ERJ Open Res. 2022 May 3;8(2):00082-2022. doi: 10.1183/23120541.00082-2022. eCollection 2022 Apr.

ABSTRACT

Patients with #IPF do not mount appreciable anti-spike antibody responses to two doses of #SARSCoV2 mRNA vaccine compared to the general population. National authorities should prioritise patients with IPF for booster doses. https://bit.ly/3K2KXQ0.

PMID:35509438 | PMC:PMC8990384 | DOI:10.1183/23120541.00082-2022

BMC Pulm Med. 2022 May 4;22(1):176. doi: 10.1186/s12890-022-01972-6.

ABSTRACT

BACKGROUND: Altered metabolic pathways have recently been considered as potential drivers of idiopathic pulmonary fibrosis (IPF) for the study of drug therapeutic targets. However, our understanding of the metabolite profile during IPF formation is lacking.

METHODS: To comprehensively characterize the metabolic disorders of IPF, a mouse IPF model was constructed by intratracheal injection of bleomycin into C57BL/6J male mice, and lung tissues from IPF mice at 7 days, 14 days, and controls were analyzed by pathology, immunohistochemistry, and Western Blots. Meanwhile, serum metabolite detections were conducted in IPF mice using LC-ESI-MS/MS, KEGG metabolic pathway analysis was applied to the differential metabolites, and biomarkers were screened using machine learning algorithms.

RESULTS: We analyzed the levels of 1465 metabolites and found that more than one-third of the metabolites were altered during IPF formation. There were 504 and 565 metabolites that differed between M7 and M14 and controls, respectively, while 201 differential metabolites were found between M7 and M14. In IPF mouse sera, about 80% of differential metabolite expression was downregulated. Lipids accounted for more than 80% of the differential metabolite species with down-regulated expression. The KEGG pathway enrichment analysis of differential metabolites was mainly enriched to pathways such as the metabolism of glycerolipids and glycerophospholipids. Eight metabolites were screened by a machine learning random forest model, and receiver operating characteristic curves (ROC) assessed them as ideal diagnostic tools.

CONCLUSIONS: In conclusion, we have identified disturbances in serum lipid metabolism associated with the formation of pulmonary fibrosis, contributing to the understanding of the pathogenesis of pulmonary fibrosis.

PMID:35509094 | DOI:10.1186/s12890-022-01972-6

Respir Res. 2022 May 4;23(1):112. doi: 10.1186/s12931-022-02002-z.

ABSTRACT

BACKGROUND: HPS-1 is a genetic type of Hermansky-Pudlak syndrome (HPS) with highly penetrant pulmonary fibrosis (HPSPF), a restrictive lung disease that is similar to idiopathic pulmonary fibrosis (IPF). Hps1ep/ep (pale ear) is a naturally occurring HPS-1 mouse model that exhibits high sensitivity to bleomycin-induced pulmonary fibrosis (PF). Traditional methods of administering bleomycin as an intratracheal (IT) route to induce PF in this model often lead to severe acute lung injury and high mortality rates, complicating studies focusing on pathobiological mechanisms or exploration of therapeutic options for HPSPF.

METHODS: To develop a murine model of HPSPF that closely mimics the progression of human pulmonary fibrosis, we investigated the pulmonary effects of systemic delivery of bleomycin in Hps1ep/ep mice using a subcutaneous minipump and compared results to oropharyngeal delivery of bleomycin.

RESULTS: Our study revealed that systemic delivery of bleomycin induced limited, acute inflammation that resolved. The distinct inflammatory phase preceded a slow, gradually progressive fibrogenesis that was shown to be both time-dependent and dose-dependent. The fibrosis phase exhibited characteristics that better resembles human disease with focal regions of fibrosis that were predominantly found in peribronchovascular areas and in subpleural regions; central lung areas contained relatively less fibrosis.

CONCLUSION: This model provides a preclinical tool that will allow researchers to study the mechanism of pulmonary fibrosis in HPS and provide a platform for the development of therapeutics to treat HPSPF. This method can be applied on studies of IPF or other monogenic disorders that lead to pulmonary fibrosis.

