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Arthritis Res Ther
Arthritis Res Ther
Arthritis Research & Therapy
1478-6354
1478-6362
BioMed Central London

3399
10.1186/s13075-024-03399-2
Review
A versatile role for lung ultrasound in systemic autoimmune rheumatic diseases related pulmonary involvement: a narrative review
Wang Yukai stzxyywyk@126.com

1
Chen Shaoqi 1036587183@qq.com

2
Zheng Shaoyu 1
Zhou Zexuan 1
Zhang Weijin 1
Du Guangzhou 3
Mikish Angelina 1
Ruaro Barbara 4
Bruni Cosimo 5
Hoffmann-Vold Anna-Maria 6
Gargani Luna 7
Matucci-Cerinic Marco 58
Furst Daniel E 5910
1 https://ror.org/04jmrra88 grid.452734.3 0000 0004 6068 0415 Department of Rheumatology and Immunology, Shantou Central Hospital, Shantou, Guangdong China
2 https://ror.org/02bnz8785 grid.412614.4 Department of Ultrasound, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong China
3 https://ror.org/04jmrra88 grid.452734.3 0000 0004 6068 0415 Department of Radiology, Shantou Central Hospital, Shantou, Guangdong China
4 grid.5133.4 0000 0001 1941 4308 Department of Pulmonology, Cattinara Hospital, University of Trieste, Trieste, 34149 Italy
5 https://ror.org/04jr1s763 grid.8404.8 0000 0004 1757 2304 Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
6 https://ror.org/00j9c2840 grid.55325.34 0000 0004 0389 8485 Department of Rheumatology, Oslo University Hospital, Oslo, Norway
7 https://ror.org/03ad39j10 grid.5395.a 0000 0004 1757 3729 Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, 56126 Italy
8 grid.18887.3e 0000000417581884 Unit of Immunology, Rheumatology, Allergy and Rare diseases (UnIRAR), IRCCS San Raffaele Hospital, Milan, Italy
9 https://ror.org/046rm7j60 grid.19006.3e 0000 0001 2167 8097 Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, USA
10 https://ror.org/00cvxb145 grid.34477.33 0000 0001 2298 6657 University of Washington, Seattle, WA USA
18 9 2024
18 9 2024
2024
26 16412 6 2024
5 9 2024
© The Author(s) 2024
2024
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Systemic autoimmune rheumatic diseases (SARDs) related pulmonary disease is highly prevalent, with variable clinical presentation and behavior, and thus is associated with poor outcomes and negatively impacts quality of life. Chest high resolution computed tomography (HRCT) is still considered a fundamental imaging tool in the screening, diagnosis, and follow-up of pulmonary disease in patients with SARDs. However, radiation exposure, economic burden, as well as lack of point-of-care CT equipment limits its application in some clinical situation. Ultrasound has found a place in numerous aspects of the rheumatic diseases, including the vasculature, skin, muscle, joints, kidneys and in screening for malignancies. Likewise it has found increasing use in the lungs. In the past two decades, lung ultrasound has started to be used for pulmonary parenchymal diseases such as pneumonia, pulmonary edema, lung fibrosis, pneumothorax, and pleural lesions, although the lung parenchymal was once considered off-limits to ultrasound. Lung ultrasound B-lines and irregularities of the pleural line are now regarded two important sonographic artefacts related to diffuse parenchymal lung disease and they could reflect the lesion extent and severity. However, its role in the management of SARDs related pulmonary involvement has not been fully investigated. This review article will focus on the potential applications of lung ultrasound in different pulmonary scenarios related with SARDs, such as interstitial lung disease, diffuse alveolar hemorrhage, diaphragmatic involvement, and pulmonary infection, in order to explore its value in clinical daily practice.

Keywords

Lung ultrasound
High resolution computed tomography
Systemic autoimmune rheumatic diseases
Interstitial lung disease
Diffuse alveolar hemorrhage
Diaphragmatic involvement
Pulmonary infection
National Natural Science Foundation of ChinaNo. 82271853 ZHONGNANSHAN MEDICAL FOUNDATION OF GUANGDONG RPOVINCEZNSXS-20240011 issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2024
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pmcIntroduction

Systemic autoimmune rheumatic diseases (SARDs) are a group of multi-system, inflammatory and autoimmune disorders arising from the loss of normal immune tolerance plus aberrant immune activation. Multiple pro-inflammatory cytokines that originate from innate and adaptive immune cells and auto-antibodies secreted by B cells are essential for the pathogenesis of SARDs [1–3]. The lung is one of the most vulnerable target organs attacked by abnormal immunity, and pulmonary involvement in SARDs is strongly associated with mortality and negatively impacts quality of life. However, due to the fact that most respiratory symptoms associated with SARDs are often insidious in onset and develop gradually, it is difficult to identify them early and intervene promptly [4]. Furthermore, joint and muscle inflammation, cardiovascular complication, and gastrointestinal symptom, can concomitantly affect the patients and mask the diagnosis of pulmonary disease.

Undoubtedly, high resolution computed tomography (HRCT) is presently the gold standard imaging modality for the identification of most pulmonary diseases associated with SARDs. It plays a critical role in the comprehensive assessment and management of SARDs-related lung disease. However, radiation exposure, economic burden, as well as lack of point-of-care CT equipment limits its application in some clinical situations.

Ultrasound has found a place in numerous aspects of the rheumatic diseases, including the vasculature, skin, muscle, joints, kidneys and in screening for malignancies. Likewise it has found increasing use in the lungs [5]. Generally, the aerated lung parenchyma is considered to be the forbidden zone for ultrasound, because the air is not an optimal medium for ultrasound wave propagation. However, in pathological conditions, when the ratio of air to non-air content in lung decreases because alveolar or interstitium space is occupied by fluid or fibrotic tissue, the resulting acoustic mismatch or the formation of an acoustic trap makes lung ultrasound feasible [6]. Although the biophysics and exact genesis of the sonographic signs have not been fully elucidated, lung ultrasound (LUS) B-lines and irregularity of the pleural line are recognized as important patterns associated with diffuse parenchymal lung disease (DPLD) [7]. B-lines, also called comet tail sign, were originally defined as discrete laser-like vertical hyperechoic reverberation artefacts which arise from the pleural line, extend to the bottom of the screen without fading and move synchronously with lung sliding [8]. Multiple B-lines patterns can be detected, such as single B-lines, numerous discrete B-lines, confluent B-lines, and sonographic white lung syndrome (Panels A-D in Fig. 1), which corresponds to different lung parenchymal alterations [9]. The identification of sonographic pleural lines is crucial during LUS performance, as they are thin, smooth, hyperechogenic linear structures that move while breathing. Below the pleural line, another normal ultrasound finding of the lung is the sonographic A-line. A-lines are repetitive reverberation horizontal artefacts, with equal distances between them and the pleural line. Compared to the normal sonographic pleural line, the irregularity of the pleural line manifests with a coarse, blurred, fragmented or thickened appearance (Panels A-D in Fig. 1). When the subpleural region is involved, subpleural nodules and consolidations can be observed [10–12].

Over the past two decades, with the accumulation of clinical experience and technology innovation, LUS has been increasingly used as a complementary modality to traditional chest radiography to diagnose and monitor DPLD. Compared to chest X-rays or computed tomography (CT) scans, LUS not only has the advantages of portability, non-radiation, user-friendliness, and real-time imaging, but also exhibits a good sensitivity and negative predicted value, particularly when detecting lesions near the pleura. Although LUS has become a useful, sophisticated, and routine examination tool in intensive care unit (ICU), emergency department as well as neonatal unit [13–15], its role in the SARDs related pulmonary involvement has not been fully investigated [16]. This review article will focus on the potential applications of LUS in different pulmonary scenarios related to SARDs, in order to explore its value in clinical daily practice.

SARDs related interstitial lung disease

SARDs related interstitial lung disease (SARDs-ILD) is a common pulmonary feature, with protean clinical manifestations, behaviors, and outcomes [17]. Nonspecific interstitial pneumonia (NSIP), characterized by ground-glass opacity (GGO), reticular abnormality, and traction bronchiectasis with basilar and peripheral predominance is the most common pattern in SARDs-ILD, followed by usual interstitial pneumonia (UIP), organizing pneumonia (OP), and lymphocytic interstitial pneumonia (LIP) [18, 19]. A proportion of patients, particularly in anti-melanoma differentiated antigen 5 (MDA-5) antibody positive dermatomyositis, anti-synthetase syndrome, as well as diffuse scleroderma and rheumatoid arthritis with UIP-like, can develop a rapidly progressive phenotype most commonly with an acute interstitial pneumonia (AIP) pattern, which can result in significant mortality. However, how to identify early, follow up regularly, and monitor the development and progression of SARDs-ILD still remains a major challenge in the rheumatology community.

