Precision medicine advances in idiopathic pulmonary fibrosis

Genetic association between smoking and DLCO in idiopathic pulmonary fibrosis patients

“…However, given the infancy of computed tomography biomarkers, estimates of disease severity and risk stratification in IPF are still based almost exclusively on functional and physiologic indices, such as forceful lung volume (FVC), diffusing capacity for carbon monoxide (DLCO), and the 6-minute walk test (6MWT), with DLCO considered one of the most valuable parameters for monitoring the progression of IPF. DLCO is considered one of the most valuable pulmonary function test parameters for monitoring the progression of IPF [ 29 – 31 ].. To the best of our knowledge, this is the first study to determine the causal links between smoking and DLCO in patients with IPF based on the MR framework. Our approach drew upon large-scale GWAS data, allowing us to analyse a substantially larger number of cases than did previous observational studies.…”

“…For example, higher levels of LOXL2 are associated with poor progression in IPF patients, and there is evidence that LOXL2 is significantly upregulated in patients who smoke. Moreover, SP-D, a serum marker, was found to be higher in smoking patients compared to non-smoking patients [ 31 , 38 , 39 ]. All these imply a potential relationship between CS and multiple IPF prognostic factors.…”

Editorial: Immune-mediated lung injury

“…For example, cellular deconvolution of the 52-gene signature, a highly reproducible biomarker in IPF, showed that monocytes are the cellular source of the upregulated genes. This paved the way for clinical studies showing the prognostic potential of monocyte count in ILDs as well as mechanistic studies investigating the role of monocytes/ myeloid derived suppressor cells in pulmonary fibrosis (5)(6)(7)(8)(9).…”

“…2) Are genes that predict mortality in IPF and COVID-19, still abundantly expressed in post-COVID-19-ILD? Extensive investigation of genes that predict mortality in IPF suggested that monocytes/myeloid derived suppressor cells persist during the disease course, while T cells might exhibit exhaustion (5)(6)(7)(8)(9)(10)(11). Similarly in COVID-19, myeloid cells have been shown to be highly activated (12), with dysfunctional HLA-DR lo CD163 hi and HLA-DR lo S100A hi CD14 + monocytes being present in patients with severe disease (13).…”

Response to: are there over 200 distinct types of interstitial lung diseases?

“…Moreover, splitting specific ILDs into subgroups based on the improving understanding of disease biology has the advantage of distinguishing prognostic trajectories and potentially identifying new targeted therapies [ 5 ]. As an example, classifying pulmonary fibrosis (PF) as MUC5B-PF or telomeropathy-PF instead of using the word “idiopathic” might be a better approach to classify the disease based on its behavior [ 6 ]. Treating endotypes with targeted therapies based on the expression of specific biomarkers could maximize the effectiveness of existing or new therapies, such as the case of synthetic androgen danazol for patients with short telomeres or the use of N-Acetylcysteine based on TOLLIP gene variants in IPF patients [ 7 , 8 ].…”