Chronic airspace disease: Review of the causes and key computed tomography findings

Table 1 Clinical, laboratory and imaging findings, and prognosis/treatment of inflammatory causes of chronic airspace disease

Causes of chronic airspace disease/ General category	Clinical information	Laboratory findings	Imaging findings	Prognosis and treatment
Alveolar sarcoidosis/ Inflammatory	History of sarcoidosis	Elevated ACE	Infiltrative and consolidative opacities with ill-defined margins and sometimes air bronchograms; Typical findings of sarcoidosis may or may not be present (perilymphatic nodules, enlarged lymph nodes in the right paratracheal region and bilateral hila)	Corticosteroids only given for active disease; Presence of alveolar sarcoidosis is more suggestive of active disease; Relatively rapid response to treatment; May recur
Chronic eosinophilic pneumonia/ Inflammatory	History of asthma in 50% of cases; Middle-aged women	Chronic eosinophilic pneumonia; Increased eosinophils in bronchoalveolar lavage; Elevated IgE	Middle/upper and peripheral lung predominant chronic airspace opacity and consolidations; Opacities may show subtle or major changes in appearance (migratory); GGO and interlobular septal thickening (crazy-paving)	Good prognosis; Often require long-term low-dose oral corticosteroid therapy in order to prevent relapse
Organizing pneumonia/ Inflammatory	No obvious cause in most of the cases (therefore cryptogenic organizing pneumonia); History of vasculitis or connective tissue disorder may be present; History of anticancer treatment may be present		Classic findings: Bilateral peribronchovascular and/or subpleural consolidations with mid-lower lung zone preference; Less common findings: Small, ill-defined peribronchial or peribronchiolar nodules large nodules or masses; Halo sign; Reverse halo sign; Crazy paving arcade-like or polygonal opacities; Opacities may show subtle changes in appearance overtime (migratory)	Most (especially cryptogenic forms) respond very well to corticosteroid treatment; A small percentage of patients many develop progressive fibrosis
EGPA (Churg-Strauss syndrome)/ Inflammatory	Small to medium vessel necrotizing pulmonary vasculitis; History of asthma is usually present; May have extrapulmonary findings (sinusitis, diarrhea, skin purpura, arthralgias)	Eosinophilia; ANCA (+)	More common: Peripheral or random parenchymal opacification either consolidation or ground glass; Opacities can be transient and change in appearance and distribution in the follow-up imaging; Less common: Centrilobular nodules and bronchial wall thickening; Cavitation is rare	Corticosteroids; May need addition immunosuppression with cyclosporine, azathioprine if there is cardiac, renal, GI or CNS involvement; Low mortality rate; Cardiac involvement is a major contributor to death
Granulomatosis with polyangiitis (Wegner granulomatosis)/ Inflammatory	Multisystem necrotizing non-caseating granulomatous vasculitis affecting small to medium; May involve sinuses and kidneys	ANCA (+)	Chronic airspace opacity and consolidation; Nodules and masses which may cavitate in 50% of cases; Halo or reverse halo sign may be present due to hemorrhage and associated ground-glass appearance	Immunosuppression with cyclophosphamide, methotrexate and/or corticosteroids; Rapidly fatal if not treated
Treatment and drug-related/ Inflammatory	History of cancer treatment; Respiratory symptoms related to pneumonitis including dyspnea and fever		Can have the following appearances; Organizing pneumonia; Nonspecific interstitial pneumonia; ARDS; Eosinophilic pneumonia; Pulmonary hemorrhage	Supportive treatment; Withholding treatment. May or may not recur after reintroduction of treatment

ACE: Angiotensin-converting enzyme; ANCA: Antineutrophil cytoplasmic antibody; ARDS: Acute respiratory distress syndrome; CNS: Central nervous system; EGPA: Eosinophilic granulomatosis with polyangiitis; GGP: Ground glass opacity; GI: Gastrointestinal.