Since the first report regarding LUS in systemic sclerosis related interstitial lung disease (SSc-ILD) published by Gargani L. et al., numerous studies have investigated its application in various rheumatic diseases related ILDs [20]. According to a meta-analysis that included 349 patients with connective tissue diseases, the diagnostic sensitivity and specificity of LUS were 0.915 (95%CI 0.845 ~ 0.96) and 0.813 (95%CI 0.746 ~ 0.869), respectively. A significant correlation was found between lung US B-line scores and HRCT Warrick scores (correlation coefficient: 0.783; P < 0.001) [21]. A recent prospective study involving 180 patients with SARDS showed the sensitivity and specificity of lung ultrasound as compared to HRCT in detecting pulmonary interstitial involvement were 99.3% and 96.4%, respectively; positive predictive value (PPV) 0.7, negative predictive value (NPV) 3.611. Excellent inter-observer agreement was found between the 2 investigators (weighted κ value between 0.846 and 0.969, and overall agreement between 92% and 97%) [22]. As per the data mentioned, LUS has the potential to be a valuable tool for managing SARDs-ILD.

LUS in rheumatoid arthritis related ILD

Rheumatoid arthritis related ILD (RA-ILD) is among the most frequent SARDs-ILDs, being the major extra-articular manifestation in this disease [23]. The prevalence of RA-ILD is reported as highly variable, owing to different methodologies, screening strategy, cohorts investigated and ILD definitions adopted [24]. The UIP pattern is more often encountered in RA-ILD than other SARDs and is associated with a poorer prognosis [25, 26]. A recent population-based cohort study revealed that even when asymptomatic and radiologically limited in extent, RA-ILD is associated with shorter survival [27]. Hence, there is no doubt that the detection of early interstitial lung lesions is of great clinical significance. Several predictive models have been constructed to identify patients at high risk of subclinical RA-ILD. These models include smoking, gender, age, disease duration, anti-cycling citrullinated peptide (CCP) antibody, rheumatoid factor, serum biomarkers, as well as the MUC5B genetic variant as predictive factors [28–31]. However, discrepancies in study results shows that these models need to be further studied and validated. Given that most RA-ILD progresses relatively slowly and is usually asymptomatic or oligosymptomatic in the early and intermediate stages. In addition, RA is more common than scleroderma and inflammatory myositis. Using HRCT to screen and monitor RA-ILD will not be available in remote and rural areas, and will place an increased burden on the radiology department, and is relatively expensive. Additionally, the low sensitivity of X-ray and pulmonary function tests (PFTs) limits their screening capacity. Therefore, LUS utilization can assist in bridging the gap in screening for early RA-ILD. Studies from different centers consistently demonstrated that LUS, and even the use of portable ultrasound devices, has good sensitivity and negative predictive value for detecting ILD in RA when compared to HRCT [32–35]. Despite most of the studies were conducted in a single center, retrospective controlled, and with small sample size. Recently, we proposed an algorithm combining lung ultrasound B-lines and serum Krebs von den Lungen-6 (KL-6), two non-invasive and radiation-free biomarkers, to screen ILD in patients with early RA [36]. If ILD is suspected in the first step (B-line number > 10 and/or KL-6 ≥ 500 U/mL), the patient is recommended to undergo chest HRCT and PFTs examination, to confirm the radiological changes and quantify the physiologic impairment. If there is no radiological evidence of ILD, LUS and KL-6 test should be performed periodically, for close sonographic monitoring of ILD development. For individuals without the evidence of pulmonary involvement in the first step (B-line number ≤ 10 and/or KL-6 < 500 U/mL), LUS and KL-6 testing might be periodically repeated, within time-frames that depend on the presence of risk factors. However, the screening and follow-up strategy requires additional testing and validation among prospective, multicenter, and large-scale studies.

In a nutshell, the role of LUS in RA-ILD should be highlighted in early screening and dynamic monitoring.

LUS in anti-MDA-5 antibody positive dermatomyositis related ILD

Anti-MDA-5 antibody positive dermatomyositis (DM) is a special clinical phenotype that very frequently presents with mild muscular involvement and severe ILD manifestation [37]. Anti-MDA-5 positive ILD is one of the most difficult problems in the rheumatic community as a significant proportion of these patients progress rapidly to severe outcomes despite receiving aggressive and supportive treatment. High mortality of this entity is associated with an elusive pathophysiology, uncontrolled cytokine storm and superimposed viral and other pathogen infections [38]. NSIP, OP and AIP are the three predominant radiological and histopathologic patterns [39]. However, data regarding lung ultrasound in idiopathic inflammatory myositis related ILD (IIM-ILD) are scarce. One mono-center retrospective study including 39 patients with IIM-ILD showed that the lung ultrasound B-lines number positively correlated with the HRCT Warrick score and serum KL-6 concentration, and correlated inversely to PFTs [40]. In a case report, bedside ultrasound and KL-6 were used to evaluate the lung lesion, and their interpretation helped make the therapeutic decision in a DM patient with rapidly progressive ILD (RP-ILD) [41]. These data indicated that B-lines combined with KL-6 could be helpful in the assessment of IIM-ILD severity and in the close monitoring of ILD development.

Although the underlying mechanism is unknown, spontaneous pneumomediastinum or pneumothorax can occur in anti-MDA5 positive DM patients with RP-ILD, and this was demonstrated to be linked with poorer prognosis and higher mortality [42, 43]. In this clinical circumstance, bedside lung ultrasound is an alternative tool that can sensitively detect pneumothorax. The absence of lung sliding, as well as the identification of the lung point sign, are strongly indicative of the presence of pneumothorax, for which a chest tube would then be considered [44]. However, the concomitant presence of subcutaneous emphysema can affect the accuracy of the ultrasound reading. At this point, bedside X-ray or chest CT scan is indispensable [45, 46].

In addition, diaphragmatic myositis in IIM, a very rare complication, was reported to contribute to respiratory failure [47]. Recently, Grignaschi et al. reported the case of a patient with MDA5 + DM who presented with progressive dyspnea due to concomitant ILD and diaphragmatic myositis. Lung and diaphragm ultrasound revealed remarkable B-lines and diaphragm dysmotility. After therapy with intravenous immunoglobulins and mycophenolate mofetil, the patient’s condition gradually improved and subsequent ultrasound examination showed marked improvement of the diaphragmatic dysfunction and a reduction of the B-lines score [48].

LUS in systemic sclerosis related ILD

SSc-ILD is a major pulmonary manifestation in this disease which deserves attention as it represents a leading cause of death [49]. HRCT is the fundamental imaging tool for identifying radiological pattern, the type of involvement, pulmonary artery enlargement as well as esophageal dilatation in SSc patients. Notwithstanding, emerging evidence indicates that lung ultrasound can play a supporting role in the whole journey of SSc-ILD [50]. The published promising data demonstrated that LUS B-lines and irregularity of the pleural line significantly correlate with HRCT score, PFTs, serological biomarkers and clinical parameters in SSc-ILD [20, 22, 51–53]. As per a recent meta-analysis that included nine studies with a total of 888 participants, LUS had high diagnostic accuracy, with good sensitivity (94%) and moderate specificity (64%) [54]. Additionally, one retrospective and mono-center study enrolled 77 patients with SSc found that LUS B-lines correlate with radiomic quantitative indexes, including mean lung attenuation (r = 0.568, P < 0.001), skewness (r=-0.368, P = 0.004), and kurtosis (r=-0.283, P = 0.028). Sub-analysis further confirmed the similar results in anterior and posterior chest separately [55]. The prognostic value of B-lines for SSc was investigated in 396 consecutive patients. The posterior B-lines ≥ 5 was found to associate with new development or worsening ILD [hazard ratio (HR) 3.38, 95% CI 1.137–9.994; P = 0.028]. The prognostic value of B-lines was further confirmed in the subgroup of patients with known ILD at baseline (HR 1.010; 95% CI 1.003–1.018; P = 0.008) [56].

In light of the fact that SSc-ILD screening is mandatory, chest HRCT scans combined with PFTs are the main modalities for this purpose. Nevertheless, LUS can serve as a complementary tool in initial clinical phase, providing baseline sonographic data as a guide for later flexible follow-up. For example, LUS can be performed more intensively depending on clinical requirements for patients at high risk of developing progressive pulmonary fibrosis (PPF). Recently, a screening strategy including LUS, HRCT, and PFTs was recommended for every patient with SSc at baseline. Routine screening for ILD through LUS andd PFTs should be done every 3 to 6 months during the first two years in cases of non-radiographic ILD. If the screening test results show signs of deterioration, chest HRCT scan is required [50].

