Indian Journal of Rheumatology

: 2021  |  Volume : 16  |  Issue : 3  |  Page : 269--275

Diagnostic validity of lung ultrasonogram in comparison with high-resolution computed tomography in interstitial lung disease associated with connective tissue disease

PV Lisha1, N Safreena Mohamed2, TP Rajagopal2, Rennis Davis1, Thomas Vadakkan Devassy1,  
1 Department of Pulmonary Medicine, Amala Institute of Medical Sciences, Thrissur, Kerala, India
2 Department of Pulmonary Medicine, Government Medical College, Kozhikode, Kerala, India

Correspondence Address:
Dr. P V Lisha
Department of Pulmonary Medicine, Amala Institute of Medical Sciences, Thrissur, Kerala


Background: Lung ultrasonography (LUS) may be a useful tool in identifying interstitial lung disease (ILD) in patients with Connective tissue disorder (CTD). The aim of the current study was to determine the diagnostic validity of LUS findings in comparison with high-resolution computed tomography (HRCT) in CTD-ILD and also determine the correlation between forced vital capacity (FVC) and 6-min walk test (6MWT) to LUS. Patients and Methods: Patients with connective tissue disorder and ILD diagnosed by HRCT were included and evaluated by physical examination, LUS, spirometry, and 6MWT. Results: Of 41 patients included, 38 (92.7%) were females. The mean age was 49.7 years. Systemic sclerosis was the most common diagnosis in 25 (61%) patients. LUS score was calculated as the total number of B-lines counted in all zones. The mean score was 20.83. B-line score showed a negative correlation with 6MWT distance (R = −0.501, P = 0.001) and FVC (R = −0.434, P = 0.005). There was a strong positive correlation between LUS and HRCT scores (R = 0.878, P = 0.0001). A LUS score of 39.5 or above has 83% sensitivity and 100% specificity (Youden index of 0.83, P = 0.001) for predicting a Class V HRCT pattern. Conclusions: There was a significant correlation between ILD with reticular pattern and honeycombing on HRCT and higher LUS B-line scores. LUS B-line scores also correlated significantly with functional parameters such as lower FVC values and 6MWT distance.

How to cite this article:
Lisha P V, Mohamed N S, Rajagopal T P, Davis R, Devassy TV. Diagnostic validity of lung ultrasonogram in comparison with high-resolution computed tomography in interstitial lung disease associated with connective tissue disease.Indian J Rheumatol 2021;16:269-275

How to cite this URL:
Lisha P V, Mohamed N S, Rajagopal T P, Davis R, Devassy TV. Diagnostic validity of lung ultrasonogram in comparison with high-resolution computed tomography in interstitial lung disease associated with connective tissue disease. Indian J Rheumatol [serial online] 2021 [cited 2021 Dec 6 ];16:269-275
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Full Text


Interstitial lung diseases (ILDs) are one of the most important causes of mortality in patients affected with connective tissue disorders (CTDs). Currently, high-resolution computed tomography (HRCT) is the gold standard for diagnosing ILD. This group of patients is also more likely to be functionally restricted due to joint deformities which can make functional tests of lung impossible.[1],[2],[3] HRCT involves a significant amount of radiation and cost. Lung ultrasonogram (LUS) is a nonionizing, portable, cheaper, and less technically demanding investigation which can be used repeatedly in these patients, especially in young females. In 1989, Daniel Lichenstein pioneered a point-of-care ultrasonogram in the intensive care unit. Since then, LUS has found its application in various settings and disease conditions of the lung. The understanding of correlation between CT and LUS findings is necessary for LUS to be useful in the context of screening, prognostication, and follow-up of connective tissue disease-associated ILDs (CTD-ILDs). Although there have been many studies comparing the LUS and HRCT in ILD, there is no agreement on the ideal scoring systems and cutoff values in LUS. The correlation between LUS findings and lung function is also not well described.

