• Humans
• Idiopathic Pulmonary Fibrosis/epidemiology
• Idiopathic Pulmonary Fibrosis/genetics
• Comorbidity
• Gastroesophageal Reflux/epidemiology
• Risk Factors
• Sleep Apnea, Obstructive/epidemiology
• Disease Progression
• Genetic Predisposition to Disease
• Lung Neoplasms/epidemiology
• Hypertension, Pulmonary/epidemiology
• Metabolic Syndrome/epidemiology
• Mendelian Randomization Analysis
• Smoking

• Connective tissue disease
• Interstitial lung disease
• Lung microbiome

• Humans
• Lung Diseases, Interstitial/microbiology
• Lung Diseases, Interstitial/immunology
• Microbiota/immunology
• Autoimmune Diseases/immunology
• Autoimmune Diseases/microbiology
• Lung/microbiology
• Lung/immunology

• fibrosis
• gerd
• interstitium
• ipf
• prevalence

• Humans
• Idiopathic Pulmonary Fibrosis/genetics
• Idiopathic Pulmonary Fibrosis/epidemiology
• Genome-Wide Association Study
• Comorbidity
• Genetic Predisposition to Disease
• Pulmonary Disease, Chronic Obstructive/genetics
• Pulmonary Disease, Chronic Obstructive/epidemiology
• Polymorphism, Single Nucleotide

• The University of Queensland

• achalasia
• acid reflux
• gerd
• ild interstitial lung disease
• microaspiration

• aspiration
• aspiration pneumonia
• bacterial aspiration pneumonia
• microbial communities
• oral care
• oral hygiene
• oral infection control
• pneumonia

• advanced delivery systems
• antifibrotic drugs
• idiopathic pulmonary fibrosis
• nanocarrier-based therapies
• preclinical efficacy

• Humans
• Pandemics
• Idiopathic Pulmonary Fibrosis/drug therapy
• Idiopathic Pulmonary Fibrosis/chemically induced
• Lung
• Drug Delivery Systems
• Pyridones/therapeutic use
• Nanoparticles

• Dyspnoea
• Hiatal hernia
• Paraoesophageal hernia

• Humans
• Middle Aged
• Aged
• Aged, 80 and over
• Hernia, Hiatal/complications
• Hernia, Hiatal/surgery
• Diaphragm/surgery
• Stomach/surgery
• Laparoscopy/adverse effects
• Laparoscopy/methods
• Herniorrhaphy/adverse effects
• Herniorrhaphy/methods
• Recurrence
• Treatment Outcome

• gerd
• national inpatient sample (nis)
• phtn
• proton-pump inhibitors (ppi)
• pulmonary hypertension

• aspiration
• endotracheal tube cuff pressure
• mechanical ventilation complication
• respiratory
• smart cuff manager
• ventilator-associated pneumonia

• adjunct
• anti-fibrotic
• etiology
• idiopathic pulmonary fibrosis (IPF)
• novel
• pathophysiology
• pharmacotherapy
• treatment

• interstitial lung abnormalities (ila)
• computed tomography
• esophageal cancer
• chemoradiotherapy
• chest radiology

• Humans
• Female
• Male
• Aged
• Prevalence
• Neoplasms, Second Primary
• Esophageal Neoplasms/diagnostic imaging
• Esophageal Neoplasms/epidemiology
• Esophageal Neoplasms/therapy
• Risk Factors
• Lung

• R01 CA203636 NCI NIH HHS
• R01 CA240592 NCI NIH HHS
• R01 HL111024 NHLBI NIH HHS
• U01 CA209414 NCI NIH HHS

• aerodigestive
• dysphagia
• pharyngeal
• pneumonia
• reflux

• Usual interstitial pneumonitis
• chest CT
• gastroesophageal reflux
• infection
• inflammation
• tensile forces
• vascular insult

• Biopsie
• Biopsy
• Common interstitial lung disease
• Fibrose pulmonaire
• Interstitial lung disease
• Pneumopathie interstitielle commune
• Pneumopathie interstitielle diffuse
• Pulmonary fibrosis

