Organizing pneumonia is a clinical,
radiological and histological pattern characterized by the presence of granulation tissue within the terminal or respiratory bronchioles,
in the alveolar ducts and surrounding alveoli (note that the bronchiolar component may be lacking) and chronic inflammation of the remaining lung parenchyma [1].
OP can be secondary to many extra-lung conditions (infections [2],
drug toxicity [3-6],
radiotherapy [4,7,8],
collagen diseases [9],
oncologic conditions [10,11] or pulmonary conditions ( pneumonia,
vasculitis,
lung cancer)or it can be cryptogenic [2].
The idiopathic form of OP is called COP and classified as an acute/subacute Interstitial Lung Disease in the ATS/ERS paper of 2013 [12].
The term Cryptogenetic Organizing Pneumonia has been first used by Davidson in 1983 [13].
The same entity was then described two years later,
by Epler but with the name of BOOP (Bronchiolitis obliterans organizing pneumonia)[1]; this term was thereafter put aside because the semantic similarity with bronchiolitis obliterans,
which is a completely different entity [14].
In this work we will use the term “COP” to refer to the nosological entity.
COP can mime many pneumopathy and it’s mandatory excludes these conditions before a COP diagnosis [12].
Epidemiology and clinical features
The incidence of Cryptogenic organizing pneumonia (COP) is not well known.
Mean age at onset varies from 50 to 60 years.
The two sexes are usually equally affected,
with a prevalence in non-smokers [15] and it’s not clear if smoke could be a protective factor [16].
It makes up between 1.8% and 13% of all interstitial lung diseases (ILDs) according to different studies [17-19].
CLINICAL FEATURES
Classic symptoms are those associated with flu-like illness (fever,
cough,
weakness) and progressively mild dyspnea (that can be severe,
associated to a rapidly progressive disease).
Uncommon manifestations include hemoptysis,
chest pain,
night sweats and mild arthralgia.
Diagnosis is often delayed because of these un-specific manifestations [12].
On physical examination,
crackles are the most common abnormality found.
There is no finger clubbing [15].
LUNG FUNCTION TESTS
At spirometry,
the most common abnormality is a restrictive ventilator defect; DLCO is reduced [12].
An obstructive ventilatory defect is present in a minority of patients (20%),
usually smokers.
More than 80% of affected individuals have mild resting hypoxemia [15].
Histopatological features
As well described by Cordier J.
in 2006 [16],
OP is the result of a lung injury in the alveolar epithelium which produces pneumocytes death and gaps in basal lamina.
Immune system reacts to this damage with the leakage of plasmatic proteins (including clotting factors) in the airspaces.
The activation of coagulation cascade leads to the formation of fibrin strands.
Inflammatory cells,
as lymphocytes,
neutrophil and eosinophil,
take part in this process too,
leading to migration of fibroblast in basal lamina [20]; fibroblast proliferates and going into a phenotypic transformation into myofibroblast [2].
At the end,
mature fibrotic buds are formed with the production of the characteristic Masson bodies: elongated polipoidal masses,
formed by granulation tissue,
whorls of fibroblast and myofibroblast in a connective matrix [14].
These masson bodies may migrate through Kohn pores to an alveolus to another,
leading to the characteristic butterfly pattern [16].
The inflammatory component can regress and the matrix can be reabsorbed [14,21].
BAL
Bronchoalveolar lavage is helpful to recognize the differential diagnosis and could be used to exclude other disorders. The pattern is described as “mixed”,
with increased lymphocytes (20–40%),
neutrophils (about 10%),
and eosinophils (about 5%) [22].