 Patients and Methods

The objectives of the study were to determine the diagnostic validity of ultrasound findings of the lung in comparison with HRCT in connective tissue disease-associated ILD and to determine the correlation between forced vital capacity (FVC) and 6-min walk test (6MWT) distance with lung ultrasound findings in these patients. The study included patients diagnosed with systemic lupus erythematosus, rheumatoid arthritis, mixed connective tissue disease, and systemic sclerosis (SS) according to internationally accepted criteria and also having a diagnosis of nonspecific interstitial pneumonia (NSIP) or usual interstitial pneumonia (UIP) by HRCT. Only individuals above 18 years of age were included in the study. The study was approved by the Institutional Ethics Committee of Government Medical College Kozhikode through order no GMCKKD/RP2017/IEC/132 dated June 9, 2017.

The rheumatological diagnosis was made in the rheumatology clinic by consultant internal medicine practitioners with recognized rheumatology degrees, and patients with respiratory symptoms were referred to the pulmonology outpatient department. Among them, a subset of patients with an HRCT diagnosis of ILD were selected for the study after obtaining due informed written consent in vernacular language. Convenient sampling methods were implemented to include 41 patients. Data collection was done from each patient through a structured questionnaire designed by the principal investigator. Demographic data related to gender, age, duration of symptom onset, and predominant respiratory symptom were collected during direct interview with the patient. As part of the dyspnea evaluation, all patients also had cardiology consultation with echocardiography. Presence of a clinical diagnosis that may mimic interstitial syndrome in LUS, for e.g, congestive cardiac failure, pneumonia, acute respiratory distress syndrome (ARDS), and those with pleural diseases were excluded from the study.

The patients were subjected to history, physical examination, FVC, 6MWT, and LUS. Patients were allowed to continue their treatment. The following were the details of scoring system used for HRCT and LUS.

Scoring of high-resolution computed tomography

HRCT is assessed using the scoring method adapted from the comparative scoring method by Morelli et al.[4] The scoring was done by a qualified radiologist from the department of radiodiagnosis, who was blinded to the LUS findings. The scoring was done by assigning scores to each zone of the lungs based on the predominant abnormality.

Parenchymal opacification alone = 1Parenchymal opacification > reticular pattern extent = 2Parenchymal opacification = reticular pattern extent = 3Reticular pattern extent > parenchymal opacification = 4Reticular pattern or honeycombing alone = 5.

A three-slice method was used – at the level of aortic arch, at the level of inferior pulmonary veins, and at the level of right hemidiaphragm. The scores at each level were added to obtain the total HRCT score. A higher score in HRCT indicated more reticular and fibrotic patterns than ground glassing or alveolar opacification.

LUS scoring

LUS scoring was done by a pulmonologist with training in LUS who was blinded to the HRCT findings but has knowledge of the clinical findings of the patient. A convex abdominal probe of 5 MHz was used. Mindray DC-7 Ultrasonogram (USG) machine was used in the study. A patient is evaluated in the sitting position with arms above the head. Six regions are scanned, as given in [Figure 1]. Three regions per side were considered for lung ultrasound examination. Three intercostal spaces were scanned with probe kept horizontally between the ribs in each zone making a total of 18 lung intercostal spaces (LISs). Zones 1 and 2 denote the right and left upper posterior chest areas, respectively. Zones 3 and 4 denote the right and left lower posterior chest areas, and areas 5 and 6 represent right and left axillary areas, respectively. The presence of B-lines generated from the thickened interlobular septa at the lung–chest wall interface is assessed. B-lines are defined as well-defined, vertical, hyperechoic, dynamic lines originating from the pleural line and spreading like a laser ray up to the edge of the screen. A positive region is defined by the presence of three or more B-lines in a horizontal plane between two ribs. The number of B-lines was determined in each of the positive zones by keeping the probe in each intercostal space of a zone and taking the average number of B-lines as the score of that zone. A total score was assigned as the sum of the scores of all the six zones.{Figure 1}

Six-minute walk test data

The 6-min walk distance test was done according to standard protocol[5] and graded according to distance walked. Distance of up to 150 m was graded as Class I, 151–250 m as Class II, 251–350 m as Class III, and above 351 m as Class IV.