Table 2 Clinical, laboratory and imaging findings, and prognosis/treatment of infectious causes of chronic airspace disease

Causes of chronic airspace disease/ General category	Clinical information	Laboratory findings	Imaging findings	Prognosis and treatment
Fungal infection, including angio-invasive aspergillosis/ Infectious	History of immunosuppression including: Neutropenia; High-dose steroid treatment; Bone marrow transplant; End-stage AIDS; Symptoms are nonspecific (fever, cough, pleuritic chest pain, hemoptysis)	Neutropenia, especially severe (absolute neutrophil count < 500 cells/µL)	Parenchymal nodules or consolidation with a surrounding area of ground glass opacity (halo sign); Reverse halo sign; Peripheral wedge-like areas of consolidation representing hemorrhagic pulmonary infarct; Pleural effusion and lymphadenopathies are rare	Intravenous amphotericin B; Poor prognosis; Early diagnosis improves survival
Pulmonary tuberculosis/ Infectious	Immunosuppression such as AIDS; Recent travel to endemic countries	Low CD4 count in AIDS patients (< 350 cells/mm3)	Primary tuberculosis: Not detectable; Patchy or even lobar consolidation; Cavitation is rare; Military (numerous tiny nodules) tuberculosis can be seen Post-primary tuberculosis: Mostly involve the posterior segments of the upper lobes or superior segments of the lower lobes; Patchy consolidation with or without ground-glass opacity; Cavitation is more common; Military (numerous tiny nodules) tuberculosis can be seen	Appropriate antibiotics based on sensitivity; Respiratory isolation if needed
Non-tuberculosis MAC infection/ Infectious	May have pre-existing pulmonary disease or depressed immunity; Can also happen in otherwise normal people; Predilection for older women who voluntary suppress cough (Lady Windermere syndrome)		Most common: Bronchiectasis and bronchial wall thickening with small centrilobular nodules and tree-in-bud appearance; Persistent consolidation and ground-glass patchy opacities; Upper lung cavitary lesions	No clear gold-standard for treatment; Usually need multiple antibiotics; May be candidate for resection of the involved lung if the disease is localized; More aggressive course in upper lung cavitary form More indolent course in nodular bronchiectatic form
Incompletely treated bacterial infection/ Infectious	History of recent bacterial pneumonia with incomplete treatment	Persistent leukocytosis	Persistent consolidation	Continued treatment with appropriate antibiotic
Pneumocystis jirovecii pneumonia/ Infectious	HIV (+) patients; Post-transplant patients; Patients undergoing chemotherapy or with hematologic malignancies; Patients with connective tissue disorder on corticosteroid treatment	CD4 counts < 200 cells/mm	Ground-glass opacity mainly with perihilar or mid zone distribution, most common findings; Less common/less typical findings septal thickening and crazy paving, pneumatocele; Pleural effusion and lymphadenopathy are unusual	Trimethoprim-sulfamethoxazole as treatment or for prophylaxis

AIDS: Autoimmune deficiency syndrome; HIV: Human immunodeficiency virus; MAC: Mycobacterium avium complex.

Table 3 Clinical, laboratory and imaging findings, and prognosis/treatment of neoplastic causes of chronic airspace disease

Causes of chronic airspace disease/ General category	Clinical information	Laboratory findings	Imaging findings	Prognosis and treatment
Pulmonary adenocarcinoma in situ or minimally invasive/ Neoplastic	History of smoking is usually present		Predominantly GGO ≤ 3 cm with or without a small solid nodular component; Fried-egg sign; Mildly hypermetabolic on FDG/PET; Pseudocavitation may be present; Fissural or pleural retraction may be seen; Adenopathy and pleural effusion are uncommon at this stage	Surgical resection; Chemotherapy; Radiation treatment
Invasive adenocarcinoma of the lung/Neoplastic	History of smoking is usually present		Solid or subsolid and sometimes even ground glass nodule or mass; Consolidation with air-bronchogram, mimicking pneumonia has been mostly described in invasive mucinous adenocarcinoma subtype	Surgical resection; Chemotherapy; Radiation treatment
Pulmonary lymphoma/ Neoplastic	Primary (usually non-Hodgkin’s lymphoma) or secondary pulmonary lymphoma (can be Hodgkin’s or non-Hodgkin’s lymphoma)		Most common imaging finding: Mass or mass-like consolidation with or without cavitation	Surgery for localized diseas;e Chemotherapy; Radiation treatment; Good prognosis
PTLD/ Neoplastic	Occurs in 10% of solid organ transplant cases; Highest incidence in small bowel transplant; Can affect multiple organs		Pulmonary consolidation; Pulmonary nodules and masses which may cavitate	Treatment depends on location and extent of the disease; Treatment options: Reduction in immunosuppression; Resection of localized disease; Radiation treatment Chemotherapy
Pulmonary metastasis/ Neoplastic	Seen in adenocarcinoma of gastrointestinal tract and less commonly of breast and ovarian origin		Uncommon appearance of pulmonary metastasis appearing as persistent airspace opacity and consolidation; Due to lepidic growth of tumor cells along the intact alveolar walls	Treatment of the underlying cancer

FDG/PET: Fluorodeoxyglucose-positron emission tomography; GGO: Ground glass opacity; PTLD: Post-transplant lymphoproliferative disorder.