PMID:35509004 | DOI:10.1186/s12931-022-02002-z

Sci Rep. 2022 May 4;12(1):7289. doi: 10.1038/s41598-022-10750-7.

ABSTRACT

The new radiological diagnostic criteria for diagnosing idiopathic pulmonary fibrosis (IPF) seek to optimize the indications for surgical lung biopsy (SLB). We applied the new criteria to a retrospective series of patients with interstitial lung disease (ILD) who underwent SLB in order to analyse the correlation between the radiological findings suggestive of another diagnosis (especially mosaic attenuation and its location with respect to fibrotic areas) and the usual interstitial pneumonia (UIP) pathologic diagnosis. Two thoracic radiologists reviewed the HRCT images of 83 patients with ILD and SLB, describing the radiological findings and patterns based on the new criteria. The association of each radiological finding with radiological patterns and histology was analysed. Mosaic attenuation is highly prevalent in both the UIP and non-UIP pathologic diagnosis and with similar frequency (80.0% vs. 78.6%). However, the presence of significant mosaic attenuation (≥ 3 lobes) only in non-fibrotic areas was observed in 60.7% of non-UIP pathologic diagnosis compared to 20.0% in UIP. This finding was associated with other diagnoses different from IPF, mostly connective tissue disease-associated interstitial lung disease (CTD-ILD) and hypersensitivity pneumonitis (HP). In our series of pathologically confirmed ILD, mosaic attenuation in non-fibrotic areas was a predictor of non-UIP pathologic diagnosis, and was associated with other diagnoses different from UIP, mostly CTD-ILD and HP. If confirmed in larger series, this finding could constitute a valuable tool for improving the interpretation of radiological.

PMID:35508493 | DOI:10.1038/s41598-022-10750-7

Cell Death Dis. 2022 May 4;13(5):435. doi: 10.1038/s41419-022-04886-7.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) was considered as a telomere-mediated disease. TERT and TERC correlated with telomere length. Although telomerase gene mutations were associated with IPF, majority patients did not carry mutations. The mechanism by which telomerase expression was regulated in IPF are still unclear. In this study, we aimed to delineate the mechanisms that how TERT protein expression were regulated in alveolar epithelial cells (AECs) in pulmonary fibrosis. Here, we found that P16, P21 and fibrosis markers (αSMA and Collagen-I) were prominently increased in lung tissues of IPF patients and bleomycin-induced mouse models, while the expression of KLF4 and TERT were decreased in AECs. In vivo experiments, AAV-6 vectors mediated KLF4 over-expression with specific SP-C promoter was constructed. Over-expression of KLF4 in AECs could protect TERT expression and suppress the development of pulmonary fibrosis in bleomycin-induced mouse models. In the mechanism exploration of TERT regulation, KLF4 and TERT were both down-regulated in bleomycin-induced senescent MLE-12 and BEAS-2B cells. Compared with control group, small-interfering RNA targeting KLF4 significantly reduced the TERT expression and telomerase activity, while overexpression of KLF4 can increased the expression of TERT and telomerase activity in senescent AECs. Furthermore, ChIP showed that KLF4 protein could bind to the TERT promoter region in MLE-12 cells, suggesting that KLF4 could implicate in pathogenesis of lung fibrosis through regulating TERT transcription in AECs. Taken together, this study identified that KLF4 might be a promising potential target for further understanding the mechanism and developing novel strategy for the treatment of lung fibrosis in IPF.

PMID:35508454 | DOI:10.1038/s41419-022-04886-7

Am J Physiol Cell Physiol. 2022 May 4. doi: 10.1152/ajpcell.00073.2022. Online ahead of print.

ABSTRACT

Idiopathic lung fibrosis (IPF) is a fatal disease that primarily affects the elderly. Up to date, the specific pathophysiology of IPF remains unknown. However, it is theorized to be caused by chronic repetitive injuries to the alveolar epithelium, eventually exhausting the stem cell capacity and activating pathological pathways. Heat shock proteins (HSPs), a category of stress response proteins, are also suggested to contribute to IPF pathophysiology. Furthermore, HSPs are key components in the regulation of cell homeostasis and act as chaperones for a multitude of new proteins. This review thoroughly evaluates the roles that specific HSPs, HSP90, HSP70, and HSP47, have in the fibrotic process. A close look into the roles of these HSPs in IPF pathophysiology will give valuable insight into the future of IPF treatment and prevention.

