Vnitr Lek. 2022 Fall;68(4):212-215.

ABSTRACT

Idiopathic pulmonary fibrosis and chronic fibrotic interstitial lung disease with progressive phenotype are characterized by fibrotic lung parenchyma. Current antifibrotic treatment does not affect pre-existing lung parenchyma fibrosis, but prevents fibrosis progression and reduces mortality by reducing fibrotization. This work summarizes fibrotic lung processes and their treatment options.

PMID:36220417

Thorax. 2022 Oct 10:thoraxjnl-2021-217703. doi: 10.1136/thorax-2021-217703. Online ahead of print.

ABSTRACT

BACKGROUND: Although genome-wide association studies (GWAS) have identified many genomic regions associated with idiopathic pulmonary fibrosis (IPF), the causal genes and functions remain largely unknown. Many single-cell expression data have become available for IPF, and there is increasing evidence suggesting a shared genetic basis between IPF and other diseases.

METHODS: We conducted integrative analyses to improve the power of GWAS. First, we calculated global and local genetic correlations to identify IPF genetically associated traits and local regions. Then, we prioritised candidate genes contributing to local genetic correlation. Second, we performed transcriptome-wide association analysis (TWAS) of 44 tissues to identify candidate genes whose genetically predicted expression level is associated with IPF. To replicate our findings and investigate the regulatory role of the transcription factors (TF) in identified candidate genes, we first conducted the heritability enrichment analysis in TF binding sites. Then, we examined the enrichment of the TF target genes in cell-type-specific differentially expressed genes (DEGs) identified from single-cell expression data of IPF and healthy lung samples.

FINDINGS: We identified 12 candidate genes across 13 genomic regions using local genetic correlation, including the POT1 locus (p value=0.00041), which contained variants with protective effects on lung cancer but increasing IPF risk. We identified another 13 novel genes using TWAS. Two TFs, MAFK and SMAD2, showed significant enrichment in both partitioned heritability and cell-type-specific DEGs.

INTERPRETATION: Our integrative analysis identified new genes for IPF susceptibility and expanded the understanding of the complex genetic architecture and disease mechanism of IPF.

PMID:36216496 | DOI:10.1136/thorax-2021-217703

Front Nutr. 2022 Sep 23;9:992331. doi: 10.3389/fnut.2022.992331. eCollection 2022.

ABSTRACT

BACKGROUND: Although fatty acid metabolism has been confirmed to be involved in the pathological process of idiopathic pulmonary fibrosis (IPF), systematic analyses on the immune process mediated by fatty acid metabolism-related genes (FAMRGs) in IPF remain lacking.

METHODS: The gene expression data of 315 patients with IPF were obtained from Gene Expression Omnibus database and were divided into the training and verification sets. The core FAMRGs of the training set were identified through weighted gene co-expression network analysis. Then, the fatty acid metabolism-related subtypes in IPF were identified on the basis of k-means unsupervised clustering. The scores of fatty acid metabolism and the expression of the fibrosis biomarkers in different subtypes were compared, and functional enrichment analysis was carried out on the differentially expressed genes between subtypes. A random forest model was used to select important FAMRGs as diagnostic markers for distinguishing between subtypes, and a line chart model was constructed and verified by using other datasets and rat models with different degrees of pulmonary fibrosis. The difference in immune cell infiltration among subtypes was evaluated with CIBERSORT, and the correlation between core diagnostic markers and immune cells were analyzed.

RESULTS: Twenty-four core FAMRGs were differentially expressed between the training set and normal samples, and IPF was divided into two subtypes. Significant differences were observed between the two subtypes in biological processes, such as linoleic acid metabolism, cilium movement, and natural killer (NK) cell activation. The subtype with high fatty acid metabolism had more severe pulmonary fibrosis than the other subtype. A reliable construction line chart model based on six diagnostic markers was constructed, and ABCA3 and CYP24A1 were identified as core diagnostic markers. Significant differences in immune cell infiltration were found between the two subtypes, and ABCA3 and CYP24A1 were closely related to NK cells.

