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Background: Childhood interstitial lung disease (chILD) encompasses a group of rare heterogeneous respiratory conditions associated with significant morbidity and mortality. Reports suggest that many patients diagnosed with chILD continue to have potentially progressive or fibrosing disease into adulthood. Over the last decade, the spectrum of conditions within chILD has widened substantially, with the discovery of novel entities through advanced genetic testing. However, most evidence is often limited to small case series, with reports disseminated across an array of subspecialty, clinical and molecular journals. In particular, the frequency, management and outcome of paediatric pulmonary fibrosis is not well characterised, unlike in adults, where clear diagnosis and treatment guidelines are available., Methods and Results: This review assesses the current understanding of pulmonary fibrosis in chILD. Based on registry data, we have provisionally estimated the occurrence of fibrosis in various manifestations of chILD, with 47 different potentially fibrotic chILD entities identified. Published evidence for fibrosis in the spectrum of chILD entities is assessed, and current and future issues in management of pulmonary fibrosis in childhood, continuing into adulthood, are considered., Conclusions: There is a need for improved knowledge of chILD among pulmonologists to optimise the transition of care from paediatric to adult facilities. Updated evidence-based guidelines are needed that incorporate recommendations for the diagnosis and management of immune-mediated disorders, as well as chILD in older children approaching adulthood., Competing Interests: Competing interests: MG reports grants from Boehringer Ingelheim for a register analysis regarding fibrosis, paid to his institution; consulting fees from Boehringer Ingelheim and Roche; speaker fees from Boehringer Ingelheim; payment for participation on an adjudication and on an advisory board from Boehringer Ingelheim; and payment for a leadership role in a board society from Vertex. GK has been a faculty member of a paediatric bronchoscopy course, unrelated to the submitted work. MC, RE and DW have nothing to disclose. GD reports grants from NIH and CZI Atlas, paid to their institution; consulting fees from Boehringer Ingelheim as a consulting pathologist on the InPedILD trial, paid to their institution; and support for attending meetings and/or travel from NIH, paid to their institution. NN reports consulting fees from AstraZeneca, unrelated to the submitted work; support for attending meetings and/or travel for COST action CA16125 and CIG16125; and serving as head of a clinical research collaboration for chILD (unpaid). NS reports grants for participation on an advisory board, an expense allowance, payment for lectures and support for attending meetings and/or travel from Boehringer Ingelheim; serving as president elect of the German Society for Pediatric Pneumology and serving as vice chair of Kinderlungenregister. JW reports personal fees and non-financial support from Boehringer Ingelheim and personal fees from Parexel/Calyx. LRY reports grants from the NIH and University of Pennsylvania, consultancy fees from Roche, Sanofi and Boehringer Ingelheim, and honoraria from NYU Langone Health. RD reports two grants from Boehringer Ingelheim; consulting fees from Boehringer Ingelheim and Roche; licensed patents and stocks for Now Vitals, of which she is a founder, EvoEndoscopy, of which she is a founder and Earable, of which she is a founder; personal fees and non-financial support from Boehringer Ingelheim; and personal fees and other from Earable Inc, Now Vitals and EvoEndoscopy., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Comprehensive care integrates individual patient needs and is highly valued for patients with pulmonary fibrosis (PF). The importance of a patient-centered care approach is rooted in the unpredictable progressiveness of the disease course in PF. The respiratory impairment associated with PF has a major impact on the quality of life for both patients and their caregivers. We believe that prioritizing patient preferences could improve the shared decision making process and may ultimately lead to better health outcomes. Despite the growing emphasis for this approach, it remains challenging to adopt it in clinical practice. In this review, we propose the comprehensive Triple A Care Model, consisting of the domains Access, Anticipate, and Act, which emphasizes core elements of patient-centered care for patients with PF. We will provide an overview of the unmet needs in care for patients with PF and elaborate on the current methods for delivering patient-centered care. The latest insights into symptom management and supportive measures and several approaches to improving access to care are discussed, in line with the most recent guidelines., (© 2024. The Author(s).)

Background: Identification of exposures in patients with interstitial lung diseases (ILDs) is essential for diagnosis and management and can be facilitated through the use of exposure questionnaires. However, for most ILDs, a patient-focused questionnaire is lacking. Cognitive interviewing is a methodology used to evaluate sources of understanding and misunderstanding in a questionnaire and to provide evidence of content validity. We developed and refined a new exposure questionnaire for patients with fibrotic ILDs by using cognitive interviewing to establish its understandability and content validity., Methods: An exposure assessment questionnaire was developed by a multidisciplinary team. Cognitive interviews with 24 patients with fibrosing ILDs were conducted by trained interviewers over the phone or Zoom using a semi-structured interview guide. The questionnaire was amended based on the interviewers' interpretation of sources of misunderstanding. The revised questionnaire was tested in a second round of cognitive interviews with a different group of 24 patients., Results: Among the 48 patients who completed interviews, mean age was 61 years, 58.3% were male and 75.0% were white. Based on the first round of cognitive interviews, the multidisciplinary team modified the questions, organization, and instructions of the questionnaire to facilitate recall, adjust for exposures that were frequently misunderstood or required clarification, and focus on clinically relevant exposures. The revised questionnaire performed well in the second round of interviews., Conclusion: An exposure questionnaire, developed with input from patients, can be used to assess clinically relevant exposures in adults with fibrosing ILDs. This is the first questionnaire for all types of fibrosing ILD to have undergone content validation., (© 2024. The Author(s).)

Background: For patients with interstitial lung diseases (ILDs) presenting with a progressive pulmonary fibrosis (PPF) phenotype, current knowledge of disease characteristics at diagnosis, patient journey, and treatment is limited. This study aimed to describe demographics and clinical experiences of patients presenting with PPF in a European real-world setting., Methods: Data were analysed from the Adelphi Real World PPF-ILD Disease Specific Programme™, a cross-sectional survey of pulmonologists and rheumatologists in five European countries (France, Germany, Italy, Spain, United Kingdom) and internal medicine specialists (France) from April to October 2022. Physicians provided data for up to 12 consecutive patients with physician-confirmed ILD with a progressive phenotype other than idiopathic pulmonary fibrosis. Analyses were descriptive., Results: Overall, 265 physicians reported on 1,335 patients. Mean (standard deviation) age at survey date was 60.4 (11.6) years, 91.2% were white, 58.1% female, 44.0% non-smokers. Most patients (63.3%) first consulted a primary care physician. There was a mean delay of 7.8 (22.7) months between first ILD symptom and healthcare professional visit, and another 7.7 (12.8) months to ILD diagnosis. At survey date, 47.7% of patients had physician-reported moderate ILD, 42.3% had mild ILD and 10.0% had severe ILD. Disease progression was reported in the 12 months prior to the survey for 19.5% of patients; of these, progression was based on worsening symptom in 27.3% and lung function decline in 25.8%. For patients experiencing symptoms prior to ILD diagnosis (72.8%), the most common symptoms were dyspnoea on exertion (80.5%) and cough (57.8%). Overall, 17.4% of patients were misdiagnosed prior to ILD diagnosis, with chronic obstructive pulmonary disease suspected in 39.2% of them. The most frequent comorbidities were anxiety (16.9%) and gastroesophageal reflux (15.5%). Although 77.8% of patients were receiving treatment for ILD at survey date, 15.6% of patients had never been prescribed treatment for ILD., Conclusions: This real-world study expands our understanding of patients, diagnostic delays and treatment gaps experienced by patients diagnosed with PPF in Europe. There was a mean delay of 15.5 months between first ILD symptoms and ILD diagnosis. Given the progressive nature of PPF, diagnostic delay may lead to poor outcomes, including shorter survival., Trial Registration: N/a., (© 2024. The Author(s).)

The term "progressive pulmonary fibrosis" or "PPF" is generally used to describe progressive lung fibrosis in an individual with an interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF). Several sets of criteria have been proposed for the identification of PPF, most of which are based on a combination of a decline in forced vital capacity, worsening of respiratory symptoms, and increase in the extent of fibrosis on radiology. Although some risk factors for faster progression of fibrosing ILD have been identified, it remains challenging to predict which individuals will develop PPF. Close monitoring, including regular pulmonary function tests, is required to detect the earliest signs of worsening disease. PPF is associated with high rates of hospitalization and death. Management of PPF requires a multidisciplinary and multimodal approach, including pharmacological therapy and supportive care. Discussions about palliative care should begin at an early stage, individualized to the needs of the patient.

