Aspiration is defined as the inhalation of oropharyngeal or gastric contents into the larynx and lower respiratory tract.1,2 Several pulmonary syndromes may occur after aspiration, depending on the amount and nature of the aspirated material, the frequency of aspiration, and the host's response to the aspirated material.2 Aspiration pneumonitis (Mendelson's syndrome) is a chemical injury caused by the inhalation of sterile gastric contents, whereas aspiration pneumonia is an infectious process caused by the inhalation of oropharyngeal secretions that are colonized by pathogenic bacteria. Although there is some overlap between these syndromes, they are distinct clinical entities (Table 1). Other . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM200103013440908

Aspiration Pneumonitis and Aspiration Pneumonia

Patients with advanced dementia frequently develop eating difficulties and weight loss. Enteral feeding tubes are often used in this situation, yet benefits and risks of this therapy are unclear. We searched MEDLINE, 1966 through March 1999, to identify data about whether tube feeding in patients with advanced dementia can prevent aspiration pneumonia, prolong survival, reduce the risk of pressure sores or infections, improve function, or provide palliation. We found no published randomized trials that compare tube feeding with oral feeding. We found no data to suggest that tube feeding improves any of these clinically important outcomes and some data to suggest that it does not. Further, risks are substantial. The widespread practice of tube feeding should be carefully reconsidered, and we believe that for severely demented patients the practice should be discouraged on clinical grounds.

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=JAMA&articleId=191992&pdfFileName=jsc90078.pdf

Tube Feeding in Patients With Advanced Dementia: A Review of the Evidence

It is well known that inflammatory conditions of the intestinal mucosa result in compromised barrier function. Inflammation is characterized by an influx into the mucosa of immune cells that influence epithelial function by releasing proinflammatory cytokines such as IFN-γ and TNF-α. Mucosal barrier function is regulated by the epithelial apical junctional complex (AJC) consisting of the tight junction and the adherens junction. Since the AJC regulates barrier function, we analyzed the influence of IFN-γ and TNF-α on its structure/function and determined the contribution of apoptosis to this process using a model intestinal epithelial cell line, T84, and IFN-γ and TNF-α. AJC structure/function was analyzed by confocal microscopy, biochemical analysis, and physiologic measurement of epithelial gate/fence function. Apoptosis was monitored by determining cytokeratin 18 cleavage and caspase-3 activation. IFN-γ induced time-dependent disruptions in epithelial gate function that were potentiated by coincubation with TNF-α. Tight junction fence function was somewhat disrupted. Cytokine treatment was associated with internalization of AJC transmembrane proteins, junction adhesion molecule 1, occludin, and claudin-1/4 with minimal effects on the cytoplasmic plaque protein zonula occludens 1. Detergent solubility profiles of junction adhesion molecule 1 and E-cadherin and their affiliation with “raft-like” membrane microdomains were modified by these cytokines. Inhibition of cytokine-induced apoptosis did not block induced permeability defects; further emphasizing their primary influence on the epithelial AJC structure and barrier function. Our findings for the first time clearly separate the proapoptotic effects of IFN-γ and TNF-α from their abilities to disrupt barrier function.

/pdf/proinflammatory-cytokines-disrupt-epithelial-barrier-4tat4c0fbm.pdf

Proinflammatory Cytokines Disrupt Epithelial Barrier Function by Apoptosis-Independent Mechanisms

https://journal.chestnet.org/article/S0012-3692(15)36028-1/pdf

Aspiration pneumonia and dysphagia in the elderly.

The goal of this review is to describe barrier function of the intestine, the structure of the tight junction, methods to evaluate intestinal permeability, and most importantly the relevance of abnormal permeability to disease. In this context, we will also present an emerging paradigm regarding the genesis of autoimmune diseases and describe the data that supports this from the perspective of both human disease and animal models. While this is a complicated area there are several points worth remembering:





From the lower oesophageal sphincter to the anus, the gastrointestinal tract has a single contiguous layer of cells that separates the inside of the body from the external environment. Separation is important as there are a wide variety of environmental agents in the lumen of the bowel that can initiate or perpetuate mucosal inflammation if they cross the epithelial barrier. While the epithelial lining of the intestine plays a critical role in preventing access of these agents, it is not the only component of what is termed barrier function. Also important are secreted products such as immunoglobulin, mucous, defensins, and other antimicrobial products.

