Prevalence of Gastro-Esophageal Reflux Disease in Patients with ‎Interstitial Lung Disease: A Case Control Study in Egyptian Patients

1-  The prevalence of GERD  was higher in the patients with interstitial lung disease than controls.

2-  Smoking, GERD and FVC were the main predictors of interstitial lung disease, while interstitial lung disease and  FEF25-75 were the most significant predictors of GERD.

3-  It is unknown whether the gastro-esophageal reflux disease (GERD) is a cause or consequence of interstitial lung disease.

Table 1: General characteristics, complaint, clinical examination and GERD of the studied ILD patients and controls:

*: Significant,                                       BMI   Body mass index

Table 2: Laboratory investigations of the studied ILD patients and controls:

*Significant

Table 3:   Binary logistic regression analysis for factors associated with ILD or GERD among the studied participants:

*: significant          FVC    Forced vital capacity,     FEV1    Forced expiratory volume,  

FEF25-75     Forced expiratory flow 25–75%.

DISCUSSION

For several decades, gastrointestinal specialists have stated that altered pulmonary  functions in patients with end stage respiratory disease may cause acid reflux especially, increases in positive intra-abdominal pressure and negative intrathoracic pressure may cause a pressure gradient-favoring reflux [7]. Survival analysis demonstrated that identifying the presence of gastro-esophageal symptoms, providing diagnosis of GERD, medication use, and anti-reflux surgery were all collectively associated with longer survival in patients with interstitial lung disease [8]. This current study showed that GERD was significantly presented among ILD patients (52.4%) compared to controls (38.6%). The high prevalence of GERD in patients with ILD has been described by previous studies. Savarino et al. [9] reported that GERD was significantly increased in patients with IPF compared with patients with other non-IPF ILD and healthy controls. Qi et al. [10] reported that frequencies of GERD ranged from 64% to 94% in patients with IPF and ranged from 33% to 50% in patients with non-IPF ILD. Moreover, Tossier et al. [11] reported the highest prevalence of GERD among patients with scleroderma ILD compared with patients with IPF (62% vs 46%). Our study had a slightly different design compared with previous studies because we included all causes of ILD either IPF or other non-IPF ILD in one group compared to controls so, the rates of GERD in ILD patients were different from those reported in prior studies. In this study, patients with ILD more frequently were current smokers compared with controls (23.3% vs 13.8%). This result agreed with this obtained byRao et al.,[12] who concluded that, inhalation of tobacco smoke is an important risk factor for smoking-related interstitial lung disease. Moreover, Lederer et al., and Armanios et al. [13,14] reported that, ILD can be considered as the result of the interaction between tissue damage caused by several agents as smoking, GERD, genetic factors, environmental factors or occupational exposure to harmful substances.  In the current study, BMI was significantly higher in ILD group (24.04± 4.92) than controls (22.52± 3.30). These data are consistent with those of a study done by Comes et al., [15] to determine the clinical significance of BMI and changes in body weight in ILD and they reported that, BMI was significantly associated with 1-year mortality in  ILD therefore, BMI may be useful prognostic indicator of ILD. Tests and methods used for diagnosis of GERD varied among studies [16, 17]. In this study we asked about any history of acid reflux symptoms and used the upper gastrointestinal endoscopic findings of reflux esophagitis for diagnosis of GERD according to Los Anglos classification after exclusion of other causes. The results of this study revealed that, the most reported complaints in ILD patients were persistent vomiting, persistent abdominal pain, dyspepsia and hoarseness of voice (21.0%, 21.4%, 17.6%, 7.1%) respectively. These data are in agreement with those obtained by Soares et al., [18] who stated that,   GERD symptoms were common in patients with ILD. However, a cause-effect relationship had not been well demonstrated and there was still confusion about the diagnostic steps necessary to confirm the presence of GERD and about the role of effective control of GERD in the natural history of ILD. However, these results were different from Lee et al. and Allaix et al. [4,8] who reported that, GERD is usually clinically silent in ILD patients and heartburn prevalence is significantly lower in ILD-GERD population than in GERD alone. Moreover some studies reported that, GERD symptoms were a less reliable indicator for presence of GERD [16, 19, 20], so we used the Hull Airway Reflux questionnaire for this purpose. Fahim et al., [21] also depended on HARQ in diagnosis of GERD and found that, 68% of ILD patients had pathological HARQ scores than controls. Gao et al., [5] also reported that GERD prevalence was 62.3% in their study and typical symptoms were present only in 58.1% of them. Furthermore, Sweet et al., [22] reported that, symptoms did not reliably predict the presence of GERD and subsequently were confirmed by pH-metry. Pulmonary function tests including FVC, FEV1, and FEF25-75 were significantly decreasing among ILD patients in our current study. When ILD patients with and without GERD were compared, the results revealed that FVC and FEF25-75 were significantly decreasing among GERD patients. These results were comparable to the previous studies. Bonacin et al. [23] demonstrated that, values of FVC and FEF25-75 were significantly lower, and the presence of intrapulmonary shunt was significantly higher in GERD group in comparison with the non-GERD group, and these findings confirmed the correlation between GERD and damaged pulmonary function. Furthermore, these results demonstrated an additional mechanism in the development of intrapulmonary shunt, as  micro-aspiration of the gastric contents causes surfactant damage and microatelectasis of both lungs . So, it is important to perform pulmonary function tests in all GERD patients. In contrast, Gao et al. [5] stated that esophageal function parameters in ILD patients presenting with GERD did not correlate with worsened pulmonary function (FVC) and there was no significant correlation between FVC and acid reflux.  There was significant negative correlations between stages of GERD and pulmonary function tests in our study. This finding was in agreement with Troshinsky et al. [24] who reported that there was no significant correlation between grades of GERD and pulmonary function tests. On the other hand, Ali et al. [25] reported that there was significant positive correlation between grades of GERD and FVC, FEV1/FVC and FEF25-75.                                                  

The limitations of this current study were that we depended on typical and atypical symptoms of GERD and upper GI endoscopy findings in diagnosis of GERD despite   pH-metry or impedance study is the gold standard method for diagnosis of GERD. Moreover, it was difficult to analyze atypical symptoms of GERD due to uncertain  relationship between GERD and these symptoms. Some researchers have showed that anti-reflux surgery can improve pulmonary function of GERD patients so further studies are required to determine whether anti-reflux surgery or using PPI might improve the prognosis of ILD patients.

CONCLUSION

Despite not reaching the high rates reported in other studies, the prevalence of GERD  was higher in the patients with interstitial lung disease than controls. Moreover, binary logistic regression analyses revealed that smoking, GERD and FVC were the main predictors of ILD, while ILD and FEF25-75 were the most significant predictors of GERD.

List of Abbreviations

 BMI  Body mass index, GERD  Gastro-esophageal reflux disease, GI Gastrointestinal,  FVC  Forced  vital capacity, FEV1  Forced expiratory volume in the first second, FEF 25-75 Forced expiratory flow 25–75%, HRCT  High resolution computed tomography, HARQ  Hull Airway Reflux  questionnaire, ILD  Interstitial lung disease, IPF Idiopathic pulmonary fibrosis, SS    Systemic sclerosis.

Acknowledgments: No acknowledgments.

Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors

Conflict of Interest:  No any relevant conflicts of interest.

Ethical approval: This study received ethics approval from the local Ethics committee of the Faculty of Medicine, Menoufia university (Approval number:42020Trop).