Abstract

Background: Dyspepsia is a common gastrointestinal condition characterized by recurrent upper abdominal pain and discomfort, significantly impacting the quality of life and increasing healthcare burdens. While various factors such as infections, dietary habits, and psychological stress contribute to dyspepsia, emerging evidence suggests that oral tobacco consumption may also play a significant role.

Objective: To assess the association between oral tobacco consumption and dyspepsia among patients presenting at a tertiary care

hospital in Karachi, Pakistan.

Methods: This case-control study was conducted from March to June 2024 at Mekran Medical College, Turbat, Baluchistan. A total of 150 adults aged 18-65 years were recruited, including 75 cases with confirmed dyspepsia, as determined by upper gastrointestinal endoscopy, and 75 controls without dyspeptic symptoms. Data on demographic information, tobacco use history, and other lifestyle factors were collected through structured questionnaires. Statistical analysis was performed using SPSS version 23.

Results: The mean of the patients was 38.89±7.5 years. Of 150 patients, 62 participants were males (41.3%) and 88 participants were females (58.7%). In univariate analysis, tobacco users were seen as likely to experience dyspepsia more compared to those who do not use tobacco (OR=4.57, 95% CI: 2.08-10.02, p=0.001). Even after adjusting for confounders such as age, gender, and socioeconomic status, oral tobacco users were significantly more likely to experience dyspepsia compared to non-users (aOR=3.9, 95% CI: 1.489-10.59, p=0.011).

Conclusion: The study found a significant association between oral tobacco consumption and dyspepsia.

Keywords: Dyspepsia, oral tobacco consumption, gastrointestinal disorders, public health, Pakistan.

INTRODUCTION

Dyspepsia is a prevalent condition defined as recurrent or persistent pain and discomfort in the upper abdomen, usually showing symptoms such as burping, bloating, and nausea [1]. This condition affects a substantial portion of the global population, leading to significant healthcare costs and diminished quality of life. The prevalence of dyspepsia is reported to be between 8% and 30% in Asia, while functional dyspepsia affects approximately 8% to 23% of individuals in the region [2].

Various factors can trigger dyspepsia, including gastrointestinal infections, dietary habits, and psychological stress [1, 2]. However, recent studies have identified oral tobacco consumption as a potential risk factor for gastrointestinal disorders [3-6]. In Southeast Asia, oral tobacco has been used in various forms including bidis or cigarettes, chewing khaini, gutka, surti, paan masala, and naswar [7, 8]. Despite its widespread use, the health implications of oral tobacco consumption are significant and multifaceted [9, 10].

The direct contact of oral tobacco with the gastric and

oral mucosa leads to inflammation and local irritation [11].

This mode of consumption exposes consumers to a range of harmful chemicals. Nicotine, a major component of tobacco, has been shown to stimulate gastric acid secretion, which can exacerbate symptoms of dyspepsia by causing acid-related damage to the stomach lining. Additionally, nicotine may impair the normal motility of the gastrointestinal tract, leading to delayed gastric emptying and increased gastroesophageal reflux, both of which are commonly associated with dyspeptic symptoms [12, 13].

In South East Asia, Pakistan is one of the countries with a high prevalence of chewing tobacco habits. In Karachi, 12% of females and 21% of males are betel consumers, 7.3% of both use paan, 6.7% use betel nuts, 14.6% use naswar, 7.5% use gutka, and 17% chew tobacco [14]. The adverse health effects of tobacco have been well- documented, encompassing a range of conditions from cardiovascular diseases to various types of cancer [15]. Despite this, the impact of oral tobacco on digestive health, specifically dyspepsia, has not received comparable attention in Pakistan.

Hence, the current study aims to assess the association between oral tobacco consumption and dyspepsia in patients presenting at a tertiary care hospital in Karachi, Pakistan. This study will help healthcare providers in the effective management of dyspeptic symptoms and

contribute to the broader understanding of the health

impacts of oral tobacco use.

METHODOLOGY

This research was designed as a case-control study conducted at the outpatient department of medicine, Mekran Medical College Turbat, Baluchistan, Pakistan from March 2024 to June 2024. The sample size was determined using the OpenEpi sample size calculator. Assuming a proportion of snuff users with dyspepsia at 34.5% [11], a 20% difference in the control group, an 80% power of the test, and a 95% confidence level, the study required 75 participants in each group (cases and controls).

