|Year : 2019 | Volume
| Issue : 2 | Page : 103-107
Asymptomatic respiratory dysfunction in patients with gastroesophageal reflux disease
K A Sudarshan Murthy1, M Bhanukumar1, CM Tejamani1, Aparna R Menon2
1 Department of General Medicine, JSS Medical College and Hospital, JSS University, Mysore, Karnataka, India
2 Department of Clinical Pharmacy, JSS Medical College and Hospital, JSS University, Mysore, Karnataka, India
|Date of Web Publication||14-May-2019|
Dr. M Bhanukumar
12213, Mathru Pithru Krupa, Second Phase, Fourth Stage, Vijaya Nagar, Mysore - 570 021, Karnataka
Source of Support: None, Conflict of Interest: None
BACKGROUND: Gastroesophageal reflux disease is the primary cause for many conditions affecting extraesophageal structures.
OBJECTIVE: The objective of the study is to investigate the relation between reflux disease and asymptomatic respiratory dysfunction and examine correlation between the respiratory dysfunction with severity of gastroesophageal reflux disease (GERD) spectrum.
METHODOLOGY: A total of 242 patients were subjected to pulmonary function test (PFT) using spirometer-G procedures. Forced expiratory volume 1 s (FEV1), forced vital capacity (FVC), FEV1/FV C ratio, and peak expiratory flow rate (PEFR) were measured. Patients in test group were treated with proton-pump inhibitor (PPI) and esomeprazole 40 mg twice daily for 3 months. They were subjected to PEFR at the end of the study. Analysis was performed using SPSS version.
RESULTS: Age and PFT parameters FEV1, forced expiratory flow (FEF) 25–75, PEF, and PEFR were compared groupwise and were found to be statistically significant except FEV. As the severity of GERD increases, severity of pulmonary disorder also increases. In Group 1A, 56.5% patients had normal PEFR and 43.4% PEFR was reduced showing statistically significant. In patients with abnormal PFT, 74.2% had mild esophagitis, 15.1% had moderate esophagitis, and 10.6% had severe esophagitis showing statistically significant. Mean PEFR before treatment showed 344.1 ± 79.22. After 3 months of esomeprazole 40 mg, twice daily mean increased 409.08 ± 100.00. In Group 1B, PEFR before treatment noted 342.0 ± 53.77. Significant improvement was seen in PEFR with mean of 506.00 ± 52.64 with PPIs.
CONCLUSIONS: GERD is associated with asymptomatic respiratory dysfunction. There is strong and direct relationship between the severity of respiratory disorders, detected by FEV1 and FEV1/FVC, FEF25–75, PEF, PEFR, and severity of GERD. This study demonstrated significant improvement in PEFR values, with adequate treatment of GERD.
Keywords: Asymptomatic respiratory dysfunction, gastroesophageal reflux disease, pulmonary function test
|How to cite this article:|
Murthy K A, Bhanukumar M, Tejamani C M, Menon AR. Asymptomatic respiratory dysfunction in patients with gastroesophageal reflux disease. Int J Health Allied Sci 2019;8:103-7
|How to cite this URL:|
Murthy K A, Bhanukumar M, Tejamani C M, Menon AR. Asymptomatic respiratory dysfunction in patients with gastroesophageal reflux disease. Int J Health Allied Sci [serial online] 2019 [cited 2019 Oct 23];8:103-7. Available from: http://www.ijhas.in/text.asp?2019/8/2/103/258181
| Introduction|| |
Gastroesophageal reflux disease (GERD) can be the primary cause of, or an aggravator to, many conditions affecting extraesophageal structures. Recently, it is being increasingly recognized as potential cause of bronchopulmonary disorders., Studies have established the relationship between GERD and symptomatic pulmonary disorders. The association of GER with a wide variety of pulmonary disorders was recognized as early as 1887. Mendelson described pulmonary aspirations producing an acute asthma-like syndrome with wheezing in some patients. Researchers have suggested that GER is one of the etiologic factors in the development of pulmonary disorders, upper respiratory symptoms such as cough, hoarseness, and throat complaints as well as an aggravating factor for the symptoms of asthma. Whether there could be respiratory dysfunction much before patients become symptomatic in those suffering from GERD is not established. Several studies have been done to assess the association of GER and pulmonary disorders, but most of these studies evaluated the effect of GER in asthmatics., Recognizing such individuals and treating GERD aggressively may help in retarding progression of the respiratory dysfunction. This study aims to investigate the relation between reflux disease and asymptomatic respiratory dysfunction and examine the correlation between the respiratory dysfunction with severity of GERD spectrum if any.
