Fig 1.
HRCT images of representative signs and CT patterns.
(A) Halo sign: the nodular consolidation surrounded by GGO. (B) Reversed halo sign: rounded area of GGO surrounded by a ring of consolidation. (C, D) OP pattern: axial and coronal HRCT images showing patchy, peripheral predominant multiple consolidation with air bronchogram. (E, F) NSIP pattern: diffuse, subpleural predominant reticulation, and GGO with traction bronchiectasis. (G, H) NSIP and OP pattern: bilateral lower zone, peribronchovascular predominant consolidation, and GGO with traction bronchiectasis. HRCT, high-resolution computed tomography; CT, computed tomography; GGO, ground-glass opacity; OP, organizing pneumonia; NSIP, nonspecific interstitial pneumonia.
Fig 2.
Flowchart of patient disposition.
Final diagnosis in 34 patients with AFOP (AFOP group) and 143 patients without AFOP (non-AFOP group). AFOP, acute fibrinous and organizing pneumonia; HP, hypersensitivity pneumonia; OP, organizing pneumonia.
Table 1.
Underlying diseases of patients.
Fig 3.
Representative radiological and histological findings of AFOP and non-AFOP.
(A–C) Patient 1, COP with AFOP. (A) The HRCT shows subpleural patchy airspace consolidation with GGO in the right upper lobe. (B, C) Histological findings obtained by TBLB show organizing pneumonia and multiple foci of fibrin in the alveoli, which are consistent findings of AFOP. (D–F) Patient 2, radiation pneumonitis with AFOP. (D) Subpleural airspace consolidation with GGO in the left upper lobe. (E, F) Histological findings obtained by TBLB showing multiple foci of intra-alveolar fibrin and infiltration of lymphocytes in the alveolar wall. (G–I) Patient 3, IgG4-related pulmonary disease with AFOP. (G) Subpleural, irregular form of consolidation and thickened intra-alveolar septa. (H, I) Histological findings obtained by surgical lung biopsy show intra-alveolar fibrin and infiltration of plasmacytes and lymphocytes in the alveolar wall. (J–L) Patient 4, COP without AFOP. (J) Subpleural airspace consolidation in the right upper lobe. (K, L) Histological findings obtained by TBLB show organizing pneumonia with intra-alveolar granulation. No intra-alveolar fibrin deposition can be observed. (B, E, H, K) Hematoxylin and eosin staining (×10). (C, F, I, L) Phosphotungstic acid-hematoxylin staining (×10). AFOP, acute fibrinous and organizing pneumonia; COP, cryptogenic organizing pneumonia; HRCT, high-resolution computed tomography; GGO, ground-glass opacity; TBLB, transbronchial lung biopsy.
Table 2.
Clinical characteristics of patients.
Table 3.
HRCT findings.
Fig 4.
Representative clinicoradiological courses of four patients in the AFOP group.
(A1-3) Patient 1. Chest CT images in a 63-year-old man with COP. (A1) Consolidation and GGO with air bronchogram in the right upper lobe at diagnosis. (A2) Three months after the administration of corticosteroids, relapse was observed in the left upper lobe. (A3) One year after the diagnosis, most of the shadow had improved, but the patient continued to experience relapses. (B1-3) Patient 2. A 65-year-old man with advanced lung cancer treated with anti-PD-1 antibody. (B1) Drug-induced pneumonia with consolidation and GGO in the left upper lobe that had developed four months after the initiation of the anti-PD-1 antibody therapy. (B2) Three weeks after corticosteroid treatment. (B3) One year after the diagnosis of drug-induced pneumonia, relapse was observed in both lower lobes. (C1-3) Patient 3. A 67-year-old woman after radiation therapy for right breast cancer. (C1) Radiation pneumonitis with halo sign developed six months after the radiation therapy. (C2) Three months after the treatment with corticosteroids. (C3) Six months after the diagnosis of radiation pneumonitis, relapse of radiation pneumonitis was observed. The therapeutic course was good with increased corticosteroid dosage. (D1-3) Patient 4. A 74-year-old man with anti-MDA5 antibody-positive dermatomyositis and rapidly progressive interstitial lung disease. (D1) Consolidation and GGO along the peripheral bronchovascular bundle predominantly in the lower lobes at the initial visit. (D2) At the time of admission, the shadow had progressed further within a week. (D3) Despite intense treatment with biweekly intravenous cyclophosphamide pulse (1000 mg/day), tacrolimus (5 mg/day), plasma exchange, and methylprednisolone pulses (1000 mg/day) followed by oral corticosteroid (1 mg/kg/day), extensive infiltrative shadow and pneumomediastinum had developed. The patient died due to acute respiratory failure four weeks after the initial visit.
Table 4.
Treatment-related characteristics of patients.
Fig 5.
Healing process after lung injury.
(1) Exudation phase: inflammation triggers exudation of fibrinogen into the alveolar space, and fibrinogen is converted into fibrin matrix (hematoxylin and eosin staining, ×20). (2) Proliferative phase: fibroblasts and macrophages migrate into the fibrin matrix (hematoxylin and eosin staining, ×20). (3) Organizing phase: the fibrin matrix is replaced by collagen tissue (phosphotungstic acid-hematoxylin staining, ×20).