scholarly journals Progressive fibrosing interstitial lung disease: a clinical cohort (the PROGRESS® study)

2020 ◽  
pp. 2002718 ◽  
Author(s):  
Mouhamad Nasser ◽  
Sophie Larrieu ◽  
Salim Si-Mohamed ◽  
Kaïs Ahmad ◽  
Loic Boussel ◽  
...  

In patients with chronic fibrosing interstitial lung disease (ILD), a progressive fibrosing phenotype (PF-ILD) may develop, but information on the frequency and characteristics of this population outside clinical trials is lacking.We assessed the characteristics and outcomes of patients with PF-ILD other than idiopathic pulmonary fibrosis (IPF) in a real-world, single-centre clinical cohort. The files of all consecutive adult patients with fibrosing ILD (2010–2017) were retrospectively examined for predefined criteria of ≥10% fibrosis on high-resolution computed tomography and progressive disease during overlapping windows of 2 years. Baseline was defined as the date disease progression was identified. Patients receiving nintedanib or pirfenidone were censored from survival and progression analyses.In total, 1395 patients were screened; 617 had ILD other than IPF or combined pulmonary fibrosis and emphysema, and 168 had progressive fibrosing phenotypes. In 165 evaluable patients, median age was 61 years; 57% were women. Baseline mean forced vital capacity (FVC) was 74±22% of predicted. Median duration of follow-up was 46.2 months. Annualised FVC decline during the first year was estimated at 136±328 mL using a linear mixed model. Overall survival was 83% at 3 years and 72% at 5 years. Using multivariate Cox regression analysis, mortality was significantly associated with relative FVC decline ≥10% in the previous 24 months (p<0.05), age ≥50 years (p<0.01) and diagnosis subgroup (p<0.01).In this cohort of patients with PF-ILD not receiving antifibrotic therapy, the disease followed a course characterised by continued decline in lung function, which predicted mortality.

2021 ◽  
Vol 12 ◽  
Author(s):  
Xianqiu Chen ◽  
Jian Guo ◽  
Dong Yu ◽  
Bing Jie ◽  
Ying Zhou

Background: Progressive fibrosing interstitial lung disease (PF-ILD) and idiopathic pulmonary fibrosis (IPF) share similar progression phenotype but with different pathophysiological mechanism. The purpose of this study was to assess clinical characteristics and outcomes of patients with PF-ILD in a single-center cohort.Methods: Patients with PF-ILD treated in Shanghai Pulmonary Hospital from Jan. 2013 to Dec. 2014 were retrospectively analyzed. Baseline characteristics and clinical outcomes were collected for survival analysis to identifying clinical predictors of mortality.Results: Among 608 patients with ILD, 132 patients met the diagnostic criteria for PF-ILD. In this single-center cohort, there were 51 (38.6%) cases with connective tissue disease-associated interstitial lung disease (CTD-ILD) and 45 (34.1%) with unclassifiable ILDs. During follow-up, 83 patients (62.9%) either died (N = 79, 59.8%) or underwent lung transplantations (N = 4, 3.0%) with a median duration follow-up time of 53.7 months. Kaplan-Meier survival curves revealed that the 1, 3 and 5-years survival of PF-ILD were 90.9, 58.8 and 48.1%, respectively. In addition, the prognosis of patients with PF-ILD was similar to those with IPF, while it was worse than non-PF-ILD ones. Multivariate Cox regression analysis demonstrated that high-resolution computed tomography (HRCT) scores (HR 1.684, 95% CI 1.017–2.788, p = 0.043) and systolic pulmonary artery pressure (SPAP) &gt; 36.5 mmHg (HR 3.619, 95%CI 1.170–11.194, p = 0.026) were independent risk factors for the mortality of PF-ILD.Conclusion: Extent of fibrotic changes on HRCT and pulmonary hypertension were predictors of mortality in patients with PF-ILD.


2021 ◽  
Vol 10 (11) ◽  
pp. 2285
Author(s):  
John N. Shumar ◽  
Abhimanyu Chandel ◽  
Christopher S. King

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.


2021 ◽  
Vol 31 (4) ◽  
pp. 505-510
Author(s):  
S. N. Avdeev ◽  
S. Yu. Chikina ◽  
I. E. Tyurin ◽  
A. S. Belevskiy ◽  
S. A. Terpigorev ◽  
...  