CONCLUSION: Fatty acid metabolism and the immune process that it mediates play an important role in the occurrence and development of IPF. The analysis of the role of FAMRGs in IPF may provide a new potential therapeutic target for IPF.

PMID:36211517 | PMC:PMC9537386 | DOI:10.3389/fnut.2022.992331

Front Immunol. 2022 Sep 20;13:997138. doi: 10.3389/fimmu.2022.997138. eCollection 2022.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal fibrotic pulmonary disease with unknow etiology. Owing to lack of reliable prognostic biomarkers and effective treatment measures, patients with IPF usually exhibit poor prognosis. The aim of this study is to establish a risk score prognostic model for predicting the prognosis of patients with IPF based on autophagy-related genes.

METHODS: The GSE70866 dataset was obtained from the gene expression omnibus (GEO) database. The autophagy-related genes were collected from the Molecular Signatures Database (MSigDB). Gene enrichment analysis for differentially expressed genes (DEGs) was performed to explore the function of DEGs. Univariate, least absolute shrinkage and selection operator (LASSO), as well as multivariate Cox regression analyses were conducted to identify a multi-gene prognostic model. Receiver operating characteristic (ROC) curve was applied to assess the prediction accuracy of the model. The expression of genes screened from the prognostic model was validated in clinical samples and human lung fibroblasts by qPCR and western blot assays.

RESULTS: Among the 514 autophagy-related genes, a total of 165 genes were identified as DEGs. These DEGs were enriched in autophagy-related processes and pathways. Based on the univariate, LASSO, and multivariate Cox regression analyses, two genes (MET and SH3BP4) were included for establishing the risk score prognostic model. According to the median value of the risk score, patients with IPF were stratified into high-risk and low-risk groups. Patients in high-risk group had shorter overall survival (OS) than low-risk group in both training and test cohorts. Multivariate regression analysis indicated that prognostic model can act as an independent prognostic indicator for IPF. ROC curve analysis confirmed the reliable predictive value of prognostic model. In the validation experiments, upregulated MET expression and downregulated SH3BP4 expression were observed in IPF lung tissues and TGF-β1-activated human lung fibroblasts, which is consistent with results from microarray data analysis.

CONCLUSION: These findings indicated that the risk score prognostic model based on two autophagy-related genes can effectively predict the prognosis of patients with IPF.

PMID:36211385 | PMC:PMC9533718 | DOI:10.3389/fimmu.2022.997138

Chest. 2022 Oct;162(4):734-735. doi: 10.1016/j.chest.2022.04.152.

NO ABSTRACT

PMID:36210098 | DOI:10.1016/j.chest.2022.04.152

Zhonghua Jie He He Hu Xi Za Zhi. 2022 Oct 12;45(10):1022-1030. doi: 10.3760/cma.j.cn112147-20220208-00097.

ABSTRACT

Objective: To explore the clinical features, laboratory examination and imaging features of microscopic polyangiitis (MPA)-associated interstitial lung disease (ILD), and to perform survival analysis. Methods: The records of 28 patients with MPA-ILD who were treated at the Affiliated Hospital of Medical School of Ningbo University were reviewed retrospectively from August 2014 to November 2021. The patients' clinical features, laboratory parameters, pulmonary function test, echocardiography, chest CT scan findings and therapeutic regimen were analyzed, and the relevant data were statistically analyzed. Results: There were 18 males and 10 females, with an average age of (70.1±9.3) years. Among them, 13 patients had a history of smoking. The main clinical manifestations were cough (14/28), fever (12/28), chest tightness, shortness of breath (12/28) and hemoptysis (3/28). Sixteen patients had renal involvement, and 78.57% (22/28) and 89.28% (25/28) of the patients had elevated C-reactive protein (CRP) and ESR respectively. Sixteen (16/28) patients had increased rheumatoid factor (RF), and the positive rate of myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) was 82.12% (23/28). 96.43% (27/28) of ILDs were diagnosed before or at the same time as MPA. The chest radiological pattern was mainly usual interstitial pneumonia (UIP) or UIP-like (15/28), followed by nonspecific interstitial pneumonia (NSIP) (8/28). Compared with non-UIP-like patients, UIP or UIP-like patients were older (P=0.018), and had higher serum LDH level (P=0.041), but serum creatinine level was significantly lower (P=0.041). Univariate and multivariate survival analysis showed that inappropriate treatment (HR=9.81, 95%CI: 1.68-57.29, P=0.011) and elevated serum LDH (HR=4.11, 95%CI: 0.99-17.00, P=0.051) were independent risk factors for shortened survival of MPA-ILD, while elevated RF (HR=0.22, 95%CI: 0.06-0.91, P=0.037) was a protective factor for prolonged survival. Conclusions: MPA-ILD patients had fewer systemic vasculitis symptoms. Most of the ILD patients were diagnosed before or at the same time as MPA. The chest radiological pattern was mainly UIP or UIP-like, followed by NSIP. Early use of glucocorticoids combined with immunosuppressant or rituximab could improve the survival rate of MPA-ILD. The elevated serum LDH was an independent risk factor for shortened survival of MPA-ILD, while elevated RF was a protective factor for prolonged survival.