LUS in SARDs related diffuse alveolar hemorrhage

Diffuse alveolar hemorrhage (DAH) is a rare but potentially life-threatening complication of some SARDs, particularly systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody associated vasculitis [57]. The alveolar capillaries are attacked by various inflammatory cytokines and abnormal immune cells, leading to increased permeability and capillaritis, and ultimately cause red blood cells accumulation within the alveolar space [58]. The triad of DAH encompasses acute dyspnea, hemoptysis and progressive hypoxemia. Chest CT reveals emerging non-specific patchy or diffuse, bilateral GGO, and alveolar consolidation with air bronchogram [59, 60]. DAH is an emergency condition that requires rapid identification and timely intervention to avoid catastrophic consequences and death [61]. Point-of-care lung ultrasound is a useful imaging modality that can be used to rapidly and sensitively detect patients with suspected DAH when related clinical features are presented. The sonographic pattern identified in DAH includes multiple confluent or discrete B-lines, with or without pleural irregularity depending on prior pleural involvement [62]. After aggressive treatment, the B-lines gradually dissolve and finally disappear. Therefore, in this context, lung ultrasound could become an applicable, rapid alternative to detect and closely follow-up DAH, as well as to identify the response to treatment. The interpretation of lung ultrasound pattern can facilitate the clinical decision making process. Panels A–H in Fig. 2 demonstrate the clinical application of lung ultrasound to identify, monitor a SLE patient with DAH.

LUS in SARDs related shrinking lung syndrome

Shrinking lung syndrome (SLS) is an uncommon complication of SARDs (mainly associated with SLE) in which the diaphragmatic muscle is involved, resulting in reduced lung volume and restrictive ventilation impairment on PFTs [63]. The patient will be highly suspected of SLS when progressive exertional dyspnea, pleuritic chest pain, and elevation of the diaphragm on chest X-rays as well as restrictive pattern on PFTs are present, but there is no obvious evidence of ILD, pulmonary vasculopathy or pleural disease is detected [64]. Although the precise mechanism of SLS is unknown, diaphragm dysfunction is suggested to play a crucial role in its pathogenesis. In this clinical scenario, diaphragm ultrasound could directly evaluate the diaphragm both structurally and functionally by measuring diaphragmatic thickness and mobility [46, 65]. Using this technique, a recent study found that SLE patients had reduced diaphragmatic muscle thickness compared to those with primary Sjögren’s syndrome (pSS). Diaphragmatic function testing by evaluating maximum expiratory pressure (MEP) and maximum inspiratory pressure (MIP), also demonstrated that SLE patients had significant lower MEP and MIP compared to pSS (80% vs. 92% and 76% vs. 120%, respectively; p < 0.05). These findings indicated that diaphragmatic muscle abnormality is common in SLE patients. To explain whether this could be the underlying reason for the increased risk of lower respiratory tract infections and SLS in SLE patients, prospective studies and larger sample size are needed [66]. One mono-center study including 11 pediatric SLE patients complicated with SLS used M-mode ultrasound and showed diaphragmatic hypomotility in 100% by obtaining the range, duration and velocity of the diaphragmatic contraction [67].

LUS in SARDs related pulmonary infection

Pulmonary infection is the most common complication of SARDs patients who receive therapy with glucocorticoids, immunosuppressants, biologic agents or Janus Kinase inhibitors, and remains a leading cause of respiratory failure and intensive care unit admission [68]. In addition to bacterial pneumonia, immunocompromised patients are prone to infection by opportunistic infections, including viral, pneumocystis, fungal, non-tuberculosis mycobacteria and other agents. Although there are no specific sonographic findings as a diagnostic hallmark of pneumonia, lung ultrasound could provide information comparable to standard radiographs. Systemic literature reviews and meta-analyses have demonstrated that lung ultrasound had higher sensitivity, specificity, and diagnostic accuracy than chest X-ray, using CT as the referent [69]. The presence of sonographic consolidation (subpleural echo-poor region or one with tissue-like echotexture), fluid or air bronchograms, focal multiple B lines, and pleural effusion would suggest pneumonia. To accurately interpret ultrasonographic patterns associated with pneumonia, a comprehensive judgment should be made by integrating clinical, serological and, when available, radiological information. After administration of antibiotic, the therapeutic efficacy can be ascertained by assessing lung reaeration and pleural fluid absorption through tracking changes in sonographic findings. However, there are no relevant recommendations or guidelines on the use of lung ultrasound to follow-up pneumonia in patients with SARDs. Panels A–H in Fig. 3 demonstrate a patient with pneumocystis jiovecii pneumonia to show HRCT findings plus use of LUS to follow a patient to resolution of her pneumonia.

LUS in SARDs patients with COVID-19 pneumonia

The vast majority of SARDs individuals are vulnerable to the SARS-CoV-2 infection, whether the illness is quiescent or active [70]. Pulmonary parenchymal involvement characterized by diffuse interstitial alterations is a feature of COVID-19 pneumonia, and contributes to a worse prognosis and significant mortality [71]. Separated and coalescent B-lines with patchy distribution, peripheral consolidation, as well as irregularities of the pleural line and rare pleural effusion are the main ultrasonographic manifestations of COVID-19 pneumonia [72, 73]. The value of lung ultrasound in the management of COVID-19 pneumonia was comprehensively reviewed previously, focused on its applications for triaging, monitoring and prognostic management of these patients [74]. Compared with classical radiological modalities, lung ultrasound could play a more flexible role in different clinical settings, from home monitoring to emergency department and ICU bedside assessment. The implementation of lung ultrasound might help minimize exposure to ionizing radiation, reduce unnecessary transport of infected patients in the hospital setting, decrease the strain on imaging modalities such as the radiology department while enabling rapid clinical decision-making [74–77].

Lung fibrosis is one of the severe complications after SARS-CoV-2 infection, also called post-COVID-19 pulmonary fibrosis (PCPF) [78]. The diagnosis of PCPF requires a combination of clinical, serological, radiological and pathological (if available) information [79]. The long-term outcome and clinical behaviour of PCPF remains unknown, and how to manage it is still uncertain. Nonetheless, close follow-up of high-risk patients, such as older age individuals, those who are immunosuppressed, those with higher acute-phase reactants and pro-inflammatory cytokine levels and with known autoantibody positivities (e.g. anti-CCP, anti-MDA-5, Ro52, Scl-70) is essential [80]. Research into this LUS use is needed because, in this context, lung ultrasound could be an excellent tool for the screening and monitoring of PCPF.

The diverse role of LUS in SARDs patients with various clinical pulmonary complications is outlined in Fig. 4.

Limitations

Although LUS is becoming increasingly popular as a new imaging modality in the field of pulmonary disease, it must be noted that there are some limitations that prevent its further clinical application. First, the standardization and validation of LUS examination in patients with SARDs have not yet been fully established. Because of acquisition of ultrasound image is mostly dependent on detecting and evaluating artefacts, which are highly dependent on imaging frequency and settings. Therefore, in order to improve the diagnostic reproducibility and accuracy, standardization of imaging protocols is urgent. Second, the calculation of the number of B-lines and the description of pleural line morphology are mainly dependent on the operator, making the results subjective and prone to variation. Third, discriminating various underlying lung pathologies by analyzing and comparing different B-lines patterns is still a challenge. In this respect, artificial intelligence and machine learning algorithms can help to interpret LUS data more accurately, thereby avoiding subjective errors and making the more correct diagnosis [81]. In addition, combining clinical, serological, and radiographic information can enhance understanding of LUS findings.

Regarding the clinical application of LUS in patients with SARDs, there is little data on other pulmonary complications except for in ILD. Moreover, most studies that were published focused on LUS as a screening, diagnostic, and monitoring tool for ILD. Therefore, it is necessary to conduct more clinical studies to establish its validity in various pulmonary diseases. Additionally, due to its high sensitivity and moderate specificity, LUS should be utilized as a promising tool for assessing therapeutic response to anti-fibrotic agents in ILD. In order to confirm this effect, a large-scale, prospective, multicenter clinical trial is needed.

Conclusion

The harmful outcomes of lung involvement in patients with SARDs has attracted increasing attention and is great challenge for most rheumatologists. Accumulated evidence and promising data in the past two decades indicate that lung ultrasound may be a useful tool to detect pulmonary abnormalities. Incorporating sonographic information into clinical and radiological data may help rheumatologists to achieve more comprehensive management of these diseases, particularly in the screening and follow-up of SARDs-related pulmonary disease. However, high-quality studies and rigorous data are still scarce in this area. Hence, its role in screening and monitoring of pulmonary alteration need to be further investigated and validated. Much work remains to be done to reach a consensus on standard practice of lung ultrasound in different clinical scenarios. In addition, lung ultrasound operation training, as well as sonographic patterns identification and interpretation, must be carried out urgently in the rheumatology community. We hope that in the near future, lung ultrasound will become a powerful stethoscope for rheumatologists in daily clinical practice.