Background: Fibrotic interstitial lung disease is often identified late due to non-specific symptoms, inadequate access to specialist care, and clinical unawareness precluding proper and timely treatment. Biopsy histological analysis is definitive but rarely performed due to its invasiveness. Diagnosis typically relies on high-resolution computed tomography, while disease progression is evaluated via frequent pulmonary function testing. This study tested the hypothesis that pulmonary fibrosis diagnosis and progression could be non-invasively and accurately evaluated from the hair metabolome, with the longer-term goal to minimize patient discomfort., Methods: Hair specimens collected from pulmonary fibrosis patients (n = 56) and healthy subjects (n = 14) were processed for metabolite extraction using 2DLC/MS-MS, and data were analyzed via machine learning. Metabolomic data were used to train machine learning classification models tuned via a rigorous combination of cross validation, feature selection, and testing with a hold-out dataset to evaluate classifications of diseased vs. healthy subjects and stable vs. progressed disease., Results: Prediction of pulmonary fibrosis vs. healthy achieved AUROC TRAIN  = 0.888 (0.794-0.982) and AUROC TEST  = 0.908, while prediction of stable vs. progressed disease achieved AUROC TRAIN  = 0.833 (0.784 - 0.882) and AUROC TEST  = 0. 799. Top metabolites for diagnosis included ornithine, 4-(methylnitrosamino)-1-3-pyridyl-N-oxide-1-butanol, Thr-Phe, desthiobiotin, and proline. Top metabolites for progression included azelaic acid, Thr-Phe, Ala-Tyr, indoleacetyl glutamic acid, and cytidine., Conclusion: This study provides novel evidence that pulmonary fibrosis diagnosis and progression may in principle be evaluated from the hair metabolome. Longer term, this approach may facilitate non-invasive and accurate detection and monitoring of fibrotic lung diseases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Lung cancer (LC), a paramount global life-threatening condition causing significant mortality, is most commonly characterized by its subtype, lung adenocarcinoma (LUAD). Concomitant with LC, pulmonary fibrosis (PF) and interstitial lung disease (ILD) contribute to an intricate landscape of respiratory diseases. Idiopathic pulmonary fibrosis (IPF) in association with LC has been explored. However, other fibrotic interrelations remain underrepresented, especially for LUAD-PF and LUAD-ILD., Methods: We analysed data with statistical analysis from 7,137 healthy individuals, 7,762 LUAD patients, 7,955 ILD patients, and 2,124 complex PF patients collected over ten years. Furthermore, to identify blood indicators related to lung disease and its complications and compare the relationships between different indicators and lung diseases, we successfully applied the naive Bayes model for a biomarker-based prediction of diagnosis and development into complex PF., Results: Males predominantly marked their presence in all categories, save for complex PF where females took precedence. Biomarkers, specifically AGR, MLR, NLR, and PLR emerged as pivotal in discerning lung diseases. A machine-learning-driven predictive model underscored the efficacy of these markers in early detection and diagnosis, with NLR exhibiting unparalleled accuracy., Conclusions: Our study elucidates the gender disparities in lung diseases and illuminates the profound potential of serum biomarkers, including AGR, MLR, NLR, and PLR in early lung cancer detection. With NLR as a standout, therefore, this study advances the exploration of indicator changes and predictions in patients with pulmonary disease and fibrosis, thereby improving early diagnosis, treatment, survival rate, and patient prognosis., (© 2024. Crown.)

Background: Pulmonary fibrosis can develop after acute respiratory distress syndrome (ARDS). The hypothesis is we are able to measure phenotypes that lie at the origin of ARDS severity and fibrosis development. The aim is an accuracy study of prognostic circulating biomarkers., Methods: A longitudinal study followed COVID-related ARDS patients with medical imaging, pulmonary function tests and biomarker analysis, generating 444 laboratory data. Comparison to controls used non-parametrical statistics; p < 0·05 was considered significant. Cut-offs were obtained through receiver operating curve. Contingency tables revealed predictive values. Odds ratio was calculated through logistic regression., Results: Angiotensin 1-7 beneath 138 pg/mL defined Angiotensin imbalance phenotype. Hyper-inflammatory phenotype showed a composite index test above 34, based on high Angiotensin 1-7, C-Reactive Protein, Ferritin and Transforming Growth Factor-β. Analytical study showed conformity to predefined goals. Clinical performance gave a positive predictive value of 95 % (95 % confidence interval, 82 %-99 %), and a negative predictive value of 100 % (95 % confidence interval, 65 %-100 %). Those severe ARDS phenotypes represented 34 (Odds 95 % confidence interval, 3-355) times higher risk for pulmonary fibrosis development (p < 0·001)., Conclusions: Angiotensin 1-7 composite index is an early and objective predictor of ARDS evolving to pulmonary fibrosis. It may guide therapeutic decisions in targeted phenotypes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. NDV and FC declare International Patent PCT/EP2023/051954 - WIPO WO2023144281A1 (European Patent Office EP22153733.5)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Progressive pulmonary fibrosis (PPF) is a general term for a class of interstitial lung diseases (ILDs) characterized by a progressive fibrosing (PF) phenotype. Patients with PPF have decreased lung function, exercise ability, and quality of life. The purpose of this study was to investigate the clinical characteristics, potential associated factors for disease progression, and survival outcomes of patients in the PPF population., Methods: This study retrospectively reviewed the data of patients diagnosed with ILD between January 2011 and December 2022 at The First Affiliated Hospital of Ningbo University. A PF phenotype was defined based on the criteria that were used in the PPF clinical practice guidelines, which led to the identification of 92 patients with a PF phenotype among the 177 patients with fibrotic ILD. Baseline clinical information and laboratory parameters were collected and analysed in our cohort., Results: Patients in the PPF group had higher tumour marker levels and lower pulmonary function test results at baseline than did those in the non-PPF group. According to the multivariate logistic regression analysis, age >65 years (OR 2.71, 95% CI 1.26-5.89; p  = 0.011), LDH >245 U/L (OR 3.07, 95% CI 1.39-6.78; p  = 0.006), CA-153 > 35 U/mL (OR 3.16, 95% CI 1.25-7.97; p  = 0.015), FVC <60% predicted (OR 4.82, 95% CI 1.60-14.51; p  = 0.005), DLCO <50% predicted (OR 3.21, 95% CI 1.43-7.21; p  = 0.005), and the UIP-like pattern on chest HRCT (OR 3.65, 95% CI 1.33-10.07; p  = 0.012) were potentially associated with the progression of fibrotic interstitial lung diseases (f-ILDs) to PPF. Furthermore, the PPF group had a poorer survival rate than the non-PPF group ( p  = 0.0045). According to the multivariate Cox regression analysis, an SPAP ≥ 37 mmHg (HR 2.33, 95% CI 1.09-5.00; p  = 0.030) and acute exacerbation (HR 2.88, 95% CI 1.26-6.59; p  = 0.012) were identified as significant prognostic factors for mortality in patients with PPFs., Conclusions: Patients who were older, had high CA-153 and LDH levels, had poor pulmonary function test results, or had a UIP-like pattern on chest HRCT were more likely to have indications for the progression of f-ILD to PPF. Increased SPAP and AE are independent risk factors for the prognosis of PPF patients, so additional attention should be given to such patients.

