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A hazy increase in opacity in the lung parenchyma without obscuring the underlying bronchovascular structures on chest CT is called a ground-glass pattern. Ground-glass opacities occur as a result of a wide variety of interstitial and alveolar diseases. It does not represent a specific finding. Coronaviruses are enveloped RNA viruses that can also infect many animal species. They also cause mild or severe respiratory infections in humans. The pandemic caused by SARS-CoV-2 has suddenly turned into the most important health problem of our day. Chest CT is frequently used due to the limited use of chest radiographs in COVID-19 disease. Thus, the ground glass pattern, which is the most common finding of this virus in CT, entered our lives intensively. In this article, we examined the concept of ground glass, its causes, and differential diagnosis.
Etimesgut Martyr Sait Ertürk State Hospital, Turkey
*Address all correspondence to: bahadirerturk@gmail.com
1. Introduction
In the last months of 2019, some viral pneumonia cases were detected in the city of Wuhan in China’s Hubei Province. A new type of coronavirus has been identified in the etiology of these cases. The virus has spread rapidly. It has created an epidemic in China. Then it spread all over the world, causing a pandemic that continues today. In February 2020, the World Health Organization identified COVID-19, which means coronavirus 2019 disease [1]. The virus that caused this disease was named SARS-CoV-2. Coronaviruses are enveloped RNA viruses that can also infect many animal species. They also cause mild or severe respiratory infections in humans. Previously, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infected humans and caused epidemics in 2002 and 2012, respectively [2]. But the pandemic caused by the SARS-CoV-2 virus, which continues today, overwhelmingly outperformed these two viruses both in terms of the number of infected people and their spread around the world, according to the epidemics caused by SARS-CoV and MERS-CoV [3]. As of May 7, 2022, more than 516 million cases have been detected worldwide. More than 6.2 million patients died from this disease.
Some of the patients have the disease asymptomatically, while others have it symptomatically. Clinically objective abnormal findings are detected in some asymptomatic patients. In the study of Hu et al., thoracic tomography was performed on patients with asymptomatic infection, and typical ground-glass opacities or patchy shadowing was detected in half of the patients, and atypical imaging abnormalities were detected in 20% (Figures 1 and 2), [4]. Some of the asymptomatic patients may become symptomatic over time.
Figure 1.
A 31-year-old male with coronavirus disease 2019 pneumonia. Ground-glass opacities (GGO) and atelectasis.
Figure 2.
A 65-year-old male with coronavirus disease 2019 pneumonia. Subpleural patchy infiltration.
Symptomatic disease can also be examined under three categories: mild illness, severe illness, and critical illness. There is a chance that mild disease accounts for the majority of cases. The incubation period for COVID-19 is within the first 14 days after exposure. In most cases, the disease occurs about 5 days after exposure [5]. Cough, myalgia, and headache are the most commonly reported symptoms in patients with symptomatic COVID-19. There are no specific symptoms to distinguish COVID-19 from other infectious diseases [6]. Symptoms such as fever and cough and parameters such as oxygen saturation and lung auscultation findings are the first and most easily accessible diagnostic information. Such information can be used to categorize COVID-19 disease and to select patients for further diagnostic testing. At the preanalytical stage, obtaining the appropriate respiratory tract sample at the right anatomical site at the right time is essential for the molecular diagnosis of COVID-19. At the analytical stage, real-time reverse transcription PCR (RT-PCR) tests are the preferred molecular test method for the etiological diagnosis of SARS-CoV-2 infection [7]. Pneumonia is a common serious symptom of infection, characterized mainly by fever, cough, dyspnea, and bilateral infiltrates on lung imaging. Methods such as chest radiography, chest computed tomography, and pulmonary ultrasonography are used for imaging the lungs.
Although chest radiography is a low-cost and easily accessible method, it has low sensitivity in screening patients with COVID-19. It may be useful in the evaluation of complications such as pneumothorax and pleural effusion in the follow-up of hospitalized patients (Figures 3 and 4), [8]. Chest radiographs may be normal in early or mild disease.
Figure 3.
A 44-year-old male with coronavirus disease 2019 pneumonia. Ground-glass opacities and crazy paving pattern.
Figure 4.
A 47-year-old male with coronavirus disease 2019 pneumonia. Ground glass nodule (4 mm).
