The classic cause of the tree-in-bud pattern is postprimary tuberculosis (Fig. 3A, 3B), a condition that develops in approximately 5% of patients with primary infection and is frequently associated with malnutrition and immune suppression. Occasionally, it may reflect reinfection with new organisms. The tree-in-bud pattern suggests active and contagious disease, especially when associated with adjacent cavitary disease within the lungs.

The most common CT findings are centrilobular nodules and branching linear and nodular opacities. This tree-in-bud pattern is due to the presence of caseation necrosis and granulomatous inflammation within and surrounding the terminal and respiratory bronchioles and alveolar ducts, reflecting endobronchial spread of tuberculosis. Other common findings include cavitary nodules, lobular consolidation, interlobular thickening, and bronchovascular distortion. Pleural effusion and enlarged lymph nodes with central low attenuation due to caseous necrosis also can be seen. After antituberculous therapy is begun, most of the centrilobular and branching opacities disappear within 5 months. However, bronchovascular distortion, fibrosis, emphysema, and bronchiectasis increase on follow-up CT.

Atypical mycobacteria may produce a pattern indistinguishable from that of tuberculosis, although without any upper lobe predominance (Fig. 4A, 4B). This is also seen with Mycobacterium avium-intracellulare or M. avium complex, notably in immunologically compromised individuals with HIV. Bronchiolitis due to Staphylococcus aureus and Haemophilus influenzae also may manifest as the peripheral tree-in-bud pattern.

Invasive airway aspergillosis causing bronchiolitis occurs most commonly in neutropenic patients and individuals who are immunologically suppressed with AIDS. Fungal hyphae are often found in the airway lumen. Other clinical manifestations of this condition are bronchopneumonia (peribronchial distribution of consolidation) and tracheobronchitis (bronchiectasis and thickening of the trachea or bronchi), which are often bilateral. Invasive airway aspergillosis should be suggested when the tree-in-bud pattern occurs in combination with a consolidation accompanied by a halo of ground-glass opacity in a patient with leukemia.

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Fig. 3A —Tuberculosis. Peripheral tree-in-bud opacities (circle, A) combine to produce more peripheral centrilobular nodules (circle, B).

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Fig. 3B —Tuberculosis. Peripheral tree-in-bud opacities (circle, A) combine to produce more peripheral centrilobular nodules (circle, B).

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Fig. 4A —Atypical mycobacterial infection. Maximum-intensity-projection images in transverse (A) and coronal (B) planes show generalized tree-in-bud opacities.

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Fig. 4B —Atypical mycobacterial infection. Maximum-intensity-projection images in transverse (A) and coronal (B) planes show generalized tree-in-bud opacities.

Cytomegalovirus infection, which typically occurs in immunologically compromised individuals, can cause bronchiolitis with centrilobular nodules and thickening of the bronchovascular bundles that produce the tree-in-bud pattern. This pattern may have a patchy and unilateral or bilateral and asymmetric distribution and may progress to areas of ground-glass opacity and consolidation. There may be poorly defined nodules with the CT halo sign. In infants and young children, the tree-in-bud pattern is most commonly caused by bronchial wall thickening and dilatation related to respiratory syncytial virus.

Cystic fibrosis is an autosomal-recessive hereditary disorder involving the exocrine glands, resulting in the production of abnormal secretions by the salivary and sweat glands, pancreas, large bowel, deferent ducts, and tracheobronchial tree. A block in the transport of chloride into the bronchial lumen and the excessive resorption of sodium leads to the production of thick and dry mucus, resulting in decreased clearance of mucus and eventually mucous plugging in small and large airways and subsequent bacterial infection.

Chronic infection and inflammatory reactions cause lung damage. The most common CT findings include bronchial wall thickening, bronchiectasis or bronchiolectasis, mucous plugging, and air trapping on expiratory scanning. Large amounts of bronchiolar secretions can produce the tree-in-bud pattern, which predominantly tends to affect the upper lobes in the early stage of the disease.

