Journal of Clinical Medicine

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11 pages, 481 KiB

Open AccessArticle

The Aggregate Index of Systemic Inflammation (AISI): A Novel Prognostic Biomarker in Idiopathic Pulmonary Fibrosis

by Angelo Zinellu, Claudia Collu, Mouhamad Nasser, Panagiotis Paliogiannis, Sabrina Mellino, Elisabetta Zinellu, Julie Traclet, Kais Ahmad, Arduino Aleksander Mangoni, Ciriaco Carru, Pietro Pirina, Alessandro Giuseppe Fois and Vincent Cottin

J. Clin. Med. 2021, 10(18), 4134; https://doi.org/10.3390/jcm10184134 - 14 Sep 2021

Cited by 46 | Viewed by 3728

Abstract

Variable patterns of disease progression are typically observed in patients with idiopathic pulmonary fibrosis (IPF). We sought to determine the prognostic capacity of blood cell count indexes, derived from routine complete blood cell (CBC) count, in a cohort of IPF patients. The neutrophil-to-lymphocyte [...] Read more.

Variable patterns of disease progression are typically observed in patients with idiopathic pulmonary fibrosis (IPF). We sought to determine the prognostic capacity of blood cell count indexes, derived from routine complete blood cell (CBC) count, in a cohort of IPF patients. The neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) were calculated at baseline in a consecutive series of 82 IPF patients followed for four years. After adjusting for age, gender, body mass index, smoking status, and disease stage, only the AISI was significantly associated with mortality (HR 1.0013, 95% CI 1.0003–1.0023, p = 0.015). Patients with AISI <434 and ≥434 had a median survival from the diagnosis of 35.3 ± 15.2 and 26.6 ± 16.3 months (p = 0.015), and a four-year survival rate of 54% and 34%, respectively. The AISI, easily derivable from routine laboratory tests, is independently associated with mortality in patients with IPF. Prospective studies in larger cohorts are required to confirm this association. Full article

(This article belongs to the Special Issue Emerging Trends in Pulmonary Fibrosis)

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15 pages, 2781 KiB

Open AccessArticle

The Extent and Diverse Trajectories of Longitudinal Changes in Rheumatoid Arthritis Interstitial Lung Diseases Using Quantitative HRCT Scores

by Jeong Seok Lee, Grace-Hyun J. Kim, You-Jung Ha, Eun Ha Kang, Yun Jong Lee, Jonathan G. Goldin and Eun Young Lee

J. Clin. Med. 2021, 10(17), 3812; https://doi.org/10.3390/jcm10173812 - 25 Aug 2021

Cited by 8 | Viewed by 2283

Abstract

We aimed to validate quantitative high-resolution computed tomography (HRCT) imaging analyses of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients, and to delineate a broad spectrum of annual longitudinal changes of ILD severity in the RA-ILD cohorts. Retrospective cohort 1 (n [...] Read more.

We aimed to validate quantitative high-resolution computed tomography (HRCT) imaging analyses of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients, and to delineate a broad spectrum of annual longitudinal changes of ILD severity in the RA-ILD cohorts. Retrospective cohort 1 (n = 26) had matched PFT results and prospective cohort 2 (n = 34) were followed for over two years with baseline serum specimen. Automated quantitative analysis of HRCT was expressed as the extent of ground-glass opacity, lung fibrosis, honeycombing, and their summation—the total extent of quantitative ILD (QILD). Higher QILD score was associated with lower pulmonary function especially for DLCO% (ρ = −0.433, p = 0.027). Higher serum level of Krebs von den Lungen 6 were significantly associated with high QILD scores (ρ = 0.400, p = 0.026). Regarding QILD score changes in whole lung, even a single point increase was significantly associated with interval progression detected by the radiologist. Four distinct patterns (improvement, worsening, convex-like, and concave-like) during the 24 months were described by QILD scores. Prolonged disease duration of ILD at baseline was significantly associated with worsening of QILD scores. QILD has the potential to reliably evaluate the dynamic severity changes in patients with RA-ILD. Full article

(This article belongs to the Special Issue Emerging Trends in Pulmonary Fibrosis)

