Key Learning Points

Lung ultrasound (LUS) has gained increasing acceptance as a bedside imaging modality for the evaluation of pulmonary disease, particularly in critical care and emergency settings. Early work by Lichtenstein and colleagues demonstrated that ultrasound artefacts generated at the pleural interface may provide valuable diagnostic information in acute respiratory failure [1,2]. Subsequently, international consensus recommendations established LUS as a useful tool for evaluating pleural and peripheral lung pathology [3]. Despite its growing clinical application, the interpretation of lung ultrasound findings remains largely artefact based.

While artefact-based terminology has provided a useful starting point, it may inadvertently favor classification over comprehension. However, many peripheral lung diseases share common structural alterations that modify the balance between alveolar air, tissue, and blood. These changes generate reproducible acoustic patterns that may be interpreted as phenotypes, while the biological mechanisms responsible for these patterns may be viewed as Endotypes, analogous to concepts widely used in asthma and acute respiratory distress syndrome research [4,5]. Acoustic patterns should not be viewed as isolated visual entities, but as expressions of underlying biological processes shaping the lung periphery.

The aim of this study is to point out the new concept of image describing based on traditional methods of radiography and computed tomography and not in artefacts. This review proposes a conceptual framework linking lung ultrasound phenotypes with underlying biological Endotypes.

Physical Basis of Lung Ultrasound Patterns

The ultrasound appearance of the lung is determined primarily by acoustic impedance differences between air, and soft tissue. Air has extremely low acoustic impedance relative to biological tissues, producing strong reflections when ultrasound waves encounter air–tissue interfaces. In normal lung, the pleural surface and subpleural interstitial tissue act as a dominant reflective boundary that prevent deeper penetration of ultrasound waves. When pathological processes alter the composition of the peripheral lung, new acoustic interfaces emerge. Edema, inflammation, hemorrhage, or atelectasis may reduce the air–tissue ratio by increasing tissue density and/or partially replacing alveolar air, thereby modifying the distribution of air–tissue interfaces. These changes generate a limited number of acoustic phenotypes observable on lung ultrasound [2,6]. In this sense, ultrasound images do not merely reflect acoustic artefacts, but dynamic relationships between air, tissue, and vascular components.[7,8].

Lung Ultrasound Phenotypes

To facilitate interpretation, lung ultrasound phenotypes can be understood along a continuum of peripheral lung aeration, ranging from air-dominant states to tissue- and fluid-dominant conditions, with intermediate mixed patterns in between (Figure nr 1,3).

Figure 1: Lung Ultrasound Phenotypes 

Normal TWA Phenotype

The normal TWA phenotype represents the baseline acoustic configuration of the peripheral lung. It is characterized by a physiologic Twinkling White Area (TWA) beneath a smooth pleural line, reflecting preserved subpleural aeration and intact air–tissue interfaces [7,8].

All pathological lung ultrasound phenotypes may be interpreted as progressive deviations from the normal TWA phenotype, driven by alterations in the peripheral air–tissue–blood-lymph balance.

Nightfall Phenotype

The nightfall phenotype is characterized by a relative increase in the air-to-tissue ratio within the peripheral lung, reflecting processes such as air trapping, alveolar destruction, loss of the vascular tree, and regional overinflation. These biological changes result in a progressive reduction of reflective subpleural interfaces and alteration of the acoustic geometry of the Twinkling White Area (TWA), typically manifested as a decrease in TWA length and an increase in TWA width. This phenotype reflects a state of hyper-aeration with reduced tissue and vascular components, leading to diminished structural complexity at the lung periphery [9,10].

Foggy Dawn Phenotype

The foggy dawn phenotype reflects a relative increase in tissue and interstitial components within the peripheral lung without overt loss of aeration. It is associated with peribronchovascular and subpleural interstitial inflammation, as well as regional hypoventilation without overinflation. These biological processes lead to increased acoustic density and preservation of partially aerated interfaces, resulting in a relative increase in TWA length and a decrease in TWA width. This phenotype represents an intermediate state between normal aeration and consolidation, where air–tissue interactions remain present but altered [9,10].

