Idiopathic pulmonary fibrosis (IPF) is a highly heterogeneous, unpredictable and ultimately lethal chronic lung disease. Over the last decade, two anti-fibrotic agents have been shown to slow disease progression, however, both drugs are administered uniformly with minimal consideration of disease severity and inter-individual molecular, genetic, and genomic differences. Advances in biological understanding of disease endotyping and the emergence of precision medicine have shown that "a one-size-fits-all approach" to the management of chronic lung diseases is no longer appropriate. While precision medicine approaches have revolutionized the management of other diseases such as lung cancer and asthma, the implementation of precision medicine in IPF clinical practice remains an unmet need despite several reports demonstrating a large number of diagnostic, prognostic and theragnostic biomarker candidates in IPF. This review article aims to summarize our current knowledge of precision medicine in IPF and highlight barriers to translate these research findings into clinical practice.

Background: Idiopathic Pulmonary Fibrosis (IPF) represents a chronic lung disease with unpredictable course. Methods: We aimed to investigate prognostic performance of complete blood count parameters in IPF. Treatment-naïve patients with IPF were retrospectively enrolled from two independent cohorts (derivation and validation) and split into subgroups (high and low) based on median baseline monocyte count and red cell distribution width (RDW). Results: Overall, 489 patients (derivation cohort: 300, validation cohort: 189) were analyzed. In the derivation cohort, patients with monocyte count ≥ 0.60 K/μL had significantly lower median FVC%pred [75.0, (95% CI 71.3–76.7) vs. 80.9, (95% CI 77.5–83.1), (P = 0.01)] and DLCO%pred [47.5, (95% CI 44.3–52.3) vs. 53.0, (95% CI 48.0–56.7), (P = 0.02)] than patients with monocyte count < 0.60 K/μL. Patients with RDW ≥ 14.1% had significantly lower median FVC%pred [75.5, (95% CI 71.2–79.2) vs. 78.3, (95% CI 76.0–81.0), (P = 0.04)] and DLCO%pred [45.4, (95% CI 43.3–50.5) vs. 53.0, (95% CI 50.8–56.8), (P = 0.008)] than patients with RDW < 14.1%. Cut-off thresholds from the derivation cohort were applied to the validation cohort with similar discriminatory value, as indicated by significant differences in median DLCO%pred between patients with high vs. low monocyte count [37.8, (95% CI 35.5–41.1) vs. 45.5, (95% CI 41.9–49.4), (P < 0.001)] and RDW [37.9, (95% CI 33.4–40.7) vs. 44.4, (95% CI 41.5–48.9), (P < 0.001)]. Patients with high monocyte count and RDW of the validation cohort exhibited a trend towards lower median FVC%pred (P = 0.09) and significantly lower median FVC%pred (P = 0.001), respectively. Kaplan–Meier analysis in the derivation cohort demonstrated higher all-cause mortality in patients with high (≥ 0.60 K/μL) vs. low monocyte count (< 0.60 K/μL) [HR 2.05, (95% CI 1.19–3.53), (P = 0.01)]. Conclusions: Increased monocyte count and RDW may represent negative prognostic biomarkers in patients with IPF.

Background: Fibrotic hypersensitivity pneumonitis (f-HP) can exhibit a progressive course similar to idiopathic pulmonary fibrosis (IPF). The lack of diagnostic guidelines and randomised controlled trials in this population represent a significant unmet need.Objectives: To describe our clinical experience with antifibrotics in patients with f-HP.Material and methods: Retrospective study of 30 patients diagnosed with f-HP upon re-evaluation within a multidisciplinary team discussion of 295 consecutive patients (January 2012 to December 2017) who had been diagnosed initially with IPF at outside facilities and were referred to our centres.Results: Pirfenidone was initially administered to 14 (46.7%) patients and nintedanib to 16 (53.3%) patients. There were 26 (86.7%) males, with mean±sdage 70.2±8.4 years. The annual rate of decline in forced vital capacity (FVC) % predicted over the 3-year treatment period adjusted for baseline FVC % pred measurement was 4.2% (95% CI 1.9–6.6%, p=0.001) and 7.5% (95% CI 3.3–11.7%; p=0.001) in imputation analysis. The annual rate of decline in diffusing capacity of the lung for carbon monoxide (D_LCO) % predicted throughout the 3-year treatment period adjusted for baselineD_LCO% pred was 5.7% (95% CI 3.1–8.4%, p<0.001) and 5.8% (95% CI 3.4–8.1%, p<0.001) in imputation analysis. The nature of adverse events was related to the type of antifibrotic agent administered.Conclusion: In patients with f-HP receiving antifibrotics there is a statistically significant annual decline in FVC % pred andD_LCO% pred over a period of 3 years. Prospective randomised trials exceeding 1 year are warranted to determine the long-term efficacy of antifibrotics.

Interstitial lung diseases (ILDs) represent a broad group of heterogeneous parenchymal lung diseases. Some ILDs progress, causing architectural distortion and pulmonary fibrosis, and thus are called fibrotic ILDs. Recent studies have shown a beneficial effect of antifibrotic therapy in fibrotic ILDs other than idiopathic pulmonary fibrosis (IPF) that manifest progressive pulmonary fibrosis (PPF). However, it remains challenging to predict which patients with fibrotic ILDs will demonstrate PPF. Precision medicine approaches could identify patients at risk for progression and guide treatment in patients with IPF or PPF. Multiple biomarkers able to highlight disease susceptibility risk, to provide an accurate diagnosis, and to prognosticate or assess treatment response have been identified. Advances in precision medicine led to the identification of endotypes that could discriminate patients with different fibrotic ILDs or patients with different disease courses. Importantly, recent studies have shown that particular compounds were efficacious only in particular endotypes. The aforementioned findings are promising. However, implementation in clinical practice remains an unmet need. Substantial progress has been observed in the context of precision medicine approaches in fibrotic ILDs in recent years. Nonetheless, infrastructure, financial, regulatory, and ethical challenges remain before precision medicine can be implemented in clinical practice. Overcoming such barriers and moving from a one-size-fits-all approach to patient-centered care could improve patient quality of life and survival substantially.