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Recommendations Summary

COPD: Assessment of Serum 25(OH)D Status 2019

Click here to see the explanation of recommendation ratings (Strong, Fair, Weak, Consensus, Insufficient Evidence) and labels (Imperative or Conditional). To see more detail on the evidence from which the following recommendations were drawn, use the hyperlinks in the Supporting Evidence Section below.


  • Recommendation(s)

    COPD: Assessment of Serum 25(OH)D Status

    The RDN should assess serum 25(OH)D levels in adults with COPD as part of a routine nutrition assessment. Evidence from 60% of studies reviewed,  found positive associations between serum 25(OH)D and lung function measures.

    Rating: Fair
    Imperative

    COPD: Assessment of Exacerbations  

    If an adult with COPD is having two or more exacerbations per year, the RDN should assess 25(OH)D levels. Evidence from adults with COPD with baseline serum 25(OH)D levels ≤10ng per ml, showed that vitamin D supplementation decreased exacerbations.

    Rating: Fair
    Conditional

    • Risks/Harms of Implementing This Recommendation

      There are no potential risks or harms associated with the application of this recommendation.

    • Conditions of Application

      • The recommendation COPD: Assessment of Exacerbations refers to COPD patients with frequent exacerbations, defined as two or more exacerbations per year (Hurst et al, 2010; Le Rouzic et al, 2018)
      • If necessary data are not available, the RDN should use professional judgment to request or obtain additional data
      • Exacerbations are clinically defined as episodes of increasing respiratory symptoms, particularly dyspnea, cough and sputum production and increased sputum purulence (Wedzicha et al, 2017). The patient perception of an exacerbation is seeking treatment for symptoms; the research criteria is treatment with antibiotics or addition of increased inhaled or systemic steroids.
      • Achievement of normal serum 25(OH)D levels may not be possible in all instances. Therefore, optimizing serum 25(OH)D levels is the goal (Rusinska et al, 2018).

    • Potential Costs Associated with Application

      • Costs may include expenses related to medical nutrition therapy (MNT) visits from an RDN
      • Costs may be incurred due to initial lab testing to evaluate serum 25(OH)D levels.

    • Recommendation Narrative

      COPD: Assessment of Serum 25(OH)D Status 

      A total of 29 papers from 28 studies provided evidence supporting the recommendation COPD: Assessment of Serum 25(OH)D Status. 

      • A total of 14 cross-sectional studies: One positive-quality (Romme et al, 2013),  twelve neutral-quality (Azargoon et al, 2011; El-Shafey and El-Srougy, 2014; Hashim Ali Hussein et al, 2015; Janssens et al, 2010; Jolliffee et al, 2018; Mahlin et al, 2014; Mekov et al, 2015; Monadi et al, 2012; Park et al, 2015; Park et al 2016; Persson et al 2012; Shaneen et al 2011) and one negative-quality (Yang et al, 2015)
      • Six prospective cohort studies: Three positive-quality (Kunisaki et al, 2012; Persson et al, 2015; Puhan et al, 2014) and three neutral-quality (Holmgaard et al, 2013; Jung et al, 2015; Quint et al, 2012)
      • Four retrospective cohort studies: Three positive-quality (Berg et al, 2013; Malinovschi et al, 2014; Mekov et al, 2016) and one neutral-quality (Moberg et al, 2014)
      • Two randomized controlled trials (RCT): One positive-quality (Sanjari et al, 2106) and one neutral-quality (Yumrutepe et al, 2015)
      • One neutral-quality before-after study (Said and Abd-Einaeem, 2015)
      • One neutral-quality descriptive study (Gouda et al, 2016)
      • One neutral-quality case-control study (Kunisaki et al, 2011).

      The overall findings were as follows:

      • Lung Function (LF) (23 studies): A total of 14 studies found significant relationships between serum 25(OH)D and LF outcomes; i.e., as serum 25(OH)D increased, LF outcomes improved (Azargoon et al, 2011; Berg et al, 2013; El-Shafey and El-Srougy, 2014; Gouda et al, 2016; Janssens et al, 2010; Jolliffee et al, 2018; Jung et al, 2015; Park et al, 2016; Persson et al, 2012; Persson et al, 2015; Romme et al, 2013; Said and Abd-Elnaeem, 2015; Yang et al, 2015; Yumrutepe et al, 2015). Nine studies did not find significant relationships between serum 25(OH)D and LF outcomes (Hashim Ali Hussein et al, 2015; Holmgaard et al, 2013; Kunisaki et al, 2011; Mahlin et al, 2014; Malinovschi et al, 2014; Monadi et al, 2012; Park et al, 2015; Sanjari et al, 2016; Shaheen et al, 2011).
      • Acute Exacerbations (AE) (11 studies): Four studies found significant relationships between serum 25(OH)D and AE outcomes; i.e., as serum 25(OH)D increased, AE outcomes improved (Gouda et al, 2016; Malinovschi et al, 2014; Persson et al, 2015; Yang et al, 2015). Seven studies did not find significant relationships between serum 25(OH)D and AE outcomes (Jung et al, 2015; Kunisaki et al, 2011; Mekov et al, 2015; Moberg et al, 2014; Persson et al, 2012; Puhan et al, 2014; Quint et al, 2012).
      • Mortality (five studies): NS relationships were found in any of the studies (Holmgaard et al, 2013; Mekov et al, 2016; Moberg et al, 2014; Persson et al, 2015; Puhan et al, 2014).

