Even though there is no consensus classification system for small airways disease, one of the most accepted and used at pathologic examinations divides these conditions into two broad categories: cellular bronchiolitis (CB) and constrictive or fibrotic bronchiolitis (FB).

Histologically, CB is characterized by inflammatory cells as the predominant feature, in contrast to FB, which refers to bronchiolar narrowing due to adventitial and submucosal fibrosis.

Various forms of CB are well acknowledged, encompassing infectious bronchiolitis (IB), respiratory bronchiolitis (RB), aspiration bronchiolitis (AB), follicular bronchiolitis (FLB), hypersensitivity pneumonitis (HP), and diffuse panbronchiolitis (DP).

On the contrary, although FB can occur in isolation, it is typically a pathologic pattern resulting from other conditions (eg, chronic rejection in the setting of transplantation, an infection, or an autoimmune process).

Chest radiographs are frequently normal in small airways diseases, however, they may manifest with nonspecific findings such as ill-defined small or hazy clustered nodules (fig.3) in CB or areas of air trapping characterized by hyperlucency in FB (fig.4).

Fig 3: Figure 3. Chest radiograph of cellular bronchiolitis: Ill-defined and small nodules with a predominance in the lower lobes, best visualized as hazy clusters within black circles.

Fig 4: Figure 4. Chest radiograph of fibrotic bronchiolitis: Hyperinflation due to air trapping and reticulonodular opacities (best observed within the black circle).

At chest CT, the primary manifestation of CB is centrilobular nodules (fig.5). These nodules can vary in size and attenuation. If they coalesce, may form nodular foci of consolidation or ground-glass opacities (fig.6).

Fig 5: Figure 5. Centrilobular nodule. A) Picture illustrating the centrilobular nodule as a poorly defined nodule located in the center of the secondary pulmonary lobule. B) Enlarged axial lung window CT slide showing multiple centrilobular nodules, cropped for detail.

Fig 6: Figure 6. Centrilobular nodules and their larger counterparts. When centrilobular nodules (triangle) coalesce, they form nodular foci of consolidation (circle). Within the square, we observe a tree-in-bud pattern.

The other important manifestation of CB is the tree-in-bud pattern, which refers to a specific subset of centrilobular nodules with multiple, branching, soft tissue attenuation opacities originating from a single stalk (fig.7).

Fig 7: Figure 7. Tree-in-bud pattern. A) Picture illustrating the tree-in-bud pattern involving the distal airways and multiple centrilobular nodules with a linear branching pattern. B) Enlarged axial lung window CT slide displaying tree-in-bud opacities, cropped for detail.

Different conditions beneath CB exhibit overlapping appearances on chest CT. However, some findings may assist in refining the differential diagnosis, in addition to using clinical information. The tree-in-bud pattern is commonly associated with IB or AB, while isolated centrilobular nodules tend to indicate conditions such as HP or RB.

A pivotal aspect of bronchiolitis assessment involves ensuring that micronodules are accurately identified as centrilobular rather than perilymphatic. This distinction is based on their anatomic distribution. Centilobular nodules are defined by their limited extent, not reaching the pleura or fissures (fig.8A-9A). In contrast, perilymphatic micronodules typically engage the pleural surfaces and fissures (fig.8B-9B).

Fig 8: Figure 8. Accurate identification of micronodules as centrilobular. Note the difference between A) centrilobular nodules not extending to the pleura (black arrowheads) in a case of infectious bronchiolitis vs. B) perilymphatic nodules involving the pleural surface (black arrows) in a patient with lymphangitic carcinomatosis due to a bronchogenic tumor (not visible) and mediastinal lymph node involvement (black asterisks).

Fig 9: Figure 9. Accurate identification of micronodules as centrilobular. Note the distinction between A) centrilobular nodules that do not extend to the oblique fissure (black arrows) in a case of infectious bronchiolitis vs. B) perilymphatic nodules causing nodular thickening of both oblique and horizontal fissures (black arrowheads) in a patient with lymphangitic carcinomatosis due to a bronchogenic tumor (not visible).

Once micronodules are established as centrilobular, it becomes crucial to ascertain their association with small airways disease and exclude vascular causes, since the other centrilobular structure is the lobular pulmonary artery. While these micronodules may be indistinguishable from those observed in bronchiolitis, they tend to be diffusely distributed throughout the lungs, stemming from hematogenous dissemination of disease and they often associate key ancillary findings (fig.10).

Fig 10: Figure 10. Vascular cause of centrilobular nodules: Granulomatosis with polyangiitis. Diffuse centrilobular nodules with A) nodule demonstrating cavitation (black arrowhead) and B) multiple nodules of variable size randomly distributed throughout the lungs (white arrowheads), both typical features of granulomatosis with polyangiitis. Centrilobular nodules are best visualized by the black arrow.