Introduction. The natural course of some interstitial lung diseases (ILD) is characterized by progressive fibrosing phenotype resembling idiopathic pulmonary fibrosis (IPF). Until recently, the antifibrotic drug nintedanib was approved for treatment of the only fibrosing ILD which was IPF. A new indication for this drug which has been registered in Russian Federation in 2021 includes other fibrosing ILDs with progressive phenotype (PF-ILDs) and ILD associated with systemic scleroderma (SS-ILD).The aim of this publication is to describe general considerations of the decision of Multidisciplinary Expert Board on diagnosis and treatment of PF-ILDs including SS-ILD.Results. According to the extension in nintedanib use mentioned above, the Expert Board created an algorithm for diagnosis and treatment of patients with PF-ILDs and criteria for nuntedanib administration in PF-ILDs.Conclusion. Antifibrotic therapy is needed for patients with PF-ILDs with the failure of the stanrard therapy. In those patients antifibrotic treatment should be initiated as early as possible to better preserve the lung function.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 993.1-993
Author(s):  
Y. H. Chiu ◽  
J. Spierings ◽  
P. De Jong ◽  
F. Mohamed Hoesein ◽  
J. M. Van Laar ◽  
...  

Background:Interstitial lung disease (ILD) is associated with decreased quality of life and higher mortality risk in patients with connective tissue disease (CTD). Outcome and treatment response to immunosuppressive therapies is unpredictable, and therefore the management of CTD-ILD can be challenging.Objectives:Our study aimed to identify clinical and imaging factors that are predictive for outcome in patients with CTD-ILD.Methods:We performed a retrospective cohort study in patients with CTD-ILD who were treated in our centre between 2004 and 2018. Clinical, biochemical data as well as pulmonary function test (PFT) and high-resolution computed tomography (HRCT) results were recorded. Two experienced chest radiologists independently and blindly reviewed the HRCT’s. When the two chest radiologists assessed the ILD pattern differently, a diagnosis was made by consultation of a third expert. The ILD patterns were classified as fibrotic or inflammatory. Overall survival and progressive fibrosing interstitial lung disease (PF-ILD, defined as a significant decline of PFT and HRCT) after two years of treatment were assessed using a Kaplan-Meier plot. Multivariable Cox regression was including for treatment, comorbidity, and age as variables. Factors with a p value < 0.2 in the univariate analysis were included in the multivariate analysis. The correlation between the variation of serum markers and PFT over-time was evaluated with Spearman’s Rho.Results:In total, 150 patients with CTD-ILD were included, of which 53 (35.3%) had systemic sclerosis, 19 (12.7%) Sjogren’s syndrome, 29 (19.3%) inflammatory myopathy, 24 (16%) rheumatoid arthritis, 5 (3.3%) systemic lupus erythematosus, 4 (2.7%) mixed connective tissue disease, and 16 (10.7%) undifferentiated connective tissue disease patients. Median disease duration of CTD was 14 months (IQR 2–73) in patients with CTD diagnosis before ILD onset. The median follow-up duration was 40 months (IQR 27.3–60.8). Thirty (20%) deaths occurred, in which the cause of death was a pulmonary infection in 6 (4%) patients and a respiratory failure due to ILD in 10 (6.7%) patients. PF-ILD occurred in 82 (54.7%) patients, which was associated with poor overall survival (HR 3.03, 95%CI 1.15–7.98) (Figure 1). Age, smoking, and steroid usage were associated with increased mortality risk as well (Table 1). There was no dose-related effect of smoking on mortality.Figure 1.The Kaplan-Meier plot for progressive fibrosing interstitial lung diseases (PF-ILD). PF-ILF was defined as pulmonary function decline or high-resolution computed tomography progression after two years of treatment.Inflammatory patterns on baseline HRCT were correlated with a lower risk of FVC decline than fibrotic patterns (OR 0.24, 95%CI 0.09–0.64). The increase in CA15.3 level was associated with the decline in FVC (Rho -0.308, p=0.037). Besides, the elevation in CRP was associated with the reduction in FVC (Rho -0.302, p=0.006) and DLCO (Rho -0.268, p=0.019).Conclusion:Our study identified several factors associated with outcomes. Age, smoking, and steroid treatment increased the risk of mortality in patient with CTD-ILD. Inflammatory HRCT pattern at baseline revealed a better pulmonary outcome than a fibrotic pattern. The patients having PF-ILD after two years of treatment showed a higher mortality risk.Table 1.Multivariable Cox-regression for the clinical risk of mortality.Clinical factorCrude HR (95%CI)PAdjusted HR (95%CI)pAge1.11 (1.06–1.15)1.7*10-61.12 (1.07–1.17)3.54*10-6Smoking1.64 (0.79–3.43)0.1872.53 (1.11–5.78)0.028Congestive heart failure1.86 (0.75–4.58)0.1791.17 (0.47–2.91)0.737MMF0.55 (0.23–1.35)0.1950.73 (0.29–1.85)0.512Steroid4.37 (1.67–11.45)0.0034.96 (1.84–13.40)0.002MMF, mycophenolate mofetil; HR, hazard ratio.Acknowledgements:We want to thank Marieke Vianen for the support in data management, Lieke Wintermans and Lisa Hessels for collecting the clinical data.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 969.1-970
Author(s):  
M. DI Carlo ◽  
M. Tardella ◽  
E. Filippucci ◽  
F. Salaffi