      COPD: Assessment of Exacerbations

      A total of eight studies were included in the evidence analysis supporting the recommendation COPD: Assessment of Exacerbations. Two of the studies evaluated exacerbation outcomes in those with serum 25(OH)D under 10ng per ml.  

      • Six RCTs: Four positive-quality (Lehouck et al, 2012; Martineau et al, 2015; Rafiq et al, 2017; Sanjari et al, 2016), one neutral-quality (Khan et al, 2017) and one negative-quality (Zendendel et al, 2015)
      • Two before-after studies: Both neutral-quality (Rezk et al, 2015; Said and Abd-Elnaeem, 2015).

      Seven studies tested oral vitamin D3 (cholecalciferol) ranging from 1, 200 IU daily for six months; subjects and controls could also take 400 IU vitamin D3 daily (Rafiq et al, 2017) to 120, 000 IU every two months for 12 months (Martineau et al, 2015). One study administered 200, 000 IU cholecalciferol intramuscularly (IM) every four weeks for six months (Said and Abd-Elnaeem, 2015). All papers either cited the Endocrine Society Clinical Practice Guideline (ESG) (Holick et al, 2011) for serum 25(OH)D classifications or did not define classifications. In addition to the ESG reference, one study (Lehouck et al, 2012) defined “severe” vitamin D deficiency as serum 25(OH)D levels under 10ng per ml. 

      Seven studies evaluated LF outcomes (Lehouck et al 2012; Martineau et al, 2015; Rafiq et al, 2017; Rezk et al, 2015; Sanjari et al, 2016; Said and Abd-Elnaeem, 2015; Zendedel et al, 2015). Six studies evaluated acute exacerbation (AE) outcomes (Khan et al, 2017; Lehouck et al, 2012; Martineau et al, 2015; Rafiq et al, 2017; Rezk et al, 2015; Zendedel et al, 2015). 

      Five studies of vitamin D supplementation included subjects’ pre- and post-supplementation levels, allowing changes in vitamin D status due to supplementation to be assessed. Results according to baseline (BL) and post-supplementation improvements in vitamin D status (ESG categories) are as follows: 

      • Deficient to sufficient 25(OH)D: Supplementation with 1, 200 IU D3 daily for six months (plus 400 IU daily, if desired) resulted in no impact on LF or AE outcomes (Rafiq et al, 2012). Supplementation with 100, 000 IU D3 every four weeks over 12 months resulted in a decrease in AE rate in a sub-group of subjects with “severe deficiency” [25(OH)D under 10ng per ml] (Lehouck et al, 2012).
      • Insufficient to sufficient 25(OH)D: Supplementation with 100, 000 IU D3 every four weeks over 12 months resulted in no impact on AE or LF outcomes (Lehouck et al, 2012). Supplementation with either 5, 000 IU D3 or 0.25mcg calcitriol every four weeks over 12 months resulted in no impact on LF outcomes (Sanjari et al, 2016).
      • Deficient to insufficient 25(OH)D: Supplementation with 50, 000 IU D3 per week for eight weeks, then 800 IU daily for 12 months resulted in a decrease in number of AEs and an improvement in maximum voluntary ventilation, but no impact on other LF outcomes in subjects with 25(OH)D under 10ng per ml at BL (Rezk et al, 2015). Supplementation with 120, 000 IU D3 every two months over 12 months resulted in improvement in AE severity and symptoms, but had no impact on other AE or LF outcomes (Martineau et al, 2015).

      The remaining three studies did not report subjects’ post-supplementation vitamin D status. One study (Said and Abd-Elnaeem, 2015) reported BL vitamin D status according to ESG categories, but did not report post-supplementation status. The second study (Khan et al, 2017) reported BL vitamin D status of subjects and controls combined and did not report pre- and post-supplementation status of subjects only. Finally, the last study (Zendedel et al, 2015) did not report either BL or post-supplementation vitamin D status.

      • Insufficient 25(OH)D (subjects + controls): Supplementation with 2, 000 IU D3 per day for six months resulted in reduced AEs (Kahn et al, 2017). Supplementation with 200, 000 IU D3 IM every four weeks for six months, resulted in no impact in LF outcomes (Said and Abd-Elnaeem, 2015)
      • Unknown 25(OHD): Supplementation with 100, 000 IU D3 every month for six months resulted in improvement in LF outcomes and a reduction in AEs (Zendedel et al, 2015).

    • Recommendation Strength Rationale

      • Conclusion statements supporting both recommendations are Grade II,  Fair
      • For recommendation COPD: Assessment of Exacerbations, synthesis of the results was challenging due to lack of consistency in vitamin D dosing, dosing frequency and delivery routes, length of intervention and baseline serum 25(OH)D levels.