The objective of the study is to determine whether patients with GERD have asymptomatic respiratory disorders and to assess the effect of GERD treatment on lung functions in these patients.
| Methodology|| |
A total of 242 patients were studied. Patients who presented with heartburn and symptoms suggestive of GERD were included as test group. Individuals with pregnancy, chronic respiratory illness, smoking, alcoholism, and other conditions which could interfere with pulmonary functions were excluded from the study.
Patients were further divided into two groups: erosive reflux disease (ERD) 1A – those who had endoscopic evidence of erosive esophagitis and nonerosive reflux disease (NERD) 1B – those who did not have evidence of erosive disease on endoscopy. Patients who underwent upper gastrointestinal (GI) endoscopy for various other indications and having normal endoscopic study (NES) were included as control group (NES) [Table 1].
All were subjected to pulmonary function test (PFT) using spirometer-G as per the standard procedures.
Forced expiratory volume 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and peak expiratory flow rate (PEFR) were measured. Predicted values for each of the parameters were obtained from standardized references.
Patients in the test group were treated with proton-pump inhibitor (PPI), esomeprazole 40 mg twice daily for 3 months. They were subjected to PEFR at the end of 3 months. Appropriate formulae were used to calculate PEFR.
Upper GI endoscopy was performed using Pentax 150 videoscope.
Esophagitis was graded by LOS ANGELES SYSTEM.
Obstructive abnormalities and restrictive abnormalities were graded as mild, moderate, severe, and very severe as per the standards.,,
Informed consent was obtained from the patients participating in this study for doing the procedures. The Institution's Ethical Committee clearance was taken.
Analysis was performed using SPSS version 15.0 software (IBM corporation).
- The statistical evaluation included descriptive statistics, frequencies, and percentages
- Continuous variable were discussed as mean ± standard deviation
- Group comparisons were made using the Student's t-test
- Correlation between GERD and PFT was assessed using nonparametric test such as Chi-square analysis and comparison of means was done using ANOVA analysis
- Student's pair t-test was done to assess the improvement in PEFR rates
- The severity of GERD and type of PFT abnormality was studied with independent t-test
- P < 0.005 was considered statistically significant, this shows that as the severity of GERD increases, severity of pulmonary disorder also increases.
| Results|| |
Analyzing the demographic study, 111 (73%) in Group A had GERD symptoms. Chest X-Ray was abnormal in 2 (1.04%) with pneumonitis and occult blood in stool was positive in 6 (17.1%).
Endoscopy revealed mild (Grade A and B) esophagitis in 114 (75%), moderate (Grade C) esophagitis in 29 (19%), and severe esophagitis (Grade D) in 9 (5.9%).
In the test Group A, 86 (56.5%) were male and 66 (43.4%) were female. The mean age was 45.69 ± 16.73 years. The mean values of FEV1, FEV1/FVC ratio, forced expiratory flow (FEF), and PEF were all reduced when compared to predicted (pred) values. The mean predicted FEV1% was 69.06 ± 14.02, the mean predicted FEV1/FVC ratio 94.45 ± 13.84, the mean FEF rates 25–75 pred 55.33 ± 19.46, and the mean predicted PEF 62.91 ± 19.07. FEV1, FEF rates 25–75, and PEF values were <70% and mean FEV1/FVC ratio was >85% (normal).
In the test Group B, 19 were male and 21 were female with abnormal PFT of NERD. The mean age was 36.89 ± 9.53 years, the mean FEV1% pred was 70.01 ± 13.09, the mean FEV1/FVC ratio pred 94.45 ± 8.95, the mean FEF rates 25–75 pred 61.66 ± 10.06, and the mean PEF pred 61.23 ± 12.59 which revealed decrease in FEV1, FEF rates 25–75, and PEF values which was <70% and mean FEV1/FVC ratio was >85% [Table 2].
