Pulmonology. 2022 Apr 12:S2531-0437(22)00084-8. doi: 10.1016/j.pulmoe.2022.04.002. Online ahead of print.

NO ABSTRACT

PMID:35504821 | DOI:10.1016/j.pulmoe.2022.04.002

Respir Investig. 2022 Apr 30:S2212-5345(22)00048-X. doi: 10.1016/j.resinv.2022.04.004. Online ahead of print.

ABSTRACT

The receptor for advanced glycation end product (RAGE) is a transmembrane receptor highly expressed in type 1 pneumocytes of healthy lungs. RAGE is considered to play a homeostatic role in the lung, as RAGE knockout mice develop lung fibrosis as they age. In contrast, RAGE can bind numerous ligands, including high-mobility group box 1 (HMGB1). These interactions initiate pro-inflammatory signaling associated with the pathogenesis of lung injury and interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF). ILD is a broad category of diffuse parenchymal lung disease characterized by various extents of lung fibrosis and inflammation, and IPF is a common and progressive ILD of unknown cause. The prognosis of patients with IPF is poor, and acute exacerbation of IPF (AE-IPF) is one of the main causes of death. Recent reports indicate that acute exacerbations can occur in other ILDs (AE-ILD). Notably, ILD is frequently observed in patients with lung cancer, and AE-ILD after surgical procedures or the initiation of chemotherapy for concomitant lung cancer are clinically important due to their association with increased mortality. In this review, we summarize the associations of RAGE/soluble RAGE (sRAGE)/RAGE ligands with the pathogenesis and clinical course of ILD, including IPF and AE-IPF. Additionally, the potential use of sRAGE and RAGE ligands as predictive markers of AE-IPF and cancer treatment-triggered AE-ILD is also discussed.

PMID:35504814 | DOI:10.1016/j.resinv.2022.04.004

Am J Respir Crit Care Med. 2022 May 3. doi: 10.1164/rccm.202203-0612ED. Online ahead of print.

NO ABSTRACT

PMID:35504013 | DOI:10.1164/rccm.202203-0612ED

Ann Am Thorac Soc. 2022 May 2. doi: 10.1513/AnnalsATS.202102-198OC. Online ahead of print.

ABSTRACT

RATIONALE: In 2018, a systematic review evaluating transbronchial lung cryobiopsy (TBLC) in patients with interstitial lung disease (ILD) was performed to inform American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Asociación Latinoamericana del Tórax (ALAT) clinical practice guidelines on the diagnosis of idiopathic pulmonary fibrosis (IPF).

OBJECTIVE: To perform a new systematic review to inform updated guidelines.

METHODS: Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CCTR) were searched through June 2020. Studies that enrolled patients with ILD and reported the diagnostic yield or complication rates of TBLC were selected for inclusion. Data was extracted and then pooled across studies via meta-analysis. The quality of the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.

RESULTS: Histopathologic diagnostic yield (number of procedures that yielded a histopathologic diagnosis divided by the total number of procedures performed) of TBLC was 80% (95% CI 76-83%) in patients with ILD. TBLC was complicated by bleeding and pneumothorax in 30% (95% CI 20-41%) and 8% (95% CI 6-11%) of patients, respectively. Procedure-related mortality, severe bleeding, prolonged air leak, acute exacerbation, respiratory failure, and respiratory infection were rare. The quality of the evidence was very low due to the uncontrolled study designs, lack of consecutive enrollment, and inconsistent results.

CONCLUSION: Very low-quality evidence indicated that TBLC has a diagnostic yield of approximately 80% in patients with ILD, with manageable complications.

PMID:35499855 | DOI:10.1513/AnnalsATS.202102-198OC

Ann Am Thorac Soc. 2022 May 2. doi: 10.1513/AnnalsATS.202103-343OC. Online ahead of print.

