Idiopathic Pulmonary Fibrosis: Molecular Endotypes of Fibrosis Stratifying Existing and Emerging Therapies.

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown causes. Current diagnostic criteria are based on radiological, clinical, and histopathological features but, unfortunately, still many patients remain undiagnosed. Two currently approved therapies, pirfenidone and nintedanib, slow down disease progression but failed to block or revert it. On the other hand, many of the therapeutic agents tested in several clinical trials have not given satisfactory answers, probably due to the pathological heterogeneity of the disease. A growing number of studies show that IPF phenotype is the common clinical outcome of a variety of different pathophysiological mechanisms that identify disease subgroups characterised by specific genetic and molecular biomarkers (endotypes). The precision medicine approach is identifying and analysing the complex system of genetic, molecular, environmental, and behavioural variables underlying the development of the disease and the response to therapy. These molecular pathways are potential targets for novel agents and useful diagnostic, prognostic, and theragnostic biomarkers. We outline the status of knowledge in this field by discussing the complex pathogenetic pathways underlying different disease subgroups and assessing a stratification approach to novel therapeutic agents based on these endotypes.

Ultrasonographic assessment of the diaphragm in chronic obstructive pulmonary disease patients: relationships with pulmonary function and the influence of body composition - a pilot study.

BACKGROUND: Skeletal muscle weakness with loss of fat-free mass (FFM) is one of the main systemic effects of chronic obstructive pulmonary disease (COPD). The diaphragm is also involved, leading to disadvantageous conditions and poor contractile capacities. OBJECTIVES: We measured the thickness of the diaphragm (TD) by ultrasonography to evaluate the relationships between echographic measurements, parameters of respiratory function and body composition data. METHODS: Thirty-two patients (23 males) underwent (1) pulmonary function tests, (2) echographic assessment of TD in the zone of apposition at various lung volumes, i.e. TD at residual volume (TDRV), TD at functional residual capacity (TDFRC) and TD at total lung capacity (TDTLC), and (3) bioelectrical body impedance analysis. The BMI and the BODE (BMI-Obstruction-Dyspnea-Exercise) index values were reported. RESULTS: TDRV, TDFRC and TDTLC measured 3.3, 3.6 and 6 mm, respectively, with good intraobserver reproducibility (0.97, 0.97 and 0.96, respectively). All the TDs were found to be related to FFM, with the relationship being greater for TDFRC (r(2) = 0.39 and p = 0.0002). With regard to lung volumes, inspiratory capacity (IC) was found to be closely related to TDTLC (r(2) = 0.42 and p = 0.0001). The difference between TDTLC and TDRV, as a thickening value (TDTLCRV), was closely related to FVC (r(2) = 0.34 and p = 0.0004) and to air-trapping indices (RV/TLC, FRC/TLC and IC/TLC): the degree of lung hyperinflation was greater and the TDTLCRV was less. Finally, we found a progressive reduction of both thicknesses and thickenings as the severity of IC/TLC increased, with a significant p value for the trend in both analyses (p = 0.02). CONCLUSIONS: Ultrasonographic assessment of the diaphragm could be a useful tool for studying disease progression in COPD patients, in terms of lung hyperinflation and the loss of FFM. © 2014 S. Karger AG, Basel.

Pulmonary fibrolysis in a patient with idiopathic pulmonary fibrosis: improvement of clinical and radiological pattern after treatment with pirfenidone.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia associated with the histologic and/or radiologic pattern of usual interstitial pneumonia (UIP). Nowadays, the high-resolution computed tomography pattern of "definite UIP" is enough to define a diagnosis of UIP without histological proof. This is pivotal especially in elderly patients with comorbidities. Early recognition of IPF is relevant for its prognostic implication. Some pharmacological strategies have been proposing novel molecules that tend to slow lung function decline, even though without healing fibrosis. We report a case of ex-heavy smoker male with IPF showing clinical and radiological improvement after 11 months of treatment with Pirfenidone. The definite diagnosis was challenging and it was reached by a multidisciplinary approach.