scholarly journals Estimates of epidemiology, mortality and disease burden associated with progressive fibrosing interstitial lung disease in France (the PROGRESS study)

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mouhamad Nasser ◽  
Sophie Larrieu ◽  
Loic Boussel ◽  
Salim Si-Mohamed ◽  
Fabienne Bazin ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Healthcare Resource ◽  
Pulmonary Function Tests ◽  
Healthcare Services ◽  
Resource Utilisation ◽  
High Resolution Computed Tomography ◽  
Healthcare Database ◽  
Healthcare Resource Utilisation ◽  
Kaplan Meier

Abstract Background There is a paucity of data on the epidemiology, survival estimates and healthcare resource utilisation and associated costs of patients with progressive fibrosing interstitial lung disease (PF-ILD) in France. An algorithm for extracting claims data was developed to indirectly identify and describe patients with PF-ILD in the French national administrative healthcare database. Methods The French healthcare database, the Système National des Données de Santé (SNDS), includes data related to ambulatory care, hospitalisations and death for 98.8% of the population. In this study, algorithms based on age, diagnosis and healthcare consumption were created to identify adult patients with PF-ILD other than idiopathic pulmonary fibrosis between 2010 and 2017. Incidence, prevalence, survival estimates, clinical features and healthcare resource usage and costs were described among patients with PF-ILD. Results We identified a total of 14,413 patients with PF-ILD. Almost half of them (48.1%) were female and the mean (± standard deviation) age was 68.4 (± 15.0) years. Between 2010 and 2017, the estimated incidence of PF-ILD ranged from 4.0 to 4.7/100,000 person-years and the estimated prevalence from 6.6 to 19.4/100,000 persons. The main diagnostic categories represented were exposure-related ILD other than hypersensitivity pneumonitis (n = 3486; 24.2%), idiopathic interstitial pneumonia (n = 3113; 21.6%) and rheumatoid arthritis-associated ILD (n = 2521; 17.5%). Median overall survival using Kaplan–Meier estimation was 3.7 years from the start of progression. During the study, 95.2% of patients had ≥ 1 hospitalisation for respiratory care and 34.3% were hospitalised in an intensive care unit. The median (interquartile range) total specific cost per patient during the follow-up period was €25,613 (10,622–54,287) and the median annual cost per patient was €18,362 (6856–52,026), of which €11,784 (3003–42,097) was related to hospitalisations. Limitations included the retrospective design and identification of cases through an algorithm in the absence of chest high-resolution computed tomography scans and pulmonary function tests. Conclusions This large, real-world, longitudinal study provides important insights into the characteristics, epidemiology and healthcare resource utilisation and costs associated with PF-ILD in France using a comprehensive and exhaustive database, and provides vital evidence that PF-ILD represents a high burden on both patients and healthcare services. Trial registration ClinicalTrials.gov, NCT03858842. ISRCTN, ISRCTN12345678. Registered 3 January 2019—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03858842

scholarly journals Epidemiology, Mortality and Healthcare Resource Utilization Associated With Systemic Sclerosis-Associated Interstitial Lung Disease in France

2021 ◽  
Vol 8 ◽  
Author(s):  
Vincent Cottin ◽  
Sophie Larrieu ◽  
Loic Boussel ◽  
Salim Si-Mohamed ◽  
Fabienne Bazin ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Resource Utilization ◽  
Healthcare Resource ◽  
Healthcare Services ◽  
Healthcare Resource Utilization ◽  
Healthcare Database ◽  
Clinical Trial Registration ◽  
Kaplan Meier