Fig. 1 Typical lung ultrasound patterns. Normal pleural line (yellow arrowheads) and A-lines (red arrows) (Panel A); two separate B-lines (red arrows) and fragmented pleural line (yellow arrowheads) (Panel B); confluent B-lines (red asterisks) and blurred and irregular pleural line (yellow arrowheads) (Panel C); sonographic white lung (delineated with red dotted line) (Panel D)

Fig. 2 A hospitalized patient with active SLE suddenly presented with hemoptysis, hypoxemia and progressive hemoglobin decline. Timely bedside lung ultrasound revealed diffuse sonographic “white lung” (confluent B-lines) (Panel A), subsequently confirmed by chest HRCT scan (Panel B and C). The patient was treated with intravenous methylprednisolone (250 mg per day for 3 days, and tapered 80 mg per day for 3 days, then 40 mg per day) combined with intravenous belimumab (10 mg/kg) injection. Intensive lung ultrasound monitoring over a period of 14 days indicated B-lines score diminished sequentially (Panel D-F), corresponding improvement in chest HRCT imaging (Panel G and H) and the patient’s condition

Fig. 3 A refractory and recurrent young lupus patient complicated with severe enteritis, thrombocytopenia, and nephropathy admitted to our department. After received high dose glucocorticoid (2 mg/kg) and cyclophosphamide (total dose 1 gram) therapy, she presented fever, dry cough, and mild exertional dyspnea. Subsequent chest HRCT examination revealed new diffuse ground-glass opacity and reticular abnormality (Panel A and B). Simultaneous bedside lung ultrasound showed multiple B-lines, blurred pleural line, and no pleural effusion (Panel C). Pneumocystis jirovecii pneumonia (PJP) was confirmed by bronchoalveolar lavage fluid smear. Trimethoprim-sulfamethoxazole (2 tablets, three time per day) was added while glucocorticoid was reduced (1 mg/kg) and cyclophosphamide was discontinued. In order to avoid radiological exposure, lung ultrasound was used to closely follow up the PJP infection. Ultrasound was performed every two weeks for the first two months, and subsequently performed monthly for follow-up. B-lines elimination and normal pleural line indicated that PJP infection was controlled (Panel D-F), further confirmed by chest HRCT findings (Panel G and H) and improved clinical symptom

Fig. 4 The diverse role of LUS in SARDs patients with various clinical pulmonary complications. DAH, Diffuse alveolar hemorrhage; ILD, Interstitial lung disease; LUS, Lung ultrasound; RP-ILD, Rapidly progressive interstitial lung disease

Acknowledgements

Not applicable.

Author contributions

YKW, SQC, BR, CB, AMHV, LG, MMC and DEF participated in the literature review, writing and reviewing of the manuscript. SYZ, ZXZ, WJZ, GZD and AM participated in the clinical data collection and preparation of Figs. 1, 2 and 3. All authors reviewed the manuscript.

Funding

This work is supported by grants from the National Natural Science Foundation of China (No. 82271853) and the ZHONGNANSHAN MEDICAL FOUNDATION OF GUANGDONG RPOVINCE (ZNSXS-20240011).

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Abbreviations

AIP Acute interstitial pneumonia

CCP Cycling citrullinated peptide

CT Computed tomography

DAH Diffuse alveolar hemorrhage

DM Dermatomyositis

DPLD Diffuse parenchymal lung disease

GGO Ground-glass opacity

HRCT High resolution computed tomography

ICU Intensive care units

IIM Idiopathic inflammatory myositis

ILD Interstitial lung disease

KL-6 Krebs von den Lungen-6

LIP Lymphocytic interstitial pneumonia

LUS Lung ultrasound

MDA-5 Melanoma differentiated pneumonia

MEP Maximum expiratory pressure

MIP Maximum inspiratory pressure

NPV Negative predictive value

NSIP Nonspecific interstitial pneumonia

OP Organizing pneumonia

PCPF Post-COVID-19 pulmonary fibrosis

PFTs Pulmonary function tests

PPF Progressive pulmonary fibrosis

PPV Positive predictive value

pSS primary Sjögren’s syndrome

RA-ILD Rheumatoid arthritis related ILD

RP-ILD Rapidly progressive ILD

SARDs Systemic autoimmune rheumatic diseases

SLE Systemic lupus erythematosus

SLS Shrinking lung syndrome

SSc-ILD Systemic sclerosis related interstitial lung disease

UIP Usual interstitial pneumonia

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Yukai Wang and Shaoqi Chen contributed equally to this work.
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References