• Biopsy
• Humans
• Idiopathic Pulmonary Fibrosis/diagnosis
• Idiopathic Pulmonary Fibrosis/epidemiology
• Idiopathic Pulmonary Fibrosis/therapy
• Lung/pathology
• Lung Transplantation
• Pulmonary Medicine

Background: Idiopathic pulmonary fibrosis (IPF) is a rare and severe disease with a median survival of ∼3 years. Several risk factors have been identified, such as age, genetic predisposition, tobacco exposure, and gastro-oesophageal reflux disease (GERD). Prevalence of GERD in IPF is high and may affect 87% of patients, of whom only half (47%) report symptoms. Objective: The aim of this study is to review current evidence regarding the correlation between GERD and IPF and to evaluate the current studies regarding treatments for GERD-IPF. Methods: A review to identify research papers documenting an association between GERD and IPF was performed. Results: We identified several studies that have confirmed the association between GERD and IPF, with an increased acid exposure, risk of gastric aspiration and bile acids levels in these patients. Few studies focused their attention on GERD treatment, showing how antiacid therapy was not able to change IPF evolution. Conclusions: This review investigating the correlation between GERD and IPF has confirmed the hypothesized association. However, further large prospective studies are needed to corroborate and elucidate these findings with a focus on preventative and treatment strategies.

• bronchoalveolar lavage fluid (BALF)
• gastro-oesophageal reflux disease (GERD)
• high-resolution computed tomography (HRTC)
• idiopathic pulmonary fibrosis (IPF)
• interstitial lung disease (ILD)
• interstitial pneumonia

Double-stranded RNA adenosine deaminase 1 (ADAR1) is significantly down-regulated in fibroblasts derived from Idiopathic Pulmonary Fibrosis (IPF) patients, and its overexpression restored levels of miRNA-21, PELI1, and SPRY2. There are two ADAR1 isoforms in humans, ADAR1-p110 and ADAR1-p150, generated by an alternative promoter. Let-7d is considered an essential microRNA in Pulmonary Fibrosis (PF). In silico analysis revealed COL3A1 and SMAD2, proteins involved in the development of IPF, as Let-7d targets. We analyzed the role of ADAR1-p110 and ADAR1-p150 isoforms in the regulation of Let-7d maturation and the effect of this regulation on the expression of COL3A1 and SMAD2 in IPF fibroblast. We demonstrated that differential expression and subcellular distribution of ADAR1 isoforms in fibroblasts contribute to the up-regulation of pri-miR-Let-7d and down-regulation of mature Let-7d. Induction of overexpression of ADAR1 reestablishes the expression of pri-miR-Let-7d and Let-7d in lung fibroblasts. The reduction of mature Let-7d upregulates the expression of COL3A1 and SMAD2. Thus, ADAR1 isoforms and Let-7d could have a synergistic role in IPF, which is a promising explanation in the mechanisms of fibrosis development, and the regulation of both molecules could be used as a therapeutic approach in IPF.

• ADAR
• IPF
• RNA edition
• miRNA

• Biopsy
• Interstitial lung disease
• Pulmonary fibrosis
• Usual interstitial pneumonia

• Aspiration
• Bile acid
• Iran
• Lung cancer

• autoantibodies
• connective tissue disease
• diagnosis
• fibromyalgia
• interstitial lung disease
• myalgia
• myositis
• tender points

Nasogastric tube (NGT) and percutaneous endoscopic gastrostomy (PEG) are widely used techniques to feed older patients with oropharyngeal dysphagia. Aspiration pneumonia is the most common cause of death in these patients. This study aimed to evaluate the role of oropharyngeal dysphagia in older patients on long-term enteral feeding for risk stratification of pneumonia requiring hospitalization.

We performed modified flexible endoscopic evaluation of swallowing to evaluate oropharyngeal dysphagia in older patients and conducted prospective follow-up for pneumonia requiring hospitalization. A total of 664 oral-feeding patients and 155 tube-feeding patients were enrolled. Multivariate Cox analysis was performed to identify risk factors of pneumonia requiring hospitalization.

