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Recent Advances in Interstitial Lung Diseases
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Recent Advances in Interstitial Lung Diseases

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 11381

Special Issue Editors

Prof. Dr. Dominique Israël-Biet

E-Mail Website
Guest Editor
Service de Pneumologie et Soins Intensifs, Assistance Publique-Hôpitaux de Paris Centre, Hôpital Européen Georges Pompidou, 75015 Paris, France
Interests: interstitial lung diseases
Prof. Dr. Hilario Nunes

E-Mail Website
Guest Editor
Service de Pneumologie, Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, 93009 Bobigny, France
Interests: interstitial lung diseases
Prof. Dr. Paolo Spagnolo

E-Mail Website
Guest Editor
Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
Interests: interstitial lung diseases
Dr. Daniel A. Culver

E-Mail Website
Guest Editor
Cleveland Clinic Respiratory Institute, Cleveland, OH 44195, USA
Interests: sarcoidosis; idiopathic pulmonary fibrosis

Special Issue Information

Dear Colleagues,

Interstitial lung diseases (ILDs) encompass a vast domain of actually different diseases, underlined by a variety of pathological mechanisms, all ending up in lesions of the alveolar and/or interstitial regions of lung parenchyma. The ultimate phase of these various processes, if not arrested, is the development of irreversible pulmonary fibrosis. When diffused and extended, it severely compromises the pulmonary function and quality of life of affected patients, as well their mortality risks.   

ILDs are the object of continuous and very active research in terms of epidemiological, clinical, pathogenic, and therapeutical issues. In 2022 alone, for instance, new guidelines of the ATS/ERS/JRS/ALAT have updated their previous recommendations on the management of idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis in adults, while the ERS has published specific guidelines about a crucial diagnostic tool: transbronchial lung cryobiopsy.

Major findings have been highlighted in recent publications such as the clear increase in incidence and mortality of ILDs over the last few decades, particularly among the ageing population. They have also showed consistent differences across regions of the world pointing out the potential responsibility of differences in genetic backgrounds, environmental exposure, access to certain diagnostic tools (novel biomarkers for instance), and drugs.

Strong predictors of mortality now exist, highlighting the requirements for early diagnosis and appropriate management.

The role of antifibrotic drugs in these conditions is now better understood, as well as that of other innovative therapeutical options. Supportive care has also been better developed in order to meet the requirements of appropriate management. Patients’ reported outcomes (PROs) are now also well known to be important markers not only in their everyday life but also as targeted endpoints in clinical studies.

Among the most severe ILDs comorbidities, the role of lung cancer has been largely stressed. The association of both conditions, in addition to strongly impacting prognosis, requires specific therapeutic measures.

All of these new data should be brought to the attention of all practitioners dealing with patients with ILDs.

Lastly, the COVID-19 pandemic, with its own impact on patients with ILDs conditions and its relationship with the potential development of irreversible fibrotic pulmonary lesions, has shed a new light on comprehension and management of ILDs.

In summary, the last years have been extremely rich in innovative concepts about ILDs. This Special Issue aims to highlight some of the most important ones.

Prof. Dr. Dominique Israël-Biet
Prof. Dr. Hilario Nunes
Prof. Dr. Paolo Spagnolo
Dr. Daniel A. Culver
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (5 papers)

