Chapter 6
Interstitial syndrome
Luna Gargani
Institute of Clinical Physiology, National Research Council, Pisa, Italy.
Correspondence: Luna Gargani, Institute of Clinical Physiology, National Research Council, via Moruzzi 1 – 56124, Pisa, Italy. E-mail: gargani@ifc.cnr.it
B-lines are probably the most “revolutionary” sign of LUS and can be used for the evaluation of interstitial syndrome. They indirectly visualise different degrees of partial deaeration of the pulmonary parenchyma, and therefore can be seen in the presence of both hydrostatic and inflammatory pulmonary oedema, as well as in pulmonary fibrosis. Assessment of B-lines can thus be applied to many different diseases, such as heart failure, end-stage renal disease, acute lung injury, interstitial lung disease and pre-eclampsia. To differentiate these conditions, a thorough integration with the clinical picture is absolutely necessary, but some LUS characteristics can also significantly improve B-line specificity and overall LUS diagnostic accuracy (pattern of distribution over the thorax, response to therapy and association with other LUS signs, such as pleural line alterations, small and large consolidations, and pleural effusion). The clinical usefulness of B-lines has been demonstrated not only for diagnosis but also for monitoring and prognosis.
Cite as: Gargani L. Interstitial syndrome. In: Laursen CB, Rahman NM, Volpicelli G, eds. Thoracic Ultrasound (ERS Monograph). Sheffield, European Respiratory Society, 2018; pp. 75–86 [https://doi.org/10.1183/2312508X.10006517].
Pulmonary interstitial syndrome comprises a group of lung disease affecting the lung interstitium. Although sonography cannot be used to evaluate the lung because the pulmonary air represents an insurmountable obstacle to the US beam, it is possible to recognise sonographic patterns, including “artefactual” B-lines, which can be used effectively in many settings. These can aid in the differential diagnosis of dyspnoea, and can be used to monitor the response to therapy.
Sonographic signs of interstitial syndrome
B-lines
Definition
In recent years, B-lines have been described as the sonographic sign of pulmonary interstitial syndrome. It is difficult to define sonographic interstitial syndrome, as this is a term derived from radiology, where it refers to a pattern that can be applied both to CXR and to chest CT, including linear, reticular, nodular and pseudonodular alterations.
B-lines have officially been defined as “discrete laser-like vertical hyperechoic reverberation artefacts that arise from the pleural line, extend to the bottom of the screen without fading, and move synchronously with lung sliding” [1]. B-lines are indeed sonographic artefacts, which do not depict real anatomical structures but rather are the result of the peculiar acoustic properties of the lung. The physical genesis of B-lines is not yet fully understood, although some sound hypotheses have been proposed [2].
To understand what B-lines represent in the context of LUS basic semiotics, we have to refer strictly to the physical interaction between the US beam and the pulmonary parenchyma. When the pulmonary parenchyma is normally or over-aerated, the US beam is usually unable to penetrate below the pleural line; the resulting image thus shows all of the structures above the pleura (e.g. adipose tissue, muscles, fascia) and the pleura itself as a hyperechoic horizontal line moving synchronously with respiration. The structures above the pleural line are sonographically portrayed as corresponding to real anatomical entities. This is not true for what is depicted below the pleural line, unless the lung is consolidated. Whether the sonographic pleural line fully corresponds to the anatomical pleura is still debated.
A reduction in pulmonary aeration changes the physical acoustic interaction between the US beam and the lung, allowing the US beam to partially penetrate the lung parenchyma, and resulting in the appearance of B-lines. A complete or almost complete pulmonary deaeration would generate the sonographic display of a consolidation, with direct imaging of the anatomical consolidated parenchyma. Milder degrees of deaeration do not allow direct imaging of the lung parenchyma but generate B-lines, which are more numerous as long as the air diminishes. It follows that B-lines are visible in the presence of a partial deaeration of the lung, which is, however, not consolidated. This condition is not necessarily linked only to alterations of the pulmonary interstitial space, making the term “interstitial syndrome” somewhat of an oversimplification, although very figurative. Referring to a condition of “partial deaeration”, which characterises the pre-consolidated lung, seems more appropriate [2, 3]. However, the term interstitial syndrome is suitable for most pathology, and it is true that those conditions that do not purely affect the interstitial space usually show additional signs to B-lines.