Black Hypoechoic Density Phenotype

The black hypoechoic density phenotype refers to peripheral lung regions appearing as relatively homogeneous, markedly hypoechoic areas on lung ultrasound, often with poorly defined internal architecture and reduced internal echogenic reflections. This pattern reflects a marked reduction or near absence of residual aerated interfaces within the affected subpleural tissue. It is most commonly observed in acute inflammatory conditions such as pneumonia, where rapid alveolar filling and tissue edema produce fluid-dominant acoustic properties. Similar appearances may also occur in malignant lesions with central necrosis, where tissue breakdown and fluid accumulation create hypoechoic acoustic environments at the lung periphery.

White Reflective Phenotype

The white reflective phenotype occurs when alveolar aeration remains partially preserved despite inflammatory or interstitial changes. Numerous air–tissue interfaces generate strong reflections, producing highly reflective ultrasound patterns. This phenotype is frequently observed during early stages of viral pneumonitis and interstitial edema [11].

During the COVID-19 pandemic, early lung involvement often demonstrated highly reflective peripheral patterns corresponding to interstitial inflammation with preserved aeration [12].

Gray Peripheral Phenotype

Peripheral lung diseases may initially present as black hypoechoic subpleural lesions on lung ultrasound and later evolve into heterogeneous gray peripheral patterns as alveolar air progressively decreases and the inflammatory and vascular composition of the lesion changes over time. The gray peripheral phenotype reflects a prolonged disturbance of alveolar aeration associated with sustained inflammatory or vascular injury. As alveolar air-tissue ratio decreases due to edema, hemorrhage, or atelectasis, hypoechoic subpleural lesions emerge. With persistence over time, tissue organization, fibrosis, and necrotic changes increase lesion density, producing heterogeneous gray patterns. The recognition of the gray peripheral phenotype has important implications for differential diagnosis. Rather than indicating a single disease, this pattern defines a restricted diagnostic field that allows clinicians to move from a broad differential diagnosis (“long list”) toward a smaller group of biologically plausible conditions (“short list”). In this context, lung ultrasound phenotypes may function as a pattern-recognition filter, helping clinicians distinguish between common diseases and less frequent but clinically important entities. This approach resembles the classical diagnostic principle often referred to as the “zebra theory,” where uncommon conditions may occasionally explain atypical imaging findings when common explanations are insufficient.

This phenotype may occur in pulmonary infarction, organizing pneumonia, contraction atelectasis, and granulomatous diseases such as tuberculosis or sarcoidosis. Pulmonary infarction represents a typical vascular Endotype, where arterial occlusion leads to alveolar hemorrhage, necrosis and surfactant dysfunction, followed by localized atelectasis and inflammatory organization [13].

Tissue-Like Consolidation Phenotype

When alveolar air is almost completely replaced by inflammatory exudate, tissue or fluid, lung ultrasound produces a tissue-like pattern resembling hepatic parenchyma. This phenotype is commonly observed in bacterial pneumonia, atelectasis and severe alveolar filling processes [6].

Streaky Panoramic Phenotype

A streaky phenotype appears when destructive lung processes disrupt normal pulmonary architecture. In these cases, ultrasound images reveal multiple elongated echogenic streaks extending across the field of view, producing a streaky panoramic appearance. This pattern may occur in lung abscesses, cavitary lung cancer, bronchiectasis with inflammatory destruction, infected pulmonary bulla, or ruptured pulmonary echinococcal cysts.

Fibro-Inflammatory Hyper-Echogenic Phenotype

Chronic inflammatory diseases associated with fibrosis may produce clusters of hyper-echogenic densities within hypoechoic heterogeneous lesions. In these cases, acoustic interfaces arise primarily from fibrotic and inflammatory tissue interfaces   rather than from air–tissue boundaries. This phenotype may be encountered in advanced tuberculosis, sarcoidosis, chronic bronchiectatic remodeling and end stage of diffuse lung diseases These patterns appear not as isolated visual signatures, but as consistent acoustic expressions of underlying biological states.

Biological Endotype of Peripheral Lung Injury

Several biological mechanisms may generate similar acoustic phenotypes:

Rather than representing fixed diagnostic categories, endotypes reflect dominant biological mechanisms that shape the acoustic phenotype. 