Objectives: To investigate the clinical characteristics, epidemiology, survival estimates and healthcare resource utilization and associated costs in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) in France.Methods: The French national administrative healthcare database, the Système National des Données de Santé (SNDS), includes data on 98.8% of the French population, including data relating to ambulatory care, hospitalizations and death. In our study, claims data from the SNDS were used to identify adult patients with SSc-ILD between 2010 and 2017. We collected data on clinical features, incidence, prevalence, survival estimates, healthcare resource use and costs.Results: In total, 3,333 patients with SSc-ILD were identified, 76% of whom were female. Patients had a mean age [standard deviation (SD)] of 60.6 (14.4) years and a mean (SD) individual study duration of 3.9 (2.7) years. In 2016, the estimated overall incidence and prevalence were 0.69/100,000 individuals and 5.70/100,000 individuals, respectively. The overall survival estimates of patients using Kaplan–Meier estimation were 93, 82, and 55% at 1, 3, and 8 years, respectively. During the study, 98.7% of patients had ≥1 hospitalization and 22.3% of patients were hospitalized in an intensive care unit. The total annual mean healthcare cost per patient with SSc-ILD was €25,753, of which €21,539 was related to hospitalizations.Conclusions: This large, real-world longitudinal study provides important insights into the epidemiology of SSc-ILD in France and shows that the disease is associated with high mortality, healthcare resource utilization and costs. SSc-ILD represents a high burden on both patients and healthcare services.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03858842.

scholarly journals Increased levels of HE4 (WFDC2) in systemic sclerosis: a novel biomarker reflecting interstitial lung disease severity?

2020 ◽  
Vol 11 ◽  
pp. 204062232095642
Author(s):  
Mingxia Zhang ◽  
Liyun Zhang ◽  
Linning E ◽  
Ke Xu ◽  
Xu Fei Wang ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Pulmonary Function Tests ◽  
Lavage Fluid ◽  
Ct Scans ◽  
Function Parameter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
High Resolution Computed Tomography

Background: Human epididymis protein 4 (HE4, also known as WFDC-2) has been implicated in fibrotic disorders pathobiology. We tested the hypothesis that HE4 may be used as a candidate biomarker for systemic sclerosis (SSc)-related interstitial lung disease (SSc-ILD). Methods: A total of 169 consecutive SSc patients and 169 age-and sex-matched healthy controls were enrolled and blood samples were collected. Pulmonary function tests (PFTs) and paired lavage was performed on 169 patients and 37 healthy controls. All patients were classified as having SSc-no ILD or SSc-ILD, based on high-resolution computed tomography (CT) scans of the chest, and a semiquantitative grade of ILD extent was evaluated through CT scans (grade 1, 0–25%; grade 2, 26–50%; grade 3, 51–75%; grade 4, 76–100%). Serum and bronchoalveolar lavage fluid (BALF) HE4 levels were measured by enzyme-linked immunosorbent assay. Results: Serum HE4 levels were higher in SSc patients [median (interquartile range), 139.4 (85.9–181.8) pmol/l] compared with healthy controls [39.5 (24.3–54.2) pmol/l, p < 0.001] and were higher in patients with SSc-ILD [172.1 (94.8–263.3) pmol/l] than in those with SSc-no ILD [97.4 (85.5–156.5) pmol/l, p < 0.001]. This observation was replicated in the BALF samples. Corresponding values were 510.8 (144.6–1013.8) pmol/l for SSc cohort, 754.4 (299–1060) pmol/l for SSc-ILD, 555.1 (203.7–776.2) pmol/l for SSc-no ILD, and 238.7 (97.7–397.6) pmol/l for controls. The semiquantitative grade of ILD on CT scan was significantly proportional to the HE4 levels and the lung function parameter (i.e., FVC) had a negative correlation with the HE4 levels. Conclusion: This is the first study to demonstrate the potential clinical utility of blood and BALF HE4 as a biomarker for SSc-ILD. Future prospective validation studies are warranted.

scholarly journals POS1419 PREDICTIVE FACTORS FOR PULMONARY PROGRESSION IN PATIENTS WITH CONNECTIVE TISSUE DISEASE AND INTERSTITIAL LUNG DISEASE

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 ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Interstitial Lung Disease ◽  
Connective Tissue ◽  
Lung Disease ◽  
Connective Tissue Disease ◽  
Mortality Risk ◽  
Cox Regression ◽  
High Resolution Computed Tomography ◽  
Kaplan Meier ◽  
Risk Of Mortality

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

Effect of Bosentan on Systemic Sclerosis-associated Interstitial Lung Disease Ineligible for Cyclophosphamide Therapy: A Prospective Open-label Study