PMID:35508189 | DOI:10.1152/ajpcell.00073.2022

BMJ Case Rep. 2022 May 3;15(5):e250362. doi: 10.1136/bcr-2022-250362.

NO ABSTRACT

PMID:35504667 | DOI:10.1136/bcr-2022-250362

Int Immunopharmacol. 2022 Apr 30;109:108805. doi: 10.1016/j.intimp.2022.108805. Online ahead of print.

ABSTRACT

Pulmonary vascular endothelial dysfunction is a key pathogenic mechanism in acute respiratory distress syndrome (ARDS), resulting in fibrosis in lung tissues, including in the context of COVID-19. Pirfenidone (PFD) has become a novel therapeutic agent for treating idiopathic pulmonary fibrosis (IPF) and can improve lung function, inhibit fibrosis and inhibit inflammation. Recently, endothelial-to-mesenchymal transition (EndMT) was shown to play a crucial role in various respiratory diseases. However, the role of PFD in the course of EndMT in LPS-induced ARDS remains poorly understood. The purpose of this study was to explore the anti-EndMT effects of PFD on pulmonary fibrosis after LPS-induced ARDS. First, we determined that PFD significantly reduced LPS-induced ARDS, as shown by significant pathological alterations, and alleviated the oxidative stress and inflammatory response in vitro and in vivo. Furthermore, PFD decreased pulmonary fibrosis in LPS-induced ARDS by inhibiting EndMT and reduced the expression levels of Hedgehog (HH) pathway target genes, such as Gli1 and α-SMA, after LPS induction. In summary, this study confirmed that inhibiting the HH pathway by PFD could decrease pulmonary fibrosis by downregulating EndMT in LPS-induced ARDS. In conclusion, we demonstrate that PFD is a promising agent to attenuate pulmonary fibrosis following ARDS in the future.

PMID:35504205 | DOI:10.1016/j.intimp.2022.108805

Cytokine. 2022 Apr 30;154:155899. doi: 10.1016/j.cyto.2022.155899. Online ahead of print.

ABSTRACT

Idiopathic inflammatory myositis (IIM) is a group of rare diseases of unknown etiology, with a pathognomonic muscular deficiency. Antisynthetase syndrome is a subtype of IIM with an associated interstitial lung disease (ILD), characterized by pulmonary inflammation and fibrosis mediated by TGF-β. Pirfenidone is a new molecule with anti-inflammatory and anti-fibrotic properties, used for the treatment of idiopathic ILD, but has never been assessed in IIM. The aim of our study is to evaluate the effect of pirfenidone on IIM-associated ILD. Thirty-two BALB/c male mice were divided into three groups: Sham, IIM-untreated (IIM), and IIM pirfenidone-treated (IIM + PIR). IIM was induced by intramuscular injections of guinea pig muscle myosin extract and intraperitoneal injections of Pertussis toxin. Pirfenidone was given orally at a dose of 30 mg kg-1 day-1 for two months. Muscle force, blood and bronchoalveolar lavage fluid samples, as well as muscle and lung tissues, were analyzed. Progressive deterioration of muscle force and infiltration of the muscular tissue by inflammatory cells were observed with IIM. Auto-immune antibodies specific to the antisynthetase syndrome were also increased in IIM mice. Pirfenidone attenuated IIM-associated ILD with anti-inflammatory properties evidenced by decreased peribronchial inflammation and TGF-β1 in bronchoalveolar lavage fluid. Likewise, pirfenidone attenuated pulmonary fibrosis by fine-tuning TGF-β1-mediated epithelial-to-mesenchymal and fibrotic signaling pathways; pro-fibrotic SMAD3, ZEB2 and STAT1 expression and activation were decreased, whereas anti-fibrotic SMAD2 activation was increased. This study unravels for the first time that pirfenidone has the potential to fine-tune TGF-β1 fibrotic signaling in IIM-associated ILD.

PMID:35504143 | DOI:10.1016/j.cyto.2022.155899

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