PMID:36207959 | DOI:10.3760/cma.j.cn112147-20220208-00097

Chron Respir Dis. 2022 Jan-Dec;19:14799731221133389. doi: 10.1177/14799731221133389.

ABSTRACT

OBJECTIVE: We aimed to explore the safety and diagnostic value of medical thoracoscopic lung biopsy in patients with unexplained diffuse interstitial lung disease (ILD) in a single center pilot study.

METHOD: We retrospectively analyzed clinical and pathological diagnostic data from 52 patients with diffuse ILD undergoing medical thoracoscopic lung biopsy.

RESULTS: Forty-four cases of diffuse ILD were confirmed pathologically, giving a diagnostic rate of 84.6%. Among these 44 patients, 11 patients were diagnosed with cancer, including eight patients with lung adenocarcinoma, three patients with metastases; two from a gastrointestinal malignancy, and one from a granulosa cell tumor of the ovary. There were 17 cases of idiopathic interstitial pneumonia, including nine cases of usual interstitial pneumonia (UIP), four cases of non-specific interstitial pneumonia (NSIP), three cases of cryptogenic organizing pneumonia (COP), and one case of acute interstitial pneumonia (AIP). There were 12 cases of rare interstitial pneumonias, which included six cases of pulmonary alveolar proteinosis, one case each of pulmonary Langerhans cell histiocytosis (LCH) and pulmonary lymphangiomyomatosis, two cases of nodular sarcoidosis, and two cases of chronic eosinophilic pneumonia. We recorded various complications, including bleeding, infection, and pneumothorax. A total of 28 patients (53.8%) experienced at least one of the above complications, but there were no deaths associated with biopsy.

CONCLUSIONS: Medical thoracoscopic lung biopsy appears a safe and effective method for diagnosing diffuse ILD of unknown cause but further prospective studies, with larger numbers, including comparison with other established techniques are required.

PMID:36206158 | PMC:PMC9549086 | DOI:10.1177/14799731221133389

Lancet Respir Med. 2022 Oct 4:S2213-2600(22)00228-4. doi: 10.1016/S2213-2600(22)00228-4. Online ahead of print.

ABSTRACT

The widespread use of smartphones and the internet has enabled self-monitoring and more hybrid-care models. The COVID-19 pandemic has further accelerated remote monitoring, including in the heterogenous and often vulnerable group of patients with interstitial lung diseases (ILDs). Home monitoring in ILD has the potential to improve access to specialist care, reduce the burden on health-care systems, improve quality of life for patients, identify acute and chronic disease worsening, guide treatment decisions, and simplify clinical trials. Home spirometry has been used in ILD for several years and studies with other devices (such as pulse oximeters, activity trackers, and cough monitors) have emerged. At the same time, challenges have surfaced, including technical, analytical, and implementational issues. In this Series paper, we provide an overview of experiences with home monitoring in ILD, address the challenges and limitations for both care and research, and provide future perspectives. VIDEO ABSTRACT.

PMID:36206780 | DOI:10.1016/S2213-2600(22)00228-4

Front Cardiovasc Med. 2022 Sep 20;9:751499. doi: 10.3389/fcvm.2022.751499. eCollection 2022.

