Respiration. 2022 Jan 25:1-13. doi: 10.1159/000520657. Online ahead of print.

ABSTRACT

BACKGROUND: Monogenic and polygenic inheritances are evidenced for idiopathic pulmonary fibrosis (IPF). Pathogenic variations in surfactant protein-related genes, telomere-related genes (TRGs), and a single-nucleotide polymorphism in the promoter of MUC5B gene encoding mucin 5B (rs35705950 T risk allele) are reported. This French-Greek collaborative study, Gen-Phen-Re-GreekS in inheritable IPF (iIPF), aimed to investigate genetic components and patients' characteristics in the Greek national IPF cohort with suspected heritability.

PATIENTS AND METHODS: 150 patients with familial PF, personal-family extrapulmonary disease suggesting short telomere syndrome, and/or young age IPF were analyzed.

RESULTS: MUC5B rs35705950 T risk allele was detected in 103 patients (90 heterozygous, 13 homozygous, allelic frequency of 39%), monoallelic TRG pathogenic variations in 19 patients (8 TERT, 5 TERC, 2 RTEL1, 2 PARN, 1 NOP10, and 1 NHP2), and biallelic ABCA3 pathogenic variations in 3. Overlapping MUC5B rs35705950 T risk allele and TRG pathogenic variations were shown in 11 patients (5 TERT, 3 TERC, 1 PARN, 1 NOP10, and 1 NHP2), MUC5B rs35705950 T risk allele, and biallelic ABCA3 pathogenic variations in 2. In 38 patients, neither MUC5B rs35705950 T risk allele nor TRG pathogenic variations were detectable. Kaplan-Meier curves showed differences in time-to-death (p = 0.025) where patients with MUC5B rs35705950 T risk allele alone or in combination with TRG pathogenic variations presented better prognosis.

CONCLUSION: The Gen-Phen-Re-GreekS in iIPF identified multiple and overlapping genetic components including the rarest, underlying disease's genetic "richesse," complexity and heterogeneity. Time-to-death differences may relate to diverse IPF pathogenetic mechanisms implicating "personalized" medical care driven by genotypes in the near future.

PMID:35078193 | DOI:10.1159/000520657

Respiration. 2022 Jan 25:1-8. doi: 10.1159/000521138. Online ahead of print.

ABSTRACT

BACKGROUND: The FIBRONET study was an observational study of patients with idiopathic pulmonary fibrosis (IPF) in Italy.

OBJECTIVES: In this post hoc descriptive analysis, we describe changes in lung function, anxiety/depression, coughing, exacerbations, and adverse events (AEs) in patients receiving nintedanib treatment.

METHODS: Patients with IPF from 20 centers in Italy, aged ≥40 years who received nintedanib for ≥7 months, were followed up for 12 months from study enrollment, attending clinic visits every 3 months. Outcomes included change in forced vital capacity (FVC)% predicted from baseline to 12 months, anxiety/depression measured by the Hospital Anxiety and Depression Scale (HADS), and the proportion of patients with cough, AEs, and exacerbations.

RESULTS: In total, 52 patients received nintedanib (mean duration of 11.6 months). Ten patients had dose reductions from 150 mg to 100 mg twice daily, due to AEs. FVC% predicted was unchanged in the overall nintedanib population (78.7% at baseline; 79.8% at 12 months) and those with a reduced dose (77.7% at baseline; 81.0% at 12 months). HADS score was low at baseline and throughout the study. The proportion of patients with cough decreased from 50.0% to 21.2% over 12 months. Two patients experienced exacerbations, 2 patients discontinued treatment, and 27 (51.9%) reported AEs. The most common AE was diarrhea (34.6%).

CONCLUSIONS: In patients with IPF who received nintedanib in the FIBRONET study, FVC% predicted was stable over 12 months, and the proportion of patients with cough decreased. The safety profile was consistent with the known safety profile for nintedanib in IPF.

