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Idiopathic Fibrosing Alveolitis

Alveolitis fibrosans idiopathica

For medical students2 min readUpdated 2026-10-10

Idiopathic fibrosing alveolitis (Alveolitis fibrosans idiopathica) is a progressive pulmonary disease with a gradual onset. The pathology is characterized by severe inflammation and sclerosis of the respiratory interstitium, culminating in the formation of a «honeycomb lung».

Leading symptomProgressive exertional dyspnea
Early changesExudative inflammation and patchy involvement
Late stageFormation of a «honeycomb lung»
Pulmonary functionBlockade of the blood-air barrier

Clinical Presentation and Diagnostics

The disease has a gradual onset and a relentlessly progressive course. The primary clinical sign is progressive dyspnea upon physical exertion.

Physical examination reveals fine bilateral crackles or crepitations in the lung bases. Most patients also experience fever, general fatigue, and weight loss. Chest radiography demonstrates bilateral accentuation of bronchovascular markings and ground-glass opacities, predominantly located in the lower lung zones.

Pathological Anatomy: Early Stages

Initial macroscopic changes may be subtle: the lungs become unevenly aerated, hyperemic, and dense.

Microscopically, early stages show:

The alveolar lumina accumulate serous exudate, accompanied by alveolar proteinosis, epithelial desquamation, and fibrin deposition leading to hyaline membrane formation. The interstitial cellular infiltrate consists predominantly of lymphohistiocytic elements.

Pathogenesis and the Role of Macrophages

Molecular factors and alveolar macrophages play a critical role in the development of early changes. The expression of c-fos and c-sis oncoproteins stimulates cell proliferation. Activated macrophages intensively produce reactive oxygen species and tumor necrosis factor-alpha (TNF-α), which damage the bronchial and alveolar epithelium.

A characteristic feature of macrophages in acute interstitial pneumonia is the predominance of a monocytoid type: they lack phagocytic activity, but enhance protein synthesis and secrete large amounts of fibronectin.

Late Stage and the «Honeycomb Lung»

A prolonged disease course leads to the terminal stage — the «honeycomb lung».

Macroscopically, the lung tissue becomes firm, acquires a rubbery consistency, and completely loses elasticity and aeration. The organ's structure is remodeled into cystic cavities.

The microscopic picture is characterized by severe interstitial sclerosis and the replacement of normal parenchyma with connective tissue. Airspaces are transformed into cystic cavities («honeycombs») surrounded by fibrosis. The epithelial lining undergoes dysregenerative changes: type I pneumocytes are replaced by hyperplastic type II pneumocytes, with foci of adenomatous hyperplasia, squamous metaplasia, and dysplasia.

Severe septal fibrosis and epithelial alterations completely block the blood-air barrier.

Mnemonic

IFA: Inflammatory mosaic at the start $\rightarrow$ Myofibroblasts and fibronectin $\rightarrow$ Cystic «honeycomb lung» at the end.

Frequently asked questions

What etiologic factors are hypothesized in the development of idiopathic fibrosing alveolitis?

Idiopathic fibrosing alveolitis belongs to the group of diffuse inflammatory lung diseases of unknown etiology. The term «idiopathic fibrosing alveolitis» reflects the primary and unclear nature of the disease. Respiratory bronchiolitis-associated interstitial lung disease is known to occur typically in smokers.

What pulmonary and extrapulmonary complications are characteristic of the terminal stage of idiopathic fibrosing alveolitis?

The terminal stage is characterized by the development of progressive cor pulmonale and heart failure. Key complications and outcomes include:

  • «Honeycomb lung» — a combination of interstitial fibrosis and cystic transformation of terminal and respiratory bronchioles and alveoli.
  • Pneumosclerosis (pulmonary cirrhosis).
  • Secondary pulmonary hypertension.
  • Right ventricular hypertrophy.

Additionally, the blood-air barrier becomes blocked and non-functional due to severe alveolar septal fibrosis and dysregenerative changes of the epithelial lining.

What histological patterns are distinguished in the modern classification of idiopathic interstitial pneumonias?

Modern morphological classification distinguishes several main histological patterns (variants). These include:

  • Usual interstitial pneumonia (usual interstitial pneumonia) — the most frequent morphological substrate.
  • Nonspecific interstitial pneumonia.
  • Organizing pneumonia.
  • Diffuse alveolar damage.
  • Respiratory bronchiolitis.
  • Desquamative interstitial pneumonia.
  • Lymphocytic interstitial pneumonia.
What pathophysiological mechanisms lead to respiratory failure in idiopathic fibrosing alveolitis?

Respiratory failure is caused by restrictive ventilatory defects and reduced carbon dioxide/oxygen diffusion capacity. These pathophysiological mechanisms are driven by the blockade of the blood-air barrier, which ceases to function. Causes of this blockade include:

  • Severe fibrosis of the alveolar septal interstitium.
  • Dysregenerative changes in the epithelial lining (replacement of type I pneumocytes by hyperplastic type II pneumocytes, focal adenomatous hyperplasia).

The consequence of these processes is a sharp, progressive decrease in total lung capacity.

What is the leading clinical symptom of idiopathic fibrosing alveolitis?

The primary symptom of the disease is progressive exertional dyspnea.

What is the characteristic distribution of the pathological process in the lungs?

The process is patchy (mosaic): widespread foci of injury alternate with preserved lung parenchyma.

What does the macroscopic appearance of the lung look like in the late stage?

The lung tissue becomes dense, acquires a «rubbery» consistency, loses elasticity, and forms honeycomb-like cystic structures («honeycomb lung»).

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