Serum Krebs von den Lungen-6 and lung ultrasound B lines as potential diagnostic and prognostic factors for rheumatoid arthritis–associated interstitial lung disease

Background:Objectives:To analyze the diagnostic utility of lung ultrasound (US) to detect interstitial lung disease (ILD) in Rheumatoid arthritis (RA) patients comparing with high-resolution computed tomography (HRCT).Methods:Study design: We performed a cross-sectional, observational study in patients with RA-ILD (cases) controlled with a gruop of RA patients without ILD (controls) paired by sex, age and time of disease evolution.Protocol: Patients were selected between May and September 2019. Patients were interwied by two rheumathologist for the protocolized collection of clinical data. The patients were assessed using HRCT, Pulmonary Function Test (PFT) and lung US.. The rheumatology who performed the lung US were blinded to patients clinical data. Variables: (1) B-lines number; (2) evaluation of the lung- ultrasound score already described: L. Gargani, Gutiérrez comprehensivo, Gutiérrez reducido and Mohhammadi;(3)pleural irregularities; (4) A pattern US lost;(5). Other variables included demographic, clinical-analytical, therapeutic and ILD-type description. Statistical analysis: descriptive, bivariant analysis. We applied Pearson’s correlation coefficient between B-lines, PFT and clinical variable.Furthermore, to establish the cut-off point of the US B-lines number for detecting the presence of significant AR-ILD in relation to HRCT, we used the receiver operating characteristic (ROC) curve analysis. A logistic regression analysis was performed to identify the intercostal spaces (IV: B-lines number in each space) wich wereindependently associated with ILD (DV: ILD in HRCT).Results:71 patients were included, 37 (52,1%) with ILD-RA and 34 (47,95) RA controls. The main characteristics are shown in Table 1. RA-ILD presented more B-lines number than control without ILD (median ICR] 91.0 [31.0-149.0] vs 6.5 [1.5-30.5]; p=<0.001) and more pleural irregularities (PI) [PI-median(ICR) 41.0 (5.0-57.5) vs 2.5 (0.0-7.2); p<0,001]. Furthermore, RA-ILD showed a negative correlation between B-lines and DLCO(r =-0.337, p=0.048)and positive with DAS28 (r =0.347, p=0.035). Regarding US score, we found that the detection of 32.5 B-lines in 72 intercostal spaces, had aSensitivity of 75.7%, Specifity=79.4%, PPV= 80% and NPV=75%,whilst in reduced score of 10 intercostal spaces, the detection of 5.5 B-lines had a sensivity= 62.2%,Specifity= 91.3%, PPV=88.4%, NPV=69.5%. In multivariate analysis, the intercostal spaces which showed independent association with ILD were 3rdright anterior axillary space(OR [IC 95%] 19.0 [1.3-27.5]), 8thright posterior axillary space (OR [IC 95%] 0.04 [0.0-0.6]), 8thright subescapular space (OR [IC 95%] 16.5 [1.8-45.5]),9thright paravertebral space (OR [IC 95%] 7.11 [1.0-37.1]) and 2ndleft clavicular middle space(OR [IC 95%] 21.9 [1,26-37.8]).Conclusion:Lung Ultrasoud could be a useful tool for interstitial lung disease diagnosis associated with Rheumatoid Artrithis. A 10 space reduced score showed a similar total predictive capacity than 72-space scoreReferences:Disclosure of Interests:None declared

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Lung ultrasound in patients with rheumatoid arthritis and the definition of significant interstitial lung disease

10.21203/rs.3.rs-18869/v2 ◽

2020 ◽

Author(s):

Marco Di Carlo ◽

Marika Tardella ◽

Emilio Filippucci ◽

Marina Carotti ◽

Fausto Salaffi

Keyword(s):

Rheumatoid Arthritis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Roc Curve ◽

