Advances in the identification and management of progressive pulmonary fibrosis: perspective from Chinese experts.

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.

Three-Month Mortality in Nonhaematological Patients with Chronic Pulmonary Aspergillosis: Differences between Subtypes.

Objectives: Chronic pulmonary aspergillosis (CPA) is a fungal lung infection characterised by the slowly progressing destruction of the lung parenchyma and has four main subtypes. The objective of this work was to evaluate the epidemiology of CPA in our area and evaluate the involvement of the different subtypes in mortality. Methods: This was a descriptive longitudinal retrospective study developed in three tertiary hospitals in Spain. Among all patients admitted with a pulmonary aspergillosis diagnosis, we selected those who fulfilled the criteria for chronic aspergillosis according to the criteria of Denning, excluding those with a haematological disorder. Results: Among 409 inpatients recorded as having a pulmonary aspergillosis infection, only 76 (18.5%) fulfilled the criteria for CPA, with an estimated incidence of 0.67 cases/100,000 inhabitants/year. The subtypes detected were subacute invasive aspergillosis (SAIA) in 33 (43.4%) patients, simple aspergilloma (SA) in 25 (32.9%) patients, cavitary chronic aspergillosis (CCPA) in 13 (17.1%) patients, and chronic fibrosis (CFPA) in five (6.5%) patients. The overall three-month mortality rate was 23%, which was higher in SAIA patients. The predictors of early mortality were age > 65 years (OR 3.0 CI 95 1.0-9.5 p = 0.043) and the SAIA subtype vs. other subtypes (OR 3.1 CI 95 1.0-9.5 p = 0.042). Conclusions: The incidence rate estimated was inferior to that previously reported. The three-month mortality in patients with CPA was high, with older age and the SAIA subtype being the variable independent predictors of a worse prognosis.

A phase 2a trial of brepocitinib for cicatricial alopecia.

BACKGROUND: Cicatricial alopecias (CA) are chronic, progressive scarring hair-loss conditions. Molecular dysregulation is not fully understood, hindering treatment development. Th1/IFNγ signaling and JAK dysregulation has shown involvement, providing rationale for this phase 2a trial with TYK2/JAK1 inhibitor brepocitinib. METHODS: Randomized, placebo-controlled phase 2a trial spanning 52 weeks. Adults (18≥years of age) with lichen planopilaris, frontal fibrosing alopecia, or central centrifugal cicatricial alopecia diagnosis were randomized 3:1 to brepocitinib 45mg daily or placebo for 24 weeks, after which all patients received brepocitinib for another 24 weeks, with a safety follow up 4 weeks later. Lesional scalp biopsies were collected at baseline, week 24, and week 48. Co-primary endpoints were changes in lesional expression of CCL5, changes in lesional expression of fibrosis-related markers, and safety at week 24. RESULTS: Patients receiving brepocitinib showed significant downregulation in CCL5 expression at week 24 (p=0.004). Enrichment analysis of a subset of fibrosis markers showed trending upregulation in placebo patients (p<0.1). Brepocitinib was well tolerated and improved clinical severity scores. LIMITATIONS: Single-dose regimen, small placebo group. CONCLUSION: Brepocitinib significantly reduces CCL5 expression and was well tolerated at week 24, meeting co-primary endpoints. Brepocitinib reduces inflammatory biomarker expression and improves clinical severity, while maintaining favorable safety profile.

Bronchial artery embolization combined with left pulmonary resection in the treatment of fibrosing mediastinitis complicated with massive hemoptysis: a case report.

Fibrosing mediastinitis (FM) is a rare and benign fibroproliferative disease that presents with the proliferation of extensive, dense fibrous tissue in the mediastinum. Hemoptysis is a common clinical manifestation of FM. Clinically, most patients exhibit mild to moderate hemoptysis. We report a case of FM complicated with life-threatening massive hemoptysis. The patient was successfully rescued through a combination of bronchoscopic balloon closure, bronchial artery embolization (BAE), and surgical interventions. Although FM is frequently benign, vascular involvement can progress to life-threatening massive hemoptysis and must be treated appropriately.

Trichoscopy of Frontal Fibrosing Alopecia Affecting Black Scalp: A Literature Review.