2011 ◽  
Vol 38 (10) ◽  
pp. 2186-2192 ◽  
Author(s):  
YOSHIAKI FURUYA ◽  
MASATAKA KUWANA
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Pulmonary Function ◽  
Lung Disease ◽  
Pulmonary Function Tests ◽  
High Dose ◽  
Open Label ◽  
High Resolution Computed Tomography ◽  
Open Label Study ◽  
Label Study

Objective.To evaluate the clinical benefits of the endothelin receptor antagonist bosentan on interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) who are ineligible for cyclophosphamide (CYC) therapy.Methods.In this prospective open-label study, 9 patients with SSc and ILD received bosentan for 24 months. The main reasons for avoiding CYC included severely impaired lung function, long disease duration, and relapse after CYC treatment. Pulmonary function tests and Doppler echocardiograms were evaluated every 6 months, and high-resolution computed tomography (HRCT) was performed every 12 months. For an extended survival analysis, 17 historical controls who met the inclusion criteria at referral and had not used any immunosuppressive or antifibrotic agents thereafter were selected from the SSc database.Results.Two patients did not finish the study; one developed vasculitis requiring high-dose corticosteroids and another died of bacterial pneumonia. The remaining 7 patients tolerated bosentan and completed the study period. There were trends toward mildly reduced forced vital capacity, total lung capacity, and diffusing capacity for carbon monoxide over time. Two patients developed pulmonary hypertension during the 24-month period. HRCT scores for ground-glass opacity, pulmonary fibrosis, and honeycomb cysts gradually increased. In the extended study, there was no difference in cumulative survival rate between the bosentan-treated and historical control groups.Conclusion.The gradual worsening of pulmonary function and HRCT findings in patients treated with bosentan was consistent with the natural course of SSc-associated ILD. This study does not support the use of bosentan for SSc-associated ILD even when CYC treatment is inadvisable.

Cyclosporine in Anti-Jo1-positive Patients with Corticosteroid-refractory Interstitial Lung Disease

2013 ◽  
Vol 40 (4) ◽  
pp. 484-492 ◽  
Author(s):  
Lorenzo Cavagna ◽  
Roberto Caporali ◽  
Lul Abdì-Alì ◽  
Roberto Dore ◽  
Federica Meloni ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Vital Capacity ◽  
Low Dose ◽  
Pulmonary Function Tests ◽  
Line Treatment ◽  
Antisynthetase Syndrome ◽  
First Line ◽  
High Resolution Computed Tomography ◽  
First Line Treatment

Objective.To describe the longterm effectiveness and safety of cyclosporine (CYC) in patients with anti-Jo1-positive antisynthetase syndrome with corticosteroid-refractory interstitial lung disease (ILD).Methods.All patients with anti-Jo1 antisynthetase syndrome referred to our division between June 1991 and February 2010 were retrospectively evaluated for ILD. ILD was assessed using pulmonary function tests (PFT) and/or high-resolution computed tomography (HRCT). Kazerooni score was used to evaluate the HRCT extent of ILD. Prednisone was the first-line treatment in all cases (1 mg/kg/day orally, then tapering). Patients with corticosteroid-refractory or relapsing ILD were then included in this retrospective study. All patients started CYC (3 mg/kg/day) without increasing prednisone dosage. Both PFT and chest HRCT were regularly reassessed during followup.Results.Over the period of study we evaluated 18 patients with antisynthetase syndrome; 17 had ILD (13 women; median age at ILD onset 57 yrs); all patients failed prednisone within 12 months of ILD onset and subsequently started CYC. The median followup on CYC was 96 months [interquartile range (IQR) 57–120 mo]. Upon starting CYC, median forced vital capacity (FVC) was 60% (IQR 56%–70%), median DLCO 60% (IQR 50%–62.75%), and median Kazerooni score 16 (IQR 7–18). After 1 year of CYC, FVC (p = 0.0006), DLCO (p = 0.0010), and total Kazerooni score (p = 0.0002) improved and prednisone was tapered (median reduced from 25 mg/day to 2.5 mg/day; p < 0.0001). The results were substantially maintained including at last available followup. CYC side effects were hypertension (5 patients) and creatinine increase (6 patients). CYC was reduced in 3 cases and withdrawn in 4. Three out of 4 patients who interrupted CYC experienced ILD relapse; 2 patients recommenced low-dose CYC with subsequent ILD control. One patient refused re-treatment and subsequently died.Conclusion.CYC is effective and substantially safe in patients with anti-Jo1 antisynthetase syndrome with corticosteroid-refractory ILD. CYC withdrawal may be associated with ILD relapse, and low-dose CYC was effective in ILD control.