PMID:35078170 | DOI:10.1159/000521138

Am J Respir Crit Care Med. 2022 Jan 25. doi: 10.1164/rccm.202110-2244ED. Online ahead of print.

NO ABSTRACT

PMID:35077663 | DOI:10.1164/rccm.202110-2244ED

IEEE Trans Biomed Eng. 2022 Jan 25;PP. doi: 10.1109/TBME.2022.3145688. Online ahead of print.

ABSTRACT

An ability to extract detailed spirometry-like breathing waveforms from wearable sensors promises to greatly improve respiratory health monitoring. Photoplethysmography (PPG) has been researched in depth for estimation of respiration rate, given that it varies with respiration through overall intensity, pulse amplitude and pulse interval. We compare and contrast the extraction of these three respiratory modes from both the ear canal and finger and show a marked improvement in the respiratory power for respiration induced intensity variations and pulse amplitude variations when recording from the ear canal. We next employ a data driven multi-scale method, noise assisted multivariate empirical mode decomposition (NA-MEMD), which allows for simultaneous analysis of all three respiratory modes to extract detailed respiratory waveforms from in-ear PPG. For rigour, we considered in-ear PPG recordings from healthy subjects, both older and young, patients with chronic obstructive pulmonary disorder (COPD) and idiopathic pulmonary fibrosis (IPF) and healthy subjects with artificially obstructed breathing. Specific in-ear PPG waveform changes are observed for COPD, such as a decreased inspiratory duty cycle and an increased inspiratory magnitude, when compared with expiratory magnitude. These differences are used to classify COPD from healthy and IPF waveforms with a sensitivity of 87% and an overall accuracy of 92%. Our findings indicate the promise of in-ear PPG for COPD screening and unobtrusive respiratory monitoring in ambulatory scenarios and in consumer wearables.

PMID:35077352 | DOI:10.1109/TBME.2022.3145688

Ann Am Thorac Soc. 2022 Jan 24. doi: 10.1513/AnnalsATS.202105-589OC. Online ahead of print.

ABSTRACT

RATIONALE: Lung transplantation offers the potential to extend life for patients with idiopathic pulmonary fibrosis (IPF), yet this therapeutic modality is only available to a small proportion of patients.

OBJECTIVE: To identify clinical characteristics and social determinants of health that differentially associate with lung transplant compared with death in patients with IPF.

METHODS: We evaluated data from the IPF-PRO Registry, a multi-center US registry of patients with IPF that was diagnosed or confirmed at the enrolling center in the previous 6 months. Patients were enrolled between June 2014 and October 2018. Patients who were listed for lung transplant were not eligible to enroll in the registry, but patients could be listed for transplant after enrollment. We performed a multivariable time-to-event analysis incorporating competing risks methodology to examine differential associations between pre-specified covariates and the risk of lung transplant versus death. Covariates included factors related to lung transplant eligibility, clinical characteristics of IPF, and social determinants of health. Covariates were modeled as time-independent or time-dependent as appropriate.

RESULTS: Among 955 patients with IPF, event rates of lung transplant and death were 7.4% and 16.3%, respectively, at 2 years. Covariates with the strongest differential association were age, median ZIP code income, and enrollment at a center with a lung transplant program. Lung transplant was less likely (HR 0.13 [95% CI 0.06, 0.28] per 5-year increase) and death more likely (HR 1.41 [95% CI 1.22, 1.64] per 5-year increase) among those aged >70. Higher median ZIP code income was associated with lung transplant (HR 1.22 [95% CI 1.13, 1.31] per $10,000 increase) but not death (HR 0.99 [95% CI 0.94, 1.04] per $10,000 increase). Enrollment at a center with a lung transplant program was associated with lung transplant (HR 4.31 [95% CI 1.76, 10.54]) but not death (HR 0.99 [95% CI 0.69, 1.43]). Oxygen use with activity was associated with both lung transplant and death, but more strongly with lung transplant. A higher number of comorbidities associated with an increased likelihood of death but not lung transplant.