ABSTRACT

Background: To inform an American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guideline, this systematic review evaluated existing interstitial lung disease (ILD) literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic nintedanib. Methods: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using nintedanib to treat patients with PPF. Mortality, disease progression, and adverse event data were extracted, and meta-analyses performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group approach was used to assess the quality of evidence. Results: Two relevant studies were selected. The annual decline in FVC was less in the nintedanib arm in the overall study population [mean difference (MD) 107 milliliters (mL)/year (yr) (95% CI 65.4-148.5 mL/yr)] and in the subgroups with usual interstitial pneumonia (UIP) pattern of pulmonary fibrosis [MD 128.2 mL/yr (95% CI 70.8-185.6 mL/yr)], non-UIP patterns of pulmonary fibrosis [MD 75.3 mL/yr (95% CI 15.5-135.0 mL/yr)], fibrotic connective tissue disease-related ILD [MD 106.2 mL/yr (95% CI 10.6-201.9 mL/yr)], fibrotic idiopathic non-specific interstitial pneumonia [MD 141.7 mL/yr (95% CI 46.0-237.4 mL/yr)], and fibrotic occupational ILD [MD 252.8 mL/yr (95% CI 79.2-426.5 mL/yr)], but not fibrotic hypersensitivity pneumonitis [MD 72.9 mL/yr (95% CI -8.9-154.7 mL/yr)], fibrotic sarcoidosis [MD -20.5 mL/yr (95% CI -337.1-296.1 mL/yr)], or unclassified fibrotic ILD [MD 68.5 mL/yr (95% CI -31.3-168.4 mL/yr)] when compared to placebo. Gastrointestinal (GI) side effects were common. Quality of evidence for the outcomes ranged from very low to moderate GRADE. Conclusions: Nintedanib use in patients with PPF is associated with a statistically significant decrease in disease progression but increase in GI side effects regardless of the radiographic pattern of pulmonary fibrosis. However, limitations in the available evidence lead to low certainty in these effect estimates and make definitive conclusions about the differential effects by subtype of ILD difficult to determine.

PMID:35499854 | DOI:10.1513/AnnalsATS.202103-343OC

Front Pharmacol. 2022 Apr 14;13:836553. doi: 10.3389/fphar.2022.836553. eCollection 2022.

NO ABSTRACT

PMID:35496286 | PMC:PMC9047939 | DOI:10.3389/fphar.2022.836553

Sarcoidosis Vasc Diffuse Lung Dis. 2022;39(1):e2022009. doi: 10.36141/svdld.v39i1.12094. Epub 2022 Mar 31.

ABSTRACT

INTRODUCTION: Investigations of muscle dysfunction in patients with idiopathic pulmonary fibrosis (IPF) are limited to peripheral muscles. However, decreased thoracic muscle mass is known and deterioration of chest wall muscle strength is not clear.

OBJECTIVE: The aims of the present study were to evaluate pectoralis muscle strength located on the chest wall and to investigate the relationship of spirometric measurements and respiratory muscle strength with pectoralis muscle strength.

METHODS: Elderly patient with IPF (mean disease duration 7.47±7.04 years) and the age-and sex-matched healthy volunteers were recruited in this cross-sectional study. The pulmonary function test was performed by a portable spirometer for spirometric variables and a gas analyzer for diffusing capacity for carbon monoxide (DLCO). Maximal inspiratory (MIP) and expiratory pressure (MEP) were measured with mouth pressure device. Modified Medical Research Council Dyspnea Scale (MMRC) was used to determined dyspnea severity. The pectoralis muscle strength was assessed isometrically during shoulder joint horizontal adduction movement with a handheld dynamometer.

RESULTS: A total of 17 patients with IPF (9 males, mean age 69.06±3.94 years) and 19 healthy controls (10 males, mean age 70.95 ±4.99 years) were included. Patients with IPF had lower pectoralis muscle strength than healthy controls (p<0.001). Significant relationships were found between pectoralis muscle strength and MIP (r=0.79, p<0.001), MEP (r=0.81, p<0.001), FEV1% (r=0.54, p=0.02), FVC% (r=0.68, p<0.003) and DLCO (r=0.61, p=0.009). With multiple linear regression analysis, pectoralis muscle strength was the only independent predictor of FVC% (adjusted R2=0.37, p<0.05).

CONCLUSION: In patients with IPF, pectoralis muscle strength decreases and is associated with pulmonary function. In particular pectoralis muscle strength is likely to have an important impact on FVC%. Therefore, we consider that this test should be included routinely in chest diseases and rehabilitation clinics. The trial was registered U.S. National Library of Medicine clinical trial registry (https://clinicaltrials.gov, Trial ID: NCT04803617).

