Am J Respir Crit Care Med. 2022 Jun 30. doi: 10.1164/rccm.202112-2824OC. Online ahead of print.

ABSTRACT

RATIONALE: Treatment options for idiopathic pulmonary fibrosis (IPF) are limited.

OBJECTIVES: To evaluate the efficacy and safety of BG00011, an anti-αvβ6 IgG1 monoclonal antibody, in the treatment of patients with IPF.

METHODS: In a phase IIb randomized, double-blind, placebo-controlled trial, patients with IPF (forced vital capacity [FVC] ≥50% predicted, on or off background therapy) were randomized 1:1 to once-weekly subcutaneous BG00011 56 mg or placebo. Primary endpoint was FVC change from baseline at Week 52. Due to early trial termination (imbalance in adverse events [AEs] and lack of clinical benefit), endpoints were evaluated at Week 26 as an exploratory analysis.

MEASUREMENTS AND MAIN RESULTS: 106 patients were randomized and received ≥1 dose of BG00011 (n = 54) or placebo (n = 52). At Week 26, there was no significant difference in FVC change from baseline (SE) between patients who received BG00011 (n = 20) or placebo (n = 23), -0.056 L (0.0593) vs. -0.097 L (0.0600), respectively; P=0.268. However, after Week 26, patients in the BG00011 group showed a worsening trend. Eight of 18 (44.4%) who received BG00011 and 4 of 22 (18.2%) who received placebo showed worsening of fibrosis on high-resolution computed tomography at end of treatment. IPF exacerbation/or progression was reported in 13 patients (all in the BG00011 group). Serious AEs occurred more frequently in BG00011 patients, including four deaths.

CONCLUSIONS: The results do not support the continued clinical development of BG00011. Further research is warranted to identify new treatment strategies that modify inflammatory and fibrotic pathways in IPF Clinical trial registration available at www.

CLINICALTRIALS: gov, ID: NCT03573505.

PMID:35771569 | DOI:10.1164/rccm.202112-2824OC

Am J Respir Crit Care Med. 2022 Jun 30. doi: 10.1164/rccm.202109-2166OC. Online ahead of print.

ABSTRACT

RATIONALE: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in SARS-CoV-2 infection and disease severity is unclear.

OBJECTIVES: To assess whether rs35705950-T confers differential risk for clinical outcomes associated with COVID-19 infection among participants in the Million Veteran Program (MVP).

METHODS: The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by trans-ancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (BMI, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease and IPF) and associations with post-COVID-19 pneumonia were performed in MVP subjects.

MEASUREMENTS AND MAIN RESULTS: The rs35705950-T allele was associated with fewer COVID-19 hospitalizations (Ncases=4,325/, Ncontrols=507,640; OR=0.89 [0.82-0.97], p=6.86 x 10-03) in trans-ancestry meta-analysis within MVP and joint meta-analyses with the HGI (Ncases=13,320, Ncontrols=1,508,841; OR=0.90 [0.86-0.95], p =8.99 x 10-05). The rs35705950-T allele was not associated reduced COVID-19 positivity in trans-ancestry meta-analysis within MVP (Ncases=19,168/Ncontrols=492,854; OR=0.98 [0.95-1.01], p=0.06) but was nominally significant (p<0.05) in the joint meta-analysis with HGI (Ncases=44,820/Ncontrols=1,775,827; OR=0.97 [0.95-1]; p=0.03). We did not observe associations with severe outcomes or mortality. Among MVP individuals of European ancestry, rs35705950-T was associated with fewer post-COVID-19 pneumonia events (OR=0.82 [0.72-0.93], p=0.001).

CONCLUSIONS: The MUC5B variant rs35705950-T may confer protection in COVID-19 hospitalizations. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

PMID:35771531 | DOI:10.1164/rccm.202109-2166OC

Front Immunol. 2022 Jun 13;13:705472. doi: 10.3389/fimmu.2022.705472. eCollection 2022.