There were 30 (60%) male and 20 (40%) female as controls. The mean age was 37.42 ± 13.31 years. The pred mean FEV1 was 100.52 ± 18.33, the pred mean FEV1/FVC ratio was 104.13 ± 7.40, the pred mean FEF25–75 was 95.39 ± 25.69, and the pred mean PEF was 100.74 ± 16.20. All the four parameters were >85% predicted and were normal.
The age and PFT parameters FEV1, FEF25–75, PEF, and PEFR were compared groupwise and were found to be statistically significant except FEV.
Of the 75 patients with abnormal PFT, mild esophagitis group had 13.8% of patients with mild obstruction, 41.4% had mild restriction, and 8.6% had mixed pattern. In moderate esophagitis, 10% were mild obstruction, 30% had mild restriction, 40% had severe restriction, and 20% had mixed pattern. In severe esophagitis, 40% mild restriction, 20% moderate restriction, and 40% mixed pattern. This shows that, as the severity of GERD increases, severity of pulmonary disorder also increases (P < 0.01) (S).
In Group 1A, 86 (56.5%) patients were male and 66 (43.4%) were female. PEFR reduced showing statistically significant. In patients with abnormal PFT, 49 (74.2%) had mild esophagitis, 10 (15.1%) had moderate esophagitis, and 7 (10.6%) had severe esophagitis which was statistically significant. A study also revealed mild obstruction in 5 males and 4 females, mild restriction was seen in 14 males and 13 females, moderate restriction was noted in 4 males and 5 females, severe restriction in 5 males and 9 females, and mixed pattern in 3 males and 4 females. The major abnormality was mild restriction in 40.9% and obstruction in 13.6%. Mean PEFR before treatment was 344.1 ± 79.22. After 3 months of esomeprazole 40 mg, twice daily mean was 409.08 ± 100.00.
Thirty-four (51.5%) had significant improvement with PPIs. Three (4.5%) with moderate-to-severe restriction had irregular and incomplete PPI treatment. No improvement noted in these. 29 patients (43.9%) were lost for follow-up.
In Group B, PEFR before treatment was 342.0 ± 53.77. Significant improvement was noted in PEFR with mean of 506.00 ± 52.64 with PPIs.
| Discussion|| |
GERD causes esophageal and extraesophageal syndromes., Recent decades have witnessed a dramatic revision of the GERD landscape as ERD or NERD. NERD comprises >60% of chronic heartburn sufferers with the prevalence of 75% and 80% in two studies.,,,,
In our study, we depended only on symptom of heartburn and endoscopic findings without pH monitoring for diagnosis. We studied the frequency and relation of asymptomatic respiratory dysfunction in GERD.
Epidemiologic studies show an association between GERD and a range of pulmonary symptoms. In many studies, PFTs were studied only in patients of GERD with chronic respiratory diseases. However, we have studied PFT in GERD patients without respiratory symptoms.
This study revealed 66 patients (43.4%) with abnormal PFT in patients with esophageal reflux disease (ERD1A) (P < 0.3). Of patients with abnormal PFT, there was mild obstruction in 5 males and 4 females, mild restriction in 14 males and 13 females, moderate restriction in 4 males and 5 females, severe restriction in 5 males and 9 females, and mixed pattern in 3 males and 4 females. The major abnormality was mild restriction in 40.9% and obstruction in 13.6%. In mild esophagitis group, 13.8% had mild obstruction, 41.4% had mild restriction, and 8.6% had mixed pattern [Table 3].
|Table 3: Distribution of gastroesophageal reflux disease and abnormal pulmonary function test cases|
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In a study conducted by Maha et al., PFT was done to all patients provisionally diagnosed as GERD and also studied the relation between PFT in the ERD and NERD subgroups. In the present study, patients were grouped as ERD, NERD, and NES/control group and PFT was done. Association between GERD and PFT was studied, compared PEFR values in patients who were on PPI therapy for 3 months.
