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

Cureus. 2022 Jun 18;14(6):e26072. doi: 10.7759/cureus.26072. eCollection 2022 Jun.

ABSTRACT

Interstitial lung disease (ILD) is a rare disease defined as a specific type of chronic fibrosing interstitial pneumonitis whose effects are limited to the lung. Nonspecific interstitial pneumonia (NSIP) was defined as a histopathological form that can be seen in the presence of large different clinical and radiological features. The exact role of thyroid hormone in the pathogenetic mechanism of idiopathic interstitial pneumonitis (IIP) is unclear. But there is a suggestion that the thyroid hormone plays a role in pulmonary inflammation and fibrosis. In this case report, we described the presentation of NSIP which was associated with Hashimoto thyroiditis.

PMID:35747121 | PMC:PMC9209344 | DOI:10.7759/cureus.26072

Life (Basel). 2022 Jun 14;12(6):887. doi: 10.3390/life12060887.

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a pandemic respiratory disease associated with high morbidity and mortality. Although many patients recover, long-term sequelae after infection have become increasingly recognized and concerning. Among other sequelae, the available data indicate that many patients who recover from COVID-19 could develop fibrotic abnormalities over time. To understand the basic pathophysiology underlying the development of long-term pulmonary fibrosis in COVID-19, as well as the higher mortality rates in patients with pre-existing lung diseases, we compared the transcriptomic fingerprints among patients with COVID-19, idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD) using interactomic analysis. Patients who died of COVID-19 shared some of the molecular biological processes triggered in patients with IPF, such as those related to immune response, airway remodeling, and wound healing, which could explain the radiological images seen in some patients after discharge. However, other aspects of this transcriptomic profile did not resemble the profile associated with irreversible fibrotic processes in IPF. Our mathematical approach instead showed that the molecular processes that were altered in COVID-19 patients more closely resembled those observed in COPD. These data indicate that patients with COPD, who have overcome COVID-19, might experience a faster decline in lung function that will undoubtedly affect global health.

PMID:35743918 | DOI:10.3390/life12060887

Int J Mol Sci. 2022 Jun 14;23(12):6613. doi: 10.3390/ijms23126613.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease with high mortality and unclear etiology. Previous evidence supports that the origin of this disease is associated with epigenetic alterations, age, and environmental factors. IPF initiates with chronic epithelial lung injuries, followed by basal membrane destruction, which promotes the activation of myofibroblasts and excessive synthesis of extracellular matrix (ECM) proteins, as well as epithelial-mesenchymal transition (EMT). Due to miRNAs' role as regulators of apoptosis, proliferation, differentiation, and cell-cell interaction processes, some studies have involved miRNAs in the biogenesis and progression of IPF. In this context, the analysis and discussion of the probable association of miRNAs with the signaling pathways involved in the development of IPF would improve our knowledge of the associated molecular mechanisms, thereby facilitating its evaluation as a therapeutic target for this severe lung disease. In this work, the most recent publications evaluating the role of miRNAs as regulators or activators of signal pathways associated with the pathogenesis of IPF were analyzed. The search in Pubmed was made using the following terms: "miRNAs and idiopathic pulmonary fibrosis (IPF)"; "miRNAs and IPF and signaling pathways (SP)"; and "miRNAs and IPF and SP and IPF pathogenesis". Additionally, we focus mainly on those works where the signaling pathways involved with EMT, fibroblast differentiation, and synthesis of ECM components were assessed. Finally, the importance and significance of miRNAs as potential therapeutic or diagnostic tools for the treatment of IPF are discussed.

PMID:35743055 | DOI:10.3390/ijms23126613

Cells. 2022 Jun 20;11(12):1973. doi: 10.3390/cells11121973.

ABSTRACT

Insulin-like growth factor (IGF) signaling controls the development and growth of many organs, including the lung. Loss of function of Igf1 or its receptor Igf1r impairs lung development and leads to neonatal respiratory distress in mice. Although many components of the IGF signaling pathway have shown to be dysregulated in idiopathic pulmonary fibrosis (IPF), the expression pattern of such components in different cellular compartments of the developing and/or fibrotic lung has been elusive. In this study, we provide a comprehensive transcriptional profile for such signaling components during embryonic lung development in mice, bleomycin-induced pulmonary fibrosis in mice and in human IPF lung explants. During late gestation, we found that Igf1 is upregulated in parallel to Igf1r downregulation in the lung mesenchyme. Lung tissues derived from bleomycin-treated mice and explanted IPF lungs revealed upregulation of IGF1 in parallel to downregulation of IGF1R, in addition to upregulation of several IGF binding proteins (IGFBPs) in lung fibrosis. Finally, treatment of IPF lung fibroblasts with recombinant IGF1 led to myogenic differentiation. Our data serve as a resource for the transcriptional profile of IGF signaling components and warrant further research on the involvement of this pathway in both lung development and pulmonary disease.