ABSTRACT

Extracellular vesicles (EVs) can regulate the polarization of macrophages in a variety of inflammatory diseases by mediating intercellular signal transduction and affecting the occurrence and development of diseases. After macrophages are regulated by EVs, they mainly show two phenotypes: the proinflammatory M1 type and the anti-inflammatory M2 type. A large number of studies have shown that in diseases such as mastitis, inflammatory bowel disease, Acute lung injury, and idiopathic pulmonary fibrosis, EVs promote the progression of the disease by inducing the M1-like polarization of macrophages. In diseases such as liver injury, asthma, and myocardial infarction, EVs can induce M2-like polarization of macrophages, inhibit the inflammatory response, and reduce the severity of the disease, thus indicating new pathways for treating inflammatory diseases. The EV/macrophage axis has become a potential target for inflammatory disease pathogenesis and comprehensive treatment. This article reviews the structure and function of the EV/macrophage axis and summarizes its biological functions in inflammatory diseases to provide insights for the diagnosis and treatment of inflammatory diseases.

PMID:35769456 | PMC:PMC9234271 | DOI:10.3389/fimmu.2022.705472

Ann Agric Environ Med. 2022 Jun 24;29(2):306-308. doi: 10.26444/aaem/148049. Epub 2022 May 6.

ABSTRACT

INTRODUCTION AND OBJECTIVE: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by iterative inhalation of various environmental agents. The clinical presentation is variable, acute HP commonly presents an inflammatory response, whereas the development and clinical consequences in chronic HP may be similar to IPF (idiopathic pulmonary fibrosis). The aim of the study is to present the latest discoveries regarding the genetic predisposition of HP.

MATERIAL AND METHODS: The appropriate scientific literature was reviewed and analyzed.

RESULTS: Studies have discovered relevant gene polymorphisms in HP, including polymorphisms in the major histocompatibility complex in the metalloproteinases genes. The length of the peripheral blood leukocyte telomere has been investigated and discovered to be important. Recently, the need to study miRNAs in ILD (interstitial lung disease) has been highlighted.

CONCLUSIONS: Exposed HP developed only in some people and a genetic susceptibility significantly increases the risk. Further more current studies on large groups of patients are needed to learn more about the genetic predisposition and risk factors of HP.

PMID:35767769 | DOI:10.26444/aaem/148049

Med Sci (Paris). 2022 Jun-Jul;38(6-7):579-584. doi: 10.1051/medsci/2022084. Epub 2022 Jun 29.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease of unknown origin. It is characterized by aberrant scarring of the alveolar epithelium leading to an accumulation of extracellular matrix (ECM). Fibroblastic foci, consisting of fibroblasts and myofibroblasts, are responsible for the excessive production of ECM. The two therapeutic molecules available on the market to date only allow to slow down the evolution of the disease. In this review, we present the mechanisms involved in the progression of the disease, its treatments and the study models.

PMID:35766856 | DOI:10.1051/medsci/2022084

Compr Physiol. 2022 Jun 29;12(3):3509-3522. doi: 10.1002/cphy.c210026.

ABSTRACT

The lungs are continually subjected to noxious and inert substances, are immunologically active, and are in a constant state of damage and repair. This makes the pulmonary system particularly vulnerable to diseases of aging. Aging can be understood as random molecular damage that is unrepaired and accumulates over time, resulting in cellular defects and tissue dysfunction. The breakdown of cellular mechanisms, including stem cell exhaustion, genomic instability, telomere attrition, epigenetic alteration, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, altered intercellular communication, and changes in the extracellular matrix is thought to advance the aging process itself. Chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and cancers illustrate a pathologic breakdown in these mechanisms beyond normal aging. The immune system becomes less effective with advancing age. There is a low-level state of chronic inflammation termed inflammaging which is thought to be driven by immunosenescence, the changes in the innate and adaptive immune systems with advancing age that lead to dysregulation and decreased effectiveness of the immune system. These processes of aging lead to expected changes in the form and function of the respiratory system, most notably a loss of lung elasticity, decrease in respiratory muscle strength, increase in ventilation-perfusion mismatching, and stiffening of the vasculature. The astute clinician is aware of these expected findings and does not often attribute dyspnea to aging alone. Maintaining a low threshold to investigate for comorbid disease and understanding how pulmonary disease presents differently in the elderly than in younger adults can improve clinical outcomes. © 2022 American Physiological Society. Compr Physiol 12:3509-3522, 2022.

