This Review provides an updated approach to the diagnosis of idiopathic pulmonary fibrosis (IPF), based on a systematic search of the medical literature and the expert opinion of members of the ...Fleischner Society. A checklist is provided for the clinical evaluation of patients with suspected usual interstitial pneumonia (UIP). The role of CT is expanded to permit diagnosis of IPF without surgical lung biopsy in select cases when CT shows a probable UIP pattern. Additional investigations, including surgical lung biopsy, should be considered in patients with either clinical or CT findings that are indeterminate for IPF. A multidisciplinary approach is particularly important when deciding to perform additional diagnostic assessments, integrating biopsy results with clinical and CT features, and establishing a working diagnosis of IPF if lung tissue is not available. A working diagnosis of IPF should be reviewed at regular intervals since the diagnosis might change. Criteria are presented to establish confident and working diagnoses of IPF.
CT is increasingly being used to stage and quantify the extent of diffuse lung diseases both in clinical practice and in treatment trials. The role of CT in the assessment of patients entering ...treatment trials has greatly expanded as clinical researchers and pharmaceutical companies have focused their efforts on developing safe and effective drugs for interstitial lung diseases, particularly for idiopathic pulmonary fibrosis. These efforts have culminated in the simultaneous approval by the US Food and Drug Administration of two new drugs for the treatment of idiopathic pulmonary fibrosis. CT features are a key part of the inclusion criteria in many drug trials and CT is now being used to refine the type of patients enrolled. Interest in the potential use of serial CT as an effectiveness endpoint is increasing. For chronic progressive diseases, mortality may not be a feasible endpoint and many surrogate markers have been explored, ranging from pulmonary function decline to biomarkers. However, these surrogate markers are not entirely reliable and combinations of endpoints, including change in disease extent on CT, are being investigated. Methods to assess disease severity with CT range from simple visual estimates to sophisticated quantification by use of software. In this Position Paper, which cannot be regarded as a comprehensive set of guidelines in view of present knowledge, we examine the uses of serial CT in clinical practice and in drug trials and draw attention to uncertainties and challenges for future research.
Objective
Tocilizumab (TCZ) has demonstrated lung function preservation in 2 randomized controlled trials in early systemic sclerosis (SSc). This effect has yet to be characterized in terms of ...radiographically evident quantitative lung involvement. We undertook this study to assess the impact of TCZ on lung function preservation in a post hoc analysis, stratifying treatment arms according to the degree of lung involvement.
Methods
The focuSSced trial was a phase III randomized placebo‐controlled trial of TCZ in patients with SSc and progressive skin disease. Participants underwent baseline and serial spirometry along with high‐resolution chest computed tomography at baseline and at week 48. Quantitative interstitial lung disease (QILD) and fibrosis scores were assessed by computer software. We classified QILD into the following categories of lung involvement: mild (>5–10%), moderate (>10–20%), and severe (>20%).
Results
Of 210 participants recruited for the trial, 136 patients (65%) had ILD. The majority of these patients (77%) had moderate‐to‐severe involvement (defined as >10% lung involvement). The TCZ arm demonstrated preservation of forced vital capacity percent predicted (FVC%) over 48 weeks (least squares mean change in FVC% = −0.1) compared to placebo (−6.3%). For mild, moderate, and severe QILD, the mean ± SD change in FVC% in the TCZ arm at 48 weeks were −4.1 ± 2.5% (n = 11), 0.7 ± 1.9% (n =19), and 2.1 ± 1.6% (n = 26), respectively, and in the placebo group were −10.0 ± 2.6% (n = 11), −5.7 ± 1.6% (n = 26), and −6.7 ± 2.0% (n = 16), respectively. Similar treatment‐related preservation findings were seen independent of fibrosis severity.
Conclusion
TCZ in early SSc–associated ILD with progressive skin disease stabilized FVC% over 48 weeks, independent of the extent of radiographically evident QILD.
In April 2023, the first American Roentgen Ray Society (ARRS) Wellness Summit was held in Honolulu, Hawaii. The Summit was a communal call to action bringing together professionals from the field of ...radiology to critically review our current state of wellness and reimagine the role of radiology and radiologists to further wellbeing. The in-person and virtual Summit was available free-of-cost to all meeting registrants and included 12 sessions with 44 invited moderators and panelists. The Summit aimed to move beyond simply rehashing the repeated issues and offering theoretical solutions, and instead focus on intentional practice evolution, identifying implementable strategies so that we as a field can start to walk our wellness talk. Here, we first summarize the thematic discussions from the 2023 ARRS Wellness Summit, and second, share several strategic action items that emerged.
The Scleroderma Lung Study II (SLS II) demonstrated significant improvements in pulmonary function and dyspnea at 24 months compared with baseline when patients with symptomatic scleroderma-related ...interstitial lung disease (SSc-ILD) were treated with either cyclophosphamide for 1 year (followed for another year on placebo) or mycophenolate mofetil for 2 years in a randomized, double-blind clinical trial. Physiologic and clinical outcomes of SLS II have been published previously.