ABSTRACT

Pirfenidone is a small drug with marked antifibrotic activity approved for the treatment of Idiopathic pulmonary fibrosis. Recently, its peculiar pharmacological profile has attracted attention for its potential therapeutic benefit for extra-pulmonary disorders characterized by pathological fibrosis, such as kidney, liver, and cardiac failure. A major pitfall of pirfenidone is the lack of consistent understanding of its mechanism of action, regardless of the target. In addition to the increasing attention to the role of inflammation and its mediators in several processes, a better knowledge of the variety of fibroblasts' population, of signals controlling their activation and trans-differentiation, and of crosstalk with other cell resident and non-resident cell types is needed for prevention, treatment and possibly reverse of fibrosis. This review will focus on pirfenidone's pharmacological profile and its effects on cardiac fibroblasts.

PMID:36204580 | PMC:PMC9530045 | DOI:10.3389/fcvm.2022.751499

Radiol Clin North Am. 2022 Nov;60(6):925-939. doi: 10.1016/j.rcl.2022.06.005. Epub 2022 Sep 3.

ABSTRACT

Acute lung injury (ALI) exists on a continuum that includes diffuse alveolar damage, acute fibrinous and organizing pneumonia, and organizing pneumonia. The primary site of injury in ALI is the same, which likely explains similar imaging patterns across the pathologic spectrum. Radiologic outcomes in ALI depend on the degree of injury and the subsequent healing response. Although ALI can heal without permanent injury, development of fibrosis is not uncommon and may be debilitating. ALI is associated with the usual interstitial pneumonia and nonspecific interstitial pneumonia patterns of fibrosis and repeated episodes of ALI are likely a cause of fibrosis progression.

PMID:36202479 | DOI:10.1016/j.rcl.2022.06.005

Sci Rep. 2022 Oct 6;12(1):16702. doi: 10.1038/s41598-022-20683-w.

ABSTRACT

The clinical implication of using serum tumor markers in patients with interstitial lung disease (ILD) is inconclusive. In this retrospective study, we analyzed the data of 1176 subjects (294 with ILDs and 882 healthy controls). Eligible patients were who had at least one or more available tumor marker results [carbohydrate antigen (CA) 19-9, CA 125, and carcinoembryonic antigen (CEA)] with no evidence of malignancies or other benign diseases that could be related to the increasing concentration of the values. The healthy controls selected from a health screening program were also screened for the presence of active cancer, and matched at a ratio of 1:3 with age and sex. The proportion of patients with abnormal values in the ILD group (121, idiopathic pulmonary fibrosis (IPF); 173, non-IPF-ILDs) was higher than in the matched control group (CEA, 21.5% vs. 5.5%; CA 19-9, 27.9% vs. 4.0%; CA 125, 36.4% vs. 2.0%). In the multivariable analysis, higher CEA levels were associated with shorter survival after adjusting for age, sex, lung function, and ILD subtypes (hazard ratio: 2.323, 95% confidence interval: 1.271-4.248, P = 0.006). In subgroup analysis, CEA remained a prognostic factor in patients with non-IPF-ILDs, but not in those with IPF.

PMID:36202924 | DOI:10.1038/s41598-022-20683-w

Radiol Clin North Am. 2022 Nov;60(6):993-1002. doi: 10.1016/j.rcl.2022.06.010. Epub 2022 Sep 3.

ABSTRACT

Interstitial lung disease (ILD) including idiopathic pulmonary fibrosis increases the risk of developing lung cancer. Diagnosing and staging lung cancer in patients with ILD is challenging and requires careful interpretation of computed tomography (CT) and fluorodeoxyglucose PET/CT to distinguish nodules from areas of fibrosis. Minimally invasive tissue sampling is preferred but may be technically challenging given tumor location, coexistent fibrosis, and pneumothorax risk. Current treatment options include surgery, radiation therapy, percutaneous thermal ablation, and systemic therapy; however, ILD increases the risks associated with each treatment option, especially acute ILD exacerbation.

