The role of screening of patients proved to have gastroesophageal reflux disease by upper gastrointestinal endoscope for early detection of interstitial lung diseases

Background Gastroesophageal reflux disease (GERD) is a frequent digestive illness in North America, causing symptoms and complications. It affects 18.1–27.28% of people and is associated with decreased quality of life. Treatment improves quality of life, but treatment costs are higher. The study aims to assess the role of screening of patients proven to have GERD by upper gastrointestinal endoscope for early detection of interstitial lung diseases. Subjects and methods This research was cross-sectional research. The study will be conducted at the Chest Diseases Department of Ain Shams University hospitals. This prospective cross-sectional research will be performed on 90 randomly selected cases diagnosed with GERD by upper gastrointestinal endoscopy. For 1 year. Result The findings of chest HRCT for enrolled patients are 15 patients (16.7%) showed positive CT findings suggestive of interstitial lung disease, whereas 75 patients (83.3%) had normal CT scans. The most common CT finding was atelectasis reported in nine patients (10%). a statistically significant correlation between age and fibrosis and reticular infiltration, female gender, and reticular infiltration. no statistically significant association between CT findings and each of the chest symptoms and GERD symptoms. Conclusion CT chest screen of patients diagnosed with GERD by upper gastrointestinal endoscopy plays a favorable role in the early detection of ILD to help in early management and treatment them. In patients diagnosed with GERD by upper gastrointestinal endoscopy, we revealed that: reticular infiltration is more prevalent in female gender. Reticu-lar infiltration and fibrosis increase with older age. Reticular infiltration and atelectasis increase in patients who have a hiatus hernia. Cough, dyspnea, and wheezes increase in older age.


Introduction
Interstitial lung diseases (ILD) are chronic and ultimately fatal conditions identified by a gradual deterioration in lung function.Pulmonary fibrosis refers to the formation of scar tissue in the lungs, which leads to a worsening of difficulty in breathing (dyspnea) [1].
The clinical characteristics exhibit variability, with a higher incidence observed in adults aged fifty or more and a lower occurrence in kids.The condition typically begins slowly in the majority of cases, with symptoms of difficulty breathing (dyspnea).It is then defined by a progressive worsening over time and a lack of response to treatment [2].
The ILD categorization system categorizes disorders depending on clinical, histological, or radiologic characteristics [3].
Gastroesophageal reflux disease (GERD) is a prevalent gastroesophageal disorder that is the result of the retrograde abrupt movement of gastric acidic content into the esophagus.This movement may reach higher levels, including the laryngopharynx.The occurrence of GERD ranges from 8.8 percent to 25.9% in European countries and from 8.7 to 33.1% in the Middle East [4,5].
The pathogenesis of GERD involves several mechanisms, including prolonged relaxation of the lower esophageal sphincter, reduced pressure in the interruption of esophageal acid clearance, lower esophageal sphincter, hiatal hernia, delayed gastric emptying, as well as higher gastric acid secretion.Abnormal gastroesophageal reflux happens when the physiological protection mechanisms fail [6,7].
GERD plays a crucial part in many different illnesses, including asthma, chest pain, chronic cough, laryngitis, sinusitis, higher risk of upper gastrointestinal hemorrhage, intestinal metaplasia, esophageal stricture, Barrett's esophagus, and esophageal cancer [8].
ILD is a diverse group of non-cancerous, non-infectious conditions that affect the lower respiratory tract.They are characterized by inflammation and scarring in the alveoli and interstitium, as seen in histological examination.These diseases have a slow onset, beginning with difficulty breathing, as well as are defined by a chronic progression and lack of response to treatment [9,10].

Aim of the work
The study aims to assess the role of screening patients proved to have GERD by upper gastrointestinal endoscope for early detection of ILD.

Patients and methods
The research was a prospective cross-sectional study performed at the Chest Diseases Department of Ain Shams University Hospitals.
The study was conducted on 90 randomly selected patients diagnosed with GERD by upper gastrointestinal endoscopy for 1 year.
Patients proved to have GERD by upper gastrointestinal endoscope for any indication with age ≥ 18 years old were included in the study.Patients previously diagnosed with ILD, pregnancy, unstable patients for example (massive pulmonary embolism or pulmonary edema), other chest diseases with radiological findings, and patients who refused to sign the study consent were excluded from the research.
All cases have been exposed to complete history taking, general examination to exclude systemic illnesses, local chest investigation, routine laboratory investigations, and radiological investigation with special emphasis on chest high-resolution computed tomography (HRCT).
The 6-min walking test (6MWT) was created by the American Thoracic Society and officially introduced in 2002, accompanied by a thorough set of instructions.6MWT is a sub-maximal exercise test utilized to evaluate aerobic capacity and endurance.The duration of six minutes was utilized as the metric to assess alterations in performance capacity.
The data collected from participants were kept confidential.The investigation participants weren't recognized by name in any report or publication that addressed this investigation.Prior to the inclusion of participants in the present investigation, they were provided with a description of the study's objectives, methodology, and the evaluation of potential risks and benefits.An informed consent has been obtained.