Imaging plays an important role in the diagnosis and follow-up of thoracic diseases. Different imaging modalities have advantages and disadvantages. Today, there have been advanced developments in cross-sectional imaging methods. In many cases, cross-sectional methods for chest diseases have replaced radiography. However, chest radiographs continue to play a basic role. In the first step, the priority is always chest radiography. Imaging of the thorax involves difficulties due to differences in tissue density and thickness. Chest radiography is used with different indications in both acute and chronic lung diseases. One of the most important advantages of chest radiography is the low dose radiation exposure. In an outpatient patient, chest radiography usually involves imaging with posteroanterior and left lateral projections in the inspirium.
Although chest CT is highly sensitive, it has a low specificity. To facilitate interpretation and reduce the variability of radiological reports, there are some standardizations in the reports. Among the current classifications for COVID-19, it is possible to divide radiological findings into typical, indeterminate, atypical, and negative findings. The structured report also includes an estimate of the extent of lung involvement [8]. As with chest radiographs, thoracic CT may be normal soon after the onset of symptoms. According to the Fleischner consensus, CT in COVID-19 should be used as an aid in medical triage to determine the basic pulmonary condition in patients with moderate to severe disease, to detect underlying cardiopulmonary abnormalities, to determine the cause in case of clinical worsening, to find limited resources in patients at risk of disease progression [9]. A meta-analysis of Bao et al., which included 13 studies, examined the coronavirus findings of CT. Common findings were ground-glass opacities in 83%, mixed consolidation with ground-glass opacities in 58%, pleural thickening in 52%, interlobular septal thickening in 48%, and air bronchograms in 46% (Figure 5). Other less common findings were crazy paving pattern, bronchiectasis, pleural effusion, pericardial effusion, and lymphadenopathy (Figures 6 and 7), [10].
Figure 5.
A 43-year-old female with coronavirus disease 2019 pneumonia. Consolidation with air bronchograms.
Figure 6.
A 56-year-old male with coronavirus disease 2019 pneumonia. Ground-glass opacification (GGO) and consolidation with air bronchograms.
Figure 7.
A 40-year-old female with coronavirus disease 2019 pneumonia. Ground-glass opacification (GGO) with inter-intralobular septal thickening and crazy paving pattern.
Chest CT has managed to become one of the indispensable diagnostic methods of today. The main disadvantage is the relatively high radio exposure. The risk of carcinogenesis from a CT scan is much lower than the benefit of screening for the appropriate indication [11]. Therefore, physicians should not hesitate to have the necessary CT scans due to radiation concerns [12]. The thickness of routine CT scan sections ranges from 3 to 5 mm. Chest CT covers the entire thorax from the apex of the lungs to the posterior costophrenic angles. Screening is mostly done in the supine position. The vast majority of cases are shot without giving a contrast agent. However, contrast material is also used in some special indications (such as pulmonary embolism and aneurysm).
Pulmonary ultrasonography can be used to evaluate lung involvement in patients with suspected COVID-19 when other imaging sources are not available. Pulmonary ultrasonography can be a helpful method for monitoring in patients, especially in intensive care units where transfer to a tomography scanner is difficult [8].
Ultrasonography has benefits such as examining vascular, cardiac, and some mediastinal abnormalities, detecting the localization of pleural fluid and air collections and guiding appropriate interventions. Transesophageal ultrasonography allows examination of some mediastinal structures, heart and aorta. Endobronchial ultrasonography is used to evaluate mediastinal lymph nodes and guides biopsy for the staging of lung cancer. Transthoracic ultrasonography is used to examine the pleural and subpleural areas. It is used to detect and localize pleural effusion and to assist in thoracentesis.
A ground-glass pattern is considered to be present when there is a hazy increase in opacity in the lung parenchyma without obscuring the underlying bronchovascular structures [13]. The increase in opacity in which bronchovascular structures are not observed is called consolidation (Figure 8) [14]. Pulmonary parenchymal opafication in CT scans is divided into ground glass and consolidation (Figures 9 and 10). Ground-glass opacities are a common and important finding on CT scanning but are often difficult to detect on chest radiography.
Figure 8.
A 37-year-old male with coronavirus disease 2019 pneumonia. Ground-glass opacification (GGO) with a peripheral distribution.
Figure 9.
A 62-year-old male with coronavirus disease 2019 pneumonia. Ground-glass opacification (GGO) with inter-intralobular septal thickening.
Figure 10.
A 56-year-old male with coronavirus disease 2019 pneumonia. Ground-glass opacities (GGO) with inter-intralobular septal thickening and cysts.
