- Association between Pepsin in Bronchoalveolar Lavage Fluid and Prognosis of Chronic Fibrosing Interstitial Lung Disease. [Journal Article]
- TJTohoku J Exp Med 2018; 246(3):147-153
- Chronic fibrosing interstitial lung disease (ILD)s are characterized by chronic progressive fibrosis of lung which include idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSI...
Chronic fibrosing interstitial lung disease (ILD)s are characterized by chronic progressive fibrosis of lung which include idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), and connective tissue disease-associated interstitial lung disease (CTD-ILD). IPF is an irreversible fibrotic lung disease which results in respiratory failure. Although NSIP and CTD-ILD can be improved or stable by treatment with corticosteroid or immunosuppressant, some of them progress to fibrotic lung diseases. Aspiration of gastric contents is suggested as an aggravating factor of ILDs. We measured pepsin, a marker of gastric aspiration, in bronchoalveolar lavage (BAL) fluid of chronic fibrosing ILD patients to evaluate the association between BAL fluid pepsin and prognosis of chronic fibrosing ILDs. Patients with chronic fibrosing ILDs, who underwent bronchoscopy between December 2010 and April 2015 were prospectively enrolled. Pepsin levels were measured using a commercial ELISA kit. Clinical characteristics, lung function data, and mortality were analyzed. Fifty-one patients with chronic fibrosing ILDs were enrolled (26 with IPF, 15 with NSIP, and 10 with CTD-ILD). Pepsin levels in BAL fluid were 69.87 ± 74.16 ng/mL in IPF, 110.68 ± 94.93 ng/mL in NSIP, and 101.87 ± 88.44 ng/mL in CTD-ILDs. There were no statistically significant differences in BAL fluid pepsin levels among patients with the different chronic fibrosing ILDs. In multivariate regression analysis, higher BAL pepsin levels were associated with higher mortality (adjusted odds ratio [aOR] = 1.021, p = 0.025). BAL fluid pepsin may be used as a prognostic marker for predicting mortality in chronic fibrosing ILD patients.
- Postprandial bile acid levels in intestine and plasma reveal altered biliary circulation in chronic pancreatitis patients. [Journal Article]
- JLJ Lipid Res 2018; 59(11):2202-2213
- Bile acid (BA) secretion and circulation in chronic pancreatitis (CP) patients with exocrine pancreatic insufficiency (EPI) were investigated by simultaneously measuring postprandial levels of indivi...
Bile acid (BA) secretion and circulation in chronic pancreatitis (CP) patients with exocrine pancreatic insufficiency (EPI) were investigated by simultaneously measuring postprandial levels of individual BAs in duodenal contents and blood plasma using LC-MS/MS. CP patients and healthy volunteers (HVs) were intubated with gastric and duodenal tubes prior to the administration of a test meal and continuous aspiration of duodenal contents. Pancreatic lipase outputs in CP patients were very low (0.7 ± 0.2 mg) versus HVs (116.7 ± 68.1 mg; P < 0.005), thus confirming the severity of EPI. Duodenal BA outputs were reduced in CP patients (1.00 ± 0.89 mmol; 0.47 ± 0.42 g) versus HVs (5.52 ± 4.53 mmol; 2.62 ± 2.14 g; P < 0.15). Primary to secondary BA ratio was considerably higher in CP patients (38.09 ± 48.1) than HVs (4.15 ± 2.37; P < 0.15), indicating an impaired transformation of BAs by gut microbiota. BA concentrations were found below the critical micellar concentration in CP patients, while a high BA concentration peak corresponding to gallbladder emptying was evidenced in HVs. Conversely, BA plasma concentration was increased in CP patients versus HVs suggesting a cholangiohepatic shunt of BA secretion. Alterations of BA circulation and levels may result from the main biliary duct stenosis observed in these CP patients and may aggravate the consequences of EPI on lipid malabsorption.
- A qualitative synthesis of gastro-oesophageal reflux in bronchiectasis: Current understanding and future risk. [Review]
- RMRespir Med 2018; 141:132-143
- Gastro-oesophageal reflux disease (GORD) is a common comorbidity in bronchiectasis, and is often associated with poorer outcomes. The cause and effect relationship between GORD and bronchiectasis has...
Gastro-oesophageal reflux disease (GORD) is a common comorbidity in bronchiectasis, and is often associated with poorer outcomes. The cause and effect relationship between GORD and bronchiectasis has not yet been fully elucidated and a greater understanding of the pathophysiology of the interaction and potential therapies is required. This review explores the underlying pathophysiology of GORD, its clinical presentation, risk factors, commonly applied diagnostic tools, and a detailed synthesis of original articles evaluating the prevalence of GORD, its influence on disease severity and current management strategies within the context of bronchiectasis. The prevalence of GORD in bronchiectasis ranges from 26% to 75%. Patients with co-existing bronchiectasis and GORD were found to have an increased mortality and increased bronchiectasis severity, manifest by increased symptoms, exacerbations, hospitalisations, radiological extent and chronic infection, with reduced pulmonary function and quality of life. The pathogenic role of Helicobacter pylori infection in bronchiectasis, perhaps via aspiration of gastric contents, also warrants further investigation. Our index of suspicion for GORD should remain high across the spectrum of disease severity in bronchiectasis. Identifying GORD in bronchiectasis patients may have important therapeutic and prognostic implications, although clinical trial evidence that treatment targeted at GORD can improve outcomes in bronchiectasis is currently lacking.