Statistical analysis
The SPSS program (Version 25) for Windows was utilized to compile, process, and analyze the data that was collected.Descriptive statistics were computed involving standard deviations, means, medians, ranges, and percentages.To compare the means of normally distributed data for continuous variables, independent t-tests have been conducted.Mann-Whitney U tests have been utilized to compare the median variances of data that were not normally distributed, and chi-square tests have been utilized for categorical data.Statistical significance is defined as a p value that is less than 0.05.

Results
A total of 130 cases underwent screening for GERD by upper endoscopy.Ninety cases met the inclusion criteria and were enrolled in our research.
Table 1 summarizes the basic demographic data that the male patients 59 (65.6%) are more than the female patients 31 (34.4%).Among all patients the most common medical comorbidities were hypertension 34 (37.8%) and diabetes 14 (15.6%).
Table 2 summarizes the disease characteristics of enrolled patients, as regards GERD symptoms, the most commonly presented symptoms were backwash (regurgitation) of food or sour liquid 90(100%) and the least common was the difficulty of swallowing (dysphagia) 65(72.2%).Regarding dietary habits, the majority of patients were those who had coffee 86(95.6%)and spicy food 87(96.7%).On the other hand, the GERD-Q score ranges from 9 to 15 which is a high value that reflects the GERD likelihood which is ranging 79-89.Table 3 summarizes the chest symptoms and signs.Seventy-two patients (80%) complained of at least one chest symptom.On the other hand, only 16 patients (17.8%) demonstrated at least one positive sign on chest examination.The most common symptom was chest pain, reported by 71 patients (78.9%).
Table 4 summarizes the results of the 6-min walking test.The mean distance walked was 543 ± 93 m, ranging from 400 to 700 m.At the end of the test, the mean HR increased from 91.7 ± 4.7 to 109.7 ± 6.4 bpm.Dyspnea was reported in 13 patients (14.4%), fatigue    was reported in 16 (17.8%),and SPO 2 declined from 98.2 ± 1.1% to 96.2 ± 1.7%.Table 5 summarizes the findings of chest HRCT for enrolled patients.Fifteen patients (16.7%) showed positive CT findings suggestive of ILD, whereas 75 patients (83.3%) had normal CT scans.The most common CT finding was atelectasis reported in nine patients (10%).
Table 6 demonstrates a statistically significant positive association between age and fibrosis and reticular infiltration.Also, Table 6 demonstrates a statistically significant association between female gender and reticular infiltration.Meanwhile, there was no statistically significant correlation between CT findings and each of the chest symptoms and GERD symptoms.
Table 7 demonstrates a statistically significant association between spices and consolidation.Also, there was a statistically significant association between the presence of hiatus hernia and atelectasis and reticular infiltration.
Table 8 demonstrates a statistically significant association between age and cough, dyspnea, and wheezes.