FB frequently manifests as mosaic attenuation due to air trapping caused by bronchiolar narrowing (fig.11).

Fig 11: Figure 11. Picture depicting concentric submucosal fibrosis (yellow) resulting in bronchiolar narrowing, leading to airflow obstruction. Narrowing of the centrilobular pulmonary artery (blue) is a common feature.

This air trapping typically exhibits sharply delineated borders where the abnormal SPLs interface with the normal ones (fig.12). Concurrent findings include bronchial wall thickening (fig.12B) and bronchiectasis.

Fig 12: Figure 12. Mosaic attenuation pattern. A) Picture showing sharply delineated borders when the abnormal SPLs interface with the normal ones. B) Mosaic attenuation pattern in a patient with chronic hypersensitivity pneumonitis. The sharp borders are best visualized by black arrowhead. Bronchial wall thickening is indicated by black arrows.

Mosaic attenuation is not always attributable to bronchiolitis. Chronic vascular diseases may manifest as mosaic attenuation on imaging. Distinguishing between airway and vascular mosaic attenuation poses challenges, but the identification of ancillary findings proves helpful, as the evidence of pulmonary hypertension or nonocclusive eccentric pulmonary artery filling defects (fig.13).

Fig 13: Figure 13. Mosaic attenuation secondary to pulmonary hypertension. A and B) Mosaic attenuation pattern, most prominently observed in the right upper lobe, along with marked enlargement of the pulmonary arteries due to pulmonary hypertension.

We provide a summary of SPL, CB and FB and their pathological findings with radiological correlation in fig.14.

Fig 14: Figure 14. Summary of secondary pulmonary lobule anatomy and the pathophysiology of cellular bronchiolitis and fibrotic bronchiolitis, along with their typical imaging features.

After reviewing the two broad categories of bronchiolitis and their associated radiological findings, next-step involves describing the various small airways diseases, starting with those included in cellular bronchiolitis.

Infectious bronchiolitis

The most common type of bronchiolitis. It can be classified as either acute (typically viral) or chronic (frequently mycobacterial or bacterial). Acute infection often manifests with scattered foci of clustered tree-in-bud opacities and bronchial wall thickening (fig.15). Chronic infectious bronchiolitis may associate other imaging findings beyond tree-in-bud opacities that indicate chronicity such as bronchiectasis (fig.16).

Fig 15: Figure 15. Acute infectious bronchiolitis secondary to Streptococcus pneumoniae and Nocardia. A) Widespread tree-in-bud involvement. B) The same patient with more pronounced tree-in-bud affectation after Maximum Intensity Projection (MIP) reconstruction.

Fig 16: Figure 16. Chronic infectious bronchiolitis secondary to Mycobacterium avium intracellulare. A) Tree-in-bud opacities and bronchiectasis involving the middle lobe (black arrow). B) Same patient displaying tree-in-bud opacities in the middle lobe (black arrow) and bronchiectasis in the right upper lobe (white arrow), middle lobe (black arrow) and lingula (black arrowhead).

Clinical manifestations include include fever, dyspnea, productive cough, and wheezing.

Aspiration bronchiolitis

The second most common type of bronchiolitis and often misdiagnosed as IB. Many clinical conditions increase the risk of aspiration, including altered mental status, neurological disorders, head and neck cancer or irradiation, as well as esophageal and gastric abnormalities.

On imaging, it typically presents with tree-in-bud opacities sometimes accompanied by bronchocentric consolidation (fig.17A-B, fig.18B). Radiologists should strive to identify associated conditions to establish a connection between bronchiolitis and aspiration (fig.17C-D, fig.18).

Fig 17: Figure 17. Aspiration bronchiolitis. A) and B) Tree-in-bud opacities (white arrowhead) with incipient formation of consolidation (black arrowhead). C) and D) The same patient displaying tracheoesophageal fistula (black arrow) secondary to proximal esophageal neoplasm (not visible).

Fig 18: Figure 18. Aspiration bronchiolitis. Oral contrast CT of a patient with proximal esophageal cancer. A) Evidence of oral contrast in the esophageal lumen (black arrow) and segmental bronchi of the right lower lobe (black arrowhead). Diffuse tree-in-bud opacities (white arrowheads). B) Evidence of oral contrast in the esophageal lumen (black arrow) and in segmental bronchi of the left lower lobe (black arrowhead). Diffuse tree-in-bud opacities (white arrowhead) and consolidation in the left lower lobe (black asterisk).

Respiratory bronchiolitis

RB almost always occurs in smokers and is considered part of the spectrum that includes desquamative interstitial pneumonia.

On imaging, it typically presents upper lobe-predominant centrilobular nodules, often associated with other smoking-related lung diseases, such as emphysema (fig.19).