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10 pages, 2676 KiB

Open AccessArticle

Differentiation of Idiopathic Pulmonary Fibrosis from Connective Tissue Disease-Related Interstitial Lung Disease Using Quantitative Imaging

by Jonathan H. Chung, Ayodeji Adegunsoye, Brenna Cannon, Rekha Vij, Justin M. Oldham, Christopher King, Steven M. Montner, Prahasit Thirkateh, Scott Barnett, Ronald Karwoski, Brian J. Bartholmai, Mary Strek and Steven D. Nathan

J. Clin. Med. 2021, 10(12), 2663; https://doi.org/10.3390/jcm10122663 - 17 Jun 2021

Cited by 15 | Viewed by 4034

Abstract

A usual interstitial pneumonia (UIP) imaging pattern can be seen in both idiopathic pulmonary fibrosis (IPF) and connective tissue disease-related interstitial lung disease (CTD-ILD). The purpose of this multicenter study was to assess whether quantitative imaging data differ between IPF and CTD-ILD in [...] Read more.

A usual interstitial pneumonia (UIP) imaging pattern can be seen in both idiopathic pulmonary fibrosis (IPF) and connective tissue disease-related interstitial lung disease (CTD-ILD). The purpose of this multicenter study was to assess whether quantitative imaging data differ between IPF and CTD-ILD in the setting of UIP. Patients evaluated at two medical centers with CTD-ILD or IPF and a UIP pattern on CT or pathology served as derivation and validation cohorts. Chest CT data were quantitatively analyzed including total volumes of honeycombing, reticulation, ground-glass opacity, normal lung, and vessel related structures (VRS). VRS was compared with forced vital capacity percent predicted (FVC%) and percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO%). There were 296 subjects in total, with 40 CTD-ILD and 85 IPF subjects in the derivation cohort, and 62 CTD-ILD and 109 IPF subjects in the validation cohort. VRS was greater in IPF across the cohorts on univariate (p < 0.001) and multivariable (p < 0.001–0.047) analyses. VRS was inversely correlated with DLCO% in both cohorts on univariate (p < 0.001) and in the derivation cohort on multivariable analysis (p = 0.003) but not FVC%. Total volume of normal lung was associated with DLCO% (p < 0.001) and FVC% (p < 0.001–0.009) on multivariable analysis in both cohorts. VRS appears to have promise in differentiating CTD-ILD from IPF. The underlying pathophysiological relationship between VRS and ILD is complex and is likely not explained solely by lung fibrosis. Full article

(This article belongs to the Special Issue Emerging Trends in Pulmonary Fibrosis)

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12 pages, 527 KiB

Open AccessArticle

Changes in Neutrophil–Lymphocyte or Platelet–Lymphocyte Ratios and Their Associations with Clinical Outcomes in Idiopathic Pulmonary Fibrosis

by Steven D. Nathan, Jayesh Mehta, John Stauffer, Elizabeth Morgenthien, Ming Yang, Susan L. Limb and Sangeeta Bhorade

J. Clin. Med. 2021, 10(7), 1427; https://doi.org/10.3390/jcm10071427 - 1 Apr 2021

Cited by 17 | Viewed by 2660

Abstract

Identification of prognostic and predictive biomarkers in idiopathic pulmonary fibrosis (IPF) could aid assessment of disease severity and prediction of progression and response to treatment. This analysis examined reference ranges for neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) in IPF, and the relationship [...] Read more.

Identification of prognostic and predictive biomarkers in idiopathic pulmonary fibrosis (IPF) could aid assessment of disease severity and prediction of progression and response to treatment. This analysis examined reference ranges for neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) in IPF, and the relationship between NLR or PLR changes and clinical outcomes over 12 months. This post hoc analysis included patients with IPF from the Phase III, double-blind trials of pirfenidone, ASCEND (NCT01366209) and CAPACITY (NCT00287716 and NCT00287729). The relationship between change from baseline to Month 12 in NLR or PLR (divided into quartiles (Q1–Q4)) and outcomes (mortality, respiratory hospitalization, declines in lung function, exercise capacity and quality of life) was assessed. Estimated reference ranges at baseline for all patients analyzed (n = 1334) were 1.1–6.4 for NLR and 56.8–250.5 for PLR. Significant trends were observed across NLR and PLR quartiles for all outcomes in placebo-treated patients, with patients manifesting the greatest NLR or PLR changes experiencing the worst outcomes. These results suggest that the greatest NLR or PLR changes over 12 months were associated with worse clinical outcomes. Further research is needed to determine the utility of NLR and PLR as prognostic biomarkers in IPF. Full article