This study was conducted after obtaining approval from the institutional review board (IRB No. 01/2024) of Mekran Medical College Turbat, Baluchistan, Pakistan. Verbal informed consent was obtained for all patients. Cases were defined as adults aged 18-65 years presenting with dyspeptic symptoms, confirmed by upper gastrointestinal endoscopy. Symptoms were assessed using a structured questionnaire based on the Rome IV diagnostic criteria, which defines functional dyspepsia as one or more of the following symptoms for at least 3 months with symptom onset at least 6 months prior: postprandial fullness, early satiation, epigastric pain, or burning in the absence of structural disease. Controls were adults aged 18-65 years presented without symptoms of dyspepsia. Individuals with a history of gastrointestinal surgery, those diagnosed with chronic gastrointestinal diseases unrelated to dyspepsia, or pregnant women were excluded from the study, due to potential confounding effects on gastrointestinal symptoms. Non-probability consecutive sampling technique was employed.

A structured questionnaire was used to gather data on demographic information, tobacco use history, and smoking history (Supplementary File 1). Participants who were current or former users of any kind of oral tobacco (defined as using at least once a day for six months or more) were classified as tobacco consumers. All collected data was securely stored and used exclusively for research purposes.

Statistical analysis was conducted using SPSS version 23. Age was summarized by calculating mean and standard deviation, while gender, residence, education level, monthly income, smoking status, and use of tobacco were described using frequencies and percentages. The chi-square test or Fisher’s exact test was employed to compare tobacco usage between cases and controls. Odds ratios (OR) with 95% confidence intervals (CI) were used to measure the strength of the association between oral tobacco use and dyspepsia. Logistic regression was utilized to adjust for potential confounding factors including age, gender, residence, education, monthly income, and smoking status, with adjusted odds ratios (aOR) and their 95% confidence

intervals also reported. A p-value of 0.05 or less was regarded as statistically significant.

RESULTS

The mean of the patients was 38.89±7.5 years. Of 150 patients, 62 participants were males (41.3%) and 88 participants were females (58.7%). About 90.7% of the patients were living in rural areas, 46.7% had no education till primary level, 56% had monthly income<20,000 PKR, and 18% were smokers (Table 1).

Table 2 compares the prevalence of dyspepsia between tobacco users and non-users. A significant association was observed between tobacco use and dyspepsia (p=0.001). Participants who use tobacco are more likely to experience dyspepsia compared to those who do not use tobacco.

Table 3 presents the results of univariate and multivariate logistic regression analyses for the association between various factors and dyspepsia. In the univariate analysis, age was not significantly associated with dyspepsia. Males had significantly lower odds of having dyspepsia compared to females (OR= 0.514, p=0.048). Urban residents had significantly higher odds of having dyspepsia compared to rural residents (OR=6.952, p=0.013). Secondary education was associated with significantly lower odds of dyspepsia compared to

Table 1: Baseline characteristics of study variables.

Data presented as Mean (SD) or n (%)

*Significant at a 5% level of significance

Table 2: Comparison between tobacco use and cases/controls.

Data presented as n (%)

*Significant at a 5% level of significance

Table 3: Association of patients’ features with dyspepsia (n=150).

CI: Confidence interval, OR: Odds ratio, aOR: Adjusted odds ratio, *Significant at p<0.05

primary education (OR=0.40, p=0.018), and higher education was also associated with lower odds (OR=0.34, p=0.013). A monthly income of 20,000-50,000 PKR was associated with lower odds of dyspepsia compared to an income of less than 20,000 PKR (OR=0.476, p=0.040), while an income greater than 50,000 PKR also showed a significant association (OR=0.247, p=0.025). Smoking was associated with higher odds of dyspepsia (OR=2.84, p=0.023), and tobacco use was significantly associated with higher odds of dyspepsia (OR=4.57, p=0.001).

In the multivariate analysis, age remained non- significant. Males continued to have significantly lower odds of dyspepsia compared to females (aOR=0.201, p=0.001). Urban residents had significantly higher odds of dyspepsia compared to rural residents (aOR=22.77, p=0.001). Secondary education remained significantly associated with lower odds of dyspepsia (aOR=0.26, p=0.010), while higher education was not significantly associated (aOR=0.43, p=0.119). A monthly income of 20,000-50,000 PKR was still significantly associated with lower odds of dyspepsia (aOR=0.30, p=0.011), but an income greater than 50,000 PKR lost its significance (aOR=0.69, p=0.611). The association between smoking and dyspepsia was not significant in the multivariate analysis (aOR=2.256, p=0.210), whereas tobacco use remained significantly associated with higher odds of dyspepsia (aOR=3.97, p=0.011).

DISCUSSION

This study aimed to assess the relationship between oral tobacco consumption and dyspepsia, revealing a strong statistical association between the two. A key finding

was the high prevalence of dyspeptic symptoms among oral tobacco users, supported by a strong statistical association (p=0.001). This highlights the role of oral tobacco in gastrointestinal distress, aligning with existing literature indicating nicotine’s impact on gastric functions, such as acid secretion and motility impairments which contribute to dyspepsia and gastroesophageal reflux [16-19].

