Chiesi Farmaceutici

The air flows in the proximal and distal portions of the human lungs are interconnected: the lower Reynolds number in the deeper generations causes a progressive flow regularization, but mass conservation requires flow rate oscillations to propagate through the airway bifurcations. To explain how these competing effects shape the flow state in the deeper generations, we have performed the first high-fidelity numerical simulation of the air flow in a lung model that includes 23 successive bifurcations of a single planar airway. Turbulence modeling or assumptions on flow regimes are not required. The chosen flow rate is steady on average, and representative of the peak inspiratory flow reached by adult patients breathing through therapeutic inhalers. As expected, advection becomes progressively less important after each bifurcation, until a time-dependent Stokes regime governed solely by viscous diffusion is established in the smallest generations. However, fluctuations in this regime are relatively fast and large with respect to the mean flow, which is in contrast with the commonly agreed picture that only the breathing frequency is relevant at the scale of the alveoli. We demonstrate that the characteristic frequency and amplitude of these fluctuations are linked to the flow in the upper part of the bronchial tree, as they originate from the time-dependent flow splitting in the upper bifurcations. Even though these fluctuations are observed here in an idealized, rigid lung model, our findings suggest that the assumptions usually adopted in many of the current lung models might need to be revised.

Digital transformation presents a strategic imperative for the pharmaceutical industry, particularly within research and development (R D), where it promises accelerated time to market and enhanced operational efficiency. Building on the foundation of the People Coordination, Ownable Focus Areas, Long-Term Roadmap, Common Digital Alphabet, Reporting, and Monitoring (P.O.L.A.R.) Star framework, this article delves into the critical soft elements—human and organizational factors—essential for deploying a successful digital transformation in the pharmaceutical R D of a midsized company. While technological roadmaps provide structure and serve as a blueprint, sustainable results depend on an organization’s ability to evolve both in its culture and approach to change. In this context, implementing new capabilities—such as centralized R D data governance and a common data model—not only requires a transparent approach to data, strong digital leadership, and deep expertise but also triggers an organizational rethinking to support this evolution. Based on the needs and current evolution phase of the digital transformation journey of the company, this rethinking can be represented by a “federated” approach based on cross-functional teams, a digital unit to centralize activities and solutions, or a hybrid model combining elements of both. In summary, this article offers a focused, actionable guide to managing digital transformation in pharmaceutical R D. It explores the concept of a digital unit or a cross-functional team as strategic options, evaluated to guide intentional, structured operations within a digital reorganization; it also highlights the cultural shift needed for long-term sustainability.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a progressive, incurable condition marked by irreversible airflow limitation and systemic inflammation. Cardiovascular comorbidities, particularly pulmonary hypertension (PH), exacerbate disease severity. While cigarette smoke is a well-known trigger, non-smoking-related inflammatory pathways remain underexplored. This study investigates vascular remodeling in a murine model of inflammation induced by chronic exposure to house dust mite Farinae (HDM). Methods: Female C57BL/6 mice were sensitized with HDM in Freund's Complete Adjuvant and challenged intranasally with HDM for six weeks. Lung inflammation, mucus hypersecretion, and vascular remodeling were evaluated via BAL, histology, immunofluorescence, echocardiography, gene expression, proteomics, and FlexiVent pulmonary function tests (FlexiVent system). Results: HDM exposure induced a mixed inflammatory response, with elevated neutrophils, monocytes, and lymphocytes in BALF. Mucus hyperproduction (increase in MUC5AC/MUC5B) and impaired lung function (reduced FEV0.1/FVC) were observed. Vascular remodeling was evidenced by increased wall thickness, α-SMA expression, and collagen deposition. Proteomic analysis revealed dysregulation of endothelial markers and protease/antiprotease imbalance. HIF1-α was significantly upregulated in lung tissue and correlated with vascular and epithelial remodeling. Conclusions: Chronic HDM exposure in mice recapitulates key features observed in subsets of COPD and PH, including inflammation-driven airway and vascular remodeling. HIF1-α emerges as a central regulator, linking hypoxia to structural changes. This model offers insights into the effect of non-smoking-related inflammatory pathways on bronchial and vascular remodeling that are potentially relevant for subgroups of COPD patients and highlights HIF1-α as a potential therapeutic target.