Mapping the future for pulmonary fibrosis:
report from the 17th International
Colloquium on Lung and Airway Fibrosis
Luca Richeldi1, Harold R. Collard2, Roland M. du Bois3, Gisli Jenkins4,
Martin Kolb5, Toby M. Maher6, Ganesh Raghu7, Carlo Vancheri8
and Geoffrey J. Laurent9,10
Affiliations:1Centre for Rare Lung Diseases, University of Modena and Reggio Emilia, Modena, and8Dept of
Internal Medicine, University of Catania, Catania, Italy.
7Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA, USA.
College London, London,
Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, and10University
College London, London, UK.
University, Hamilton, Canada.9University of Western Australia, Perth, Australia. All authors were members of
the scientific committee of the 17th ICLAF meeting.
2University of California, San Francisco, CA, and
4University of Nottingham, Nottingham,
6Interstitial Lung Disease Unit, Royal
5Dept of Respiratory Medicine, Pathology and Molecular Medicine, McMaster
Correspondence: L. Richeldi, Centre for Rare Lung Diseases, University Hospital of Modena, Via del Pozzo 71,
41124 Modena, Italy. E-mail: firstname.lastname@example.org
which have a dismal prognosis. Pulmonary fibrosis, therefore, represents a critical unmet medical need.
Progress in research over the past 30 years has been encouraging. This work, which has been funded by
governments, charitable trusts, industries and patient groups, has resulted in clinical trials testing novel
drugs, giving hope to patients. In late September 2012, representatives from academia, industry and funding
agencies met at the 17th International Colloquium on Airway and Lung Fibrosis to discuss state-of-the-art
knowledge of pulmonary fibrosis. This manuscript summarises the outcomes of the meeting, highlighting
the most relevant results and discoveries. It also attempts to provide a roadmap for future studies. It is
hoped that such a roadmap may help interested parties to generate new research, which will be vital to
continued progress. We are encouraged by the commitment expressed by all participants at this meeting
and the shared vision of promoting future progress through international collaboration, the pooling of
valuable resources, and the involvement of a new generation of physicians and scientists.
Pulmonary fibrosis is the ultimate outcome of various interstitial lung diseases, many of
Progress report from the 17th international colloquium on lung and airway fibrosis: a roadmap for
future studies http://ow.ly/kUltb
Received: March 04 2013 | Accepted after revision: April 17 2013 | First published online: May 16 2013
Conflict of interest: Disclosures can be found alongside the online version of this article at www.erj.ersjournals.com
Copyright ?ERS 2013
THE FUTURE FOR PULMONARY FIBROSIS
Eur Respir J 2013; 42: 230–238 | DOI: 10.1183/09031936.00038613 230
ICLAF: a long journey
The International Colloquium on Lung Fibrosis began in 1980, in London, UK, intended as a forum for
intimate, in depth discussion of the basic and clinical science of fibrotic lung disease. With evolving
knowledge of the pathogenesis of pulmonary fibrosis and the recognition that fibrosis within the lumen of
distal airways is a component of some fibrotic lung diseases, the acronym ICLAF (International Colloquium
on Lung and Airway Fibrosis) was coined, to include airway fibrosis, in 2008. The 17th ICLAF meeting took
place between September 29 and October 3, 2012 (www.iclaf2012.unimore.it), when 258 participants from
22 different countries gathered together in Modena, Italy, for four days of presentations, lectures, posters
and small group discussions. In attendance was a dynamic mix of clinicians, basic scientists, clinical
researchers, industry colleagues and advocacy groups. This manuscript reviews the highlights of the
conference and provides a ‘‘road map’’ for further research in this area, touching upon the main spheres of
research in this rapidly evolving area of respiratory medicine (fig. 1). All sessions during the conference
were video recorded and are freely available to everyone on a dedicated website .
DavidWarburton (LosAngeles,CA,USA) placedfibrotic lung diseasesin a developmental context, suggesting
that abnormal development might contribute to the susceptibility to adult lung fibrosis and emphysema.
Pulmonary emphysema and fibrosis may represent a useful model for the study of the potential synergistic
effects of genetic defects in chronic lung disorders . Microinjection of amniotic fluid stem cells (AFSC) into
embryonic lungs showed that AFSC can differentiate into type II pneumocytes, while in the presence of an
oxidative stress AFSC can integrate into the epithelium of the upper airways and alveoli. Moreover,
transplantation of AFSC, which are safely collectable through amniocentesis samples without major ethical
concerns, can retard the progression of bleomycin-induced lung fibrosis in the mouse via a type II cell
dependent mechanism. These studies pave the way for a new approach using stem cells in pulmonary fibrosis.
Victor J. Thannickal (Birmingham, AL, USA) identified and attempted to reconcile some apparent paradoxes
in our current understanding of the pathogenesis of idiopathic pulmonary fibrosis (IPF). Specifically, he
discussed the ‘‘matrix paradox’’ and the ‘‘ageing paradox’’. Matrix stiffness transduces nuclear signalling
events that regulate myofibroblast differentiation and survival via an intrinsic mechanotransduction pathway
. This mechanosensitive signalling pathway could be a target for anti-fibrotic therapies involving Rho-
associated protein kinase (ROCK) inhibitors such as fasudil, a molecule capable of inducing in vivo apoptosis
of myofibroblasts following fibrogenic lung injury. Interestingly, inhibition of this mechanosensitive Rho
kinase pathway with fasudil induces activation of the intrinsic mitochondrial apoptosis pathway in fibroblasts
derived from patients with IPF, but not in fibroblasts from healthy donors. Furthermore, this approach
ameliorates experimental pulmonary fibrosis . Age-related diseases such as IPF may be associated with
cellular senescence of specific lung cells. The data presented demonstrated that fibroblastic foci in IPF lungs
express senescence markers; however, fibrosis appears to ‘‘paradoxically’’ require the proliferative expansion
of fibroblasts. One oxidative stress-dependent pathway that leads to myofibroblast senescence and apoptosis
resistance is NADPH oxidase 4 (NOX4). This might represent a promising therapeutic target in IPF  and
potentially other chronic fibrotic disorders.
Seamas Donnelly (Dublin, Ireland) explored the complex interrelationships between viral infections and
IPF. In particular, he presented new data supporting the hypothesis that repeated viral infection would
predispose towards a more aggressive fibrotic response via a Toll-like receptor 3 (TLR3)-dependant process.
The post hoc analysis of TLR3 polymorphisms in the cohort of a large, historical trial on the use of interferon
(IFN)-c in IPF  showed that a single genetic polymorphism of the TLR3 gene is associated with
accelerated lung function decline and enhanced mortality. These intriguing data prompted in vitro and
animal studies, confirming the critical role of TLR3 and IFN in driving a more aggressive clinical phenotype
in pulmonary fibrosis. This work highlights a significant genetic marker for enriching clinical trial
FIGURE 1 Key research steps in
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