Chronic Obstructive Pulmonary Disease (COPD) is a complex pulmonary condition characterized by chronic airflow limitation. Within the spectrum of COPD, distinct overlap conditions exist, including Asthma-COPD Overlap (ACO), COPD-Obstructive Sleep Apnea (COPD-OSA), Combined Pulmonary Fibrosis and Emphysema (CPFE), and Bronchiectasis-COPD Overlap (BCO). This review provides a comprehensive overview of the clinical and therapeutic implications of these conditions, highlighting the differences in complications compared with COPD alone in addition to the diagnostic challenges of identifying these conditions. Therapeutically tailored approaches are necessary for COPD overlap conditions considering the unique complications that may arise. Optimal pharmacological management, disease-specific interventions, and comprehensive patient-centered care are crucial components of treatment strategies. This review provides insights for healthcare professionals by enhancing their understanding and management of these conditions. This emphasizes the importance of accurate diagnosis and individualized treatment plans, considering the specific complications associated with each COPD overlap condition., Competing Interests: Declaration of competing interest No conflicts of interest or relationship with the industry to disclose by any of the authors. No funding or financial interests., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Telomere biology disorder (TBD) can present within a wide spectrum of symptoms ranging from severe congenital malformations to isolated organ dysfunction in adulthood. Diagnosing TBD can be challenging given the substantial variation in symptoms and age of onset across generations. In this report, we present two families, one with a pathogenic variant in ZCCHC8 and another with a novel variant in TERC. In the literature, only one family has previously been reported with a ZCCHC8 variant and TBD symptoms. This family had multiple occurrences of pulmonary fibrosis and one case of bone marrow failure. In this paper, we present a second family with the same ZCCHC8 variant (p.Pro186Leu) and symptoms of TBD including pulmonary fibrosis, hematological disease, and elevated liver enzymes. The suspicion of TBD was confirmed with the measurement of short telomeres in the proband. In another family, we report a novel likely pathogenic variant in TERC. Our comprehensive description encompasses hematological manifestations, as well as pulmonary and hepatic fibrosis. Notably, there are no other reports which associate this variant to disease. The families expand our understanding of the clinical implications and genetic causes of TBD., (© 2024 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Aims: Progressive pulmonary fibrosis (PPF) is a newly recognised clinical phenotype of interstitial lung diseases in the 2022 interstitial pulmonary fibrosis (IPF) guidelines. This category is based entirely on clinical and radiological factors, and the background histopathology is unknown. Our objective was to investigate the histopathological characteristics of PPF and to examine the correlation between usual interstitial pneumonia (UIP) and prognosis in this new disease type. We hypothesised that the presence of UIP-like fibrosis predicts patients' survival in PPF cases., Methods and Results: We selected 201 cases fulfilling the clinical criteria of PPF from case archives. Cases diagnosed as IPF by a multidisciplinary team were excluded. Whole slide images were evaluated by three pathologists who were blinded to clinical and radiological data. We measured areas of UIP-like fibrosis and calculated what percentage of the total lesion area they occupied. The presence of focal UIP-like fibrosis amounting to 10% or more of the lesion area was seen in 148 (73.6%), 168 (83.6%) and 165 (82.1%) cases for each pathologist, respectively. Agreement of the recognition of UIP-like fibrosis in PPF cases was above κ = 0.6 between all pairs. Survival analysis showed that the presence of focal UIP-like fibrosis correlated with worsened survival under all parameters tested (P < 0.001)., Conclusions: The presence of UIP-like fibrosis is a core pathological feature of clinical PPF, and its presence within diseased areas is associated with poorer prognosis. This study highlights the importance of considering the presence of focal UIP-like fibrosis in the evaluation and management of PPF., (© 2024 John Wiley & Sons Ltd.)

Introduction: Pulmonary fibrosis is a characteristic of various interstitial lung diseases (ILDs) with differing etiologies. Clinical trials in progressive pulmonary fibrosis (PPF) enroll patients based on previously described clinical criteria for past progression, which include a clinical practice guideline for PPF classification and inclusion criteria from the INBUILD trial. In this study, we compared the ability of past FVC (forced vital capacity) progression and baseline biomarker levels to predict future progression in a cohort of patients from the PFF Patient Registry., Methods: Biomarkers previously associated with pathobiology and/or progression in pulmonary fibrosis were selected to reflect cellular senescence (telomere length), pulmonary epithelium (SP-D, RAGE), myeloid activation (CXCL13, YKL40, CCL18, OPN) and fibroblast activation (POSTN, COMP, PROC3)., Results: PFF or INBUILD-like clinical criteria was used to separate patients into past progressor and non-past progressor groups, and neither clinical criterion appeared to enrich for patients with greater future lung function decline. All baseline biomarkers measured were differentially expressed in patient groups compared to healthy controls. Baseline levels of SP-D and POSTN showed the highest correlations with FVC slope over one year, though correlations were low., Conclusions: Our findings provide further evidence that prior decline in lung function may not predict future disease progression for ILD patients, and elevate the need for molecular definitions of a progressive phenotype. Across ILD subtypes, certain shared pathobiologies may be present based on the molecular profile of certain biomarker groups observed. In particular, SP-D may be a common marker of pulmonary injury and future lung function decline across ILDs., (© 2024. The Author(s).)

Introduction: Progressive pulmonary fibrosis (PPF) is a manifestation of a heterogenous group of underlying interstitial lung disease (ILD) diagnoses, defined as non-idiopathic pulmonary fibrosis (IPF) progressive fibrotic ILD meeting at least two of the following criteria in the previous 12 months: worsening respiratory symptoms, absolute decline in forced vital capacity (FVC) more than or equal to 5% and/or absolute decline in diffusing capacity for carbon monoxide (DLCO) more than or equal to 10% and/or radiological progression., Areas Covered: The authors subjectively reviewed a synthesis of literature from PubMed to identify recent advances in the diagnosis and characterisation of PPF, treatment recommendations, and management challenges. This review provides a comprehensive summary of recent advances and highlights future directions for the diagnosis, management, and treatment of PPF., Expert Opinion: Recent advances in defining the criteria for PPF diagnosis and licensing of treatment are likely to support further characterisation of the PPF patient population and improve our understanding of prevalence. The diagnosis of PPF remains challenging with the need for a specialised ILD multidisciplinary team (MDT) approach. The evidence base supports the use of immunomodulatory therapy to treat inflammatory ILDs and antifibrotic therapy where PPF develops. Treatment needs to be tailored to the specific underlying disease and determined on a case-by-case basis.

Pulmonary fibrosis (PF) is the major complication and death-related factor of acute respiratory distress syndrome (ARDS). This study evaluated the significance of miR-141-3p in ARDS and its complication of PF aiming to identify a potential biomarker for screening ARDS and predicting the occurrence of PF. A total of 137 ARDS patients and 69 healthy individuals were enrolled in this study and the serum samples were collected from all participants. The serum miR-141-3p levels were analyzed by polymerase chain reaction. The significance of miR-141-3p in the diagnosis and development of ARDS, and the occurrence of PF was evaluated by receiver operating curve, Chi-square test, and logistic regression analysis. MiR-141-3p was downregulated in ARDS patients and showed significant potential in its diagnosis. Reduced miR-141-3p was significantly associated with the increasing Murray and APACHEII score and the occurrence of PF in ARDS patients. MiR-141-3p, Murray score, and APACHEII score were identified as risk factors for the occurrence of PF in ARDS, and miR-141-3p was also found to be downregulated in ARDS patients with PF. Additionally, miR-141-3p could discriminate ARDS patients with PF and without PF, and was closely associated with the decreased total lung capacity, carbon monoxide diffusing capacity, and forced vital capacity of ARDS patients with PF. Downregulated miR-141-3p served as a biomarker for ARDS screening disease onset and indicating the severity. Reduced miR-141-3p was also identified as a risk factor for PF in ARDS patients and was associated with the severe progression of PF.