Ground-glass opacities are nonspecific and can occur in a variety of diseases (Figure 11). The differential diagnosis is related to the duration of the symptoms. Ground-glass opacities associated with acute symptoms usually indicate atypical pneumonia (such as Pneumocystis pneumonia or COVID-19 viral pneumonia), edema, bleeding, aspiration, or acute hypersensitivity pneumonia. Ground-glass opacities associated with chronic symptoms are usually associated with subacute hypersensitivity pneumonia, nonspecific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP), invasive mucinous adenocarcinoma, lipoid pneumonia, and pulmonary alveolar proteinosis.
Figure 11.
A 27-year-old male with coronavirus disease 2019 pneumonia. Ground-glass opacification (GGO) with a peripheral distribution.
Although these opacities are not specific, differential diagnosis can be significantly reduced by evaluating the presence of associated signs such as concomitant nodules or reticulation (Figure 12). If the ground glass pattern does not include other interstitial or alveolar manifestations, it is called isolated. The ground-glass pattern, which includes most of both lungs, is also characterized as diffuse. Miller et al. emphasize that clinical knowledge is essential in the evaluation and differential diagnosis of patients with isolated and diffuse ground-glass patterns [15].
Figure 12.
A 41-year-old male with coronavirus disease 2019 pneumonia. Ground-glass opacities (GGO) and crazy paving pattern. Consolidation with air bronchograms and subsegmental atelectasis.
Ground-glass opacities may result from reduced air in alveolar air spaces, partial filling of alveolar air spaces, thickening of parenchymal interstitium and alveolar walls, relative increase in perfusion, or a combination of these factors [16]. Ground-glass opacities are classified into seven different groups according to their morphological patterns: diffuse, centrilobular, nodular, mosaic attenuation, crazy paving, halo sign, and reversed halo sign (Figure 13). The causes of isolated diffuse ground glass, which is also an important imaging finding of COVID-19, are shown in Table 1.
Figure 13.
A 63-year-old male with coronavirus disease 2019 pneumonia. Ground-glass opacification (GGO) with a peripheral distribution and crazy paving pattern.
Bronchiolitis Obliterans with Organizing Pneumonia (BOOP, COP)
Bronchoalveolar Carcinoma
Table 1.
Causes of ısolated diffuse ground-glass opacity [15].
Chest CT findings are variable in COVID-19 pneumonia. The typical CT findings of COVID-19 are bilateral and peripheral ground-glass opacities (Figures 14 and 15). Features such as bilaterality, involvement of the lower lobes, and extension to the pleural surfaces can help distinguish COVID-19 pneumonia from other causes of lung diseases. It should be noted that the probability that CT findings represent COVID-19 is closely related to the prevalence of SARS-CoV-2 infection in society. The period at which the CT scan is performed has a direct relationship with the imaging findings. In COVID-19 pneumonia, ground-glass opacities, consolidations, posterior and lower lobes involvement, peripheral and bilateral involvement are widely monitored, while the unilateral and central involvement, nodules, Crazy Paving Pattern, and the reversed halo sign are less monitored (Figures 16 and 17). If the prevalence of disease in society is high, even atypical involvement is likely to represent COVID-19. Conversely, if the prevalence of the disease is low, the CT findings, which are quite typical for COVID-19, may have been caused by another disease [17].
Figure 14.
A 45-year-old male with coronavirus disease 2019 pneumonia. Ground-glass opacification (GGO) with a peripheral distribution and pneumothorax.
Figure 15.
A 21-year-old female with coronavirus disease 2019 pneumonia. Pneumomediastinum.
Figure 16.
A 28-year-old female with coronavirus disease 2019 pneumonia. Multilober ground-glass opacities (GGO) and subpleural consolidation.
Figure 17.
A 40-year-old male with coronavirus disease 2019 pneumonia. Linear atelectasis.
Unlike COVID-19, bacterial pneumonias characteristically produce focal segmental or lobar pulmonary opacities. Complications such as cavitation, lung abscess, lymphadenopathy, parapneumonic effusions, empyema, and associated tomography findings are not monitored in COVID-19 unless patients are superinfected with bacterial pneumonia. Therefore, these findings are distinctive in imaging [18]. Pneumocystis jirovecii is a common opportunistic infection that usually causes pneumonia in immunosuppressed patients. Pneumocystis jirovecii pneumonia has diffuse ground-glass opacities in CT. Unlike COVID-19, it occurs in immunosuppressed patients and more often in the upper lobes of the lungs.