Multivariate analyses showed that the risk of pneumonia requiring hospitalization significantly increased in older patients and in patients with neurological disorders, tube feeding, and oropharyngeal dysphagia. Subgroup analysis revealed that the risk of pneumonia requiring hospitalization was significantly lower in patients with PEG than in those with NGT among the patients with oropharyngeal dysphagia (adjusted hazard ratio 0.26, 95% confidence interval: 0.11–0.63, P = 0.003).

For older patients with oropharyngeal dysphagia requiring long-term enteral tube feeding, PEG is a better choice than NGT. Further research is needed to elucidate the role of oropharyngeal dysphagia in enteral feeding in older patients.

• aspiration pneumonia
• enteral feeding
• nasogastric tube
• older patients
• oropharyngeal dysphagia
• percutaneous endoscopic gastrostomy
• tube feeding

Idiopathic pulmonary fibrosis (IPF) is one of interstitial lung diseases (ILDs) with poor prognosis. S100 calcium binding protein A12 (S100A12) has been reported as a prognostic serum biomarker in the IPF, but its correlation with IPF remains unclear in the lung tissue and bronchoalveolar lavage fluids (BALF).

Datasets were collected from the Gene Expression Omnibus (GEO) database. Person correlation coefficient, Kaplan–Meier analysis, Cox regression analysis, functional enrichment analysis and so on were used. And single cell RNA-sequencing (scRNA-seq) analysis was also used to explore the role of S100A12 and related genes in the IPF.

S100A12 was mainly and highly expressed in the monocytes, and its expression was downregulated in the lung of patients with IPF according to scRNA-seq and the transcriptome analysis. However, S100A12 expression was upregulated both in blood and BALF of patients with IPF. In addition, 10 genes were found to interact with S100A12 according to protein–protein interaction (PPI) network, and the first four transcription factors (TF) targeted these genes were found according to hTFtarget database. Two most significant co-expression genes of S100A12 were S100A8 and S100A9. The 3 genes were significantly negatively associated with lung function and positively associated with the St. George’s Respiratory Questionnaire (SGRQ) scores in the lung of patients with IPF. And, high expression of the 3 genes was associated with higher mortality in the BALF, and shorter transplant-free survival (TFS) and progression-free survival (PFS) time in the blood. Prognostic predictive value of S100A12 was more superior to S100A8 and S100A9 in patients with IPF, and the composited variable [S100A12 + GAP index (gender, age, and physiological index)] may be a more effective predictive index.

These results imply that S100A12 might be an efficient disease severity and prognostic biomarker in patients with IPF.

• Aged
• Biomarkers/metabolism
• Bronchoalveolar Lavage Fluid/cytology
• Databases, Factual
• Female
• Gene Expression Profiling
• Humans
• Idiopathic Pulmonary Fibrosis/genetics
• Idiopathic Pulmonary Fibrosis/metabolism
• Idiopathic Pulmonary Fibrosis/mortality
• Lung/metabolism
• Male
• Middle Aged
• Prognosis
• RNA-Seq
• S100A12 Protein/genetics
• S100A12 Protein/metabolism
• Severity of Illness Index
• Survival Analysis

• Science and Technology Department, Heilongjiang Province

• Aged
• Aged, 80 and over
• Antimicrobial Peptides/analysis
• Bacteria/classification
• Bacteria/genetics
• Bacteria/isolation & purification
• Bronchoalveolar Lavage Fluid/chemistry
• Bronchoalveolar Lavage Fluid/microbiology
• Case-Control Studies
• Female
• Humans
• Idiopathic Pulmonary Fibrosis/metabolism
• Idiopathic Pulmonary Fibrosis/microbiology
• Male
• Microbiota
• Middle Aged
• Phylogeny
• Pulmonary Disease, Chronic Obstructive/metabolism
• Pulmonary Disease, Chronic Obstructive/microbiology
• RNA, Ribosomal, 16S/genetics
• Secretory Leukocyte Peptidase Inhibitor/metabolism
• Sequence Analysis, DNA
• beta-Defensins/analysis