Characteristics
There are some typical features of B-lines that help in the differentiation from other artefacts. Table 1 presents the main B-line characteristics. These elements are especially useful to differentiate B-lines from Z-lines. Z-lines are vertical hyperechoic artefacts that, similar to B-lines, arise from the pleural line, although the pleural origin is better defined for B-lines. Moreover, Z-lines do not reach the edge of the screen and do not clearly move with lung sliding [4]. Z-lines are usually less hyperechoic than the relative pleural line. Z-lines do not seem to have pathological meaning. Figure 1 shows a Z-line and B-lines.
Table 1. Characteristics of sonographic B-lines
Characteristic | Comments |
|---|---|
Arise from the pleural line | Always true |
Common feature to Z-lines (whose origin is, however, less defined) | |
Move synchronously with lung sliding (with respiration) | Always true |
Z-lines do not clearly move with lung sliding | |
Erase A-lines | A-lines may still be visible, but are covered/erased by B-lines at the intersection point |
Z-lines do not erase A-lines | |
Hyperechoic | Similar echogenicity as the pleural line |
Z-lines are usually less hyperechoic than the pleural line | |
Well defined | Quite subjective |
Usually better defined compared with Z-lines | |
Extend to the bottom of the screen without fading | May partially depend on the machine setting |
Z-lines usually fade away before reaching the bottom of the screen |
Figure 1. a) Z-line (arrow). b) B-lines (arrow).
Pleural line
The pleural line is a cornerstone of LUS. It is the first structure that should be searched for, and its movement, referred to as lung sliding, should always be identified before moving on to further evaluations. When lung sliding is not apparent, the different potential causes of absent lung sliding should be taken into account, and the LUS examination should continue to exclude or confirm the main clinical suspicion.
The normal pleura is visualised by LUS as a hyperechoic horizontal thin line, representing the apposition of the parietal with the visceral pleura layers (figure 1). The pleural line may appear abnormal in some pathological conditions, such as acute lung injury/acute respiratory distress syndrome (ALI/ARDS) or interstitial lung disease (ILD). The appearance of the pleural line can be helpful in contributing to the differential diagnosis of the aetiology of B-lines [5–7], as detailed in the following section.
Diffuse versus focal interstitial syndrome
The mere presence of B-lines is not enough to characterise a lung from the sonographic point of view. A few B-lines, especially at the lung bases, can be present in healthy subjects and do not have a specific pathological meaning. A positive examination for B-lines needs the presence of multiple, diffuse, bilateral B-lines. Multiple B-lines means at least three B-lines between two ribs when applying the probe longitudinally, or at least three close B-lines along the intercostal space when applying the probe obliquely or transversally. Diffuse B-lines means that multiple B-lines should be seen in at least two regions of the lung and bilaterally (i.e. in both hemithoraxes) [1]. As thoracic regions, the eight-region scanning scheme proposed by Volpicelli et al. [1] is usually accepted. Another scanning scheme that is accepted and has been used in many studies is the 28-scanning-site scheme [8], which is more time consuming but allows a type of quantification of B-lines that, although imprecise, has been shown to correlate with clinical [9, 10], biochemical [11], radiological [12, 13], echocardiographic [9], gravimetric [14] and invasive [15] parameters related to the interstitial involvement of the lung. Moreover, it has shown clear prognostic value in both acute and chronic patients [16–20].
The definition of multiple B-lines as at least three B-lines between two ribs can be in part subjective and does not take into account different thoracic dimensions. In acute conditions, this is usually not so relevant, because the US patterns tend to be clear and straightforward. However, clinical reasoning is mandatory, and a blind adherence to the US picture, unrelated to the patient’s characteristics, should be avoided.
It is also crucial to distinguish between the abovementioned situation of positive scanning for multiple, diffuse, bilateral B-lines and so-called focal interstitial syndrome, which refers to multiple B-lines, usually limited to one region, and monolateral. This condition can be present in healthy asymptomatic subjects (probably linked to previous pulmonary parenchymal involvement), whereas, in a patient with signs/symptoms such as dyspnoea, tachypnoea, fever or chest pain, multiple focal B-lines should raise the suspicion of pulmonary abnormalities not clearly visible by LUS at that time. It is typical to find multiple focal B-lines in a patient with fever and/or chest pain, especially if scanned early after the appearance of symptoms, and then to visualise a consolidation in the same area after a few hours. Multiple focal B-lines may represent the perilesional oedema of the consolidation that is being formed, or a consolidation that is not peripheral enough to be detected clearly by LUS. Thus, the clinical context must always be the guide to orient these findings.