Background: Frontal fibrosing alopecia (FFA) is a primary lymphocytic scarring alopecia characterized by progressive recession of the frontotemporal hairline, affecting mainly postmenopausal and, lately, premenopausal women of African descent. Considering the importance of trichoscopy on FFA diagnosis and the peculiarities found in patients with higher skin phototypes, this study aimed to review the FFA trichoscopy in the black scalp (Fitzpatrick IV-VI), a topic that remains sparsely described in the existing literature. Summary: In black patients, FFA may manifest singular features on presentation posing diagnostic clinical and trichoscopic challenges. This group has lower prevalence of the FFA compared to other alopecias. It may have an earlier age of onset and often exhibits more severe manifestations due to the coexistence of other types of alopecia and delay in diagnosis. The early signs of the disease in black patients may manifest in the eyebrows before scalp hair loss and lichen planus pigmentosus may be a herald sign. Key Messages: Our research analyzes FFA trichoscopy findings in black patients to help precise diagnosis and treatment. Raising awareness of the disease characteristics on trichoscopy contributes to improving hair care in this population.

Perioperative Anesthetic Considerations for Catheter-Based Pulmonary Vein Interventions in Fibrosing Mediastinitis.

INTRODUCTION: Fibrosing mediastinitis (FM) is a rare disease characterized by abnormal proliferation of fibrous tissue, causing compression and narrowing of the airway, blood vessels, and other mediastinal structures, including the pulmonary veins. Catheter-based interventions are available as palliative strategies. Due to the complex nature of the disease and the profound respiratory and hemodynamic sequelae that may ensue, anesthetic management requires meticulous interdisciplinary planning. METHODS: We performed a retrospective descriptive study including patients with FM undergoing catheter-based interventions for pulmonary vein stenosis from January 2020 to April 2024. A total of 14 patients underwent chart review, and we reported patient sex, preprocedural pulmonary artery pressures, comorbidities, lung isolation strategies, intraprocedural anesthetic complications, postprocedural intensive care unit admissions, and length of stay. RESULTS: All patients underwent pulmonary vasculature angioplasty, with or without stent placement, under general anesthesia with lung isolation capabilities and echocardiogram guidance. Eleven of 18 (61%) patients were uncomplicated. Four of 18 (22%) patients required unanticipated postoperative intensive care unit care: 2 (11%) in the setting of pulmonary hemorrhage, 1 due to hypoxic respiratory failure, and 1 due to difficult airway. One patient developed self-limiting postoperative hemoptysis on 2 different occasions, and 1 patient developed a vascular access-related complication. Mean hospital length of stay was 2.6 days (0-13 days), and mean intensive care unit length of stay was 1.75 days (1-4 days). One patient presented 6 weeks postoperatively with massive hemoptysis likely secondary to pulmonary vein rupture and died away after a protracted intensive care unit course. CONCLUSION: Patients with FM can achieve successful intraprocedural outcomes by ensuring a comprehensive understanding of the disease, addressing significant anesthetic concerns and considerations, and engaging a multidisciplinary team.

Incidence and predictors of in-stent restenosis following intervention for pulmonary vein stenosis due to fibrosing mediastinitis.

BACKGROUND: Fibrosing mediastinitis (FM) is a rare yet fatal condition, caused by different triggers and frequently culminating in the obstruction of the pulmonary vasculature and airways, often leading to pulmonary hypertension and right heart failure. Percutaneous transluminal pulmonary venoplasty (PTPV) is an emerging treatment for pulmonary vein stenosis (PVS) caused by FM. Our previous study showed as high as 24% of in-stent restenosis (ISR) in FM. However, the predictors of ISR are elusive. OBJECTIVES: We sought to identify the predictors of ISR in patients with PVS caused by extraluminal compression due to FM. METHODS: We retrospectively enrolled patients with PVS-FM who underwent PTPV between July 1, 2018, and December 31, 2022. According to ISR status, patients were divided into two groups: the ISR group and the non-ISR group. Baseline characteristics (demographics and lesions) and procedure-related information were abstracted from patient records and analyzed. Univariate and multivariate analyses were performed to determine the predictors of ISR. RESULTS: A total of 142 stents were implanted in 134 PVs of 65 patients with PVS-FM. Over a median follow-up of 6.6 (3.4-15.7) months, 61 of 134 PVs suffered from ISR. Multivariate analysis demonstrated a significantly lower risk of ISR in PVs with a larger reference vessel diameter (RVD) (odds ratio (OR): 0.79; 95% confidence interval [CI]: 0.64 to 0.98; P = 0.032), and stenosis of the corresponding pulmonary artery (Cor-PA) independently increased the risk of restenosis (OR: 3.41; 95% CI: 1.31 to 8.86; P = 0.012). The cumulative ISR was 6.3%, 21.4%, and 39.2% at the 3-, 6-, and 12-month follow-up, respectively. CONCLUSION: ISR is very high in PVS-FM, which is independently associated with RVD and Cor-PA stenosis. TRAIL REGISTRATION: Chinese Clinical Trials Register; No.: ChiCTR2000033153. URL: http://www.chictr.org.cn .

