Transthoracic Ultrasound in the Detection of Interstitial Pulmonary Fibrosis in Patients with Rheumatic Connective Tissue Diseases.
High-resolution CT (HRCT) is the gold standard method for diagnosis of SSc related interstitial lung disease. (7) Ultrasound (US) is increasing its potential in the assessment of several rheumatic disorders. (8) Recently, different applications of this imaging technique have emerged. Interesting data supporting its utility and validity in the assessment of the lung to detect and quantify interstitial pulmonary fibrosis in rheumatic diseases, even in subclinical phases, have been reported. (9) The main purpose of this review is to provide an overview of the role of US in the assessment of interstitial pulmonary fibrosis in connective tissue rheumatic disorders and to discuss the current evidence supporting its clinical relevance in daily practice.
The role of transthoracic ultrasound (TTUS) in the assessment of a various pulmonary conditions has been previously reported. (10) The ultrasonographic feature of pulmonary fibrosis consists of detection and quantification of the US lung comet tail sign (B-line artifacts); this sign is generated by the reflection of the US beam from the thickened subpleural interlobar septum. Previous studies have reported extensive assessment of the lung by examining a great number of intercostal spaces, which is difficult and time consuming. (11) The aim of our study was to examine only selective intercostal spaces--10 locations (modified TTUS)--and to compare the results of this new scoring system with the HRCT findings according to the Warrick score.
The aim of our study was to examine only selective intercostal spaces--10 locations (modified TTUS) (10)--and to compare the results of this scoring system with the HRCT findings according to the Warrick score. (7)
Sixty two consecutive patients who had a suspected diagnosis of rheumatic lung involvement clinically were referred to the rheumatology outpatient clinic of the Aswan University Hospital and who then underwent chest HRCT were included in the study. The diagnosis of each rheumatologic disorder was made according to the American College of Rheumatology classification criteria. (12)
Inclusion criteria were a confirmed diagnosis of rheumatologic disease and chest HRCT performed no longer than 1 week prior to the beginning the study. Patients with a history of pulmonary neoplasia or other causes of interstitial fluid, such as asthma or pulmonary edema and history of smoking were excluded from the study.
After complete history taking all the patients were completely evaluated by a one cardiologist, one pulmonologist, and one rheumatologist in order to confirm the diagnosis and exclude other causes of pulmonary and cardiac conditions that induce US B-lines. The confirmation of the exclusion criteria were made mainly on the aspects of the clinical evaluation and an echocardiogram to rule out cardiac disease.
All of the chest HRCT and TTUS examinations were performed at the radiology departments of Aswan University hospital. All chest HRCT examinations were interperateted and scored by one radiologist who had experience in pulmonary HRCT manifestations of interstitial lung disease and was blinded to the study design.
All TTUS examinations were performed by one chest physician who had 8 years of experience in TTUS pulmonary assessment and intervention. The TTUS examiner was blinded to both the clinical data and HRCT findings. Moreover, patients were asked not to talk about their disease withUS examiners. Ethical approval was obtained from the Ethics Committee and informed consent was obtained from all patients.
For the echocardiographic study, all patients were studied in left lateral decubitus position using an ultrasound system (Philips IE 33; Philips North America Corporation, Andover, Massachusetts) using an S5 transducer standard two dimensional M mode and apical 4 and 2 chamber view and left parasternal view according to the American Society of echocardiography guidelines. (13)
Chest HRCT examination was performed by using a MDCT scanner (GE Light Speed RT 16 CT Scanner; GE, Milwaukee, Wisconsin) at full inspiration in the supine position (120 kV and 300 mAs). The lung parenchyma was imaged in prone sections from the apex to base with a table increment of 10 mm and a slice thickness of 1 mm with a bone plus reconstruction with lung window. No intravenous contrast material was used. Pulmonary involvement was identified and scored according to the Warrick score, then scores obtained at HRCT assessments were evaluated with a semiquantitative scoring: 0 = negative (0 points), 1 = mild (< 8 points), 2 = moderate (from 8 to 15 points), and 3 = severe (> 15 points). (14)
The TTUS examination was performed using an US machine (Medison, Seoul, South Korea) equipped with a 7 to 13 MHz broadband linear multi-frequency transducer. Patients were examined in the supine position for assessment of the anterior chest wall and in the sitting position for assessment of the posterior chest wall. Ultrasound images were obtained by moving the probe longitudinally along anatomical reference lines.
