Inflammation, Not Acid, Cause of GERD, Study Suggests

  • metta

    Posts: 39104

    May 18, 2016 4:05 PM GMT
    Inflammation, Not Acid, Cause of GERD, Study Suggests

    Gastroesophageal reflux disease (GERD) may be caused by an immune reaction, rather than direct chemical injury from stomach acids, according to results from a small, single-center study published online May 17 in JAMA. http://jama.jamanetwork.com/article.aspx?articleid=2521970

    "In this preliminary study of 12 patients with severe reflux esophagitis successfully treated with PPI therapy, stopping PPI medication was associated with T lymphocyte–predominant esophageal inflammation and basal cell and papillary hyperplasia without loss of surface cells," write first author Kerry Dunbar, MD, PhD, from the Dallas Veterans Affairs Medical Center in Texas, and colleagues.

    "If replicated, these findings suggest that the pathogenesis of reflux esophagitis may be cytokine-mediated rather than the result of chemical injury," they add.

    Since 1935, convention has held that GERD, which affects about 20% of Americans, results from irritation of the esophageal lining as a result of refluxed acid from the stomach. A recent study in rats, however, has suggested that GERD may not be a result of chemical injury but, rather, a result of an immune reaction. That prompted researchers to test this new hypothesis in humans.

    The study included 12 patients (11 men; mean age, 57.6 years) seen at the Dallas Veterans Affairs Medical Center for severe reflux esophagitis successfully treated with PPIs. Participants were told to stop taking their PPIs and received evaluations at baseline, as well as 1 and 2 weeks after stopping medication. Assessments included 24-hour esophageal pH and impedance monitoring (an index of mucosal integrity) and esophagoscopy (which included high-resolution confocal laser endomicroscopy). Researchers biopsied noneroded areas of the esophagus, where immune activity was assumed to be lower than in eroded areas.

    At baseline, almost all participants (11/12) had no visible evidence of esophagitis. By 2 weeks after stopping PPIs, all participants developed esophagitis, and five had severe esophagitis.

    Within 2 weeks of stopping PPIs, all participants developed abnormalities characteristic of GERD: basal cell and papillary hyperplasia (P < .01), papillary elongation (P < .01), dilated intercellular spaces in the esophageal squamous cell epithelium (P <. 001), reduced mucosal impedance (P = .001), and increased distal esophageal acid exposure. Between baseline and 2 weeks, acid exposure increased by 16.2% (95% confidence interval, 4.4% - 26.5%; P = .005).

    Biopsies showed significant increases in infiltration of intraepithelial lymphocytes 1 and 2 weeks after stopping PPIs, with predomination of T cells (week 1, P = .005; week 2, P = .002) and few or no neutrophils and eosinophils.

    "[E]sophageal basal cell and papillary hyperplasia developed in areas without surface erosions. If the traditional notion were true, that acute GERD is caused by refluxed acid directly inflicting lethal, chemical injury to surface epithelial cells, then basal cell and papillary hyperplasia would have been expected only in areas with surface erosions, and the infiltrating inflammatory cells would have been granulocytes primarily," the authors write. They note that further studies are needed to confirm these results.

    In a linked editorial, Peter Kahrilas, MD, from Northwestern Feinberg School of Medicine, Chicago, Illinois, notes that the "provocative findings from this investigation are in the details": the earliest pathology occurred deep in the epithelium, not at the mucosal surface, and repair mechanisms started before the death of surface cells previously thought to provoke these changes.

    "[A]lthough the inciting pathophysiology is unquestionably the reflux of gastric and duodenal secretions into the esophagus, this evidence suggests that the effect of that reflux is the initiation of cytokine-triggered inflammation rather than the long held belief of a direct chemical effect of acid, pepsin, and bile on the esophageal epithelium," he wrote.

    He notes that the participants in this study — men with high-grade erosive GERD and hiatal hernias — probably represent between 1% and 5% of all patients with GERD, so the findings may not apply to all patients with GERD. However, shifting the focus away from the "burning" effect of stomach acid toward an immune reaction may help explain subtypes of GERD that have been recently recognized.

    The findings may also have implications for therapy, he notes. Although PPIs will probably remain the backbone of treatment, new therapies that target the inflammatory cascade may help treat patients with more severe or refractory GERD.

    "Based on these findings, perhaps the mantra for treating refractory GERD should be 'divide and conquer,' according to the clinical findings and this new information about the disease process," he concluded, "This is a heterogeneous patient group, and the therapeutic puzzle will only be solved piece by piece. Dunbar et al may have just placed a very important piece."