Peribronchovascular–Subpleural Interstitial Inflammatory endotype

 (Foggy Dawn-associated) The corresponding Endotype is characterized by predominant interstitial inflammation involving both the peribronchovascular and subpleural interstitial tissue. This process is associated with increased interstitial cellular infiltration and fluid accumulation in interstitial compartments leading to a relative increase in tissue density without complete loss of aeration. In addition, regional hypoventilation due to bronchial obstruction contributes to reduced air turnover, further altering the local air–tissue balance. Importantly, this Endotype is not associated with overinflation or structural destruction, but rather with a tissue-enriched state in which alveolar architecture remains partially preserved. The combined effect of interstitial inflammation and hypoventilation results in complex but still structured air–tissue interfaces, corresponding to the characteristic acoustic pattern of the foggy dawn phenotype.  Regional hypoventilation due to bronchial obstruction further alters the air–tissue balance. Unlike hyper aerated or destructive states, this pattern reflects a tissue-enriched but structurally preserved lung, corresponding to the foggy dawn phenotype.

Hyper-aeration with Structural Loss, Air Trapping, and Overinflation Endotype (Nightfall-associated) 

The underlying Endotype is defined by structural and functional loss of the alveolar–vascular unit, driven by mechanisms such as alveolar wall destruction, reduced capillary network, and impaired perfusion. These changes increase the relative proportion of air within the lung while reducing tissue and blood components, resulting in altered acoustic reflection and simplified subpleural architecture. The dominant pathophysiological feature is a shift toward an air-dominant state with loss of normal air–tissue–vascular interfaces.

Necrotic / Fluid-Dominant Endotype

Acute inflammatory injury may result in alveolar flooding with inflammatory exudate, cellular debris, and interstitial edema, leading to a substantial reduction in air content. In malignant disease, tumor necrosis and liquefaction may generate similar fluid-rich microenvironments. In both situations, the dominant pathophysiological mechanism is the replacement of aerated alveolar structures by fluid or necrotic material, shifting the local air–tissue balance toward a fluid-dominant state and producing the hypoechoic acoustic pattern observed on lung ultrasound.

The vascular endotype 

Encompasses processes such as vascular thrombosis, pulmonary necrosis, hemorrhage, increased hydrostatic pressure, and alterations in oncotic balance, all of which modify perfusion and the air–tissue–blood interface. 

The inflammatory endotype 

Reflects parenchymal inflammation driven by viral, bacterial, autoimmune, drug-induced, or radiation-related mechanisms, leading to increased tissue density and altered aeration. 

The granulomatous endotype 

Is characterized by structured inflammatory responses with varying stages of granuloma formation and organization.

The mechanical endotype 

Includes obstructive, compressive, or contraction atelectasis associated with impaired ventilation and surfactant dysfunction. 

Destructive Structural Endotype 

Represents advanced architectural disruption, where combinations of tissue destruction and intra-parenchymal fluid or secretions create complex air–fluid interfaces (Figure 2). 

Pleural Ultrasound Phenotypes 

Linking Morphology, Mechanisms, and Disease Lung ultrasound provides direct visualization of the pleural interface and the pleural cavity, allowing pleural abnormalities to be interpreted through recognizable morphological phenotypes. Pleural ultrasound morphology has been previously described in terms of echogenic patterns and structural characteristics of pleural fluid and pleural surfaces [14–17]. These phenotypes should not be viewed as disease-specific entities but rather as structural expressions of different biological processes occurring within the pleural space. In this framework, ultrasound phenotypes reflect underlying pleural Endotypes, which in turn may arise from a range of clinical conditions. 

The free pleural effusion phenotype

Represents the simplest structural configuration. Ultrasound demonstrated a homogeneous anechoic fluid layer separating the pleural surfaces while preserving smooth pleural boundaries and free gravitational redistribution. [15,16]. Mechanistically, this pattern reflects fluid accumulation without significant fibrin organization, typically associated with hydrostatic imbalance, reduced oncotic pressure, or early inflammatory exudation. Such mechanisms are commonly encountered in heart failure–related transudative effusions, hypoalbuminemia, early parapneumonic effusions, or early malignant pleural effusion. 

The septated pleural effusion phenotype 

Reflects progressive organization of the pleural fluid. Echogenic fibrinous strands traverse the effusion and divide it into loculated compartments, restricting fluid mobility. This morphology corresponds to Endotypes characterized by fibrin deposition and inflammatory organization within the pleural cavity [16,17]. While classically associated with empyema and tuberculous pleuritis, similar septated patterns may also occur in malignant pleural effusions where tumor-related inflammation or hemorrhage promotes fibrin formation.

