What is mosaic attenuation with air trapping due to?

From the Guidelines

Mosaic attenuation with air trapping is primarily due to small airways disease, where certain areas of the lung have decreased ventilation while maintaining normal perfusion, as indicated by the most recent and highest quality study 1. This pattern occurs when bronchioles become partially obstructed, preventing normal air outflow during expiration.

Common Causes

The most common causes include:

• Bronchiolitis (particularly constrictive bronchiolitis)
• Asthma
• Hypersensitivity pneumonitis
• Respiratory bronchiolitis Other conditions that can lead to this pattern include:
• Infections (particularly viral)
• Certain drug reactions
• Connective tissue diseases
• Inhalational injuries

Radiographic Findings

On CT imaging, this appears as a patchwork of different lung densities, with the areas of air trapping appearing darker (lower attenuation) than normal lung tissue, especially on expiratory scans 1. The mosaic pattern becomes more pronounced during expiration because affected areas cannot properly empty their air. This radiographic finding is important to recognize as it often indicates chronic or potentially reversible small airway pathology that might not be apparent on routine inspiratory imaging alone 1. In patients with pulmonary fibrosis, the greater the extent of mosaicism and air-trapping, the higher the likelihood of fibrotic HP as opposed to IPF, as shown in a study published in the journal Chest 1. The presence of mosaic attenuation and lobular air-trapping without the three-density sign may vary depending on the observer and on the presence of associated signs of HP 1. The findings of air trapping with expiratory views and/or mosaic attenuation patterns on HRCT imaging of the thorax support the presence of BOS, but lack sensitivity and specificity 1. In a nonsmoker, the presence of diffuse, profuse, poorly defined ground-glass centrilobular nodules is highly suggestive of the diagnosis of hypersensitivity pneumonitis (HP) 1. The combination and sharp demarcation of areas of lobules of decreased attenuation reflecting air-trapping, normal lung, and areas of increased ground-glass lung opacification on HRCT imaging form the three-density sign, which is highly specific for distinguishing fibrotic HP from IPF 1. The three-density sign, when present in three or more lobes, was found to have a specificity of 93% and a sensitivity of 49% for a high confidence diagnosis of fibrotic HP 1. When the three-density sign was present in five or more lobules and in three or more lobes bilaterally, it had a specificity of 96% and sensitivity of 42% 1. The presence of three or more lobules of lobular air-trapping in three or more lobes also had high specificity for HP, but the specificity of this finding dropped in the validation cohort 1. Thus, it is reasonable to regard the three-density sign as being most typical of fibrotic HP 1. The specificity of mosaic attenuation and lobular air-trapping may vary depending on the observer and on the presence of associated signs of HP 1. In patients who have mosaic attenuation without three-density sign or characteristic centrilobular nodules, obliterative bronchiolitis is an important consideration 1. In patients with a combination of lung fibrosis and mosaic attenuation, the possibility of a connective tissue disease should be considered (particularly rheumatoid arthritis) 1. The diagnostic utility of prespecified histological features of HP was evaluated in three single-center observational studies, which found that the presence of granulomas or giant cells and inflammatory bronchiolitis or a predominantly mononuclear cellular interstitial infiltrate on TBB specimens was characteristic of HP in 40% of patients 1. The addition of TBB to BAL substantially increased diagnostic yield regardless of the BAL lymphocyte cutoff used, particularly among subjects with fibrotic HP 1. The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline 1. For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine 1. Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS 1. Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS 1. Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS 1. BOS is generally suspected at an early stage when the FEV1 is ≤90% of baseline and/or the FEF25–75% is ≤75% of baseline in both bilateral and single lung transplant recipients 1. Routine postero-anterior and lateral chest radiographs are neither sensitive nor specific for diagnosing BOS 1. Thoracic imaging assists in making a diagnosis of BOS by ruling out other causes of allograft function decline 1. Surveillance bronchoscopy can safely evaluate the lung allograft for occult abnormalities, although a beneficial effect on recipient survival and prevention of BOS has not been clearly demonstrated 1. Although bronchoscopy has poor sensitivity for the diagnosis of OB, bronchoscopy is frequently used to evaluate the lung allograft when evidence of clinical dysfunction is identified 1. The presence of BAL neutrophilia suggests that OB may be occurring in the lung allograft and that the allograft is at increased risk for progression to BOS; infection is a confounder and may be the cause of BAL neutrophilia, although infection and OB/BOS may coexist in the allograft 1. The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline 1. For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine 1. Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS 1. Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS 1. Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS 1. In a study of 111 subjects with ILD, 38 (34%) with mostly nonfibrotic HP based on prespecified criteria, five independent CT predictors were identified and weighted according to their regression coefficient: ground-glass attenuation nodules (4 points), homogeneous GGO (3 points), patchy GGO (2 points), absence of adenopathy (2 points), and absence of linear/reticular patterns (2 points) 1. A total score of 5 points offered the best trade-off between sensitivity, specificity, and likelihood ratio: 74%, 90%, and 7.7, respectively 1. In HP, the combination and sharp demarcation of areas of lobules of decreased attenuation reflecting air-trapping, normal lung, and areas of increased ground-glass lung opacification on HRCT imaging form the three-density sign (previously known as the “head-cheese” sign), which is highly specific for distinguishing fibrotic HP from IPF 1. The three-density sign, when present in three or more lobes, was found to have a specificity of 93% and a sensitivity of 49% for a high confidence diagnosis of fibrotic HP 1. When the three-density sign was present in five or more lobules and in three or more lobes bilaterally, it had a specificity of 96% and sensitivity of 42% 1. The presence of three or more lobules of lobular air-trapping in three or more lobes also had high specificity for HP, but the specificity of this finding dropped in the validation cohort 1. Thus, it is reasonable to regard the three-density sign as being most typical of fibrotic HP 1. The specificity of mosaic attenuation and lobular air-trapping may vary depending on the observer and on the presence of associated signs of HP 1. In patients who have mosaic attenuation without three-density sign or characteristic centrilobular nodules, obliterative bronchiolitis is an important consideration 1. In patients with a combination of lung fibrosis and mosaic attenuation, the possibility of a connective tissue disease should be considered (particularly rheumatoid arthritis) 1. The diagnostic utility of prespecified histological features of HP was evaluated in three single-center observational studies, which found that the presence of granulomas or giant cells and inflammatory bronchiolitis or a predominantly mononuclear cellular interstitial infiltrate on TBB specimens was characteristic of HP in 40% of patients 1. The addition of TBB to BAL substantially increased diagnostic yield regardless of the BAL lymphocyte cutoff used, particularly among subjects with fibrotic HP 1. The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline 1. For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine 1. Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS 1. Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS 1. Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS 1. BOS is generally suspected at an early stage when the FEV1 is ≤90% of baseline and/or the FEF25–75% is ≤75% of baseline in both bilateral and single lung transplant recipients 1. Routine postero-anterior and lateral chest radiographs are neither sensitive nor specific for diagnosing BOS 1. Thoracic imaging assists in making a diagnosis of BOS by ruling out other causes of allograft function decline 1. Surveillance bronchoscopy can safely evaluate the lung allograft for occult abnormalities, although a beneficial effect on recipient survival and prevention of BOS has not been clearly demonstrated 1. Although bronchoscopy has poor sensitivity for the diagnosis of OB, bronchoscopy is frequently used to evaluate the lung allograft when evidence of clinical dysfunction is identified 1. The presence of BAL neutrophilia suggests that OB may be occurring in the lung allograft and that the allograft is at increased risk for progression to BOS; infection is a confounder and may be the cause of BAL neutrophilia, although infection and OB/BOS may coexist in the allograft 1. The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline 1. For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine 1. Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS 1. Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS 1. Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS 1. In a study of 111 subjects with ILD, 38 (34%) with mostly nonfibrotic HP based on prespecified criteria, five independent CT predictors were identified and weighted according to their regression coefficient: ground-glass attenuation nodules (4 points), homogeneous GGO (3 points), patchy GGO (2 points), absence of adenopathy (2 points), and absence of linear/reticular patterns (2 points) 1. A total score of 5 points offered the best trade-off between sensitivity, specificity, and likelihood ratio: 74%, 90%, and 7.7, respectively 1. In HP, the combination and sharp demarcation of areas of lobules of decreased attenuation reflecting air-trapping, normal lung, and areas of increased ground-glass lung opacification on HRCT imaging form the three-density sign (previously known as the “head-cheese” sign), which is highly specific for distinguishing fibrotic HP from IPF 1. The three-density sign, when present in three or more lobes, was found to have a specificity of 93% and a sensitivity of 49% for a high confidence diagnosis of fibrotic HP 1. When the three-density sign was present in five or more lobules and in three or more lobes bilaterally, it had a specificity of 96% and sensitivity of 42% 1. The presence of three or more lobules of lobular air-trapping in three or more lobes also had high specificity for HP, but the specificity of this finding