Objective: Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome characterized by the coexistence of emphysema and fibrotic interstitial lung disease (ILD). The aim of this study was to examine the effect of CPFE on lung cancer risk and lung cancer-related mortality in patients with rheumatoid arthritis (RA)., Methods: We conducted a multicenter retrospective cohort study of patients newly diagnosed with lung cancer at five community hospitals between June 2006 and December 2021. Patients were followed until lung cancer-related death, other-cause death, loss to follow-up, or the end of the study. We used the cumulative incidence function with Gray's test and Fine-Gray regression analysis for survival analysis., Results: A total of 563 patients with biopsy-proven lung cancer were included (82 RA patients and 481 non-RA patients). The prevalence of CPFE was higher in RA patients than in non-RA patients (40.2% vs.10.0%) at lung cancer diagnosis. During follow-up, the crude incidence rate of lung cancer-related death was 0.29 and 0.10 per patient-year (PY) in RA and non-RA patients, and 0.32 and 0.07 per PY in patients with CPFE and patients without ILD or emphysema, respectively. The estimated death probability at 5 years differed between RA and non-RA patients (66% vs. 32%, p<0.001) and between patients with CPFE and patients without ILD or emphysema (71% vs. 24%, p<0.001). In addition to clinical cancer stage and no surgery within 1 month, RA and CPFE were identified as independent predictive factors for increased lung cancer-related mortality (RA: adjusted hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.65-4.76; CPFE: adjusted HR 2.01; 95% CI 1.24-3.23)., Conclusions: RA patients with lung cancer had a higher prevalence of CPFE and increased cancer-related mortality compared with non-RA patients. Close monitoring and optimal treatment strategies tailored to RA patients with CPFE are important to improve the poor prognosis of lung cancer., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: S. Mori received honoraria for lectures from AbbVie GK, Eli Lilly Japan K.K., Pfizer Japan Inc., Chugai Pharmaceutical Co. Ltd., Janssen Pharmaceutical K.K., Boehringer Ingelheim Japan, and Taisho Pharma Co., Ltd. and received research funds from AbbVie GK, Asahikasei Pharma Corp, and Chugai Pharmaceutical Co., Ltd. Y. Ueki received honoraria for lectures from AbbVie GK, Eli Lilly Japan K.K., Pfizer Japan Inc., Asahikasei Pharma Corp., Astellas Pharma Inc., Bristol-Myers K.K., Chugai Pharmaceutical Co. Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Ono Pharmaceutical Co., and Takeda Pharmaceutical Co., Ltd. T. Hidaka received honoraria for lectures from AbbVie GK, Eli Lilly Japan K.K., Pfizer Japan Inc., Asahi Kasei Pharma Corp., Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd., and Eisai Co. K. Nakamura received honoraria for lectures from AstraZeneca K.K. The other authors had no financial relationships that could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Mori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Progressive pulmonary Fibrosis Abstract: Cough and dyspnea on excertion are common and early symptoms of interstitial lung diseases (ILD). Thoracic imaging (particularly computed tomography) detects such lung structural alterations early in the disease course. Knowledge of these diseases and their management is necessary in the daily business. The term "progressive pulmonary fibrosis" subsumes a heterogene group of interstitial lung diseases with a similar course of progressive fibrosis. The management of these diseases should be discussed interdisciplinary, similar to the management of the Idiopathic pulmonary fibrosis (IPF). Antifibrotic drugs are new therapeutic options., Competing Interests: Die Autoren haben keine Interessenskonflikte im Zusammenhang mit diesem Artikel deklariert., (© 2024 Aerzteverlag medinfo AG.)

Fibrosing interstitial lung diseases (FILDs) other than idiopathic pulmonary fibrosis (IPF) can develop into progressive pulmonary fibrosis (PPF) despite initial management. A substantial proportion of patients with non-IPF interstitial lung diseases (ILDs) progress to PPF, including connective tissue disease-associated ILD (such as rheumatoid arthritis-associated ILD, systemic sclerosis-associated ILD, and idiopathic inflammatory myositis-associated ILD), fibrosing hypersensitivity pneumonitis, and fibrosing occupational ILD. The concept of PPF emerged only recently and several studies have confirmed the impact of PPF on mortality. In addition to poor prognosis among patients with PPF, there remains a lack of consensus in the diagnosis and treatment of PPF across different types of ILDs. There is a need to raise awareness of PPF in FILDs and to explore measures to improve PPF diagnosis and treatment, which in turn could potentially reduce the progression from FILD to PPF. This review discusses the disease burden of PPF and recent advances in the management of PPF among patients with ILDs, including antifibrotic medications that have emerged as promising treatment options. Additionally, this review highlights the perspectives of expert Chinese physicians with regard to their experience in managing PPF in clinical practice.

Research on the condition of the lungs in senile people is an urgent task. This is due to the fact that degenerative or age-associated changes in the respiratory system play an important role in the formation of senile asthenia syndrome and a decrease in the age-related viability of the body as a whole. CT-scans of patients aged 80-90 years were analyzed (n=31). Age-associated changes were evaluated: the presence of linear fibrosis, increased pulmonary pattern by the type of reticular (reticular) changes, the presence of gross fibrous reticular changes with cystic cavities and air bullae (by the type of «cellular lung»), as well as the presence of pulmonary emphysema. Most naturally, senile people show changes characteristic of linear pulmonary fibrosis and emphysema. The progression of the process leads to diffuse reticular changes in the interalveolar and intersegmental septa and, in adverse cases, to the formation of gross changes in the type of «cellular lung». Fibro-emphysematous changes are significantly more common in men. A microbiological study of the microbiota of the lower respiratory tract in elderly people was also carried out (n=16). When studying the microbiocenosis of the lower respiratory tract in elderly people, the following data were obtained: resident microflora was found in 71% and clinically significant microorganisms were found in 29%.

Pulmonary fibrosis (PF) encompasses a spectrum of chronic lung diseases that progressively impact the interstitium, resulting in compromised gas exchange, breathlessness, diminished quality of life (QoL), and ultimately respiratory failure and mortality. Various diseases can cause PF, with their underlying causes primarily affecting the lung interstitium, leading to their referral as interstitial lung diseases (ILDs). The current understanding is that PF arises from abnormal wound healing processes triggered by various factors specific to each disease, leading to excessive inflammation and fibrosis. While significant progress has been made in understanding the molecular mechanisms of PF, its pathogenesis remains elusive. This review provides an in-depth exploration of the latest insights into PF pathophysiology, diagnosis, treatment, and future perspectives., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The most effective method for encouraging self-management in individuals with pulmonary fibrosis (PF) is unclear. This review aimed to identify common self-management components, the outcome measures used and the impact of these components in PF., Methods: A scoping review was conducted according to the Joanna Briggs Institute Manual for Evidence Synthesis using Medline, Embase, PsychInfo, CINAHL and the Cochrane Central Register of Controlled Trials. Eligible studies included those with educational, behavioural or support components aimed at facilitating self-management among adults with PF and employed quantitative and/or qualitative methods., Results: 87 studies were included. Common self-management components included education (78%), managing physical symptoms (66%) and enhancing psychosocial wellbeing (54%). Components were predominantly delivered in a pulmonary rehabilitation setting (71%). No studies tested a PF-specific self-management package. Common outcome measures were 6-min walk distance (60%), St George's Respiratory Questionnaire (37%) and the Medical Research Council Dyspnoea scale (34%). Clinically significant improvements in these outcomes were seen in ≥50% of randomised controlled trials. Qualitative data highlighted the importance of healthcare professional and peer support and increased confidence in managing PF., Conclusion: Self-management components are commonly incorporated into pulmonary rehabilitation programmes rather than being offered as standalone packages. Future research should focus on testing PF-specific self-management packages and employ standardised outcome assessments that include self-efficacy and health-related behaviours., Competing Interests: Conflict of interest: J.Y.T. Lee has nothing to disclose. G. Tikellis has nothing to disclose. L. Dowman has nothing to disclose. A.W. Jones reports funding from a Lung Foundation Australia Boehringer Ingelheim Fellowship and unpaid committee positions with Thoracic Society of Australia and New Zealand. M. Hoffman has nothing to disclose. C.R. Mellerick has nothing to disclose. C. Malaguti has nothing to disclose. Y.H. Khor reports grants from National Health and Medical Research Council, Medical Research Future Fund, Lung Foundation Australia, and Austin Medical Research Foundation, and nonfinancial support from Air Liquide Healthcare during the conduct of the study, outside the submitted work. A.E. Holland reports grants from National Health and Medical Research Council and Medical Research Future Fund; nonfinancial support from Air Liquide Healthcare during the conduct of the study, outside the submitted work; and unpaid positions with Thoracic Society of Australia and New Zealand and Lung Foundation Australia., (Copyright ©The authors 2023.)