• Helse Vest
• Norske Legeforening
• Boehringer Ingelheim

Acute exacerbation is a major cause of morbidity and mortality in patients with idiopathic pulmonary fibrosis. Although the real nature of it is still not clear and there is no proven effective therapy, progress has been made since the consensus definition and diagnostic criteria were proposed. The trial results of several new innovative therapies in idiopathic pulmonary fibrosis have suggested a potential for benefit in acute exacerbation of idiopathic pulmonary fibrosis, leading to double blind randomized clinical trials in this area. This article reviews the present knowledge on acute exacerbation of idiopathic pulmonary fibrosis, focusing on the triggering factors and treatment.

• CD247
• biomarker
• idiopathic pulmonary fibrosis
• immune response
• inflammation response
• prognosis

• biomarkers
• gastrointestinal disease
• interstitial lung disease
• systemic sclerosis

• Dilatation
• Humans
• Lung/diagnostic imaging
• Lung Diseases, Interstitial/diagnostic imaging
• Lung Diseases, Interstitial/etiology
• Scleroderma, Systemic/complications
• Scleroderma, Systemic/diagnostic imaging
• Vital Capacity

• UL1 TR000150 NCATS NIH HHS
• R01 AR073270 NIAMS NIH HHS
• P60 AR064464 NIAMS NIH HHS
• KL2 TR001424 NCATS NIH HHS
• P30 AR072579 NIAMS NIH HHS
• K23 AR059763 NIAMS NIH HHS

• Disease classification
• Immune infiltration analysis
• Protein interaction network
• Weighted correlation network analysis

Pulmonary manifestation of gastro-oesophageal reflux disease (GORD) is a well-recognised entity; however, little primary reported data exists on presenting symptoms of patients in whom reflux micro-aspiration is confirmed. The aim of this study is to report symptoms and presenting patterns of a large group of patients with confirmed reflux micro-aspiration.

Data was extracted from a prospectively populated database of patients referred to a tertiary specialist centre with severe, refractory or atypical reflux. Patients with reflux micro-aspiration on scintigraphy were included in this study. A separate group included patients with evidence of proximal reflux to the level of pharynx when supine and/or upright.

Inclusion criteria were met by 243 patients with confirmed reflux micro-aspiration (33% males; mean age 59). Most common symptoms amongst patients with micro-aspiration were regurgitation (72%), cough (67%), heartburn (66%), throat clearing (65%) and dysphonia (53%). The most common two-symptom combinations were heartburn/regurgitation, cough/throat clearing, regurgitation/throat clearing, cough/regurgitation and dysphonia/throat clearing. The most common three-symptom combinations were cough/heartburn/regurgitation, cough/regurgitation/throat clearing and dysphonia/regurgitation/throat clearing. Cluster analysis demonstrated two main symptom groupings, one suggestive of proximal volume reflux symptoms and the other with motility/inflammatory bowel syndrome-like symptoms (bloat, constipation).

The combination of typical symptoms of GORD such as heartburn or regurgitation and a respiratory or upper aero-digestive complaint such as cough, throat clearing or voice change should prompt consideration of reflux micro-aspiration.

Patients with reflux micro-aspiration most commonly present with a combination of regurgitation and/or heartburn and cough and/or throat clearinghttps://bit.ly/3GM8cNS

• Interstitial lung abnormalities
• biomarkers
• imaging
• management
• prevalence
• subclinical interstitial lung diseases

Lung cancer is the leading disease of cancer-related deaths worldwide. Since the beginning of the 20th century, various infectious agents associated with lung cancer have been identified. The mechanisms that include systemic inflammatory pathways as effect of microbial persistence in the lung can secondarily promote the development of lung carcinogenesis. Chronic inflammation associated with lung-cancer infections is known to precede tumor development, and it has a strong effect on the response(s) to therapy. In fact, both viral and bacterial infections can activate inflammatory cells and inflammatory signaling pathways. In this review, an overview of critical findings of recent studies investigating associations between each of viral and bacterial pathogens and lung carcinoma is provided, with particular emphasis on how infectious organisms can interfere with oncogenic processes and all the way through immunity. Moreover, a discussion of the direct crosstalk between lung tumor development and inflammatory processes is also presented.