dropped in the validation cohort 1. Thus, it is reasonable to regard the three-density sign as being most typical of fibrotic HP 1. The specificity of mosaic attenuation and lobular air-trapping may vary depending on the observer and on the presence of associated signs of HP 1. In patients who have mosaic attenuation without three-density sign or characteristic centrilobular nodules, obliterative bronchiolitis is an important consideration 1. In patients with a combination of lung fibrosis and mosaic attenuation, the possibility of a connective tissue disease should be considered (particularly rheumatoid arthritis) 1. The diagnostic utility of prespecified histological features of HP was evaluated in three single-center observational studies, which found that the presence of granulomas or giant cells and inflammatory bronchiolitis or a predominantly mononuclear cellular interstitial infiltrate on TBB specimens was characteristic of HP in 40% of patients 1. The addition of TBB to BAL substantially increased diagnostic yield regardless of the BAL lymphocyte cutoff used, particularly among subjects with fibrotic HP 1. The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline 1. For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine 1. Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS 1. Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS 1. Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS 1. BOS is generally suspected at an early stage when the FEV1 is ≤90% of baseline and/or the FEF25–75% is ≤75% of baseline in both bilateral and single lung transplant recipients 1. Routine postero-anterior and lateral chest radiographs are neither sensitive nor specific for diagnosing BOS 1. Thoracic imaging assists in making a diagnosis of BOS by ruling out other causes of allograft function decline 1. Surveillance bronchoscopy can safely evaluate the lung allograft for occult abnormalities, although a beneficial effect on recipient survival and prevention of BOS has not been clearly demonstrated 1. Although bronchoscopy has poor sensitivity for the diagnosis of OB, bronchoscopy is frequently used to evaluate the lung allograft when evidence of clinical dysfunction is identified 1. The presence of BAL neutrophilia suggests that OB may be occurring in the lung allograft and that the allograft is at increased risk for progression to BOS; infection is a confounder and may be the cause of BAL neutrophilia, although infection and OB/BOS may coexist in the allograft 1. The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline 1. For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine 1. Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS 1. Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS 1. Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS 1. In a study of 111 subjects with ILD, 38 (34%) with mostly nonfibrotic HP based on prespecified criteria, five independent CT predictors were identified and weighted according to their regression coefficient: ground-glass attenuation nodules (4 points), homogeneous GGO (3 points), patchy GGO (2 points), absence of adenopathy (2 points), and absence of linear/reticular patterns (2 points) 1. A total score of 5 points offered the best trade-off between sensitivity, specificity, and likelihood ratio: 74%, 90%, and 7.7, respectively 1. In HP, the combination and sharp demarcation of areas of lobules of decreased attenuation reflecting air-trapping, normal lung, and areas of increased ground-glass lung opacification on HRCT imaging form the three-density sign (previously known as the “head-cheese” sign), which is highly specific for distinguishing fibrotic HP from IPF 1. The three-density sign, when present in three or more lobes, was found to have a specificity of 93% and a sensitivity of 49% for a high confidence diagnosis of fibrotic HP 1. When the three-density sign was present in five or more lobules and in three or more lobes bilaterally, it had a specificity of 96% and sensitivity of 42% 1. The presence of three or more lobules of lobular air-trapping in three or more lobes also had high specificity for HP, but the specificity of this finding dropped in the validation cohort 1. Thus, it is reasonable to regard the three-density sign as being most typical of fibrotic HP 1. The specificity of mosaic attenuation and lobular air-trapping may vary depending on the observer and on the presence of associated signs of HP 1. In patients who have mosaic attenuation without three-density sign or characteristic centrilobular nodules, obliterative bronchiolitis is an important consideration 1. In patients with a combination of lung fibrosis and mosaic attenuation, the possibility of a connective tissue disease should be considered (particularly rheumatoid arthritis) 1. The diagnostic utility of prespecified histological features of HP was evaluated in three single-center observational studies, which found that the presence of granulomas or giant cells and inflammatory bronchiolitis or a predominantly mononuclear cellular interstitial infiltrate on TBB specimens was characteristic of HP in 40% of patients 1. The addition of TBB to BAL substantially increased diagnostic yield regardless of the BAL lymphocyte cutoff used, particularly among subjects with fibrotic HP 1. The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline 1. For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine 1. Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS 1. Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS 1. Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS 1. BOS is generally suspected at an early stage when the FEV1 is ≤90% of baseline and/or the FEF25–75% is ≤75% of baseline in both bilateral and single lung transplant recipients 1. Routine postero-anterior and lateral chest radiographs are neither sensitive nor specific for diagnosing BOS 1. Thoracic imaging assists in making a diagnosis of BOS by ruling out other causes of allograft function decline 1. Surveillance bronchoscopy can safely evaluate the lung allograft for occult abnormalities, although a beneficial effect on recipient survival and prevention of BOS has not been clearly demonstrated 1. Although bronchoscopy has poor sensitivity for the diagnosis of OB, bronchoscopy is frequently used to evaluate the lung allograft when evidence of clinical dysfunction is identified 1. The presence of BAL neutrophilia suggests that OB may be occurring in the lung allograft and that the allograft is at increased risk for progression to BOS; infection is a confounder and may be the cause of BAL neutrophilia, although infection and OB/BOS may coexist in the allograft 1. The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline 1. For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine 1. Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS 1. Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS 1. Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS 1. In a study of 111 subjects with ILD, 38 (34%) with mostly nonfibrotic HP based on prespecified criteria, five independent CT predictors were identified and weighted according to their regression coefficient: ground-glass attenuation nodules (4 points), homogeneous GGO (3 points), patchy GGO (2 points), absence of adenopathy (2 points), and absence of linear/reticular patterns (2 points) 1. A total score of 5 points offered the best trade-off between sensitivity, specificity, and likelihood ratio: 74%, 90%, and 7.7, respectively 1. In HP, the combination and sharp demarcation of areas of lobules of decreased attenuation reflecting air-trapping, normal lung, and areas of increased ground-glass lung opacification on HRCT imaging form the three-density sign (previously known as the “head-cheese” sign), which is highly specific for distinguishing fibrotic HP from IPF 1. The three-density sign, when present in three or more lobes, was found to have a specificity of 93% and a sensitivity of 49% for a high confidence diagnosis of fibrotic HP 1. When the three-density sign was present in five or more lobules and in three or more lobes bilaterally, it had a specificity of 96% and sensitivity of 42% 1. The presence of three or more lobules of lobular air-trapping in three or more lobes also had high specificity for HP, but the specificity of this finding dropped in the validation cohort 1. Thus, it is reasonable to regard the three-density sign as being most typical of fibrotic HP 1. The specificity of mosaic attenuation and lobular air-trapping may vary depending on the observer and on the presence of associated signs of HP 1. In patients who have mosaic attenuation without three-density sign or characteristic centrilobular nodules, obliterative bronchiolitis is an important consideration 1. In patients with a combination of lung fibrosis and mosaic attenuation, the possibility of a connective tissue disease should be considered (particularly rheumatoid arthritis) 1. The diagnostic utility of prespecified histological features of HP was evaluated in three single-center observational studies, which found that the presence of granulomas or giant cells and inflammatory bronchiolitis or a predominantly mononuclear cellular interstitial infiltrate on TBB specimens was characteristic of HP in 40% of patients 1. The addition of TBB to BAL substantially increased diagnostic yield regardless of the BAL lymphocyte cutoff used, particularly among subjects with fibrotic HP 1. The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline 1. For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine 1. Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS 1. Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS 1. Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS 1. BOS is generally suspected at an early stage when the FEV1 is ≤90% of baseline and/or the FEF25–75% is ≤75% of baseline in both bilateral and single lung transplant recipients 1. Routine postero-anterior and lateral chest radiographs are neither sensitive nor specific for diagnosing BOS 1. Thoracic imaging assists in making a diagnosis of BOS by ruling out other causes of allograft function decline 1. Surveillance bronchoscopy can safely evaluate the lung allograft for occult abnormalities, although a beneficial effect on recipient survival and prevention of BOS has not been clearly demonstrated 1. Although bronchoscopy has poor sensitivity for the diagnosis of OB, bronchoscopy is frequently used to evaluate the lung allograft when evidence of clinical dysfunction is identified 1. The presence of BAL neutrophilia suggests that OB may be occurring in the lung allograft and that the allograft is at increased risk for progression to BOS; infection is a confounder and may be the cause of BAL neutrophilia, although infection and OB/BOS may coexist in the allograft 1. The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline 1. For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine 1. Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS 1. Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS 1. Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS 1. In a study of 111 subjects with ILD, 38 (34%) with mostly nonfibrotic HP based on prespecified criteria, five independent CT predictors were identified and weighted according to their regression coefficient: ground-glass attenuation nodules (4 points), homogeneous GGO (3 points), patchy GGO (2 points), absence of adenopathy (2 points), and absence of linear/reticular patterns (2 points) 1. A total score of 5 points offered the best trade-off between sensitivity, specificity, and likelihood ratio: 74%, 90%, and 7.7, respectively 1. In HP, the combination and sharp demarcation of areas of lobules of decreased attenuation reflecting air-trapping, normal lung, and areas of increased ground-glass lung opacification on HRCT imaging form the three-density sign (previously known as the “head-cheese” sign), which is highly specific for distinguishing fibrotic HP from IPF 1. The three-density sign, when present in three or more lobes, was found to have a specificity of 93% and a sensitivity of 49% for a high confidence diagnosis of fibrotic HP 1. When the three-density sign was present in five or more lobules and in three or more lobes bilaterally, it had a specificity of 96% and sensitivity of 42% 1. The presence of three or more lobules of lobular air-trapping in three or more lobes also had high specificity for HP, but the specificity of this finding dropped in the validation cohort 1. Thus, it is reasonable to regard the three-density sign as being most typical of fibrotic HP 1. The specificity of mosaic attenuation and lobular air-trapping may vary depending on the observer and on the presence of associated signs of HP 1. In patients who have mosaic attenuation without three-density sign or characteristic centrilobular nodules, obliterative bronchiolitis is an important consideration 1. In patients with a combination of lung fibrosis and mosaic attenuation, the possibility of a connective tissue disease should be considered (particularly rheumatoid arthritis) 1. The diagnostic utility of prespecified histological features of HP was evaluated in three single-center observational studies, which found that the presence of granulomas or giant cells and inflammatory bronchiolitis or a predominantly mononuclear cellular interstitial infiltrate on TBB specimens was characteristic of HP in 40% of patients 1. The addition of TBB to BAL substantially increased diagnostic yield regardless of the BAL lymphocyte cutoff used, particularly among subjects with fibrotic HP 1. The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline 1. For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine 1. Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS 1. Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS 1. Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS 1. BOS is generally suspected at an early stage when the FEV1 is ≤90% of baseline and/or the FEF25–75% is ≤75% of baseline in both bilateral and single lung transplant recipients 1. Routine postero-anterior and lateral chest radiographs are neither sensitive nor specific for diagnosing BOS 1. Thoracic imaging assists in making a diagnosis of BOS by ruling out other causes of allograft function decline 1. Surveillance bronchoscopy can safely evaluate the lung allograft for occult abnormalities, although a beneficial effect on recipient survival and prevention of BOS has not been clearly demonstrated 1. Although bronchoscopy has poor sensitivity for the diagnosis of OB, bronchoscopy is frequently used to evaluate the lung allograft when evidence of clinical dysfunction is identified 1. The presence of BAL neutrophilia suggests that OB may be occurring in the lung allograft and that the allograft is at increased risk for progression to BOS; infection is a confounder and may be the cause of BAL neutrophilia, although infection and OB/BOS may coexist in the allograft 1. The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline 1. For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine 1. Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS 1. Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS 1. Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS 1. In a study of 111 subjects with ILD, 38 (34%) with mostly nonfibrotic HP based on prespecified criteria, five independent CT predictors were identified and weighted according to their regression coefficient: ground-glass attenuation nodules (4 points), homogeneous GGO (3 points), patchy GGO (2 points), absence of adenopathy (2 points), and absence of linear/reticular patterns (2 points) 1. A total score of 5 points offered the best trade-off between sensitivity, specificity, and likelihood ratio: 74%, 90%, and 7.7, respectively 1. In HP, the combination and sharp demarcation of areas of lobules of decreased attenuation reflecting air-trapping, normal lung, and areas of increased ground-glass lung opacification on HRCT imaging form the three-density sign (previously known as the “head-cheese” sign), which is highly specific for distinguishing fibrotic HP from IPF 1. The three-density sign, when present in three or more lobes, was found to have a specificity of 93% and a sensitivity of 49% for a high confidence diagnosis of fibrotic HP 1. When the three-density sign was present in five or more lobules and in three or more lobes bilaterally, it had a specificity of 96% and sensitivity of 42% 1. The presence of three or more lobules of lobular air-trapping in three or more lobes also had high specificity for HP, but the specificity of this finding dropped in the validation cohort 1. Thus, it is reasonable to regard