CONCLUSIONS: For patients in the IPF-PRO Registry, median ZIP code income and access to a lung transplant center differentially impact the risk of lung transplantation compared with death, irrespective of disease severity measures or other transplant eligibility factors. Interventions are needed to mitigate inequalities in lung transplantation based on socioeconomic status. Clinical trial registered with ClinicalTrials.gov (NCT01915511).

PMID:35073248 | DOI:10.1513/AnnalsATS.202105-589OC

Am J Respir Cell Mol Biol. 2022 Jan 24. doi: 10.1165/rcmb.2020-0581OC. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis is a chronic, progressive lung disease characterized by fibroproliferative matrix molecule accumulation, collagen deposition, and apoptosis. Activated leukocyte cell-adhesion molecule (ALCAM; CD166) is a cell adhesion molecule that has been implicated in adhesive and migratory attribution including leukocyte homing and trafficking and cancer metastasis. We investigated the role of ALCAM on pulmonary fibrosis development in murine models. Thus, a bleomycin-induced pulmonary fibrosis model was established with wild type and ALCAM-/- mice. Pulmonary fibrosis was also induced in transforming growth factor-β1 (TGF-β1) transgenic mice that conditionally overexpress TGF-β1 upon doxycycline administration. In both models, observed reduced ALCAM levels in lung tissue and bronchoalveolar lavage fluid (BALF) in pulmonary fibrosis-induced wild type mice compared to control mice. We also observed reduced ALCAM expression in the lung tissue of pulmonary fibrosis patients compared to normal lung tissue. ALCAM-/- mice showed an exacerbated lung fibrosis response compared to wild-type mice and this was accompanied by increased cell death. Further investigation for identification of the signaling pathway revealed that PI3K and ERK signaling pathways are involved in bleomycin-induced fibrosis. Collectively, these results highlight that ALCAM contributes to bleomycin-induced pulmonary fibrosis associated with apoptosis through PI3K and ERK signaling pathways in response to TGF-β. Our findings demonstrate the potential of ALCAM as a therapeutic target for IPF and may aid the development of new strategies for the management and treatment of IPF patients.

PMID:35073245 | DOI:10.1165/rcmb.2020-0581OC

Ann Transl Med. 2021 Dec;9(24):1755. doi: 10.21037/atm-21-5404.

ABSTRACT

BACKGROUND: Iron overload has been found in the lungs of patients with idiopathic pulmonary fibrosis (IPF) and is thought to be involved in disease progression; however, the underlying mechanism is complex and not yet fully understood. We sought to assess the in vitro role of iron in the progression of fibrosis in lung epithelial cells, and examine the possible regulation of iron and IPF.

METHODS: Erastin was used to establish a cell model of iron accumulation in mouse lung epithelial cell line 12 (MLE-12). A Cell Counting Kit-8 assay and annexin V staining were applied to measure cell viability and apoptosis, quantitative polymerase chain reaction (qPCR) and quantitative immunoblot analysis of the protein was conducted to analyze the expression of E-cadherin, N-cadherin, α-smooth muscle actin (α-SMA), Vimentin and β-Actin. The autophagy was visualized by microtubule-associated protein 1A/1B-light chain 3 (LC3) staining and western blot.

RESULTS: The results showed that cell proliferation was significantly inhibited and apoptotic and necrotic cells were significantly increased with 2 µM of erastin treatment. Western blotting showed that reactive oxygen species (ROS) production and the level of heme oxygenase-1 were increased in the cells. Epithelial-mesenchymal transition (EMT) represented by the suppression of E-cadherin and the upregulation of α-smooth muscle actin (α-SMA) and Vimentin was induced by erastin. Additionally, autophagy represented by activated LC3B and up-regulated Beclin-1 were also induced by erastin. To further ascertain the role of autophagy in erastin-induced EMT, chloroquine, which is an autophagy inhibitor, was employed, and was found to effectively reduce EMT in this process.

