• chronic rhino-sinusitis
• obesity
• severe asthma

Background. Severe asthma (SA) is a heterogeneous disease with variability in clinical history, physiologic abnormalities, pattern of airway inflammation and responses to therapy, and often associated with comorbidities that can influence these characteristics. The WHO document has classified SA in two principal groups: difficult-to-treat (DT)-SA and treatment-resistant (TR)-SA, in which the poor control of asthma is due respectively to other factors than asthma, in particular comorbidities, and poor sentitivity to asthma treatment. Aims of this study are: 1) to characterize and compare demographic, functional and inflammatory parameters and the level of control of the patients with DT-SA and TR-SA, 2) to evaluate the prevalence of comorbidities and their combined effect on asthma control, asthma related quality of life, lung function and airway inflammation in severe asthmatics, 3) to adapt the treatment to the different asthma phenotypes and to evaluate the effect on indices of control, quality of life, pulmonary function and number of exacerbations.
Patients and methods. We studied 72 patients with SA. We collected for each patient demographic data, smoking habit, asthma history, assessment of comorbidities. Pulmonary function, inflammatory biomarkers, upper airway disease evaluation, control of asthma and quality of life were carefully assessed. 49 patients entered in a longitudinal phase: 15 obese patients were sent to obesity center for weight loss program, 23 patients with chronic rhino-sinusitis (CRS) were sent to ENT to optimize the treatment of upper airway disease and 11 patients were randomized to increase inhaled corticosteroid to 2000 mcg/day of fluticasone propionate. These patient were assessed after one years to evaluate the effect on airway inflammation, pulmonary function, asthma control, asthma related quality of life and exacerbations.
Results. No significant differences between TR-SA and DT-SA were observed for demographic, clinical, functional and biological features of the disease. We observed a high prevalence of CRS with nasal polyps (CRSwNP), obesity and gastro-esophageal reflux (GER), respectively 34.7%, 34.7% and 40.3%. Asthmatics with CRSwNP had lower lung function and higher sputum eosinophilia; obese asthmatics had worse asthma control and quality of life and a trend to have lower sputum eosinophilia; asthmatics with GER showed worse quality of life. In multivariate analysis, obesity was the only independent factor associated with poor control (OR: 4.9), while CRSwNP and duration of asthma were the only independent factors associated with airway eosinophilia (OR: 16.2 and 0.1, respectively). Lower lung function was associated with the male gender and the longer duration of asthma (OR: 3.9 and 5.1, respectively) and showed a trend for the association with CRSwNP (OR 2.9, p=0.06). In the longitudinal phase of our study, despite the small number of patients included in the different intervention programs, we observed that the weight loss in obese SA could induce an improvement in control of asthma and asthma-related quality of life and an effective treatment of CRS in SA could determine a reduction in asthma exacerbations. An increase of ICS at 2000 mcg/day of fluticasone propionate does not seem to make any benefit in asthma outcomes.
Conclusions. Our study confirms the high prevalence of coexisting comorbidities in SA patients, which are associated with different asthma features. In particular, the association between obesity and poor asthma control, between CRSwNP and airway eosinophilia and lower lung function, and between GER and lower quality of life suggests the importance of the rigorous characterization of severe asthmatics for obtaining a better management. The weight loss in obese patients can induce an improvement in asthma control and asthma-related quality of life and the optimal treatment of CRS can reduce asthma exacerbations.