• bacteria
• immune system
• lung cancer
• virus

• biomarker
• innate immunity
• macrophage
• microenvironment
• pulmonary fibrosis

• Idiopathic interstitial pneumonia
• Idiopathic pulmonary fibrosis
• Interstitial lung disease
• Usual interstitial pneumonia

Mortality from idiopathic pulmonary fibrosis (IPF) is increasing in most European countries, but there are no data for Italy. We analysed the registry data from a region in northeastern Italy to assess the trends in IPF-related mortality during 2008–2019, to compare results of underlying vs. multiple cause of death analyses, and to describe the impact of the COVID-19 epidemic in 2020. We identified IPF (ICD-10 code J84.1) among the causes of death registered in 557,932 certificates in the Veneto region. We assessed time trends in annual age-standardized mortality rates by gender and age (40–74, 75–84, and ≥85 years). IPF was the underlying cause of 1310 deaths in the 2251 certificates mentioning IPF. For all age groups combined, the age-standardized mortality rate from IPF identified as the underlying cause of death was close to the European median (males and females: 3.1 and 1.3 per 100,000/year, respectively). During 2008–2019, mortality rates increased in men aged ≥85 years (annual percent change of 6.5%, 95% CI: 2.0, 11.2%), but not among women or for the younger age groups. A 72% excess of IPF-related deaths was registered in March–April 2020 (mortality ratio 1.72, 95% CI: 1.29, 2.24). IPF mortality was increasing among older men in northeastern Italy. The burden of IPF was heavier than assessed by routine statistics, since less than two out of three IPF-related deaths were directly attributed to this condition. COVID-19 was accompanied by a remarkable increase in IPF-related mortality.

• COVID-19
• epidemiology
• idiopathic pulmonary fibrosis
• mortality
• multiple cause of death
• time trends analysis
• underlying cause of death

It is not well-known if diagnosing and treating sleep breathing disorders among individuals with idiopathic pulmonary fibrosis (IPF) improves health outcomes. We evaluated the association between receipt of laboratory-based polysomnography (which is the first step in the diagnosis and treatment of sleep breathing disorders in Ontario, Canada) and respiratory-related hospitalization and all-cause mortality among individuals with IPF.

We used a retrospective, population-based, cohort study design, analyzing health administrative data from Ontario, Canada, from 2007 to 2019. Individuals with IPF were identified using an algorithm based on health administrative codes previously developed by IPF experts. Propensity score matching was used to account for potential differences in 41 relevant covariates between individuals that underwent polysomnography (exposed) and individuals that did not undergo polysomnography (controls), in order minimize potential confounding. Respiratory-related hospitalization and all-cause mortality were evaluated up to 12 months after the index date.

Out of 5044 individuals with IPF identified, 201 (4.0%) received polysomnography, and 189 (94.0%) were matched to an equal number of controls. Compared to controls, exposed individuals had significantly reduced rates of respiratory-related hospitalization (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.24–0.75), p = 0.003) and all-cause mortality (HR 0.49, 95% CI 0.30–0.80), p = 0.004). Significantly reduced rate of respiratory-related hospitalization (but not all-cause mortality) was also observed among those with >  = 1 respiratory-related hospitalization (HR 0.38, 95% CI 0.15–0.99) and systemic corticosteroid receipt (HR 0.37, 95% CI 0.19–0.94) in the year prior to the index date, which reflect sicker subgroups of persons.

Undergoing polysomnography was associated with significantly improved clinically-important health outcomes among individuals with IPF, highlighting the potential importance of incorporating this testing in IPF disease management.

The online version contains supplementary material available at 10.1186/s12890-021-01555-x.

