Chronic Obstructive Pulmonary Disease is a very complex and multiscalar respiratory disease manifested by incompletely reversible airflow limitation. COPD is a debilitating disease with two major components: chronic bronchitis and emphysema-usually coexisting and contributing importantly to the overall clinical expression of COPD. The most important cause of COPD is long-term exposition to harmful particles and gases, with tobacco smoke as the most significant risk factor that induces chronic inflammatory responses of airways and lung parenchyma [1]. This precipitates a number of pathologic events like mucus hyper secretion, structural change, alveolar attachment destruction, leading to obstruction in airflow and impairment of gas exchange. COPD is increasingly common, representing a major public health issue, since, according to estimates made by GOLD, by 2030; it will be the third leading cause of mortality in the world [2].

Diagnosis of COPD is essentially clinical, supported by spirometric measurements. The spirometric trademark is presented as a low FEV1 to FVC ratio, FEV1/FVC < 0.70, which persists after the use of bronchodilators. This reflects the chronic and progressive nature of airflow limitation that is characteristic of COPD. However, assessment of the severity of COPD should be more than spirometric findings; it also needs to become a global assessment of symptoms, health status, and risk of exacerbations. Several tools and indices have been developed that quantify the severity and impact of COPD on patients, among which the most in use are the BODE index and the COPD Assessment Test score [3, 4].

The BODE index unifies the four important dimensions: body mass index, airflow obstruction, dyspnea, and exercise capacity. It gives a complex estimation of the severity of COPD. This is a very multidimensional concept that helps provide a deeper insight into the impacts of the diseased condition on the patient [5]. It is also good for prognosis and highly correlates with mortality and morbidity. Indeed, higher BODE scores have also been shown to relate to the risk of hospitalization and mortality; this therefore enables clinicians to identify those patients who are at high risk and who may be considered for more aggressive therapeutic interventions [6].

By contrast, the score from the CAT provides a simple, patient-reported questionnaire assessing the impact of COPD on an individual's general health status. Indeed, the CAT includes eight items assessing different symptoms such as cough, sputum production, chest tightness, breathlessness, activity limitation, and sleep quality. The focus of this instrument on the subjective experience of COPD, by the nature of this patient-centric assessment, enables health professionals to tailor management accordingly [7, 8].

In the last ten years, there has been an increasing interest in the role that the levels of serum Vitamin D play in patients suffering from COPD. Vitamin D is a fat-soluble vitamin that is mostly derived from dietary sources, sun exposure, and supplements with a highly significant role in many aspects of the physiological functions of the body, including bone health and immune function [9]. Emerging evidence points to a possible association of Vitamin D deficiency with enhanced susceptibility to respiratory infections, deterioration in lung function, and higher rates of exacerbations in COPD patients. A number of proposed mechanisms explain these associations, including the functions of Vitamin D in modulating immune responses, reducing inflammation, and enhancing the production of antimicrobial peptides within the respiratory epithelium [10].

The relationship between the severity of COPD, as measured using the BODE index and CAT score, and serum levels of Vitamin D remains a critical area of active investigation. Elucidation of this relationship could give further insights into the pathophysiology of COPD and inform the development of new management and interventional strategies. For example, should a strong correlation be demonstrated, and then supplementation with Vitamin D might join the growing list of adjunctive treatments for COPD patients, particularly for those individuals with documented deficiencies [11].

Moreover, the effect of Vitamin D on other co-morbidities commonly associated with COPD includes osteoporosis, cardiovascular diseases, and muscle weakness; thus, it is a more holistic approach toward ensuring the welfare of the patient. Nutritional assessment and optimization, to be inclusive of Vitamin D status monitoring, should be included in COPD management strategies as ways to provide better overall health outcomes and an improved quality of life for the patients [12].

Assessment of COPD severity is not only important for clinical management, but also for prognosis, treatment strategies, and the advancement of research studies. Standardized tools include the BODE index, CAT score, and levels of serum Vitamin D that contribute to a full understanding of the severity of COPD and thus provide meaningful comparisons among studies and evaluations of intervention effectiveness. The integration of new biomarkers, such as serum Vitamin D, into COPD assessment seems an interesting direction of future research. The relationship between the level of Vitamin D and the severity of COPD may be analyzed in search of some new pathways implicated in disease pathogenesis and/or representing new therapeutic targets [13].

The present study will find the correlation of COPD severity as measured by the BODE index with CAT score and serum Vitamin D levels. Some of our objectives are to study the primary correlations between the BODE index and the CAT score, and between the BODE index and serum Vitamin D levels. We also discuss the BODE index-COPD severity by GOLD staging association. By this comprehensive analysis, we attempt to add a little more to the available literature regarding COPD in order to hopefully improve clinical management and outcomes of these patients.