PMID:35741102 | DOI:10.3390/cells11121973

Biomolecules. 2022 Jun 13;12(6):823. doi: 10.3390/biom12060823.

ABSTRACT

Reactive oxygen species (ROS) can be beneficial or harmful in health and disease. While low levels of ROS serve as signaling molecules to regulate vascular tone and the growth and proliferation of endothelial cells, elevated levels of ROS contribute to numerous pathologies, such as endothelial dysfunctions, colon cancer, and fibrosis. ROS and their cellular sources have been extensively studied as potential targets for clinical intervention. Whereas various ROS sources are important for different pathologies, four NADPH oxidases (NOX1, NOX2, NOX4, and NOX5) play a prominent role in homeostasis and disease. NOX1-generated ROS have been implicated in hypertension, suggesting that inhibition of NOX1 may be a promising therapeutic approach. NOX2 and NOX4 oxidases are of specific interest due to their role in producing extra- and intracellular hydrogen peroxide (H2O2). NOX4-released hydrogen peroxide activates NOX2, which in turn stimulates the release of mitochondrial ROS resulting in ROS-induced ROS release (RIRR) signaling. Increased ROS production from NOX5 contributes to atherosclerosis. This review aims to summarize recent findings on NOX enzymes and clinical trials inhibiting NADPH oxidases to target pathologies including diabetes, idiopathic pulmonary fibrosis (IPF), and primary biliary cholangitis (PBC).

PMID:35740948 | DOI:10.3390/biom12060823

Biomedicines. 2022 Jun 15;10(6):1423. doi: 10.3390/biomedicines10061423.

ABSTRACT

In the lungs, fibrosis is a growing clinical problem that results in shortness of breath and can end up in respiratory failure. Even though the main fibrotic disease affecting the lung is idiopathic pulmonary fibrosis (IPF), which affects the interstitial space, there are many fibrotic events that have high and dangerous consequences for the lungs. Asthma, chronic obstructive pulmonary disease (COPD), excessive allergies, clearance of infection or COVID-19, all are frequent diseases that show lung fibrosis. In this review, we describe the different kinds of fibrosis and analyse the main types of cells involved-myofibroblasts and other cells, like macrophages-and review the main fibrotic mechanisms. Finally, we analyse present treatments for fibrosis in the lungs and highlight potential targets for anti-fibrotic therapies.

PMID:35740444 | DOI:10.3390/biomedicines10061423

Chest. 2022 Jun 20:S0012-3692(22)01102-3. doi: 10.1016/j.chest.2022.06.013. Online ahead of print.

ABSTRACT

Recent clinical practice guidelines have addressed the diagnosis of idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (fHP). These disease-specific guidelines were developed independently, without clear direction on how to concurrently apply their respective recommendations within a single patient, where discrimination between these two fibrotic interstitial lung diseases represents a frequent diagnostic challenge. The objective of this document, created by an international group of experts, was to suggest a pragmatic approach on how to apply existing guidelines to distinguish IPF and fHP. Key clinical, radiological, and pathological features described in previous guidelines are integrated in a set of diagnostic algorithms, which are then placed in the broader context of multidisciplinary discussion to guide the generation of a consensus diagnosis. While these algorithms necessarily reflect some uncertainty wherever strong evidence is lacking, they provide insight into the current approach favored by experts in the field based on currently available knowledge. The authors further identify priorities for future research to clarify ongoing uncertainties in the diagnosis of fibrotic interstitial lung diseases.

PMID:35738345 | DOI:10.1016/j.chest.2022.06.013

Radiologie (Heidelb). 2022 Jun 23. doi: 10.1007/s00117-022-01025-3. Online ahead of print.

ABSTRACT

CLINICAL ISSUE: Smoking-related interstitial lung diseases are a heterogeneous group of pulmonary abnormalities. The correct diagnosis has prognostic and therapeutic implications. This article introduces the most common smoking-related interstitial lung diseases and describes a structured approach to support the diagnostic workflow.

PRACTICAL RECOMMENDATIONS: Computed tomography is pivotal in the diagnostic workflow of smoking-related interstitial lung diseases and may reduce the number of unnecessary lung biopsies. To achieve high diagnostic accuracy, a standardized scanning protocol, and a structured assessment approach should be utilized. During inflammatory stages of respiratory bronchiolitis (RB), respiratory bronchiolitis interstitial lung diseases (RB-ILD), and desquamative interstitial pneumonia (DIP), cessation of smoking as well as the use of steroids are the treatment of choice. In case of fibrotic changes (e.g., in idiopathic pulmonary fibrosis [IPF]), antifibrotic therapy with nintedanib and pirfenidone may be used. Patients with suspected smoking-related interstitial lung disease should be discussed in interdisciplinary board meetings.

PMID:35736996 | DOI:10.1007/s00117-022-01025-3