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Research

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17 pages, 1688 KiB  
Article
Molecular Factors in PAD2 (PADI2) and PAD4 (PADI4) Are Associated with Interstitial Lung Disease Susceptibility in Rheumatoid Arthritis Patients
by Karol J. Nava-Quiroz, Jorge Rojas-Serrano, Gloria Pérez-Rubio, Ivette Buendia-Roldan, Mayra Mejía, Juan Carlos Fernández-López, Pedro Rodríguez-Henríquez, Noé Ayala-Alcantar, Espiridión Ramos-Martínez, Luis Alberto López-Flores, Alma D. Del Ángel-Pablo and Ramcés Falfán-Valencia
Cells 2023, 12(18), 2235; https://doi.org/10.3390/cells12182235 - 8 Sep 2023
Cited by 3 | Viewed by 1824
Abstract
Around 50% of rheumatoid arthritis (RA) patients show some extra-articular manifestation, with the lung a usually affected organ; in addition, the presence of anti-citrullinated protein antibodies (ACPA) is a common feature, which is caused by protein citrullination modifications, catalyzed by the peptidyl arginine [...] Read more.
Around 50% of rheumatoid arthritis (RA) patients show some extra-articular manifestation, with the lung a usually affected organ; in addition, the presence of anti-citrullinated protein antibodies (ACPA) is a common feature, which is caused by protein citrullination modifications, catalyzed by the peptidyl arginine deiminases (PAD) enzymes. We aimed to identify single nucleotide variants (SNV) in PADI2 and PADI4 genes (PAD2 and PAD4 proteins, respectively) associated with susceptibility to interstitial lung disease (ILD) in RA patients and the PAD2 and PAD4 levels. Material and methods: 867 subjects were included: 118 RA-ILD patients, 133 RA patients, and 616 clinically healthy subjects (CHS). Allelic discrimination was performed in eight SNVs using qPCR, four in PADI2 and four in PADI4. The ELISA technique determined PAD2 and PAD4 levels in serum and bronchoalveolar lavage (BAL) samples, and the population structure was evaluated using 14 informative ancestry markers. Results: The rs1005753-GG (OR = 4.9) in PADI2 and rs11203366-AA (OR = 3.08), rs11203367-GG (OR = 2.4) in PADI4 are associated with genetic susceptibility to RA-ILD as well as the ACTC haplotype (OR = 2.64). In addition, the PAD4 protein is increased in RA-ILD individuals harboring the minor allele homozygous genotype in PADI4 SNVs. Moreover, rs1748033 in PADI4, rs2057094, and rs2076615 in PADI2 are associated with RA susceptibility. In conclusion, in RA patients, single nucleotide variants in PADI4 and PADI2 are associated with ILD susceptibility. The rs1748033 in PADI4 and two different SNVs in PADI2 are associated with RA development but not ILD. PAD4 serum levels are increased in RA-ILD patients. Full article
(This article belongs to the Special Issue Recent Advances in Interstitial Lung Diseases)
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Review