Background:In recent years, a growing interest has grown around interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). While high resolution computed tomography (HRCT) of the chest remains the diagnostic method of choice, increasing attention has been directed towards lung ultrasound (LUS) in the diagnosis of ILD in connective tissue diseases. LUS allows the detection of artifacts (B-lines) characteristic of ILD, without the need to use ionizing radiation. However, it is not yet well defined how to interpret the LUS findings under suspicion of RA-ILD.Objectives:To determine the cut-off number of LUS B-lines that identifies a significant RA-ILD.Methods:A cross sectional study was conducted on consecutive RA patients with suspected RA-ILD. The inclusion criteria were clinical (dyspnea, velcro sounds), instrumental (suggestive anomalies on conventional radiography, DLco reduction), or in presence of at least two of the following risk factors for RA-ILD: smoking habit, male sex, advanced age, and ACPA presence.Patients underwent LUS, chest HRCT, pulmonary function tests, and clinical evaluation. The diagnosis of RA-ILD was based on a semi-quantitative evaluation of HRCT using a computer-aided method (CaM). The 10% of fibrosis, measured with this method, was considered as a cut-off for the presence of significant RA-ILD. The LUS was carried out in 14 defined intercostal spaces using a linear multifrequency probe 6-18 MHz (MyLab Class C, Esaote S.p.A., Genoa, Italy) and the number of B-lines present in each intercostal space was counted and summed up (Figure 1). The discriminating validity of the LUS versus HRCT has been studied by using the receiver operating characteristic (ROC) curve analysis.Figure 1.LUS B-line illustrative.Results:72 consecutive RA patients (21 male, 51 female) were evaluated, with a mean age of 63.0 (SD 11.5 years), a mean ACPA titre of 327.6 (SD 633.3) U/ml and a rheumatoid factor of 324.6 (SD 748.7) U/ml. The mean estimate of pulmonary fibrosis using the CaM was 11.2% (SD 7.5) at HRCT, while at LUS the mean number of B-lines was 10.6 (SD 15.1). Pulmonary fibrosis of 10% as measured by the CaM at HRCT was detected in 25 patients (34.72%). Applying this HRCT cut-off point as an estimate of significant fibrosis, the presence of 9 B-lines was found to be the optimal cut-off at ROC curve analysis. This LUS cut-off defines the presence of significant fibrosis with a sensitivity of 70.0%, a specificity of 97.62%, and a positive likelihood ratio of 29.4 (Figure 2).Figure 2.Area under the ROC curve to determine the number of B-lines at LUS to define a significant RA-ILD, applying the 10% of fibrosis at chest HRCT measured by OsiriX as external criterion.Conclusion:The present study provided data to determine the number of B-lines to identify a significant RA-ILD. LUS may represent a useful technique to select RA patients to be assessed by chest HRCT.References:[1] Tardella M, et al. Ultrasound B-lines in the evaluation of interstitial lung disease in patients with systemic sclerosis: Cut-off point definition for the presence of significant pulmonary fibrosis. Medicine (Baltimore). 2018;97(18):e0566.[2] Salaffi F, et al. High-resolution computed tomography of the lung in patients with rheumatoid arthritis: Prevalence of interstitial lung disease involvement and determinants of abnormalities. Medicine (Baltimore). 2019;98(38):e17088.Disclosure of Interests:Marco Di Carlo: None declared, Marika Tardella: None declared, Emilio Filippucci Speakers bureau: Dr. Filippucci reports personal fees from AbbVie, personal fees from Bristol-Myers Squibb, personal fees from Celgene, personal fees from Roche, personal fees from Union Chimique Belge Pharma, personal fees from Pfizer, outside the submitted work., Fausto Salaffi: None declared


2021 ◽  
Author(s):  
Xianhua Gui ◽  
Shenyun Shi ◽  
Tingting Zhao ◽  
Yuying Qiu ◽  
Min Yu ◽  
...  

