Keywords

Key Messages

  • LUS is however useful in diagnosis, monitoring the response to therapy and follow up of patients with pneumonia

  • POCUS findings correspond to anatomo-pathologic modifications found in pneumonia. Among the most common POCUS signs we found B lines, pleural abnormalities (thickness and irregularity), meta-pneumonic effusions and consolidations with either static or dynamic air bronchogram

  • For assessment and the follow up of the severity of illness, it is useful to adopt the lung ultrasound aeration score.

Introduction

Pneumonia is a common infective disease, involving patients from childhood to old age, with a wide range of clinical presentations with a notable morbidity and mortality [1].

In the last few decades, there has been increasing interest in LUS application for the diagnosis and monitoring in numerous cardiopulmonary conditions, as well as pneumonia.

In this chapter we will try to discuss and summarize the evidence about the use of LUS in pneumonia and elucidate the role of this exam for the diagnosis and follow up of pneumonic patients (Fig. 1).

Fig. 1
figure 1

Search results in Pubmed for “Pneumonia” and “Lung Ultrasound”—published articles increased in time, and COVID-19 was a clear source of interest for researching and publishing in LUS

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Clinical Aspects of Pneumonia

Pneumonia is a lower respiratory tract infection that represents the most common infection worldwide, associated with high morbidity and mortality [1]. Its presentation varies from mild symptoms such as fever, cough and sputum production, to severe forms characterised by increased work of breath, respiratory distress and sepsis. Severity scores can be helpful tools to stratify the severity of illness together with the clinical judgment, in order to define the most appropriate level of care. Commonly used assessment tools are the “Pneumonia Severity Index” (PSI or PORT) and the CURB-65 [2].

Classification of pneumonia is based on the place where the patient contracted the infection, and in particular:

Community-acquired pneumonia (CAP) refers to an acute infection of the pulmonary parenchyma acquired outside of the hospital.

Nosocomial pneumonia refers to a pneumonia that occurs 48 h or more after admission and does not appear to be incubating at the time of admission. It includes ventilator-associated pneumonia (VAP) if acquired ≥48 h after endotracheal intubation.

The suspicion of pneumonia requires a compatible clinical presentation with suggestive signs and symptoms, with a consistent radiographical finding as a fundamental component of the diagnosis [3]. Indeed, the latest guidelines consider chest X-ray (CXR) the gold standard technique, yet the role of thoracic ultrasound was not mentioned despite it being routinely applied in clinical practice [4, 5].

The patterns found on CXR are usually related to the causative agent. We can distinguish between a lobar pneumonia, a bronchopneumonia or lobular pneumonia and an interstitial pneumonia.

Lobar pneumonia involves single or multiple lobes and is the most common radiographic pattern of CAP, usually caused by typical bacteria as S. pneumoniae. Bronchopneumonia is most commonly caused by S. aureus, H. influenzae, and fungi, and is characterised by multiple small nodular or reticulonodular opacities which tend to be patchy and/or confluent. Interstitial pneumonia presents itself as diffuse bilateral peri-bronchial thickening and ill-defined reticulonodular opacities. The prevalent pathogens of interstitial pneumonia are viruses and M. pneumoniae [6].

Chest radiography can sometimes be normal, especially in the early phases of the disease process or in interstitial pneumonia, that has a preference for lower lung areas behind the heart and the diaphragm; in this case chest CT can be a useful alternative thanks to its higher sensitivity [7]. However, CT has only a limited role in the everyday practice due to its costs, radiation exposure, needing to move the patient to the radiology unit and low time-resolution. Therefore, CT is commonly preferred in the most severe forms, to better characterize pneumonia and its complications, and to rule out other diagnoses.