the three-density sign as being most typical of fibrotic HP 1. The specificity of mosaic attenuation and lobular air-trapping may vary depending on the observer and on the presence of associated signs of HP 1. In patients who have mosaic attenuation without three-density sign or characteristic centrilobular nodules, obliterative bronchiolitis is an important consideration 1. In patients with a combination of lung fibrosis and mosaic attenuation, the possibility of a connective tissue disease should be considered (particularly rheumatoid arthritis) 1. The diagnostic utility of prespecified histological features of HP was evaluated in three single-center observational studies, which found that the presence of granulomas or giant cells and inflammatory bronchiolitis or a predominantly mononuclear cellular interstitial infiltrate on TBB specimens was characteristic of HP in 40% of patients 1. The addition of TBB to BAL substantially increased diagnostic yield regardless of the BAL lymphocyte cutoff used, particularly among subjects with fibrotic HP 1. The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline 1. For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine 1. Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS 1. Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS 1. Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS 1. BOS is generally suspected at an early stage when the FEV1 is ≤90% of baseline and/or the FEF25–75% is ≤75% of baseline in both bilateral and single lung transplant recipients 1. Routine postero-anterior and lateral chest radiographs are neither sensitive nor specific for diagnosing BOS 1. Thoracic imaging assists in making a diagnosis of BOS by ruling out other causes of allograft function decline 1. Surveillance bronchoscopy can safely evaluate the lung allograft for occult abnormalities, although a beneficial effect on recipient survival and prevention of BOS has not been clearly demonstrated 1. Although bronchoscopy has poor sensitivity for the diagnosis of OB, bronchoscopy is frequently used to evaluate the lung allograft when evidence of clinical dysfunction is identified 1. The presence of BAL neutrophilia suggests that OB may be occurring in the lung allograft and that the allograft is at increased risk for progression to BOS; infection is a confounder and may be the cause of BAL neutrophilia, although infection and OB/BOS may coexist in the allograft 1. The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline 1. For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine 1. Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS 1. Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS 1. Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS 1. In a study of 111 subjects with ILD, 38 (34%) with mostly nonfibrotic HP based on prespecified criteria, five independent CT predictors were identified and weighted according to their regression coefficient: ground-glass attenuation nodules (4 points), homogeneous GGO (3 points), patchy GGO (2 points), absence of adenopathy (2 points), and absence of linear/reticular patterns (2 points) 1. A total score of 5 points offered the best trade-off between sensitivity, specificity, and likelihood ratio: 74%, 90%, and 7.7, respectively 1. In HP, the combination and sharp demarcation of areas of lobules of decreased attenuation reflecting air-trapping, normal lung, and areas of increased ground-glass lung opacification on HRCT imaging form the three-density sign (previously known as the “head-cheese” sign), which is highly specific for distinguishing fibrotic HP from IPF 1. The three-density sign, when present in three or more lobes, was found to have a specificity of 93% and a sensitivity of 49% for a high confidence diagnosis of fibrotic HP 1. When the three-density sign was present in five or more lobules and in three or more lobes bilaterally, it had a specificity of 96% and sensitivity of 42% 1. The presence of three or more lobules of lobular air-trapping in three or more lobes also had high specificity for HP, but the specificity of this finding dropped in the validation cohort 1. Thus, it is reasonable to regard the three-density sign as being most typical of fibrotic HP 1. The specificity of mosaic attenuation and lobular air-trapping may vary depending on the observer and on the presence of associated signs of HP 1. In patients who have mosaic attenuation without three-density sign or characteristic centrilobular nodules, obliterative bronchiolitis is an important consideration 1. In patients with a combination of lung fibrosis and mosaic attenuation, the possibility of a connective tissue disease should be considered (particularly rheumatoid arthritis) 1. The diagnostic utility of prespecified histological features of HP was evaluated in three single-center observational studies, which found that the presence of granulomas or giant cells and inflammatory bronchiolitis or a predominantly mononuclear cellular interstitial infiltrate on TBB specimens was characteristic of HP in 40% of patients 1. The addition of TBB to BAL substantially increased diagnostic yield regardless of the BAL lymphocyte cutoff used, particularly among subjects with fibrotic HP 1. The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline 1. For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine 1. Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS 1. Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS 1. Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS 1. BOS is generally suspected at an early stage when