Maha et al. showed a statistically significant difference of prevalence of all respiratory symptoms in ERD as compared with NES groups (63% vs. 37.2%, respectively). However, in our study, the controls had no respiratory symptoms.
Raghu G et al. found no correlation between the severity of reflux and severity of restrictive defect by PFT. In other studies, there is significant positive correlation between asthma, chronic bronchitis, and endoscopic grading Grade C and D (P < 0.001, P < 0.003, respectively) and significant correlation between severity of PFT and severity of GERD.
Thus, in the absence of an identifiable etiology for interstitial lung disease (ILD), speculation is that reflux may be associated with pathogenesis or progression of idiopathic pulmonary fibrosis (IPF).
In a study done by Räihä et al., patients with GERD had lower VC (percentage of predicted value) than those with normal pH (92 vs. 102, P = 0.032). FEV1% did not differ between these two groups. About 33% of patients with slight and 73% of patients with moderate or severe reflux in pH monitoring had abnormal VC%, FVC%, or FEV1% (<80% of predicted value) at spirometry (vs. 30% of patients without reflux, P = 0.039). Mainly, a restrictive ventilatory defect was associated with GERD in elderly patients.
Raghu et al. found a prevalence of distal and proximal reflux of 76% and 63%, respectively, among 46 patients with IPF. The possible mechanism of IPF was due to microaspiration of gastric contents into extra-esophageal structures.
In this study, there were statistically significant differences in FEV1, FEF25–75, PEF, and PEFR (P < 0.02) in ERD as compared with NES group (mean FEV1% pred was 69.06 ± 14.02, the mean FEF rates 25–75 pred 55.33 ± 19.46, the mean PEF pred 62.91 ± 19.07, and mean PEFR was 344.1 ± 79.22). On the other hand, there were insignificant differences between both groups in measuring FEV1/FVC. Therefore, results in this study established the presence of large airway obstruction, small airway narrowing, and restrictive pattern in ERD group as compared to controls. There were 20 female (40%) and 30 male (60%) in the control group. The pred mean FEV1% was 100.52 ± 18.33, the pred mean FEV1% was 104.13 ± 7.40, the pred mean FEF25–75 was 95.39 ± 25.69, the pred mean PEF was 100.74 ± 16.20, and mean PEFR 587.98 ± 58.53. All the parameters were >85% pred matched against age, height, and weight and were found to be normal. Mean PEFR before treatment was of 344.1 ± 79.22; after 3 months of PPI treatment, improvement in the mean value of 409.08 ± 100.00 was noticed. Nine individuals who had received PPIs in Group 1B also showed significant improvement in PEFR.
Vraney and Pokorny measured PFT in GERD. Results of PFT were grouped according to the smoking history and demonstrated reflux. The difference noted between the smoker and nonsmoker groups was slightly greater than that between the reflux and nonreflux groups. One of the strengths of the present study is exclusion of smokers. Many reviews reported beneficial results of antireflux therapy on asthma outcome.
Strength of this study
In our study, we have demonstrated the respiratory dysfunction in individuals with GERD but remaining asymptomatic. Further, we have also shown that the severity of GERD is correlated with respiratory abnormalities. Adequate treatment with PPIs improves respiratory dysfunction significantly.
| Conclusions|| |
This study confirms strong link between GERD and respiratory disorders both obstruction and restriction. It is clear that GERD can be associated with asymptomatic respiratory dysfunction [Graph 1]. There is strong and direct relationship between the severity of respiratory disorders, detected by FEV1 and FEV1/FVC, FEF25–75, PEF, PEFR, and severity of GERD. This study also demonstrated significant improvement in PEFR values, with adequate treatment of GERD.
Hence, patients with GERD should be adequately treated to prevent the development and progression of respiratory disorders. All patients with GERD need to be evaluated for asymptomatic respiratory dysfunction. Further prospective studies in this category of patients will help us to know the future outcome of respiratory dysfunction. We hypothesize that many cases of ILD which are labeled to idiopathic may have GERD as the possible etiology which had to be explored with proper clinical trials.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Farup C, Kleinman L, Sloan S, Ganoczy D, Chee E, Lee C, et al.