CONCLUSIONS: These results support the role of the enhanced accumulation of iron as a mechanism for increasing the vulnerability of lung epithelial cells to iron-driven oxidant injury that triggers further autophagy during EMT.

PMID:35071449 | PMC:PMC8756254 | DOI:10.21037/atm-21-5404

Front Med (Lausanne). 2022 Jan 6;8:768770. doi: 10.3389/fmed.2021.768770. eCollection 2021.

ABSTRACT

Aim: Whether accelerated aging, reflected by sirtuin 1 (SIRT1) expression, is implicated in bronchiectasis remains largely unknown. We sought to determine the patterns of SIRT1 and other aging markers in systemic circulation and airways and their expression levels associated with bronchiectasis severity and exacerbation. Methods: We enrolled 132 patients with bronchiectasis and 50 healthy subjects in a prospective cohort study to profile aging markers in systemic circulation and recruited 36 patients with bronchiectasis and 32 disease controls (idiopathic pulmonary fibrosis or tumors) in a cross-sectional study to profile aging markers in bronchial epithelium of both large-to-medium and small airways. We profiled aging marker expression from peripheral blood mononuclear cells and enumerated the positively stained cells for detection of aging marker expression in bronchial epithelium. Results: Compared with healthy controls, the relative telomere length (median: 0.88 vs. 0.99, p = 0.009), SIRT1 (median: 0.89 vs. 0.99, p = 0.002), and Ku80 (median: 0.87 vs. 0.96, p < 0.001) expression levels were consistently lower in the peripheral blood mononuclear cells among patients with bronchiectasis and modestly discriminated patients with bronchiectasis from healthy controls. No remarkable changes in SIRT1, telomere length, or Ku70 were identified at onset of exacerbation. Within the bronchial epithelium, the percentage of positively stained cells was lower for SIRT1 (median: 25.1 vs. 57.2%, p < 0.05) and numerically lower for p16 (median: 40.0 vs. 45.1%) and p21 (median: 28.9 vs. 35.9%) in patients with bronchiectasis than in disease controls (p > 0.05). Conclusion: SIRT1 was downregulated in systemic circulation and bronchiectatic airways, which was independent of disease severity and lung function impairment.

PMID:35071262 | PMC:PMC8770945 | DOI:10.3389/fmed.2021.768770

Exp Ther Med. 2022 Feb;23(2):185. doi: 10.3892/etm.2021.11108. Epub 2021 Dec 30.

ABSTRACT

The aim of this overview was to outline the pathophysiology, common comorbidities and current therapeutic modalities in the treatment/management of restless legs syndrome (RLS) a sensorimotor neurological disorder. The main symptom in RLS is a compelling compulsion to move the legs and a sense of restlessness at rest most commonly occurring during the night and improving with movement. The prevalence of secondary RLS among comorbid conditions such as idiopathic pulmonary fibrosis, end-stage renal disease, irritable bowel syndrome and attention deficit/hyperactivity disorder have further elucidated our understanding of the role of the iron-dopamine hypothesis as an etiopathogenetic hallmark in RLS and the efficacy of therapeutic approaches in milder to more severe forms. Currently, RLS treatment uses only symptomatic agents, since a disease-modifying therapy does not yet exist. The phenomena of rebound and augmentation have become central phenomena in overcoming the pharmacotherapeutic challenges when treating with dopaminergic agents in RLS. Considering alternative nonpharmacological therapies, especially for the treatment of RLS in pregnancy has a significant role and positive clinical outcome for patients in controlling symptoms.

PMID:35069866 | PMC:PMC8764906 | DOI:10.3892/etm.2021.11108

Front Genet. 2022 Jan 6;12:788417. doi: 10.3389/fgene.2021.788417. eCollection 2021.