Combined pulmonary fibrosis and emphysema (CPFE) syndrome refers to co-occurrence of two disease processes in the lung that can be difficult to diagnose but is associated with high morbidity and mortality burden. Diagnosis of CPFE is challenging because the two diseases can counterbalance respective impairments resulting in deceivingly normal-appearing chest radiography and spirometry in a dyspneic patient. Although an international committee published the terminology and definitions of CPFE in 2022, consensus on exact diagnostic criteria and optimal management strategy is yet to be determined. Herein, we provide a narrative review summarizing the literature on CPFE from 1990 to 2022, including historical background, epidemiology, pathogenesis, clinical features, imaging and pulmonary function findings, diagnosis, prognosis, complications, and treatment. Although CPFE was initially conceived as a variant presentation of idiopathic pulmonary fibrosis, it has been recognized to occur in patients with a wide variety of interstitial lung diseases, including connective tissue disease-associated interstitial lung diseases, and hypersensitivity pneumonitis. The affected patients have a heightened risk for pulmonary hypertension and lung cancer. Clinicians need to recognize the characteristic presenting features of CPFE along with prognostic implications of this entity., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. A minority of patients with sarcoidosis develop sarcoidosis-associated pulmonary fibrosis (SAPF), which may become progressive. Genetic profiles differ between patients with progressive and self-limiting disease. The mechanisms of fibrosis in SAPF are not fully understood, but SAPF is likely a distinct clinicopathological entity, rather than a continuum of acute inflammatory sarcoidosis. Risk factors for the development of SAPF have been identified; however, at present, it is not possible to make a robust prediction of risk for an individual patient. The bulk of fibrotic abnormalities in SAPF are located in the upper and middle zones of the lungs. A greater extent of SAPF on imaging is associated with a worse prognosis. Patients with SAPF are typically treated with corticosteroids, second-line agents such as methotrexate or azathioprine, or third-line agents such as tumour necrosis factor inhibitors. The antifibrotic drug nintedanib is an approved treatment for slowing the decline in lung function in patients with progressive fibrosing interstitial lung diseases, but more evidence is needed to assess its efficacy in SAPF. The management of patients with SAPF should include the identification and treatment of complications such as bronchiectasis and pulmonary hypertension. Further research is needed into the mechanisms underlying SAPF and biomarkers that predict its clinical course., Competing Interests: Conflict of interest: D. Bandyopadhyay reports a research grant from Boehringer Ingelheim Pharmaceuticals, Inc.; fees for speaking from Boehringer Ingelheim Pharmaceuticals, Inc. and United Therapeutics; and support for attending advisory board meetings and research meetings from Boehringer Ingelheim Pharmaceuticals, Inc. and United Therapeutics. M.S. Mirsaeidi has nothing to disclose., (Copyright ©The authors 2023.)

Objective: The comorbidity of pulmonary fibrosis and COPD/emphysema has garnered increasing attention. However, no bibliometric analysis of this comorbidity has been conducted thus far. This study aims to perform a bibliometric analysis to explore the current status and cutting-edge trends in the field, and to establish new directions for future research., Methods: Statistical computing, graphics, and data visualization tools such as VOSviewer, CiteSpace, Biblimatrix, and WPS Office were employed., Results: We identified a total of 1827 original articles and reviews on the comorbidity of pulmonary fibrosis and COPD/emphysema published between 2004 and 2023. There was an observed increasing trend in publications related to this comorbidity. The United States, Japan, and the United Kingdom were the countries with the highest contributions. Professor Athol Wells and the University of Groningen had the highest h-index and the most articles, respectively. Through cluster analysis of co-cited documents, we identified the top 17 major clusters. Keyword analysis predicted that NF-κB, oxidative stress, physical activity, and air pollution might be hot spots in this field in the future., Conclusion: This bibliometric analysis demonstrates a continuous increasing trend in literature related to the comorbidity of pulmonary fibrosis and COPD/emphysema. The research hotspots and trends identified in this study provide a reference for in-depth research in this field, aiming to promote the development of the comorbidity of pulmonary fibrosis and COPD/emphysema., Competing Interests: The authors declare that there is no conflict of interest in this work., (© 2023 Fang et al.)

Pleuroparenchymal fibroelastosis (PPFE) is a rare condition characterized by pleural and subpleural lung fibroelastosis with an upper lobe predominance. We present the third case of idiopathic PPFE from India, as well as the second ante-mortem diagnosis. A 27-year-old man presented with a 1-year history of modified Medical Research Council class II shortness of breath and dry cough. He described a 15-kg weight loss. After a clinico-radiological diagnosis, he was given anti-tubercular treatment and referred because he showed no improvement. A high-resolution computed tomography of the chest revealed bilateral upper lobe bullae, parenchymal and subpleural fibrosis, and irregular pleural thickening. PPFE was found in surgical lung and pleural biopsies. He was given systemic glucocorticoids but did not respond clinically or radiologically. Pirfenidone and a lung transplant were out of reach for him. He died 9 months after being diagnosed with his condition. Finally, idiopathic PPFE is an extremely rare entity, with only three cases reported from our subcontinent. As a result, it is easily underdiagnosed or misdiagnosed; clinician awareness of this condition is critical for better diagnosis and management.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel coronavirus that caused an ongoing pandemic of a pathology termed Coronavirus Disease 19 (COVID-19). Several studies reported that both COVID-19 and RTEL1 variants are associated with shorter telomere length, but a direct association between the two is not generally acknowledged. Here we demonstrate that up to 8.6% of severe COVID-19 patients bear RTEL1 ultra-rare variants, and show how this subgroup can be recognized., Methods: A cohort of 2246 SARS-CoV-2-positive subjects, collected within the GEN-COVID Multicenter study, was used in this work. Whole exome sequencing analysis was performed using the NovaSeq6000 System, and machine learning methods were used for candidate gene selection of severity. A nested study, comparing severely affected patients bearing or not variants in the selected gene, was used for the characterisation of specific clinical features connected to variants in both acute and post-acute phases., Results: Our GEN-COVID cohort revealed a total of 151 patients carrying at least one RTEL1 ultra-rare variant, which was selected as a specific acute severity feature. From a clinical point of view, these patients showed higher liver function indices, as well as increased CRP and inflammatory markers, such as IL-6. Moreover, compared to control subjects, they present autoimmune disorders more frequently. Finally, their decreased diffusion lung capacity for carbon monoxide after six months of COVID-19 suggests that RTEL1 variants can contribute to the development of SARS-CoV-2-elicited lung fibrosis., Conclusion: RTEL1 ultra-rare variants can be considered as a predictive marker of COVID-19 severity, as well as a marker of pathological evolution in pulmonary fibrosis in the post-COVID phase. This notion can be used for a rapid screening in hospitalized infected people, for vaccine prioritization, and appropriate follow-up assessment for subjects at risk. Trial Registration NCT04549831 ( www., Clinicaltrial: org )., (© 2023. The Author(s).)

