Background and objective:
Chronic obstructive pulmonary disease and low vitamin D status predict mortality, but their combined effect on mortality remains inconclusive. We aimed to investigate a joint effect of airway obstruction and vitamin D status on mortality in a nationally representative cohort.
We analysed data of 6676 Finnish adults participating between 1978 and 1980 in a national health examination survey, undergoing spirometry and having all necessary data collected. We followed them up in national registers through record linkage until 31 December 2011. We categorised the subjects with obstruction using the lower limit of normal (LLN) and the measured serum 25-hydroxyvitamin-D (s-25(OH)D) into tertiles.
Both obstruction and low s-25(OH)D independently predicted mortality in a multivariate model adjusted also for age, sex, smoking, education, leisure physical activity, body mass index, asthma and serum C-reactive protein. However, a statistically significant (p = 0.007) interaction emerged: the adjusted mortality HRs (95% CI’s) for s-25(OH)D in tertiles among the subjects without and with obstruction were 1.00 (lowest), 0.96 (0.87–1.05) and 0.89 (0.81–0.98); and 1.00, 0.96 (0.71–1.31) and 0.57 (0.40–0.80), respectively.
In conclusion, obstruction and low s-25(OH)D predict mortality independently of each other. Our findings suggest that low vitamin D status might be particularly detrimental among subjects with obstruction.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $53.83 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Kokturk N, Baha A, Oh YM, Young Ju J, Jones PW. Vitamin D deficiency: What does it mean for chronic obstructive pulmonary disease (COPD)? a compherensive review for pulmonologists. Clin Respir J. 2016;12:382–97.
Jaaskelainen T, Itkonen ST, Lundqvist A, Erkkola M, Koskela T, Lakkala K, et al. The positive impact of general vitamin D food fortification policy on vitamin D status in a representative adult Finnish population: evidence from an 11-y follow-up based on standardized 25-hydroxyvitamin D data. Am J Clin Nutr. 2017;105:1512–20.
Quint JK, Wedzicha JA. Is vitamin D deficiency important in the natural history of COPD? Thorax. 2010;65:192–4.
Institute of Medicine Food and Nutrition Board. Dietary reference intakes for adequacy: calcium and vitamin D. Washington DC: National Academies Press; 2011.
Kilkkinen A, Knekt P, Aro A, Rissanen H, Marniemi J, Heliovaara M, et al. Vitamin D status and the risk of cardiovascular disease death. Am J Epidemiol. 2009;170:1032–9.
Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary. Eur Respir J. 2017;49:411–2.
Vasankari TM, Impivaara O, Heliovaara M, Heistaro S, Liippo K, Puukka P, et al. No increase in the prevalence of COPD in two decades. Eur Respir J. 2010;36:766–73.
Buist AS, McBurnie MA, Vollmer WM, Gillespie S, Burney P, Mannino DM. et al. International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study. Lancet. 2007;370:741–50.
Janssens W, Bouillon R, Claes B, Carremans C, Lehouck A, Buysschaert I, et al. Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene. Thorax. 2010;65:215–20.
Zhu M, Wang T, Wang C, Ji Y. The association between vitamin D and COPD risk, severity, and exacerbation: an updated systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2016;11:2597–607.
Afzal S, Lange P, Bojesen SE, Freiberg JJ, Nordestgaard BG. Plasma 25-hydroxyvitamin D, lung function and risk of chronic obstructive pulmonary disease. Thorax. 2014;69:24–31.
Janssens W, Decramer M, Mathieu C, Korf H. Vitamin D and chronic obstructive pulmonary disease: hype or reality? Lancet Respir Med. 2013;1:804–12.
Miller J, Edwards LD, Agusti A, Bakke P, Calverley PM, Celli B, et al. Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort. Respir Med. 2013;107:1376–84.
Khaw KT, Luben R, Wareham N. Serum 25-hydroxyvitamin D, mortality, and incident cardiovascular disease, respiratory disease, cancers, and fractures: a 13-y prospective population study. Am J Clin Nutr. 2014;100:1361–70.
Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S. Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies. Am J Clin Nutr. 2012;95:91–100.
Baughman P, Marott JL, Lange P, Martin CJ, Shankar A, Petsonk EL, et al. Combined effect of lung function level and decline increases morbidity and mortality risks. Eur J Epidemiol. 2012;27:933–43.
Ford ES, Zhao G, Tsai J, Li C. Vitamin D and all-cause mortality among adults in USA: findings from the National Health and Nutrition Examination Survey Linked Mortality Study. Int J Epidemiol. 2011;40:998–1005.
Gaksch M, Jorde R, Grimnes G, Joakimsen R, Schirmer H, Wilsgaard T. et al. Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium. PLoS ONE. 2017;12:e0170791
Ford ES. Lung function, 25-hydroxyvitamin D concentrations and mortality in US adults. Eur J Clin Nutr. 2015;69:572–8.
