Differences and similarities in inflammatory mechanisms between asthma and chronic obstructive pulmonary disease (COPD)

Asthma and chronic obstructive pulmonary disease (COPD) are the two most common respiratory chronic diseases worldwide, which are increasing in prevalence and have an enormous impact on the lives of patients and their caregivers. Both diseases are characterized by chronic inflammation of the lung, but the nature of the inflammatory response differs between diseases and shows a high degree of heterogeneity within each disease, accounting for a large number of endotypes and phenotypes. During my PhD various lines of research have been explored either by the research group in Padova or in partnerships with both national and international colleagues. We performed two clinical “real life” studies on two large cohorts of adult asthmatics and patients with COPD followed at our Centre, observing the existence of multiple phenotypes and inflammatory endotypes of these two diseases. In adult asthmatics, we differentiated patients with early onset asthma (EOA) from late onset asthma (LOA). In EOA patients, we observed a crucial role of allergic rhinitis and eosinophilic inflammation on disease control and pulmonary function. Conversely, in patients with LOA, rhinitis was not linked to poor asthma control while obesity, associated with a neutrophilic profile, had a major impact. In the cohort of COPD patients we observed that blood lymphopenia was related to a more severe disease with a predominant emphysematous component, while high levels of neutrophils and monocytes were related to chronic bronchitis and bronchiectasis. My main research field was the investigation of the immunopathology of asthma and its etiology at the beginning of the natural history of the disease. We performed a series of studies on a cohort of wheezing children who underwent bronchoscopy for clinical purposes in whom bronchial biopsies were available for research. We first observed that airway remodeling and inflammatory hallmarks of adult asthma are also present in preschool wheezing and that phenotypes and endotypes of asthma are already recognizable. In particular, we observed that basement membrane thickening, a putative sign of epithelial-mesenchymal activation, is a very early sign that may precede inflammation and predict asthma development. Furthermore, we highlighted the presence of the eosinophilic non-atopic (T2H-nA) endotype where type 2 inflammation is present in absence of atopy. In these patients we described the presence of innate lymphoid cells type 2 (ILC2) as major drivers of type 2 inflammation. Of note, ILC2 infiltration was associated with persistence of asthma in a longitudinal follow-up, while we observed a shift toward the development of atopy with growth. In subsequent analyses we investigated the effects of air pollution and viral infections on the pathological hallmarks of asthma. We observed a direct relationship linking type 2 inflammation to both outdoor air pollution exposure and antiviral innate immune response impairment hypothesizing a possible existence in asthma of a pathogenetic intersection between atopy, air pollution and viral infections. Finally, we also described in a cohort of COPD patients that underwent lung surgery a deranged interferon-response mediated by NK, whose impairment was related to increased disease severity. These observations complement those of a different study, in which we studied the involvement of innate lymphoid cells type 1 (ILC1). Finally, addressing the interaction between COPD and viral infections we investigated the risk factors for the development and severity of COVID-19 in patients with COPD. We reported that cardio-metabolic conditions were the main risk factors for development of COVID-19 in COPD patients. Emphysema and low DLCO, were related to a more severe disease and need for intensive care, remarking a possible relationship between COPD severity and impaired antiviral responses.