This expert group consensus statement emphasises the need for standardising the definition of progressive fibrosing interstitial lung diseases (F-ILDs), with an accurate initial diagnosis being of paramount importance in ensuring appropriate initial management. Equally, case-by-case decisions on monitoring and management are essential, given the varying presentations of F-ILDs and the varying rates of progression. The value of diagnostic tests in risk stratification at presentation and, separately, the importance of a logical monitoring strategy, tailored to manage the risk of progression, are also stressed. The term "progressive pulmonary fibrosis" (PPF) exactly describes the entity that clinicians often face in practice. The importance of using antifibrotic therapy early in PPF (once initial management has failed to prevent progression) is increasingly supported by evidence. Artificial intelligence software for high-resolution computed tomography analysis, although an exciting tool for the future, awaits validation. Guidance is provided on pulmonary rehabilitation, oxygen and the use of non-invasive ventilation focused specifically on the needs of ILD patients with progressive disease. PPF should be differentiated from acute deterioration due to drug-induced lung toxicity or other forms of acute exacerbations. Referral criteria for a lung transplant are discussed and applied to patient needs in severe diseases where transplantation is not realistic, either due to access limitations or transplantation contraindications. In conclusion, expert group consensus guidance is provided on the diagnosis, treatment and monitoring of F-ILDs with specific focus on the recognition of PPF and the management of pulmonary fibrosis progressing despite initial management., Competing Interests: Conflict of interest: S.K. Rajan reports grants to their institution, consulting fees and lecture fees from Cipla and Boehringer Ingelheim; speaker fees from the Indian Chest Society; and support from Cipla to attend a European Respiratory Society meeting, all in the 36 months prior to manuscript submission. V. Cottin reports an unrestricted grant to their institution from Boehringer Ingelheim; consulting fees from Boehringer Ingelheim, Roche, Galapagos, Galecto, Shionogi, Fibrogen, RedX Pharma and PureTech; payment or honoraria and support for attending meetings from Boehringer Ingelheim and Roche; and participation on a data safety monitoring board or advisory board for Roche/Promedior, Celgene/Bristol Myers Squibb and Galapagos, all in the 36 months prior to manuscript submission. R. Dhar reports external expert contracts from Cipla and Boehringer Ingelheim; speaker fees from the Indian Chest Society, Cipla and Boehringer Ingelheim; and support for attendance at a European Respiratory Society meeting from Cipla. S. Danoff reports grant funding from Bristol Myers Squibb (Myositis ILD Trial), Boehringer Ingelheim (INBUILD and INBUILD-ON Trials) and Roche/Genentech (TRAIL Trial); royalties from UpToDate; advisory board fees from Boehringer Ingelheim and Lupin Pharma; payment for presentations from the France Foundation; funding for travel to present lectures from Boehringer Ingelheim; and participation on data safety monitoring boards for Galecto and Galapagos, all in the 36 months prior to manuscript submission; as well as a role as senior medical adviser and interim CMO for the Pulmonary Fibrosis Foundation and membership of the board of directors of the American Thoracic Society. K.R. Flaherty reports research grants paid to their institution by Boehringer Ingelheim; and consulting fees paid to them by Boehringer Ingelheim, Roche/Genentech, Blade Therapeutics, Shionogi, DevPro, AstraZeneca, Pure Health, Fibrogen, Sun Pharmaceuticals, Pliant, United Therapeutics, Arrowhead, Lupin, Polarean and PureTech, all in the 36 months prior to manuscript submission. K.K. Brown reports lung fibrosis research grants from the National Heart, Lung, and Blood Institute; being an external science advisor to AbbVie, CSL Behring, Dispersol, Huitai Biomedicine, Lilly, RedX Pharma, Theravance and Translate Bio; being a DMC chair for Biogen; scientific advisory board membership for Blade Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, DevPro Biopharma, Galapagos NV, Galecto, Open Source Imaging Consortium, Pliant, Sanofi and Third Pole; DMC membership for Humanetics; and a scientific collaboration with Sekisui Medical Co., all in the 36 months prior to manuscript submission; as well as leadership or fiduciary roles for the Fleischner Society and Open Source Imaging Consortium. A. Mohan declares no competing interests. E. Renzoni declares a research contract payment and advisory board meeting payment to their institution by Boehringer Ingelheim; lecture fees paid to their institution by Boehringer Ingelheim, Roche and Chiesi; and registration and travel expenses for the American Thoracic Society conference, paid by Boehringer Ingelheim, all in the 36 months prior to manuscript submission. M. Mohan reports no competing interests. Z. Udwadia reports no competing interests. P. Shenoy reports no competing interests. D. Currow reports intellectual property payments and royalties from Mayne Pharma International Pty Ltd, a manufacturer of sustained-release morphine; and consulting fees from Helsinn Pharmaceuticals, in the 36 months prior to manuscript submission; as well as leadership or fiduciary roles for the Dust Diseases Board of New South Wales and the Board of the Cancer Institute NSW. A. Devraj reports consulting fees from Boehringer Ingelheim, Roche, Galecto, Galapagos, Brainomix and Vicore, all in the 36 months prior to manuscript submission. B. Jankharia reports payment or honoraria to their institution from Cipla India, Lupin India, Boehringer Ingelheim and German Remedies India, all in the 36 months prior to manuscript submission; as well as being a past president of the Indian Musculoskeletal Society and the Indian Radiology and Imaging Association. R. Kulshrestha reports no competing interests. S. Jones reports grants to their institution from Boehringer Ingelheim and Trevi for being Chair of Action for Pulmonary Fibrosis (APF) and President of the European Pulmonary Fibrosis Federation (EU-IPFF) (both these organisations implement projects in partnership with industry; the author is not involved in these projects and does not gain personally); reports payment or honoraria from Boehringer Ingelheim, Vicore and Roche (paid to their institution); and participation on a data safety monitoring board or advisory board as Galecto DSMB for an anti-fibrotic therapy, in the 36 months prior to manuscript submission. C. Ravaglia reports no competing interests. S. Quadrelli reports speaker fees from Boehringer Ingelheim in the 36 months prior to manuscript submission. R. Iyer reports no competing interests. S. Dhooria reports no competing interests. M. Kolb reports research funding for pre-clinical work from Boehringer Ingelheim and Pieris; research funding for a clinical project from Roche; consulting fees from Boehringer Ingelheim, Roche, Horizon, Cipla, AbbVie, Belerophon, Algernon, CSL Behring, United Therapeutics and AstraZeneca; payment or honoraria from Novartis, Boehringer Ingelheim and Roche; payment for court testimony from Roche; participation on a data safety monitoring board or advisory board for Covance and United Therapeutics; and an allowance paid to their institution from the European Respiratory Society relating to their duties as European Respiratory Journal Chief Editor, all in the 36 months prior to manuscript submission. A.U. Wells reports payments or honoraria from Boehringer Ingelheim and Roche; and participation on a data safety monitoring board or advisory board for Boehringer Ingelheim, Roche and Veracyte, all in the 36 months prior to manuscript submission., (Copyright ©The authors 2023.)

Background: Pulmonary fibrosis (PF) is caused by a heterogeneous group of diseases, with a high inter-individual variability in disease trajectory. Identifying disease progression in patients with PF has impact on clinical management decisions. However, strategies to early identify and predict disease progression for these patients are currently lacking. In this study, we aim to assess long-term FVC change in patients with PF measured with home spirometry, and evaluate the feasibility of a multinational patient-led registry in PF. In addition, we will assess validity of patient-reported outcomes (PROMs) for the different subgroups of patients with PF., Methods: In this international, prospective, multicenter, observational study, we aim to include 700 patients across seven European countries. Patients will monitor their disease course for a period of two years using an online home monitoring program (I-FILE), which includes home spirometry, pulse oximetry, and PROMs. Results will be directly sent to the hospital via the online application. Patients will be asked to perform daily home spirometry and pulse oximetry in the first three months, followed by once weekly measurements for a period of two years. PROMs will be completed in the online I-FILE application every six months, including the King's brief Interstitial Lung Disease Health Status, The EuroQol five dimensions five-level, Visual Analogue Scales on cough, dyspnea, fatigue and general complaints, Leicester Cough Questionnaire, Fatigue Assessment Scale, Work Productivity and Activity Impairment Questionnaire, Global Rating of Change Scale, and Living with Pulmonary Fibrosis questionnaire., Discussion: This study will provide much needed insights in disease trajectories of the different subgroups of patients with PF. Simultaneously, the I-FILE study will yield valuable information on the use and feasibility of home-based data collection. This international patient-led registry will facilitate trans-border collaboration to further optimize care and research for patients with PF., Trial Registration: The study was registered on the 12th of March 2020 in the International Clinical Trial Registry, www., Clinicaltrials: gov ; Identifier: NCT04304898., (© 2023. The Author(s).)

Introduction: Advanced pulmonary sarcoidosis refers to phenotypes of pulmonary sarcoidosis that often lead to significant loss of lung function, respiratory failure, or death. Around 20% of patients with sarcoidosis may progress to this state which is mainly driven by advanced pulmonary fibrosis. Advanced fibrosis often presents with associated complications of sarcoidosis including infections, bronchiectasis, and pulmonary hypertension., Areas Covered: This article will focus on the pathogenesis, natural history of disease, diagnosis, and potential treatment options of pulmonary fibrosis in sarcoidosis. In the expert opinion section, we will discuss the prognosis and management of patients with significant disease., Expert Opinion: While some patients with pulmonary sarcoidosis remain stable or improve with anti-inflammatory therapies, others develop pulmonary fibrosis and further complications. Although advanced pulmonary fibrosis is the leading cause of death in sarcoidosis, there are no evidence-based guidelines for the management of fibrotic sarcoidosis. Current recommendations are based on expert consensus and often include multidisciplinary discussions with experts in sarcoidosis, pulmonary hypertension, and lung transplantation to facilitate care for such complex patients. Current works evaluating treatments include the use of antifibrotic therapies for treatment in advanced pulmonary sarcoidosis.

Competing Interests: Declaration of interests Author declares no competing interests. DKM acknowledge the support of HL163556, HL152960, DK054759, HL091842, HL147366 and Cystic Fibrosis Foundation.