The aim of the study was to assess changes from baseline in the extent of SSc-ILD on high-resolution computed tomography (HRCT) measured in the SLS II participants using quantitative image analysis after 2 years and to determine whether these HRCT changes were correlated with the changes in physiologic and clinical measures over the same time interval.
Ninety-seven of the 142 randomized subjects (cyclophosphamide group, 47 subjects; mycophenolate mofetil group, 50 subjects) participating in SLS II underwent thoracic volumetric thin-section HRCT at both baseline and 24 months. Quantitative computer-aided diagnosis scores using volumetric HRCT scans were obtained using a previously developed computer-aided system. The scores were quantitative lung fibrosis, quantitative ground glass, quantitative honeycomb, and quantitative interstitial lung disease (QILD), the latter representing the sum of quantitative lung fibrosis, quantitative ground glass, and quantitative honeycomb. These scores were obtained both for the whole lung and for individual lobes. Paired t tests were used for the combined (pooled) cyclophosphamide and mycophenolate mofetil groups to compare 24-month changes from baseline in both the whole lung and the lobe of maximal involvement as determined at baseline (worst lobe).
At the end of the 24-month trial, QILD in the whole lung was significantly reduced by a mean of 2.51% in the pooled groups (adjusted 95% confidence interval, -4.00 to -1.03%; P = 0.001). There was no significant difference in the QILD score improvement between the cyclophosphamide (-2.66%) and mycophenolate (-2.38%) groups when assessed separately (P = 0.88). For the pooled group, the 24-month changes in QILD scores in the whole lung correlated significantly with other outcomes, including 24-month changes in forced vital capacity (ρ = -0.37), single-breath diffusing capacity of the lung for carbon monoxide (ρ = -0.22), and breathlessness as measured by the Transition Dyspnea Index (ρ = -0.26).
Treatment of SSc-ILD with either cyclophosphamide for 1 year, followed by placebo for a second year, or mycophenolate for 2 years was associated with a significant reduction (improvement) in the extent of HRCT SSc-ILD assessed by computer-aided diagnosis scores, which correlated well with one or more other measures of treatment response. These findings demonstrate that actual changes in lung structure accompany improvements in physiologic and/or symptomatic measures in SSc-ILD.
Tocilizumab, an anti-IL-6 receptor antibody, had no statistically significant effect on skin sclerosis but preserved lung function over 48 weeks in patients with early systemic sclerosis ...(SSc)-associated interstitial lung disease (ILD) in a phase 3 randomized controlled trial.
Assess long-term safety and efficacy of tocilizumab.
Adults with diffuse cutaneous SSc for ⩽60 months and elevated acute-phase reactants, including those with ILD, received weekly placebo or tocilizumab 162 mg subcutaneously in the 48-week, double-blind period and then open-label tocilizumab from Weeks 48 to 96 (placebo-tocilizumab; continuous-tocilizumab).
Eighty-two of 107 patients in the placebo-tocilizumab group and 85 of 105 patients in the continuous-tocilizumab group completed 96 weeks. Mean age and disease duration were 48 years and 23 months; high-resolution computed tomography revealed ILD in 61%. Mean (95% confidence interval CI) change in modified Rodnan skin score from baseline to week 96 was -8.4 (-10.0 to -6.8) for placebo-tocilizumab and -9.6 (-10.9 to -8.4) for continuous-tocilizumab. Mean (95% CI) change in FVC (percent predicted) from baseline to week 96 was -3.3 (-5.1 to -1.5) for placebo-tocilizumab and -0.5 (-2.4 to 1.3) for continuous-tocilizumab among completers and, in a
analysis, -4.1 (-6.7 to -1.6) and -0.6 (-3.1 to 2.0), respectively, among completers with ILD (mean 95% CI change from Weeks 48 to 96: 0.9 -0.8 to 2.7 and -0.4 -2.3 to 1.5, respectively). Rates per 100 patient-years of serious adverse events from Weeks 48 to 96 were 14.8 for placebo-tocilizumab and 15.8 for continuous-tocilizumab.
Tocilizumab preserved lung function, slowing decline in FVC, in patients with SSc, including those with ILD. Long-term safety was consistent with the known safety profile of tocilizumab. Clinical trial registered with www.clinicaltrials.gov (NCT02453256).