Holmgaard DB, Mygind LH, Titlestad IL, Madsen H, Fruekilde PB, Pedersen SS. et al. Serum vitamin D in patients with chronic obstructive lung disease does not correlate with mortality--results from a 10-year prospective cohort study. PLoS ONE. 2013;8:e53670
Lee HM, Liu M, Lee K, Luo Y, Wong ND. Does low vitamin D amplify the association of COPD with total and cardiovascular disease mortality? Clin Cardiol. 2014;37:473–8.
National Institute for Health and Welfare in Finland. https://www.thl.fi/en/web/thlfi-en/research-and-expertwork/population-studies/finnish-mobile-clinic/mini-finland-health-survey. Accessed 25 Oct 2017.
Aromaa A, Heliövaara M, Impivaara O, et al. Health, functional limitations and need for care in Finland. Basic results from the Mini-Finland Health Survey (in Finnish with English Summary). Publications of the Social Insurance Institution 1989. Helsinki and Turku. http://hdl.handle.net/10138/162843. Accessed 25 Oct 2017.
Aromaa A, Heliövaara M, Knekt P, Reunanen A, Impivaara O, Maatela J Cardiovascular and respiratory survey methods. Part 2 (in Finnish with English summary). Publications of the Social Insurance Institution 1985. Helsinki and Turku. http://hdl.handle.net/10138/162384. Accessed 25 Oct 2017.
Mattila T, Vasankari T, Kanervisto M, Laitinen T, Impivaara O, Rissanen H, et al. Association between all-cause and cause-specific mortality and the GOLD stages 1-4: A 30-year follow-up among Finnish adults. Respir Med. 2015;109:1012–8.
Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26:948–68.
Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, et al. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012;40:1324–43.
Konstari S, Paananen M, Heliovaara M, Knekt P, Marniemi J, Impivaara O, et al. Association of 25-hydroxyvitamin D with the incidence of knee and hip osteoarthritis: a 22-year follow-up study. Scand J Rheumatol. 2012;41:124–31.
Statistics Finland. Causes of deaths. http://www.stat.fi/til/ksyyt/2005/ksyyt_2005_2006-10-31_luo_002.html. Accessed 31 Dec 2011.
Jaaskelainen T, Knekt P, Marniemi J, Sares-Jaske L, Mannisto S, Heliovaara M, et al. Vitamin D status is associated with sociodemographic factors, lifestyle and metabolic health. Eur J Nutr. 2013;52:513–25.
Virtanen JK, Nurmi T, Voutilainen S, Mursu J, Tuomainen TP. Association of serum 25-hydroxyvitamin D with the risk of death in a general older population in Finland. Eur J Nutr. 2011;50:305–12.
Sluyter JD, Camargo CA, Waayer D, Lawes CMM, Toop L, Khaw KT, et al. Effect of monthly, high-dose, long-term vitamin d on lung function: a randomized controlled trial. Nutrients. 2017;9 https://doi.org/10.3390/nu9121353.
Zendedel A, Gholami M, Anbari K, Ghanadi K, Bachari EC, Azargon A. Effects of vitamin D intake on FEV1 and COPD exacerbation: a randomized clinical trial study. Glob J Health Sci. 2015;7:243–8.
World Health Organization (WHO). Noncommunicable diseases and mental health. http://www.who.int/nmh/events/ncd_action_plan/en. Accessed 25 Oct 2017.
Menotti A, Mulder I, Nissinen A, Giampaoli S, Feskens EJ, Kromhout D. Prevalence of morbidity and multimorbidity in elderly male populations and their impact on 10-year all-cause mortality: The FINE study (Finland, Italy, Netherlands, Elderly). J Clin Epidemiol. 2001;54:680–6.
Agborsangaya C, Toriola AT, Grankvist K, Surcel HM, Holl K, Parkkila S, et al. The effects of storage time and sampling season on the stability of serum 25-hydroxy vitamin D and androstenedione. Nutr Cancer. 2010;62:51–7.
Mattila T, Vasankari T, Rissanen H, Knekt P, Puukka P, Heliovaara M. Airway obstruction and the risk of myocardial infarction and death from coronary heart disease: a national health examination survey with a 33-year follow-up period. Eur J Epidemiol. 2017;33:89–98.
Jorde R, Sneve M, Hutchinson M, Emaus N, Figenschau Y, Grimnes G. Tracking of serum 25-hydroxyvitamin D levels during 14 years in a population-based study and during 12 months in an intervention study. Am J Epidemiol. 2010;171:903–8.
Jousilahti P, Borodulin K. [Suomalaisten tupakointi vähenee. Tutkimuksesta tiiviisti 3 (in Finnish)]. Helsinki, Finland: National Institute for Health and Welfare; 2012.
The University of Helsinki/Hospital District of Helsinki and Uusimaa awarded to the first author a Doctoral Candidate Position (from June 2016 to December 2017) which allowed for the write-up of our analysis.
The University of Helsinki/Hospital District of Helsinki and Uusimaa awarded to the first author a doctoral candidate position from June 2016 to December 2017.
Conflict of interest
TM completed this study through financial support from the Hospital District of Helsinki and Uusimaa (a Doctoral Candidate Position in the Doctoral Programme of Clinical Research at the University of Helsinki/Hospital District of Helsinki and Uusimaa from June 2016 to December 2017). The remaining authors declare that they have no conflict of interest.