Fig 19: Figure 19. Respiratory bronchiolitis. A) and B) Diffuse centrilobular nodules involvement. Mild centroacinar emphysema (white arrowheads). Mild predominance of centrilobular nodules in the upper lobes. Notice the subpleural and fissural sparing of centrilobular nodules.

Hypersensitivity pneumonitis

HP is an allergic lung disease caused by inhalational exposure to numerous offending agents. This condition presents a wide spectrum of signs and symptoms, with the key challenge being identifying the antigen exposure.

Active HP often manifests with diffuse or lower lobe-predominance (fig.20), symmetric, poorly defined centrilobular nodules or groud-glass opacities (fig.21A). Air trapping is not uncommon and can serve as a valuable distinguishing factor between HP and other conditions featuring ground-glass centrilobular nodules. It also indicates a component of FB (fig.21B).

Fig 20: Figure 20. Hypersensitivity pneumonitis. Chest radiograph revealing micronodular affectation with a marked lower lobes predominance.

Fig 21: Figure 21. Hypersensitivity pneumonitis. A) A CT image of a HP secondary to bird exposure displays diffuse and symmetric centrilobular nodules, in the absence of other findings. B) CT scan of another patient with subacute hypersensitivity pneumonitis secondary to chemicals exposure reveals an extensive mosaic attenuation pattern, indicating a component of fibrotic bronchiolitis.

Follicular bronchiolitis

FLB represents peribronchiolar lymphoid hyperplasia along the small airways. It typically presents centrilobular nodules corresponding to nodular lymphoid aggregates (fig.22). FLB is part of a spectrum of lymphoproliferative lung disorders of the lung, which includes lymphoid interstitial pneumonia (fig.23).

Fig 22: Figure 22. Follicular bronchiolitis. A) and B) CT scans of a patient with underlying rheumatoid arthritis. Reticular opacities (black arrows) and mild honeycombing (white arrows) related to usual interstitial pneumonia are observed. During an immunosuppression period, the patient develops diffuse asymmetric bilateral centrilobular nodules (black arrowheads).

Fig 23: Figure 23. Lymphoid interstitial pneumonia. A) and B) CT scan of the same patient with underlying Sjögren syndrome revealing multiple cysts (white arrowheads) and small, centrilobular, pulmonary nodules (black arrowheads).

FB usually occurs in middle-aged adults with progressive cough and dyspnea and underlying immunodeficiency.

Diffuse panbronchiolitis

DP is the rarest form of CB and predominantly affects middle-aged Japanese men. The etiology remains unknown.

DP often involves both upper and lower respiratory systems. On imaging, it typically presents with lower lobe-predominant centrilobular nodules and tree-in-bud opacities, which may progress to brochiolectasis and bronchiectasis. Additionally, mosaic attenuation and the presence of cystic spaces are indicative of FB.

Fibrotic bronchiolitis

Constrictive or fibrotic bronchiolitis refers to bronchiolar narrowing resulting from irreversible concentric submucosal fibrosis, leading to airflow obstruction and subsequent mosaic attenuation pattern.

FB represents a pattern of lung response to a variety of insults. The most relevant etiologies include:

Childhood infection: Swyer-Javes-MacLeod syndrome represents a post-infectious FB that involves the lungs in a non-uniform manner (fig.24).

Fig 24: Figure 24. Fibrotic bronchiolitis due to Swyer-James-MacLeod syndrome. A) Inspiratory CT scan displaying bronchiectasis in the right lower lobe, lingula, and left lower lobe (black arrows). The left lower lobe shows marked reduced volume (compare the situation of oblique fissures). B) Expiratory CT scan revealing mosaic attenuation pattern. Note the difference in attenuation between the left lower lobe, left upper lobe (black arrowheads) and right lower lobe (grey arrow). Appreciate the diminished vascularity in left lower lobe.

Transplant-related: Bronchiolitis obliterans syndrome is a well-known complication occurring at least 3 months after lung transplantation. It is also common in graft-versus-host disease associated with hematopoietic stem cell transplantation.

Inhalational lung disease: Various inhalational exposures have been implicated in the development of FB.

Connective tissue disease: FB has been described in connective tissue diseases, most commonly observed in women with advanced rheumatoid arthritis (fig.25).

Fig 25: Figure 25. Fibrotic bronchiolitis secondary to rheumatoid arthritis. A) and B) CT scans showing a pronounced mosaic attenuation pattern with bronchial wall thickening (black arrowheads) in hyperinflated areas, in contrast to nearly normal bronchial walls in areas with normal attenuation (white arrowheads). Notice the reduced vascularity in air trapping areas.

Some etiologies described in CB (as HP or DP) may manifest FB findings.