PMID:36202484 | DOI:10.1016/j.rcl.2022.06.010

Radiol Clin North Am. 2022 Nov;60(6):873-888. doi: 10.1016/j.rcl.2022.06.012. Epub 2022 Aug 29.

ABSTRACT

The major role of imaging (CT) in usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) is in the initial diagnosis. We propose several modifications to existing guidelines to help improve the accuracy of this diagnosis and to enhance interobserver agreement. CT detects the common complications and associations that occur with UIP/IPF including acute exacerbation, lung cancer, and dendriform pulmonary ossification and is useful in informing prognosis based on baseline fibrosis severity. Serial CT imaging is a topic of great interest; it may identify disease progression before FVC decline or clinical change.

PMID:36202475 | DOI:10.1016/j.rcl.2022.06.012

Eur Respir J. 2022 Oct 6:2102269. doi: 10.1183/13993003.02269-2021. Online ahead of print.

ABSTRACT

BACKGROUND: Antifibrotic therapies are available to treat chronic fibrosing interstitial lung diseases (CF-ILDs), including idiopathic pulmonary fibrosis. Early use of these treatments is recommended to slow deterioration of respiratory function and to prevent acute exacerbation. However, identifying patients in the early stages of CF-ILD using chest radiographs (CRs) is challenging. In this study, we developed and tested a deep learning algorithm to detect CF-ILD using CR images.

METHOD: From the image archive of Sapporo Medical University Hospital, 653 CRs from 263 patients with CF-ILDs and 506 from 506 patients without CF-ILD were identified; 921 were used for deep learning and 238 were used for algorithm testing. The algorithm was designed to output a numerical score ranging from 0 to 1, representing the probability of CF-ILD. Using the testing dataset, the algorithm's capability to identify CF-ILD was compared with that of doctors. A second dataset, in which CF-ILD was confirmed using computed tomography images, was used to further evaluate the algorithm's performance.

RESULTS: The area under the curve of the receiver operating characteristic curve, which indicates the algorithm's detection capability, was 0.979. Using a score cutoff of 0.267, the sensitivity and specificity of detection were 0.896 and 1.000, respectively. These data showed that the algorithm's performance was non-inferior to that of doctors, including pulmonologists and radiologists; performance was verified using the second dataset.

CONCLUSIONS: We developed a deep learning algorithm to detect CF-ILDs using CR images. The algorithm's detection capability was non-inferior to that of doctors.

PMID:36202411 | DOI:10.1183/13993003.02269-2021

Intractable Rare Dis Res. 2022 Aug;11(3):96-104. doi: 10.5582/irdr.2022.01093.

ABSTRACT

The current study updated data on the incidence and prevalence of 121 rare diseases listed in China's First List of Rare Diseases to provide rationales and references for the development and promotion of rare-disease-related policies. The National Health Commission of the People's Republic of China issued the Rare Disease Diagnosis and Treatment Guide (2019) (denoted here as China's Rare Disease Diagnosis and Treatment Guide). Then 121 diseases were registered with the national rare disease diagnosis and treatment network. The incidence/prevalence of 121 rare diseases varied from country to country. Data are available for a total of 76 rare diseases (76 of 121 rare diseases, 62.81%) in China, including data on the incidence of 23 rare diseases (19.01%) and data on the prevalence of 66 (54.55%). There are data on the incidence/prevalence of 112 rare diseases (112 of 121 rare diseases, 92.56%) at the global level, including data on the incidence of 86 rare diseases (71.07%) and data on the prevalence of 91 (75.21%). On average, the incidence of progressive muscular dystrophies, hyperphenylalaninemia, citrullinemia, and methylmalonic acidemia is over 1/10,000 in China. The prevalence of coronary artery ectasia, congenital scoliosis, retinitis pigmentosa, severe congenital neutropenia, congenital hyperinsulinemic hypoglycemia, and osteogenesis imperfecta is over 1/10,000 in China. All of these figures are beyond the cut-off of 1/10,000 according to the 2021 definition of rare diseases in China. As registration and investigation of rare diseases continues, the spectrum of rare diseases in some provinces is expanding. Diseases such as idiopathic pulmonary arterial hypertension, hepatolenticular degeneration, hemophilia, amyotrophic lateral sclerosis, idiopathic pulmonary fibrosis, and multiple sclerosis are relatively prevalent in some regions and cities of China. Registration efforts promote the correction of incidence/prevalence data, development of orphan drugs, coverage by medical insurance, and development of clinical and diagnostic pathways.

