Table 1 Association between VD deficiency and COPD exacerbation

Rafiq et al. 2022 [93]

Multicenter, double-blind, randomized controlled trial.

Study the effect of vitamin D supplementation on exacerbation frequency in COPD patients with vitamin D deficiency and focus on exacerbation rate, time to first and second exacerbations, hospitalizations, use of antibiotics and corticosteroids, pulmonary function, respiratory mouth pressure, physical performance, skeletal muscle strength, inflammatory markers, nasal microbiota composition, and quality of life.

Vitamin D supplementation did not reduce the exacerbation rate in COPD patients with a vitamin D deficiency, with no significant differences regarding time to first and second exacerbations, hospitalizations, use of antibiotics and corticosteroids, pulmonary function, respiratory mouth pressure, physical performance, skeletal muscle strength, inflammatory markers, nasal microbiota composition, and quality of life between the intervention and placebo groups.

The study suggested that vitamin D supplementation may not effectively reduce exacerbation rates in COPD patients with a vitamin D deficiency.

Further research may be needed to confirm these findings and to determine the optimal treatment for COPD patients with vitamin D deficiency.

Soeroto et al. 2021 [94]

Cross-sectional.

Investigate how vitamin D levels impact FEV1, exacerbation frequency, and symptom severity, as evaluated by the COPD assessment test (CAT), in individuals with stable COPD.

Low vitamin D levels are associated with more frequent exacerbations and higher CAT scores in stable COPD patients but are not associated with FEV1 (%) predicted.

Assessing the level of VD in patients with stable COPD is crucial.

It is advisable to conduct additional research on the connection between COPD and VD.

Jorde et al. 2021

[95]

Cross-sectional.

Explore the potential connection between COPD and serum vitamin D levels and investigate whether low 25-OHD levels impact COPD symptoms, inflammation, exacerbations, and lung function.

COPD patients often have vitamin D deficiency, and 25-OHD levels are linked to inflammation, severity, and disease progression.

Serum 25-OHD is slightly connected to FEV1 and varies among COPD patients; it has weak negative correlations with annual FEV1 change, C-reactive protein, and interleukin-6.

The research paper sheds light on the correlation between serum 25-OHD levels and COPD, which can assist in developing new treatment approaches for COPD patients.

Lokesh et al. 2021

[96]

Case-control study

Investigate the relationship between vitamin D deficiency and COPD in a rural population in South India. It examined the serum levels of 25-OH-vitamin-D in COPD patients and matched individuals from the MUDHRA cohort, as well as risk factors contributing to deficiency. Moreover, it determined the optimal vitamin D levels for COPD and AECOPD.

In South India, over 60% of people with COPD lacked vitamin D, even with sunlight exposure. Those with a deficiency were three times more likely to have exacerbations. Low Vitamin D levels were linked to both COPD and AECOPD.

It is recommended that people with COPD get tested for vitamin D deficiency and receive appropriate treatment.

Research shows that maintaining sufficient levels of vitamin D may lower the likelihood of COPD exacerbations.

However, more studies are necessary to establish the ideal amount of vitamin D supplementation for individuals with COPD.

Pandey et al. 2021

[97]

Case-control.

To understand how inflammation and imbalances in antioxidants and oxidants contribute to COPD. Researchers will measure levels of vitamin D, C-reactive protein (CRP), superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) in both COPD patients and healthy individuals.

COPD patients have an imbalance between oxidants and antioxidants, a vitamin D deficiency, lower SOD and Catalase levels, and higher MDA and CRP levels than healthy individuals.

The study recommends that a biomarker-based study testing the efficacy of novel antioxidants or other agents will help modify the course of COPD.

The study suggests further research to determine the effectiveness of novel antioxidants or other agents as VD supplementation in treating COPD.

Ghosh et al. 2020

[98]

Cohort study.

To study the link between vitamin D levels and respiratory symptoms in smokers with and without COPD and to see if low vitamin D levels lead to poorer respiratory outcomes.

Vitamin D deficiency is associated with increased respiratory symptoms, decreased functional status, increased frequency of severe exacerbations, and airway wall thickening on chest CT scans in current and former smokers with and without COPD.