The impact of nocturnal symptoms associated with gastroesophageal reflux disease on health-related quality of life. Arch Intern Med 2001;161:45-52.
Shaker R, Castell DO, Schoenfeld PS, Spechler SJ. Nighttime heartburn is an under-appreciated clinical problem that impacts sleep and daytime function: The results of a Gallup survey conducted on behalf of the American Gastroenterological Association. Am J Gastroenterol 2003;98:1487-93.
Lung function testing: Selection of reference values and interpretative strategies. American Thoracic Society. Am Rev Respir Dis 1991;144:1202-18.
Fass R, Quan SF, O'Connor GT, Ervin A, Iber C. Predictors of heartburn during sleep in a large prospective cohort study. Chest 2005;127:1658-66.
Eamonn M, Quigley M. The spectrum of gastroesophageal reflux disease – A new perspective. U S Gasrtroenterol Rev 2007; 41:S175-80.
Orr WC, Allen ML, Robinson M. The pattern of nocturnal and diurnal esophageal acid exposure in the pathogenesis of erosive mucosal damage. Am J Gastroenterol 1994;89:509-12.
DiBaise JK. The LA classification for esophagitis: A call for standardization. Am J Gastroenterol 1999;94:3403-4.
Harding SM, Guzzo MR, Richter JE. The prevalence of gastroesophageal reflux in asthma patients without reflux symptoms. Am J Respir Crit Care Med 2000;162:34-9.
El-Serag HB, Sonnenberg A. Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in United States military veterans. Gastroenterology 1997;113:755-60.
Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R; Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: A global evidence-based consensus. Am J Gastroenterol 2006;101:1900-20.
Dent J, Armstrong D, Delaney B, Moayyedi P, Talley NJ, Vakil N, et al.
Symptom evaluation in reflux disease: Workshop background, processes, terminology, recommendations, and discussion outputs. Gut 2004;53 Suppl 4:iv1-24.
Quigley EM. Non-erosive reflux disease: Part of the spectrum of gastro-oesophageal reflux disease, a component of functional dyspepsia, or both? Eur J Gastroenterol Hepatol 2001;13 Suppl 1:S13-8.
Malfertheiner P, Fass R, Quigley EM, Modlin IM, Malagelada JR, Moss SF, et al.
Review article: From gastrin to gastro-oesophageal reflux disease – A century of acid suppression. Aliment Pharmacol Ther 2006;23:683-90.
Ronkainen J, Aro P, Storskrubb T, Lind T, Bolling-Sternevald E, Junghard O, et al.
Gastro-oesophageal reflux symptoms and health-related quality of life in the adult general population – The Kalixanda Study. Aliment Pharmacol Ther 2006;23:1725-33.
Mishima I, Adachi K, Arima N, Amano K, Takashima T, Moritani M, et al.
Prevalence of endoscopically negative and positive gastroesophageal reflux disease in the Japanese. Scand J Gastroenterol 2005;40:1005-9.
Kiljander TO, Laitinen JO. The prevalence of gastroesophageal reflux disease in adult asthmatics. Chest 2004;126:1490-4.
Nordenstedt H, Nilsson M, Johansson S, Wallander MA, Johnsen R, Hveem K, et al.
The relation between gastroesophageal reflux and respiratory symptoms in a population-based study: The Nord-Trøndelag Health Survey. Chest 2006;129:1051-6.
Raghu G, Freudenberger TD, Yang S, Curtis JR, Spada C, Hayes J, et al.
High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Respir J 2006;27:136-42.
Raghu G. The role of gastroesophageal reflux in idiopathic pulmonary fibrosis. Am J Med 2003;115 Suppl 3A: 60S-64S.
Räihä IJ, Ivaska K, Sourander LB. Pulmonary function in gastro-oesophageal reflux disease of elderly people. Age Ageing 1992;21:368-73.
DeVault KR. Extraesophageal symptoms of GERD. Cleve Clin J Med 2003;70 Suppl 5:S20-32.
[Table 1], [Table 2], [Table 3]