scholarly journals Interstitial lung disease is not rare in immune-mediated necrotizing myopathy with anti-signal recognition particle antibodies

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Yongpeng Ge ◽  
Hanbo Yang ◽  
Xinyue Xiao ◽  
Lin Liang ◽  
Xin Lu ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Pulmonary Function Tests ◽  
Signal Recognition Particle ◽  
Ground Glass Opacity ◽  
Signal Recognition ◽  
High Resolution Computed Tomography ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Long Term Follow Up

Abstract Objectives The purpose was to clarify the characteristics of interstitial lung disease (ILD) in immune-mediated necrotizing myopathy (IMNM) patients with anti-signal recognition particle (SRP) antibodies. Methods Medical records of IMNM patients with anti-SRP antibodies were reviewed retrospectively. Results A total of 60 patients were identified. Twenty-seven (45.0%) patients were diagnosed with ILD based on lung imaging: nonspecific interstitial pneumonia (NSIP) in 17 patients (63.0%) and organizing pneumonia in 9 patients (33.3%). Reticulation pattern was identified in 17 patients (63.0%) whereas 10 cases (37.0%) showed ground glass opacity and patchy shadows by high-resolution computed tomography (HRCT). Pulmonary function tests (PFTs) were available in 18 patients, 6 (33.3%) and 10 (55.6%) patients were included in the mild and moderate group, respectively. The average age at the time of ILD onset was significantly older than those without ILD (48.6 ± 14.4 years vs. 41.2 ± 15.4 years, p < 0.05), and the frequency of dysphagia in the ILD group was higher than the group without ILD (p < 0.05). Long-term follow-up was available on 9 patients. PFTs were stable in 8 (88.9%), and the HRCT remained stable in 6 (66.7%) patients. Conclusions ILD is not rare in IMNM patients with anti-SRP antibodies, most being characterized as mild to moderate in severity. NSIP is the principal radiologic pattern, and ILD typically remains stable following treatment.

scholarly journals Interstitial lung disease in systemic sclerosis: where do we stand?

2015 ◽  
Vol 24 (137) ◽  
pp. 411-419 ◽  
Author(s):  
Susanna Cappelli ◽  
Silvia Bellando Randone ◽  
Gianna Camiciottoli ◽  
Amato De Paulis ◽  
Serena Guiducci ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Pulmonary Function Tests ◽  
Treatment Strategies ◽  
Haematopoietic Stem Cell ◽  
High Resolution Computed Tomography ◽  
Cellular Targets ◽  
Need For Treatment ◽  
Risk Of Progression

Interstitial lung disease (ILD) is common in systemic sclerosis (SSc) patients and despite recent advances in the treatment is, at present, the major cause of death. Today, an early diagnosis of ILD is possible, and is mandatory to improve the prognosis of the disease.Pulmonary function tests and high-resolution computed tomography remain the mainstay for the diagnosis of SSc-ILD, but there is a growing interest in lung ultrasound. Recently, the correlation between severity of fibrosis and some peripheral blood biomarkers has been described.Nonselective immunosuppressors are still the main treatment for ILD, with cyclophosphamide (CYC) most widely used to obtain remission. Novel therapies towards specific molecular and cellular targets have been suggested; in particular, rituximab (RTX) has shown promising results, but further research is needed. It is of paramount importance to define the severity of the disease and the risk of progression in order to define the need for treatment and the treatment intensity. We propose the division of the treatment strategies at our disposal to induce remission into three categories: high intensity (haematopoietic stem cell transplantation), medium intensity (CYC and RTX) and low intensity (azathioprine (AZA) and mycophenolate mofetil (MMF)). After obtaining remission, maintenance treatment with AZA or MMF should be started.In this review we explore new advances in the pathogenesis, diagnosis and treatment of SSc-ILD.

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