The biological mechanisms underlying this association are multifactorial. Nicotine, a principal active compound in oral tobacco, has been shown to increase gastric acid secretion via direct stimulation of the vagus nerve and parietal cells [20]. This excessive acid production can irritate the gastric mucosa, leading to symptoms characteristic of dyspepsia such as epigastric pain and burning [1, 21]. Moreover, nicotine reduces lower esophageal sphincter pressure and delays gastric emptying, promoting acid reflux and bloating; both key features of dyspepsia [22]. Chronic exposure to tobacco- specific nitrosamines and other harmful constituents also leads to local mucosal inflammation and impaired gastrointestinal motility, contributing further to symptom persistence [23].

In line with previous studies, our results reinforce the notion that tobacco use negatively impacts gastrointestinal health. For instance, Bilgili explored the relationship between smoking and gastrointestinal histopathologies, like Helicobacter pylori (HP) infection and intestinal metaplasia, both common in smokers [2]. Their findings showed elevated rates of HP and intestinal changes among smokers compared to non-smokers, suggesting that tobacco smoking, like oral consumption,

significantly impacts gastrointestinal health. However, our study specifically focuses on oral tobacco, which has been less examined in existing literature, thereby filling a critical research gap.

Further insights are drawn from broader studies on tobacco impacts. For instance, the study on smoking’s systemic effects detailed its role in various malignancies and chronic conditions, extending to the gastrointestinal system where smoking exacerbates conditions like dyspepsia and peptic ulcers [21, 24, 25]. This aligns with our observations of exacerbated dyspeptic symptoms linked to oral tobacco.

Another parallel can be drawn with the research on dietary habits in patients with functional dyspepsia, which emphasized the role of diet in managing symptoms [26, 27]. While our study did not focus on diet, the findings suggest that lifestyle modifications, including tobacco cessation, could significantly alleviate dyspeptic symptoms, a theme also highlighted by investigations into the health impacts of quitting smoking.

Hence, the robust associations observed in our study between oral tobacco use and dyspepsia contribute to the growing body of evidence on the negative impacts of tobacco on gastrointestinal health. These findings should guide public health policies and patient education, emphasizing the gastrointestinal risks associated with tobacco use and the benefits of cessation. The consistent evidence across studies highlights the potential of targeted interventions in tobacco cessation to significantly improve gastrointestinal health and reduce the clinical and economic burdens of dyspepsia.

This study has several limitations that should be considered when interpreting the findings. First, the modest sample size may limit the generalizability of the results to the broader population. The case-control design also restricts the ability to establish causal relationships. Additionally, reliance on self-reported data introduces the possibility of recall bias. A key limitation is the lack of information on the temporal relationship between the onset of dyspeptic symptoms and the initiation of tobacco use; an important factor in assessing causality. The study also did not evaluate the duration or intensity of tobacco use in detail, which could influence the severity of gastrointestinal effects; prolonged exposure to nicotine and other tobacco-related compounds may increase the risk of mucosal damage and exacerbate symptoms. Furthermore, unmeasured confounders such as dietary habits, alcohol consumption, and the use of non-steroidal anti-inflammatory drugs (NSAIDs) were not accounted for, potentially affecting the observed associations.

Future research should address these gaps by employing larger, more diverse samples and longitudinal study designs to better assess causality and dose-response relationships.  Incorporating  comprehensive  lifestyle

assessments; including diet, alcohol use, and medication history; would also enhance analytical accuracy. Public health efforts should focus on developing targeted interventions for tobacco cessation and educational programs to raise awareness of the gastrointestinal risks of oral tobacco use. Additionally, stronger regulatory policies on smokeless tobacco products could play a significant role in mitigating these health risks.

CONCLUSION

The study found a strong association between oral tobacco consumption and dyspepsia. These findings suggest that oral tobacco use may be a significant risk factor for dyspepsia, highlighting the need for targeted public health interventions and educational programs to reduce oral tobacco consumption and manage dyspeptic symptoms effectively.

ETHICS APPROVAL

This study was conducted after obtaining approval from the institutional review board (IRB No. 01/2024) of Mekran Medical College Turbat, Baluchistan, Pakistan. All procedures performed in studies involving human participants followed the ethical standards of the institutional and/ or national research committee and the Helsinki Declaration.

CONSENT FOR PUBLICATION

Verbal informed consent was obtained from study

participants.

AVAILABILITY OF DATA

Upon a reasonable request, the corresponding author

will provide the data.

FUNDING

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

ACKNOWLEDGEMENTS

The authors would like to express their sincere gratitude to hospital administrations.

AUTHORS’ CONTRIBUTION

review

SUPPLEMENTARY MATERIAL

Supplementary material is available on the journal’s website.

REFERENCES