Study Design

This is a prospective observational study designed to assess the association of the severity of Chronic Obstructive Pulmonary Disease with various clinical indices like the BODE index, COPD Assessment Test score, and serum levels of Vitamin D. The study was conducted in a tertiary care institute of India named Raipur Institute of Medical Sciences. Patients for the present study were selected from patients attending the outpatient department in the Department of General Medicine.

Setting and duration of the study

The present study was conducted in RIMS Hospital for two years because of its wide coverage of facilities and patients to obtain as much information as possible on severity stages of COPD and factors associated with them. It also tries to develop better knowledge about the interaction between nutritional statues, represented by serum Vitamin D level and clinical severity, in regard to the management strategy for COPD.

Calculation of Sample Size

Sample size was pre-calculated using the formula, and it emerged that a minimum sample size of 62 patients would be required to achieve the desired level of significance in the results. To further enhance the validity of the outcome, a sample size of 100 participants was used for this study. The formula below was employed in the calculation:

N = [(Za + Z*beta) / C] ^ 2 + 3

Where:

• The standard normal deviate for a = Z_{a} = 1.96
• The standard normal deviate for ẞ at 80% power Z_{f} = 0.84
• C is calculated based on the anticipated correlation coefficient.
•  

Note that this sample size is sufficiently robust to provide a good chance of finding meaningful correlations across variables in question.

Inclusion and Exclusion Criteria

The selection was carried out in accordance with well-set inclusion and exclusion criteria. Eligible patients included those aged 18 years or older from both genders who gave informed consent, had a diagnosis of COPD as per the GOLD guidelines, and were specifically classified within Grade 1 and Grade 2.

The exclusion criteria included those without consent, patients suffering from an acute exacerbation of COPD, and those with other pre-existing nonrespiratory illnesses like severe anemia, chronic cardiac diseases, chronic renal disease, or other respiratory diseases such as pneumonia or bronchial asthma that could impact the study outcome

.

Participant Examination: With ethical clearance, a comprehensive examination was conducted on each participant. It included history taking, general physical examination, and lung function testing by spirometry. Spirometry provided the very important parameters: FEV1, FVC, and the ratio of FEV1/FVC-all crucial in the diagnosis of COPD and staging its severity.

Sample Processing: Blood samples were collected from the participants to check the level of Vitamin D in the serum, done on a quantitative CLIA. A complete hemogram was conducted, along with tests for blood sugar and a lipid profile, to identify underlying comorbidities.

Data Collection Tools: The CAT test was conducted on all cases to analyze the effects of COPD on daily activities. The BODE index was calculated using the BMI, FEV1 percentage, dyspnea score, and exercise capacity from the 6-minute walk test result. To have an easy correlation, the BODE index, CAT scores, and GOLD levels were classified using the GOLD classification of severity of COPD. 

Data Analysis

Data were analyzed using SPSS software to ensure strict statistical evaluation. Continuous variables were summarized as means and standard deviations or medians with interquartile ranges, depending on distribution. Categorical variables were expressed as frequencies and percentages. Relationships between categorical variables were assessed using the Chi-Square test, while Pearson's correlation coefficient was used in the analysis of COPD severity, Vitamin D levels, BODE index, and CAT scores. All statistical analyses were performed with a significance level of p < 0.05.

Ethical Approval: The protocol for this study was presented for consideration and approval by the institutional ethics committee to ensure that all ethical considerations pertaining to patient rights and confidentiality were followed

The study aimed to assess the correlation between clinical parameters and serum Vitamin D levels among COPD patients. The findings reveal that Vitamin D levels are significantly associated with the severity of COPD, smoking history, BMI, and clinical markers like FeV1% and 6-minute walk distance (6MWD). Notably, patients with lower BMI and higher spirometric severity tend to have lower Vitamin D levels. Additionally, smokers showed a strong negative correlation with Vitamin D levels.

Table 1: Demographic Characteristics and Vitamin D Levels (n = 100)

The Table 1 shows that gender and smoking status were not significantly correlated with serum Vitamin D levels, whereas patients with a lower CAT score (<10) had significantly higher Vitamin D levels (p = 0.001).

Table 2: Spiro metric Severity (FeV1%) and Vitamin D Levels (n = 100)

The table 2 highlights the significant association between spirometric severity (FeV1%) and Vitamin D levels. Patients with mild obstruction had the highest Vitamin D levels, while those with severe and very severe obstruction had much lower levels (p = 0.001).

Table 3: BMI Category and Vitamin D Levels (n = 100)

This table 3 shows that BMI is a highly significant factor (p = 0.004) affecting Vitamin D levels. Overweight and obese individuals had the lowest Vitamin D levels, while those with a normal BMI had higher levels.

Figure 1: Bar chart of showing distribution of Study Participants by Gender and Age (n = 100)

Figure 1 consisted of 77% males and 23% females. The average age for men was 57.18 years (±8.28) and for women 52.81 years (±7.76); thus, the mean age of the responding participants was 56.41 years (±8.25).

