Dyspepsia is a medical disorder that is characterized by persistent or recurring upper abdominal pain , and typically is classified into organic part and functional part , which may be associated by other symptoms of the gastrointestinal tract, such as belching, vomiting, nausea, fullness and early satiety postprandial . It is one of the most common issues for patients referring to the endoscopists . In addition, for conditions such as peptic ulcers and gastric cancers, dyspepsia is frequently the first warning sign . Previously, multiple variables have been seemed to be closely linked to symptoms of dyspepsia which involving age, gender, non-steroidal anti-inflammatory drugs and antacids usage, H. pylori Infection and smoking   .
Helicobacter pylori is a gram-negative microaerophilic bacillus likely to be placed in the deep sections of the mucosal gel over the gastric mucosa or even between the mucous layer and the epithelium of the stomach . In developing nations, H. Pylori is generally acquired in early childhood and can continue to exist if left untreated for a lifetime  . Whereas the bacterium is assessed to be embedded in the gastric mucosa of half the global population, only about 15 - 20 percent of colonised persons contributes to the development of such diseases . Chronic H. infection Pylori activates the immune response of the host, induces active chronic inflammation and damage to the mucosa, giving rise to multifocal atrophic gastritis, glandular dysplasia, intestinal metaplasia and adenocarcinoma .
There are between 1014 and 1016 free radicals in cigarette smoke , which can induce the formation of reactive oxygen species which really cause extensive damage to tissue. Cigarette smoking has also been shown to increase the frequency and recurrence of peptic ulcer disease  and several studies have also shown a significant link between smoking and the threat of H. pylori infection, as well as the development of the disease . Furthermore, prolonged cigarette smoking really seemed to alter mucus production by the gastric mucosa . Although the association between smoking and atrophic gastritis (AG) and intestinal metaplasia (IM) remains controversial  , numerous researchers have associated cigarette consumption with an increased risk of AG, IM and dysplasia largely dependent on histopathologic diagnosis  . This work aimed to determine the different endoscopic and histological changes in gastric mucosa promoted by smoking among H. pylori-positive and H. pylori-negative Egyptian patients with dyspepsia.
2. Patients and Methods
2.1. Study Design and Setting
A cross-sectional study was conducted among two hundred forty consecutive patients who presented with dyspepsia symptoms and had been attending endoscopic units of the Tropical Medicine Department at Zagazig University Hospital, Egypt and Tanta University Hospital, Egypt between August 2019 and March 2020. The patients who agreed to participate were enrolled in this study after taking informed written consent. Studied patients with dyspepsia were divided according to their current smoking status into two groups (smoker and non-smoker) and based on H. pylori status; patients were divided into H. pylori positive and H. pylori negative.
Inclusion criteria: Patients who presented with dyspepsia, were advised for upper GI endoscopic (UGIE) evaluation with gastric biopsies evaluation and agreed to participate included in the study. Smoker patients, in this study, must smoke more than 5 cigarettes in the day for at least 3 years before.
Exclusion criteria: Patients refused to participate in the study or to undergo UGIE; patients were previously diagnosed to have H. pylori infection; patients had history the use of certain medications (NSAIDs, H2-receptor antagonists, proton pump inhibitors, alcohol and antibiotics) one month ago prior the endoscope; x smoker not current were excluded from the study.
All patients were subjected to history taking, clinical examination, laboratory investigation, abdominal ultrasonography, H.pylori stool antigen (Epitope Diagnostics, Inc. (EDI) Fecal Helicobacter pylori Antigen ELISA kit) at the time of endoscopy.
UGIE (Olympus CV-150 or Pentax EPM3500) was performed for all the patients with dyspepsia as an objective assessment for the diagnosis of causes was also performed.