The complex pleural effusion phenotype

Is characterized by heterogeneous internal echoes resulting from suspended cellular elements, fibrin aggregates, hemorrhagic components, or necrotic ones [14,16]. This phenotype reflects a pleural environment with high inflammatory or cellular activity and may be observed in complicated parapneumonic effusions, malignant pleural effusions, or hemothorax. Alterations of the pleural surface itself produce distinct structural phenotypes. 

The pleural thickening phenotype 

manifests as focal or diffuse enlargement of the pleural line, frequently associated with irregular contours, increased echogenicity, and reduced pleural sliding. This pattern reflects Endotypes related to chronic pleural remodeling, fibrotic transformation, or tumor infiltration, as encountered in chronic pleuritis, asbestos-related pleural disease, or pleural metastases [17-21]. 

The pleural nodular phenotype

Is defined by focal nodules or mass-like protrusions arising from the pleural surface, producing an irregular pleural profile and heterogeneous acoustic reflections. These structures typically reflect infiltrative or proliferative Endotypes of the pleura, most commonly associated with pleural metastases, mesothelioma, or granulomatous pleuritis [17,18,20,21]. 

Pleural separation phenotype

 In acute microbial pleuritis, the inflammatory process is characterized by edema, fibrin deposition, and a reactive exudate that increases pleural reflectivity but keeps adherence between layers. Consequently, the pleural complex appears thickened but unified. In contrast, during chronic or post-inflammatory stages, fibrosis, focal retraction, or partial detachment of the visceral pleura can create a pleura separation. This may produce two parallel hyper echoic lines — the parietal and visceral pleurae - separated by a narrow hypo echoic interspace corresponding to fibrotic or residual fluid tissue. Thus, the probability of visualizing separated pleural layers may be lower in acute inflammation (due to adhesion and exudate) and higher in chronic pleuritic remodeling (due to fibrosis and mechanical decoupling) [22] (Table 1, 2). Taken together, pleural ultrasound phenotypes represent different structural expressions of pleural interface alteration. Interpreting these patterns within a phenotype–Endotype framework may help bridge ultrasound morphology with the biological mechanisms shaping pleural disease. This approach allows ultrasound findings to be interpreted within a physiological and pathological context, rather than as isolated acoustic events.

Diagnostic Value of Spatial Patterns in Lung Ultrasound Phenotypes

The anatomical distribution of lung lesions may provide additional diagnostic clues. Granulomatous diseases frequently involve the apical lung zones, whereas vascular processes such as pulmonary infarction tend to affect posterior, basal lung regions. Diffuse inflammatory diseases such as viral pneumonitis, connective tissue diseases often involve the basal part of peripheral lung bilaterally.

Lung ultrasound reveals a structured spectrum of reproducible acoustic phenotypes that reflect structural responses of the peripheral lung to injury. These phenotypes arise from multiple biological Endotypes affecting the balance between alveolar air, tissue, lymph, and blood. Integrating acoustic phenotypes with their biological Endotypes and spatial distribution may provide a more pathophysiologically grounded framework for interpreting lung ultrasound findings. In this review, we introduce several conceptual descriptors for peripheral lung ultrasound morphology, including the terms” nightfall “phenotype, “foggy dawn” phenotype, streaky panoramic phenotype,” heterogeneous gray hypo echoic density,” phenotype, “fibro-inflammatory hyper echoic density,” phenotype, “pleural rupture phenotype”, and “pleural separation” phenotype. These terms are proposed as descriptive phenotypic categories reflecting different air–tissue–vascular configurations at the lung periphery. 

This phenotype–Endotype framework may help bridge the gap between traditional artefact-based lung ultrasound interpretation and a more biologically grounded understanding of peripheral lung pathology. Lung ultrasound phenotypes may function as a clinically useful pattern-recognition filter, helping clinicians distinguish between common diseases and less frequent but clinically important entities. In this context, lung ultrasound becomes not only a tool for detection, but a means of interpretation, bridging image and biology at the bedside.  It is time to move beyond uncertainty and toward consistent clinical application.” Here we are no longer in "what if", but in "let's do it"