PMID:35766832 | DOI:10.1002/cphy.c210026

Stem Cell Res Ther. 2022 Jun 28;13(1):279. doi: 10.1186/s13287-022-02966-1.

ABSTRACT

BACKGROUND: As a fatal interstitial lung disease, idiopathic pulmonary fibrosis (IPF) was characterized by the insidious proliferation of extracellular matrix (ECM)-producing mesenchymal cells. Recent studies have demonstrated that lung resident mesenchymal/stromal cells (LR-MSC) are the source of myofibroblasts. Endoplasmic reticulum (ER) stress is prominent in IPF lung. This study sought to investigate the effects of ER stress on the behavior of LR-MSC during pulmonary fibrosis.

METHODS: ER stress and myofibroblast differentiation of LR-MSC in patients with IPF were evaluated. Primary mouse LR-MSC was harvested and used in vitro for testing the effects of ER stress and C/EBP homologous protein (CHOP) on LR-MSC. Adoptive transplantation of LR-MSC to bleomycin-induced pulmonary fibrosis was done to test the in vivo behavior of LR-MSC and its influence on pulmonary fibrosis.

RESULTS: We found that myofibroblast differentiation of LR-MSC is associated with ER stress in IPF and bleomycin-induced mouse fibrotic lung. Tunicamycin-induced ER stress impairs the paracrine, migration, and reparative function of mouse LR-MSC to injured type 2 alveolar epithelial cells MLE-12. Overexpression of the ER stress responder C/EBP homologous protein (CHOP) facilitates the TGFβ1-induced myofibroblast transformation of LR-MSC via boosting the TGFβ/SMAD signaling pathway. CHOP knockdown facilitates engraftment and inhibits the myofibroblast transformation of LR-MSC during bleomycin-induced pulmonary fibrosis, thus promoting the efficacy of adopted LR-MSC in alleviating pulmonary fibrosis.

CONCLUSION: Our work revealed a novel role that ER stress involved in pulmonary fibrosis by influencing the fate of LR-MSC and transformed to "crime factor" myofibroblast, during which CHOP acts as the key modulator. These results indicate that pharmacies targeting CHOP or therapies based on CHOP knockdown LR-MSC may be promising ways to treat pulmonary fibrosis.

PMID:35765096 | DOI:10.1186/s13287-022-02966-1

Respirology. 2022 Jun 28. doi: 10.1111/resp.14320. Online ahead of print.

NO ABSTRACT

PMID:35764391 | DOI:10.1111/resp.14320

Curr Opin Gastroenterol. 2022 Jul 1;38(4):411-416. doi: 10.1097/MOG.0000000000000841.

ABSTRACT

PURPOSE OF REVIEW: Idiopathic pulmonary fibrosis (IPF) is a prevalent subset of interstitial lung disease (ILD) that often progresses to require lung transplantation. Gastroesophageal reflux disease (GERD) is common in the IPF population, and GER-related micro-aspiration appears to be an important risk factor for IPF pathogenesis and for the deterioration of transplanted lung function.

RECENT FINDINGS: Many patients with IPF have elevated esophageal acid exposure on reflux testing despite having no or minimal symptoms. Studies on the effects of medical GERD therapy on IPF-related outcomes have had mixed results. Antireflux surgery is safe in appropriately selected IPF patients, and appears to have potential for slowing the decline of lung function. GERD can persist, improve or develop after lung transplantation, and the presence of GERD is associated with allograft injury and pulmonary function decline in lung transplant recipients.