ABSTRACT

Objective: Ferroptosis has an important role in developing pulmonary fibrosis. The present project aimed to identify and validate the potential ferroptosis-related genes in pulmonary fibrosis by bioinformatics analyses and experiments. Methods: First, the pulmonary fibrosis tissue sequencing data were obtained from Gene Expression Omnibus (GEO) and FerrDb databases. Bioinformatics methods were used to analyze the differentially expressed genes (DEGs) between the normal control group and the pulmonary fibrosis group and extract ferroptosis-related DEGs. Hub genes were screened by enrichment analysis, protein-protein interaction (PPI) analysis, and random forest algorithm. Finally, mouse pulmonary fibrosis model was made for performing an exercise intervention and the hub genes' expression was verified through qRT-PCR. Results: 13 up-regulated genes and 7 down-regulated genes were identified as ferroptosis-related DEGs by comparing 103 lung tissues with idiopathic pulmonary fibrosis (IPF) and 103 normal lung tissues. PPI results indicated the interactions among these ferroptosis-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment and Genome-Ontology (GO) enrichment analyses showed that these ferroptosis-related genes involved in the organic anion transport, response to hypoxia, response to decrease oxygen level, HIF-1 signaling pathway, renal cell carcinoma, and arachidonic acid metabolism signaling pathway. The confirmed genes using PPI analysis and random forest algorithm included CAV1, NOS2, GDF15, HNF4A, and CDKN2A. qRT-PCR of the fibrotic lung tissues from the mouse model showed that the mRNA levels of NOS2 and GDF15 were up-regulated, while CAV1 and CDKN2A were down-regulated. Also, treadmill training led to an increased expression of CAV1 and CDKN2A and a decrease in the expression of NOS2 and GDF15. Conclusion: Using bioinformatics analysis, 20 potential genes were identified to be associated with ferroptosis in pulmonary fibrosis. CAV1, NOS2, GDF15, and CDKN2A were demonstrated to be influencing the development of pulmonary fibrosis by regulating ferroptosis. These findings suggested that, as an aerobic exercise treatment, treadmill training reduced ferroptosis in the pulmonary fibrosis tissues, and thus, reduces inflammation in the lungs. Aerobic exercise training initiate concomitantly with induction of pulmonary fibrosis reduces ferroptosis in lung. These results may develop our knowledge about pulmonary fibrosis and may contribute to its treatment.

PMID:35069688 | PMC:PMC8770739 | DOI:10.3389/fgene.2021.788417

Front Immunol. 2022 Jan 5;12:760138. doi: 10.3389/fimmu.2021.760138. eCollection 2021.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a group of chronic interstitial pulmonary diseases characterized by an inexorable decline in lung function with limited treatment options. The abnormal expression of transforming growth factor-β (TGF-β) in profibrotic macrophages is linked to severe pulmonary fibrosis, but the regulation mechanisms of TGF-β expression are incompletely understood. We found that decreased expression of E3 ubiquitin ligase Fbxw7 in peripheral blood mononuclear cells (PBMCs) was significantly related to the severity of pulmonary fibrosis in IPF patients. Fbxw7 is identified to be a crucial suppressing factor for pulmonary fibrosis development and progression in a mouse model induced by intratracheal bleomycin treatment. Myeloid cell-specific Fbxw7 deletion increases pulmonary monocyte-macrophages accumulation in lung tissue, and eventually promotes bleomycin-induced collagen deposition and progressive pulmonary fibrosis. Notably, the expression of TGF-β in profibrotic macrophages was significantly upregulated in myeloid cell-specific Fbxw7 deletion mice after bleomycin treatment. C-Jun has long been regarded as a critical transcription factor of Tgfb1, we clarified that Fbxw7 inhibits the expression of TGF-β in profibrotic macrophages by interacting with c-Jun and mediating its K48-linked ubiquitination and degradation. These findings provide insight into the role of Fbxw7 in the regulation of macrophages during the pathogenesis of pulmonary fibrosis.

PMID:35069531 | PMC:PMC8767095 | DOI:10.3389/fimmu.2021.760138

Front Pharmacol. 2022 Jan 5;12:805535. doi: 10.3389/fphar.2021.805535. eCollection 2021.