The modified TTUS B-lines assessment consisted of a total of 10 intercostal spaces (ICS) bilaterally. In the anterior chest wall, we examined the fourth ICS along the midclavicular line and the anterior and mild-axillary lines. In the posterior chest, the eighth ICS in the posterior axillary lines and subscapular area were examined. (10) These 10 sites were selected according to the higher prevalence of involvement in interstitial lung disease and accessibility by TTUS. The ultrasonographic investigator was unaware of chest HRCT results and clinical data of the patients.
In TTUS, the artifact generated from the thickened interlobular septa at lung surface was considered as TTUS B-line. The TTUS B-line is a hyperechoic narrow-based reverberation artifact that generally are not visible in normal lung parenchyma. (10)
Comet-tail images arising from the pleural line can be localized or disseminated to the whole lung surface. They are considered multiple when at least three artifacts are visible in a frozen image in one longitudinal scan with a distance of less than 7 mm between two artifacts. (15) A positive study is defined as bilateral multiple comet-tail images, either disseminated (defined as all over the anterolateral lung surface) or lateral (defined as limited to the lateral lung surface). A negative study is defined as an absence of comet-tail images, isolated two comet-tail images visible, or when multiple comet-tail images are confined laterally to the last intercostal space above the diaphragm. The TTUS assessment was scored semi-quantitatively (to correlate with HRCT results) as 0 = negative (as mentioned before 2 B-lines), 1 = mild (from 3 to 10 B-lines), 2 = moderate (from 11 to 18 B-lines), and 3 = severe (> 18 B-lines). (16)
Statistical analysis was performed using IBM SPSS Statistics software version 16 (IBM, Armonk, New York). Descriptive results were expressed as mean and standard deviation (SD). P-values below 0.05 were considered statistically significant. We calculate sensitivity, specificity, and positive and negative predictive value of TTUS in comparison with HRCT as the gold standard.
Sixty two consecutive patients (58 females and 4 males) with a diagnosis of rheumatologic lung disease were included in the study. The mean and standard deviation for age was 47.5 [+ or -]8.9 years (range: 21 to 76 years). The mean and standard deviation for the disease duration was 56 [+ or -] 27.9 months (range: 18 to 130 months).
The underlying disease was rheumatoid arthritis in 36 patients (58%), progressive systemic sclerosis in 21 patients (34%), overlap syndrome in 3 patients (4.8%), 1 patient (1.6%) had Sjogren's syndrome, and 1 patient (1.6%) had dermatomyositis.
Ultrasound lung comment (ULC) assessment was obtained in all patients (feasibility is 100%). The imaging and analysis time was always less than 5 minutes.
The New York Heart Association (NYHA) functional class at admission was significantly related to number of ULCs as the ULC number increases with increasing degrees of NYHA class (p < 0.0001), (Table 1). Also the nine patients admitted with acute heart failure had a higher number of ULC's when compared to the 53 patients without acute heart failure.
Echocardiographic characteristics of the 62 patients showed correlation between ultrasound lung comets and clinical and echocardiographic parameters. There was a significant linear correlation between ULCs and pulmonary artery systolic pressure (p < 0.0001). We found that the ULC number increases with increasing degrees of diastolic dysfunction. There was an inverse relationship between the number of ULCs and the ejection fraction (though ejection fractions were within normal levels), (Fig.1), so that the degree of diastolic dysfunction is a stronger determinant of ULC than the ejection fraction.
In comparison with HRCT (as shown in Figures 2 and 3), disease severity was comparable with numbers of ULCs (Table 2) and HRCT as the gold standard method, the sensitivity, specificity, and positive and negative predictive value of TTUS was 69.9%, 84.8%, 93.5%, and 49.7%, respectively.