SUMMARY: Clinicians should have a low threshold to assess for objective evidence of GERD in IPF patients. Antireflux surgery in IPF patients with GERD appears to improve lung function, but further studies are needed before surgical treatment can be recommended routinely in this setting. In lung transplant recipients, reflux testing after transplant is the most accurate way to guide GERD treatment decisions.

PMID:35762701 | DOI:10.1097/MOG.0000000000000841

Lancet Respir Med. 2022 Jun 24:S2213-2600(22)00223-5. doi: 10.1016/S2213-2600(22)00223-5. Online ahead of print.

NO ABSTRACT

PMID:35760077 | DOI:10.1016/S2213-2600(22)00223-5

Respir Med. 2022 Jun 21;200:106922. doi: 10.1016/j.rmed.2022.106922. Online ahead of print.

ABSTRACT

BACKGROUND: The use of a transbronchial lung cryobiopsy (TBLC) is increasing as a diagnostic method of interstitial lung diseases (ILD). This study aimed to evaluate risk factors associated with clinically significant complications of TBLC in ILD patients.

METHODS: Patients referred to Kuopio or Tampere university hospitals, in Finland, for a suspected ILD were included. The TBLC was performed in an outpatient setting for 100 patients. Patients were mechanically ventilated in general anesthesia. Fluoroscopy guidance and prophylactic bronchial balloon were used. Complications, such as bleeding, pneumothorax, infections, and mortality were recorded. Moderate or serious bleeding, pneumothorax, or death ≤90 days were defined as clinically significant complications. A multivariable model was created to assess clinically significant complications.

RESULTS: The extent of traction bronchiectasis (Odds ratio [OR] 1.30, Confidence interval [CI] 1.03-1.65, p = 0.027) and young age (OR 7.96, CI 2.32-27.3, p = 0.001) were associated with the risk of clinically significant complications whereas the use of oral corticosteroids ≤30 days before the TBLC (OR 3.65, CI 0.911-14.6, p = 0.068) did not quite reach statistical significance. A history of serious cough was associated with the risk of pneumothorax (OR 4.18, CI 1.10-16.0, p = 0.036). Procedure associated mortality ≤90 days was 1%.

CONCLUSION: The extent of traction bronchiectasis on HRCT and young age were associated with the risk of clinically significant complications whereas oral corticosteroid use did not quite reach statistical significance. A history of serious cough was associated with the risk of clinically significant pneumothorax.

PMID:35759888 | DOI:10.1016/j.rmed.2022.106922

Clin Transl Immunology. 2022 Jun 16;11(6):e1398. doi: 10.1002/cti2.1398. eCollection 2022.

ABSTRACT

OBJECTIVES: The contribution of adaptive vs. innate lymphocytes to IL-17A and IL-22 secretion at the end stage of chronic lung diseases remains largely unexplored. In order to uncover tissue- and disease-specific secretion patterns, we compared production patterns of IL-17A and IL-22 in three different human end-stage lung disease entities.

METHODS: Production of IL-17A, IL-22 and associated cytokines was assessed in supernatants of re-stimulated lymphocytes by multiplex assays and multicolour flow cytometry of conventional T cells, iNKT cells, γδ T cells and innate lymphoid cells in bronchial lymph node and lung tissue from patients with emphysema (n = 19), idiopathic pulmonary fibrosis (n = 14) and cystic fibrosis (n = 23), as well as lung donors (n = 17).

RESULTS: We detected secretion of IL-17A and IL-22 by CD4+ T cells, CD8+ T cells, innate lymphoid cells, γδ T cells and iNKT cells in all end-stage lung disease entities. Our analyses revealed disease-specific contributions of individual lymphocyte subpopulations to cytokine secretion patterns. We furthermore found the high levels of microbial detection in CF samples to associate with a more pronounced IL-17A signature upon antigen-specific and unspecific re-stimulation compared to other disease entities and lung donors.