Lung Ultrasound ◽

Smoking Habit ◽

Curve Analysis ◽

Roc Curve Analysis ◽

The Mean ◽

B Lines

Abstract 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. However, in patients with RA it is not yet clear how to interpret, in quantitative terms, the presence of B-lines, the LUS artifact indicative of ILD. The aim of this study was 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 (carried out in 14 defined intercostal spaces), chest HRCT, pulmonary function tests, and clinical evaluation. The diagnosis of RA-ILD was based on a semi-quantitative evaluation of chest HRCT using a computer-aided method (CaM). The discriminative validity of the LUS versus HRCT has been studied by using the receiver operating characteristic (ROC) curve analysis.Results. 72 consecutive RA patients (21 male, 51 female) were evaluated, with a mean age of 63.0 (SD 11.5 years). The mean estimate of pulmonary fibrosis using the CaM was 11.20% (SD 7.48) at chest HRCT, while at LUS the mean number of B-lines was 10.65 (SD 15.11). A significant RA-ILD, as measured by the CaM at HRCT, was detected in 25 patients (34.7%). 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 RA-ILD with a sensitivity of 70.0%, a specificity of 97.62%, and a positive likelihood ratio of 29.4.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.

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Lung ultrasound in patients with rheumatoid arthritis and the definition of significant interstitial lung disease

10.21203/rs.3.rs-18869/v1 ◽

2020 ◽

Author(s):

Marco Di Carlo ◽

Marika Tardella ◽

Emilio Filippucci ◽

Marina Carotti ◽

Fausto Salaffi

Keyword(s):

Rheumatoid Arthritis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Roc Curve ◽

Lung Ultrasound ◽

Smoking Habit ◽

Curve Analysis ◽

Roc Curve Analysis ◽

The Mean ◽

B Lines

Abstract 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. However, it is not yet well defined how to interpret the LUS findings under suspicion of RA-ILD. The aim of this study was 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 (carried out in 14 defined intercostal spaces), chest HRCT, pulmonary function tests, and clinical evaluation. The diagnosis of RA-ILD was based on a semi-quantitative evaluation of chest HRCT using a computer-aided method (CaM). The discriminative validity of the LUS versus HRCT has been studied by using the receiver operating characteristic (ROC) curve analysis. Results 72 consecutive RA patients (21 male, 51 female) were evaluated, with a mean age of 63.0 (SD 11.5 years). The mean estimate of pulmonary fibrosis using the CaM was 11.20% (SD 7.48) at chest HRCT, while at LUS the mean number of B-lines was 10.65 (SD 15.11). A significant RA-ILD, as measured by the CaM at HRCT, was detected in 25 patients (34.7%). 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 RA-ILD with a sensitivity of 70.0%, a specificity of 97.62%, and a positive likelihood ratio of 29.4. 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.

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The role of lung ultrasound B-lines and serum KL-6 in the screening and follow-up of rheumatoid arthritis patients for an identification of interstitial lung disease: review of the literature, proposal for a preliminary algorithm, and clinical application to cases

Arthritis Research & Therapy ◽

10.1186/s13075-021-02586-9 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Yukai Wang ◽

Shaoqi Chen ◽

Shaoyu Zheng ◽

Jianqun Lin ◽

Shijian Hu ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Practice ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Lung Ultrasound ◽