Viruses are the most common cause of respiratory tract infections. The clinical signs and symptoms of viral pneumonia are diverse. The immunization status of the host is an important criterion for determining the prognosis of pneumonia. CT findings of viral pneumonias can be examined in four different categories: ground-glass opacities and consolidation, nodules, micronodules and tree-in-bud opacities, interlobular septal thickening, bronchial and/or bronchiolar wall thickening (Figures 18 and 19) [19]. One of these findings that may be confused with COVID-19 pneumonia is ground-glass opacities. Many viruses, such as cytomegalovirus (CMV), herpes simplex virus (HSV), respiratory syncytial virus, adenovirus, and influenza viruses, produce ground-glass opacities in CT.
Figure 18.
A 32-year-old male with coronavirus disease 2019 pneumonia. Ground-glass opacification (GGO) with a peripheral distribution. Pleural effusion and fibroatelectatic bands.
Figure 19.
A 61-year-old male with coronavirus disease 2019 pneumonia. Ground-glass opacification (GGO) with a peripheral distribution. Fibrosis and inter-intralobular septal thickening.
Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, occurs as a result of inhalation of organic or inorganic particles by sensitive people [20]. In acute cases, the capillary permeability secondary to the allergy increases and leads to pulmonary edema. The disease is divided into acute, subacute, and chronic phases. In the acute phase, the ground-glass opacities are monitored as diffuse.
Desquamative interstitial pneumonia (DIP) is characterized by interstitial inflammation and fibrosis following the accumulation of alveolar macrophages [21]. CT scans show diffuse ground-glass opacities in many patients.
Respiratory-bronchiolitis-associated interstitial lung disease (RBILD) is a rare, mild inflammatory lung disease [22]. Central and peripheral bronchial wall thickening and centrilobular nodules are detected in CT, and ground-glass opacities associated with centrilobular emphysema are monitored in the upper lobes.
Nonspecific interstitial pneumonia is a histological subtype of idiopathic interstitial pneumonia [23]. CT scans monitor ground-glass opacities, various amounts of interstitial changes, and honeycomb appearance in most patients.
Acute interstitial pneumonia (AIP) is an acute, fast-progressing idiopathic lung disease that often leads to fulminant respiratory failure and acute respiratory distress syndrome (ARDS) [24]. Ground-glass opacities and alveolar consolidations accompanied by traction bronchiectasis are monitored on CT.
Lymphocytic interstitial pneumonia (LIP) is a rare lung disease on the spectrum of benign pulmonary lymphoproliferative disorders. Ground-glass opacities, centrilobular and subpleural nodules, and randomly distributed thin-walled cysts are observed on CT [25].
Sarcoidosis is a multisystemic granulomatous disease that affects people of all ages, especially young adults [26]. Sarcoidosis has a wide range of CT findings. Ground-glass opacities are rarely detected.
Pulmonary edema consists of imbalances in the starling forces that manage the transport of liquids between the vascular and interstitial gaps of the lung [15]. Pulmonary edema etiology is examined in two subcategories: hydrostatic pulmonary edema and edema due to increased permeability. Hydrostatic pulmonary edema is most commonly monitored in left heart failure. Pulmonary edema due to increased permeability is most often the result of Acute Respiratory Distress Syndrome (ARDS). The most common symptom of cardiogenic pulmonary edema on CT is isolated diffuse ground-glass opacities. ARDS is the most common cause of non-cardiogenic pulmonary edema. Bilateral ground-glass opacities and pulmonary consolidation are monitored on CT.
Diffuse alveolar hemorrhage is a potentially life-threatening clinical syndrome that leads to rare respiratory failure [27]. Diffuse ground-glass opacities and consolidation are often observed on CT.
Pulmonary drug toxicity is increasingly diagnosed as a cause of acute and chronic pulmonary disease. Drugs that can cause pulmonary edema due to increased permeability include cyclophosphamide, bleomycin, carmustine and methotrexate. The toxicity of these drugs causes ground-glass opacities on CT [28].
Pulmonary alveolar proteinosis (PAP) is a syndrome characterized by the accumulation of alveolar surfactants and dysfunction of alveolar macrophages [29]. Isolated diffuse ground-glass opacities and their associated interlobular septa thickenings are observed on CT.
Organized pneumonia is a consequence of the inability to fully resolve inflammation in the distal lung structures (alveoli, alveolar ducts, and respiratory bronchioles) [30]. Organized pneumonia with bronchiolitis obliterans is a histological pattern of lung damage. CT usually shows multifocal alveolar opacities scattered throughout the lungs. It is rarely accompanied by isolated diffuse ground-glass opacities.