Vitamin D deficiency was associated with worse quality of life, increased dyspnea, and decreased exercise tolerance.

The study recommends more research identifying how vitamin D supplementation can enhance disease outcomes.

Future studies could explore the impact of vitamin D metabolism on COPD development, its various phenotypes, and its role in preventing COPD exacerbations.

Burkes et al. 2020

[99]

Cross-sectional.

To investigate the link between 25-OH-vitamin D levels and COPD outcomes, such as lung function and exacerbations. It may also identify vitamin D levels as a marker for adverse COPD-related outcomes.

21% of the SPIROMICS cohorts have insufficient levels of vitamin D, mainly young, active smokers and black individuals. This deficiency has been associated with reduced lung function, a higher risk of COPD exacerbation, and unfavorable outcomes. A drop of 10 ng/mL in 25-OH-vitamin D can serve as an indicator of poor COPD-related results.

The study recommended monitoring the level of VD in COPD patients and commenced vitamin D supplementation to improve COPD-related outcomes. However, it is essential to note that further research is needed to determine the optimal dose and duration of vitamin D supplementation in this population.

Köktürk et al. 2020

[100]

Cross-sectional.

To measure vitamin D deficiency in COPD patients and its link to exacerbation and mortality.

Many COPD patients in Turkey have severe vitamin D deficiency, but it does not affect their survival or the likelihood of exacerbation. Vitamin D levels are not linked with exacerbation frequency, microorganism growth, hospital stay length, FEV1, or survival rates.

It suggests that carefully designed randomized controlled studies are needed to clarify the issues related to the effect of vitamin D supplementation in preventing COPD exacerbations.

Li et al. 2020

[101]

Systematic review and meta-analysis of RCT

This study analyzes different RCTs to measure the effectiveness of vitamin D therapy on patients with COPD. It evaluates the impact on lung function, exacerbations, sputum volume, 6-min walk distance, and COPD assessment test score.

After analyzing 25 articles with 2670 participants, the study concluded that vitamin D therapy had a significant positive effect on lung function (FEV1, FEV1/FVC), 6-min walk distance, and reduced acute exacerbation, sputum volume, and COPD assessment test score.

The study suggests that vitamin D therapy could be a potential treatment option for improving lung function and reducing exacerbations in patients with COPD.

Further research is needed to determine the optimal dosage and duration of vitamin D therapy for COPD patients.

Jolliffe et al. 2019

[102]

Systematic review and meta-analysis of RCT

To review data from past trials on vitamin D's impact on COPD, look for variations in results, and see if it reduces exacerbations in patients with low VD levels.

Vitamin D supplementation did not influence the overall rate of moderate/severe COPD exacerbations.

However, vitamin D supplementation safely and substantially reduced the rate of moderate/severe COPD exacerbations in patients with baseline 25-hydroxyvitamin D levels.

The study suggests that vitamin D supplementation may be beneficial in reducing the rate of moderate/severe COPD exacerbations in patients with baseline 25-hydroxyvitamin D levels. Further research is needed to confirm these findings and to determine the optimal dose and duration of vitamin D supplementation for COPD patients.

Mishra et al. 2019

[103]

Case-control

A study compared vitamin D levels in COPD patients and healthy individuals and examined the relationship between vitamin D levels and lung function.

Low vitamin D levels are linked to lower lung function, especially in COPD patients. This effect is more potent in COPD patients, and their expiratory airflow limitation worsens. COPD patients also have lower predicted postbronchodilator FEV1% severity than healthy volunteers.

The study recommended regularly checking vitamin D levels to prevent the negative impact on lung function. However, further research is needed to validate this connection, specifically in India.

Ferrari et al. 2018

[104]

Review and meta-analysis

The literature review investigates the relationship between vitamin D and COPD exacerbation. It analyzes data on a diet, 25(OH)D, and polymorphism to identify the best vitamin D marker, patient groups that may benefit, and safe supplement dosages.

