Journal of Clinical Medicine

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17 pages, 1208 KiB

Open AccessArticle

Prognostic Role and Determinants of Ascending Aorta Dilatation in Non-Advanced Idiopathic Pulmonary Fibrosis: A Preliminary Observation from a Tertiary University Center

by Andrea Sonaglioni, Antonella Caminati, Greta Behring, Gian Luigi Nicolosi, Gaetana Anna Rispoli, Maurizio Zompatori, Michele Lombardo and Sergio Harari

J. Clin. Med. 2025, 14(4), 1300; https://doi.org/10.3390/jcm14041300 - 15 Feb 2025

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Abstract

Background: Patients with idiopathic pulmonary fibrosis (IPF) have a high prevalence of cardiovascular (CV) risk factors and an increased CV disease burden. The aim of this study was to investigate the prognostic role of the ascending aorta (AA) diameter in patients with mild-to-moderate [...] Read more.

Background: Patients with idiopathic pulmonary fibrosis (IPF) have a high prevalence of cardiovascular (CV) risk factors and an increased CV disease burden. The aim of this study was to investigate the prognostic role of the ascending aorta (AA) diameter in patients with mild-to-moderate IPF and to identify the main determinants of AA dilatation. Methods: All IPF patients without severe pulmonary hypertension who underwent a multi-instrumental evaluation, comprehensive of high-resolution computed tomography (HRCT) and transthoracic echocardiography (TTE), between September 2017 and November 2023, were retrospectively analyzed. The primary endpoint was the composite of “all-cause mortality or re-hospitalization for all causes”, over a medium-term follow-up. The secondary endpoint was to evaluate the independent predictors of AA dilatation. Additionally, Bland–Altman analysis was used to assess the accuracy and precision of echocardiography-derived AA diameters compared with non-ECG gated HRCT measurements. Results: A total of 105 IPF patients and 102 age-, sex-, and CV risk factor-matched controls without IPF were evaluated retrospectively. Over a follow-up of 3.9 ± 1.9 yrs, 31 patients died and 47 were re-hospitalized. AA/height (HR 1.15, 95% CI 1.06–1.25, p < 0.001) was independently associated with the primary endpoint, whereas unindexed AA (HR 1.01, 95% CI 0.96–1.06, p = 0.83) and AA/BSA (HR 1.00, 95% CI 0.89–1.11, p = 0.39) were not. An AA/height > 20 mm/m showed 100% sensitivity and 63% specificity (AUC = 0.78) for predicting the primary endpoint. C-reactive protein (OR 1.87; 95% CI 1.21–2.89, p = 0.005) and left ventricular mass index (OR 1.13, 95% CI 1.04–1.24, p = 0.006) were independently associated with an AA/height > 20 mm/m in the whole study group. The Bland–Altman analysis revealed a bias of +2.51 mm (with the 95% limits of agreement ranging from −3.62 to 8.65 mm) for AA estimation, suggesting a general overestimation of the AA diameter by TTE in comparison to HRCT. Conclusions: AA dilatation is predictive of poor outcomes in IPF patients without advanced lung disease over a mid-term follow-up. The AA/height assessment may improve the prognostic risk stratification of IPF patients. Full article

(This article belongs to the Special Issue Updates on Interstitial Lung Disease)

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16 pages, 1974 KiB

Open AccessArticle

Exercise-Induced Oxygen Desaturation and Outcomes After Nintedanib Therapy for Fibrosing Interstitial Lung Disease in Patients Without Dyspnea

by Masaki Okamoto, Toyoshi Yanagihara, Kiminori Fujimoto, Tomonori Chikasue, Kazuhiro Tabata, Yoshiaki Zaizen, Masaki Tominaga, Akiko Sumi, Yuuya Nishii, Norikazu Matsuo, Takashi Nouno, Shuji Matsuura, Atsushi Kawaguchi and Tomoaki Hoshino

J. Clin. Med. 2024, 13(24), 7865; https://doi.org/10.3390/jcm13247865 - 23 Dec 2024

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Abstract

Background: The degree of exercise-induced oxygen desaturation and outcomes following antifibrotic drug therapy in asymptomatic patients with fibrosing interstitial lung disease (FILD) remain unclear. Methods: We compared clinical data, incidence of annual FILD progression, overall survival, and tolerability after initiating nintedanib between 58 [...] Read more.