FG-3019 is a fully human monoclonal antibody that interferes with the action of connective tissue growth factor, a central mediator in the pathogenesis of fibrosis.This open-label phase 2 trial ...evaluated the safety and efficacy of two doses of FG-3019 administered by intravenous infusion every 3 weeks for 45 weeks in patients with idiopathic pulmonary fibrosis (IPF). Subjects had a diagnosis of IPF within the prior 5 years defined by either usual interstitial pneumonia (UIP) pattern on a recent high-resolution computed tomography (HRCT) scan, or a possible UIP pattern on HRCT scan and a recent surgical lung biopsy showing UIP pattern. Pulmonary function tests were performed every 12 weeks, and changes in the extent of pulmonary fibrosis were measured by quantitative HRCT scans performed at baseline and every 24 weeks.FG-3019 was safe and well-tolerated in IPF patients participating in the study. Changes in fibrosis were correlated with changes in pulmonary function.Further investigation of FG-3019 in IPF with a placebo-controlled clinical trial is warranted and is underway.
Multidetector row computed tomography (MDCT) is increasingly taking a central role in identifying subphenotypes within chronic obstructive pulmonary disease (COPD), asthma, and other lung-related ...disease populations, allowing for the quantification of the amount and distribution of altered parenchyma along with the characterization of airway and vascular anatomy. The embedding of quantitative CT (QCT) into a multicenter trial with a variety of scanner makes and models along with the variety of pressures within a clinical radiology setting has proven challenging, especially in the context of a longitudinal study. SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), sponsored by the National Institutes of Health, has established a QCT lung assessment system (QCT-LAS), which includes scanner-specific imaging protocols for lung assessment at total lung capacity and residual volume. Also included are monthly scanning of a standardized test object and web-based tools for subject registration, protocol assignment, and data transmission coupled with automated image interrogation to assure protocol adherence. The SPIROMICS QCT-LAS has been adopted and contributed to by a growing number of other multicenter studies in which imaging is embedded. The key components of the SPIROMICS QCT-LAS along with evidence of implementation success are described herein. While imaging technologies continue to evolve, the required components of a QCT-LAS provide the framework for future studies, and the QCT results emanating from SPIROMICS and the growing number of other studies using the SPIROMICS QCT-LAS will provide a shared resource of image-derived pulmonary metrics.
Significant heterogeneity of clinical presentation and disease progression exists within chronic obstructive pulmonary disease (COPD). Although FEV(1) inadequately describes this heterogeneity, a ...clear alternative has not emerged. The goal of phenotyping is to identify patient groups with unique prognostic or therapeutic characteristics, but significant variation and confusion surrounds use of the term "phenotype" in COPD. Phenotype classically refers to any observable characteristic of an organism, and up until now, multiple disease characteristics have been termed COPD phenotypes. We, however, propose the following variation on this definition: "a single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes (symptoms, exacerbations, response to therapy, rate of disease progression, or death)." This more focused definition allows for classification of patients into distinct prognostic and therapeutic subgroups for both clinical and research purposes. Ideally, individuals sharing a unique phenotype would also ultimately be determined to have a similar underlying biologic or physiologic mechanism(s) to guide the development of therapy where possible. It follows that any proposed phenotype, whether defined by symptoms, radiography, physiology, or cellular or molecular fingerprint will require an iterative validation process in which "candidate" phenotypes are identified before their relevance to clinical outcome is determined. Although this schema represents an ideal construct, we acknowledge any phenotype may be etiologically heterogeneous and that any one individual may manifest multiple phenotypes. We have much yet to learn, but establishing a common language for future research will facilitate our understanding and management of the complexity implicit to this disease.
Median survival of patients with idiopathic pulmonary fibrosis (IPF) is 2-5 years. Sensitive imaging metrics can play a role in detecting early changes in therapeutic development. The aim of the ...present study was to compare known computed tomography (CT) histogram kurtosis and a classifier-based quantitative score to assess baseline severity and change over time in patients with IPF.
A total of 57 patients with at least baseline and paired follow-up scans were selected from an imaging database of standardized CT scans obtained from patients with IPF. CT histogram measurement of kurtosis and quantitative lung fibrosis (QLF) and quantitative interstitial lung disease (QILD) scores from a classification algorithm were calculated. Spearman rank correlations were used to assess associations between baseline severity and changes for all CT-derived measures compared to forced vital capacity (FVC) and carbon monoxide diffusion capacity (DLCO) (percent predicted).
At baseline, mean (±SD) of kurtosis was 2.43 (±1.83). Mean (±SD) values of QLF and QILD scores were 20.7% (±13.4) and 43.3% (±20.0), respectively. All baseline histogram indices and QLF and QILD scores were correlated well with baseline FVC and DLCO. When assessing associations with changes in FVC and DLCO over time, only QLF score was statistically significant (ρ = -0.57; P < .0001 for FVC and ρ = -0.34; P = .025 for DLCO), whereas kurtosis was not.
Classifier-model-derived scores (QLF and QILD), based on a set of texture features, are associated with baseline disease extent and are also a sensitive measure of change over time. A QLF score can be used for measuring the extent of disease severity and longitudinal changes.
PDF