PMID:35494168 | PMC:PMC9007028 | DOI:10.36141/svdld.v39i1.12094

Sarcoidosis Vasc Diffuse Lung Dis. 2022;39(1):e2022006. doi: 10.36141/svdld.v39i1.12269. Epub 2022 Mar 31.

ABSTRACT

INTRODUCTION: The aim of our study is to investigate the etiological distribution of ILD in Turkey by stratifying the epidemiological characteristics of ILD cases, and the direct cost of initial diagnosis of the diagnosed patients.

MATERIAL-METHOD: The study was conducted as a multicenter, prospective, cross-sectional, clinical observation study. Patients over the age of 18 and who accepted to participate to the study were included and evaluated as considered to be ILD. The findings of diagnosis, examination and treatment carried out by the centers in accordance with routine diagnostic procedures were recorded observationally.

RESULTS: In total,1070 patients were included in this study. 567 (53%) of the patients were male and 503 (47%) were female. The most frequently diagnosed disease was IPF (30.5%). Dyspnea (75.9%) was the highest incidence among the presenting symptoms. Physical examination found bibasilar inspiratory crackles in 56.2 % and radiological findings included reticular opacities and interlobular septal thickenings in 55.9 % of the cases. It was observed that clinical and radiological findings were used most frequently (74.9%) as a diagnostic tool. While the most common treatment approaches were the use of systemic steroids and antifibrotic drugs with a rate of 30.7% and 85.6%, respectively. The total median cost from the patient's admission to diagnosis was 540 Turkish Lira.

CONCLUSION: We believe that our findings compared with data from other countries will be useful in showing the current situation of ILD in our country to discuss this problem and making plans for a solution.

PMID:35494165 | PMC:PMC9007027 | DOI:10.36141/svdld.v39i1.12269

Transpl Immunol. 2022 Apr 28:101608. doi: 10.1016/j.trim.2022.101608. Online ahead of print.

ABSTRACT

BACKGROUND: The major obstacle for long-term survival after successful lung transplantation is the development of bronchiolitis obliterans (BO) which is one phenotype of chronic lung allograft dysfunction (CLAD). Nintedanib has beneficial effects treating neoplastic diseases and idiopathic pulmonary fibrosis by blocking tyrosine kinase receptors. These receptors play an important role in alloimmune-mediated proliferative diseases. The aim of this study was to determine the effect of nintedanib on proliferative airway changes after orthotopic trachea transplantation in mice.

METHODS: C57BL/6 mice (H-2b) donor tracheas were orthotopically transplanted into CBA/J mice (H-2k). After transplantation, recipients were daily treated with nintedanib (60 mg/kg; p.o.). Histological and immunofluorescence analysis were performed after 30 days and intragraft gene expression measurements after 14 days of treatment, respectively.

RESULTS: Tracheal allografts from mice treated with nintedanib showed significantly less features of chronic rejection than untreated allografts reflected in a higher epithelium/lamina propria ratio (ELR) [ELR: 0.65 ± 0.13 nintedanib vs. 0.50 ± 0.07 untreated controls; p < 0.05] and a reduced submucosal smooth muscle actin (SMA) content [SMA: 1.26% ± 0.78% nintedanib vs. 2.18% ± 1.01% untreated controls; p < 0.01]. Furthermore, lower T cell, macrophage and dendritic cell infiltration was detected in the nintedanib treated grafts. The protein and intragraft mRNA expression of receptor subtypes was considerably decreased in grafts of nintedanib treated mice. The mRNA expression of relevant immune mediators was affected by nintedanib treatment.

CONCLUSION: Receptor blocking by nintedanib reduced alloimmune-induced inflammation and chronic airway changes in mouse trachea allografts and might be a promising approach to diminish the development of BO in lung transplants.

PMID:35490983 | DOI:10.1016/j.trim.2022.101608

Lung India. 2022 May-Jun;39(3):279-285. doi: 10.4103/lungindia.lungindia_89_22.

