The document discusses mechanisms of intra-alveolar organization in cryptogenic organizing pneumonia (COP). It describes the process by which epithelial injury leads to fibrin deposition and proliferation of fibroblasts within the alveolar lumen. Mature fibrotic buds form due to production of connective matrix by myofibroblasts. In contrast to diffuse alveolar damage, COP does not form hyaline membranes. Prominent capillarization of intra-alveolar buds resembles granulation tissue. Angiogenesis factors may contribute to resolution of buds in organizing pneumonia.

1. Photomicrograph of specimen from open lung biopsy in a patient with cryptogenic organizing pneumonia. A
polypoid mass of granulation tissue is filling the lumen of an alveolar duct (Masson body).

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Mechanisms of intra-alveolar organisation. a) Normal alveolus. b) Epithelial alveolar injury with necrosis of
pneumocytes (especially type I pneumocytes; P1),
formation of gaps in the basal lamina, and intra-alveolar leakage of coagulation plasma proteins. The balance
between coagulation and fibrinolytic cascades favours
coagulation and results in intra-alveolar deposits of fibrin. c) Activation, proliferation and migration of the
fibroblasts (F) within the alveolar lumen through gaps in the basal
lamina. d) Most fibroblasts have acquired a phenotype of myofibroblasts (MF) and produce connective matrix
proteins forming mature fibrotic intra-alveolar buds composed
of concentric circular layers of MF and connective matrix. CAP: capillary; P2: type 2 pneumocyte; F/M: fibroblast
undergoing mitosis; C: connective matrix (collagens,
fibronectin, glycoproteins

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In contrast with diffuse alveolar damage, no hyaline
membranes are found

4. Characteristic of the intra-alveolar buds in COP is the
prominent capillarisation, which is reminiscent of granulation
Vascular endothelial growth factor and basic fibroblast growth factor are widely expressed
Angiogenesis mediated by these
growth factors could contribute to the reversal of buds in
organising pneumonia.

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(when arthralgia is prominent and/ or associated with myalgia an underlying connective tissue disease should be
suspected

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Thirty-seven year old woman with a two week history of cough, dyspnea with exertion, fatigue, and fever. She
developed respiratory failure and was hospitalized. Posteroanterior roentgenogram reveals bilateral patchy
opacities and volume loss. An open lung biopsy confirmed an extensive COP pattern. There was complete
resolution following glucocorticoid therapy without recurrence after glucocorticoids were discontinued

7. Typical cryptogenic organising pneumonia showing patchy
bilateral alveolar opacities on a) chest radiograph and b) high-resolution computed
tomography scan.

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each defined by an alveolar-arterial oxygen gradient greater than 20 mmHg)

9. as
demonstrated by increased alveolar–arterial oxygen difference
on breathing 100% oxygen and negative contrast echocardiography
[160, 161]. This is likely to result from defective
vasoconstriction in areas of nonventilated alveoli because of
intra-alveolar buds occupying the entire lumen of alveoli

10. In two retrospective studies, focal organizing pneumonia was found in resected solitary pulmonary nodules in a
combined total of 43 patients [32,33]. No further therapy was given and there was no recurrence in 41 patients;
the two patients with local recurrences were treated successfully with glucocorticoids.

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Review of nine major published reports in 157 subjects with COP and IPF in whom the diagnosis was confirmed
by lung biopsy. The rate of recovery is much higher and that of persistent disease is much lower in the patients
with COP. Patients with IPF rarely improved completely with therapy.