What causes ground glass opacities (GGOs) on an x-ray?

Causes of Ground Glass Opacities on X-ray

Ground glass opacities (GGOs) on x-ray represent a hazy increase in lung density that does not obscure underlying bronchial and vascular structures, and can be caused by multiple pathological processes including inflammation, infection, edema, hemorrhage, and early fibrosis.

Primary Causes of Ground Glass Opacities

Inflammatory and Infectious Processes

• Various interstitial pneumonia patterns including organizing pneumonia (OP), diffuse alveolar damage (DAD), nonspecific interstitial pneumonia (NSIP), hypersensitivity pneumonitis (HP), and pulmonary eosinophilia can present as GGOs 1
• Pneumocystis carinii pneumonia and other opportunistic infections commonly present with GGOs, particularly in immunocompromised patients 2
• Bacterial and viral pneumonias may present with GGOs before progressing to consolidation 3

Pulmonary Edema

• Both hydrostatic (cardiac or renal failure) and permeability edema can cause GGOs 4
• Radiographic findings include hazy opacities, Kerley lines, and sometimes a batwing appearance in hydrostatic edema 1
• Expansion of connective tissue space around conducting airways, accompanying vessels, and interlobular septa occurs in hydrostatic edema 1

Interstitial Lung Diseases

• Idiopathic pulmonary fibrosis (IPF) may show GGOs, though extensive ground glass opacity (>30% of lung involvement) should prompt consideration of diagnoses other than IPF 1
• Desquamative interstitial pneumonitis (DIP) typically presents with extensive GGOs 1
• Respiratory bronchiolitis-interstitial lung disease shows GGOs often with centrilobular nodules 1
• Nonspecific interstitial pneumonia (NSIP) frequently presents with GGOs without basal or peripheral predominance 1

Drug-Related and Radiation-Induced Causes

• Drug-related pneumonitis from molecular targeting agents and immune checkpoint inhibitors can present as various interstitial pneumonia patterns with GGOs 1
• Radiation pneumonitis typically shows GGOs within the radiation portal or roughly within the area of high-dose radiation 1
• GGOs may appear 3-12 weeks after radiation exposure 1

Other Causes

• Alveolar hemorrhage can present with bilateral patchy GGOs in middle and lower lung zones 1
• Pulmonary alveolar proteinosis typically shows GGOs with a geographic distribution 2
• Neoplastic processes, particularly bronchioloalveolar carcinoma (now classified as adenocarcinoma in situ) and lymphangitic carcinomatosis can present with GGOs 5, 6

Pathophysiologic Mechanisms of GGO Formation

GGOs represent several possible pathophysiologic processes:

• Partial filling of alveolar spaces with fluid, cells, or other material 6, 7
• Inflammatory or fibrotic thickening of the interstitium 6
• Increased capillary blood volume 6
• Combination of alveolar and interstitial processes 7

Diagnostic Approach to GGOs

When evaluating GGOs, consider:

• Distribution pattern (diffuse, patchy, peripheral, basal, etc.) 1
• Associated findings such as reticular opacities, honeycombing, traction bronchiectasis, centrilobular nodules 1
• Clinical context including patient's immune status, medication history, and chronicity of symptoms 7

Important Clinical Considerations

• When GGOs occur with reticular lines and traction bronchiectasis/bronchiolectasis, they indicate lung fibrosis 1
• Isolated GGOs without fibrotic features are usually associated with inflammatory cells in the alveolar septum or lumen (alveolitis) 1
• GGOs may represent active and potentially treatable disease in conditions like idiopathic pulmonary fibrosis and sarcoidosis 2
• The extent of GGOs on CT correlates with physiologic impairment and can help predict response to treatment 1
• GGOs may progress to reticular opacity or honeycombing on follow-up evaluation in fibrotic processes 1

Distinguishing Features

• Mosaic attenuation (alternating areas of increased and decreased attenuation) should be distinguished from true GGOs and may suggest small airway disease or vascular pathology 1, 6
• The "three-density pattern" (hypoattenuating, normal, and hyperattenuating lobules in close proximity) is highly specific for fibrotic hypersensitivity pneumonitis 1
• GGOs should be differentiated from consolidation, in which bronchovascular structures are obscured 6

Understanding the various causes and patterns of GGOs is essential for narrowing the differential diagnosis and guiding appropriate management to improve patient outcomes.