ABSTRACT

In coronavirus disease 2019 (COVID-19) patients, dysregulated release of matrix metalloproteinases occurs during the inflammatory phase of acute respiratory distress syndrome (ARDS), resulting in epithelial and endothelial injury with excessive fibroproliferation. COVID-19 resembles idiopathic pulmonary fibrosis (IPF) in several aspects. The fibrotic response in IPF is driven primarily by an abnormally activated alveolar epithelial cells (AECs) which release cytokines to activate fibroblasts. Endoplasmic reticulum (ER) stress is postulated to be one of the early triggers in both diseases. Systemic sclerosis (SSc) is a heterogeneous autoimmune rare connective tissue characterised by fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is a common complication and the leading cause of SSc-related death. Several corollaries have been discussed in this paper for new drug development based on the pathogenic events in these three disorders associated with pulmonary fibrosis. A careful consideration of the similarities and differences in the pathogenic events associated with the development of lung fibrosis in post-COVID patients, IPF patients and patients with SSc-ILD may pave the way for precision medicine. Several questions need to be answered through research, which include the potential role of antifibrotics in managing IPF, SSc-ILD and post-COVID fibrosis. Many trials that are underway will ultimately shed light on their potency and place in therapy.

PMID:35488687 | DOI:10.4103/lungindia.lungindia_89_22

J Thorac Cardiovasc Surg. 2022 Apr 1:S0022-5223(22)00363-4. doi: 10.1016/j.jtcvs.2022.01.055. Online ahead of print.

ABSTRACT

OBJECTIVE: The decision to perform single lung transplants or double lung transplants is usually made before the operation. We have previously reported that a proportion of single lung transplants were unexpectedly performed in the setting of an aborted double lung transplant, and these patients may be at a higher risk of worse short-term outcomes. Long-term outcomes in unplanned single lung transplants remain unknown.

METHODS: We analyzed a single-center database of lung transplants from 2000 to 2020. Single lung transplants were classified into planned and unplanned groups after reviewing operative notes. Root cause analysis was performed for unplanned single lung transplants.

RESULTS: Of the 1326 lung transplants, 1265 (95%) were double lung transplants and 61 (5%) were single lung transplants (22 planned [36%], 39 unplanned [64%]). Underlying indications for transplant were significantly different; planned single lung transplant: chronic obstructive pulmonary disease (55%) and idiopathic pulmonary fibrosis (45%); unplanned single lung transplants: chronic obstructive pulmonary disease (23%), idiopathic pulmonary fibrosis (39%), and bronchiolitis obliterans syndrome (13%). The primary reasons for unplanned single lung transplant were donor-related (3, 7.7%), recipient-related (31, 80%), and donor and recipient-related factors (5, 13%). Unplanned single lung transplants were more likely to require cardiopulmonary bypass during the operation (planned: 4/22, 18% vs unplanned: 20/39, 51%) but had shorter ischemic times (planned: 251 ± 58 minutes vs unplanned: 221 ± 48 minutes). The 5-year overall survival was 53% in the planned and 58% in the unplanned groups, respectively (P = .323). No difference in chronic lung allograft dysfunction-free survival (P = .995) was observed.

CONCLUSIONS: Unplanned single lung transplants in the setting of aborted double lung transplant may be associated with acceptable long-term outcomes.

PMID:35487803 | DOI:10.1016/j.jtcvs.2022.01.055

Differentiation. 2022 Apr 14;125:35-44. doi: 10.1016/j.diff.2022.03.004. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal lung disease that is characterized by enhanced changes in stem cell differentiation and fibroblast proliferation. Lung resident mesenchymal stem cells (LR-MSCs) are important regulators of pathophysiological processes including tissue repair and inflammation, and evidence suggests that this cell population also plays an essential role in fibrosis. Our previous study demonstrated that Wnt/β-catenin signaling is aberrantly activated in the lungs of bleomycin-treated mice and induces myofibroblast differentiation of LR-MSCs. However, the underlying correlation between LR-MSCs and the Wnt/β-catenin signaling remains poorly understood. We found that Wnt8b was highly expressed by LR-MSCs undergoing myofibroblast differentiation. In vitro, Wnt8b promoted LR-MSCs differentiate into myofibroblasts via activating Wnt/β-catenin signaling. Moreover, siRNA-mediated inhibition of Wnt8b prevented Transforming growth factor (TGF)-β1-induced myofibroblast differentiation of LR-MSCs in vitro and ameliorated pulmonary fibrotic lesions. Our study identified Wnt proteins and Wnt/β-catenin signaling in pulmonary fibrosis in vitro and in vivo, and highlighted Wnt8b as a potential therapeutic target in pulmonary fibrosis. Moreover, these finding might provide a new perspective in the development of treatment strategies for IPF.