Background: The degree of exercise-induced oxygen desaturation and outcomes following antifibrotic drug therapy in asymptomatic patients with fibrosing interstitial lung disease (FILD) remain unclear. Methods: We compared clinical data, incidence of annual FILD progression, overall survival, and tolerability after initiating nintedanib between 58 patients with dyspnea and 18 patients without. Annual FILD progression was defined as >10% decrease in forced vital capacity (FVC), >15% decrease in diffusing capacity of the lungs for carbon monoxide (D_LCO), developing acute exacerbations, or FILD-related death within 1 year of starting nintedanib. Outcomes between the two groups were adjusted for covariates, including age, gender, FVC, D_LCO, and diagnosis of idiopathic pulmonary fibrosis, all known prognostic factors for FILD. Results: In 6-min walk test, incidence of decrease to <90% of SpO₂ was significantly lower in non-dyspnea group than in dyspnea group (24% vs. 55%, p = 0.028), but incidence of >4% decreases showed no significant difference (71% vs. 89%, p = 0.11) The incidence of annual progression was significantly lower in non-dyspnea than in dyspnea group (17% vs. 53%, adjusted p = 0.026). The relative change in D_LCO was significantly slower in non-dyspnea group (adjusted p = 0.036), but FVC was not (adjusted p = 0.067). Overall survival was longer in non-dyspnea group (adjusted p = 0.0089). The discontinuation rate and therapeutic period of nintedanib were not significantly different between the groups. Conclusions: Asymptomatic patients with FILD have severe exercise-induced oxygen desaturation and better outcomes after nintedanib therapy than symptomatic patients. Antifibrotic drug therapy should not be avoided solely because of a lack of symptoms. Full article

(This article belongs to the Special Issue Updates on Interstitial Lung Disease)

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Review

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14 pages, 1404 KiB

Open AccessReview

Updates in Diagnostic Tools for ILD

by Arsal Tharwani and Manuel L. Ribeiro Neto

J. Clin. Med. 2025, 14(9), 2924; https://doi.org/10.3390/jcm14092924 - 24 Apr 2025

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Abstract

Interstitial lung disease (ILD) is a group of diffuse parenchymal disorders, which are diagnosed in many cases by multidisciplinary discussion (MDD). In some cases, diagnosis can be challenging, and the addition of histopathology can increase diagnostic confidence. The tools to obtain a histopathological [...] Read more.

Interstitial lung disease (ILD) is a group of diffuse parenchymal disorders, which are diagnosed in many cases by multidisciplinary discussion (MDD). In some cases, diagnosis can be challenging, and the addition of histopathology can increase diagnostic confidence. The tools to obtain a histopathological sample to diagnose ILD are expanding. In this review, we will discuss the various modalities, their sensitivities and specificities, and procedural complication rates. In this review, we conducted a comprehensive review of literature focusing on emerging and established diagnostic tools for ILD. A systematic search of peer-reviewed publications was performed using PubMed with a focus on clinical trials, retrospective and prospective cohort studies, and systematic reviews. The key diagnostic modalities in focus were genomic classifier (GC), transbronchial cryobiopsy (TBLC), surgical lung biopsy (SLB), endobronchial ultrasound cryobiopsy (EBUS-C), genetic testing, and speckled transthoracic echocardiography (STE). Data extracted from these studies focused on diagnostic yield, specificity, sensitivity, and procedural complication rate. Genomic classifier, a gene-based molecular diagnostic tool, has a high specificity for histological usual interstitial pneumonia (UIP). However, in cases of a negative result, it often results in a need for further invasive sampling by TBLC or SLB. TBLC results in a larger histological sample, which can increase diagnostic yield and increase diagnostic confidence at MDD. Recent prospective trials have compared this modality with SLB and found 63–77% interobserver agreement between pathologists. SLB remains the gold standard with diagnostic yields reported to be more than 90%. EBUS-C has shown promising results increasing diagnostic yield in patients with suspected sarcoidosis or lymphoma. All diagnostic modalities have procedural complications with most common being pneumothorax, bleeding and, rarely, death. Advancements in diagnostic tools for interstitial lung disease (ILD) have significantly improved accuracy. Even though surgical lung biopsy remains the gold standard, the alternative modalities are promising and provide a promising yield with a lower procedural risk. Full article