PMID:36200031 | PMC:PMC9438002 | DOI:10.5582/irdr.2022.01093

Crit Care Res Pract. 2022 Sep 26;2022:9972846. doi: 10.1155/2022/9972846. eCollection 2022.

ABSTRACT

BACKGROUND: Lung fibrosis is a sequela of COVID-19 among patients with severe pneumonia. Idiopathic pulmonary fibrosis and lung fibrosis due to COVID-19 may share many similar features. There are limited data on effects of antifibrotic treatment of infection-related lung fibrosis. This study aimed to evaluate the effect of nintedanib on patients' post-COVID-19 lung fibrosis.

METHODS: A retrospective, matched case-control study was performed on hospitalized patients with COVID-19 pneumonia. Patients who received nintedanib treatment for COVID-19 pulmonary fibrosis (nintedanib group) were compared to patients with standard treatment (control group). The primary outcome was oxygen improvement. The secondary outcomes were chest X-ray improvement, SpO2/FiO2 ratio improvement, mortality rates at 60 days, and adverse events.

RESULTS: A total of 42 patients with COVID-19 pneumonia were included (21 in each group). Mean age was 64.43 ± 14.59 years, and 54.8% were men. At baseline, SpO2/FiO2 ratio before treatment was 200.57 ± 105.77 in the nintedanib group and 326.90 ± 137.10 in the control group (P = 0.002). Oxygen improvement and chest X-ray improvement were found in 71.4% and 71.4% in the nintedanib group and in 66.7% and 66.7% in the control group (P = 0.739). The nintedanib group had more improvement in SpO2/FiO2 ratio than in the control group (144.38 ± 118.05 vs 55.67 ± 75.09, P = 0.006). The 60-day mortality rates of the nintedanib and the control groups were 38.1% vs 23.8%, P = 0.317. Hepatitis and loss of appetite were common adverse events (9.5% and 9.5%), while the incidence of diarrhea was 4.8%.

CONCLUSIONS: Nintedanib as add-on treatment in post-COVID-19 lung fibrosis did not improve oxygenation, chest X-ray findings, or the 60-day mortality. However, this antifibrotic drug improved SpO2/FiO2 ratio in our patients. Further randomized controlled trials are needed to determine the efficacy of nintedanib for treatment of patients with post-COVID-19 lung fibrosis. Trial Registration. This study was registered in TCTR20220426001.

PMID:36199668 | PMC:PMC9529527 | DOI:10.1155/2022/9972846

Egypt J Immunol. 2022 Oct;29(4):25-32.

ABSTRACT

Asthma is a common chronic inflammatory condition with a highly complex genetic predisposition and environmental factors which play an important role in its development. Polymorphism in FOXO3a transcription factor has been linked to a number of inflammatory and respiratory diseases such as bronchiolitis and idiopathic pulmonary fibrosis suggesting that it may be implicated in the pathogenesis of asthma. This study aimed to investigate FOXO3a SNP (rs13217795) association with bronchial asthma and its degree of severity in adult Egyptian population. This case control study included 60 asthmatic patients and 40 apparently healthy controls. Peripheral blood samples were collected from all participants. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The study revealed high frequency of the mutant TT genotype of FOXO3a gene in asthma patients (51.7%) than controls (12.5%) with OR= 7.48 & 95% CI (2.58-21.71) (P˂0.05) and in severe cases (41.9%) compared to mild and moderate cases (25.8% and12.5%, respectively). T allele frequency showed significant statistical association with asthma, OR= 12.40, 95% CI (5.65-27.19) (P˂0.05). However, there was no association between T allele and disease severity. The high frequency of the mutant TT genotype among patients and sever cases may indicates that FOXO3a rs13217795 C>T single nucleotide polymorphism can be considered as a risk factor in development and severity of asthma.