CONCLUSION: Our results show that both adaptive and innate lymphocyte populations contribute to IL-17A-dependent pathologies in different end-stage lung disease entities, where they establish an IL-17A-rich microenvironment. Microbial colonisation patterns and cytokine secretion upon microbial re-stimulation suggest that pathogens drive IL-17A secretion patterns in end-stage lung disease.

PMID:35757569 | PMC:PMC9202301 | DOI:10.1002/cti2.1398

Comput Intell Neurosci. 2022 Jun 16;2022:5607358. doi: 10.1155/2022/5607358. eCollection 2022.

ABSTRACT

OBJECTIVE: Using data investigation, the microbiology of bacterial infection in patients with pulmonary infection was discussed, and its clinical characteristics were analyzed.

METHODS: The clinical data of 160 patients with pulmonary infection in our hospital from March 2019 to March 2021 were collected and analyzed. Blood samples were collected and cultured, and the pathogens were identified. The distribution, constituent ratio, and drug resistance of pathogens in elderly patients with pulmonary infection were analyzed. Logistics regression analysis was adopted to analyze the risk factors of pulmonary infection.

RESULTS: Of the 160 patients with pulmonary infection, 107 were males (66.88%) and 53 were females (33.13%). The age ranged from 12 to 97 years old, with an average of 63.82 ± 12.64 years old. Sevent-six patients (47.50%) were over 65 years old. Urban patients accounted for 71.88%, and rural patients accounted for 28.13%, of which workers accounted for 46.25%, and farmers and cadres each accounted for about 4%. 85.62% of smokers have smoked for more than 4 years. Eighty-five patients had chronic diseases such as coronary heart disease, hypertension, diabetes, and cerebrovascular disease. Heart failure occurred in 10.00%, old tuberculosis in 11.25%, and new tuberculosis in 5.63%. The average hospital stay of the patients was 14.93 days, and the improvement rate was 91.25%. Eleven patients died. Among the 160 patients with pulmonary infection, COPD, pneumonia, and lung cancer accounted for the highest proportions, and idiopathic pulmonary fibrosis, bronchitis dilatation, tuberculosis, and bronchial asthma also played an important role. Pathogenic bacteria were detected in 104 of the 160 elderly patients with pulmonary infection, and the detection rate was 65.00%. A total of 444 strains of pathogenic bacteria were detected, including 328 strains of Gram-negative bacteria (73.87%, mainly Klebsiella pneumoniae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Serratia marcescens), 28 strains of Gram-positive bacteria (6.30%, mainly Staphylococcus aureus), and 88 strains of fungi (20.00%, mainly Candida albicans). Regarding Klebsiella pneumoniae in elderly patients with pulmonary infection, the drug resistance rates were 59.72% for amoxicillin-clavulanate potassium, 52.78% for ampicillin sodium-sulbactam sodium, and 51.39% for cefazolin sodium. Regarding Pseudomonas aeruginosa, the drug resistance rates were 29.31% for ticarcillin sodium-potassium clavulanate, 27.59% for piperacillin sodium, and 24.14% for gentamicin. Regarding Stenotrophomonas maltophilia, the drug resistance rates were 79.55% for ceftazidime, 38.64% for chloramphenicol, and 31.82% for levofloxacin. Regarding Serratia marcescens, the drug resistance rates from high to low were 74.42% for cefotaxime, 72.09% for moxifloxacin, and 69.77% for gentamicin. Regarding Staphylococcus aureus in elderly patients with pulmonary infection, the drug resistance rates were 100.00% for penicillin, 61.54% for erythromycin, 61.54% for clarithromycin, and 61.54% for azithromycin. Regarding Candida albicans, the drug resistance rates from high to low were 22.41% for caspofungin, 15.52% for itraconazole, and 9.09% for fluconazole. The results of univariate analysis of pulmonary bacterial infection indicated that there were no significant differences in sex and body mass index between nonbacterial infection group and bacterial infection group (P > 0.05). There were significant differences in terms of dust or harmful gas exposure, family member smoking, chronic lung disease history, age, smoking, family cooking, hospital stay, and indwelling catheter (P < 0.05). Exposure to dust or harmful gases, family cooking, age, history of chronic lung disease, indwelling catheter, and length of hospital stay were risk factors for pulmonary bacterial infection (P < 0.05).