Four gastric biopsies were performed for all the included patients. After the endoscopy the biopsy samples were transferred to the lab under an appropriate condition for histological examination. Microscopic slices of the gastric mucosa were stained with hematoxylineosin and Giemsa. All the samples were additionally evaluated by the rapid urease test (CLO test; Kimberly-Clark Ltd., Draper, Utah, USA) at least in one of two gastric locations (antrum or corpus) and the results were read up to 24 hours at room temperature as a part of histological diagnosis to confirm H. pylori-positive status when the test showed red-violet color.
2.3. Ethical Considerations
The research steps were explained and the permission for conducting the research was obtained by the ethics committee of the Faculty of Medicine, Zagazig University, Egypt. This study was performed in accordance with the Declaration of Helsinki, Good Clinical Practice and applicable regulatory requirements.
2.4. Statistical Analysis
Analysis of data was done using SPSS version 20 (Armonk, NY: IBM Corp). Data were presented as mean ± SD if they were quantitative or percentage if they were qualitative. Comparisons between qualitative variables were done using the Chi-square test while quantitative variables were assessed using the Unpaired Student t-test. Results were considered significant when P-value ≤ 0.05.
Overall, 240 patients with dyspepsia were enrolled during the study period. The mean age ± SD was 44.18 ± 6.9 and the majority were male (91.7%). H. pylori infection was detected in 88 patients. As regard smoking, only 25.0% were smoker (60 cases). (Table 1)
Gastritis and reflux were the most common endoscopic findings in this study 208 (86.7%) and 104 (43.3%) cases respectively. (Table 2)
As regard histological examination, 51.7% of the patient had chronic inactive gastritis. 45% had chronic active gastritis, 23.3% had erosive gastritis, and no biopsies revealed dysplasia. (Table 3)
As Table 4 shows, there is a significant statistical relationship between smoking and histopathological findings including erosive gastritis. Also, smokers more significantly showed reflux, erosion, peptic ulcer and mucosal nodularity in gastric endoscopic examination (P-value < 0.01).
In this study, patients with H. pylori infection were significantly higher regard age. There was a statistically significant relationship between H. pylori infection; detection of erosion in the gastric endoscopic examination and erosive gastritis in histological examination (P-value < 0.01). (Table 5)
The additive effects of smoking on endoscopic and histo-pathological findings in H. pylori-positive patients is shown in Table 6, this patient group was significantly showed a picture of intestinal metaplasia, erosive gastritis, glandular atrophy and reactive gastropathy in their histological examination. Also, these patients significantly had more erosion and peptic ulcer during endoscopic examination (P-value < 0.01).
Table 1. Distribution of dyspeptic patient according to demographic data, current H. pylori infection and smoking status.
Table 2. Endoscopic findings among the studied dyspeptic patients.
Table 3. Histological findings among the studied dyspeptic patients.
Table 4. Comparison of endoscopic and histological finding between the smoker and non-smokers dyspeptic patients.
Table 5. Comparison of endoscopic and histological finding between the studied H. pylori-positive and -negative dyspeptic patients.
Table 6. Relation between the studied dyspeptic H. pylori-positive smokers and endoscopic and histological finding.
In the current study, the prevalence of H. pylori positivity among dyspeptic patients was 36.7%. These results are consistent with those of another Egyptian study by Khalifa et al., in which the prevalence of H. pylori positivity was 43% . However, a study in North Sulawesi and Indonesia, reported lower H. pylori prevalence in patients referred for endoscopy (14.3%) . These differences in prevalence may be due to the overcrowded conditions and poor socioeconomic status  as in Egypt, it has been reported that the prevalence of H. pylori infection is 90% in adults . We found that H. pylori infection was most commonly observed in adults with an average age of 46 years which is in accordance with the result of Basílio et al. . This may be explained by an increase the prevalence of infection in the community with increase the age . Furthermore, aging is linked to a reduced turnover rate of epithelial cells as well as the potential for gastric mucosa repair .