(This article belongs to the Special Issue Emerging Trends in Pulmonary Fibrosis)

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13 pages, 971 KiB

Open AccessArticle

Predictors of Mortality in Patients with Interstitial Lung Disease-Associated Pulmonary Hypertension

by Esam H. Alhamad, Joseph G. Cal, Nuha N. Alrajhi and Waleed M. Alharbi

J. Clin. Med. 2020, 9(12), 3828; https://doi.org/10.3390/jcm9123828 - 26 Nov 2020

Cited by 21 | Viewed by 3376

Abstract

Background: Pulmonary hypertension (PH) is a well-established complication in interstitial lung disease (ILD) patients. The aim of this study is to investigate the physiological and hemodynamic parameters that predict mortality in patients with ILD-PH. Methods: Consecutive ILD patients who underwent right heart catheterization [...] Read more.

Background: Pulmonary hypertension (PH) is a well-established complication in interstitial lung disease (ILD) patients. The aim of this study is to investigate the physiological and hemodynamic parameters that predict mortality in patients with ILD-PH. Methods: Consecutive ILD patients who underwent right heart catheterization (n = 340) were included. The information analyzed included demographics and physiological and hemodynamic parameters. Cox regression models were used to identify independent predictors of survival. Results: In total, 96 patients had PH and an additional 56 patients had severe PH. The overall survival of idiopathic pulmonary fibrosis (IPF) patients with PH was significantly worse than the survival of patients with other types of ILD with PH (p < 0.0001 by log-rank analysis). Patients with a reduced diffusing capacity of the lung for carbon monoxide (DLco) (<35% predicted), six-minute walk test final oxygen saturation by pulse oximetry (SpO₂) < 88% and pulmonary vascular resistance ≥4.5 Wood units in the ILD-PH cohort had significantly worse survival. IPF diagnosis, forced vital capacity, DLco, systolic pulmonary artery pressure and cardiac index were identified as independent predictors of survival among the ILD-PH cohort. Conclusions: Patients with ILD-PH have poor prognosis. Physiological and hemodynamic parameters were important factors independently associated with outcome. Full article

(This article belongs to the Special Issue Emerging Trends in Pulmonary Fibrosis)

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11 pages, 432 KiB

Open AccessArticle

Automated CT Analysis of Major Forms of Interstitial Lung Disease

by Marlee S. Crews, Brian J. Bartholmai, Ayodeji Adegunsoye, Justin M. Oldham, Steven M. Montner, Ronald A. Karwoski, Aliya N. Husain, Rekha Vij, Imre Noth, Mary E. Strek and Jonathan H. Chung

J. Clin. Med. 2020, 9(11), 3776; https://doi.org/10.3390/jcm9113776 - 23 Nov 2020

Cited by 16 | Viewed by 2703

Abstract

This study aimed to determine diagnostic and prognostic differences in major forms of interstitial lung disease using quantitative CT imaging. A retrospective study of 225 subjects with a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF), interstitial pneumonia with autoimmune features (IPAF), connective tissue [...] Read more.

This study aimed to determine diagnostic and prognostic differences in major forms of interstitial lung disease using quantitative CT imaging. A retrospective study of 225 subjects with a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF), interstitial pneumonia with autoimmune features (IPAF), connective tissue disease (CTD), or chronic hypersensitivity pneumonitis (cHP) was conducted. Non-contrast CT scans were analyzed using the Computer Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) program. Resulting data were analyzed statistically using ANOVA and Student’s t-test. Univariate, multivariable, and receiver operating characteristic analyses were conducted on patient mortality data. CALIPER analysis of axial distribution on CT scans in those with IPF demonstrated greater peripheral volumes of reticulation than either CTD (p = 0.033) or cHP (p = 0.007). CTD showed lower peripheral ground-glass opacity than IPF (p = 0.005) and IPAF (p = 0.004). Statistical analysis of zonal distributions revealed reduced lower zone ground-glass opacity in cHP than IPF (p = 0.044) or IPAF (p = 0.018). Analysis of pulmonary vascular-related structure (VRS) volume by diagnosis indicated greater VRS volume in IPF compared to CTD (p = 0.003) and cHP (p = 0.003) as well as in IPAF compared to CTD (p = 0.007) and cHP (p = 0.007). Increased reticulation (p = 0.043) and ground glass opacity (p = 0.032) were predictive of mortality on univariate analysis. Increased pulmonary VRS volume was predictive of mortality (p < 0.001) even after multivariate analysis (p = 0.041). Quantitative CT imaging revealed significant differences between ILD diagnoses in specific CT findings in axial and, to a lesser degree, zonal distributions. Increased pulmonary VRS volume seems to be associated with both diagnosis and survival. Full article