CONCLUSION: Gram-negative bacteria are the main pathogens in elderly patients with pulmonary infection. Antibiotics should be administered reasonably according to the results of the drug sensitivity test. Older age, history of chronic lung disease, catheter indwelling, and length of stay are the risk factors for pulmonary bacterial infection.

PMID:35755768 | PMC:PMC9225854 | DOI:10.1155/2022/5607358

Front Med (Lausanne). 2022 Jun 9;9:861076. doi: 10.3389/fmed.2022.861076. eCollection 2022.

ABSTRACT

A timely, confirmed diagnosis of Idiopathic Pulmonary Fibrosis (IPF) has a significant impact on the evolution of the disease. The current model of care in the Lazio region (in Italy) was assessed on the basis of real-world data provided by the four reference centers responsible for diagnosing and treating IPF. The 5-year, population-based, retrospective longitudinal study provided the data that is at the basis of the current proposal for a new clinical and therapeutic pathway (DTCP) and has been shared with regional decision makers. A DTCP must be defined and based on four pillars: GPs, pulmonologists, IPF centers, and telemedicine. Each must play a role within a sort of hub-and-spoke model. IPF centers remain the hubs, while spokes are identified in trained GPs and pulmonologists.

PMID:35755040 | PMC:PMC9228027 | DOI:10.3389/fmed.2022.861076

Front Genet. 2022 Jun 9;13:890530. doi: 10.3389/fgene.2022.890530. eCollection 2022.

ABSTRACT

Background: Idiopathic pulmonary fibrosis (IPF) is the interstitial lung disease with the highest incidence and mortality. The lack of specific markers results in limited treatment methods for IPF patients. Numerous prognostic signatures represented effective indexes in predicting the survival of patients in various diseases; however, little is investigated on their application in IPF. Methods: This study attempted to explore the clinical markers suitable for IPF by constructing a prognostic signature from the perspective of 7-methylguanosine (m7G). An m7G-related prognostic signature (m7GPS) was established based on the discovery cohort with the LASSO algorithm and was verified by internal and external validation cohorts. The area under the curve (AUC) values were utilized to assess the accuracy of m7GPS in predicting the prognosis of IPF patients and the ability of m7GPS in screening IPF patients. Kaplan-Meier curves and Cox regression analyses were used to identify the relationship of m7GPS with the prognosis of IPF individuals. Enrichment analyses, CIBERSORT algorithm, and weighted gene co-expression network analysis were applied to explore the underlying mechanisms and correlation of m7GPS in IPF. Results: The two m7G regulatory genes can divide IPF into subtypes 1 and 2, and subtype 2 demonstrated a poor prognosis for IPF patients (p < 0.05). For the first time in this field, the m7GPS was constructed. m7GPS made it feasible to predict the 1-5 years survival status of IPF patients (AUC = 0.730-0.971), and it was an independent prognostic risk factor for IPF patients (hazard ratio > 1, p < 0.05). The conspicuous ability of m7GPS to screen IPF patients from the healthy was also revealed by an AUC value of 0.960. The roles of m7GPS in IPF may link to inflammation, immune response, and immune cell levels. Seven genes (CYR61, etc.) were identified as hub genes of m7GPS in IPF. Three drugs (ZM447439-1050, AZD1332-1463, and Ribociclib-1632) were considered sensitive to patients with high m7GPS risk scores. Conclusion: This study developed a novel m7GPS, which is a reliable indicator for predicting the survival status of IPF patients and is identified as an effective marker for prognosis and screening of IPF patients.