ABSTRACT

COVID-19 is a highly contagious respiratory disease, which mainly affects the lungs. Critically ill patients are easily complicated by cytokine storms, acute respiratory distress syndrome (ARDS), and respiratory failure, which seriously threaten their lives. Pulmonary fibrosis (PF) is a common interstitial lung disease, and its pathogenesis may involve the participation of a variety of immune cells and inflammatory factors. Current studies have shown that patients with COVID-19 may be complicated by pulmonary fibrosis, and patients with pulmonary fibrosis may also be at higher risk of contracting COVID-19 than healthy people. Pulmonary fibrosis is an important risk factor leading to the aggravation of COVID-19 disease. COVID-19 complicated by cytokine storm and ARDS mechanism pathways are similar to the pathogenesis of pulmonary fibrosis. The potential interaction between pulmonary fibrosis and COVID-19 can cause acute exacerbation of the patient's condition, but the potential mechanism between the two has not been fully elucidated. Most of the drug treatment programs for COVID-19-related pulmonary fibrosis are currently formulated about the relevant guidelines for idiopathic pulmonary fibrosis (IPF), and there is no clear drug treatment program recommendation. This article aims to summarize the relevant mechanism pathways of COVID-19 and pulmonary fibrosis, explore the interrelationships and possible mechanisms, and discuss the value and risks of existing and potential COVID-19-related pulmonary fibrosis treatment drugs, to provide reference for anti-fibrosis treatment for patients.

PMID:35069217 | PMC:PMC8766975 | DOI:10.3389/fphar.2021.805535

Mol Biol Rep. 2022 Jan 23. doi: 10.1007/s11033-021-07045-x. Online ahead of print.

ABSTRACT

BACKGROUND: Many studies have revealed that microRNA (miRNA) molecules may take part in idiopathic pulmonary fibrosis (IPF). But, the role of miRNAs in the development of IPF is not yet clear.

METHODS: We investigated the plasma levels of miR-21, miR-590, miR-192, and miR-215 in IPF (n = 88) and healthy control (n = 20) groups in this study. We compared the expression levels of target miRNAs in patients with IPF and healthy participants. We grouped the patients with IPF according to age, forced vital capacity, carbon monoxide diffusing capacity (DLCO), gender-Age-pulmonary physiology (GAP) score, the presence of honeycombing and compared the expression levels of target miRNAs in these clinical subgroups.

RESULTS: 82 (93.18%) of the patients with IPF were male and the mean age was 66.6 ± 8.6 years. There was no significant difference between the gender and age distributions of IPF and the control group. The mean plasma miR-21 and miR-590 levels in IPF group were significantly higher than in the control group (p < 0.0001, p < 0.0001, respectively). There was no significant difference between the miR-192 and miR-215 expression levels of the IPF and control group. Both miR-21 and miR-590 correlated positively with age (p = 0.041, p = 0.007, respectively) while miR-192 and miR-215 displayed a negative correlation with age (p = 0.0002, p < 0.0001, respectively). The levels of miR-192 and miR-215 increased as the GAP score decreased. The levels of miR-192 in patients with honeycombing were significantly lower than in those without honeycombing (p = 0.003).

CONCLUSIONS: Our study showed that both miR-21 and miR-590 were overexpressed in IPF. The miR-21 and miR-590 were associated with DLCO, while miR-192 and miR-215 were associated with the GAP score and honeycombing.

PMID:35066768 | DOI:10.1007/s11033-021-07045-x

Lung. 2022 Jan 23. doi: 10.1007/s00408-021-00505-y. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease with a variable clinical course. Biomarkers that predict patient outcomes are needed. We leveraged data from 300 patients in the multicenter IPF-PRO Registry to determine associations between circulating proteins and the composite outcome of respiratory death or lung transplant. Plasma collected at enrollment was analyzed using aptamer-based proteomics (1305 proteins). Over a median follow-up of 30.4 months, there were 76 respiratory deaths and 26 lung transplants. In unadjusted univariable analyses, 61 proteins were significantly associated with the outcome (hazard ratio > 2 or < 0.5, corrected p ≤ 0.05). In multivariable analyses, a set of 4 clinical measures and 47 unique proteins predicted the probability of respiratory death or lung transplant with an optimism-corrected C-index of 0.76. Our results suggest that select circulating proteins strongly associate with the risk of mortality in patients with IPF and confer information independent of clinical measures.