Discussion
Our study aimed to assess the role of screening of patients proved to have GERD by upper gastrointestinal endoscope for early detection of ILD.Our study was conducted at the chest diseases departments of Ain Shams University Hospitals and conducted on 90 randomly selected patients diagnosed with GERD by upper gastrointestinal endoscopy for 1 year.
Our results showed that the mean age of the studied cases was 41.8 ± 15.6 years with a range of 18-74 years, the male patients were 59 (65.6%) more than the female patients 31 (34.4%).Among all patients the most common medical comorbidities were hypertension 34 (37.8%) and diabetes mellitus 14 (15.6%).
The findings of our study were consistent with those of Nazemiyeh et al. [13], who conducted a study to assess the impact of GERD on pulmonary volumes, airflows, and airway resistance in cases without respiratory symptoms.They compared these measurements between cases with GERD and healthy subjects.The study included a total of 78 cases with GERD, with a mean age of 37.30 ± 9.76 years.Of these cases, 53.8% were male.Also, our results were supported by Fidler et al. [14] who reported that in cases with GERD, the mean age was 63.4 ± 7.0 years, there were (60.0%) males.
In addition, our results matched with Abdullah et al. [15] who aimed to research the presence of chest illnesses in non-smoker cases complaining of GERD, they reported that fifty patients with heartburn and respiratory symptoms with a mean age of 43.58 ± 10.14 years.Also, our results agree with Ali et al. [16] who aimed to evaluate the impacts of GERD on spirometry, lung diffusion, and impulse oscillometry, they reported that a total of 24 women and 24 men with GERD with a mean age of 42.38 ± 11.72 years were assessed in their research.
Conversely, our results disagree with Cuña et al. [17] who stated that among 70 patients enrolled in their study, there were 90% females.
As regards GERD symptoms, our results revealed that the most commonly presented symptoms were backwash (regurgitation) of food or sour liquid 90(100%), 97.8% heartburn, 85.6% epigastric pain, 95.6% lump sensation, and the least common was the difficulty of swallowing (dysphagia) 72.2%.Regarding dietary habits, the majority of patients were those who had coffee (95.6%) and spicy food (96.7%), and associated hiatus hernia was present  The findings of our study were consistent with Allaix et al. [18] who reported that among 80 patients with GERD, there were 67 (83.8%) with heartburn.Otherwise, they reported that hiatus hernia was present in 52% of GERD patients was 39.5 ± 24.9 in GERD group.
In contrast, our results different from Houghton et al. [19] who reported that among 56 patients, heartburn present in (54%) of the patients, acid regurgitation present in (43%), nausea present in (20%), chest pain present in (12%), and vomiting present in (9%), while 12% of the patients did not have reflux symptoms.
Also, Our results disagree with Fidler et al. [14] who stated that in patients with GERD, there were 55.5% with heartburn, 55.5% regurgitation, and 22.2% dysphagia.Also, Kanemitsu et al. [20] differed with our results who reported that among 47 patients, there were 62.8% heartburn and 50% dysphagia.In addition, our results disagree with Soares et al. [21] who reported that in patients with GERD, there were 70% heartburn, 43.3% regurgitation, and 30% dysphagia.
Regarding chest symptoms and signs, our results showed that there were 12.2% with cough, 30% dyspnea, 7.8% with wheezes, 1.1% expectoration, no patients with hemoptysis, the most common symptom was chest pain, reported by 71 patients (78.9%).On the other hand, only 16 patients (17.8%) demonstrated at least one positive sign on chest examination.
The findings of our study were consistent with Fidler et al. [14] who stated that in patients with GERD, the most common symptom was chest pain present in 66.6% of the patients.
In addition, our results disagree with Renzoni et al. [22] who reported that among 54 patients with interstitial pneumonia, there were 45 (84%) had cough and 50 of 53 (94%) had dyspnea.
Regarding the results of the 6-min walking test, our current study revealed that the mean distance walked was 543 ± 93 m, ranging from 400 to 700 m.At the end of the test, the mean HR increased from 91.7 ± 4.7 to 109.7 ± 6.4 bpm.Dyspnea was reported in 13 patients (14.4%), fatigue was reported in 16 (17.8%)and SPO 2 declined from 98.2 ± 1.1% to 96.2 ± 1.7%.
The findings of our study are consistent with those of Li et al. [23], who conducted a study to characterize the outcomes of the 6-min walk test and examine their associations with cardiopulmonary and lung function in cases with interstitial lung disease, including those with conditions other than idiopathic pulmonary fibrosis, they reported that at 6-min the mean HR increased from 90.97 ± 14.48 at baseline to 117.97 ± 18.00 at 6-min, SPO 2 declined from 95.49 ± 2.23% at baseline to 90.54 ± (6.43) at 6-min.Also, Veit et al. [24] reported that in the IPF group, the mean distance walked was 431.2 ± 89.5 m.
Regarding the findings of chest HRCT for enrolled patients, our results showed that 15 patients (16.7%) showed positive CT findings suggestive of ILD, whereas 75 patients (83.3%) had normal CT scans.The most common CT finding was atelectasis reported in 9 (10%) patients, fibrosis found in 8 (8.9%) of the studied patients, reticular infiltration found in 6 (6.7%) of the studied patients, consolidation found in 5(5.6%) of the studied patients in and no patient with a honeycomb appearance.