1. Reynolds JA Briggs TA Rice GI Darmalinggam S Bondet V Bruce E Type I interferon in patients with systemic autoimmune rheumatic disease is associated with haematological abnormalities and specific autoantibody profiles Arthritis Res Ther 2019 21 1 147 10.1186/s13075-019-1929-4 31200750
Reynolds JA, Briggs TA, Rice GI, Darmalinggam S, Bondet V, Bruce E, et al. Type I interferon in patients with systemic autoimmune rheumatic disease is associated with haematological abnormalities and specific autoantibody profiles. Arthritis Res Ther. 2019;21(1):147.31200750
2. Hudson M Bernatsky S Colmegna I Lora M Pastinen T Klein OK Novel insights into systemic autoimmune rheumatic diseases using shared molecular signatures and an integrative analysis Epigenetics-Us 2017 12 6 433 40 10.1080/15592294.2017.1303581
Hudson M, Bernatsky S, Colmegna I, Lora M, Pastinen T, Klein OK, et al. Novel insights into systemic autoimmune rheumatic diseases using shared molecular signatures and an integrative analysis. Epigenetics-Us. 2017;12(6):433–40.
3. Ribeiro F Romao VC Rosa S Jesus K Agua-Doce A Barreira SC Different antibody-associated autoimmune diseases have distinct patterns of T follicular cell dysregulation Sci Rep-Uk 2022 12 1 17638 10.1038/s41598-022-21576-8
Ribeiro F, Romao VC, Rosa S, Jesus K, Agua-Doce A, Barreira SC, et al. Different antibody-associated autoimmune diseases have distinct patterns of T follicular cell dysregulation. Sci Rep-Uk. 2022;12(1):17638.
4. Panagopoulos P Goules A Hoffmann-Vold AM Matteson EL Tzioufas A Natural history and screening of interstitial lung disease in systemic autoimmune rheumatic disorders Ther Adv Musculoskel 2021 13 1759720X211037519
Panagopoulos P, Goules A, Hoffmann-Vold AM, Matteson EL, Tzioufas A. Natural history and screening of interstitial lung disease in systemic autoimmune rheumatic disorders. Ther Adv Musculoskel. 2021;13:1759720X211037519.
5. Hughes M Bruni C Cuomo G Delle SA Gargani L Gutierrez M The role of ultrasound in systemic sclerosis: on the cutting edge to foster clinical and research advancement J Scleroderma Relat 2021 6 2 123 32 10.1177/2397198320970394
Hughes M, Bruni C, Cuomo G, Delle SA, Gargani L, Gutierrez M, et al. The role of ultrasound in systemic sclerosis: on the cutting edge to foster clinical and research advancement. J Scleroderma Relat. 2021;6(2):123–32.
6. Demi M Prediletto R Soldati G Demi L Physical mechanisms providing clinical information from Ultrasound Lung images: hypotheses and early confirmations Ieee T Ultrason Ferr 2020 67 3 612 23 10.1109/TUFFC.2019.2949597
Demi M, Prediletto R, Soldati G, Demi L. Physical mechanisms providing clinical information from Ultrasound Lung images: hypotheses and early confirmations. Ieee T Ultrason Ferr. 2020;67(3):612–23.
7. Wang Y Gargani L Barskova T Furst DE Cerinic MM Usefulness of lung ultrasound B-lines in connective tissue disease-associated interstitial lung disease: a literature review Arthritis Res Ther 2017 19 1 206 10.1186/s13075-017-1409-7 28923086
Wang Y, Gargani L, Barskova T, Furst DE, Cerinic MM. Usefulness of lung ultrasound B-lines in connective tissue disease-associated interstitial lung disease: a literature review. Arthritis Res Ther. 2017;19(1):206.28923086
8. Volpicelli G Elbarbary M Blaivas M Lichtenstein DA Mathis G Kirkpatrick AW International evidence-based recommendations for point-of-care lung ultrasound Intens Care Med 2012 38 4 577 91 10.1007/s00134-012-2513-4
Volpicelli G, Elbarbary M, Blaivas M, Lichtenstein DA, Mathis G, Kirkpatrick AW, et al. International evidence-based recommendations for point-of-care lung ultrasound. Intens Care Med. 2012;38(4):577–91.
9. Buda N Piskunowicz M Porzezinska M Kosiak W Zdrojewski Z Lung Ultrasonography in the evaluation of interstitial lung disease in systemic connective tissue diseases: Criteria and Severity of Pulmonary Fibrosis - Analysis of 52 patients Ultraschall Med 2016 37 4 379 85 26713499
Buda N, Piskunowicz M, Porzezinska M, Kosiak W, Zdrojewski Z. Lung Ultrasonography in the evaluation of interstitial lung disease in systemic connective tissue diseases: Criteria and Severity of Pulmonary Fibrosis - Analysis of 52 patients. Ultraschall Med. 2016;37(4):379–85.26713499
10. Pinal-Fernandez I Pallisa-Nunez E Selva-O’Callaghan A Castella-Fierro E Simeon-Aznar CP Fonollosa-Pla V Pleural irregularity, a new ultrasound sign for the study of interstitial lung disease in systemic sclerosis and antisynthetase syndrome Clin Exp Rheumatol 2015 33 4 Suppl 91 S136 41 26315813
Pinal-Fernandez I, Pallisa-Nunez E, Selva-O’Callaghan A, Castella-Fierro E, Simeon-Aznar CP, Fonollosa-Pla V, et al. Pleural irregularity, a new ultrasound sign for the study of interstitial lung disease in systemic sclerosis and antisynthetase syndrome. Clin Exp Rheumatol. 2015;33(4 Suppl 91):S136–41.26315813
11. Moazedi-Fuerst FC Kielhauser S Brickmann K Tripolt N Meilinger M Lufti A Sonographic assessment of interstitial lung disease in patients with rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosus Clin Exp Rheumatol 2015 33 4 Suppl 91 S87 91
Moazedi-Fuerst FC, Kielhauser S, Brickmann K, Tripolt N, Meilinger M, Lufti A, et al. Sonographic assessment of interstitial lung disease in patients with rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosus. Clin Exp Rheumatol. 2015;33(4 Suppl 91):S87–91.
12. Sperandeo M De Cata A Molinaro F Trovato FM Catalano D Simeone A Ultrasound signs of pulmonary fibrosis in systemic sclerosis as timely indicators for chest computed tomography Scand J Rheumatol 2015 44 5 389 98 10.3109/03009742.2015.1011228 26099251
Sperandeo M, De Cata A, Molinaro F, Trovato FM, Catalano D, Simeone A, et al. Ultrasound signs of pulmonary fibrosis in systemic sclerosis as timely indicators for chest computed tomography. Scand J Rheumatol. 2015;44(5):389–98.26099251
13. Smit MR Hagens LA Heijnen N Pisani L Cherpanath T Dongelmans DA Lung Ultrasound Prediction Model for Acute Respiratory Distress Syndrome: a Multicenter prospective observational study Am J Resp Crit Care 2023 207 12 1591 601 10.1164/rccm.202210-1882OC
Smit MR, Hagens LA, Heijnen N, Pisani L, Cherpanath T, Dongelmans DA, et al. Lung Ultrasound Prediction Model for Acute Respiratory Distress Syndrome: a Multicenter prospective observational study. Am J Resp Crit Care. 2023;207(12):1591–601.
14. Biasucci DG Loi B Centorrino R Raschetti R Piastra M Pisapia L Ultrasound-assessed lung aeration correlates with respiratory system compliance in adults and neonates with acute hypoxemic restrictive respiratory failure: an observational prospective study Resp Res 2022 23 1 360 10.1186/s12931-022-02294-1
Biasucci DG, Loi B, Centorrino R, Raschetti R, Piastra M, Pisapia L, et al. Ultrasound-assessed lung aeration correlates with respiratory system compliance in adults and neonates with acute hypoxemic restrictive respiratory failure: an observational prospective study. Resp Res. 2022;23(1):360.
15. Bhalla D Naranje P Jana M Bhalla AS Pediatric lung ultrasonography: current perspectives Pediatr Radiol 2022 52 10 2038 50 10.1007/s00247-022-05412-9 35716179
Bhalla D, Naranje P, Jana M, Bhalla AS. Pediatric lung ultrasonography: current perspectives. Pediatr Radiol. 2022;52(10):2038–50.35716179
16. Buda N, Wojteczek A, Masiak A, Piskunowicz M, Batko W, Zdrojewski Z. Lung Ultrasound in the screening of pulmonary interstitial involvement secondary to systemic connective tissue disease: a prospective pilot study involving 180 patients. J Clin Med. 2021; 10(18).
17. Shao T Shi X Yang S Zhang W Li X Shu J Interstitial lung disease in connective tissue disease: a common lesion with heterogeneous mechanisms and treatment considerations Front Immunol 2021 12 684699 10.3389/fimmu.2021.684699 34163483
Shao T, Shi X, Yang S, Zhang W, Li X, Shu J, et al. Interstitial lung disease in connective tissue disease: a common lesion with heterogeneous mechanisms and treatment considerations. Front Immunol. 2021;12:684699.34163483