As mentioned above, clinical applications of LUS have increased in the last decades. It has become part of the clinical management in several pulmonary conditions, and in many different settings, such as in the emergency departments, intensive care units (ICUs), internal medicine wards and even in outpatient evaluation. In 2008 Lichtenstein and Mezière published one of the first protocols, called the BLUE Protocol (Bedside Lung Ultrasound in Emergency, Fig. 2), which assesses the use of LUS in diagnosing the most frequent causes of acute respiratory failure [8]. Since then, many experimental and clinical studies protocols and rating systems have been presented, mostly regarding the ability of LUS to detect loss of aeration or gain of extravascular lung water [7, 9,10,11,12].

Fig. 2
figure 2

Modified from Lichtenstein et al. [8]. COPD: chronic obstructive pulmonary disease. PLAPS: posterolateral alveolar and/or pleural syndrome

The Blue Protocol.

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Many studies compared LUS to CXR in terms of sensitivity and specificity in pneumonia diagnosis; in the emergency room, LUS is considered a valid alternative for early diagnosis of pneumonia in adults [8, 13,14,15,16]. In this setting, consolidations have 93% sensitivity and 98% specificity for the diagnosis of community-acquired pneumonia [16]. For Reissig et al. combination of LUS and auscultation findings resulted in a positive likelihood-ratio of diagnosis of 42.9 (CI 10.8, 17.0) and a negative likelihood-ratio of 0.04 (CI 0.02, 0.09) [17]. The high reliability of LUS for detection of consolidations was confirmed when compared to chest CT imaging as well [18, 19].

Moreover, LUS tends to detect pulmonary infiltrates more often than CXR; the same applies to Covid-19 pneumonia where more than half of the patients had an initially normal CXR [20].

For what concerns VAP diagnosis, clinical and microbiological information are fundamental and should always be considered together with the imaging findings. The ‘Chest Echography and Procalcitonin Pulmonary Infection Score’ (CEPPIS) encompasses all these components in order to improve the diagnostic accuracy of POCUS, which included for the first time the presence of infiltrates on LUS, in addition to other clinical and laboratory parameters (type of tracheal secretions, cultures of tracheal secretions, procalcitonin levels, fever or hypothermia, and worsening of oxygenation index PaO2/FiO2). This tool seems to have higher sensitivity, specificity, positive and negative predictive value when compared with LUS alone or LUS plus proca

Table 1 Chest Echography and Procalcitonin Pulmonary Infection Score (CEPPIS).
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lcitonin (Table 1) [22].

How to Perform Lung Ultrasound

As Mayo et al. [21] wrote in their review, “There is no best way to perform image acquisition for thoracic ultrasonography”.

Linear, curvilinear abdominal or cardiac probes can all be used, based on the physician preference and the clinical need. The high frequency probe is mostly used to acquire a detailed image of the pleural line. The cardiac phase array probe has a small footprint that allows to better scan the intercostal space.

Regarding the scanning technique, two anterior zones can be sufficient to formulate a rough differential diagnosis between a cardiogenic pulmonary oedema and a primary parenchymal respiratory dyspnoea (e.g. chronic obstructive pulmonary disease exacerbation), but this should not be recommended for the systematic examination of the lungs in order to detect infectious consolidations [23].

The BLUE Protocol [8] proposed an examination method that included three scanning points per chest side, anterior, lateral and posterolateral, in a supine position and consists in scanning each rib interspace moving the probe longitudinally and transversally. The international recommendations for point-of-care LUS [24] described other possible techniques. The basic eight-region sonographic technique [25] for antero-lateral field examination considers four areas per side, upper and lower anterior, upper lateral and basal lateral and has been suggested to be used in the emergency department. In critically ill patients, a more comprehensive examination is often applied, that considers six scans per side: superior and inferior regions for the anterior, lateral and posterior fields [26, 27] (Fig. 3). In this case, placing the probe as posteriorly as possible, even in the supine critically ill patients is important to explore the posterior areas of the thorax which are frequently involved in the critically ill patients. Whenever possible, it is recommended to place the patient in the lateral decubitus position to fully explore these fields. This approach has been recently used in the evaluation of LUS aeration scores as well as in the evaluation of COVID-19 pneumonia and it has the advantage of providing a complete exam in a short time period time, ranging from 8 min (for experts) to 10 min (for trainees) [28,29,30].