Our results disagree with Eldahdouh et al. [25] who reported that, as regards chest high-resolution computed tomography, there were 29 (58%) patients with normal chest high-resolution computed tomography and 21 (42%) cases with fibrotic patterns coinciding with IPF in chest high-resolution CT.
Also, our results are in contrast with Khanna et al. [26] who stated that among 162 patients, there were 145 (92.9%) fibrosis.
Furthermore, Atwa et al. [28] reported that all cases with GERD grades A and B had normal chest highresolution CT, 11 patients with GERD grade C had ILD pattern on chest high-resolution CT, 5 cases had a ground-glass appearance and 6 patients had a reticulonodular pattern, 14 cases with GERD grade D had ILD patterns on chest high-resolution CT 4 patients had a ground-glass pattern, 9 patients had a reticulonodular pattern, and 1 patient had a honeycomb pattern.
Regarding the relation between CT findings and age, our results showed that a statistically significant positive correlation was found between age and fibrosis and reticular infiltration.Regarding the relation between CT findings and gender, there was a statistically significant association between female gender and reticular infiltration.
Our results agreed with Navaratnam et al. [29] and Navaratnam et al. [30] who reported that many fibrotic ILDs including IPF increase in incidence with age.
Bai et al. [31] reported that ILD was significantly greater in elderly cases.However, Kanemitsuet al. [20] discovered that there was no correlation between the age of cases and the occurrence of ILD in cases with GERD.
Our study remarks that there was no statistically significant association between CT results and each of the chest symptoms and GERD symptoms.
Our findings contrast the findings of Theodore et al. [32] and Tashkinet al. [33], who discovered a correlation between the frequency of cough in ILD cases and the amount of fibrosis visible on HRCT pictures.Also, Veit et al. [24] reported that patients with IPF had a significantly higher prevalence of cough (p = 0.020).Also, Atwa et al. [28] reported that there was a statistically significant positive association between chest high-resolution computed tomography and grades of gastroesophageal reflux disease.In addition, Baqir et al. [34] reported that IPF remained significantly associated with a GERD diagnosis (P = 0.02).
Regarding the relation between CT findings and dietary habits, a statistically significant correlation between spices and consolidation.Ando et al. [35] concluded that the patient's lung disease was associated with the spices.
Our current study showed a statistically significant correlation between the presence of hiatus hernia and atelectasis and reticular infiltration which goes with Balbay et al. [36] results who reported that the prevalence of bronchiectasis was significantly high in large hernias with an 81.4% rate (P = 0.009).However, George et al. [37] reported that, regardless of size, the presence of a hiatus hernia was not associated with ILD, p = 0.94.
Our work showed a statistically significant correlation between age and cough, dyspnea, and wheezes.This agreed with Abozid et al. [38] who reported that the prevalence of chronic cough increased with age both in males and females.Similarly, our findings aligned with Huang et al. [39], who observed that the occurrence of chronic cough rose with age.Among those aged 20 to 49 years, the prevalence was 2.4% (95% confidence interval 1.9-3.1),but among those aged 50 years or more, it was 6% (95% confidence interval 5.3-6.8)(p < 0.0001).As well, Mahler et al. [40] reported that older women (> 80 years tended to report moderate to severe Dyspnea more frequently than younger women.In addition, Aviles-Solis et al. [41] reported that in the univariable analysis, wheezes were associated with age (10-year increase).

Conclusion
CT chest screen of patients diagnosed with GERD by upper gastrointestinal endoscopy plays a favorable role in the early detection of ILD to help early management and treatment them.In patients diagnosed with GERD by upper gastrointestinal endoscopy, we revealed that: Reticular infiltration is more prevalent in female gender.Reticular infiltration and fibrosis increase with older age.Reticular infiltration and atelectasis increase in patients who have a hiatus hernia.Cough, dyspnea, and wheezes increase in older age.

Table 1
Baseline characteristics

Table 2
Symptoms of GERD, dietary habits, GERD-Q Score and Vital Signs-SPO2

Table 3
Respiratory symptoms and signs

Table 4 6
-min walking test and lab results among studied patientsHgb hemoglobin, WBC white blood cell, ALT alanine transaminase, AST aspartate aminotransferase

Table 5
Chest CT findings

Table 6
Relation between CT Findings and each of age, gender, chest symptoms, and GERD symptoms *Indicates statistically significant (P value <0.05)

Table 7
Relation between CT Findings and each of dietary habits, hiatal hernia, atelectasis, and reticular infiltration * P

Table 8
Relation between chest symptoms and age *Indicates statistically significant (P value <0.05)