen, M., Epton, M., Frampton, C. M. A., Glover, M., & Lea, R. A. (2009). Hand-rolled cigarette smoking patterns compared with factory-made cigarette smoking in New Zealand men. BMC Public Health, 9, 194. doi: 10.1186/1471-2458-9-194

Epton, M. J., Ledingham, K., Dummer, J., Hu, W.-P., Rhodes, B., Senthilmohan, S. T., Scotter, J. M., Allardyce, R., Cook, J., & Swanney, M. P. (2009). Interference of chlorofluorocarbon (CFC)-containing inhalers with measurements of volatile compounds using selected ion flow tube mass spectrometry. Rapid Communications in Mass Spectrometry, 23(3), 443-447. doi: 10.1002/rcm.3875

Epton, M. J., Dawson, R. D., Brooks, W. M., Kingham, S., Aberkane, T., Cavanagh, J. E., Frampton, C. M., Hewitt, T., Cook, J. M., … Brown, L. (2008). The effect of ambient air pollution on respiratory health of school children: A panel study. Environmental Health, 7. doi: 10.1186/1476-069X-7-16

Tashkin, D. P., Celli, B., Senn, S., Burkhart, D., Kesten, S., Menjoge, S., … UPLIFT Study Investigators, including Epton, M. (2008). A 4-year trial of tiotropium in chronic obstructive pulmonary disease. New England Journal of Medicine, 359(15), 1543-1554. doi: 10.1056/nejmoa0805800

Taylor, D. R., Jayaram, L., Asher, M. I., & Epton, M. J. (2008). ″As-required″ combination therapy with inhaled corticosteroids and long-acting beta-2 agonists for asthma: Current evidence and recommendations [Review article]. New Zealand Medical Journal, 121(1285). Retrieved from http://journal.nzma.org.nz/journal/121-1285/3346/content.pdf

Wickens, K., Ingham, T., Epton, M., Pattemore, P., Town, I., Fishwick, D., Crane, J., and the New Zealand Asthma and Allergy Cohort Study Group, including Duignan, M., Irvine, V., Lampshire, P., Leadbitter, P., & Siebers, R. (2008). The association of early life exposure to antibiotics and the development of asthma, eczema and atopy in a birth cohort: Confounding or causality? Clinical & Experimental Allergy, 38, 1318-1324. doi: 10.1111/j.1365-2222.2008.03024.x

Kingham, S., Durand, M., Harrison, J., Cavanagh, J., & Epton, M. (2008). Temporal variations in particulate exposure to wood smoke in a residential school environment. Atmospheric Environment, 42(19), 4619-4631.

Senthilmohan, S. T., Kettle, A. J., McEwan, M. J., Dummer, J., Edwards, S. J., Wilson, P. F., & Epton, M. J. (2008). Detection of monobromamine, monochloramine and dichloramine using selected ion flow tube mass spectrometry and their relevance as breath markers. Rapid Communications in Mass Spectrometry, 22(5), 677-681. doi: 10.1002/rcm.3418

Young, R. P., Hopkins, R. J., Hay, B. A., Epton, M. J., Black, P. N., & Gamble, G. D. (2008). Lung cancer gene associated with COPD: Triple whammy or possible confounding effect? European Respiratory Journal, 32(5), 1158-1164. doi: 10.1183/09031936.00093908

Sabel, C. E., Wilson, J. G., Kingham, S., Tisch, C., & Epton, M. (2007). Spatial implications of covariate adjustment on patterns of risk: Respiratory hospital admissions in Christchurch, New Zealand. Social Science & Medicine, 65, 43-59. doi: 10.1016/j.socscimed.2007.02.040

Cavanagh, J.-A. E., Brown, L., Trought, K., Kingham, S., & Epton, M. J. (2007). Elevated concentrations of 1-hydroxypyrene in schoolchildren during winter in Christchurch, New Zealand. Science of the Total Environment, 374, 51-59. doi: 10.1016/j.scitotenv.2006.11.042

Epton, M. J., Town, G. I., Ingham, T., Wickens, K., Fishwick, D., Crane, J., and the New Zealand Asthma and Allergy Cohort Study Group, including Duignan, M., Fitzharris, P., … Lampshire, P., Leadbitter, P., Nicholson, A., Pattemore, P., Siebers, R., Silvers, K. M., & Withell, K. (2007). The New Zealand Asthma and Allergy Cohort Study (NZA2CS): Assembly, demographics and investigations. BMC Public Health, 7, 26. doi: 10.1186/1471-2458-7-26

Kingham, S., Durand, M., Aberkane, T., Harrison, J., Wilson, J. G., & Epton, M. (2006). Winter comparison of TEOM, MiniVol and DustTrak PM10 monitors in a woodsmoke environment. Atmospheric Environment, 40, 338-347.

Gillespie, J., Wickens, K., Siebers, R., Howden-Chapman, P., Town, I., Epton, M., Fitzharris, P., … Crane, J., and the New Zealand Asthma and Allergy Birth Cohort Study Group, including Ingham, T., Irvine, V., Lampshire, P., Leadbitter, P., & Silvers, K. M. (2006). Endotoxin exposure, wheezing, and rash in infancy in a New Zealand birth cohort. Journal of Allergy & Clinical Immunology, 118, 1265-1270. doi: 10.1016/j.jaci.2006.07.051

Kelly, M. G., Frizelle, F. A., Thornley, P. T., Beckert, L., Epton, M., & Lynch, A. C. (2006). Inflammatory bowel disease and the lung: Is there a link between surgery and bronchiectasis? International Journal of Colorectal Disease, 21(8), 754-757.

Brooks, W. M., Lash, H., Kettle, A. J., & Epton, M. J. (2006). Optimising hydrogen peroxide measurement in exhaled breath condensate. Redox Report, 11(2), 78-84.

McGeoch, G. R. B., Willsman, K. J., Dowson, C. A., Town, G. I., Frampton, C. M., McCartin, F. J., Cook, J. M., & Epton, M. J. (2006). Self-management plans in the primary care of patients with chronic obstructive pulmonary disease. Respirology, 11, 611-618.

Richards, D. A., Toop, L. J., Epton, M. J., McGeoch, G. R. B., Town, G. I., Wynn-Thomas, S. M. H., Dawson, R. D., Hlavac, M. C., Werno, A. M., & Abernethy, P. D. (2005). Home management of mild to moderately severe community-acquired pneumonia: A randomised controlled trial. Medical Journal of Australia, 183(5), 235-238.

Taylor, D. R., Epton, M. J., Kennedy, M. A., Smith, A. D., Iles, S., Miller, A. L., Littlejohn, M. D., Cowan, J. O., Hewitt, T., Swanney, M. P., Brassett, K. P., & Herbison, G. P. (2005). Bronchodilator response in relation to β2-adrenoceptor haplotype in patients with asthma. American Journal of Respiratory & Critical Care Medicine, 172(6), 700-703.

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