PMID:36197151

Pulm Pharmacol Ther. 2022 Oct 1:102168. doi: 10.1016/j.pupt.2022.102168. Online ahead of print.

ABSTRACT

Pulmonary fibrosis (PF) represents the end stage of a broad range of interstitial lung diseases (ILDs). Statins are among the compounds which have been implicated in drug-induced ILD development. However, recent studies (both in vitro and in vivo) have provided evidence that statins may exert anti-inflammatory and anti-fibrotic effects potentially offering benefits to patients with PF. Several protective molecular mechanisms including the suppression of mevalonic acid pathway, the inhibition of NADPH oxidase activation in macrophages and the inhibition of several profibrotic mediators have been proposed to explain the observed in vivo decrease of the oxidative stress in the lung and the preservation of lung function in patients. Earlier clinical studies relating statins with drug-induced ILD development are contradicted by increasing new data showing the beneficial effects of statins in clinical outcomes in ILD patients who receive statins for concomitant cardiovascular indications. Future research may further elucidate the wide spectrum of pathways of IPF pathogenesis, and genetic heterogeneity, identifying clinically applicable biomarkers and specific endotypes thus recognizing in which patients statins could confer benefit and in which they might cause detrimental effects.

PMID:36195297 | DOI:10.1016/j.pupt.2022.102168

J Control Release. 2022 Sep 30:S0168-3659(22)00649-6. doi: 10.1016/j.jconrel.2022.09.054. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial lung disease in which collagen progressively deposits in the supporting framework of the lungs. The pathological collagen creates a recalcitrant barrier in mesenchyme for drug penetration, thus greatly restricting the therapeutical efficacy. On the other hand, this overloaded collagen is gradually exposed to the bloodstream at fibrotic sites because of the vascular hyperpermeability, thus serving as a potential target. Herein, pathological collagen targeting and penetrating liposomes (DP-CC) were constructed to deliver anti-fibrotic dual drugs including pirfenidone (PFD) and dexamethasone (DEX) deep into injured alveoli. The liposomes were co-decorated with collagen binding peptide (CBP) and collagenase (COL). CBP could help vehicle recognize the pathological collagen and target the fibrotic lungs efficiently because of its high affinity to collagen, and COL assisted in breaking through the collagen barrier and delivering vehicle to the center of injured sites. Then, the released dual drugs developed a synergistic anti-fibrotic effect to repair the damaged epithelium and remodel the extracellular matrix (ECM), thus rebuilding the lung architecture. This study provides a promising strategy to deliver drugs deep into pathological collagen accumulated sites for the enhanced treatment of IPF.

PMID:36191673 | DOI:10.1016/j.jconrel.2022.09.054

Front Rehabil Sci. 2021 Nov 16;2:744102. doi: 10.3389/fresc.2021.744102. eCollection 2021.

ABSTRACT

Interstitial lung diseases (ILDs) comprise a heterogeneous group of disorders (such as idiopathic pulmonary fibrosis, sarcoidosis, asbestosis, and pneumonitis) characterized by lung parenchymal impairment, inflammation, and fibrosis. The shortness of breath (i.e., dyspnea) is a hallmark and disabling symptom of ILDs. Patients with ILDs may also exhibit skeletal muscle dysfunction, oxygen desaturation, abnormal respiratory patterns, pulmonary hypertension, and decreased cardiac function, contributing to exercise intolerance and limitation of day-to-day activities. Pulmonary rehabilitation (PR) including physical exercise is an evidence-based approach to benefit functional capacity, dyspnea, and quality of life in ILD patients. However, despite recent advances and similarities with other lung diseases, the field of PR for patients with ILD requires further evidence. This mini-review aims to explore the exercise-based PR delivered around the world and evidence supporting prescription modes, considering type, intensity, and frequency components, as well as efficacy and safety of exercise training in ILDs. This review will be able to strengthen the rationale for exercise training recommendations as a core component of the PR for ILD patients.

PMID:36188788 | PMC:PMC9397914 | DOI:10.3389/fresc.2021.744102