18. Castelino FV Varga J Interstitial lung disease in connective tissue diseases: evolving concepts of pathogenesis and management Arthritis Res Ther 2010 12 4 213 10.1186/ar3097 20735863
Castelino FV, Varga J. Interstitial lung disease in connective tissue diseases: evolving concepts of pathogenesis and management. Arthritis Res Ther. 2010;12(4):213.20735863
19. Ruaro B, Baratella E, Confalonieri P, Confalonieri M, Vassallo FG, Wade B et al. High-resolution computed Tomography and Lung Ultrasound in patients with systemic sclerosis: which one to choose? Diagnostics. 2021; 11(12).
20. Gargani L Doveri M D’Errico L Frassi F Bazzichi ML Delle SA Ultrasound lung comets in systemic sclerosis: a chest sonography hallmark of pulmonary interstitial fibrosis Rheumatology 2009 48 11 1382 7 10.1093/rheumatology/kep263 19717549
Gargani L, Doveri M, D’Errico L, Frassi F, Bazzichi ML, Delle SA, et al. Ultrasound lung comets in systemic sclerosis: a chest sonography hallmark of pulmonary interstitial fibrosis. Rheumatology. 2009;48(11):1382–7.19717549
21. Song G Bae SC Lee YH Diagnostic accuracy of lung ultrasound for interstitial lung disease in patients with connective tissue diseases: a meta-analysis Clin Exp Rheumatol 2016 34 1 11 6 26812366
Song G, Bae SC, Lee YH. Diagnostic accuracy of lung ultrasound for interstitial lung disease in patients with connective tissue diseases: a meta-analysis. Clin Exp Rheumatol. 2016;34(1):11–6.26812366
22. Tardella M Gutierrez M Salaffi F Carotti M Ariani A Bertolazzi C Ultrasound in the assessment of pulmonary fibrosis in connective tissue disorders: correlation with high-resolution computed tomography J Rheumatol 2012 39 8 1641 7 10.3899/jrheum.120104 22753655
Tardella M, Gutierrez M, Salaffi F, Carotti M, Ariani A, Bertolazzi C, et al. Ultrasound in the assessment of pulmonary fibrosis in connective tissue disorders: correlation with high-resolution computed tomography. J Rheumatol. 2012;39(8):1641–7.22753655
23. Laria A Lurati AM Zizzo G Zaccara E Mazzocchi D Re KA Interstitial lung disease in rheumatoid arthritis: a practical review Front Med-Lausanne 2022 9 837133 10.3389/fmed.2022.837133 35646974
Laria A, Lurati AM, Zizzo G, Zaccara E, Mazzocchi D, Re KA, et al. Interstitial lung disease in rheumatoid arthritis: a practical review. Front Med-Lausanne. 2022;9:837133.35646974
24. McDermott GC Doyle TJ Sparks JA Interstitial lung disease throughout the rheumatoid arthritis disease course Curr Opin Rheumatol 2021 33 3 284 91 10.1097/BOR.0000000000000787 33625044
McDermott GC, Doyle TJ, Sparks JA. Interstitial lung disease throughout the rheumatoid arthritis disease course. Curr Opin Rheumatol. 2021;33(3):284–91.33625044
25. Spagnolo P Lee JS Sverzellati N Rossi G Cottin V The lung in rheumatoid arthritis: focus on interstitial lung disease Arthritis Rheumatol 2018 70 10 1544 54 10.1002/art.40574 29806092
Spagnolo P, Lee JS, Sverzellati N, Rossi G, Cottin V. The lung in rheumatoid arthritis: focus on interstitial lung disease. Arthritis Rheumatol. 2018;70(10):1544–54.29806092
26. England BR Hershberger D Management issues in rheumatoid arthritis-associated interstitial lung disease Curr Opin Rheumatol 2020 32 3 255 63 10.1097/BOR.0000000000000703 32141954
England BR, Hershberger D. Management issues in rheumatoid arthritis-associated interstitial lung disease. Curr Opin Rheumatol. 2020;32(3):255–63.32141954
27. Samhouri BF, Vassallo R, Achenbach SJ, Kronzer VL, Davis JR, Myasoedova E et al. ,. Incidence, Risk Factors, and Mortality of Clinical and Subclinical Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Population-Based Cohort. Arthrit Care Res. 2022; 74(12):2042–2049.
28. Juge PA Granger B Debray MP Ebstein E Louis-Sidney F Kedra J A risk score to Detect Subclinical Rheumatoid Arthritis-Associated interstitial lung disease Arthritis Rheumatol 2022 74 11 1755 65 10.1002/art.42162 35583934
Juge PA, Granger B, Debray MP, Ebstein E, Louis-Sidney F, Kedra J, et al. A risk score to Detect Subclinical Rheumatoid Arthritis-Associated interstitial lung disease. Arthritis Rheumatol. 2022;74(11):1755–65.35583934
29. Xue J Hu W Wu S Wang J Chi S Liu X Development of a risk Nomogram Model for identifying interstitial lung disease in patients with rheumatoid arthritis Front Immunol 2022 13 823669 10.3389/fimmu.2022.823669 35784288
Xue J, Hu W, Wu S, Wang J, Chi S, Liu X. Development of a risk Nomogram Model for identifying interstitial lung disease in patients with rheumatoid arthritis. Front Immunol. 2022;13:823669.35784288
30. Doyle TJ Patel AS Hatabu H Nishino M Wu G Osorio JC Detection of rheumatoid arthritis-interstitial lung disease is enhanced by serum biomarkers Am J Resp Crit Care 2015 191 12 1403 12 10.1164/rccm.201411-1950OC
Doyle TJ, Patel AS, Hatabu H, Nishino M, Wu G, Osorio JC, et al. Detection of rheumatoid arthritis-interstitial lung disease is enhanced by serum biomarkers. Am J Resp Crit Care. 2015;191(12):1403–12.
31. Brito Y Glassberg MK Ascherman DP Rheumatoid arthritis-Associated interstitial lung disease: current concepts Curr Rheumatol Rep 2017 19 12 79 10.1007/s11926-017-0701-5 29119259
Brito Y, Glassberg MK, Ascherman DP. Rheumatoid arthritis-Associated interstitial lung disease: current concepts. Curr Rheumatol Rep. 2017;19(12):79.29119259
32. Fotoh DS Helal A Rizk MS Esaily HA Serum Krebs von den Lungen-6 and lung ultrasound B lines as potential diagnostic and prognostic factors for rheumatoid arthritis-associated interstitial lung disease Clin Rheumatol 2021 40 7 2689 97 10.1007/s10067-021-05585-y 33474659
Fotoh DS, Helal A, Rizk MS, Esaily HA. Serum Krebs von den Lungen-6 and lung ultrasound B lines as potential diagnostic and prognostic factors for rheumatoid arthritis-associated interstitial lung disease. Clin Rheumatol. 2021;40(7):2689–97.33474659
33. Huang Y Liu T Huang S Qiu L Luo F Yin G Screening value of lung ultrasound in connective tissue disease related interstitial lung disease Heart Lung 2023 57 110 6 10.1016/j.hrtlng.2022.09.011 36182861
Huang Y, Liu T, Huang S, Qiu L, Luo F, Yin G, et al. Screening value of lung ultrasound in connective tissue disease related interstitial lung disease. Heart Lung. 2023;57:110–6.36182861
34. Cogliati C Antivalle M Torzillo D Birocchi S Norsa A Bianco R Standard and pocket-size lung ultrasound devices can detect interstitial lung disease in rheumatoid arthritis patients Rheumatology 2014 53 8 1497 503 10.1093/rheumatology/keu033 24692573
Cogliati C, Antivalle M, Torzillo D, Birocchi S, Norsa A, Bianco R, et al. Standard and pocket-size lung ultrasound devices can detect interstitial lung disease in rheumatoid arthritis patients. Rheumatology. 2014;53(8):1497–503.24692573
35. Mena-Vazquez N Jimenez-Nunez FG Godoy-Navarrete FJ Manrique-Arija S Aguilar-Hurtado MC Romero-Barco CM Utility of pulmonary ultrasound to identify interstitial lung disease in patients with rheumatoid arthritis Clin Rheumatol 2021 40 6 2377 85 10.1007/s10067-021-05655-1 33611648
Mena-Vazquez N, Jimenez-Nunez FG, Godoy-Navarrete FJ, Manrique-Arija S, Aguilar-Hurtado MC, Romero-Barco CM, et al. Utility of pulmonary ultrasound to identify interstitial lung disease in patients with rheumatoid arthritis. Clin Rheumatol. 2021;40(6):2377–85.33611648
36. Wang Y Chen S Zheng S Lin J Hu S Zhuang J 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 Res Ther 2021 23 1 212 10.1186/s13075-021-02586-9 34391465
Wang Y, Chen S, Zheng S, Lin J, Hu S, Zhuang J, et al. 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 Res Ther. 2021;23(1):212.34391465
37. Wu W Guo L Fu Y Wang K Zhang D Xu W Interstitial lung disease in Anti-MDA5 positive dermatomyositis Clin Rev Allerg Immu 2021 60 2 293 304 10.1007/s12016-020-08822-5
Wu W, Guo L, Fu Y, Wang K, Zhang D, Xu W, et al. Interstitial lung disease in Anti-MDA5 positive dermatomyositis. Clin Rev Allerg Immu. 2021;60(2):293–304.
38. Zuo Y Ye L Liu M Li S Liu W Chen F Clinical significance of radiological patterns of HRCT and their association with macrophage activation in dermatomyositis Rheumatology 2020 59 10 2829 37 10.1093/rheumatology/keaa034 32065646