Percent Predicted vs. Absolute Six-Minute Walk Distance as Predictors of Lung Transplant-Free Survival in Fibrosing Interstitial Lung Diseases.

INTRODUCTION: Fibrosing interstitial lung diseases (ILDs) often progress despite treatment and become life-threatening, with lung transplant (LTx) remaining the only curative option. Six-minute walk distance (6MWD) is increasingly recognized as reliable predictor of clinical course, especially when longitudinally considered. The use of reference equations to express 6MWD as percent predicted (6MWD%) has not been previously studied in fibrosing ILDs. We sought to investigate whether the prognostic power of 6MWD% is superior to that of 6MWD expressed in meters (6MWD-m). METHODS: A retrospective, multicenter cohort analysis was conducted on both idiopathic pulmonary (IPF) and non-IPF fibrosing ILD patients. Patients were divided into a discovery (n = 211) and a validation (n = 260) cohort. Longitudinal changes of 6MWD% and lung function parameters were simultaneously considered. LTx-free survival at 3 years from baseline was the endpoint. Competing risks of death and LTx were considered. RESULTS: Baseline 6MWD% and its longitudinal changes were significant predictors of LTx-free survival and independent from lung function variables. In both cohorts, on multivariate cox proportional hazard regression analysis, receiver operating characteristics analysis and Kaplan-Meier estimates, 6MWD% was consistently, but only slightly superior to 6MWD-m as a predictor of LTx-free survival. CONCLUSION: 6MWD% has only a slight, yet detectable advantage over 6MWD-m as a predictor of survival in fibrosing ILDs. Utilizing 6MWD% may aid in risk stratification, treatment monitoring, and LTx timing optimization. However, available reference equations do have predicting limitations. Refined predictive equations and standardizing reporting practices are therefore needed to further enhance the clinical utility of 6MWD% in fibrosing ILDs.

Send in the Clowns: A Special Tribute to Medical Clowning and Clown Eponyms in Dermatology.

Clowns have long delighted circus crowds and are celebrated not only in popular culture but also in the dermatology literature as medical eponyms. This contribution discusses four such eponyms: 1) clown nose-like lesion, 2) clown eczema (perioral dermatitis) 3) clown alopecia pattern in frontal fibrosing alopecia and 4) clown's face of Brachman de Lange syndrome (Cornelia de Lange syndrome). This contribution also highlights the role of medical clowning in patient care by paying tribute to Cobo the Clown, also known as Barbara Joyce Cohen, who has served as a dedicated caring clown for over thirty years.

Pilot study of home-based monitoring for early prediction of acute exacerbations in patients with fibrosing interstitial lung diseases.

This study aimed to assess the potential of home monitoring using a monitoring application for the early prediction of acute exacerbations (AEs) in patients with fibrosing interstitial lung diseases (F-ILDs) by tracking symptoms, peripheral blood oxygen saturation (SpO2), and heart rate (HR). Data on symptoms, SpO2, and HR before and after a 1-min sit-to-stand test (1STST) were collected using an online home monitoring application. Symptoms were recorded at least 3 times a week, including cough intensity and frequency (Cough Assessment Test scale (COAT) score), breathlessness grade (modified Medical Research Council (mMRC) score), and SpO2 and HR before and after 1STST. Eighty-five patients with stable F-ILDs were enrolled. We observed a significant increase in COAT and mMRC scores, alongside a significant decrease in SpO2 before and after 1STST, 2 weeks before the first recorded AE. Furthermore, a combination of variables-an increase in COAT (≥ 4) and mMRC(≥ 1) scores, a decrease in SpO2 at rest (≥ 5%), and a decrease in SpO2 after 1STST (≥ 4%)- proved the most effective in predicting AE onset in patients with F-ILDs at 2 weeks before the first recorded AE. Home telemonitoring of symptoms, SpO2 holds potential value for early AE detection in patients with F-ILDs.

