Chronic obstructive pulmonary disease (COPD) is a serious lung disease and the third leading cause of death worldwide(1). Many risk factors may contribute to the symptoms of COPD, like smoking, indoor and outdoor air pollution, genetic susceptibility, occupational exposure, and childhood infections(2).  

At a global level, studies have estimated COPD prevalence in 2020, across both males and females, to be 10.6%, which translates to 480 million cases. The number is projected to increase by 112 million, reaching 592 million by 2050, a relative increase of 23.3%(2). According to the Global Burden of Disease Study, in 2021, a total of 213.39 million prevalent cases of COPD were reported globally since 1990(3). Country specific age-standardized mortality for COPD remains high, particularly in countries such as India (3).

The World Health Organization. Global Health Observatoryhas predicted that the prevalence of COPD will continue to increase due to ongoing exposure to risk factors and the aging populations worldwide.  

Magnesium (Mg²⁺) is an intracellular cation that regulates the bronchial tone and respiratory muscle function. Consequently, magnesium deficiency may contribute to exacerbations of pulmonary diseases by alleviating bronchospasm (1). It counteracts bronchoconstriction induced by calcium, inhibits acetylcholine release from cholinergic nerve endings, and reduces histamine release from mast cells (4). Additionally, low dietary magnesium intake has been identified as a potential risk factor for the development of asthma and COPD (5).

In patients with acute exacerbation of COPD (AECOPD), serum magnesium level have been reported to be inversely correlated with the frequency of exacerbation. Lower serum magnesium levels are associated with more frequent exacerbations and worsened pulmonary function  (6). In a singlecenter retrospective cohort study, early administration of magnesium sulfatein critically ill patients with COPD excerbation was associated with lower 28-day mortality (7). A systematic review also indicated that intravenous magnesium was associated with decreased hospital admission rates, shorter stays, and improved dyspnea scores during acute exacerbations (8).

The role of magnesium level in COPD exacerbation patients remains underexplored. Although data from around the world is available, data from Asia is limited and from Pakistan is almost scarce. Given regional variations in lifestyle, environmental exposure, management, diet, socioeconomic and healthcare access.  

This was a descriptive cross-sectional study conducted at the Department of Chest Medicine Jinnah Postgraduate Medical Centre, Karachi . A total of 53 patients diagnosed with acute exacerbations of COPD were included. Patients presented either to the outpatient department (OPD) or the emergency department (ED) based on specified inclusion and exclusion criteria. INCLUSION CRITERIA • Patients between the age group 40 to 70 years. • Patients with COPD exacerbation in accordance with operational definition. • Duration of COPD >2 years. EXCLUSION CRITERIA • Patients taking medications affecting magnesium levels (diuretics, antidepressants and pain medications). • Patients with heart, kidney or liver disease. • Patients with syndrome of inappropriate anti-diuretic hormone (SIADH). • Patients with chronic, severe vomiting or diarrhea and other causes of dehydration. • Patients with hormonal disorders affecting electrolyte balance. Data Collection Basic demographic data and detailed information about each participants were recorded. Vital signs, arterial blood gas analysis, and chest X-rays were obtained for all patients. According to GOLD guidelines (2026), an exacerbation of COPD is defined an acute worsening of respiratory symptoms over a few days (up to 14 days),characterized by increased dyspnea and/or cough and sputum production, which may be accompanied by tachypnea and/or tachycardia. Serum magnesium levels were measured using standard biochemical methods. A serum magnesium level below 1.7 mg/dL was diagnosed as hypomagnesemia (9). Statistical Analysis Data was analyzed on SPSS Version 22.0. The normality of the continuous variables was assessed using the Shapiro-Wilk test. Mean ± standard deviations (SD) was calculated for the normally distributed quantitative variables such as age, height, weight, BMI, serum magnesium level and duration of COPD. Median with interquartile range (IQR) was calculated for non normally distributed variables. Frequencies and percentages were calculated for the gender, residential status, smoking status, hypertension, and diabetes mellitus. Effect modifiers were controlled through stratification of age, gender, residential status, smoking status, Diabetes mellitus, hypertension, BMI and duration of COPD. Post stratification, independent sample t-test was applied taking P ≤ 0.05 as statistical criteria of significance.

A total of 53 patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) were included in this study.

Baseline Characteristics

The mean age of the patients was 63.74 ± 6.20 years. The majority of patients were male (75.5%), while females constituted 24.5% of the study population. The mean body mass index (BMI) was 24.98±3.87 kg/m², and the mean duration of COPD was 9.15±10.72 years. The baseline demographic and clinical characteristics of the study population are presented in Table 1.

