Sabato 27 ottobre 2012 - Pacini Editore

RElaziONi
The pathogenesis of idiopathic pulmonary
fibrosis: new perspectives
M. Chilosi
Anatomia Patologica, Department of Pathology, University of Verona
Idiopathic pulmonary fibrosis (IPF) is the most common and
severe form of idiopathic interstitial pneumonia, and its median
survival is 3-4 years. New concepts have been recently
proposed regarding the biology and pathogenesis of this
devastating disease, focused on a sequential epithelial cell
injury, followed by deranged activation of lung reparative
processes 1-3 . Accumulating evidence is available that in IPF
the abnormal re-epithelialization after injury can be related
to a progressive and localized stem-cell exhaustion due to intrinsic
cellular defects either related to a predisposing genetic
background (familial IPF is a well recognized entity), or to the
aging-related accumulation of metabolic alterations (e.g. due
to toxic effects of smoking, pollution, metabolic abnormalities,
or other causes) 2 . The remodeling process in this scheme
is likely related to the abnormal triggering at sites of disease
development of different molecular pathways crucial to lung
tissue development and regeneration, including the wnt-betacatenin
pathway, TGF-beta, NOTCH, and others 4 5 .
Nevertheless, a missing point in this pathogenic scenario is
related to the peculiar localization of IPF lesions, that typically
start at the bases of the lower lobes, progressively extending in
a caudal-cranial mode. Several lines of evidence suggest that
these anatomical parts of the lung are in fact sites where mechanical
forces can be particularly concentrated, thus triggering
the formation of microscopic tears in the alveolar structure,
which may result in repetitive small scarring events (fibroblast
foci), and eventual honeycomb changes 6-8 . The microscopic
Fig. 1.
Venerdì, 26 ottobre 2012
Sala Giotto – 08.30-10.30
Patologia polmonare 1
Patologie polmonari diffuse: una sfida per il patologo
Moderatori: Camilla Comin (Firenze), Oscar Nappi (Napoli)
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damages due to chronic mechanical stress located in these
areas can in fact cooperate in a sequence of pathogenic events,
including 1: localized accelerated pneumocyte turnover, with
eventual increase of replicative senescence, 2: occurrence of
a “senescence-induced hypersecretive phenotype” (SASP) 9
within these parts of the lung parenchyma, 3: abnormal activation
of reparative molecular pathways (e.g. wnt-pathway) 4 5 ,
leading to abnormal remodeling of the lung parenchyma.
references
1 Selman M, Pardo A. Idiopathic pulmonary fibrosis: an epithelial/
fibroblastic cross-talk disorder. Respir Res 2002;3:3.
2 Chilosi M, Doglioni C, Murer B, et al. Epithelial stem cell exhaustion
in the pathogenesis of idiopathic pulmonary fibrosis. Sarcoidosis Vasc
Diffuse Lung Dis 2010;27:7-18.
3 Chilosi M, Poletti V, Rossi A. The pathogenesis of COPD and IPF:
distinct horns of the same devil? Respir Res 2012;13:3.
4 Chilosi M, Poletti V, Zamò A, et al. Aberrant Wnt/beta-catenin
pathway activation in idiopathic pulmonary fibrosis. Am J Pathol
2003;162:1495-502.
5 Königshoff M, Balsara N, Pfaff EM, et al. Functional Wnt signaling is
increased in idiopathic pulmonary fibrosis. PLoS One 2008;3:e2142.
6 Dail-DH. Pulmonary apical cap. Am J Surg Pathol 2001;25:1344.
7 Cabrera-Benítez NE, Parotto M, Post M, et al. Mechanical stress
induces lung fibrosis by epithelial-mesenchymal transition. Crit Care
Med 2012;40:510-7.
8 Leslie KO. Idiopathic pulmonary fibrosis may be a disease of recurrent,
tractional injury to the periphery of the aging lung: a unifying
hypothesis regarding etiology and pathogenesis. Arch Pathol Lab
Med. 2012;136:591-600.
9 Coppé JP, Desprez PY, Krtolica A, et al. The senescence-associated
secretory phenotype: the dark side of tumor suppression. Annu Rev
Pathol 2010;5:99-118.
Smoking-related interstitial lung disease
(Modified from Caminati et al. An integrated clinical-radiological-pathological
approach to smoking-related interstitial
lung disease. Eur Respir Rev, in press).
A. Cavazza, M. Ragazzi, E. Tagliavini
Unità Operativa di Anatomia Patologica, Ospedale S. Maria Nuova-
IRCCS, Reggio Emilia
In the lung, apart being the main cause of emphysema/COPD,
carcinoma and idiopathic spontaneous pneumothorax, tobacco
smoke is associated with several interstitial lung diseases
(ILD) including respiratory bronchiolitis-associated ILD (RB-
ILD), desquamative interstitial pneumonia (DIP), Langerhans
cell histiocytosis (LCH), idiopathic pulmonary fibrosis (IPF),
acute eosinophilic pneumonia, ILD in rheumatoid arthritis and
pulmonary hemorrhage in Goodpasture syndrome. This talk
will focus on the histological features of the first three diseases,
which have the strongest epidemiological association
with smoke. Their main clinical, radiological and histological
features are summarized in the following table.
Respiratory bronchiolitis. The most characteristic effect of
tobacco smoke on lung parenchyma is respiratory bronchi-