PMID:35066606 | DOI:10.1007/s00408-021-00505-y

Adv Mater. 2022 Jan 22:e2108972. doi: 10.1002/adma.202108972. Online ahead of print.

ABSTRACT

Lung-on-a-chip models hold great promise for disease modeling and drug screening in the past decade. Herein, inspired by the iridescence phenomenon of soap bubbles, we present a novel biomimetic 3D microphysiological lung-on-a-chip system with breathing visuality. The system with an array of pulmonary alveoli at the physiological scale was constructed and coated with structural color materials. Cyclic deformation was induced by regular airflow, resembling the expansion and contraction of the alveoli during the rhythmic breathing. As the deformation were accompanied with corresponding synchronous shifts in the structural colors, the constructed system offered the self-reporting of cell mechanics and enabled real-time monitoring of the cultivation process. Using this system, we have investigated the dynamic relationships between color atlas and disease symptoms, showing the essential role of mechanical stretch in the phenotypes of idiopathic pulmonary fibrosis. These features make this human lung system ideal in biological study, disease monitoring and drug discovery. This article is protected by copyright. All rights reserved.

PMID:35065539 | DOI:10.1002/adma.202108972

Gen Thorac Cardiovasc Surg. 2022 Jan 21. doi: 10.1007/s11748-022-01774-x. Online ahead of print.

ABSTRACT

We report our successful experience in two lung transplant cases in which ex vivo lung perfusion (EVLP) was used to evaluate the function of injured brain-dead donor lungs that were otherwise initially unacceptable. After the donor's lungs were declined for transplantation by all other transplant centers, the lungs were offered to the patients listed for lung transplantation in our hospital. The donor lung function was considered acceptable for transplantation after the 3-h EVLP assessment. In the first case, a 32-year-old man with bronchiolitis obliterans after hematopoietic stem cell transplantation underwent hybrid lung transplantation, that was right brain-dead donor lung transplantation, combined with native-upper lobe sparing living-donor lobar lung transplantation on the left side. In the second case, a 61-year-old woman received the right single lung transplantation for idiopathic pulmonary fibrosis. Both patients are doing well at one and a half years after lung transplantation.

PMID:35064474 | DOI:10.1007/s11748-022-01774-x

Sci Rep. 2022 Jan 21;12(1):1134. doi: 10.1038/s41598-022-05138-6.

ABSTRACT

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is often fatal. A straightforward staging system for AE-IPF would improve prognostication, guide patient management, and facilitate research. The aim of study is to develop a multidimensional prognostic AE-IPF staging system that uses commonly measured clinical variables. This retrospective study analyzed data from 353 consecutive patients with IPF admitted to our hospital during the period from January 2008 through January 2018. Multivariate analysis of information from a database of 103 recorded AE-IPF cases was used to identify factors associated with 3-month mortality. A clinical prediction model for AE-IPF was developed by using these retrospective data. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of this model. Logistic regression analysis showed that PaO2/FiO2 ratio, diffuse HRCT pattern, and serum C-reactive protein (CRP) were significantly associated with 3-month mortality; thus, PaO2/FiO2 ratio < 250 (P), CRP ≥ 5.5 (C), and diffuse HRCT pattern (radiological) (R) were included in the final model. A model using continuous predictors and a simple point-scoring system (PCR index) was developed. For the PCR index, the area under the ROC curve was 0.7686 (P < 0.0001). The sensitivity of the scoring system was 78.6% and specificity was 67.8%. The PCR index identified four severity grades (0, 1, 2, and 3), which were associated with a 3-month mortality of 7.7%, 29.4%, 54.8%, and 80%, respectively. The present PCR models using commonly measured clinical and radiologic variables predicted 3-month mortality in patients with AE-IPF.