(This article belongs to the Special Issue Updates on Interstitial Lung Disease)

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20 pages, 2393 KiB

Open AccessReview

Review of the Diagnosis and Management of Pulmonary Hypertension Associated with Interstitial Lung Disease (ILD-PH)

by Zein Kattih, Ho Cheol Kim, Shambhu Aryal and Steven D. Nathan

J. Clin. Med. 2025, 14(6), 2029; https://doi.org/10.3390/jcm14062029 - 17 Mar 2025

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Abstract

Pulmonary hypertension associated with interstitial lung disease (ILD-PH) frequently complicates the course of patients with fibrotic ILD. In this narrative review, the authors assess current diagnostic tools and management considerations in ILD-PH patients. ILD-PH is associated with increased morbidity and mortality and may [...] Read more.

Pulmonary hypertension associated with interstitial lung disease (ILD-PH) frequently complicates the course of patients with fibrotic ILD. In this narrative review, the authors assess current diagnostic tools and management considerations in ILD-PH patients. ILD-PH is associated with increased morbidity and mortality and may be suggested by the presence of symptoms out of proportion to the extent of the ILD. There are other clues to the presence of PH in the context of ILD including the need for supplemental oxygen, a reduced DLCO especially if accompanied by a disproportionately higher forced vital capacity, imaging demonstrating an enlarged pulmonary artery or a dilated right ventricle, or objective evidence of a reduced exercise capacity. While echocardiography is one screening tool, right heart catheterization remains the gold standard for the diagnosis of PH. When appropriate, treatment with inhaled treprostinil, or possibly other pulmonary vasodilators, may be indicated. Full article

(This article belongs to the Special Issue Updates on Interstitial Lung Disease)

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15 pages, 549 KiB

Open AccessReview

Telomeropathies in Interstitial Lung Disease and Lung Transplant Recipients

by Brian D. Southern and Shruti K. Gadre

J. Clin. Med. 2025, 14(5), 1496; https://doi.org/10.3390/jcm14051496 - 24 Feb 2025

Viewed by 815

Abstract

Telomeropathies, or telomere biology disorders (TBDs), are syndromes that can cause a number of medical conditions, including interstitial lung disease (ILD), bone marrow failure, liver fibrosis, and other diseases. They occur due to genetic mutations to the telomerase complex enzymes that result in [...] Read more.

Telomeropathies, or telomere biology disorders (TBDs), are syndromes that can cause a number of medical conditions, including interstitial lung disease (ILD), bone marrow failure, liver fibrosis, and other diseases. They occur due to genetic mutations to the telomerase complex enzymes that result in premature shortening of telomeres, the caps on the ends of cellular DNA that protect chromosome length during cell division, leading to early cell senescence and death. Idiopathic pulmonary fibrosis (IPF) is the most common manifestation of the telomere biology disorders, although it has been described in other interstitial lung diseases as well, such as rheumatoid arthritis-associated ILD and chronic hypersensitivity pneumonitis. Telomere-related mutations can be inherited or can occur sporadically. Identifying these patients and offering genetic counseling is important because telomerapathies have been associated with poorer outcomes including death, lung transplantation, hospitalization, and FVC decline. Additionally, treatment with immunosuppressants has been shown to be associated with worse outcomes. Currently, there is no specific treatment for TBD except to transplant the organ that is failing, although there are a number of promising treatment strategies currently under investigation. Shortened telomere length is routinely discovered in patients undergoing lung transplantation for IPF. Testing to detect early TBD in patients with suggestive signs or symptoms can allow for more comprehensive treatment and multidisciplinary care pre- and post-transplant. Patients with TBD undergoing lung transplantation have been reported to have both pulmonary and extrapulmonary complications at a higher frequency than other lung transplant recipients, such as graft-specific complications, increased infections, and complications related to immunosuppressive therapy. Full article