From the Research

Mosaic Attenuation with Air Trapping

Mosaic attenuation with air trapping is a radiological finding that can be caused by various conditions. The following are some of the possible causes:

• Constrictive bronchiolitis, which is characterized by concentric fibrosis in the bronchiolar submucosal layer with continual external circular scarring 2
• Small airway diseases, such as chronic bronchitis, asthma, and bronchiolitis obliterans 3, 4
• Interstitial lung disease, including sarcoidosis, hypersensitivity pneumonitis, and unspecified interstitial lung disease 3
• Bronchiectasis, which can be caused by nontuberculous mycobacteria, cystic fibrosis, idiopathic bronchiectasis, and transplant-related bronchiolitis obliterans 3
• Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH), which is characterized by multifocal proliferation of neuroendocrine cells 5
• Connective tissue diseases, such as rheumatoid arthritis, Sjögren syndrome, and undifferentiated connective tissue disease 6

Common Causes

The most common causes of mosaic attenuation with air trapping include:

• Constrictive bronchiolitis obliterans, which is an irreversible fibrotic process that can be caused by various factors, including toxic fumes, connective tissue diseases, and certain medications 2
• Small airway diseases, which can be caused by chronic inflammation and obstruction of the small airways 4
• Interstitial lung disease, which can be caused by various factors, including genetic predisposition, environmental exposures, and autoimmune disorders 3

Diagnostic Approach

The diagnostic approach to mosaic attenuation with air trapping typically involves a combination of clinical evaluation, pulmonary function testing, and imaging studies, including chest computed tomography (CT) scans 3, 4, 6, 5, 2. The presence of air trapping on expiratory CT scans can help to narrow the differential diagnosis and guide further evaluation and management.