• Health administrative database research
• Health outcomes research
• Pulmonary fibrosis
• Sleep breathing disorder
• Sleep testing

We developed two models of chemically induced chronic lung injury and pulmonary fibrosis in mice (intratracheally administered hydrochloric acid (HCl) and intratracheally administered nitrogen mustard (NM)) and investigated male–female differences. Female mice exhibited higher 30-day survival and less weight loss than male mice. Thirty days after the instillation of either HCl or NM, bronchoalveolar lavage fluid displayed a persistent, mild inflammatory response, but with higher white blood cell numbers and total protein content in males vs. females. Furthermore, females exhibited less collagen deposition, milder pulmonary fibrosis, and lower Ashcroft scores. After instillation of either HCl or NM, all animals displayed increased values of phosphorylated (activated) Heat Shock Protein 90, which plays a crucial role in the alveolar wound-healing processes; however, females presented lower activation of both transforming growth factor-β (TGF-β) signaling pathways: ERK and SMAD. We propose that female mice are protected from chronic complications of a single exposure to either HCl or NM through a lesser activation of TGF-β and downstream signaling. The understanding of the molecular mechanisms that confer a protective effect in females could help develop new, gender-specific therapeutics for IPF.

• fibrosis
• gender differences
• heat shock proteins
• hydrochloric acid
• idiopathic pulmonary fibrosis (IPF)
• nitrogen mustard

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia of unknown cause, occurring in adults and limited to the lungs. In the past, treatment was aimed at minimizing inflammation and slowing the progression of inflammation to fibrosis. However, the underlying lesion in IPF may be more fibrotic than inflammatory, explaining why few patients respond to anti-inflammatory therapies and the prognosis remains poor.

In this review of literature, we will be focusing on main lines of treatment including current medications, supportive care, lung transplantation evaluation, and potential future strategies of treatment.

• future management
• ipf
• literature review of disease
• progressive interstitial lung disease
• pulmonary disease

• Aptides
• Cell penetrating peptides
• Lipid nanoparticles
• Pulmonary delivery
• Pulmonary fibrosis
• Signal transducer and activator of transcription 3 (STAT3)

• Pneumothorax
• Prognosis
• Progressive fibrosing interstitial lung disease

• Aspiration
• Gastric emptying
• Gastro-oesophageal reflux
• Oesophageal dysmotility
• Scintigraphy

In patients with chronic pulmonary microaspiration (CPM) the recognition of high-resolution computed tomographic (HRCT) findings and their pattern is important.

To investigate the HRCT detections in patients with CPM.

This descriptive study enrolled 100 consecutive patients with CPM underwent HRCT of the lungs between 2017 and 2018 in Tehran and Zahedan Hospitals and private centers. The required variables were recorded for each patient with a questionnaire. Subsequently, HRCT was performed and abnormalities were then reported by two radiologists.

Most of patients exhibited bronchial thickening in 33.6% of cases, followed by ground-glass opacity (12.4%), emphysema (11.1%), and bronchiectasis (8.5%). In addition, the most common HRCT findings were found in left lower lobe (LLL) (37.1%), followed by right lower lobe (RLL) (35.9 %), right upper lobe (RUL) (6,2%), and left upper lobe (LUL) (6%).

Our data showed the most common findings in HRCT were bronchial thickening ground-glass opacity, emphysema, and bronchiectasis, where these findings was dominantly found in LLL, RLL, RUL, and LUL, indicating its high tendency to dependent areas.

• Imaging
• chronic lung microaspiration
• high-resolution computed tomographic

• Bronchiectasis
• Chronic Disease
• Emphysema
• Female
• Humans
• Lung/diagnostic imaging
• Male
• Middle Aged
• Pneumonia, Aspiration/diagnostic imaging
• Retrospective Studies
• Tomography, X-Ray Computed/methods

Idiopathic pulmonary fibrosis (IPF) is characterised by constant threat of acute exacerbation of IPF (AE-IPF). It would be significant to identify risk factors of AE-IPF. We sought to determine the prognostic value of lung transplantation candidacy testing for AE-IPF and describe explant pathology of recipients with and without AE-IPF before lung transplantation.