(This article belongs to the Special Issue Updates on Interstitial Lung Disease)

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11 pages, 243 KiB

Open AccessReview

Non-Pharmacological Management of Idiopathic Pulmonary Fibrosis

by Jon B. Mullholand, Catherine E. Grossman and Apostolos Perelas

J. Clin. Med. 2025, 14(4), 1317; https://doi.org/10.3390/jcm14041317 - 17 Feb 2025

Viewed by 1079

Abstract

Idiopathic pulmonary fibrosis (IPF) is a relatively common progressive fibrotic interstitial lung disease associated with significant morbidity and mortality. The available medications for IPF only slow down the disease process, with lung transplantation the only option for a cure. Non-pharmacological therapies are significant [...] Read more.

Idiopathic pulmonary fibrosis (IPF) is a relatively common progressive fibrotic interstitial lung disease associated with significant morbidity and mortality. The available medications for IPF only slow down the disease process, with lung transplantation the only option for a cure. Non-pharmacological therapies are significant adjuncts that can improve symptom burden and quality of life with minimal or no side effects. Supplemental oxygen can improve exercise capacity and the sensation of dyspnea in a significant portion of patients with resting or exertional hypoxemia and has been supported by several professional societies. Pulmonary rehabilitation is a comprehensive program that includes education and therapeutic exercises to improve patient stamina and strength. It is one of the few interventions that have been shown to produce a meaningful increase in a patient’s exercise capacity, but its wide adoption is limited by availability, especially in rural areas. Sleep optimization with supplemental oxygen and positive airway pressure therapy should actively be investigated for all patients diagnosed with IPF. Although gastroesophageal reflux control with non-pharmacological means is still controversial as an intervention to reduce the rate of lung function decline, it can help control reflux symptoms and improve cough intensity. IPF patients should be educated on the importance of balanced nutrition and the potential benefits of screening for lung transplantation. Palliative medicine can help with symptom control and should be considered for all patients regardless severity, but especially in those in the later stages of disease. Full article

(This article belongs to the Special Issue Updates on Interstitial Lung Disease)

18 pages, 294 KiB

Open AccessReview

Beyond the Graft: Recurrence of Interstitial Lung Diseases Post Transplant

by Prince Ntiamoah and Atul C. Mehta

J. Clin. Med. 2025, 14(4), 1093; https://doi.org/10.3390/jcm14041093 - 8 Feb 2025

Viewed by 566

Abstract

Interstitial lung diseases (ILDs) represent a heterogenous group of lung disorders marked by inflammation and/or fibrosis of the lung parenchyma, often leading to progressive shortness of breath and end-stage respiratory failure. In the U.S., ILDs affect approximately 650,000 individuals and cause approximately 25,000–30,000 [...] Read more.

Interstitial lung diseases (ILDs) represent a heterogenous group of lung disorders marked by inflammation and/or fibrosis of the lung parenchyma, often leading to progressive shortness of breath and end-stage respiratory failure. In the U.S., ILDs affect approximately 650,000 individuals and cause approximately 25,000–30,000 deaths annually. Lung transplantation (LTx) offers definitive treatment for advanced ILD, with improved survival attributed to advancements in immunosuppression, organ preservation, surgical techniques, and postoperative care. However, disease recurrence in transplanted lungs remains a significant concern. Understanding the risk factors and mechanisms underlying recurrence is critical for refining recipient selection and improving outcomes. This review examines ILD recurrence post LTx and its implications for lung transplantation success. Full article

(This article belongs to the Special Issue Updates on Interstitial Lung Disease)

31 pages, 4653 KiB

Open AccessReview

Examining Cough’s Role and Relief Strategies in Interstitial Lung Disease

by Chee Yao Lim, Sanam Wasim Khan, Tarek Alsibai and Gayathri Sathiyamoorthy

J. Clin. Med. 2025, 14(1), 291; https://doi.org/10.3390/jcm14010291 - 6 Jan 2025

Viewed by 1656

Abstract

Chronic cough is a distressing and prevalent symptom in interstitial lung disease (ILD), significantly impairing quality of life (QoL) and contributing to disease progression, particularly in idiopathic pulmonary fibrosis (IPF). It is associated with physical discomfort, psychological distress, and social isolation and is [...] Read more.