Clinical applications
Cardiogenic pulmonary oedema
In recent years, many studies have confirmed that B-lines can be useful in the detection, monitoring and prognosis of patients with cardiogenic pulmonary oedema [6, 21, 22]. The first published data were about the differential diagnosis of patients with acute dyspnoea. In this setting, a positive LUS scanning for B-lines can help differentiate from other causes of acute dyspnoea, in particular from exacerbation of COPD [11, 23–25]. Again, it is important not to refer to the mere presence of B-lines but to assess multiple, diffuse, bilateral B-lines, as patients with COPD, as well as healthy subjects, may show a few B-lines. In a large multicentric prospective study on >1000 patients with acute dyspnoea, adding LUS to the standard clinical evaluation in the emergency department improved the accuracy of acute heart failure (AHF) diagnosis (sensitivity and specificity 97%), with a net reclassification index of the LUS-implemented approach compared with the standard work-up of 19.1% [25]. This study addressed the diagnostic performance of LUS, whereas an improvement in outcomes was not evaluated in the LUS-implemented group. LUS evaluation of B-lines for the differential diagnosis of AHF compared with other causes of acute dyspnoea also seemed a more effective method of implementation of PoCUS in a large cohort of consecutive adult patients presenting with dyspnoea and admitted after emergency department evaluation [26]. The presence of multiple bilateral B-lines increased the sensitivity of the diagnosis of AHF from 77% (standard evaluation) to 88% (p<0.001), with a slight reduction in specificity (98% versus 96%; p<0.001) [26].
B-lines can also be used effectively for monitoring decongestion in heart failure [16, 27–29], with a potential additional impact on accelerating discharge [30]. Indeed, LUS is particularly suitable for monitoring, being a noninvasive, bedside, user-friendly imaging tool; it is therefore promising for checking day-to-day changes in extravascular lung water with high versatility, although no clear data are available about the use of B-lines to guide therapy as yet [31]. The advantage of using LUS for monitoring pulmonary congestion in AHF is also linked to the possibility of reducing ionising radiation exposure due to serial CXR, although the dose of a single CXR is relatively small (∼0.02 mSv for a single posteroanterior film) [32].
Encouraging data have been published on the prognostic value of B-lines. Persistent B-lines at discharge after hospitalisation for AHF predict readmission for decompensated heart failure at 3 and 6 months [16, 17, 19]. Similar results have been published for outpatients: patients with a higher number of B-lines during a routine ambulatory office visit were more prone to be readmitted for decompensated heart failure in the following months [18, 33].
Noncardiogenic pulmonary oedema
LUS signs are quite different in cardiogenic compared with noncardiogenic pulmonary oedema. When the pathophysiology of extravascular lung water accumulation is an increase in the alveolar–capillary membrane permeability instead of an increase in hydrostatic pressure, not only is the pulmonary interstitium affected but also the alveoli. From a sonographic point of view, this translates into the presence of multiple, diffuse, bilateral B-lines, as in AHF, but also into alveolar consolidations of different sizes. Very small, subpleural consolidations are thought to be the reason why the pleural line in ALI/ARDS looks so different from the pleural line in AHF. The latter condition is characterised by a rather thin and regular hyperechoic horizontal line, whereas in ALI/ARDS the pleural line looks irregular with hypo/anechoic spaces just below it, which are likely to be the sonographic imaging of small peripheral consolidations (figure 2) [5]. This is not the only sonographic difference, although it is probably the most striking and easy to detect: the geographical distribution of B-lines is also different, because cardiogenic pulmonary oedema tends to follow a gravity-related gradient with B-lines appearing before and more frequently in the dependent zones, and later and less frequently in the most anteroapical regions of the chest [6]. This typical distribution also slightly affects the sensitivity of LUS in diagnosing pulmonary oedema when evaluating only the anteroapical regions [34]. Moreover, ALI/ARDS US alterations show a jeopardised distribution, with highly damaged areas close to completely spared areas [5]. B-lines in ALI/ARDS are correlated with lung weight and density, determined by gravimetry in an experimental model in pigs [14, 35], as well in humans, determined by CT [36].