Abstract Objectives: The prognosis of anti-melanoma differentiation-associated gene (MDA5) antibody-positive dermatomyositis (DM)-interstitial lung disease (ILD) (anti-MDA5 -positive DM-ILD) is often poor, especially in rapidly progressive interstitial lung disease (RPILD). So far there is no established therapy. This study evaluated the efficacy and safety of pharmacological treatments for anti-MDA5-positive DM-ILD. Methods: This retrospective study comprised 87 anti-MDA5-positive DM-ILD patients. We reviewed the clinical characteristics, laboratory findings, lung function treatments, and outcomes of the 87 patients. Cox regression analysis was used to identify predictors of 6-month survival. The association between different combined immunosuppressive regimen and 6-month survival were evaluated.Results: High level of CYFRA21-1 and low PaO2/FiO2 ratio were associated with poor prognosis. Corticosteroid (CS) alone treatment group with higher CYFRA21-1 and lower PaO2/FiO2 ratio showed worse 6-month survival than the combination of CS with immunosuppressants group (p<0.01). In addition, tacrolimus/cyclosporine-treated anti-MDA5-positive DM Non-RPILD exhibited a better survival, comparing with tacrolimus/cyclosporine combined intravenous cyclophosphamide (IVCY)-treated patients (p<0.05). Conclusion: Addition of immunosuppressants to CS, were associated with better 6-month survival in anti-MDA5-positive DM-ILD. The triple regimen (CS, tacrolimus/cyclosporine and IVCY) was not superior to duple one (CS, tacrolimus/cyclosporine) in anti-MDA5-positive DM Non-RPILD.


2020 ◽  
Vol 14 ◽  
pp. 175346662096849
Author(s):  
Steven D. Nathan ◽  
Jean Pastre ◽  
Inga Ksovreli ◽  
Scott Barnett ◽  
Christopher King ◽  
...  

Background and aims: Chest high-resolution computed tomography (HRCT) is the central diagnostic tool in discerning idiopathic pulmonary fibrosis (IPF) from other interstitial lung disease (ILDs). In 2018, new guidelines were published and the nomenclature for HRCT interpretation was changed. We sought to evaluate how clinicians’ interpretation would change based on reading HRCTs under the framework of the old versus new categorization. Materials and methods: We collated HRCTs from 50 random cases evaluated in the Inova Fairfax ILD clinic. Six ILD experts were provided the deidentified HRCTs. They were all instructed to independently provide two reads of each HRCT, based on the old and the new guidelines. Results: The kappa statistic for concordance for HRCT reads under old guidelines was 0.5, while for the new guidelines it was 0.38. Under the framework of the old guidelines, there were 22 HRCTs with unanimous consensus reads, while only 15 with the new guidelines. There were 12 HRCTs read unanimously as usual interstitial pneumonia (UIP) pattern based on both the old and the new guidelines. Ten HRCTs were read as a possible UIP pattern based on the old guidelines and were classified in nine cases as probable UIP and one indeterminate based on the new guidelines. Of the 28 inconsistent UIP HRCTs (old guidelines), 25 were read as alternative diagnosis suggested, two were read as indeterminate and one as probable UIP. Conclusion: Implementation of the new guidelines to categorize HRCTs in ILD patients appears to be associated with greater inter-interpreter variability. How or whether new guidelines improve the care and management of ILD patients remains unclear. The reviews of this paper are available via the supplemental material section.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Regina Celia Carlos Tibana ◽  
Maria Raquel Soares ◽  
Karin Mueller Storrer ◽  
Gustavo de Souza Portes Meirelles ◽  
Katia Hidemi Nishiyama ◽  
...  

