Predictors for progressive fibrosis in patients with connective tissue disease associated interstitial lung diseases

Chiu, Yu-Hsiang; Spierings, Julia; Jong, Pim A. de; Hoesein, Firdaus Mohamed; Grutters, Jan C.; Laar, Jacob M. van; Voortman, Mareye

doi:10.1016/j.rmed.2021.106579

Cited by 27 publications

(37 citation statements)

References 48 publications

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“…ILD may be highly misdiagnosed or delay-diagnosed in patients with pSS, 3 although the progression of ILD is relatively less frequent in patients with pSS than other CTD. 33 The pSS patients who developed ILD exhibited increased morbidity and mortality, and required additional medical resources. Our data support that KL-6 is a valuable biomarker in identifying hidden ILD in patients with pSS.…”

Section: Discussionmentioning

confidence: 99%

KL-6 as a Biomarker of Interstitial Lung Disease Development in Patients with Sjögren Syndrome: A Retrospective Case–Control Study

Chiu¹,

Chu²,

Lu³

et al. 2022

JIR

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Objective Krebs von den Lungen-6 (KL-6) is expressed on regenerating type II pneumocytes and has been recognized as biomarkers in interstitial lung disease (ILD). We aim to identify the role of the serum KL-6 level in patients with newly diagnosed Sjögren syndrome (SS), as well as the correlation between the immunoassays. Methods Patients with newly diagnosed SS and receiving HRCT for clinical reason during follow-up were included. Baseline KL-6 level was measured via enzyme-linked immunosorbent assay (ELISA) and latex particle-enhanced turbidimetric immunoassay (LETIA). Results Of the 39 patients, 21 (53.85%) developed interstitial lung disease (ILD) by the conclusion of the follow-up period. The median time to diagnosis of ILD was 2.24 years (IQR 1.15–4.34) in the ILD group. The median serum KL-6 level, measured using ELISA, was 1232 U/mL (IQR 937–2242) and 764.5 U/mL (IQR 503.25–1035.75) in the ILD group and the non-ILD group, respectively (p = 0.001). The median LETIA for serum KL-6 was 329 U/mL (IQR 235–619) and 245 U/mL (IQR 215.25–291) in the ILD group and the non-ILD group, respectively (p = 0.074). Conclusion Serum KL-6 levels were higher in newly diagnosed SS patients with ILD diagnosis during follow-up. Thus, the serum KL-6 level can serve as a valuable biomarker to identify hidden ILD in patients with newly diagnosed SS patients. However, the immunoassay procedure may influence the efficacy of the prediction and its clinical association.

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Section: Discussionmentioning

confidence: 99%

KL-6 as a Biomarker of Interstitial Lung Disease Development in Patients with Sjögren Syndrome: A Retrospective Case–Control Study

Chiu¹,

Chu²,

Lu³

et al. 2022

JIR

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“…However, PF-ILD other than IPF, such as idiopathic nonspecific interstitial pneumonia (iNSIP), fibrotic hypersensitivity pneumonitis (HP), connective tissue diseases (CTD)-ILD or autoimmune-ILD, also have a progressive phenotype, manifesting as a worsening of dyspnea, decline in lung function, and increased extent of fibrosis on high-resolution computed tomography (HRCT), with high morbidities, such as PVD. In Taiwan, we defined PF-ILD as developing any of the following within 2 years of diagnosis: (1) a relative decline in forced vital capacity (FVC) ≥ 10%; (2) a relative decline in diffusion capacity of carbon monoxide (DLCO) ≥ 15%; (3) worsening of radiological appearance or symptoms and a relative decline in FVC from 5~10% [ 1 , 2 ].…”

Section: Methodsmentioning

confidence: 99%

“…Meanwhile, the PVD, in the late course of lupus with PF-ILD, was life-threatening [ 25 , 26 ]. In the recent Chiu et al study, they found that (20/150, 22%) with HCQ use and (17/150, 11.3%) with PAH in the 150 patients had ILD (33/150, 33% fibrotic predominant, PF-ILD) [ 2 ]. In this study, fibrosing CTD-ILD or IPF was grouped as fibrosing-ILD.…”

