The nasal epithelium of patients with idiopathic pulmonary fibrosis (IPF) shows different levels of gene expression implicated in inflammatory and immune responses than those without the disease, a study reports.
According to the researchers, these findings support nasal sampling as a noninvasive and inexpensive approach to identify and monitor IPF patients.
The study, “Inflammatory pathways are upregulated in the nasal epithelium in patients with idiopathic pulmonary fibrosis,” was published in the journal Respiratory Research.
High-resolution computed tomography of the chest is the only current noninvasive approach to screen for IPF. However, its high cost, IPF’s low prevalence, and the risk of radiation exposure mean that this strategy is not feasible as a screening tool, resulting in diagnostic delay. In addition, studies of blood biomarkers for IPF have not been successful.
Other studies have shown increased levels of several proteins in IPF, including those of the extracellular matrix — which provides structural and biochemical support to cells and drives fibrosis, or scarring — and growth factors, as well as epithelial-related genes. But because these studies require lung biopsies, they have limited applicability for screening or disease management.
Work in lung cancer has shown that the expression level of 11 genes in epithelial tissues from the bronchi helps to manage small asymptomatic nodules in the lung. Later studies in the nasal epithelium — the surface layer of the nasal mucosa — led to similar results, supporting the idea that epithelial changes are a consequence of changes throughout the respiratory tract. This opened the possibility for a noninvasive test to inform the management of suspected lung cancer.
A team from the U.S. and Mexico aimed to find out whether a similar approach would be possible in IPF. For this purpose, the scientists compared the transcriptome — which refers to the entire collection of messenger RNAs (generated from DNA for protein production) — of the nasal epithelium of 10 IPF patients, at a mean age of 68 years, and 23 age-matched healthy individuals, at a mean age of 64.4 years, used as controls. All participants were of Mexican-Mestizo ancestry and lived in Mexico City.
Five biopsies of the nasal mucosa from each participant were collected in an outpatient setting at Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas in Mexico.
All IPF patients were clinically stable. The average duration of symptoms before IPF diagnosis was 28 months.
A total of 224 genes in IPF samples had different levels of expression than controls, 222 of which were increased, while only two were decreased in patients with IPF.
A functional analysis then showed that most genes with different levels of expression were associated with pattern-recognition receptor functions — implicated in immune function — receptor activity, binding to the major histocompatibility complex (a set of cell surface proteins that boost immune responses), and peptide-antigen binding, as well as enzyme and cytokine (molecules involved in inflammation) binding.
Concerning more specific pathways, these genes were found to be implicated in pathways involved in the innate and adaptive immune system, interferons (proteins secreted by immune cells), neutrophil degranulation (a feature of inflammatory disorders), the NF-κB pathway, toll-like receptor and endoplasmic reticulum-phagosome pathways — all also implicated in immune response — antigen presentation, cytokine signaling, and response to bacteria and viruses.
“Pathway enrichment analysis revealed upregulation of pathways related to immune response and inflammatory signaling in IPF patients compared with controls,” the researchers wrote.
When examining the genes with the highest expression, the team obtained a list of 12 that were upregulated in most patients, keeping most of the identified biological processes. These results were not influenced by gender differences, nor by smoking exposure.
Despite the small number of participants in the study, the team believes their findings “support further studies of the nasal transcriptome to identify biomarkers that can identify patients with or at risk for IPF earlier in their disease.”
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