Idiopathic Pulmonary Fibrosis: Can This Disease Be Named More Precisely?
Much about idiopathic pulmonary fibrosis (IPF) is still unknown. Some experts would like to reclassify this disease. What classification options are available? What would a focus on the "progressive fibrotic phenotype" in research mean? And what would a change in classification mean for patients?
Introduction
IPF remains a disease with unclear pathogenesis, where we know only some genetic predispositions and possible provoking factors, but we cannot fully explain its onset in patients without a genetic burden.
Experts have been debating for years whether the term “idiopathic pulmonary fibrosis” is sufficient. It is probable that in the next decade, IPF will be reclassified, either by division into subgroups or by merging IPF with other forms of progressive fibrotic lung diseases (with the same pathogenetic mechanisms and similar behavior).
IPF Consensus Working Group justifies the clinical and pathogenetic focus of future clinical studies on the “progressive fibrotic phenotype.” A change in classification would also benefit patients without an IPF diagnosis, who, however, have clinical symptoms where treatments effective for IPF patients could apply.
Future naming options for IPF
Among the proposals for new names for IPF are “epithelial pulmonary fibrosis,” “primary pulmonary fibrosis,” or “progressive age-dependent pulmonary fibrosis.” Proponents of these terms believe that the term “idiopathic” is obsolete in this context. They base their claims on the fact that we now know many genetic, environmental, cellular, and molecular mechanisms of IPF onset. They derive from the currently most preferred hypothesis of IPF pathogenesis, which suggests that fibrosis primarily arises from epithelial cell dysfunction. Furthermore, they emphasize that fibrosis is not the only pathogenetic process changing lung structure and leading to epithelial dysfunction in IPF.
Potential pitfalls of renaming
However, a change in nomenclature may be premature at this moment. The term “idiopathic” simply states that the key mechanism of disease onset is unknown. Despite advances in research, the onset of IPF in individual patients without a genetic burden remains unclear.
Moreover, epithelial dysfunction is not the only cause of IPF onset. The pathobiological mechanisms of this disease also include disruption of host defense, T-cell exhaustion, fibroblast activation, oxidative stress, vascular remodeling, alternative macrophage activation, and aging.
IPF Consensus Working Group also questions the inadequacy of the term “fibrosis.” Fibrosis is precisely what makes IPF a lethal disease. The fibrotic basis of IPF is more extensive and progressive than fibrosis in other interstitial lung diseases, such as hypersensitivity pneumonitis or nonspecific interstitial pneumonia.
Division into subtypes or merging?
IPF Consensus Working Group further points out that if we could identify biomarkers associated with the key signaling pathways for IPF, we could identify its subtypes that would selectively respond to targeted personalized therapy. However, until these phenotypic subtypes of IPF are identified and validated, sub-classification of IPF cannot be useful for clinical practice.
The presence of fibrosis is a defining characteristic of a group of progressive lung diseases, including IPF. The authors of the cited work argue that research should focus on the onset and progression of organ fibrosis common to both IPF and other interstitial lung diseases. Combining IPF patients into one group with patients without IPF who, however, have a “progressive fibrotic phenotype” could be a reasonable and scientifically justified step in studies.
Conclusion
Members of the IPF Consensus Working Group believe that the term idiopathic pulmonary fibrosis should remain. Our current understanding of IPF will expand as we discover new information about its subtypes and key pathobiological mechanisms that may also be present in other interstitial lung diseases. Rather than changing IPF nomenclature based on subtypes, it would be more beneficial to explore the progressive fibrotic phenotype. IPF should be retained for comparison with other interstitial diseases.
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Source:
Wells A. U., Brown K. K., Flaherty K. R. et al.; IPF Consensus Working Group. What's in a name? That which we call IPF, by any other name would act the same. Eur Respir J 2018; 51 (5): 1800692, doi: 10.1183/13993003.00692-2018.
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