Section: Methodsmentioning

confidence: 99%

“…Progressive fibrosing interstitial lung disease (PF-ILD) is another form of interstitial lung disease (ILD) and consists of a diverse group of ILDs characterized by a different amount of inflammation and fibrosis, frequent disease exacerbation and earlier mortality [ 1 , 2 ]. ILD, especially PF-ILD, may develop into pulmonary heart disease, including pulmonary embolism, pulmonary artery hypertension (PAH), and pulmonary circulation disease—pulmonary vascular diseases (PVD) [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Hydroxychloroquine on the Pulmonary Vascular Diseases in Interstitial Lung Disease: Immunologic Effects, and Virus Interplay

et al. 2022

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To investigate the effects of hydroxychloroquine (HCQ) drug use on the risk of pulmonary vascular disease (PVD) in an interstitial lung disease cohort (ILD cohort, ILD+ virus infection), we retrospectively enrolled the ILD cohort with HCQ (HCQ users, N = 4703) and the ILD cohort without HCQ (non-HCQ users, N = 4703) by time-dependence after propensity score matching. Cox models were used to analyze the risk of PVD. We calculated the adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) for PVD after adjusting for sex, age, comorbidities, index date and immunosuppressants, such as steroids, etc. Compared with the HCQ nonusers, in HCQ users, the aHRs (95% CIs) for PVD were (2.24 (1.42, 3.54)), and the women’s aHRs for PVD were (2.54, (1.49, 4.35)). The aHRs based on the days of HCQ use for PVD of 28–30 days, 31–120 days, and >120 days were (1.27 (0.81, 1.99)), (3.00 (1.81, 4.87)) and (3.83 (2.46, 5.97)), respectively. The medium or long-term use of HCQ or young women receiving HCQ were associated with a higher aHR for PVD in the ILD cohort. These findings indicated interplay of the primary immunologic effect of ILD, comorbidities, women, age and virus in the HCQ users.

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“…For this study, patients with two or more outpatient visits or one hospitalization for ILD (new ILD, ICD-9-CM codes 135, 237. (12)(13)(14). Patients aged ≥ 18 years with ILD and viral infection were included in the ILD cohort.…”

Section: Patient Enrollment and Sample Collectionmentioning

confidence: 99%

Colchicine Is a Weapon for Managing the Heart Disease Among Interstitial Lung Disease With Viral Infection: Have We Found the Holy Grail?

Yeh

Hung

Lin

et al. 2022

Front. Cardiovasc. Med.

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BackgroundThis study investigated the effect of colchicine use on the risks of heart disease (HD), pericarditis, endocarditis, myocarditis, cardiomyopathy, cardiac arrhythmia, and cardiac failure in patients having interstitial lung disease (ILD) with virus infection (ILD cohort).MethodsWe retrospectively enrolled ILD cohort between 2000 and 2013 from the Longitudinal Health Insurance Database and divided them into colchicine users (n = 12,253) and colchicine non-users (n = 12,253) through propensity score matching. The event of interest was the diagnosis of HD. The incidence of HD was analyzed using multivariate Cox proportional hazards models between colchicine users and the comparison cohort after adjustment for age, sex, medication, comorbidities, and index date based on the time-dependent analysis.ResultsColchicine users had a significantly lower risk of HD (aHR = 0.87, 95% confidence interval (CI]) = 0.82–0.92) than did the colchicine non-user. For colchicine non-users as the reference, the aHR (95% CI) of the patients who received colchicine of 2–7, 8–30, 31–150, and > 150 days were 0.89 (0.81–0.98), 0.84 (0.76–0.94), 090 (0.80–0.99), and 0.83 (0.74–0.93), respectively; regardless of duration use, the lower risk of HD persisted in colchicine users. The cumulative incidence of HD in colchicine users was significantly lower than that in the colchicine non-users (log-rank p < 0.001).ConclusionThe addition of short-term or long-term colchicine to standard medical therapy may have benefits to prevent the HD among the ILD patients concurrent with a virus infection or comorbidities even in elderly patients.

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Predictors for progressive fibrosis in patients with connective tissue disease associated interstitial lung diseases

Cited by 27 publications

References 48 publications

KL-6 as a Biomarker of Interstitial Lung Disease Development in Patients with Sjögren Syndrome: A Retrospective Case–Control Study

KL-6 as a Biomarker of Interstitial Lung Disease Development in Patients with Sjögren Syndrome: A Retrospective Case–Control Study

Hydroxychloroquine on the Pulmonary Vascular Diseases in Interstitial Lung Disease: Immunologic Effects, and Virus Interplay

Colchicine Is a Weapon for Managing the Heart Disease Among Interstitial Lung Disease With Viral Infection: Have We Found the Holy Grail?

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