Pulmonary Function Tests ◽

Usual Interstitial Pneumonia ◽

Long Term Outcome ◽

B Lines

AbstractScreening and follow-up of interstitial lung disease associated with rheumatoid arthritis (RA-ILD) is a challenge in clinical practice. In fact, the majority of RA-ILD patients are asymptomatic and optimal tools for early screening and regular follow-up are lacking. Furthermore, some patients may remain oligosymptomatic despite significant radiological abnormalities. In RA-ILD, usual interstitial pneumonia (UIP) is the most frequent radiological and pathological pattern, associated with a poor prognosis and a high risk to develop acute exacerbations and infections. If RA-ILD can be identified early, there may be an opportunity for an early treatment and close follow-up that might delay ILD progression and improve the long-term outcome.In connective tissue disease–associated interstitial lung disease (CTD-ILD), lung ultrasound (LUS) with the assessment of B-lines and serum Krebs von den Lungen-6 antigen (KL-6) has been recognized as sensitive biomarkers for the early detection of ILD. B-line number and serum KL-6 level were found to correlate with high-resolution computed tomography (HRCT), pulmonary function tests (PFTs), and other clinical parameters in systemic sclerosis–associated ILD (SSc-ILD). Recently, the significant correlation between B-lines and KL-6, two non-ionizing and non-invasive biomarkers, was demonstrated. Hence, the combined use of LUS and KL-6 to screen and follow up ILD in RA patients might be useful in clinical practice in addition to existing tools. Herein, we review relevant literature to support this concept, propose a preliminary screening algorithm, and present 2 cases where the algorithm was used.

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POS0842 LUNG ULTRASOUND TO ASSESS THE SEVERITY OF INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1350 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 675.1-675

Author(s):

C. Bruni ◽

L. Mattolini ◽

L. Tofani ◽

L. Gargani ◽

N. Landini ◽

...

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Quantitative Methods ◽

Lung Ultrasound ◽

Significant Negative Correlation ◽

High Resolution Computed Tomography ◽

Quantitative Score ◽

Quantitative Scoring ◽

B Lines

Background:Interstitial lung disease (ILD) is one of the most common complications and one of the main causes of morbidity and mortality in Systemic Sclerosis (SSc). High-resolution computed tomography (HRCT) is the gold standard for the diagnosis of ILD and it allows its quantification. Among semi-quantitative methods, Goh et al proposed a semi-quantitative scoring system to visually quantify ILD extent, with categorical cut-off of 20% to distinguish limited and extensive parenchymal involvement with prognostic implications. More recently, the use of radiomics has allowed the objective quantification of ILD through the use of dedicated software, which calculate different parameters of lung density.Given the exposure to ionizing radiation that the procedure entails, other methods of ILD evaluation are being studied, among which lung ultrasound (LUS) identifies the B-lines as a main feature of ILD. So far, different evidences have proposed the use of LUS for the screening of ILD, even in the early phases of the disease and in subclinical lung involvement.Objectives:the aim of this study is to test the role of LUS in quantifying the severity of SSc-ILD, evaluated with both semi-quantitative visual radiological and quantitative radiomic scores.Methods:Adult SSc patients classified according to the ACR/EULAR 2013 criteria patients were assessed with pulmonary function test (PFTs), lung ultrasound and HRCT over 60 days. CT images were analysed qualitatively (by presence/absence of ILD), semi-quantitatively (categorical Goh score <20% vs> 20% of extent and the continuous extent Goh score made from 5 levels’ assessment– 0 to 100%) and quantitatively [with the densitometric radiomic data obtained through the Horos software - Mean lung attenuation (MLA), Standard Deviation (SD), Kurtosis, Skewness and Lung volume (LV)]. LUS was used to quantify the B-lines detected in each patient by scanning a total of 13 intercostal spaces, on both anterior and posterior chest wall.Results:Among 59 SSc patients (81% women, mean age 48±14 years, 45% anti-Scl70 positive), 23 (39%) presented ILD on HRCT, of which 14 limited and 9 extensive. The mean visual semi-quantitative score was 6%, ranging from 0 to 66%. Our data showed a significantly different number of B-Lines in ILD vs non-ILD patients (median 38 vs 9, p <.005), a result which was further confirmed among non-ILD vs ILD> 20% (median 47 vs 9, p=.001) and ILD <20% (median 36 vs 9, p=.001) patients. Conversely, the number of B-lines was not statistically different between patients with ILD <20% and >20% (median 47 vs 36, p=.78). We observed a significant negative correlation between the number of B-lines and FVC (r=-.472, p<.05) TLC (r=-.436, p=.003), DLco (r=-.515, p<.001), DLCO/VA (r=.-306, p=.03). Finally, the number of B-lines showed a statistically significant correlation with the Goh score on 5 levels (r=.437, p=.001), MLA (r=.571, p<.001), kurtosis (r=-.285, p=.028), skewness (r=-.370, p = .004) and LV (r=-.277, p=.033). All data were confirmed analysing anterior and posterior B-Lines separately.Conclusion:Our study confirms that LUS represents a useful tool for the identification of SSc-ILD. In addition, we showed that LUS may be useful also for the quantification of the severity of SSc-ILD, by correlating with PFT parameters, radiomics parameters and visual radiological evaluation. Together with the PFTs, LUS could be used to increase the accuracy of the screening and, potentially, of the follow-up of SSc-ILD patients.Disclosure of Interests:Cosimo Bruni: None declared, Lavinia Mattolini: None declared, Lorenzo Tofani: None declared, Luna Gargani Consultant of: GE Healthcare, Philips Healthcare and Caption Health, Nicholas Landini: None declared, Gemma Lepri: None declared, Martina Orlandi: None declared, Serena Guiducci: None declared, Silvia Bellando Randone: None declared, Marco Matucci-Cerinic: None declared