Zuo Y, Ye L, Liu M, Li S, Liu W, Chen F, et al. Clinical significance of radiological patterns of HRCT and their association with macrophage activation in dermatomyositis. Rheumatology. 2020;59(10):2829–37.32065646
39. Nombel A Fabien N Coutant F Dermatomyositis with Anti-MDA5 antibodies: Bioclinical Features, Pathogenesis and emerging therapies Front Immunol 2021 12 773352 10.3389/fimmu.2021.773352 34745149
Nombel A, Fabien N, Coutant F. Dermatomyositis with Anti-MDA5 antibodies: Bioclinical Features, Pathogenesis and emerging therapies. Front Immunol. 2021;12:773352.34745149
40. Wang Y Chen S Lin J Xie X Hu S Lin Q Lung ultrasound B-lines and serum KL-6 correlate with the severity of idiopathic inflammatory myositis-associated interstitial lung disease Rheumatology 2020 59 8 2024 9 10.1093/rheumatology/kez571 31794028
Wang Y, Chen S, Lin J, Xie X, Hu S, Lin Q, et al. Lung ultrasound B-lines and serum KL-6 correlate with the severity of idiopathic inflammatory myositis-associated interstitial lung disease. Rheumatology. 2020;59(8):2024–9.31794028
41. Wang Y Chen S Lin Z Lin J Xie X Lin Q Utilize lung ultrasound B-lines and KL-6 to monitor anti-MDA-5 antibody-positive clinically amyopathic dermatomyositis-associated interstitial lung disease: a case report and literature review Clin Rheumatol 2019 38 5 1433 6 10.1007/s10067-019-04462-z 30746580
Wang Y, Chen S, Lin Z, Lin J, Xie X, Lin Q, et al. Utilize lung ultrasound B-lines and KL-6 to monitor anti-MDA-5 antibody-positive clinically amyopathic dermatomyositis-associated interstitial lung disease: a case report and literature review. Clin Rheumatol. 2019;38(5):1433–6.30746580
42. Abe K, Furuta S, Kobayashi Y, Sugiyama T, Kagami SI, Nakagomi D et al. Prognosis of spontaneous pneumomediastinum occurring in dermatomyositis or polymyositis patients with interstitial lung disease according to antimelanoma differentiation-associated gene 5 antibody status: a retrospective cohort study. Rmd Open 2023; 9(1).
43. Hervier B Uzunhan Y Inflammatory myopathy-related interstitial lung disease: from pathophysiology to treatment Front Med-Lausanne 2019 6 326 10.3389/fmed.2019.00326 32010700
Hervier B, Uzunhan Y. Inflammatory myopathy-related interstitial lung disease: from pathophysiology to treatment. Front Med-Lausanne. 2019;6:326.32010700
44. Zanforlin A Giannuzzi R Nardini S Testa A Soldati G Copetti R The role of chest ultrasonography in the management of respiratory diseases: document I Multidiscip Resp Med 2013 8 1 54 10.1186/2049-6958-8-54
Zanforlin A, Giannuzzi R, Nardini S, Testa A, Soldati G, Copetti R, et al. The role of chest ultrasonography in the management of respiratory diseases: document I. Multidiscip Resp Med. 2013;8(1):54.
45. Kubodera T Adachi YU Hatano T Ejima T Numaguchi A Matsuda N Subcutaneous emphysema and ultrasound sonography J Intensive Care 2013 1 1 8 10.1186/2052-0492-1-8 25705402
Kubodera T, Adachi YU, Hatano T, Ejima T, Numaguchi A, Matsuda N. Subcutaneous emphysema and ultrasound sonography. J Intensive Care. 2013;1(1):8.25705402
46. Diaz RL Callejas RJ Martin-Rodriguez JL The utility of diaphragmatic Ultrasound in the Radiological diagnosis of systemic Lupus Erythymatosus patients with shrinking lung syndrome Arch Bronconeumol 2017 53 12 702 3 10.1016/j.arbr.2017.10.004 28669416
Diaz RL, Callejas RJ, Martin-Rodriguez JL. The utility of diaphragmatic Ultrasound in the Radiological diagnosis of systemic Lupus Erythymatosus patients with shrinking lung syndrome. Arch Bronconeumol. 2017;53(12):702–3.28669416
47. Teixeira A Cherin P Demoule A Levy-Soussan M Straus C Verin E Diaphragmatic dysfunction in patients with idiopathic inflammatory myopathies Neuromuscul Disord 2005 15 1 32 9 10.1016/j.nmd.2004.09.006 15639118
Teixeira A, Cherin P, Demoule A, Levy-Soussan M, Straus C, Verin E, et al. Diaphragmatic dysfunction in patients with idiopathic inflammatory myopathies. Neuromuscul Disord. 2005;15(1):32–9.15639118
48. Grignaschi S Mongodi S Alfonsi E Mojoli F Vertui V Zanframundo G Respiratory failure due to concomitant interstitial lung disease and diaphragmatic involvement in a patient with anti-MDA5 dermatomyositis: a case report Clin Exp Rheumatol 2022 40 Suppl 134 121 3 10.55563/clinexprheumatol/0u7vdc 35238770
Grignaschi S, Mongodi S, Alfonsi E, Mojoli F, Vertui V, Zanframundo G, et al. Respiratory failure due to concomitant interstitial lung disease and diaphragmatic involvement in a patient with anti-MDA5 dermatomyositis: a case report. Clin Exp Rheumatol. 2022;40(Suppl 134):121–3.35238770
49. Denton CP Wells AU Coghlan JG Major lung complications of systemic sclerosis Nat Rev Rheumatol 2018 14 9 511 27 10.1038/s41584-018-0062-0 30111804
Denton CP, Wells AU, Coghlan JG. Major lung complications of systemic sclerosis. Nat Rev Rheumatol. 2018;14(9):511–27.30111804
50. Cappelli S Bellando RS Camiciottoli G De Paulis A Guiducci S Matucci-Cerinic M Interstitial lung disease in systemic sclerosis: where do we stand? Eur Respir Rev 2015 24 137 411 9 10.1183/16000617.00002915 26324802
Cappelli S, Bellando RS, Camiciottoli G, De Paulis A, Guiducci S, Matucci-Cerinic M. Interstitial lung disease in systemic sclerosis: where do we stand? Eur Respir Rev. 2015;24(137):411–9.26324802
51. Wang Y Xie X Zheng S Du G Chen S Zhang W Serum B-cell activating factor and lung ultrasound B-lines in connective tissue disease related interstitial lung disease Front Med-Lausanne 2022 9 1066111 10.3389/fmed.2022.1066111 36590969
Wang Y, Xie X, Zheng S, Du G, Chen S, Zhang W, et al. Serum B-cell activating factor and lung ultrasound B-lines in connective tissue disease related interstitial lung disease. Front Med-Lausanne. 2022;9:1066111.36590969
52. Wang Y Chen S Lin Z Du G Lin J Lin Q Imaging and serum biomarkers in connective tissue disease-associated interstitial lung diseases: correlation between lung ultrasound B-lines and KL-6 levels Ann Rheum Dis 2019 78 4 573 5 10.1136/annrheumdis-2018-214098 30352891
Wang Y, Chen S, Lin Z, Du G, Lin J, Lin Q, et al. Imaging and serum biomarkers in connective tissue disease-associated interstitial lung diseases: correlation between lung ultrasound B-lines and KL-6 levels. Ann Rheum Dis. 2019;78(4):573–5.30352891
53. Gigante A Rossi FF Lucci S Barilaro G Quarta S Barbano B Lung ultrasound in systemic sclerosis: correlation with high-resolution computed tomography, pulmonary function tests and clinical variables of disease Intern Emerg Med 2016 11 2 213 7 10.1007/s11739-015-1329-y 26494471
Gigante A, Rossi FF, Lucci S, Barilaro G, Quarta S, Barbano B, et al. Lung ultrasound in systemic sclerosis: correlation with high-resolution computed tomography, pulmonary function tests and clinical variables of disease. Intern Emerg Med. 2016;11(2):213–7.26494471
54. Radic M, Dogas H, Gelemanovic A, Juric PS, Skopljanac I, Radic J. Pulmonary Ultrasonography in systemic sclerosis-Induced interstitial lung Disease-A systematic review and Meta-analysis. Diagnostics. 2023; 13(8).
55. Bruni C, Mattolini L, Tofani L, Gargani L, Landini N, Roma N et al. Lung Ultrasound B-Lines in the evaluation of the extent of interstitial lung disease in systemic sclerosis. Diagnostics. 2022; 12(7).
56. Gargani L Bruni C Romei C Frumento P Moreo A Agoston G Prognostic value of lung ultrasound B-Lines in systemic sclerosis Chest 2020 158 4 1515 25 10.1016/j.chest.2020.03.075 32360727
Gargani L, Bruni C, Romei C, Frumento P, Moreo A, Agoston G, et al. Prognostic value of lung ultrasound B-Lines in systemic sclerosis. Chest. 2020;158(4):1515–25.32360727
57. Kambhatla S Vipparthy S Manadan AM Rheumatic diseases associated with alveolar hemorrhage: analysis of the national inpatient sample Clin Rheumatol 2023 42 4 1177 83 10.1007/s10067-022-06449-9 36396790
Kambhatla S, Vipparthy S, Manadan AM. Rheumatic diseases associated with alveolar hemorrhage: analysis of the national inpatient sample. Clin Rheumatol. 2023;42(4):1177–83.36396790
58. Park JA. Treatment of diffuse alveolar hemorrhage: Controlling inflammation and obtaining Rapid and Effective Hemostasis. Int J Mol Sci 2021; 22(2).