PMID:35064161 | DOI:10.1038/s41598-022-05138-6

Eur J Hosp Pharm. 2022 Jan 21:ejhpharm-2021-003202. doi: 10.1136/ejhpharm-2021-003202. Online ahead of print.

NO ABSTRACT

PMID:35064020 | DOI:10.1136/ejhpharm-2021-003202

Intern Emerg Med. 2022 Jan 20. doi: 10.1007/s11739-021-02889-4. Online ahead of print.

ABSTRACT

Extrinsic causes of restrictive lung syndrome in idiopathic pulmonary fibrosis (IPF) patients have been poorly investigated. We aimed to investigate the influence of the anterior chest wall deformity, noninvasively assessed by modified Haller index (MHI), on spirometry parameters and outcome in a consecutive population of patients with mild-to-moderate IPF. Sixty consecutive IPF patients (73.8 ± 6.6 years, 45 males) were included in this retrospective study. All patients underwent physical examination, spirometry, blood tests, conventional transthoracic echocardiography and MHI assessment (chest transverse diameter over the distance between sternum and spine) at basal evaluation. During follow-up, we evaluated the composite endpoint of (1) pulmonary or cardiovascular hospitalizations and (2) all-cause mortality. IPF patients with concave-shaped chest wall (MHI > 2.5) (36.7% of total) and those with normal chest shape (MHI ≤ 2.5) (63.3%) were separately analyzed. In comparison to IPF patients with MHI ≤ 2.5, those with MHI > 2.5: were less likely to be men and smokers; had a more severe restrictive pattern; had significantly smaller cardiac chamber dimensions and significantly higher systolic pulmonary artery pressure (51.9 ± 15.1 vs 42.4 ± 14.3 mmHg, p = 0.02). Mean follow-up time was 2.5 ± 1.4 years. During follow-up, 13 deaths and 16 pulmonary or cardiovascular hospitalizations were detected. At multivariate Cox regression analysis, concave-shaped chest wall (MHI > 2.5) (HR 4.55, 95% CI 1.02-20.4), increased C-reactive protein (HR 1.68, 95% CI 1.08-2.61) and absence of beta-blocker therapy (HR 0.13, 95% CI 0.01-0.26) were independently associated to the investigated outcome. MHI assessment and implementation may help the clinician to identify, among IPF patients, those with poorer prognosis over a medium-term follow-up.

PMID:35059991 | DOI:10.1007/s11739-021-02889-4

Respirol Case Rep. 2022 Jan 12;10(2):e0902. doi: 10.1002/rcr2.902. eCollection 2022 Feb.

ABSTRACT

Treating advanced lung cancer in patients with pulmonary fibrosis can be challenging due to increased risks of drug-induced and radiation-induced pneumonitis. We present the case of a 78-year-old female with stage IIIB lung adenocarcinoma and idiopathic pulmonary fibrosis (IPF). Following partial response to platinum-based chemotherapy, she was started on maintenance pemetrexed, but this was stopped due to bone marrow suppression and kidney injury. She received no further chemotherapy. Nintedanib was subsequently commenced for treatment of IPF. Remarkably, progress imaging at 2 years showed further regression of her lung adenocarcinoma, with stability of IPF. Nintedanib is a multi-target tyrosine kinase inhibitor with anti-cancer effects due to inhibition of angiogenesis. Nintedanib with chemotherapy has shown improvements in survival in non-small cell lung cancer (NSCLC). This case report and literature review discuss the effectiveness of nintedanib in treating patients with concurrent IPF and NSCLC, in particular for patients poorly tolerant of conventional chemotherapy.

PMID:35059200 | PMC:PMC8756078 | DOI:10.1002/rcr2.902