Idiopathic pulmonary fibrosis (IPF) is a chronic, rare, and fatal disease that is the consequence of aberrant remodeling and defective repair mechanisms within the lung, culminating in the loss of alveolar integrity. Although significant progress has been made in understanding the pathogenesis, it would be crucial to identify biomarkers for diagnosis, prognosis, and prediction of therapy response to improve the management of this challenging and debilitating disease. Omics technologies have profoundly advanced the understanding of disease mechanisms, presenting considerable potential for the identification of clinically relevant biomarkers. To date, specific molecular pathways have been implicated in the onset and progression of idiopathic pulmonary fibrosis, including abnormal wounding, fibroblast proliferation, inflammation, deposition of the extracellular matrix, oxidative stress, endoplasmic reticulum stress, and the coagulation system. This review highlights the role of proteomics in identifying key biomarkers for IPF, focusing on their clinical relevance, including diagnosis, prognosis, disease progression, and the identification of new therapeutic options, in light of the most recent technological advancements in mass spectrometry.

Background: The molecular pathways involved in the onset and progression of idiopathic pulmonary fibrosis (IPF) still need to be fully clarified as some are shared with lung cancer development. HOXB7, a member of the homeobox (Hox) gene family, has been found involved in various cancers. Methods: Immunohistochemical (IHC) analysis was run on lung tissue samples from surgical lung biopsy (SLB) of 19 patients with IPF, retrospectively selected from the IPF database of the University Hospital of Modena. HOXB7 expression was analyzed and compared with that of five patients with no evidence of pulmonary fibrosis as controls. Results: The semi-quantitative analysis of IHC showed that HOXB7 protein expression was higher in IPF patients compared to controls (difference between means = 6.2 ± 2.37, p = 0.0157). Further, HOXB7 expression was higher in IPF patients with a higher extent of fibrosis (50–75%)—measured with high-resolution computer tomography—compared to those with a lower extent (0–25%) (difference between means = 25.74 ± 6.72, p = 0.004). Conclusions: The expression of HOXB7 is higher in the lung of IPF patients compared to controls, and was represented in different cellular compartments within the lung niche. Further investigations are needed to clarify its role in the pathogenesis and progression of IPF.

Recent advances in genetics and epigenetics have provided critical insights into the pathogenesis of both idiopathic and non-idiopathic interstitial lung diseases (ILDs). Mutations in telomere-related genes and surfactant proteins have been linked to familial pulmonary fibrosis, while variants in MUC5B and TOLLIP increase the risk of ILD, including idiopathic pulmonary fibrosis and rheumatoid arthritis-associated ILD. Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs such as miR-21 and miR-29, regulate fibrotic pathways, influencing disease onset and progression. Although no standardized genetic panel for ILD exists, understanding the interplay of genetic mutations and epigenetic alterations could aid in the development of personalized therapeutic approaches. This review highlights the genetic and epigenetic factors driving ILD, emphasizing their potential for refining diagnosis and treatment.

In recent years, several studies have examined the impact of sleep-disordered breathing (SBD) on the quality of life and prognosis of patients with idiopathic pulmonary fibrosis (IPF). Among these disorders, obstructive sleep apnea (OSA) and nocturnal hypoxemia (NH) are the most prevalent and extensively studied, whereas central sleep apnea (CSA) has only been documented in recent research. The mechanisms underlying the relationship between IPF and SBDs are complex and remain an area of active investigation. Despite growing recognition of SBDs in IPF, no standardized guidelines exist for their management and treatment, particularly in a population characterized by distinct structural pulmonary abnormalities. This review outlines the pathophysiological connections between sleep-breathing disorders (SBDs) and idiopathic pulmonary fibrosis (IPF), as well as current therapeutic options. A comprehensive literature search using PubMed identified relevant studies, confirming the efficacy of CPAP in treating severe OSA and CSA. While high-flow oxygen therapy has not been validated in this patient cohort, it may offer a potential solution for select patients, particularly the elderly and those with low compliance. Conventional oxygen therapy, however, is limited to cases of isolated nocturnal hypoxemia or mild central sleep apnea.

Idiopathic pulmonary fibrosis (IPF) is a chronic, rare and fatal disease that is the conse-quence of aberrant remodeling and defective repair mechanisms within the lung cul-minating in the loss of alveolar integrity. Although significant progress has been made in understanding the pathogenesis, it would be crucial to identify biomarkers for diagnosis, prognosis and prediction of therapy response to improve management of this challenging and debilitating disease. Omics technologies have profoundly advanced the under-standing of disease mechanisms, presenting considerable potential for the identification of clinically relevant biomarkers. To date, specific molecular pathways have been impli-cated in the onset and progression of idiopathic pulmonary fibrosis, including abnormal wounding, fibroblast proliferation, inflammation, deposition of extracellular matrix, oxidative stress, endoplasmic reticulum stress and coagulation system. This review highlights the role of proteomics in identifying key biomarkers for IPF, focusing on their clinical relevance, including diagnosis, prognosis, disease progression and the identifi-cation of new therapeutic options, in light of the most recent technological advancements in mass spectrometry.

Background: Generic formulations of pirfenidone are increasingly adopted in idiopathic pulmonary fibrosis (IPF), yet real-world evidence supporting their clinical equivalence to the originator remains limited. We aimed to evaluate whether switching from branded pirfenidone (Esbriet ^® ) to a generic formulation affects treatment efficacy or tolerability. Methods: We conducted a retrospective, within-patient observational study including consecutive patients with IPF treated with Esbriet ^® for ≥ 6 months before switching to generic pirfenidone. Pulmonary function was assessed at three time points: 6 months before the switch (T − 6), at switch (T0), and 6 months after (T + 6). The primary endpoint was the within-patient percentage change in FVC over two consecutive 6-month periods (T − 6 → T0 vs T0 → T + 6), analysed within a pre-specified equivalence framework (± 5 percentage points). Secondary endpoints included DLCO changes and treatment-related adverse events (AEs), analysed at the patient level using paired comparisons. Results: Sixty-five patients (median age 77.0 years [72.3–80.0] years, 78% male) had complete functional follow-up. The mean percentage decline in FVC was − 1.9% before the switch and − 1.7% after the switch. The estimated between-period difference in FVC change was 0.2 percentage points (95% CI − 1.1 to 1.5), fully contained within the pre-specified equivalence margins. Similar findings were observed for DLCO, with no significant difference between periods. Overall, 43% of patients experienced at least one AE during treatment. Gastrointestinal AEs were the most frequent, but paired analyses showed no significant difference in patient-level AE occurrence between branded and generic periods. No severe AEs or treatment discontinuations were observed. Conclusions: In this real-world cohort of patients with IPF, switching from branded to generic pirfenidone was not associated with clinically meaningful differences in lung function decline or treatment tolerability.