Spirometry was performed according to standard technique[6] and classified into groups, as shown in [Table 1].{Table 1}

Statistical analysis

The baseline demographic and clinical variables are presented as mean and standard deviation for continuous variables and frequency and percentage for discrete variables. The Chi-square test was used to compare the categorical variables. Spearman correlation coefficient (R) was used to test the correlation between continuous variables as these variables were not normally distributed. All tests were two-tailed, and P < 0.05 was considered statistically significant. All statistical analyses were done using the Statistical Package for the Social Sciences software (version 20.0. IBM Corp., Armonk, NY, USA). Receiver operating characteristic (ROC) curve was plotted to define the diagnostic ability of binary classifiers. Area under curve (AUC) estimation with Youden index was done to estimate the accuracy of LUS scores for diagnosing ILD.


A total of 45 patients were subjected to HRCT and were considered for the study, of which it was possible to include 41 patients whose data could be obtained.

Demographic data

The analysis of demographic data revealed that of the 41 patients, 3 (7.3%) were males and 38 (92.7%) were females. The age of the patients ranged from 25 to 66 years with a mean age of 49.7 years. Sixteen (39.0%) persons belonged to the under 50 age group and 25 (61%) patients belonged to the age group above 50.

Clinical data

Dyspnea on exertion was present in all patients. Thirty-five patients (85.3%) had either Modified Medical Research Council (MMRC) Grade 2 or 3 dyspnea on exertion. MMRC Grade 4 dyspnea was found in five patients. All patients had cough which was nonproductive in 82% of the patients. The duration of symptoms ranged from 2 weeks to 104 weeks. The average duration after onset of symptoms at the time of analysis was 30.5 weeks. Clubbing was not detected in any patient. All patients had fine crackles on auscultation of the chest. All the females were nonsmokers. There were two males who were smokers with smoking index above 300. SS was the most common CTD diagnosis followed by RA. Majority of the patients had a 6MWT distance between 250 and 350 m [Table 2]. FVC classification is given in Table 2. Pulmonary hypertension was assessed by echo color Doppler.{Table 2}

High-resolution computed tomography scores

The HRCT thorax was scored by assigning scores to each zone of the lungs based on the predominant abnormality. The distribution of HRCT scores is given in [Table 2].

LUS scoring

The score was calculated as the total number of B-lines counted in all zones. More than three B-lines in any zone were considered significant. The mean score was 20.83. The scores ranged from a minimum of 0 to a maximum of 52. Nine (31%) patients had a low score of <10. Four (13.8%) patients had a score between 11 and 20. Five (17.2%) patients had a score between 21 and 30. Eleven (37.9%) patients had a high score above 30, as given in [Table 2].

Correlation between LUS scores, high-resolution computed tomography, forced vital capacity, and 6-min walk test distances

The correlation of severity grading based on B-lines in LUS was done with HRCT score, FVC, and 6MWT data. A positive correlation was noted between LUS and HRCT classes, indicating that higher LUS score correlated with a more fibrotic or reticular pattern in HRCT. There was a negative correlation between LUS score and 6MWT distance and FVC. The details are given in [Table 3].{Table 3}

Receiver operating curve of LUS score and high-resolution computed tomography classes

A LUS score of 39.5 or above has 83% sensitivity and 100% specificity (Youden index of 0.83) of predicting a Class V hCT patterns with P = 0.001 as analyzed in the ROC curve and AUC analysis, as given in [Figure 2]. An LUS score of 20 had 100% sensitivity but specificity of only 64% (Youden index of 0.64) for a fibrotic pattern on HRCT [Figure 2].{Figure 2}


Lung involvement is one of the most important causes of fatality in CTD, especially in SS-associated ILD.[7] The patients are more likely to be females in the younger age group which may limit the use of CT in follow-up of these patients. Moreover, the limitation of mobility due to joint involvement or critical illness may preclude the performance of functional tests such as 6MWT. Thus, an alternate diagnostic or screening modality in the form of LUS may be beneficial. Furthermore, the maximum effectiveness of ultrasound is obtained through a clinically driven focused assessment.[8]

Chest HRCT is presently considered as the diagnostic gold standard to assess pulmonary fibrosis.[9],[10] Various scoring patterns have been described previously,[10] which can be comparative, semi-quantitative, or quantitative. We have used a comparative scoring system for HRCT grading in this study. Ideally, only a computer-based quantitative scoring gives the actual extent of lung involvement.