Fig. 3
figure 3

Suggested scans in LUS examination. ML: midline. AAL: anterior axillary line. PAL: posterior axillary line

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In our experience, we suggest to follow a mental algorithm called the “SAFED approach” in order to interpret LUS findings and achieve a diagnosis regardless of the chosen scanning protocol and depending on different clinical contexts and the level of urgency [31].

“S” for anatomical Size to measure subpleural consolidations whenever present.

“A” for Air, to detect and characterize air bronchograms.

“F” for Fluids, looking for meta-pneumonic effusion.

“E” for Excursion, looking for “lung pulse” suggesting atelectasis with pleural involvement.

“D” for Doppler, because a highly perfused lung consolidation with loss of aeration will likely correspond to intrapulmonary shunt suggesting a significant contribution of the consolidation to arterial hypoxemia.

Anatomopathological Modifications in Pneumonia

Understanding anatomopathological modifications of lung parenchyma in pneumonia is crucial to comprehend sonographic alterations. In fact, POCUS reveals nothing but alterations in the mode of reflecting and absorbing US waves; the variations in tissue impedance causes reflection of waves, creating images.

Modifications occurring in pneumonia are typically different depending on the pathogenetic mechanisms and aetiologic agent [32].

In lobar pneumonia, an entire lobe is involved, and there are subsequent phases with different involvement of the parenchyma:

  • Congestion phase: the lung has high water content, is heavy and oedematous; this stage is characterised by vascular congestion, so anatomically the tissues appear red. The alveoli are still partially aerated.

  • Red hepatization phase: this second stage is characterized by a fibrinous exudate in the alveoli, rich in proteins, red and white cells. Alveoli are almost not aerated, and the parenchyma appears to be red and stiff.

  • Grey hepatization phase: the lung is no longer wet, but a fibrinous purulent exudate is still present; the lobe appears to be grey-brownish.

  • Resolution phase: in this phase there is a granulomatous reaction mediated by immune cells (macrophages), gradual enzymatic digestion and reabsorption of semifluid substances produced during inflammation phases. Fibroblasts contribute in this phase to organizing the pulmonary parenchyma and reconstitution of tissue [33].

Pleural involvement is seldom detected, but when it is, it results in pleural thickening, purulent and fibrinous reaction.

Another type of lung involvement is the bronchopneumonia. In this case a diffuse patchy multilobar and often bilateral involvement of lungs is seen. Lesions appear to be granular, prominent, not well defined, and there is always an airway inflammation with abundant secretions. These latter are often purulent and accumulate in the lower regions; fibrin rich exudate can fill the alveoli.

In some cases, we can find complications of pneumonia such as abscesses, meta-pneumonic pleural effusion, or empyema.

Based on the host-causal agent interaction, the tissue response patterns are quite different. However, patterns of lobar, interstitial, and bronchopneumonia can overlap, and are not mutually exclusive.

It is mandatory to keep in mind all the macroscopic modifications of the lung parenchyma as well as the location of consolidations in the lung parenchyma to be able to match these with LUS patterns and modification of echogenicity. Indeed, LUS is a key to interpret the changes in tissue impedance, thus an anatomical parenchymal consolidation can be visualized by LUS either as an ultrasonographic consolidation or as an ultrasonographic alveolo-interstitial syndrome depending on the distance from the pleural line (Fig. 4). Knowledge of tissue modification in lung disease is crucial to understand LUS images and provide their interpretation.

Fig. 4
figure 4

Representative echo images (left) and quantitative lung ultrasonography analysis (right) for three patients with normal hemi-thorax (upper panels), sub-pleural consolidation (middle panels), and non-sub-pleural consolidation (lower panels). Upper panels show the echo intensities against distance from the pleural line; in the middle panels, notice the frequency distribution of echo intensities for the whole image. Note the progressive attenuation of the echo intensity going deep into the lung in the normal hemi-thorax as compared with the increasing echo intensity in the sub-pleural consolidation (indicating acoustic enhancement artifact), and the biphasic pattern in the non-sub-pleural consolidation (suggesting acoustic scattering). Computer aided techniques allow to detect signal pattern distribution of a consolidative lesion in the deep lung that does not reach the pleural line [7]

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Sonographic Findings in Pneumonia

Pneumonia can appear with different images, depending on the severity, the diffusion in the parenchyma and the underlying pathogenetic mechanism.