The viral infectious disease pandemic caused by SARS-CoV-2 has affected over 500 million people and killed over 6 million. This is the official data provided by the WHO as of the end of May 2022. Among people who have recovered from COVID-19, post-COVID syndrome is quite common. Scattered epidemiological studies on post-COVID syndrome, however, indicate its high relevance. One of the manifestations of post-COVID syndrome is the development of pulmonary fibrosis (PF). This article is devoted to the analysis of literature data on epidemiology, immunomorphology, as well as X-ray morphological and functional characteristics of PF in patients with post-COVID syndrome. Attention is drawn to the various phenotypes of the post-COVID syndrome and the incidence of PF, which, as clinical practice shows, is most common in people who have had severe COVID-19. This article discusses in detail the molecular biological and immunological mechanisms of PF development. The fibrotic process of the lung parenchyma is not an early manifestation of the disease; as a rule, radiomorphological signs of this pathological process develop after four weeks from the onset of acute manifestations of a viral infection. The characteristic signs of PF include those that indicate the process of remodulation of the lung tissue: volumetric decrease in the lungs, "cellular" degeneration of the lung parenchyma, bronchiectasis and traction bronchiolectasis. The process of remodulating the lung tissue, in the process of fibrosis, is accompanied by a violation of the lung function; a particularly sensitive test of functional disorders is a decrease in the diffusion capacity of the lung tissue. Therefore, in the process of monitoring patients with post-COVID syndrome, a dynamic study of the ventilation function of the lungs is recommended. The main clinical manifestation of PF is dyspnea that occurs with minimal exertion. Shortness of breath also reflects another important aspect of fibrous remodulation of the lung parenchyma - oxygen dissociation is disturbed, which reflects a violation of the gas exchange function of the lungs. There are no generally accepted treatments for PF in post-COVID syndrome. The literature considers such approaches as the possibility of prescribing antifibrotic therapy, hyaluronidase, and medical gases: thermal helium, nitric oxide, and atomic hydrogen. The article draws attention to the unresolved issues of post-covid PF in people who have had COVID-19.

Background: Hypersensitivity pneumonitis (HP) is a type of interstitial lung disease (ILD) with a variable disease course and prognosis ranging from inflammatory and self-limiting to irreversible and progressive pulmonary fibrosis. Comorbidities are common in HP and may have an impact on prognosis. Due to the heterogeneity of HP presentation and progression, the identification of specific phenotypes in relationship to disease course and outcome is essential. The aim of this study was to identify clusters of comorbidities which could represent phenotypes in fibrotic HP and examine their impact on prognosis., Methods: Patients diagnosed with fibrotic HP at a tertiary referral center for ILD were included. Comorbidities were systematically registered and clusters of comorbidities were identified using cluster analyses. Disease progression and survival was estimated for each cluster., Results: The cohort comprised 211 patients with 53.6% males, mean age 63.0, baseline FVC 72.7%, DLCO 44.1%. Median follow-up time was 1.8 years (IQR 0.7-3.9). Three clusters with distinct comorbidity profiles and clinical characteristics were identified. One cluster dominated by elder male patients with predominantly cardiovascular diseases was associated with more respiratory hospitalizations and a worse prognosis. Differences in pulmonary function or exercise capacity trajectories between clusters were not observed., Conclusions: Three clusters with distinct comorbidities were identified and could represent phenotypes in fibrotic HP not previously recognized. The worst prognosis was observed in a cluster dominated by elder males with cardiovascular diseases. Increased focus on prevention and treatment of comorbidities could potentially improve the prognosis of patients with fibrotic HP., (© 2022. The Author(s).)

POIKiloderma, tendon contractures, myopathy, pulmonary fibrosis is a congenital multisystem disorder due to FAM111B dominant variants. We present a literature review focusing on the frequency and the impact of hepatic involvement and a case report of a patient with severe end-stage liver disease. Whole exome sequencing (WES) was conducted on the proband and his parents. A de novo FAM111B: c.1879A > G; (p.Arg627Gly) variant was identified. Hepatic involvement is present in 11 out of the 30 patients described in the literature, with different levels of dysfunction ranging from mild transaminitis to liver fibrosis found in three different cases by liver biopsies. Liver involvement seems to be a significant cause of morbidity. We propose to modify the previous acronym in POIK-TMPL: including POIKiloderma, tendon contractures, myopathy, pulmonary fibrosis/pancreas insufficiency and cancer, liver involvement/lymphedema. Moreover, we suggest screening patients with FAM111B variants for liver involvement from the first month of life and continue with an appropriate follow-up. Further studies are needed to better understand this frequent complication., (© 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Sarcoidosis is the most frequent immunologically related granulomatous disease and can serve as a model for understanding diseases within this category. The evidence on the diagnostics and treatment is so far limited. It is therefore all the more important that two new and significant guidelines on diagnosis and treatment of sarcoidosis were published during the last 2 years. Additionally, there were more new publications, which were considered for this review article. In this context, this review article provides a current update and overview of sarcoidosis. Pathophysiologically, there is an increasing understanding of the complex processes and interactions involved in the inflammatory processes and granuloma formation. The probability of a diagnosis of sarcoidosis is determined by compatible histology, the exclusion of differential diagnoses and if possible evidence of a multiorgan manifestation. The clinical course is variable and ranges from an asymptomatic manifestation to severe life-threatening organ failure. The most frequently affected organ are the lungs. Pulmonary fibrosis is the most severe form and is also decisive for mortality. An increasing focus is on the extrapulmonary organ manifestations, in particular, cardiac, hepatosplenic, gastrointestinal, renal, ocular and neurological involvement. Treatment, which consists primarily of immunosuppression, should be initiated in cases of organ-threatening or quality of life-impairing activity of the disease. Additional organ-specific management must also be evaluated. In cases of organ failure transplantation should be considered. Due to the limited evidence especially for the treatment of multiorgan sarcoidosis, when possible, patients with this disease should be included in clinical trials., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Combined pulmonary fibrosis and emphysema (CPFE) is a novel clinical entity with a poor prognosis. This study aimed to develop a clinical nomogram model to predict the 1-, 2- and 3-year mortality of patients with CPFE by using the machine learning approach, and to validate the predictive ability of the interstitial lung disease-gender-age-lung physiology (ILD-GAP) model in CPFE., Methods: The data of CPFE patients from January 2015 to October 2021 who met the inclusion criteria were retrospectively collected. We utilized LASSO regression and multivariable Cox regression analysis to identify the variables associated with the prognosis of CPFE and generate a nomogram. The Harrell's C index, the calibration curve and the area under the receiver operating characteristic (ROC) curve (AUC) were used to evaluate the performance of the nomogram. Then, we performed likelihood ratio test, net reclassification improvement (NRI), integrated discrimination improvement (IDI) and decision curve analysis (DCA) to compare the performance of the nomogram with that of the ILD-GAP model., Results: A total of 184 patients with CPFE were enrolled. During the follow-up, 90 patients died. After screening out, diffusing lung capacity for carbon monoxide (DLCO), right ventricular diameter (RVD), C-reactive protein (CRP), and globulin were found to be associated with the prognosis of CPFE. The nomogram was then developed by incorporating the above five variables, and it showed a good performance, with a Harrell's C index of 0.757 and an AUC of 0.800 (95% CI 0.736-0.863). Moreover, the calibration plot of the nomogram showed good concordance between the prediction probabilities and the actual observations. The nomogram also improved the discrimination ability of the ILD-GAP model compared to that of the ILD-GAP model alone, and this was substantiated by the likelihood ratio test, NRI and IDI. The significant clinical utility of the nomogram was demonstrated by DCA., Conclusion: Age, DLCO, RVD, CRP and globulin were identified as being significantly associated with the prognosis of CPFE in our cohort. The nomogram incorporating the 5 variables showed good performance in predicting the mortality of CPFE. In addition, although the nomogram was superior to the ILD-GAP model in the present cohort, further validation is needed to determine the clinical utility of the nomogram., (© 2022. The Author(s).)

Background: Pulmonary fibrosis is common in primary Sjögren's syndrome (pSS)-related interstitial lung disease (ILD). However, research is lacking on the diagnostic immunological examination of pSS-related pulmonary fibrosis. Particularly, the value of detecting anti-Ro52 antibody in pulmonary fibrosis is unclear., Objective: To evaluate the potential diagnostic value of anti-SSA, anti-SSB, and anti-Ro52 autoantibodies as markers of pSS-related pulmonary fibrosis., Methods: One-hundred seventy-nine patients with pSS were analyzed retrospectively at our hospital. They were divided into the fibrosis and non-fibrosis groups. Pulmonary fibrosis was classified as mild, moderate, or severe based on the patients' computed tomography (CT) findings. Laboratory examinations, including anti-SSA, anti-SSB, and anti-Ro52 antibody evaluations, were performed. The influencing factors of pulmonary fibrosis were analyzed using logistic regression., Results: Chest CT revealed pulmonary fibrosis in 45 patients with pSS (25.1%). The positive rates of anti-SSA and anti-Ro52 antibodies in the fibrosis group were lower than in the non-fibrosis group (P=0.04, P=0.001). The frequency of anti-Ro52 antibody showed no significant differences between mild-to-moderate (53.8%) and severe (47.3%) pulmonary fibrosis. The anti-Ro52 antibody was identified as a potentially protective factor against pSS (P=0.041)., Conclusions: Patients with pSS and pulmonary fibrosis had a low frequency of anti-SSA and anti-Ro52 antibodies. In patients with pSS and negative anti-Ro52 antibody, a chest CT is recommended to further understand the patients' condition.