Table 4 Clinical, laboratory and imaging findings, and prognosis/treatment of miscellaneous causes of chronic airspace disease

Causes of chronic airspace disease/ General category	Clinical information	Laboratory findings	Imaging findings	Prognosis and treatment
Lipoid pneumonia/ Miscellaneous	Usually elderly individuals; History of chronic inflammation in primary (endogenous) form; History of chronic constipation and aspiration in the secondary (exogenous) form		Chronic consolidative and GGOs; Nodules and masses; More in the dependent portions of the lungs; May or may not have fat attenuation	Biopsy may be needed in lipid poor cases to exclude malignancy
Alveolar hemorrhage/ Miscellaneous	May have history of vasculitides, connective tissue disorders, or coagulation disorders		GGO or consolidation in the acute phase; GGO and interlobular septal thickening in subacute phase; May develop fibrosis if recurrent or chronic; Opacities may show subtle or major changes in appearance (migratory)	Supportive treatment; Treatment of underlying disease
PAP/ Miscellaneous	Due to abnormal intra-alveolar accumulation of surfactant-like material; More common in smokers		Crazy-paving which is due to combination of GGO and smooth interlobular septal thickening; This finding is very suggestive but not pathognomonic; Usually bilateral and extensive, with more severe involvement of the lower lobes	Whole-lung bronchoalveolar lavage to remove alveolar material; Variable prognosis, ranging from improvement with treatment to a chronic and terminal course.

GGO: Ground glass opacity; PAP: Pulmonary alveolar proteinosis.

Table 5 Key imaging findings and imaging signs in chronic airspace disease

Imaging finding/sign	Cause
Imaging signs	Halo sign: Fungal infection including angio-invasive pulmonary aspergillosis, pulmonary tuberculosis, lung adenocarcinoma, organizing pneumonia, granulomatosis with polyangiitis
	Reverse halo sign: Fungal infection including angio-invasive aspergillosis, organizing pneumonia, granulomatosis with polyangiitis, pulmonary tuberculosis, alveolar sarcoidosis
	1-2-3 sign (right paratracheal and bilateral hilar lymphadenopathy): Alveolar sarcoidosis
	Crazy paving: Pulmonary alveolar proteinosis, pulmonary hemorrhage, chronic eosinophilic pneumonia, organizing pneumonia, alveolar sarcoidosis
	Pseudocavitation: Lung adenocarcinoma
	Fried egg sign: Lung adenocarcinoma
	Fissural retraction: Lung adenocarcinoma
Distribution	Upper lung: Sarcoid, chronic eosinophilic pneumonia (mid and upper), tuberculosis
	Lower lung: Lipoid pneumonia, organizing pneumonia (mid and lower)
Ground glass vs consolidation	Ground-glass opacity: Adenocarcinoma, pulmonary hemorrhage
	Mixed: Adenocarcinoma, organizing pneumonia, angio-invasive aspergillosis
	Consolidation: Invasive mucinous adenocarcinoma, lymphoma, PTLD
Presence of cavitary lesion	Pulmonary tuberculosis
	Granulomatosis with polyangiitis and other vasculitis
	Fungal infection
Peri-lymphatic nodules	Alveolar sarcoidosis
Minor or major change in the distribution and severity	Chronic eosinophilic pneumonia
	Organizing pneumonia
	Pulmonary hemorrhage
Arcade-like or polygonal opacities	Organizing pneumonia
Fat density	Lipoid pneumonia
Interlobular septal thickening and subpleural sparing	Organizing pneumonia
	Pulmonary hemorrhage
Involvement of other organs	Liver and bowel: PTLD
	Renal involvement: Granulomatosis with polyangiitis
	Involvement of upper respiratory tracts and paranasal sinuses: Granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis

PTLD: Post-transplant lymphoproliferative disorder.