B-lines are vertical hyperechoic artifacts that arise from the pleural line, move with lung sliding, spread to the edge of the screen without fading, and erase A lines [24]. First described in 1982 in relation to an intra-hepatic gunshot, they were associated to alveolar-interstitial syndrome in 1997 by Lichtenstein [34] and only recently have been proved to occur due to the different acoustic impedances between an object and its surroundings, such as the presence of liquid filled areas next to alveolar air and thus a direct representation of air-to-water ratio. B-lines artifacts are associated, among other conditions, with pneumonia, due to the increased extravascular lung water or partial loss of aeration of the lung, probably as consequences of the neutrophil rich exudate that floods peripheral alveoli as an inflammatory reaction [7].

For this reason, B-lines represent the fundamental components of the LUS aeration score, that is used to determine the rate of involvement of lung parenchyma. Score 0 corresponds to A-lines or two or fewer B-lines and identifies a normally aerated parenchyma. Score 1 is defined by three or more B-lines involving 50% or less of the pleural line; in score 2 B-lines involve more than 50% of the imaged pleural line, as they represent a worsening of lung aeration. The last one, score 3, is characterised by a tissue-like pattern and corresponds to a complete loss of aeration (Fig. 5). The final aeration score is given by the sum of the maximum score visualized in each area, ranging from 0 to 36 if the twelve regions protocol is adopted [9] (see Chapter “POCUS in Monitoring: How Monitor Pulmonary Aeration/Deaeration?” for more details).

Fig. 5
figure 5

Lung ultrasound aeration score based on lung aeration. See text for details

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In pneumonia, the changes in the characteristics, number, coalescence, intensity and persistence of B-lines may help to define the characteristics of the pneumonia, including its severity, residual aeration with potential recruitment, bronchial patency and response to treatments [28].

A pneumonia consolidation is usually visualized by LUS as a subpleural hypoechoic area with irregular margins sometimes with reduced or absent lung sliding. The lower and deeper irregular margins of the consolidation constitute the so called “shred sign” (Fig. 6). Frequently, from the shredded boundaries of consolidations, multiple spreading B-lines can be seen, representing the transition zone caused by the presence of perilesional oedema surrounding the focus of pneumonia [35].

Fig. 6
figure 6

Image acquired with the linear probe. Subpleural consolidation; Pleural line (*) results distorted and retracted. It is possible to see a minimal quote of pleural effusion, probably reactive to the inflammatory process. For a dynamic image check the online supplement video, v1

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Sometimes, in the context of consolidations, we can recognize hyperechoic intraparenchymal images consisting of few millimetres spots or tree-shaped structures: the so called “air bronchograms”. They can be either dynamic, when moving synchronous with tidal ventilation, or static, when no movement is detected. Dynamic behavior indicates patency of airways as it seems to be generated by the movement of air within the bronchi, while an absent or static bronchogram indicates that there is no gas transit in the corresponding airway. (Figs. 7 and 8, video v2–3 in online supplement material).