Retrospective cohort study of 89 IPF patients listed for lung transplantation. Data included pulmonary function testing, echocardiography, right heart catheterisation, imaging, oesophageal pH/manometry and blood tests. Explanted tissue was evaluated by pulmonary pathologists and correlated to computed tomography (CT) findings.

Out of 89 patients with IPF, 52 were transplanted during stable IPF and 37 had AE-IPF before transplantation (n=28) or death (n=9). There were no substantial differences in candidacy testing with and without AE-IPF. AE-IPF had higher rate of decline of forced vital capacity (FVC) (21±22% versus 4.8±14%, p=0.00019). FVC decline of >15% had a hazard ratio of 7.2 for developing AE-IPF compared to FVC decline of <5% (p=0.004). AE-IPF had more secondary diverse histopathology (82% versus 29%, p<0.0001) beyond diffuse alveolar damage. There was no correlation between ground-glass opacities (GGO) on chest CT at any point to development of AE-IPF (p=0.077), but GGO during AE-IPF predicted secondary pathological process beyond diffuse alveolar damage.

Lung transplantation candidacy testing including reflux studies did not predict AE-IPF besides FVC absolute decline. CT did not predict clinical or pathological AE-IPF. Secondary diverse lung pathology beyond diffuse alveolar damage was present in most AE-IPF, but not in stable IPF.

Transplant candidacy testing fails to predict acute exacerbation of IPF besides FVC absolute decline. Patients transplanted during acute exacerbation of IPF reveal multiple secondary lung histopathological processes beyond the expected DAD.https://bit.ly/3e1CPjO

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by interstitial remodeling and pulmonary dysfunction. The etiology of IPF is not completely understood but involves pathologic inflammation and subsequent failure to resolve fibrosis in response to epithelial injury. Treatments for IPF are limited to anti-inflammatory and immunomodulatory agents, which are only partially effective. Prostaglandin E2 (PGE2) disrupts TGFβ signaling and suppresses myofibroblast differentiation, however practical strategies to raise tissue PGE2 during IPF have been limited. We previously described the discovery of a small molecule, (+)SW033291, that binds with high affinity to the PGE2-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and increases PGE2 levels. Here we evaluated pulmonary 15-PGDH expression and activity and tested whether pharmacologic 15-PGDH inhibition (PGDHi) is protective in a mouse model of bleomycin-induced pulmonary fibrosis (PF). Long-term PGDHi was well-tolerated, reduced the severity of pulmonary fibrotic lesions and extracellular matrix remodeling, and improved pulmonary function in bleomycin-treated mice. Moreover, PGDHi attenuated both acute inflammation and weight loss, and decreased mortality. Endothelial cells and macrophages are likely targets as these cell types highly expressed 15-PGDH. In conclusion, PGDHi ameliorates inflammatory pathology and fibrosis in murine PF, and may have clinical utility to treat human disease.

• Esophageal motility
• GERD
• LPR
• Reflux aspiration
• Scintigraphy

• Adult
• Aged
• Data Management
• Esophageal Motility Disorders/complications
• Esophageal Motility Disorders/diagnosis
• Esophageal pH Monitoring/methods
• Esophageal pH Monitoring/statistics & numerical data
• Female
• Gastroesophageal Reflux/diagnosis
• Gastroesophageal Reflux/etiology
• Gastroesophageal Reflux/physiopathology
• Humans
• Laryngopharyngeal Reflux/diagnosis
• Laryngopharyngeal Reflux/etiology
• Male
• Manometry/methods
• Manometry/statistics & numerical data
• Middle Aged
• Predictive Value of Tests
• Prospective Studies
• Radionuclide Imaging/methods
• Radionuclide Imaging/statistics & numerical data
• Respiratory Aspiration/diagnosis
• Respiratory Aspiration/etiology
• Severity of Illness Index