Moving to a Personalized Approach in Respiratory Medicine. From Academic Research to Regulatory Intervention

Abstract

In recent years, interest in respiratory diseases has increased significantly after a long period of relative stagnation that followed the apparent control of tuberculosis. Indeed, for decades the focus of researchers was mainly on bronchial asthma, with little interest in COPD, and minimal attention on other lung diseases. Despite the widespread prevalence of pulmonary diseases, there has been, and still is, a considerable delay in understanding their etiopathogenesis, and, as a result, the therapeutic approach to these diseases has not developed adequately. For as long as anyone can remember, it has generally been limited to the use of bronchodilators, corticosteroids, mucolytics and antibiotics. Recent advances in biomedical research and bioinformatics approaches, in particular the commodification of high-throughput biotechnology, are now enabling the understanding of various aspects of biological systems. Insights generated by these advances have gone beyond the limitations of simplistic hypotheses. The obvious consequence of this is that the fundamental mechanisms that regulate biological processes in the lungs are increasingly being discovered, and, as a cascade, several disease endotypes and new therapies that may be effective in selected individuals are also being identified (Hemnes, 2018). Nonetheless, these approaches still have serious limitations due to a high chance of potentially false discovery with low patient numbers, inexact phenotyping, and bioinformatics challenges. However, the broadening of our knowledge of the underlying mechanisms involved in at least some phenotypes and endotypes of asthma and/or COPD has provided access to innovative therapies, especially for asthma (Cazzola et al., 2017; Martin et al., 2019; Rogliani et al., 2020; Cazzola et al., 2021; Matera et al., 2021). Unfortunately, however, it is becoming increasingly accepted that asthma and COPD are chronic inflammatory airway disorders that are highly heterogeneous in terms of pathogenic manifestations, symptom severity and outcome (Sterk, 2016). There is growing evidence that asthma and COPD are umbrella terms used to group endotypes characterised by different underlying mechanisms (Rogliani et al., 2016). These endotypes probably represent diseases that are different and therefore each characterised by clinical and pathological heterogeneity, although there may also be overlapping features (Rogliani et al., 2016). Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease (ILD) with a poor prognosis, which has received much attention in recent years, is also difficult to classify because it is extremely heterogeneous in terms of clinical progression rates, worsening in lung function decline, and treatment response (Clarke et al., 2017). IPF represents the archetype of progressive fibrosing ILD, but many patients with other ILD subtypes also develop progressive fibrosing ILD (Bowman et al., 2021). Furthermore, the variability in clinical progression with rapid deterioration and death within a few months in some patients, while in other patients there is a slower decline in disease progression and relatively limited associated disability, or even periods of relative stability alternating with periods of acute respiratory decline, suggests that it is likely that the biological factors or drivers involved may be different (Clarke et al., 2017). In any case, predicting a progressive phenotype remains difficult. Edited and reviewed by: Gianluca Trifirò, University of Verona, Italy