Endoscopy revealed mostly gastritis, esophageal reflux or both in our study. This is similar to what has been described by Vasiliou et al. who showed that the major endoscopic findings among 160 patients with dyspeptic were chronic gastritis (83.8%), and erosive esophagitis (34.4%) . moreover, the prevalence of gastritis, in a similar study, of Sahin et al. was 48.4% . However, in another Egyptian study, irrelevant findings in 65%, peptic ulcer in 18%, esophagitis in 14% and erosive gastroduodenitis in 8% were detected during endoscopy of patients presenting with dyspepsia where 82% of these patients younger than 30 years . This controversy among both of Egyptian studies may be due to the difference in age between the studied patients.
Surprisingly, the researchers have detected contradictory results about the relation between H. pylori and smoking. We found no statistically significant difference between smokers, non-smokers in the positivity rate of H. pylori (P = 0.536) and similar results have been reported by Khalifa et al. among dyspepsia Egyptian patients . In contrary to the findings of Rajashekhar et al. who had found an association of smoking with H. pylori positivity in dyspepsia patients . The latter finding is not in line with the current data which demonstrate that H. pylori infection acquired during childhood when smoking has no role .
In this study, the number of the smoker was higher among men, which is expected in our community . In addition, there was statistically significant difference in the endoscopic findings including; reflux, erosion, peptic ulcer and mucosal nodularity between smokers and non-smokers. Our findings are in agreement with those of Namiot et al. who observed that most ulcer disease patients were men and smokers . Regarding histological examination, smoker patients were statistically significantly higher only in erosive gastritis. Our results concur well with another study by El Hamshary et al. conducted in Fayoum governorate that demonstrated a highly significant association between chronic gastritis and smoking habit . This may be due to aggressive gastric factors (such as duodenogastric reflux acid, pepsin secretion, and free-radical production) and impair mucosal defenses (such as prostaglandin synthesis, mucus production, and epidermal growth factor secretion) which are potentiated by nicotine .
Moreover, we found that H. pylori-positive patients showed more erosion and erosive gastritis compared to H. pylori-negative patients and we support the results of Banik et al. who detected that erosive gastritis and non-erosive gastritis patients were H. pylori sero-positive . We observed that dyspeptic H. pylori-positive smokers more likely had erosion and peptic ulcer than dyspeptic H. pylori-positive non-smokers. This result is consistent with the finding of Martin et al. who reported that smokers with positive H. pylori were more likely to have a peptic or duodenal ulcer (73%) compared to H. pylori-positive nonsmokers (29%) . Also, McColl et al. have demonstrated that smokers with positive H. pylori were more likely to have a peptic or duodenal ulcer (67%) than H. pylori-positive nonsmokers (46%) . Koivisto et al., on the other hand found that smoking reduced gastric body inflammation and atrophy as well as humeral response to H. pylori among H. pylori-positive patients with gastritis . As regard histological findings, dyspeptic H. pylori-positive smokers developed more intestinal metaplasia, erosive gastritis, glandular atrophy and reactive gastropathy rather than dyspeptic H. pylori-positive non-smokers. These results were in agreement with Russo et al. who found that among H. pylori-positive patients, there was a strong association amongst gastric IM and smoking . Nakamura et al. also found that In H. pylori positive patients, smoking can play a key role in the pathogenesis of IM and AG . An in vitro research has also revealed that nicotine enhanced the activity of H. pylori vacuolating toxin .
5. Limitations of the Study
Firstly, this research was conducted on a small number of population samples with no matching groups according to sex and smoking habit as all of the smokers were men and none of females were smokers according to their cultural aspect. Secondly, we didn’t classify the smokers according to its smoking intensity and duration to be compared with the endoscopic and histological finding of them.
On the basis of the findings of the present study, there is no association between H. pylori infection and smoking. However, we confirmed that smoking triggered endoscopic finding including gastritis and histological changes were associated with H. pylori infection including intestinal metaplasia, erosive gastritis, glandular atrophy and reactive gastropathy.
Thanks to members of endoscopic units in the Tropical Medicine Department of both Zagazig and Tanta University Hospital, Egypt who participated and cooperated in the study.
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