The mean serum magnesium level was 2.17 ± 0.50 mg/dL. Serum magnesium levels were normally distributed (p=0.463). Among the study participants, low serum magnesium levels were observed in 2 (3.8%) patients, normal levels in 39 (73.6%) patients, and elevated levels in 12 (22.6%) patients. The distribution of serum magnesium levels is summarized in Table 2.

Stratification analysis demonstrated a statistically significant association between serum magnesium levels and body mass index (p=0.0001), as well as hypertension (p=0.030).

No statistically significant association was found between serum magnesium levels and age, gender, smoking status, diabetes mellitus, or duration of COPD (p>0.05). The stratification of serum magnesium levels with selected clinical variables is presented in Table 3.

Chronic obstructive pulmonary disease (COPD) represents an overlap of chronic bronchitis and emphysema and is associated with airway hyperresponsiveness and bronchospasm. These pathophysiological changes contribute to impaired mucociliary clearance, reduced pulmonary gas exchange, and an increased risk of recurrent exacerbations and hospitalizations. COPD remains a major global health burden and continues to be a leading cause of morbidity and mortality worldwide (10–12).

Magnesium plays a critical role in respiratory physiology, particularly in regulating bronchial smooth muscle tone. It exerts bronchodilatory effects by antagonizing calcium-mediated bronchoconstriction, reducing acetylcholine release from cholinergic nerve terminals, and inhibiting histamine release from mast cells (13,14). In addition, emerging evidence suggests that magnesium may modulate airway inflammation and improve pulmonary function in obstructive airway diseases (15).

In the present study, the mean serum magnesium level was 2.17±0.50 mg/dL.

These findings are comparable to previously reported values in patients with  COPD exacerbations. Bhatt et al. reported a mean magnesium level of 1.77±0.19 mg/dL, while Gumus et al. observed levels of 1.88±0.26 mg/dL (16,17). More recent studies have also demonstrated similar trends, supporting the potential role of magnesium in COPD exacerbations (5,6).

An important observation in this study was that the majority of patients  (73.6%) had normal serum magnesium levels, while only a small proportion (3.8%) exhibited hypomagnesemia. This suggests that overt magnesium deficiency may not be highly prevalent in all patients presenting with acute exacerbations. Rather, magnesium may play a modulatory role in disease pathophysiology, influencing airway responsiveness and exacerbation severity rather than acting as a primary causative factor. Similar findings have been reported in recent observational studies, where most patients maintained magnesium levels within the normal range despite clinical exacerbation (5).

Stratification analysis demonstrated a statistically significant association between serum magnesium levels and body mass index (p=0.0001), as well as hypertension (p=0.030). Patients with higher BMI had relatively lower magnesium levels compared to those with lower BMI. This may be explained by altered magnesium metabolism in individuals with increased adiposity, as obesity has been associated with chronic low-grade inflammation and increased renal magnesium loss (18). Similarly, hypertensive patients were found to have lower serum magnesium levels compared to non-hypertensive individuals. Magnesium deficiency has been linked to vascular dysfunction, increased peripheral resistance, and impaired endothelial function, which may contribute to the observed association (19).

No statistically significant association was found between serum magnesium levels and age, gender, smoking status, diabetes mellitus, or duration of COPD. These findings are consistent with other studies that have reported weak or no association between magnesium levels and demographic variables in COPD patients (6,20). This suggests that serum magnesium levels may be influenced more by metabolic and systemic factors rather than demographic characteristics in the setting of acute exacerbations.

The findings of this study support the growing body of evidence suggesting a potential role of magnesium in COPD pathophysiology. However, the exact relationship between serum magnesium levels and disease severity, frequency of exacerbations, and clinical outcomes remains unclear. Recent systematic reviews have emphasized the need for further research to establish the clinical utility of magnesium in the management of COPD (8,21).

A notable strength of this study is the evaluation of serum magnesium levels in a local population where data are limited. Given regional differences in environmental exposure, dietary habits, and healthcare access, these findings provide valuable insight into the role of magnesium in COPD exacerbations in the Pakistani population.

Limitations

This study has several limitations. It was conducted at a single tertiary care center with a relatively small sample size, which may limit the generalizability of the findings. The cross-sectional design does not allow for establishing a causal relationship between serum magnesium levels and COPD exacerbations. Additionally, other potential confounding factors, including dietary magnesium intake and medication use, were not extensively evaluated.

Clinical Implications

These findings highlight the potential clinical relevance of serum magnesium assessment in patients with COPD exacerbations, particularly in those with metabolic comorbidities such as obesity and hypertension. Although routine magnesium supplementation cannot be recommended based on current evidence, monitoring magnesium levels may provide additional insight into disease status. Further large-scale, multicenter studies are required to clarify the role of magnesium in disease progression and to evaluate its potential therapeutic implications.