Fig. 7
figure 7

Image acquired with curvilinear probe, in a patient with nosocomial pneumonia. The image shows right inferior lobe, completely consolidated. It is possible to note some static air bronchogram in the context. In the lower and upper region pleural effusion (star keys). Probably there is a fibrinous effusion that makes consolidated parenchyma with the parietal pleura adhere to the diaphragm (arrow). This image is part of the online supplement video v2

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Fig. 8
figure 8

Image acquired with curvilinear probe The left lung scanned in coronal plane at its base. Lobar pneumonia caused by Enterobacter aerogenes. A static arboriform air bronchogram is visible (arrow). Star key: pleural effusion. Ao: Aorta. Look for the online supplement video v3 to note the completely loss of aeration of parenchyma. Lung pulse (sinchronous movement of parenchyma with the heart pulse) is also present

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Bronchograms may help distinguish infective consolidation from resorptive atelectasis. The dynamic bronchogram, in fact, is a specific sign of pneumonia, with a 94% specificity and a 97% positive predictive value for the diagnosis and helps rule out atelectasis as the movement of air, by definition, cannot be detected in atelectasis. Nevertheless, a static or absent bronchogram can be present in both conditions, and is detected in most cases of late resorptive atelectasis, and in one third of cases of pneumonia [36].

Less frequently, we can also recognize a “fluid bronchogram” within the consolidated parenchyma, which is seen as a tubular, echo-free structure, that reflects a stenotic airway filled with exudate, and that can be differentiated from vascular structures using color Doppler [35].

Sonographic findings in interstitial pneumonia reflect the underlying inflammatory process; this is characterised by thickened subpleural interlobular septa, as a result of fibroblast proliferation and increased number of collagen fibres. B-lines are the principal sonographic artifacts seen in interstitial pneumonia and their number correlates with the extent of fibrosis and reticular pattern. They are generally diffuse in both lungs, with a non-homogeneous distribution; areas of B lines alternate with spared areas of A-lines, and are likely non-gravity distributed, feature that help differentiate interstitial pneumonia from pulmonary congestion in heart failure or end stage renal disease (where B-lines are diffuse, homogeneous, bilateral and gravity distributed) (Fig. 9).

Fig. 9
figure 9

Image acquired with linear probe. B-lines in a patient with community acquired pneumonia. Star key: pleural line. This image is part of video v4 in the online supplement material

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Pleural involvement is typical in interstitial pneumonia. It demonstrates alterations of the sonographic pleural line, which looks thick (more than 2 mm), irregular and fragmented, with multiple spots of small subpleural consolidation and abolished lung sliding, resulting from pleural layers adherences [37].

Ultrasound in COVID-19

Coronavirus disease 19 (COVID-19) is the viral pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that, starting as an epidemic cluster in Wuhan, a city in the Hubei Province of China, in November 2019, spreaded worldwide and became a pandemic emergency with 109.068.745 confirmed cases and 2.409.011 deaths, at the time of writing [45].

It has a wide range of clinical presentations, from asymptomatic or mild disease with fever, cough, loss of smell and taste and fatigue, to severe forms of pneumonia or even critical forms of respiratory and multiorgan failure.

In the context of a pandemic infective disease, lung ultrasound has become a valuable tool in diagnosis, evaluation of severity and monitoring in every setting: from home to emergency department and ICU. As previously mentioned, LUS was already part of the everyday clinical practice, thanks to its characteristics of rapidity, point-of-care feasibility and short learning curve; moreover, during the pandemic the possibility of performing a complete examination of the chest without moving the patient reduced the number of healthcare providers exposed [46].

To describe COVID-19 behavior, Gattinoni et al. [47] proposed two phenotypes: “Type L, characterized by Low elastance (i.e., high compliance), Low ventilation-to-perfusion ratio, Low lung weight and Low recruitability”, with predominant groundglass opacities; “Type H, characterized by High elastance, High right-to-left shunt, High lung weight and High recruitability”, where lobar consolidations may be evidenced. This pattern seems to correspond to a more advanced stage of the disease, with a decrease in gas volume and increased oedema.

In COVID-19 we can describe all LUS findings typical of pneumonia: B-lines may be separated, coalescent, with areas of white lung and spared areas of A-lines. Pleural line can be regular in some regions, but often it is irregular, thick and fragmented (Fig. 10), with subpleural consolidations and abolished lung sliding, or with large consolidations, typical of phenotype H [48,49,50].