59. Palmucci S Galioto F Fazio G Ferlito A Cancemi G Di Mari A Clinical and radiological features of lung disorders related to connective-tissue diseases: a pictorial essay Insights Imaging 2022 13 1 108 10.1186/s13244-022-01243-2 35767157
Palmucci S, Galioto F, Fazio G, Ferlito A, Cancemi G, Di Mari A, et al. Clinical and radiological features of lung disorders related to connective-tissue diseases: a pictorial essay. Insights Imaging. 2022;13(1):108.35767157
60. Kim MJ Shin K Interstitial lung disease and diffuse alveolar hemorrhage, the two Key Pulmonary manifestations in Microscopic Polyangiitis Tuberc Respir Dis 2021 84 4 255 62 10.4046/trd.2021.0065
Kim MJ, Shin K. Interstitial lung disease and diffuse alveolar hemorrhage, the two Key Pulmonary manifestations in Microscopic Polyangiitis. Tuberc Respir Dis. 2021;84(4):255–62.
61. Mirouse A Parrot A Audigier V Demoule A Mayaux J Geri G Severe diffuse alveolar hemorrhage related to autoimmune disease: a multicenter study Crit Care 2020 24 1 231 10.1186/s13054-020-02936-0 32423434
Mirouse A, Parrot A, Audigier V, Demoule A, Mayaux J, Geri G, et al. Severe diffuse alveolar hemorrhage related to autoimmune disease: a multicenter study. Crit Care. 2020;24(1):231.32423434
62. Buda N Masiak A Zdrojewski Z Utility of lung ultrasound in ANCA-associated vasculitis with lung involvement PLoS ONE 2019 14 9 e0222189 10.1371/journal.pone.0222189 31504049
Buda N, Masiak A, Zdrojewski Z. Utility of lung ultrasound in ANCA-associated vasculitis with lung involvement. PLoS ONE. 2019;14(9):e0222189.31504049
63. Chen XC He S Xue J Shrinking lung syndrome in autoimmune inflammatory diseases: a case series and review of literature World J Emerg Med 2022 13 3 254 6 10.5847/wjem.j.1920-8642.2022.041 35646220
Chen XC, He S, Xue J. Shrinking lung syndrome in autoimmune inflammatory diseases: a case series and review of literature. World J Emerg Med. 2022;13(3):254–6.35646220
64. Depascale R Del FG Gasparotto M Manfre V Gatto M Iaccarino L Diagnosis and management of lung involvement in systemic lupus erythematosus and Sjogren’s syndrome: a literature review Ther Adv Musculoskel 2021 13 1759720X211040696
Depascale R, Del FG, Gasparotto M, Manfre V, Gatto M, Iaccarino L, et al. Diagnosis and management of lung involvement in systemic lupus erythematosus and Sjogren’s syndrome: a literature review. Ther Adv Musculoskel. 2021;13:1759720X211040696.
65. Sferrazza PG Pellegrino GM Di Marco F Imeri G Brochard L Goligher E A review of the Ultrasound Assessment of diaphragmatic function in clinical practice Respiration 2016 91 5 403 11 10.1159/000446518 27216909
Sferrazza PG, Pellegrino GM, Di Marco F, Imeri G, Brochard L, Goligher E, et al. A review of the Ultrasound Assessment of diaphragmatic function in clinical practice. Respiration. 2016;91(5):403–11.27216909
66. Satis H Cindil E Salman RB Yapar D Temel E Demir NB Diaphragmatic muscle thickness and diaphragmatic function are reduced in patients with systemic lupus erythematosus compared to those with primary Sjogren’s syndrome Lupus 2020 29 7 715 20 10.1177/0961203320919848 32338144
Satis H, Cindil E, Salman RB, Yapar D, Temel E, Demir NB, et al. Diaphragmatic muscle thickness and diaphragmatic function are reduced in patients with systemic lupus erythematosus compared to those with primary Sjogren’s syndrome. Lupus. 2020;29(7):715–20.32338144
67. Torres JA Ruiz VN Cespedes CA Velazquez CA Bernardino GA Shrinking lung syndrome in pediatric systemic lupus erythematosus Lupus 2021 30 7 1175 9 10.1177/09612033211010331 33888011
Torres JA, Ruiz VN, Cespedes CA, Velazquez CA, Bernardino GA. Shrinking lung syndrome in pediatric systemic lupus erythematosus. Lupus. 2021;30(7):1175–9.33888011
68. Van de Louw A Mirouse A Peyrony O Lemiale V Azoulay E Bacterial pneumonias in immunocompromised patients Semin Resp Crit Care 2019 40 4 498 507 10.1055/s-0039-1696961
Van de Louw A, Mirouse A, Peyrony O, Lemiale V, Azoulay E. Bacterial pneumonias in immunocompromised patients. Semin Resp Crit Care. 2019;40(4):498–507.
69. Llamas-Alvarez AM Tenza-Lozano EM Latour-Perez J Accuracy of Lung Ultrasonography in the diagnosis of pneumonia in adults: systematic review and Meta-analysis Chest 2017 151 2 374 82 10.1016/j.chest.2016.10.039 27818332
Llamas-Alvarez AM, Tenza-Lozano EM, Latour-Perez J. Accuracy of Lung Ultrasonography in the diagnosis of pneumonia in adults: systematic review and Meta-analysis. Chest. 2017;151(2):374–82.27818332
70. Chen H Ai L Lu H Li H Clinical and imaging features of COVID-19 Radiol Infect Dis 2020 7 2 43 50 10.1016/j.jrid.2020.04.003 32346593
Chen H, Ai L, Lu H, Li H. Clinical and imaging features of COVID-19. Radiol Infect Dis. 2020;7(2):43–50.32346593
71. Miledi S Bouzid S Fazaa A Sallemi M Bousaa H Ben AK COVID-19 in patients with systemic inflammatory diseases: Impact on Disease Activity Curr Rheumatol Rev 2023 19 3 330 5 10.2174/1573397119666230116151541 36650623
Miledi S, Bouzid S, Fazaa A, Sallemi M, Bousaa H, Ben AK, et al. COVID-19 in patients with systemic inflammatory diseases: Impact on Disease Activity. Curr Rheumatol Rev. 2023;19(3):330–5.36650623
72. Volpicelli G Gargani L Perlini S Spinelli S Barbieri G Lanotte A Lung ultrasound for the early diagnosis of COVID-19 pneumonia: an international multicenter study Intens Care Med 2021 47 4 444 54 10.1007/s00134-021-06373-7
Volpicelli G, Gargani L, Perlini S, Spinelli S, Barbieri G, Lanotte A, et al. Lung ultrasound for the early diagnosis of COVID-19 pneumonia: an international multicenter study. Intens Care Med. 2021;47(4):444–54.
73. Volpicelli G Gargani L Sonographic signs and patterns of COVID-19 pneumonia Ultrasound J 2020 12 1 22 10.1186/s13089-020-00171-w 32318891
Volpicelli G, Gargani L. Sonographic signs and patterns of COVID-19 pneumonia. Ultrasound J. 2020;12(1):22.32318891
74. Gargani L Soliman-Aboumarie H Volpicelli G Corradi F Pastore MC Cameli M Why, when, and how to use lung ultrasound during the COVID-19 pandemic: enthusiasm and caution Eur Heart J-Card Img 2020 21 9 941 8
Gargani L, Soliman-Aboumarie H, Volpicelli G, Corradi F, Pastore MC, Cameli M. Why, when, and how to use lung ultrasound during the COVID-19 pandemic: enthusiasm and caution. Eur Heart J-Card Img. 2020;21(9):941–8.
75. Soldati G, Demi M. What Is COVID 19 Teaching Us about Pulmonary Ultrasound? Diagnostics. 2022; 12(4).
76. Sansone F, Attanasi M, Di Filippo P, Sferrazza PG, Di Pillo S, Chiarelli F. Usefulness of Lung Ultrasound in Paediatric Respiratory diseases. Diagnostics. 2021; 11(10).
77. Piccolo CL Liuzzi G Petrone A Fusco N Blandino A Monopoli F The role of Lung Ultrasound in the diagnosis of SARS-COV-2 disease in pregnant women J Ultrasound 2023 26 2 497 503 10.1007/s40477-022-00745-5 36574192
Piccolo CL, Liuzzi G, Petrone A, Fusco N, Blandino A, Monopoli F, et al. The role of Lung Ultrasound in the diagnosis of SARS-COV-2 disease in pregnant women. J Ultrasound. 2023;26(2):497–503.36574192
78. Ambardar SR, Hightower SL, Huprikar NA, Chung KK, Singhal A, Collen JF. Post-COVID-19 pulmonary fibrosis: Novel Sequelae of the current pandemic. J Clin Med. 2021; 10(11).
79. Kostopanagiotou K Schuurmans MM Inci I Hage R COVID-19-related end stage lung disease: two distinct phenotypes Ann Med 2022 54 1 588 90 10.1080/07853890.2022.2039954 35168461
Kostopanagiotou K, Schuurmans MM, Inci I, Hage R. COVID-19-related end stage lung disease: two distinct phenotypes. Ann Med. 2022;54(1):588–90.35168461
80. Lazar M, Barbu EC, Chitu CE, Tiliscan C, Stratan L, Arama SS et al. Interstitial lung fibrosis following COVID-19 pneumonia. Diagnostics. 2022; 12(8).
81. Demi L Wolfram F Klersy C De Silvestri A Ferretti VV Muller M New International guidelines and Consensus on the Use of Lung Ultrasound J Ultras Med 2023 42 2 309 44 10.1002/jum.16088
Demi L, Wolfram F, Klersy C, De Silvestri A, Ferretti VV, Muller M, et al. New International guidelines and Consensus on the Use of Lung Ultrasound. J Ultras Med. 2023;42(2):309–44.