(This article belongs to the Special Issue Emerging Trends in Pulmonary Fibrosis)

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Review

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12 pages, 446 KiB

Open AccessReview

Post-COVID-19 Pulmonary Fibrosis: Novel Sequelae of the Current Pandemic

by Shiva Rattan Ambardar, Stephanie L. Hightower, Nikhil A. Huprikar, Kevin K. Chung, Anju Singhal and Jacob F. Collen

J. Clin. Med. 2021, 10(11), 2452; https://doi.org/10.3390/jcm10112452 - 1 Jun 2021

Cited by 79 | Viewed by 12687

Abstract

Since the initial identification of the novel coronavirus SARS-CoV-2 in December 2019, the COVID-19 pandemic has become a leading cause of morbidity and mortality worldwide. As effective vaccines and treatments begin to emerge, it will become increasingly important to identify and proactively manage [...] Read more.

Since the initial identification of the novel coronavirus SARS-CoV-2 in December 2019, the COVID-19 pandemic has become a leading cause of morbidity and mortality worldwide. As effective vaccines and treatments begin to emerge, it will become increasingly important to identify and proactively manage the long-term respiratory complications of severe disease. The patterns of imaging abnormalities coupled with data from prior coronavirus outbreaks suggest that patients with severe COVID-19 pneumonia are likely at an increased risk of progression to interstitial lung disease (ILD) and chronic pulmonary vascular disease. In this paper, we briefly review the definition, classification, and underlying pathophysiology of interstitial lung disease (ILD). We then review the current literature on the proposed mechanisms of lung injury in severe COVID-19 infection, and outline potential viral- and immune-mediated processes implicated in the development of post-COVID-19 pulmonary fibrosis (PCPF). Finally, we address patient-specific and iatrogenic risk factors that could lead to PCPF and discuss strategies for reducing risk of pulmonary complications/sequelae. Full article

(This article belongs to the Special Issue Emerging Trends in Pulmonary Fibrosis)

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12 pages, 1031 KiB

Open AccessReview

Antifibrotic Therapies and Progressive Fibrosing Interstitial Lung Disease (PF-ILD): Building on INBUILD

by John N. Shumar, Abhimanyu Chandel and Christopher S. King

J. Clin. Med. 2021, 10(11), 2285; https://doi.org/10.3390/jcm10112285 - 25 May 2021

Cited by 24 | Viewed by 6508

Abstract

Progressive fibrosing interstitial lung disease (PF-ILD) describes a phenotypic subset of interstitial lung diseases characterized by progressive, intractable lung fibrosis. PF-ILD is separate from, but has radiographic, histopathologic, and clinical similarities to idiopathic pulmonary fibrosis. Two antifibrotic medications, nintedanib and pirfenidone, have been [...] Read more.

Progressive fibrosing interstitial lung disease (PF-ILD) describes a phenotypic subset of interstitial lung diseases characterized by progressive, intractable lung fibrosis. PF-ILD is separate from, but has radiographic, histopathologic, and clinical similarities to idiopathic pulmonary fibrosis. Two antifibrotic medications, nintedanib and pirfenidone, have been approved for use in patients with idiopathic pulmonary fibrosis. Recently completed randomized controlled trials have demonstrated the clinical efficacy of antifibrotic therapy in patients with PF-ILD. The validation of efficacy of antifibrotic therapy in PF-ILD has changed the treatment landscape for all of the fibrotic lung diseases, providing a new treatment pathway and opening the door for combined antifibrotic and immunosuppressant drug therapy to address both the fibrotic and inflammatory components of ILD characterized by mixed pathophysiologic pathways. Full article

(This article belongs to the Special Issue Emerging Trends in Pulmonary Fibrosis)

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