B-lines in LUS have been studied extensively as a way to identify interstitial syndrome and whether it correlates with HRCT findings of ILD. B-lines or lung comets are formed from reflection of the ultrasound beam from thickened interlobular septa. The thickening can occur due to inflammation, edema, or fibrosis as in pneumonia, pulmonary edema, or ILD, respectively.[11],[12],[13] Only a clinically directed examination can differentiate these causes. Hence, other interstitial syndromes such as cardiac failure and ARDS have been excluded from our study.

LUS can detect ILD only if the interstitium of the peripheral lung is involved.[13] In NSIP and UIP patterns, the peripheral and subpleural lung is commonly involved. The lung involvement in CTD-ILDs, especially SS, usually starts in the peripheral lower posterior subpleural lung, which is easily accessible using LUS. These are also the predominant patterns in CTD-ILDs. This makes these ILDs suitable for a LUS assessment.

The probe used in the current study was a medium-frequency convex abdominal probe. This aspect has previously been studied by many. Sperandeo et al. stated that B-line was detected better with low–medium-frequency convex probes of 3–5 MHz rather than with high-frequency linear probe of 8–12 MHz. Later, other more accepted studies performed with convex probe, linear probe, cardiac probe, and microconvex probe showed similar findings on the visualization of B-lines in a variety of settings and patients and using different machines.[11],[12],[14],[15],[16],[17],[18]

In the current study, comparing B-line scores with the HRCT scores, we have got a strong positive correlation (r = 0.847, P = 0.0001), indicating that as B-lines increased the fibrotic pattern in HRCT also increased. The ROC curve plotted between USG scores and HRCT scores showed that above a cutoff value of 39.5 the USG B-line score had 100% specificity in predicting a predominantly fibrotic pattern of ILD. A score of 20 gives 100% sensitivity for detecting ILD.

A similar outcome has been discussed in various other studies also. However, the ideal scoring method or scores is still a matter of question. Srivastava et al.[19] studied the correlation between various lung ultrasonological features in 50 patients with HRCT diagnosis of ILD. They diagnosed a B-pattern if three or more B-lines were present between two ribs in two or more regions. No scoring was used for LUS. Other features such as pleural line irregularity, pleural line thickening, lung sliding, and subpleural irregularities were also studied. They found that B-pattern was the most common finding found in 80% of the patients with an HRCT diagnosis of ILD. Pleural line thickening was found in 56% only in this study. Hasan and Makhlouf studied[20] the B-line score and distance between B-lines in relation to HRCT findings. They found that a ground glassing or alveolar pattern correlated with lesser distance of around 3 mm between B-lines causing a white lung appearance on sonogram, whereas distance of 7 mm or more correlated with a more fibrotic pattern. In our study, the correlation between LUS scores and predominantly fibrotic pattern on HRCT increased with higher LUS scores. In a study by Tardella et al.,[21] 34 patients with CTD were assessed by the 50 scoring site system and compared with HRCT. Fifty LISs were scored and a B-line score of 10 was identified as a cutoff. A significant linear correlation was found between the US score and the HRCT score (P < 0.001; correlation coefficient ρ = 0.875).

Gigante et al.[22] found that LUS score correlated not only with HRCT but functional parameters and progression of the capillaroscopic damage. A statistically significant difference in the number of B-lines was found between patients with and without digital ulcers (42 [3–84] vs. 16 [4–55]). They concluded that LUS could determine the ideal time for HRCT investigation in Systemic Sclerosis (SSc) ILD patients.