Chronic cough is a distressing and prevalent symptom in interstitial lung disease (ILD), significantly impairing quality of life (QoL) and contributing to disease progression, particularly in idiopathic pulmonary fibrosis (IPF). It is associated with physical discomfort, psychological distress, and social isolation and is often refractory to conventional therapies. The pathophysiology of cough in ILD is complex and multifactorial, involving neural hypersensitivity, structural lung changes, inflammatory processes, and comorbid conditions such as gastroesophageal reflux disease (GERD). Evaluating cough in ILD relies on subjective and objective tools to measure its severity, frequency, and impact on daily life, although standardization of these measures remains challenging. Management strategies span pharmacological interventions, including neuromodulators such as opiates, antifibrotic agents, pharmacologic and surgical GERD treatments, and non-pharmacological approaches like behavioral therapies, cough suppression techniques, and pulmonary rehabilitation and physiotherapy. Emerging treatments, such as P2X3 receptor antagonists and airway hydration therapies, offer promising avenues but require further investigation through robust clinical trials. This review aims to demonstrate the importance of addressing cough in ILD as a significant symptom and present objective and subjective methods of quantifying coughs, while providing insights into effective and emerging therapeutic options. By highlighting these potential therapies, we hope to guide healthcare practitioners in considering them through a thorough evaluation of benefits and risks on a case-by-case basis, with relevance both in the U.S. and internationally. Full article

(This article belongs to the Special Issue Updates on Interstitial Lung Disease)

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17 pages, 6623 KiB

Open AccessEditor’s ChoiceReview

The Management of Interstitial Lung Disease in the ICU: A Comprehensive Review

by Zehra Dhanani and Rohit Gupta

J. Clin. Med. 2024, 13(22), 6657; https://doi.org/10.3390/jcm13226657 - 6 Nov 2024

Viewed by 4956

Abstract

Interstitial lung disease (ILD) encompasses a diverse group of parenchymal lung diseases characterized by varying degrees of inflammation and/or fibrosis. Patients with ILD frequently require hospitalization, with many needing intensive care unit (ICU) admission, most often due to respiratory failure. The diagnosis and [...] Read more.

Interstitial lung disease (ILD) encompasses a diverse group of parenchymal lung diseases characterized by varying degrees of inflammation and/or fibrosis. Patients with ILD frequently require hospitalization, with many needing intensive care unit (ICU) admission, most often due to respiratory failure. The diagnosis and management of ILD in the ICU present unique challenges. Diagnosis primarily relies on chest CT imaging to identify fibrosis and inflammation. Acute exacerbations, whether in idiopathic pulmonary fibrosis (IPF) or non-IPF ILD, require careful evaluation of potential triggers and differential diagnoses. Bronchoalveolar lavage may provide valuable information, such as the identification of infections, but carries risks of complications. Biopsies, whether transbronchial or surgical, can also be informative but pose significant procedural risks. Corticosteroids are the cornerstone of treatment for acute exacerbations of IPF, with higher doses potentially benefiting non-IPF ILD. Additional immunosuppressive agents may be used in cases with evidence of inflammation. Oxygen supplementation, particularly with high-flow nasal cannula, is often employed to manage severe hypoxemia, while noninvasive ventilation can be useful for worsening hypoxemia and/or hypercapnia. When mechanical ventilation is used, it is recommended to target low tidal volumes to minimize lung injury; high PEEP may be less effective and even associated with increased mortality. Prone positioning can improve oxygenation in severely hypoxemic patients. In addition to ventilatory strategies, careful fluid management and addressing concomitant pulmonary hypertension are essential components of care. Extracorporeal membrane oxygenation is a high-risk intervention reserved for the most severe cases. Lung transplantation may be considered for end-stage ILD patients in the ICU, with outcomes dependent on the urgency of transplantation and the patient’s overall condition. Managing ILD in the ICU requires a multidisciplinary approach, and despite recent advances, mortality remains high, emphasizing the need for continued research and individualized treatment strategies. Full article