    The study was supported by a grant from the US Department of Veterans Affairs, the National Institutes of Health, and the American Gastroenterological Association. One or more authors reports consulting for one or more of the following: Interpace Diagnostics, Ironwood Pharmaceuticals, and Takeda Pharmaceuticals. The editorial was supported by a grant from the Public Health Service. Dr Kahrilas has disclosed no relevant financial relationships.

    JAMA. 2016;315:2104-2112. Article abstract, Editorial extract

    http://www.medscape.com/viewarticle/863413
  • Posted by a hidden member.
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    May 18, 2016 4:35 PM GMT
    This site apparently requires membership to view, which I'm not gonna do. Any chance you can paste some of it, or find it at an open site?
  • metta

    Posts: 39104

    May 18, 2016 7:18 PM GMT
    That's strange. I can see it and I'm not a member.


    Here is another story:
    This is the Real Cause of Acid Reflux Disease, Study Says
    For over 80 years, scientists have said that the condition is caused by stomach acid backing up through the esophagus – until now.


    http://www.usnews.com/news/articles/2016-05-18/reflux-disease-not-caused-by-acid-but-inflammation-study-shows
  • Posted by a hidden member.
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    May 18, 2016 9:40 PM GMT
    metta saidThat's strange. I can see it and I'm not a member.

    Here is another story:
    This is the Real Cause of Acid Reflux Disease, Study Says
    For over 80 years, scientists have said that the condition is caused by stomach acid backing up through the esophagus – until now.

    http://www.usnews.com/news/articles/2016-05-18/reflux-disease-not-caused-by-acid-but-inflammation-study-shows

    First, thanks for pasting something we all can read.

    Second, the newly speculated cause of GERD (with which I have been diagnosed) is interesting. But in the short term, using a PPI (proton pump inhibitor) provides my only relief.

    Stopping acid from entering my esophagus relieves my pain & symptoms. And VA doctors, when they scoped me, found actual perforations (aka ulcers). And prescribed a PPI, now available off the shelf.

    Now whether the actual mechanism is something else like an immune reaction is kinda immaterial to me, until another method is devised to address it. In the meantime, a PPI gives me the only relief I experience. And my husband as well, also diagnosed with GERD. I always carry PPI pills for us both in my iPad shoulder bag.
  • Posted by a hidden member.
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    May 24, 2016 2:22 AM GMT
    Predominant esophageal inflammation? Immune reaction? icon_confused.gif

    Inflammation where? as a person who suffers from this, at least in my case, appears to be mechanical rather than acid or inflammation. This article only subtly mentioned the hiatal hernia which if in a fixed position, is considered a "genetic defect" and must be surgically repaired at some time in the persons adult life.

    In my case, I have a sliding hiatal hernia which means I can 'manually' manipulate or massage my stomach in the downward direction to relieve the 'burning' sensation. The burning, at least with a sliding hernia, is when the top of the stomach gets caught in the diaphragm opening, "pinching" the stomach, if there is acids (on a full stomach), in the top part of the stomach that got caught in the diaphragm, then those acids back up into the esophagus because they become trapped by the pinch.

    Inflammation maybe with those people who do not have a hernia, whether fixed or sliding. The hiatal hernia is the most cause of GERD or acid reflux but the powers that be, either in the medical or pharma industry, don't want most people to know this. If I had the money, I would have my sliding hernia fixed by surgery, because the PPI drugs (that are pushed by pharma), are considered "treatment" for these hernias, health insurance considers surgery "elective" and will not cover the cost of this common defect. Insurance will cover the cost of an upper GI endoscopy, which discovers the hernia but then will not cover the cost to really fix it, the "cheaper" fix for them is to push PPI drugs because these drugs relieve the symptoms, but to get off these meds, takes expensive surgery

    There are now lawsuits flying off the shelf regarding these PPI drugs that have now affected or damaged the kidneys. I buy the OTC Zantac, 75 mg, the lowest dose since I don't have insurance anymore to cover the brand names that my doctor had once prescribed. I manually move my stomach down when I feel chest pain

    Here is the real reason so many people suffer from GERD, acid back up or inflammation are only symptoms of the problem, PPI drugs only mask the symptoms, its unfortunate most people lack the knowledge because they "trust" their doctor icon_confused.gif

    Immune response? Its a genetic, mechanical issue, this has nothing to do with ones immune system, just throwing more confusion icon_mad.gif






    For those without a hernia, its pressure build up in the stomach, another mechanical issue




    It appears to be the same theory, as to why the lid on these yogurt containers "bulge", the bacteria is fermenting causing the gas to expand the container. As explained in the video above, our stomach fills with gas. With a sliding hernia, some of this gas escapes into the pipe along with acid

    chobani-bloated-top.jpg