Impact of H . Pylori on Severity of Chronic Obstructive Pulmonary Disease

Background and aim of the work: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Many studies reported a high prevalence of Helicobacter pylori (H. pylori) infection in COPD patients and this may have a role on severity of COPD. To estimate impact of H. pylori infection on exacerbation and severity of COPD. 
Patients and Methods: A prospective observative study was conducted for one year and included 142 well controlled COPD patients. Participants were classified into two groups; group 1 which included 72 COPD patients with +ve H. pylori infection and group 2 which included 70 COPD patients with -ve H. pylori infection. All participants were submitted to full clinical examination, routine laboratory investigations, CXR, arterial blood gases analysis, spirometry, H. pylori serology and stool antigen and COPD assessment test (CAT). Patients were followed monthly for at least three months. 
Results: High significant statistical differences were found between both groups regarding; FEV1, FVC, PH, PaO2, which were lower in group 1 when compared to group 2. While CRP, CAT score, PCO2, HCO3 were significantly higher in group 1. COPD severity was higher in group 1 when compared to group 2 where the sever and very sever COPD cases were more abundant in group1. 
Conclusion: H. pylori infection adds an inflammatory burden in the COPD patients by increasing their CAT and number of COPD exacerbations per year.


INTRODUCTION
Helicobacter pylori (H.pylori) is a gram-negative anaerobic spiral-shaped rods.It develops several mechanisms for its survival and replication in the acidic environment of the stomach.H. pylori synthesizes urease enzyme which catalyze the hydrolysis of urea to ammonia, which in turn decreases the stomach pH and produces a neutral environment around the bacteria [1].H. pylori was reported globally to colonizes the gastric mucosal lining of ~50% to 60% of the world population, with increased prevalence in those patients with other inflammatory diseases including autoimmune, vascular and skin diseases [2].In Egypt, prevalence of H. pylori is much higher in the healthy asymptomatic population both in adults and in pediatric populations.Low socioeconomic status, low body mass index, living in rural areas and low educational status were multiple risk factors for the acquisition of H. pylori in most of the Egyptian studies [3].Chronic obstructive pulmonary disease (COPD) represents an important public health challenge and is a major cause of chronic morbidity and mortality worldwide [4].Gastro-oesophageal reflux disease (GERD) is one of the most common causes of chronic cough and a potential risk factor for COPD exacerbation [5,6].GERD is a relatively common condition, affecting ~10 to 29% of the western population [7].Gastro-oesophageal reflux (GER) can heighten bronchial reactivity and micro-aspiration [8].Abnormal GER was associated to lung diseases [9].Moreover, most COPD patients have flat diaphragm and increased intraabdominal and negative intra-thoracic pressure, which could aggravate GER [10].GERD is more common in patients with COPD than in those without COPD [11].Also, it has been suggested that an increase in the frequency of COPD exacerbation can be associated with GERD [12].The possible mechanisms for the relationship between H. pylori and COPD might be the systemic effect of certain gastrointestinal peptides as gastrin, somatostatin, and cytokine release or due to direct injury and chronic inflammation of airways due to aspiration and/or inhalation, most probably activation of inflammatory mediators by H. pylori is the pathogenic mechanism of extragastric manifestations of H. pylori infection [13].The aim of our work was to estimate impact of H. pylori infection on the severity of COPD and clarifying a role for H. pylori infection in COPD exacerbation.

Study design and settings
This observative prospective study was conducted at Tropical medicine, Internal medicine and Chest departments, Zagazig university hospitals, Egypt, through a twelve months period from October 2017 to October 2018.

Target population
Out of 300 well controlled COPD patients attending our outpatient clinics, one hundred forty-two patients fulfilling inclusion and exclusion criteria were randomly chosen to participate in this study.

Exclusion criteria
Those patients with asthma, known peptic ulcers, acute exacerbation of COPD, used antibiotics within and PPIs within the last month, histamine-2-receptor antagonists within the last week, an antacid within the last 24 hours and those having H. pylori eradication treatment within the last 6 months were excluded from beginning of the study.

Patients classification
According to presence of H. pylori, participants were classified into two groups; group 1 which included 72 COPD patients with positive H. pylori infection and group 2 which included 70 COPD patients with negative H. pylori infection.

Data processing and analysis
All statistical calculations were done using the computer programs SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA version 20.0).Data were statistically described in terms of mean ± SD, median and range, or frequencies and percentages when available.To determine the significant independent predictors for the occurrence of EVs, the grade and occurrence of significant EVs, univariate and multivariate regression models were constructed.P values <0.05 was considered statistically significant.

RESULTS
There were no significant differences between both groups regarding mean age, gender, smoking pattern and the prevalence of comorbidities.(Table 1).2).High significant statistical differences were found between both groups regarding; FEV1, FVC, PH, PaO2, which were lower in group 1 when compared to group 2. While CRP, CAT score, PCO2, HCO3 were significantly higher in group 1 (Table 3).Moreover, there was a high significant statistical difference in the severity of COPD which was higher in group 1 when compared to group 2 where the sever and very sever COPD cases were more abundant in group 1 (Table 4).

CONCLUSION
This study clearly demonstrated that H. pylori infection may play a role in COPD initiation and exacerbation in predisposed patients, due to high prevalence of both H. pylori and COPD.More randomized controlled studies are needed before confirming this interplay as a tight relation of just co-association.

Table (
1) :The demographic data and co-morbidities of both groups

pylori stool Ag +ve) Group 2 (H. pylori stool Ag -ve)
In this work, H. pylori seropositivity was found in 73.2% of participants and H. pylori stool Ag were positive in 50.7%.The frequencies of H.This goes in agreement with Gencer et al., who reported a negative relationship between FEV1and H. pylori serum IgG levels in all patients with COPD [21].A second study of Nahla F. Khattab, et al. compared pulmonary function tests of H. pylori seropositive COPD patients and controls.Pulmonary functions were significantly lower among COPD patients with H. pylori when compared to those of the controls [35] which agree with our results.These findings suggesting that H. pylori infection is associated with more severe airway inflammation.Fullerton et al. attributed similar findings of FEV1 among seropositive COPD patients to the ability of H. pylori to produce a lot of enzymes, including urease, catalase, protease, lipase and phospholipase, and its ability to release proinflammatory mediators that cause gastric mucosa inflammation [36].Inhalation of H. pylori or H. pylori exotoxins may cause tissue damage in the bronchial system and hence can affect the pulmonary function tests especially FEV1 [37].Roussos et al., found higher serum H. pylori seropositivity and serum H. pylori IgG levels in COPD patients, but they could not detect an association with lung function parameters (27).
[20]ylori infection might play a proinflammatory role and co-trigger COPD with other more specific environmental, genetic and yet, unknown factors.The association between H. pylori infection and COPD is based only on serologic case-control studies with low socioeconomic status and tobacco abuse as confounding factors[20].