(This article belongs to the Special Issue Updates on Interstitial Lung Disease)

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19 pages, 359 KiB

Open AccessFeature PaperReview

What Is on the Horizon for Treatments in Idiopathic Pulmonary Fibrosis?

by Teng Moua, Misbah Baqir and Jay H. Ryu

J. Clin. Med. 2024, 13(21), 6304; https://doi.org/10.3390/jcm13216304 - 22 Oct 2024

Cited by 1 | Viewed by 2379

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal lung disease most commonly encountered in older individuals. Several decades of research have contributed to a better understanding of its pathogenesis, though only two drugs thus far have shown treatment efficacy, i.e., by [...] Read more.

Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal lung disease most commonly encountered in older individuals. Several decades of research have contributed to a better understanding of its pathogenesis, though only two drugs thus far have shown treatment efficacy, i.e., by slowing the decline of lung function. The pathogenesis of IPF remains incompletely understood and involves multiple complex interactions and mechanisms working in tandem or separately to result in unchecked deposition of extracellular matrix components and collagen characteristic of the disease. These mechanisms include aberrant response to injury in the alveolar epithelium, inappropriate communication between epithelial cells and mesenchymal cells, imbalances between oxidative injury and tissue repair, recruitment of inflammatory pathways that induce fibrosis, and cell senescence leading to sustained activation and proliferation of fibroblasts and myofibroblasts. Targeted approaches to each of these mechanistic pathways have led to recent clinical studies evaluating the safety and efficacy of several agents. This review highlights selected concepts in the pathogenesis of IPF as a rationale for understanding current or future therapeutic approaches, followed by a review of several selected agents and their recent or active clinical studies. Current novel therapies include approaches to attenuating or modifying specific cellular or signaling processes in the fibrotic pathway, modifying inflammatory and metabolic derangements, and minimizing inappropriate cell senescence. Full article

(This article belongs to the Special Issue Updates on Interstitial Lung Disease)

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9 pages, 450 KiB

Open AccessBrief Report

Improved Survival in Patients with Idiopathic Pulmonary Fibrosis Hospitalized for Acute Exacerbation

by Federico Lionello, Giovanna Arcaro, Leonardo Bertagna De Marchi, Fausto Braccioni, Alessia Achille, Sara Lococo, Michele Ciresi, Gabriella Guarnieri and Andrea Vianello

J. Clin. Med. 2025, 14(5), 1693; https://doi.org/10.3390/jcm14051693 - 3 Mar 2025

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Abstract

Background: Patients suffering from idiopathic pulmonary fibrosis (IPF) may experience acute exacerbation (AE-IPF), which frequently results in acute respiratory failure (ARF) requiring hospitalization. Objective: This study aims to determine if survival has improved over the last decade in patients hospitalized for [...] Read more.

Background: Patients suffering from idiopathic pulmonary fibrosis (IPF) may experience acute exacerbation (AE-IPF), which frequently results in acute respiratory failure (ARF) requiring hospitalization. Objective: This study aims to determine if survival has improved over the last decade in patients hospitalized for ARF consequent to AE-IPF, in view of the progress recently made in pharmacological and supportive treatment strategies. Methods: This was an observational retrospective single-center study. The data of 14 patients admitted to an Intermediate Respiratory Care Unit (IRCU) between 1 January 2004 and 31 December 2013 (group A) were compared with those of 26 patients admitted between 1 January 2014 and 31 December 2023 (group B). This study’s primary endpoint was survival following IRCU admission. Results: Survival time was significantly longer in the second group of patients compared to the first one [median survival time: 134 (31–257) vs. 25.5 (20–50) days; p < 0.001]. Group B patients also had a lower IRCU mortality rate (6/26 vs. 10/14; p = 0.003) and a significantly shorter stay in the IRCU [6 (1–60) vs. 14 (1–43) days; p = 0.039]. Conclusions: Innovative pharmacologic treatments and supportive therapeutic strategies are able to prolong survival and reduce the risk of in-hospital mortality in patients with AE-IPF hospitalized for ARF. Full article

(This article belongs to the Special Issue Updates on Interstitial Lung Disease)

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