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18 pages, 1022 KiB  
Review
Peptidyl Arginine Deiminases in Chronic Diseases: A Focus on Rheumatoid Arthritis and Interstitial Lung Disease
by Karol J. Nava-Quiroz, Luis A. López-Flores, Gloria Pérez-Rubio, Jorge Rojas-Serrano and Ramcés Falfán-Valencia
Cells 2023, 12(24), 2829; https://doi.org/10.3390/cells12242829 - 13 Dec 2023
Viewed by 2186
Abstract
Protein citrullination is accomplished by a broad enzyme family named Peptidyl Arginine Deiminases (PADs), which makes this post-translational modification in many proteins that perform physiological and pathologic mechanisms in the body. Due to these modifications, citrullination has become a significant topic in the [...] Read more.
Protein citrullination is accomplished by a broad enzyme family named Peptidyl Arginine Deiminases (PADs), which makes this post-translational modification in many proteins that perform physiological and pathologic mechanisms in the body. Due to these modifications, citrullination has become a significant topic in the study of pathological processes. It has been related to some chronic and autoimmune diseases, including rheumatoid arthritis (RA), interstitial lung diseases (ILD), multiple sclerosis (MS), and certain types of cancer, among others. Antibody production against different targets, including filaggrin, vimentin, and collagen, results in an immune response if they are citrullinated, which triggers a continuous inflammatory process characteristic of autoimmune and certain chronic diseases. PAD coding genes (PADI1 to PADI4 and PADI6) harbor variations that can be important in these enzymes’ folding, activity, function, and half-life. However, few studies have considered these genetic factors in the context of chronic diseases. Exploring PAD pathways and their role in autoimmune and chronic diseases is a major topic in developing new pharmacological targets and valuable biomarkers to improve diagnosis and prevention. The present review addresses and highlights genetic, molecular, biochemical, and physiopathological factors where PAD enzymes perform a major role in autoimmune and chronic diseases. Full article
(This article belongs to the Special Issue Recent Advances in Interstitial Lung Diseases)
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21 pages, 2993 KiB  
Review
Hypoxia Induces Alterations in the Circadian Rhythm in Patients with Chronic Respiratory Diseases
by Manuel Castillejos-López, Yair Romero, Angelica Varela-Ordoñez, Edgar Flores-Soto, Bianca S. Romero-Martinez, Rafael Velázquez-Cruz, Joel Armando Vázquez-Pérez, Víctor Ruiz, Juan C. Gomez-Verjan, Nadia A. Rivero-Segura, Ángel Camarena, Ana Karen Torres-Soria, Georgina Gonzalez-Avila, Bettina Sommer, Héctor Solís-Chagoyán, Ruth Jaimez, Luz María Torres-Espíndola and Arnoldo Aquino-Gálvez
Cells 2023, 12(23), 2724; https://doi.org/10.3390/cells12232724 - 29 Nov 2023
Cited by 2 | Viewed by 2331
Abstract
The function of the circadian cycle is to determine the natural 24 h biological rhythm, which includes physiological, metabolic, and hormonal changes that occur daily in the body. This cycle is controlled by an internal biological clock that is present in the body’s [...] Read more.
The function of the circadian cycle is to determine the natural 24 h biological rhythm, which includes physiological, metabolic, and hormonal changes that occur daily in the body. This cycle is controlled by an internal biological clock that is present in the body’s tissues and helps regulate various processes such as sleeping, eating, and others. Interestingly, animal models have provided enough evidence to assume that the alteration in the circadian system leads to the appearance of numerous diseases. Alterations in breathing patterns in lung diseases can modify oxygenation and the circadian cycles; however, the response mechanisms to hypoxia and their relationship with the clock genes are not fully understood. Hypoxia is a condition in which the lack of adequate oxygenation promotes adaptation mechanisms and is related to several genes that regulate the circadian cycles, the latter because hypoxia alters the production of melatonin and brain physiology. Additionally, the lack of oxygen alters the expression of clock genes, leading to an alteration in the regularity and precision of the circadian cycle. In this sense, hypoxia is a hallmark of a wide variety of lung diseases. In the present work, we intended to review the functional repercussions of hypoxia in the presence of asthma, chronic obstructive sleep apnea, lung cancer, idiopathic pulmonary fibrosis, obstructive sleep apnea, influenza, and COVID-19 and its repercussions on the circadian cycles. Full article
(This article belongs to the Special Issue Recent Advances in Interstitial Lung Diseases)
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13 pages, 843 KiB  
Review
Pulmonary Hypertension in Interstitial Lung Disease: Updates in Disease, Diagnosis, and Therapeutics
by Zachary A. Haynes, Abhimanyu Chandel and Christopher S. King
Cells 2023, 12(19), 2394; https://doi.org/10.3390/cells12192394 - 1 Oct 2023
Cited by 2 | Viewed by 2404
Abstract
Pulmonary hypertension is a debilitating condition that frequently develops in the setting of interstitial lung disease, likely related to chronic alveolar hypoxemia and pulmonary vascular remodeling. This disease process is likely to be identified more frequently by providers given recent advancements in definitions [...] Read more.
Pulmonary hypertension is a debilitating condition that frequently develops in the setting of interstitial lung disease, likely related to chronic alveolar hypoxemia and pulmonary vascular remodeling. This disease process is likely to be identified more frequently by providers given recent advancements in definitions and diagnostic modalities, and provides practitioners with emerging opportunities to improve patient outcomes and quality of life. Despite years of data suggesting against the efficacy of pulmonary vasodilator therapy in patients with pulmonary hypertension due to interstitial lung disease, new data have emerged identifying promising advancements in therapeutics. The authors present to you a comprehensive review of pulmonary hypertension in interstitial lung disease, reviewing our current understanding of pathophysiology, updates in diagnostic approaches, and highlights of recent clinical trials which provide an effective approach for medical management. Full article
(This article belongs to the Special Issue Recent Advances in Interstitial Lung Diseases)
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19 pages, 666 KiB  
Review
Pulmonary Sequelae of COVID-19: Focus on Interstitial Lung Disease
by Janet Johnston, Delia Dorrian, Dermot Linden, Stefan Cristian Stanel, Pilar Rivera-Ortega and Nazia Chaudhuri
Cells 2023, 12(18), 2238; https://doi.org/10.3390/cells12182238 - 8 Sep 2023
Cited by 2 | Viewed by 2134
Abstract
As the world transitions from the acute phase of the COVID-19 pandemic, a novel concern has arisen—interstitial lung disease (ILD) as a consequence of SARS-CoV-2 infection. This review discusses what we have learned about its epidemiology, radiological, and pulmonary function findings, risk factors, [...] Read more.
As the world transitions from the acute phase of the COVID-19 pandemic, a novel concern has arisen—interstitial lung disease (ILD) as a consequence of SARS-CoV-2 infection. This review discusses what we have learned about its epidemiology, radiological, and pulmonary function findings, risk factors, and possible management strategies. Notably, the prevailing radiological pattern observed is organising pneumonia, with ground-glass opacities and reticulation frequently reported. Longitudinal studies reveal a complex trajectory, with some demonstrating improvement in lung function and radiographic abnormalities over time, whereas others show more static fibrotic changes. Age, disease severity, and male sex are emerging as risk factors for residual lung abnormalities. The intricate relationship between post-COVID ILD and idiopathic pulmonary fibrosis (IPF) genetics underscores the need for further research and elucidation of shared pathways. As this new disease entity unfolds, continued research is vital to guide clinical decision making and improve outcomes for patients with post-COVID ILD. Full article
(This article belongs to the Special Issue Recent Advances in Interstitial Lung Diseases)
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