PMID:35754799 | PMC:PMC9218869 | DOI:10.3389/fgene.2022.890530

Rev Mal Respir. 2022 Jun 22:S0761-8425(22)00035-3. doi: 10.1016/j.rmr.2022.01.014. Online ahead of print.

ABSTRACT

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated.

METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale.

RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis.

CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

PMID:35752506 | DOI:10.1016/j.rmr.2022.01.014

Curr Opin Pulm Med. 2022 Jul 1;28(4):296-302. doi: 10.1097/MCP.0000000000000876.

ABSTRACT

PURPOSE OF REVIEW: Growing evidence suggests that ageing-associated alterations occur in both idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Here, we review the most recent literature on dysregulated ageing pathways in IPF and COPD and discuss how they may contribute to disease pathogenesis.

RECENT FINDINGS: Recent studies have shown that alveolar epithelial type II (ATII) cells undergo premature senescence under stress and that senescent ATII cells promote lung fibrogenesis. Some studies have explored the role of mitochondrial dysfunction in IPF. They have provided evidence that dysfunctional mitochondria are important contributors to fibrogenesis through release of damaged DNA and excessive formation of reactive oxygen species, whereas restoration of mitochondrial homeostasis may attenuate lung fibrosis. Insufficient autophagy has been shown to promote epithelial-to-mesenchymal transition and aberrant epithelial-fibroblast crosstalk, suggesting that autophagy augmentation may represent a potential therapeutic strategy. A number of studies have also explored the role of cellular senescence, mitochondrial homeostasis and autophagy in COPD.

SUMMARY: Several ageing mechanisms are dysregulated in the lungs of patients with IPF and COPD, although how they contribute to disease development and progression remains elusive. Genetic or pharmacologic attenuation of senescence-related pathways and elimination of senescent cells may represent a promising therapeutic strategy.

PMID:35749794 | DOI:10.1097/MCP.0000000000000876

PLoS One. 2022 Jun 24;17(6):e0270297. doi: 10.1371/journal.pone.0270297. eCollection 2022.

ABSTRACT

INTRODUCTION: Inflammatory bowel disease is a relapsing chronic gastrointestinal inflammatory disease. Idiopathic pulmonary fibrosis is a rare but serious extraintestinal pulmonary manifestation of inflammatory bowel disease. However, the relationship between these two conditions is unclear. Therefore, this study aims to elucidate this relationship through a systematic review and meta-analysis, focusing on the risk of idiopathic pulmonary fibrosis in patients with inflammatory bowel disease.

METHODS: The systematic review will be outlined according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols and its extension statement for reporting systematic reviews incorporating network meta-analyses of healthcare interventions: checklist and explanations. Original articles published in any language will be searched in the following databases: PubMed, Web of Science, EMBASE, Google Scholar, and Ovid. Observational studies that reveal an association measure between idiopathic pulmonary fibrosis and inflammatory bowel disease will be included (cross sectional, cohort, and case-control trials). Two independent reviewers will be assigned to evaluate study quality using the Newcastle-Ottawa scale for assessing the quality of non-randomized studies in meta-analyses. Sensitivity analyses will be conducted based on the quality of included studies. All relevant studies will be assessed based on the study type, sample size, inflammatory bowel disease subtype, odds ratio, confidence interval, treatment strategy, and follow-up. The Grading of Recommendations Assessment, Development, and Evaluation approach will be used to rate the quality of the evidence.

DISCUSSION: The results of this meta-analysis may show that patients with inflammatory bowel disease are at higher risk of developing idiopathic pulmonary fibrosis. This study will be the first meta-analysis to focus on the association between inflammatory bowel disease and idiopathic pulmonary fibrosis. Exploring the relationship between the two conditions may further enhance our understanding of the pathogenesis of inflammatory bowel disease and idiopathic pulmonary fibrosis and promote the development of related research fields.