Currently, chest HRCT is considered the "gold-standard" methodforthe diagnosis of disease activity inboth early pulmonary involvement and subclinical lung involvement. (7,10,11)
HRCT is the gold-standard method for detection and quantification of lung fibrosis in SSc, especially in early stages of lung involvement. (11)
According to Lichtenstein (11), transthoracic chest US was previously described in many studies for assessing some pulmonary conditions, such as pulmonary interstitial edema, atelectases, and pleural effusions, and to guide for interventional lung and pleural lesion biopsy. Currently the role of TTUS for investigation of pulmonary fibrosis in systemic sclerosis has been described. (7)
Our problem with previous US scoring systems is that it needs to assess the US B-lines in more than 50 LIS, which is time consuming and is difficult to employ as a daily practical clinical method. (10) In our study, US B-line assessment is composed of 10 intercostal spaces, chosen on the basis of the major prevalence of lung segment involvement during HRCT assessment. Diagnosis and quantification of lung involvement in patients with SSc has therapeutic and prognostic significance. (7,10,11)
This study evaluated the presence of interstitial lung involvement as US B-lines by modified TTUS in patients with rheumatologic disease in comparison with the HRCT as gold-standard method. Transthoracic ultrasound is usually performed by low to medium (3.5 to 5 MHz) frequency transducers, whereas high frequency linear transducers are considered to be the best tool for investigation of the pleural line. The differential diagnosis of US B-lines includes cardiac manifestions caused by the thickening of the interlobular septa, such as in pulmonary edema. (11)
According to our study, TTUS can be helpful in identifying and quantifying pulmonary fibrosis, as assessed by HRCT. From a cost effective standpoint, the accessibility and rapid performance time (less than 6 minutes) of TTUS demonstrates the clinical impact of this method, which was also emphasized in the study by Sartori and Tombesi. (17)
It seems that HRCT remains the gold-standard method for assessing interstitial lung involvement because only HRCT allows the investigation of the entire lung parenchyma. In comparison with HRCT, TTUS allows the assessment of only the surface of the lung and may be useful as an adjunctive method for the follow-up of patients, especially during treatment, because it can reduce radiation exposure especially in young women who have a higher cancer risk than men (18)
The results of current research on TTUS in pulmonary interstitial lung disease showed a good correlation with HRCT as a "gold standard" method. Ultrasound can be a valuable diagnostic modality for the assessment of the chest because it is widely available, inexpensive, is a bedside procedure, and is safer. The lung surface can be easily investigated by TTUS, so the comet tail sign "artifacts" are quickly detectable with small surface high frequency probe. (17)
Interstitial pulmonary fibrosis involvement in patients with rheumatic CTDs may be diagnosed by TTUS even in early stages. The presence US B-lines upon TTUS examination has good sensitivity for diagnosis of lung involvement at HRCT. Modified TTUS is a rapid imaging modality in the evaluation of pulmonary involvement in rheumatic CTDs.
None of the authors have a financial or proprietary interest in the subject matter or materials discussed, including, but not limited to, employment, consultancies, stock ownership, honoraria, and paid expert testimony.
(1.) Gutsche M, Rosen GD, Swigris JJ. Connective Tissue Disease-associated Interstitial Lung Disease: A review. Curr Respir Care Rep. 2012 Sep 21;l:224-32.
(2.) Corte TJ, Collard H, Wells AU. A new era in idiopathic interstitial pneumonias: Epilogue to a review series. Respirology. 2017 Jan;22(l):14-6.
(3.) Vij R, Strek ME. Diagnosis and treatment of connective tissue disease-associated interstitial lung disease. Chest. 2013 Mar;143(3):814-24.
(4.) Alhamad EH, Cal JG, Alboukai AA, et al. Autoimmune symptoms in idiopathic pulmonary fibrosis: clinical significance. Clin Respir J. 2016 May;10(3):350-8.
(5.) Tomassetti S, Ryu JH, Piciucchi S, et al. Nonspecific Interstitial Pneumonia: What Is the Optimal Approach to Management? Semin Respir Crit Care Med. 2016 Jun;37(3):378-94.
(6.) Mosca M, Tani C, Neri C, et al. Undifferentiated connective tissue diseases (UCTD). Autoimmun Rev. 2006 Nov;6(1): 1-4.
(7.) Bellia M, Cannizzaro F, Scichilone N, et al. HRCT and scleroderma: semiquantitative evaluation of lung damage and functional abnormalities. Radiol Med. 2009 Mar; 114(2): 190-203.