Evaluation of hair surface structure and morphology of patients with lichen planopilaris (LPP) by atomic force microscopy (AFM).

BACKGROUND: Lichen planopilaris (LPP) is a chronic lymphocytic skin disease manifested by progressive scarring alopecia. The diagnosis of LPP is made based on histopathological examination, although it is not always definite. The current study evaluates the effectiveness of non-invasive atomic force microscopy (AFM) hair examination in detecting morphological differences between healthy and diseased hair. MATERIALS AND METHODS: Here, three to five hairs from lesional skin of 10 LPP patients were collected and examined at nine locations using AFM. At least four images were taken at each of the nine sites. Metric measurements were taken and metric (length, width, and scale step height) and morphological features (striated and smooth surface of scales, the presence of endocuticle and cortex, shape of scales edges, scratches, pitting, cracks, globules, and wavy edge) were compared with hair from healthy controls. In addition, areas on diseased hair where the process of pathological, unnatural delamination of the hair fiber occurs are described. RESULTS: There was a statistically significant difference in the number of scratches in the initial sections of the LPP hair, in the intensity of wavy edges along the entire length of the tested hair, and in the number of scales with pitting in the middle section of the hair. In addition, a statistically significant higher number of scales with striated surface was found in LPP group starting at 3.5 cm from the root continuing towards the free end of the hair. Other morphological changes such as presence of cortex, globules, oval indentations, and rod-like macrofibrillar elements were also assessed, however, detailed results are not presented, as the differences shown in the number of these morphological changes were not significantly different. CONCLUSION: This publication outlines the differences between virgin, healthy Caucasian hair, and the hair of LPP patients. The results of this study can be used for further research and work related to LPP. This is the first attempt to characterize the hair of LPP patients using AFM.

Evaluation of fibroblast activation protein-specific PET/CT in a patient with post-COVID pneumonitis.

Coronavirus disease 2019 (COVID-19) often leads to a spectrum of pulmonary complications, including interstitial lung disease (ILD) with the potential for fibrotic sequelae. Assessing the presence of ongoing active inflammation versus established residual fibrosis as a result of lung parenchymal injury and repair in these patients is a clinical challenge. Better understanding of the disease process is crucial for guiding appropriate therapeutic strategies. We aim to investigate the use of positron emission tomography / computer tomography (PET/CT) scans and their role in diagnosing interstitial pneumonitis (IP) post COVID infections.

The impact of psoriasis on idiopathic pulmonary fibrosis: a two-sample Mendelian randomization study.

BACKGROUND: The association between psoriasis and pulmonary fibrosis has been reported in observational studies. However, the association is vulnerable to bias from using immunosuppressants such as methotrexate, which can cause fibrosis in multiple organs. The present study is to investigate whether psoriasis could independently increase the risk of idiopathic pulmonary fibrosis (IPF). METHODS: We conducted a two-sample Mendelian randomization (MR) study using summary statistics from genome-wide association studies. The random-effects inverse variance weighted analysis was used as the primary method. Some secondary analyses were further performed, including a sensitivity analysis using a genetic instrument that excluded extended single nucleotide polymorphisms (SNPs) in the major histocompatibility complex (MHC) gene region. RESULTS: Our study included 9267 cases and 364,071 controls for psoriasis, 2018 cases, and 373,064 controls for IPF of European ancestry, respectively. Genetically predicted psoriasis was associated with a higher risk of IPF (odds ratio (OR), 1.14; 95% confidence interval (CI), 1.08-1.22; P < 0.001). Sensitivity analyses did not uncover any statistically significant evidence of bias resulting from pleiotropy or the genetic instruments, including SNPs in the MHC gene region. CONCLUSIONS: These MR analyses support that genetically predicted psoriasis was associated with the risk of IPF, implying that pulmonary fibrosis in patients with psoriasis should not be neglected, even if they are not receiving immunosuppressant therapy.