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Lung ultrasound B-lines and serum KL-6 correlate with the severity of idiopathic inflammatory myositis-associated interstitial lung disease

Rheumatology ◽

10.1093/rheumatology/kez571 ◽

2019 ◽

Vol 59 (8) ◽

pp. 2024-2029 ◽

Cited By ~ 1

Author(s):

Yukai Wang ◽

Shaoqi Chen ◽

Jianqun Lin ◽

Xuezhen Xie ◽

Shijian Hu ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Pulmonary Function ◽

Lung Disease ◽

Lung Ultrasound ◽

Pulmonary Function Tests ◽

Forced Expiratory Volume ◽

Inflammatory Myositis ◽

Idiopathic Inflammatory Myositis ◽

Function Tests ◽

B Lines

Abstract Objective Idiopathic inflammatory myositis-associated interstitial lung disease (IIM-ILD) significantly increases morbidity and mortality. Lung ultrasound B-lines and Krebs von den Lungen-6 (KL-6) are identified as new sonographic and serum markers of ILD, respectively. The aim of our work was to assess the role of B-lines and KL-6 as markers of the severity of IIM-ILD. For this purpose, the correlation among B-lines score, serum KL-6 levels, high-resolution CT (HRCT) score, and pulmonary function tests were investigated in IIM-ILD patients. Methods Thirty-eight patients with IIM-ILD underwent chest HRCT scans, lung ultrasound and pulmonary function tests (independently performed within 1 week) examination. To assess severity and extent of ILD at HRCT, the Warrick score was used. The B-lines score denoting the extension of ILD was calculated by summing the number of B-lines on a total of 50 scanning sites. Serum KL-6 levels (U/ml) was measured by chemiluminescent enzyme immunoassay. Results A significant correlation was found between the B-lines score and serum KL-6 levels (r = 0.43, P < 0.01), and between the Warrick score and serum KL-6 levels (r = 0.45, P < 0.01). A positive correlation between B-lines score and the Warrick score (r = 0.87, P < 0.0001) was also confirmed. Both B-lines score and KL-6 levels inversely correlated to diffusion capacity for carbon monoxide (r = −0.77, P < 0.0001 and r = −0.42, P < 0.05, respectively) and total lung capacity (r = −0.73, P < 0.0001 and r = −0.36, P < 0.05, respectively). Moreover, B-lines correlated inversely with forced vital capacity (r = −0.73, P < 0.0001), forced expiratory volume in 1 s (r = −0.69, P < 0.0001). Conclusion B-lines score and serum KL-6 levels correlate with HRCT findings and pulmonary function tests, supporting their use as measures of IIM-ILD severity.

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