The United States Preventive Services Task Force recommends screening for lung cancer with low-dose computed tomography (LDCT) in adults between the ages of 55 and 80 who have given up in the last 15 years or have a history of smoking 30 pack-years of smoking and still smoke [31]. Effective screening should be limited to individuals at high risk of death from lung cancer. It should be noted that false-positive results indicate a risk of harm due to overdiagnosis and unnecessary invasive tests. As a result of these scans, physicians will encounter more ground-glass opacities. In the study of Lee et al., it was revealed that a significant part of permanent ground-glass opacities may be adenocarcinoma, and the risk of invasion will increase as the diameter increases [32]. Predicting the biological behavior of a tumor based on the findings of computed tomography has significant effects on the choice of treatment. Patients with tumors with ground-glass opacity may be the group that benefits most from sublobar resection or, from another perspective, may not have to endure overtreatment with more extensive lung resection [33].
Bronchoalveolar carcinoma, a type of well-differentiated pulmonary adenocarcinoma, has a wide variety of radiographic appearances, including solitary pulmonary nodules, pneumonia-like focal alveolar opacities, ground-glass nodules, diffuse alveolar consolidation, and isolated diffuse ground-glass opacities [15].
The current staging system for lung cancer does not distinguish between tumors with and without ground-glass opacity. In the study of Watanabe et al., it was revealed that non-small-cell lung tumors with a solid component smaller than 3 cm accompanied by a ground glass component had a better prognosis compared with completely solid ones [34]. Therefore, clinical stage IA non-small-cell lung cancers should be evaluated separately as ground-glass opacity tumors and pure solid tumors. So if even the presence of a small ground-glass component in clinical stage I non-small-cell lung cancer is so protective, is this feature associated with a similar benefit in patients with larger tumors? [35]. Time and new studies will show that ground-glass opacities occur in many diseases. With the emergence of COVID-19, it has gained an important place in chest CT. In case of detection on CT, the morphology and distribution of these opacities should be revealed first. Then, a differential diagnosis should be made in the light of clinical history and examination findings. The use of such a systemic approach will play a key role in the success of diagnosis and treatment. It should be noted that the detection of this finding will also help in early diagnosis, differential diagnosis, and assessment of pulmonary activity.
In the twenty-first century, humans have three pandemics associated with coronaviruses: SARS, MERS, and COVID-19 [36]. Different strategies for effective vaccines and therapeutic combinations must be developed as soon as possible to deal with these viral pandemics. It will all become clear in time whether the SARS-CoV-2 virus will turn into an endemic virus. Lack of effective surveillance or adequate response could enable a new pandemic of SARS-CoV-2 [37]. There are many lessons to come out of this pandemic. But the most important one is to work together as a global community [38].
In summary, a hazy increase in opacity in the lung parenchyma without obscuring the underlying bronchovascular structures on chest CT is called a ground-glass pattern. Ground-glass opacities occur as a result of a wide variety of interstitial and alveolar diseases. The pandemic caused by SARS-CoV-2 has suddenly turned into the most important health problem of our day. Chest CT is frequently used due to the limited use of chest radiographs in COVID-19 disease. Thus, the ground glass pattern, which is the most common finding of this virus in CT, entered our lives intensively. Pneumonia is a common serious symptom of infection, characterized mainly by fever, cough, dyspnea, and bilateral infiltrates on lung imaging. Methods such as chest radiography, chest computed tomography, and pulmonary ultrasonography are used for imaging the lungs. Different imaging modalities have advantages and disadvantages. Today, there have been advanced developments in cross-sectional imaging methods. In many cases, cross-sectional methods for chest diseases have replaced radiography. However, chest radiographs continue to play a basic role. In the first step, the priority is always chest radiography. Although chest CT is highly sensitive, it has a low specificity. To facilitate interpretation and reduce the variability of radiological reports, there are some standardizations in the reports. Among the current classifications for COVID-19, it is possible to divide radiological findings into typical, indeterminate, atypical, and negative findings. Ground-glass opacities are classified into seven different groups according to their morphological patterns: diffuse, centrilobular, nodular, mosaic attenuation, crazy paving, halo sign, and reversed halo sign. New studies will both allow us to better recognize these viruses and improve the examination and treatment.
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Written By
Bahadır Ertürk and Zamir Kemal Ertürk
Submitted: 15 May 2022Reviewed: 10 August 2022Published: 16 November 2022
Open access peer-reviewed chapter