The importance of epithelial barrier function in normal homeostasis can be appreciated from experiments performed in the early 1990s where cell wall extracts from luminal bacteria were injected into the colonic wall of rats.1 This simple manoeuvre of bypassing the epithelial barrier and placing luminal compounds directly into the colonic wall initiated an …

Alterations in intestinal permeability

OBJECTIVE--To compare percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with persisting neurological dysphagia. DESIGN--Randomised 28 day study of inpatients requiring long term enteral nutrition. SETTING--Three Glasgow teaching hospitals. SUBJECTS--40 patients with dysphagia for at least four weeks secondary to neurological disorders: 20 patients (10 women) were randomised to nasogastric feeding and 20 (eight women) to endoscopic gastrostomy. MAIN OUTCOME MEASURES--Treatment failure (blocked or displaced tubes on three or more occasions or refusal to continue treatment); duration of feeding; intake of liquid diets; complications; nutritional status at end of trial. RESULTS--One patient in each group died before starting feeding. Treatment failure occurred in 18 of the 19 nasogastric patients and in none of the gastrostomy group. The mean (SE) duration of feeding for the nasogastric group was 5.2 (1.5) days. No complications occurred in the nasogastric group but three (16%) of the gastrostomy group developed minor problems (aspiration pneumonia (two patients) wound infection (one)). Gastrostomy patients received a significantly greater proportion of their prescribed feed (93% (2%)) compared with the nasogastric group, (55% (4%); p less than 0.001) and also gained significantly more weight after seven days of feeding (1.4 (0.5) kg v 0.6 (0.1) kg; p less than 0.05). Analyses at days 14, 21, and 28 were not possible due to the small numbers remaining in the nasogastric group. CONCLUSION--Percutaneous endoscopic gastrostomy tube feeding is a safe and effective method of providing long term enteral nutrition to patients with neurological dysphagia and offers important advantages over nasogastric tube feeding.

https://www.bmj.com/content/bmj/304/6839/1406.full.pdf

Randomised comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with persisting neurological dysphagia.

Intestinal permeability in patients with Crohn's disease and their first-degree relatives

SUMMARY Acidintragastric pH isbelieved tobe mandatory formucosal protective action of sucralfate, butevidence foritsefficacy atneutral pHislacking. Theeffect ofsucralfate on gastric mucosal erosions induced byoral administration ofaspirin andbile acids atacidic pHof1.5and3.9, andnearneutral pHof6.5 wasinvestigated in320rats. Theeffect ofsucralfate ontheintragastric pH fourhoursafter theingestion oftestsolutions was alsoexamined. Theincidence andseverity of mucosal erosions induced byaspirin andbile acids werelower inanimals treated withsucralfate at acidic (p<0.001) andnearneutral (p<0.01) intragastric pH.Mucosal protection wasgreater with ingestion ofsucralfate 300mg/kgand200mg/kg, thanwith100mg/kg. Theintragastric pH was higher (p<0.001) insucralfate treated groupsatpH3.9and6.5. Thisstudy provides evidence that sucralfate protects against mucosal injuryatnearneutral, aswell asatacidic pH. Theulcer healing properties ofsucralfatel-3 andits ability toprotect thegastric mucosafromacute experimental injury'- arerelated toits local actions6 rather thantheinhibition ofacid secretion. Itsmode ofaction is, however, multifactorial inthat its acute administration hasbeenfound tostimulate arange of mucosal defence factors including prostaglandins,' mucus,8 andbicarbonate.9 Inaddition, however, the physiochemical properties ofthedrugallow ittobind tothemucosa,""'2 andmoreselectively toulcer sites,'3 forming abarrier against thediffusion ofacid, pepsin, andother noxious agents. Sucralfate may also deactivate pepsin'4 1 andadsorb bile salts,'6 17but these effects havebeenthought torequire anacid environment.`'0" Forexample, thebinding ofbile salts invitro isconsiderably less underneutral as opposed toacidconditions.'7 Forthese reasons the efficacy ofsucralfate intheprotection ofthemucosa against damaging agents suchasaspirin andbile acids, hasbeenquestioned underconditions where acid secretion isitself inhibited orabsent. Previous studies which haveexamined themucosal protective effects ofsucralfate against acuteinjury haveingeneral beenconducted underacidpH conditions. Thepresent study hasbeendesigned to

B J Z Danesh

Papers

Randomised comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with persisting neurological dysphagia.

Intestinal permeability in patients with Crohn's disease and their first-degree relatives

Effect ofintragastric pHonmucosal protective action ofsucralfate