Abstract Background Usual interstitial pneumonia can present with a probable pattern on high-resolution computed tomography (HRCT), but the probability of identifying usual interstitial pneumonia by surgical lung biopsy in such cases remains controversial. We aimed to determine the final clinical diagnosis in patients with a probable usual interstitial pneumonia pattern on HRCT who were subjected to surgical lung biopsy. Methods HRCT images were assessed and categorized by three radiologists, and tissue slides were evaluated by two pathologists, all of whom were blinded to the clinical findings. The final clinical diagnosis was accomplished via a multidisciplinary discussion. Patients with a single layer of honeycombing located outside of the lower lobes on HRCT were not excluded. Results A total of 50 patients were evaluated. The most common final clinical diagnosis was fibrotic hypersensitivity pneumonitis (38.0%) followed by idiopathic pulmonary fibrosis (24.0%), interstitial lung disease ascribed to gastroesophageal reflux disease (12.0%) and familial interstitial lung disease (10.0%). In the group without environmental exposure (n = 22), 10 patients had a final clinical diagnosis of idiopathic pulmonary fibrosis (45.5%). Irrespective of the final clinical diagnosis, by multivariate Cox analysis, patients with honeycombing, dyspnoea and fibroblastic foci on surgical lung biopsy had a high risk of death. Conclusions The most common disease associated with a probable usual interstitial pneumonia pattern on HRCT is fibrotic hypersensitivity pneumonitis followed by idiopathic pulmonary fibrosis and interstitial lung disease ascribed to gastroesophageal reflux disease. In patients without environmental exposure, the frequencies of usual interstitial pneumonia and a final clinical diagnosis of idiopathic pulmonary fibrosis are not sufficiently high to obviate the indications for surgical lung biopsy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hye Jin Jang ◽  
Seung Hyun Yong ◽  
Ah Young Leem ◽  
Su Hwan Lee ◽  
Song Yee Kim ◽  
...  

AbstractInterstitial lung disease (ILD), particularly idiopathic pulmonary fibrosis (IPF), has a poor prognosis. Corticosteroids are widely used in the treatment of acute exacerbation of ILD (AE-ILD). This study aimed to clarify the causes of AE-ILD, determine the efficacy of corticosteroids for treating AE-ILD, and detect differences in the mortality rate among subgroups of ILD. This was an observational retrospective single-center study. Patients with ILD who presented to the emergency department with acute respiratory symptoms from January 1, 2016, to December 31, 2018, were included. Patients with AE-ILD were classified into two groups depending on the prednisolone dose: low dose (0 to 1.0 mg/kg) or high dose (> 1.0 mg/kg). Mortality rates between patients with and without IPF were compared. This study included 182 patients with AE-ILD, including IPF (n = 117) and non-IPF (n = 65). Multivariate Cox regression analysis showed that corticosteroid dose (HR: 0.221, CI: 0.102–0.408, P < 0.001), initial P/F ratio (HR:0.995, CI:0.992–0.999, P = 0.006), and mechanical ventilation within 3 days of hospitalization (HR:4.205, CI:2.059–8.589, P < 0.001) were independent risk factors for mortality in patients with AE-ILD. This study showed that outcomes improve with higher doses of corticosteroids (> 1 mg/kg prednisolone) in patients with AE-non-IPF-ILD. However, this was not the case in patients with AE-IPF.


Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1794
Author(s):  
Natalia Mena-Vázquez ◽  
Marta Rojas-Gimenez ◽  
Carmen María Romero-Barco ◽  
Sara Manrique-Arija ◽  
Ana Hidalgo Conde ◽  
...  

Objectives: To describe the characteristics and progression of interstitial lung disease in patients with associated systemic autoimmune disease (ILD-SAI) and to identify factors associated with progression and mortality. Patients and methods: We performed a multicenter, retrospective, observational study of patients with ILD-SAI followed between 2015 and 2020. We collected clinical data and performed pulmonary function testing and high-resolution computed tomography at diagnosis and at the final visit. The main outcome measure at the end of follow-up was forced vital capacity (FVC) >10% or diffusing capacity of the lungs for carbon monoxide >15% and radiological progression or death. Cox regression analysis was performed to identify factors associated with worsening of ILD. Results: We included 204 patients with ILD-SAI: 123 (60.3%) had rheumatoid arthritis (RA), 58 had (28.4%) systemic sclerosis, and 23 (11.3%) had inflammatory myopathy. After a median (IQR) period of 56 (29.8–93.3) months, lung disease had stabilized in 98 patients (48%), improved in 33 (16.1%), and worsened in 44 (21.5%). A total of 29 patients (14.2%) died. Progression and hospitalization were more frequent in patients with RA (p = 0.010). The multivariate analysis showed the independent predictors for worsening of ILD-SAI to be RA (HR, 1.9 [95% CI, 1.3–2.7]), usual interstitial pneumonia pattern (HR, 1.7 [95% CI, 1.0–2.9]), FVC (%) (HR, 2.3 [95% CI, 1.4–3.9]), and smoking (HR, 2.7 [95%CI, 1.6–4.7]). Conclusion: Disease stabilizes or improves after a median of 5 years in more than half of patients with ILD-SAI, although more than one-third die. Data on subgroups and risk factors could help us to predict poorer outcomes.


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