Kartagener syndrome is one of the dyskinetic cilia syndromes, a set of autosomal-recessive disorders in which inherited abnormalities in ciliary structure and function result in abnormal mucociliary clearance and chronic infection. It is characterized by the clinical triad of situs inversus, sinusitis, and bronchiectasis. Symptoms of recurrent bronchitis, pneumonia, and sinusitis often date from childhood. In men, the syndrome may be associated with immotile spermatozoa and infertility.

The typical chest CT findings in Kartagener syndrome include bilateral bronchiectasis with a basal predominance. Airway damage can extend to the smaller airways, causing bronchiolectasis, air trapping, and centrilobular opacities producing the tree-in-bud pattern.

Obliterative bronchiolitis, also known as constrictive bronchiolitis, is an irreversible fibrosis of small airway walls that narrows or obliterates the lumen, leading to chronic airway obstruction. The most common causes include infection (viral, bacterial, mycoplasma), inhalation of toxic fumes, drug treatment (penicillamine or gold), collagen vascular disease (rheumatoid arthritis, especially after the therapies mentioned), chronic lung transplant rejection, and bone marrow transplantation with chronic graft-versus-host disease. Nevertheless, obliterative bronchiolitis is often idiopathic. Patients usually present with shortness of breath and evidence of airway obstruction. CT findings include bronchial wall thickening, central and peripheral bronchiectasis, mosaic perfusion, and air trapping on expiratory CT scans (the most sensitive sign). Centrilobular nodules from luminal impaction produce the tree-in-bud pattern (Fig. 5).

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Fig. 5 —Obliterative bronchiolitis. CT image shows extensive right lower lobe area of peripheral tree-in-bud opacities (arrows). Nodular component of opacities is smaller but well defined.

Diffuse panbronchiolitis is a progressive inflammatory disease of unknown cause that has been reported almost exclusively in Japan and Eastern Asia. It represents a transmural infiltration of lymphocytes and plasma cells, with mucus and neutrophils filling the lumen of affected bronchioles. Most affected individuals are nonsmokers and have chronic sinusitis. The natural history of the disease is progressive respiratory failure leading to cor pulmonale and ultimately death. In addition to thick-walled bronchioles filled with mucus and producing the tree-in-bud pattern, there may be nodules, bronchiectasis, large cystic opacities accompanied by dilated proximal bronchi, and mosaic perfusion or air trapping.

Rheumatoid arthritis is twice as common in women, although extraarticular manifestations (including lung disease) are more common in men. About 90% of patients have a positive serum rheumatoid factor and show clinical evidence of arthritis before developing pulmonary or pleural disease. The most common thoracic abnormalities include interstitial pneumonia and fibrosis, pleural effusion or pleural thickening, necrobiotic nodules, organizing pneumonia, bronchiectasis, and obliterative bronchiolitis.

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Fig. 8 —Rheumatoid arthritis. Axial CT image shows tree-in-bud opacities (arrows) in lingula.

A lymphoid interstitial infiltrate in the walls of the small airways (follicular bronchiolitis) may cause small centrilobular nodules and the tree-in-bud pattern (Fig. 8). More extensive lymphocytic infiltrations may be associated with lymphoid interstitial pneumonia (LIP), with ground-glass opacities, consolidation, septal thickening mimicking the lymphangitic spread of carcinoma, and cystic air spaces. This condition progresses to fibrosis in about one third of patients.

Sjögren syndrome consists of the clinical triad of keratoconjunctivitis sicca, xerostomia, and recurrent swelling of the parotid gland. The most common thoracic manifestations include LIP (more common than in rheumatoid arthritis), follicular bronchiolitis, interstitial pneumonia, organized pneumonia, tracheobronchial gland inflammation, and pleuritis with or without effusion. As with rheumatoid arthritis, lymphoid interstitial infiltrate in the walls of the small airways may produce the tree-in-bud pattern.