PMID:35487030 | DOI:10.1016/j.diff.2022.03.004

Ann Am Thorac Soc. 2022 May;19(5):833-844. doi: 10.1513/AnnalsATS.202102-172OC.

ABSTRACT

Rationale: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial pneumonia with impaired survival. Previous guidelines recommend antacid medication to improve respiratory outcomes in patients with IPF. Objectives: This systematic review was undertaken during the development of an American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax guideline. The clinical question was, "Should patients with IPF who have documented abnormal gastroesophageal reflux (GER) with or without symptoms of GER disease 1) be treated with antacid medication or 2) undergo antireflux surgery to improve respiratory outcomes?" Methods: Medline, Embase, the Cochrane Central Register of Controlled Trials, and the gray literature were searched through June 30, 2020. Studies that enrolled patients with IPF and 1) compared antacid medication to placebo or no medication or 2) compared antireflux surgery to no surgery were selected. Meta-analyses were performed when possible. Outcomes included disease progression, mortality, exacerbations, hospitalizations, lung function, respiratory symptoms, GER severity, and adverse effects/complications. Results: For antacid medication, when two studies were aggregated, there was no statistically significant effect on disease progression, defined as a 10% or more decline in FVC, more than 50-m decline in 6-minute walking distance, or death (risk ratio [RR], 0.88; 95% confidence interval [CI], 0.76-1.03). A separate study that could not be included in the meta-analysis found no statistically significant effect on disease progression when defined as a 5% or more decline in FVC or death (RR, 1.10; 95% CI, 1.00-1.21) and an increase in disease progression when defined as a 10% or more decline in FVC or death (RR, 1.28; 95% CI, 1.08-1.51). For antireflux surgery, there was also no statistically significant effect on disease progression (RR, 0.29; 95% CI, 0.06-1.26). Neither antacid medications nor antireflux surgery was associated with improvements in the other outcomes. Conclusions: There is insufficient evidence to conclude that antacid medication or antireflux surgery improves respiratory outcomes in patients with IPF, most of whom had not had abnormal GER confirmed. Well-designed and adequately powered prospective studies with objective evaluation for GER are critical to elucidate the role of antacid medication and antireflux surgery for respiratory outcomes in patients with IPF.

PMID:35486080 | DOI:10.1513/AnnalsATS.202102-172OC

Am J Respir Crit Care Med. 2022 May 1;205(9):e18-e47. doi: 10.1164/rccm.202202-0399ST.

ABSTRACT

Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results: 1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.

PMID:35486072 | DOI:10.1164/rccm.202202-0399ST

PLoS Genet. 2022 Apr 28;18(4):e1010113. doi: 10.1371/journal.pgen.1010113. eCollection 2022 Apr.

ABSTRACT

The study aims to determine the shared genetic architecture between COVID-19 severity with existing medical conditions using electronic health record (EHR) data. We conducted a Phenome-Wide Association Study (PheWAS) of genetic variants associated with critical illness (n = 35) or hospitalization (n = 42) due to severe COVID-19 using genome-wide association summary data from the Host Genetics Initiative. PheWAS analysis was performed using genotype-phenotype data from the Veterans Affairs Million Veteran Program (MVP). Phenotypes were defined by International Classification of Diseases (ICD) codes mapped to clinically relevant groups using published PheWAS methods. Among 658,582 Veterans, variants associated with severe COVID-19 were tested for association across 1,559 phenotypes. Variants at the ABO locus (rs495828, rs505922) associated with the largest number of phenotypes (nrs495828 = 53 and nrs505922 = 59); strongest association with venous embolism, odds ratio (ORrs495828 1.33 (p = 1.32 x 10-199), and thrombosis ORrs505922 1.33, p = 2.2 x10-265. Among 67 respiratory conditions tested, 11 had significant associations including MUC5B locus (rs35705950) with increased risk of idiopathic fibrosing alveolitis OR 2.83, p = 4.12 × 10-191; CRHR1 (rs61667602) associated with reduced risk of pulmonary fibrosis, OR 0.84, p = 2.26× 10-12. The TYK2 locus (rs11085727) associated with reduced risk for autoimmune conditions, e.g., psoriasis OR 0.88, p = 6.48 x10-23, lupus OR 0.84, p = 3.97 x 10-06. PheWAS stratified by ancestry demonstrated differences in genotype-phenotype associations. LMNA (rs581342) associated with neutropenia OR 1.29 p = 4.1 x 10-13 among Veterans of African and Hispanic ancestry but not European. Overall, we observed a shared genetic architecture between COVID-19 severity and conditions related to underlying risk factors for severe and poor COVID-19 outcomes. Differing associations between genotype-phenotype across ancestries may inform heterogenous outcomes observed with COVID-19. Divergent associations between risk for severe COVID-19 with autoimmune inflammatory conditions both respiratory and non-respiratory highlights the shared pathways and fine balance of immune host response and autoimmunity and caution required when considering treatment targets.