PMID:35749541 | DOI:10.1371/journal.pone.0270297

Front Pharmacol. 2022 Jun 7;13:771031. doi: 10.3389/fphar.2022.771031. eCollection 2022.

ABSTRACT

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by myofibroblast accumulation and extracellular matrix deposition, which lead to irreversible damage of the lung's architecture and the formation of fibrotic lesions. IPF is also a sequela in serious patients with the coronavirus disease 2019 (COVID-19). The molecular mechanisms under pulmonary fibrosis remain unclear, and there is no satisfactory treatment currently available. Piceatannol (PIC) is a naturally occurring resveratrol analog found in a variety of dietary sources such as grapes, passion fruit, and white tea. It has been reported to inhibit liver fibroblast growth and exhibited various antitumor activities, although its role in pulmonary fibrosis has not been established yet. In the present study, we evaluated the anti-fibrotic role of PIC in bleomycin (BLM)-induced pulmonary fibrosis in mice. Methods: Mice with BLM-induced pulmonary fibrosis were treated with PIC, and fibrotic changes were measured by hematoxylin-eosin (H&E) staining and hydroxyproline assay. Luciferase assay, Western blot assay, histological analysis, and immunofluorescence staining were used to evaluate the effect of PIC on fibroblast activation and autophagy in mouse embryonic fibroblast cells (NIH-3T3) and human lung fibroblast cells (HFL1). The anti-fibrotic mechanisms of PIC were either confirmed in vivo. Results: Our results showed that PIC significantly alleviated the bleomycin-induced collagen deposition and myofibroblast accumulation. In vitro and in vivo studies indicated that PIC plays a role in activating autophagy in the process of anti-fibroblast activation. Further mechanism studies demonstrated that PIC can promote autophagy via inhibiting the TGF-β1-Smad3/ERK/P38 signaling pathway, which leads to a decreased number of activated myofibroblasts. Conclusion: Our study demonstrated for the first time that PIC possesses the protective effects against bleomycin-induced pulmonary fibrosis due to the direct pulmonary protective effects which enhance the effect of autophagy in vitro and in vivo and finally leads to the decreased number of activated myofibroblasts. PIC may serve as a candidate compound for pulmonary fibrosis therapy and attenuates the sequelae of SARS-COV-2 pulmonary fibrosis.

PMID:35747752 | PMC:PMC9209743 | DOI:10.3389/fphar.2022.771031

ERJ Open Res. 2022 Jun 20;8(2):00115-2022. doi: 10.1183/23120541.00115-2022. eCollection 2022 Apr.

ABSTRACT

Patients with progressive fibrosing interstitial lung diseases (fILD) have increased morbidity and mortality. Lung fibrosis can be associated with lung cancer. The pathogenesis of both diseases shows similarities, although not all mechanisms are understood. The combination of the diseases is challenging, due to the amplified risk of mortality, and also because lung cancer treatment carries additional risks in patients with underlying lung fibrosis. Acute exacerbations in fILD patients are linked to increased mortality, and the risk of acute exacerbations is increased after lung cancer treatment with surgery, chemotherapy or radiotherapy. Careful selection of treatment modalities is crucial to improve survival while maintaining acceptable quality of life in patients with combined lung cancer and fILD. This overview of epidemiology, pathogenesis, treatment and a possible role for antifibrotic drugs in patients with lung cancer and fILD is the summary of a session presented during the virtual European Respiratory Society Congress in 2021. The review summarises current knowledge and identifies areas of uncertainty. Most current data relate to patients with combined idiopathic pulmonary fibrosis and lung cancer. There is a pressing need for additional prospective studies, required for the formulation of a consensus statement or guideline on the optimal care of patients with lung cancer and fILD.

PMID:35747227 | PMC:PMC9209850 | DOI:10.1183/23120541.00115-2022