- Early Immune Response to Acute Gastric Fluid Aspiration in a Rat Model of Lung Transplantation. [Journal Article]
- ECExp Clin Transplant 2018 Apr 26
- CONCLUSIONS: The acute inflammatory response observed in the present study is consistent with changes found in chronic models of aspiration-associated injury and suggests a potentially important role for mast cells in the development of obliterative bronchiolitis.
- [The Prevalence of Nontuberculous Mycobacterial Lung Disease with orwithout Reflux Esophagitis]. [Journal Article]
- KJKorean J Gastroenterol 2018 01 25; 71(1):18-23
- CONCLUSIONS: We showed a greater prevalence of RE minimal change in patients with NTM than those without NTM with statistical significance.
- Histopathological Findings Associated With Gastroesophageal Reflux Disease and Aspiration After Lung Transplantation: Initial Brazilian Single-Center Experience. [Journal Article]
- TPTransplant Proc 2017; 49(4):886-889
- CONCLUSIONS: Surveillance transbronchial biopsies may provide useful information other than the evaluation of acute cellular rejection and can help to identify high-risk patients for allograft dysfunction related to gastro-esophageal reflux.
- Weakly acidic pH reduces inflammatory cytokine expression in airway epithelial cells. [Journal Article]
- RRRespir Res 2016 Jul 15; 17(1):82
- CONCLUSIONS: AEC inflammatory responses to bacterial stimuli is markedly reduced in a mildly acidic environment.
- Could prominent airway-centered fibroblast foci in lung biopsies predict underlying chronic microaspiration in idiopathic pulmonary fibrosis patients? [Journal Article]
- HPHum Pathol 2016; 53:1-7
- Chronic occult aspiration of small droplets (microaspiration) due to gastroesophageal reflux disease (GERD) and/or hiatal hernia is postulated to be a contributing factor in the pathogenesis of idiop...
Chronic occult aspiration of small droplets (microaspiration) due to gastroesophageal reflux disease (GERD) and/or hiatal hernia is postulated to be a contributing factor in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Usual interstitial pneumonia (UIP) is the histopathologic correlate of IPF. We hypothesized that chronic microaspiration may manifest as prominent airway-centered fibroblastic foci (FFs) in IPF. UIP cases diagnosed by wedge biopsies over a 6-year period (2006-2011) were identified and scored (1-3) for the prominence of airway-centered FFs by 2 authors blinded for clinical history. Relevant clinical information was obtained. Thirty-seven patients (22 men) were diagnosed with IPF by multidisciplinary approach. Thirteen cases (35.1%) demonstrated high airway-centered FF score (score 3). Twenty (54.1%) patients carried a clinical diagnosis of GERD, and 3 patients (8.1%) had hiatal hernia. High airway-centered FF score was significantly associated with hiatal hernia diagnosis (P=.037) but not with a diagnosis of GERD or the use of proton pump inhibitors/histamine-2 receptor antagonists. High airway-centered FF score was associated with airway-centered acute inflammation (P=.028) and peribronchiolar granulomas (P=.042). In summary, IPF cases with hiatal hernia were more likely to have a prominent airway-centered FF. Given the strong association between hiatal hernia and GERD and their risk for developing chronic microaspiration, the prominent airway-centered FF in UIP might predict the presence of chronic microaspiration, acknowledging that GERD and proton pump inhibitor/histamine-2 receptor antagonist use failed to demonstrate a significant association. Larger studies are warranted for further investigation.
- Association Between Chronic Aspiration and Chronic Airway Infection with Pseudomonas aeruginosa and Other Gram-Negative Bacteria in Children with Cerebral Palsy. [Journal Article]
- LUNGLung 2016; 194(2):307-14
- CONCLUSIONS: Colonization with P. aeruginosa and other Gram-negative organisms in children with CP is associated with increased morbidity, prolonged hospitalization, and severity of pneumonia including need for PICU admission and intervention. Further research is required to determine causality, the role of antimicrobials active against Gram negative in pneumonia treatment, and the role of GNB eradication therapy in children with CP.
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- Gastroesophageal reflux disease in COPD: links and risks. [Review]
- IJInt J Chron Obstruct Pulmon Dis 2015; 10:1935-49
- COPD is a long-term condition associated with considerable disability with a clinical course characterized by episodes of worsening respiratory signs and symptoms associated with exacerbations. Gastr...
COPD is a long-term condition associated with considerable disability with a clinical course characterized by episodes of worsening respiratory signs and symptoms associated with exacerbations. Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal conditions in the general population and has emerged as a comorbidity of COPD. GERD may be diagnosed by both symptomatic approaches (including both typical and atypical symptoms) and objective measurements. Based on a mix of diagnostic approaches, the prevalence of GERD in COPD ranges from 17% to 78%. Although GERD is usually confined to the lower esophagus in some individuals, it may be associated with pulmonary microaspiration of gastric contents. Possible mechanisms that may contribute to GERD in COPD originate from gastroesophageal dysfunction, including altered pressure in the lower esophageal sphincter (which normally protect against GERD) and changes in esophageal motility. Proposed respiratory contributions to the development of GERD include respiratory medications that may alter esophageal sphincter tone and changes in respiratory mechanics, with increased lung hyperinflation compromising the antireflux barrier. Although the specific cause and effect relationship between GERD and COPD has not been fully elucidated, GERD may influence lung disease severity and has been identified as a significant predictor of acute exacerbations of COPD. Further clinical effects could include a poorer health-related quality of life and an increased cost in health care, although these factors require further clarification. There are both medical and surgical options available for the treatment of GERD in COPD and while extensive studies in this population have not been undertaken, this comorbidity may be amenable to treatment.