PMID:35482673 | DOI:10.1371/journal.pgen.1010113

Clin Rehabil. 2022 Apr 28:2692155221095481. doi: 10.1177/02692155221095481. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of pulmonary rehabilitation for exercise tolerance and quality of life improvement in idiopathic pulmonary fibrosis.

METHODS: We searched PubMed, Cochrane Library, Embase, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Database, and Chongqing VIP for randomized controlled trials that compared pulmonary rehabilitation with usual care for idiopathic pulmonary fibrosis. The risk of bias and certainty of evidence were assessed using Cochrane Collaboration's Risk of Bias tool and the Grading of Recommendations, Assessment, Development and Evaluation criteria.

RESULTS: Eleven trials in total with 549 participants. Compared with usual care, pulmonary rehabilitation significantly increased 6-minute walking distance (mean difference: 35.2m, 95% confidence intervals: 25.4m-44.9m; ten trials; 447 participants; moderate), decreased the St George's Respiratory Questionnaire total scores (mean difference: -9.11, 95% confidence intervals: -10.78 to -7.43; six trials; 303 participants; moderate), and reduced the modified Medical Research Council scores were lower (mean difference: -0.76, 95% confidence intervals: -1.25 to -0.27; three trials; 196 participants; low). Improvements were noted in forced vital capacity percent-predicted (mean difference: 4.88, 95% confidence intervals: 2.67 to 7.10; four trials; 214 participants; moderate) and diffusing capacity for carbon monoxide (mean difference: 4.71, 95% confidence intervals: 0.96 to 8.46; six trials; 358 participants; low).

CONCLUSIONS: Pulmonary rehabilitation may significantly improve exercise tolerance and quality of life in idiopathic pulmonary fibrosis patients, but the quality of evidence was low to moderate. Large sample, multicenter, randomized controlled trials are needed to verify the efficacy and safety of pulmonary rehabilitation.

PMID:35481421 | DOI:10.1177/02692155221095481

Open Med (Wars). 2022 Apr 7;17(1):689-693. doi: 10.1515/med-2022-0466. eCollection 2022.

ABSTRACT

The present report investigates the impact of a Telemedicine Service (TMS) on the management of Idiopathic Pulmonary Fibrosis (IPF) during coronavirus disease of 2019 (COVID-19) outbreak in Italy. The TMS comprised 3 phone numbers, active 12 h per day, and an email address, monitored every 4 h by trained physicians; chat- and videoconference-services were also offered. At the end of the study period, our staff contacted all patients, to get information about the final outcome (i.e. composite hospitalisations/all causes of death). Outcomes were compared with a cohort of patients who attended our unit in the same period of the previous year (when no TMS was available). 189 patients participated in the present study. From 11th March to 4th May 2020, 61% of patients made at least one TMS access, mostly by emails (53%), followed by phone calls (33%). With regard to the primary outcome, TMS patients experienced a significant lower rate of events of the 182 patients of the no-TMS cohort (p < 0.001). Specifically, a significant difference was observed for IPF hospitalisation (p < 0.001) whereas no differences were observed with regard to deaths (p = 0.64). TMS permits patients to be followed up even during COVID-19 lockdown, with an encouraging impact on outcomes.