Figure 2: Bar chart of showing distribution of Study Participants by Smoking Status and Average Pack-Years (n = 100)

In Figure 2 distribution of smokers, ex-smokers, and nonsmokers in the study cohort is 33%, 53%, and 14%, respectively. Of these, the mean pack-years for the smokers were 63.41±37.61 years and that of ex-smokers was 41.24±22.98 pack-years. No data on average pack years is available for nonsmokers.

Figure 3: Bar chart of showing distribution of Study Participants by COPD Stage and Spirometric Severity (n = 100)

In figure 3 participants according to the COPD stages by the GOLD criteria is Stage A: 10%; Stage B: 66%; Stage C: 5%; and Stage D: 19%. Meanwhile, according to the spirometric severity of airway obstruction, 5% have mild obstruction, 40% have moderate obstruction, 30% have severe obstruction, and 25% have a very severe obstruction. This structure allows both classifications to be represented easily graphically.

Various important findings have been unraveled by assessing the relationship between the severity of COPD as per the BODE index and CAT score combined with serum levels of Vitamin D. The gender distribution is also typical: 77% were males, reflecting traditional demographics where higher rates of male involvement in COPD can be related to historical smoking patterns and occupational exposures. Regardless of this, studies such as Ntritsos G et al., 2018 show a reduced gender gap; this may be due to increased smoking among females and more efficient diagnostic techniques. Therefore, from the findings, no noticeable difference in the outcomes based on gender is elaborated for COPD [14].

There is a slight difference, with regard to the mean age from one gender to another in this particular cohort. Other similar studies have results showing mean ages that are similar in presentation as per Martinez CH et al., 2016; they also showed that age impacts the severity and progression of COPD, as mirrored in the BODE index and CAT score. The smokers among them had a pack-year history averaging 63.41 years, while former smokers averaged 41.24 years. This again points out that a long history of smoking may well be a contributor to the severity of COPD. Other studies are different, but, in general, smoking is considered an important factor in COPD aggravation and mostly in current smokers with higher tobacco exposition [15, 16].

The distribution of smoking status in our study-33% of current smokers, 53% ex-smoking patients, and 14% non-smoking patients-indicates that the significant number of COPD patients stops smoking after the diagnosis. This probably might affect the severity and outcome of the disease. However, the presence of non-smokers indicated other risk factors for COPD, such as environmental exposure. The point, however, is that in their findings, 66.9% of participants fell into GOLD Stage B, which was a moderate severity. This is slightly higher compared to the findings by Vestbo J et al. (2013), whose majority of participants were Stage A participants; this might therefore indicate regional or health care system differences in the diagnosis and management of COPD [17, 18].

It was found that 55% had severe to very severe airway obstruction, which corroborates the high disease burden in the current study population. This again corroborates findings from other studies showing the high prevalence of advanced COPD in these kinds of populations. Interestingly, no significant difference by gender and smoking status was observed in serum Vitamin D levels within this population. However, Vitamin D level was significantly related to the CAT scores: patients with lower CAT score (<10) had higher levels of Vitamin D (p = 0.001). There was also an inverse relation between Vitamin D levels and spirometric severity (FeV1%). Patients with mild obstruction had the highest level of Vitamin D, and severe and very severe obstruction showed a significant decrease in its level (p = 0.001). These findings are in agreement with the results of Burkes RM et al. in 2021, where poor outcomes in COPD were associated with low levels of Vitamin D [19, 20].

In this study, there was an overall highly significant inverse correlation between BMI and Vitamin D levels, extending even to overweight or obese subjects, confirming the hypothesis of sequestration of Vitamin D in fat tissue and its decreased bioavailability in higher BMI COPD patients (p=0.004). Vitamin D levels were positively related to better lung function, represented by FeV1%, improved exercise capacity, as represented by the 6-minute walk distance, and lower scores on the CAT. This therefore might imply a potential role of vitamin D in symptom improvement of COPD and improving its clinical course, which also supports the current literature on supplementation of the beneficial effect of adequate vitamin D in COPD management.

It is in this regard that the study focuses on complicated interactions between the severity of COPD and multidimensional indices of the BODE index, CAT score, and serum level of Vitamin D. Such findings confirm the utility of the BODE index as a broad predictor of the results of COPD, which underlines its utility in clinical practice. The CAT score well reflects the symptomatic burden of patients, while Vitamin D level is inversely related to the markers of worse disease.

These may indicate a benefit from the inclusion of Vitamin D supplementation in the management of COPD, especially in those with severe symptoms and low levels of the vitamin. Regular BODE and CAT score monitoring could permit early modification of this treatment and provide an opportunity to offer more individualized therapy, with an overall benefit to patients. Longitudinal studies are now needed which confirm the added benefits of supplementation with Vitamin D and identify further biomarkers which may enhance the assessment of COPD severity.

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