Fig. 10
figure 10

Image from a COVID 19 patient, acquired with a curvilinear probe. Note the pleural thickness and irregularity, with few B-lines. Search for video v5 on online supplement material

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An artifact firstly described in COVID-19 pneumonia, that seems to be typical of it, is a shining vertical band arising from a large portion of pleural line, that appears and disappears with respiration, sometimes with a normal A-pattern visible on the background. This image has been called the “light beam” [38] and seems the result of an acute phase of groundglass opacity, as it reflects the presence of lesions next to preserved areas of parenchyma [48].

Usefulness of Lung Ultrasonography in Pneumonia

LUS is a non-invasive technique that is very advantageous for a lot of reasons. It is readily available almost everywhere and in different clinical settings (emergency departments, intensive care units, wards, and also in out of hospital settings); it can be practiced by members of various medical specialties and is characterized by a steep learning curve with minimal costs and biological impact.

In addition, POCUS is typically performed at the bedside without the need to move the patient to the radiology department, and this is particularly notable for ICU patients, especially those with severe respiratory failure and hemodynamic instability.

LUS is often chosen for its rapidity and ability to provide rapid answers to clinical questions and confirm or exclude alternative diagnostic hypothesis in a few minutes. An expert operator can perform the exam in 5–15 min [30] and this rapidity of execution makes it available for following up pathologic processes, and checking the response to therapies.

Daily LUS monitoring has been successfully applied to estimate antibiotic-induced reaeration in ventilator-associated pneumonia (VAP) [45].

Limitations of Lung Ultrasonography in Pneumonia

While there are advantages offered by LUS, there are some limits clinicians must be aware of:

  • Physicians should always be aware that LUS is a layer technique, therefore it can only detect consolidations that reach the pleural line. Therefore, visualization of consolidations is dependent on their distance from the pleura and the size of consolidations. Hence, LUS may miss findings with minimal or no extension to the peripheral field (e.g. pneumonias located centrally, deep within the lung) [7]

  • POCUS is an operator-dependent examination, and the co-existence of different scoring systems and scanning protocols to grade lung aeration may be confusing for the non-experts. Thus, novel automated ultrasound techniques could be considered as ‘a second opinion’ in order to create a unique quantification system, standardize diagnostic and monitoring scores and reduce inter and intra-observer variability, especially when LUS is handled by novice operators [11, 46,47,48,49].

  • Pneumonia is a frequent complication in patients with COPD, but it is not always easy to distinguish it from a COPD exacerbation. Moreover, in COPD, POCUS has not been widely used as the acoustic window is believed to be unfavourable due to the large air content, particularly in patients with lung hyperinflation [50].

  • Lung consolidation with massive aeration loss is a differential diagnoses between atelectasis and pneumonia. In mechanically ventilated patients, the presence of atelectasis is very common. During examination, we can observe some clues that can guide us towards the correct diagnosis. For example, the presence of abundant pleural effusion can imply a compression atelectasis; generally, the presence of a dynamic air bronchogram excludes obstructive atelectasis, however, its absence doesn’t rule out pneumonia. In fact, a study involving examination of ICU patients with alveolar consolidation and bronchograms, demonstrated that static air bronchograms were seen in most resorptive atelectasis but also in almost 30% of cases of pneumonia [36]. Interpretation of POCUS findings within the clinical context is thus fundamental in POCUS practice.

Conclusions

Pneumonia can be diagnosed and followed up by LUS that has been shown to have an excellent diagnostic accuracy in most cases. In the critically ill patients, especially those on invasive mechanical ventilation, the physician should be aware that positive end expiratory pressure may hamper the visualization of some subpleural consolidations or B-lines. LUS represents a layer technique, thus a CT scan should be performed if the clinical suspicious of non-subpleural pulmonary consolidation is suspected or in order to characterize a pulmonary consolidation with complete loss of aeration; indeed air bronchograms become less pronounced with time in case of pneumonias treated with antibiotic therapy, and atelectasis and cancers usually do not reveal any air bronchogram; these consolidations are thus indistinguishable. Interpretation of images within the clinical context is mandatory.