The relationship between how often COPD patients experience exacerbations and their vitamin D levels is still debated in observational studies. However, a meta-analysis has found a negative connection between serum vitamin D and exacerbations. Additionally, two clinical trials have shown that vitamin D3 supplementation can lower the risk of moderate and severe exacerbations in COPD patients. It is worth noting that a patient's susceptibility to exacerbations may be affected by their vitamin D binding protein (VDBP) polymorphisms.

Supplementing with vitamin D may help prevent the worsening of COPD in patients with low levels of the vitamin.

However, more research is necessary to determine the most helpful marker for vitamin D, which subgroups of patients will benefit from, and the appropriate dosage of supplements to avoid toxicity.

Khan et al. 2017

[105]

Randomized controlled trial.

To assess whether vitamin D supplementation can decrease the frequency of acute exacerbations in individuals with Chronic Obstructive Pulmonary Disease (COPD).

Vitamin D supplements reduced acute exacerbations in COPD patients. 25(OH) levels increased from 24.08 ± 2.58 to 29.60 ± 8.74 after 6 months. FVC increased from 77.83 ± 5.49 to 91.34 ± 5.52. Only four patients (3.3%) had exacerbations after 6 months.

The study recommends that vitamin D supplementation be considered a potential intervention to reduce the number of acute exacerbations in COPD patients.

However, further studies are needed to confirm the effectiveness of vitamin D supplementation in COPD patients.

It is also important to note that vitamin D supplementation should be given for a prolonged period and monitored to avoid exceeding the optimum vitamin D level in the blood.

Rafiq et al. 2017

[106]

Randomized, double-blind, placebo-controlled pilot trial.

To investigate the effects of vitamin D supplementation on COPD patients with a deficiency in vitamin D and how it affects respiratory muscle strength, physical performance, pulmonary function, handgrip strength, exacerbation rate, and quality of life.

Adding vitamin D supplements did not improve respiratory muscle strength or physical performance in COPD patients who lacked vitamin D. Despite increased serum 25(OH)D levels after 6 months, there were no significant differences in primary outcomes compared to the placebo group.

The study recommended that more studies are needed to determine if higher doses of vitamin D supplements can improve muscle function and slow the progression of COPD.

Park et al. 2016

[107]

Cross-sectional

To examine the possible link between vitamin D levels and GC polymorphisms with clinical outcomes in COPD patients.

The study found that vitamin D status and GC polymorphisms were associated with airway obstruction, exercise capacity, and emphysema severity but not disease exacerbation.

The study recommended that more research is needed to understand the correlation between GC polymorphisms and vitamin D deficiency in diverse patients.

Zendedel et al. 2015

[108]

Double-blind placebo-controlled randomized clinical trial.

To evaluate the effects of vitamin D intake on COPD exacerbation and FEV1 in patients with severe and very severe COPD.

Vitamin D intake decreased COPD exacerbation in patients with severe and very severe COPD.

Vitamin D intake improved FEV1 in patients with severe and very severe COPD.

There were significant differences in FEV1 and the number of COPD exacerbations between the case and control group patients after the intervention.

The case group showed a significant increase in FEV1 and a significant decrease in the number of COPD exacerbations after the study.

It is suggested that baseline serum vitamin D levels should be recorded in similar studies, and the effect of vitamin D intake should be evaluated regarding the baseline serum vitamin D levels.

Martineau et al. 2015

[109]

Multicentre, double-blind, randomized controlled trial.

The study investigates if vitamin D3 supplements reduce moderate to severe COPD exacerbations and respiratory infections, with consideration of patients’ initial vitamin D levels.

Vitamin D3 supplementation did not affect the time to first moderate or severe exacerbation or upper respiratory infection compared to placebo. However, a prespecified subgroup analysis showed that vitamin D3 was protective against moderate or severe exacerbation in participants with baseline serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L.

The study recommended that vitamin D3 supplementation be considered for patients with COPD with a baseline serum 25-hydroxyvitamin D concentration of less than (50 nmol/L) to reduce the risk of moderate or severe exacerbation.

However, further research is needed to determine the optimal dose and duration of vitamin D3 supplementation for patients with COPD.