The second aim of the current study was to determine the correlation of LUS findings with functional parameters. We found a strong negative correlation of B-lines with FVC (r = −0.412, P = 0.007) and 6MWT distance (r = −0.453, P = 0.003). The correlation of LUS findings with functional parameters such as FVC, Diffusing capacity of lung for Carbon Monoxide (DLCO), and 6MWT is important because many CTD patients are unable to perform lung function tests including 6MWT due to restriction of mobility, poor respiratory effort, pregnancy, critical illness, etc. Hasan and Makhlouf[20] studied the correlation of distance between B-lines with functional parameters and found that the distance between B-lines inversely correlated with FVC (r = −0.452, P < 0.001), TLC (r = −0.276, P = 0.03), DLCO (r = −0.445, P < 0.001), and PaO<Subscript>2</Subscript> (r = −0.241, P < 0.001). Hasan and Makhlouf stated that a decreased distance between B-lines (B3-3 mm distance between B-lines) represents early alveolar wall affection and little pulmonary function impairment, whereas wide distances between B-lines (B7-7 mm distance between B-lines) indicate thickened septa and marked lung function impairment. Other authors like Srivastava et al.,[19] Tardella et al.,[21] Gigante et al.,[22] Hassan et al.,[23] Cömert et al.,[24] and others[25] have stated similar correlations.

The patients included in this study were cases diagnosed to have ILD by HRCT. All were symptomatic also. The idea was to find the correlation and a cutoff LUS score for a particular HRCT pattern. Further studies would be needed to see if the same could be used in the asymptomatic population of patients. HRCT patterns such as ground glassing or alveolar patterns were less likely to be picked up by LUS. In the current study, it was noted that the lower LUS scores of 20 had high sensitivity for the fibrotic pattern with much less specificity. A role of LUS in early disease or as a screening tool is doubtful when the predominant pattern is ground glassing or alveolar infiltrates. Studies by Govind et al.[19] and Hasan and Makhlouf[20] discussed this aspect and stated that the ground glassing in HRCT correlated with decrease in distance between two B-lines and confluence of B-lines giving a white lung appearance in LUS. LUS B-line score alone cannot detect these changes in HRCT. However, if other parameters such as thickness and irregularity of pleural lines and subpleural opacities are considered, the detection rate would be higher. The question whether LUS B-line score could be used as a screening tool in CTD-ILD was also addressed by Barskova et al.[26] in their study of 58 patients with SS who were screened with HRCT and USG. It was found that with HRCT, ILD was detected in 88% of the SSc population and in 41% of the very early SSc population. A significant difference in the number of B-lines was found in patients with and without ILD on HRCT (57 ± 53 vs. 9 ± 9; P < 0.0001), with a concordance rate of 83%. All discordant cases were false positive at LUS, providing a sensitivity and negative predictive value of 100% in both SSc and very early SSc. Thus, they propose utilizing lung ultrasound for screening of ILD in early SS. Therefore, it can be concluded that LUS would detect a fibrotic pattern early, but other patterns of lung involvement need HRCT.

A comparison of the scoring system and correlation of LUS scores with HRCT and functional parameters in various studies is given in [Table 4].{Table 4}

LUS has been recently proposed as a prognostic marker. The presence of higher number of B-lines has been found to correlate with rapidly deteriorating lung function by Gargani and Volpicelli.[27]

The limitation of the current study is the small study sample with a fairly homogeneous group which may not bring forth the lacunae in LUS compared to the gold standard of HRCT. The fact that interobserver variation in LUS assessment was not studied is another pitfall. With regard to LUS, only B-line scoring was analyzed whereas other parameters such as pleural line thickening were not analyzed in this study.

The patients included in this study were cases diagnosed to have ILD by HRCT. All were symptomatic also. The idea was to find the correlation and a cutoff LUS score for a particular HRCT pattern. Further studies would be needed to see if the same could be used in the asymptomatic population of patients. ILD may not be the only cause for dyspnea and cough in a patient with CTD. Various forms of lung involvement from cricoarytenoiditis, asthma, bronchiectasis, bronchiolitis, organizing pneumonia, NSIP or UIP, respiratory muscle dysfunction, and cardiovascular involvement can cause exertional dyspnea. Whether LUS can be used as a point-of-care investigation to identify the interstitial thickening due to ILD and how to do it was one of the aspects which we tried to bring some light into.


There was a significant correlation between ILD with reticular pattern and honeycombing on HRCT and higher LUS B-line scores. LUS B-line scores also correlated significantly with functional parameters such as lower FVC values and lower 6MWT distance. The correlation between LUS B-line scores and lung involvement with predominant ground glassing on HRCT was lower.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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