Background: The combination of pulmonary fibrosis and emphysema (CPFE) has been recently defined as a syndrome, it is radiologically recognized and is characterized by the simultaneous coexistence of emphysema of superior pulmonary location and fibrosis predominantly in lower lobes., Case Presentation: We present three patients with CPFE, who underwent right cardiac catheterization for pulmonary hemodynamic assessment, finding mean pulmonary artery pressure (mPAP) between 37-52 mm Hg (mean 45 mm Hg), who received treatment with specific vasodilators for pulmonary arterial hypertension (PAH)., Discussion and Conclusions: The three patients had higher mPAP than expected for Group III (Pulmonary hypertension due to lung disease and/or hypoxia) of the classification of pulmonary hypertension (PH) by the World Health Organization (WHO), in whom the use of Sildenafil was justified by the presence of progressive dyspnea, and no symptoms suggestive of infectious exacerbation associated with right ventricular failure., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Acute manifestations of SARS-CoV-2 infection continue to impact the lives of many across the world. Post-acute sequelae of coronavirus disease 2019 (COVID-19) may affect 10-30% of survivors of COVID-19, and post-acute sequelae of COVID-19 (PASC)-pulmonary fibrosis is a long-term outcome associated with major morbidity. Data from prior coronavirus outbreaks (severe acute respiratory syndrome and Middle East respiratory syndrome) suggest that pulmonary fibrosis will contribute to long-term respiratory morbidity, suggesting that PASC-pulmonary fibrosis should be thoroughly screened for through pulmonary function testing and cross-sectional imaging. As data accumulates on the unique pathobiologic mechanisms underlying critical COVID-19, a focus on corollaries to the subacute and chronic profibrotic phenotype must be sought as well. Key aspects of acute COVID-19 pathobiology that may account for increased rates of pulmonary fibrosis include monocyte/macrophage-T-cell circuits, profibrotic RNA transcriptomics, protracted elevated levels of inflammatory cytokines, and duration of illness and ventilation. Mechanistic understanding of PASC-pulmonary fibrosis will be central in determining therapeutic options and will ultimately play a role in transplant considerations. Well-designed cohort studies and prospective clinical registries are needed. Clinicians, researchers and healthcare systems must actively address this complication of PASC to minimise disability, maximise quality of life and confront a post-COVID-19 global health crisis., Competing Interests: Conflict of interest: R.J. Mylvaganam reports grant from Janssen Actelion Intelligence Award, outside the submitted work. Conflict of interest: J.I. Bailey has nothing to disclose. Conflict of interest: J.I. Sznajder has nothing to disclose. Conflict of interest: M.A. Sala reports grants or contracts from NIH – 5R01HL122477-07, CF Foundation – SALA18I0, and consulting fees from Medscape/WedMD, outside the submitted work., (Copyright ©The authors 2021.)

Introduction: Survivors of COVID-19 infection may develop post-covid pulmonary fibrosis (PCF) and suffer from long term multi-system complications. The magnitude and risk factors associated with these are unknown., Objectives: We investigated the prevalence and risk factors associated with PCF and other complications in patients discharged after COVID-19 infection., Methods: Patients had phone assessment 6 weeks post hospital discharge after COVID-19 infection using a set protocol. Those with significant respiratory symptoms were investigated with a CTPA, Pulmonary Function Tests and echocardiogram. Prevalence of myalgia, fatigue, psychological symptoms and PCF was obtained. Risk factors associated with these were investigated., Results: A large number of patients had persistent fatigue (45.1%), breathlessness (36.5%), myalgia (20.5%) and psychological symptoms (19.5%). PCF was seen in 9.5% of the patients and was associated with persistent breathlessness at 6 weeks and inpatient ventilation [adjusted OR 5.02(1.76-14.27) and 4.45(1.27-15.58)] respectively. It was more common in men and in patients with peak CRP >171.5 mg/L, peak WBC count ≥12 × 10 9/L, severe inpatient COVID-19 CXR changes and CT changes. Ventilation was also a risk factor for persisting fatigue and myalgia, the latter was also more common in those with severe cytokine storm and severe COVID-19 inpatient CXR changes., Conclusions: All the patients discharged after COVID-19 should be assessed using a set protocol by a multidisciplinary team. Patients who had severe COVID-19 infection particularly those who were intubated and who have persistent breathlessness are at risk of developing PCF. They should have a CT Chest and have respiratory follow-up., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

One of the common long-term consequences observed in survivors of COVID-19 pneumonia is the persistence of respiratory symptoms and/or radiological lung abnormalities. The exact prevalence of these post-COVID pulmonary changes is yet unclear. Few authors, based on their early observations, have labeled these persistent computed tomography (CT) abnormalities as post-COVID lung fibrosis, which appears to be an overstatement. Lately, it is being observed that many of the changes seen in post-COVID lungs are temporary and tend to show resolution on follow-up, with only a few developing into lung fibrosis. Thus, based on the presumptive diagnosis of lung fibrosis, these patients should not be blindly started on anti-fibrotic drugs. One must not forget that these drugs can do more harm than good, if used injudiciously. It is better to use the term "post-COVID interstitial lung changes", which covers a broader spectrum of pulmonary changes seen in patients who have recovered from COVID-19 pneumonia. At the same time, it is essential to identify the sub-set of COVID-19 survivors who are at an increased risk of developing lung fibrosis and to carefully chalk out management strategies so as to modify the course of the disease and prevent irreversible damage. Meticulous and systematic longitudinal follow-up studies consisting of clinical, laboratory, imaging, and pulmonary function tests are needed for the exact estimation of the burden of lung fibrosis, to understand the nature of residual pulmonary changes, and to predict the likelihood of development of lung fibrosis in COVID-19 survivors., Competing Interests: None

An interstitial lung disease represents a relevant organ manifestation in many systemic rheumatic diseases (connective tissue disease-interstitial lung disease, CTD-ILD). In 10% of the cases pulmonary fibrosis even results in an underlying systemic disease. The CTD-ILDs are frequently associated with a poor prognosis. Therefore, it is important to test patients with systemic rheumatic diseases timely and regularly for the presence of an ILD. Treatment decisions should be made together with pneumologists and rheumatologists, particularly with respect to the initiation of a specific treatment. Treatment is based on randomized studies only in a few cases and can mostly be derived from case control studies. For systemic sclerosis-associated ILD (SSc-ILD) antifibrotic treatment with nintedanib has also now been approved in addition to an immunosuppressive treatment. For other CTD-ILDs an antifibrotic treatment should be discussed in an interdisciplinary approach depending on the underlying disease corresponding to a progressively fibrosing ILD., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

There have been no studies on the effects of polyhexamethylene guanidine phosphate (PHMG) after a long period of exposure in the rodent model. We aimed to evaluate long-term lung damage after PHMG exposure using conventional chest computed tomography (CT) and histopathologic analysis in a rat model. A PHMG solution was intratracheally administrated to 24 male rats. At 8, 26, and 52 weeks after PHMG instillation, conventional chest CT was performed in all rats and both lungs were extracted for histopathologic evaluation. At 52 weeks after PHMG instillation, four carcinomas had developed in three of the eight rats (37.5%). Bronchiolo-alveolar hyperplasia and adenoma were found in rats at 8, 26, and 52 weeks post-instillation. The number of bronchiolo-alveolar hyperplasia significantly increased over time (P-value for trend< 0.001). The severity of lung fibrosis and fibrosis scores significantly increased over time (P-values for trend = 0.002 and 0.023, respectively). Conventional chest CT analysis showed that bronchiectasis and linear density scores suggestive of fibrosis significantly increased over time (P-value for trend < 0.001). Our study revealed that one instillation of PHMG in a rat model resulted in lung carcinomas and progressive and irreversible fibrosis one year later based on conventional chest CT and histopathologic analysis. PHMG may be a lung carcinogen in the rat model., Competing Interests: The authors have declared that no competing interests exist.