PMID:35480400 | PMC:PMC8990874 | DOI:10.1515/med-2022-0466

Front Genet. 2022 Apr 11;13:855789. doi: 10.3389/fgene.2022.855789. eCollection 2022.

ABSTRACT

Background: Lung cancer is the most common comorbidity of idiopathic pulmonary fibrosis. Thus there is an urgent need for the research of IPF and carcinogenesis Objective: The objective of this study was to explore hub genes which are common in pulmonary fibrosis and lung cancer progression through bioinformatic analysis. Methods: All the analysis was performed in R software. Differentially expressed genes (DEGs) were explored by comparing gene expression profiles between IPF tissues and healthy lung tissues from GSE24206, GSE53845, GSE101286 and GSE110147 datasets. Venn Diagram analysis was used to identify the overlapping genes, while GO and KEGG pathway enrichment analysis were used to explore the biological functions of the DEGs using clusterprofiler package. Hub genes were identified by analyzing protein-protein interaction networks using Cytoscape software. Nomogram was constructed using the rms package. Tumor immune dysfunction and exclusion (TIDE) and Genomics of Drug Sensitivity in Cancer (GDSC) analysis was used to quantify the immunotherapy and chemotherapy sensitivity of non-small cell lung cancer (NSCLC) patients. Results: COL1A1, COL3A1, MMP1, POSTN1 and TIMP3 were identified as the top five hub genes. The five hub genes were used to construct a diagnostic nomogram that was validated in another IPF dataset. Since the hub genes were also associated with lung cancer progression, we found that the nomogram also had diagnostic value in NSCLC patients. These five genes achieved a statistically difference of overall survival in NSCLC patients (p < 0.05). The expression of the five hub genes was mostly enriched in fibroblasts. Fibroblasts and the hub genes also showed significant ability to predict the susceptibility of NSCLC patients to chemotherapy and immunotherapy. Conclusion: We identified five hub genes as potential biomarkers of IPF and NSCLC progression. This finding may give insight into the underlying molecular mechanisms of IPF and lung cancer progression and provides potential targets for developing new therapeutic agents for IPF patients.

PMID:35480306 | PMC:PMC9038140 | DOI:10.3389/fgene.2022.855789

J Bras Pneumol. 2022 Apr 20;48(2):e20210513. doi: 10.36416/1806-3756/e20210513.

NO ABSTRACT

PMID:35475868 | DOI:10.36416/1806-3756/e20210513

Toxicol Lett. 2022 Apr 23:S0378-4274(22)00086-8. doi: 10.1016/j.toxlet.2022.04.003. Online ahead of print.

ABSTRACT

Transforming growth factor (TGF)-β1-induced fibrotic changes in alveolar epithelium is a critical event in pulmonary fibrosis. Herein, we recognized that lncRNA mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG) was abnormally upregulated within human idiopathic pulmonary fibrosis (IPF) lung tissue, bleomycin (BLM)-caused pulmonary fibrotic model mice and TGF-β1-stimulated mice type II alveolar epithelial cells. In vivo, MIR100HG knockdown attenuated BLM-caused lung fibrogenesis in mice; in vitro, MIR100HG knockdown attenuated TGF-β1-induced fibrotic changes in mice type II alveolar epithelial cells. Through direct binding, MIR100HG knockdown upregulated microRNA-29a-3p (miR-29a-3p) expression; through serving as competing endogenous RNA for miR-29a-3p, MIR100HG knockdown downregulated TGF-beta activated kinase 1/MAP3K7 binding protein 1 (Tab1) expression. Finally, under TGF-β1 stimulation, Tab1 knockdown attenuated TGF-β1-induced fibrotic changes and partially attenuated the effects of miR-29a-3p inhibition. In conclusion, we demonstrated the aberrant upregulation of lncRNA MIR100HG in BLM-caused lung fibrogenesis and TGF-β1-stimulated MLE 12 cells. The MIR100HG/miR-29a-3p/Tab1 axis could modulate TGF-β1-induced fibrotic changes in type II alveolar epithelial cells and, thus, might be promising targets for pulmonary fibrosis therapy.

PMID:35472619 | DOI:10.1016/j.toxlet.2022.04.003