(8.) Assayag D, Kaduri S, Hudson M, et al. High Resolution Computed Tomography Scoring Systems for Evaluating Interstitial Lung Disease in Systemic Sclerosis Patients. Rheumatology: Current Research. 2012; https//doi.org/10.4172/2161-1149.S1-003.
(9.) Gutierrez M, Gomez-Quiroz LE, Clavijo-Cornejo D, et al. Ultrasound in the interstitial pulmonary fibrosis. Can it facilitate a best routine assessment in rheumatic disorders? Clin Rheumatol. 2016 Oct;35(10):2387-95.
(10.) Jambrik Z, Monti S, Coppola V, et al. Usefulness of ultrasound lung comets as a nonradiologic sign of extravascular lung water. Am J Cardiol. 2004 May;93(10): 1265-70.
(11.) Lichtenstein DA. Lung ultrasound in the critically ill. Ann Intensive Care. 2014 Jan;4(1):1.
(12.) Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010 Sep;62(9):2569-81.
(13.) Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjuction with the European Association of Echocardiography, a branch of European Society of Cardiology. JAm Soc Echocardiogr. 2005 Dec;18(12):1440-63.
(14.) Gutierrez M, Salaffi F, Carotti M, et al. Utility of a simplified ultrasound assessment to assess interstitial pulmonary fibrosis in connective tissue disorders--preliminary results. Arthritis Res Ther. 2011 Aug 18;13(4):R134.
(15.) Saraogi A. Lung ultrasound: Present and future. Lung India. 2015 May-Jun;32(3):250-7.
(16.) Gupta D, Agarwal R, Aggarwal AN, et al. Guidelines for diagnosis and management of community-and hospital-acquired pneumonia in adults: Joint ICS/NCCP(I) recommendations. Lung India. 2012 Jul;29(Suppl 2):S27-62.
(17.) Sartori S, Tombesi P. Emerging roles for transthoracic ultrasonography in pulmonary diseases. World J Radiol. 2010 Jun;2(6): 203-14.
(18.) Kalra MK, Maher MM, Rizzo S, et al. Radiation exposure from chest CT: issues and strategies. J Korean Med Sci. 2004 Apr;19(2):159-66.
Amal Fehr, MD, Shazly Baghdady, MD, Ramadan Ghaleb, MD, and Salah Maklad, MD
Amal Fehr, MD, Department of Rheumatology and Rehabilitation, Helwan University Egypt. Shazly Baghdady, MD, Department of Pulmonology, Ramadan Ghaleb, MD, Department of Cardiology, and Salah Maklad, MD, Department of Diagnostic Radiology, Aswan University, Egypt.
Correspondence: Amal Fehr MD, Rheumatology and Physical Medicine Department, Faculty of Medicine, Helwan University, Egypt; firstname.lastname@example.org.
Caption: Figure 1 ULCs number and ejection fraction.
Caption: Figure 2 A, HRCT showing the mild form of interstitial pulmonary fibrosis (Warrick score = 4). B, The comet tail sign (two B-lines in the mild form of interstitial pulmonary fibrosis.
Caption: Figure 3 A, HRCT showing the moderate form of interstitial pulmonary fibrosis (Warrick score = 8). B, The comet tail sign (two B-lines) in the moderate form of interstitial pulmonary fibrosis.
Table 1 Clinical Data and TTUs of the Patients (N = 62) NYHA Functional Class on Admission TTUS Severity Score N (%) N (%) Class I 29 (47%) Negative 29 (47%) Class II 13 (21%) Negative 2 (3%) & Mild 13 (20%) Class III 11 (17%) Moderate 9 (15%) Class IV 9 (15%) Severe 9 (15%) Table 2 Severity of Lung Interstitial Severity Score Assessed by TTUS Severity Score and HRCT of Patients (N = 62) Severity Score Class TTUS Severity Score HRCT Severity Score N (%) N (%) Negative 31 (50%) 29 (47%) Mild 13 (20%) 16 (26%) Moderate 9 (15%) 7 (11%) Severe 9 (15%) 10 (16%)
Please Note: Illustration(s) are not available due to copyright restrictions.
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|Author:||Fehr, Amal; Baghdady, Shazly; Ghaleb, Ramadan; Maklad, Salah|
|Publication:||Bulletin of the NYU Hospital for Joint Diseases|
|Date:||Jul 1, 2018|
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