Influence of comorbidities on severe asthma

Focus on obesity and nasal polyps

Background. Asthma is often associated with comorbidities (e.g. upper airway disease, obesity, gastro-oesophageal reflux disease, psychological disturbances, obstructive sleep apnoea) and they can influence its control, phenotype and response to treatment. The prevalence of comorbidities seems to be particularly high in severe asthma, and their treatment is a critical step in the therapeutic course of these patients. In these patients the asthma control is difficult to reach despite multiple and high-dose of asthma therapy, that can include therapeutic options associated with medical side effects, eg. chronic oral corticosteroids, or expensive alternative, eg. biological therapy or bronchial thermoplasty. Therefore, the identification and optimally treatment of comorbidities should be an early medical intervention in the management of these patients.

Chronic rhinosinusitis with nasal polyps and obesity are two major comorbidities often associated with severe asthma. Many studies showed that obese patients have poorly controlled asthma and reduced responce to controller therapy, probably due to mechanical and metabolic factors: obesity can reduce pulmonary compliance, lung volume and diameter of respiratory airways and adipose tissue produce mediators (adipokine) that can influence airway inflammation and the responce to inhaled corticosteroids. The weight loss can improve asthma control and pulmonary function. Even the association between chronic rhinosynusitis and asthma has been clearly estabilished: rhinitis nasal symptoms and radiological severity of chronic rhinosinusitis are related to asthma severity and airway inflammation (sputum eosinophilia). Medical or surgical treatment of chronic rhinosinusitis seems improve asthma control.

Aim of our research program: to assess the role of comorbidities in the level of cotrol of patients with severe asthma, and to evaluate if an appropriate management of these conditions may improve the level of asthma control in this special goup of patients.

Preliminary results. We studied 64 patients with severe asthma to investigate the influence of obesity and chronic rhinosinusitis with nasal polyps on pulmonary function, airway inflammation, asthma control and quality of life. At this scope all patients performed spirometry, collection of induced sputum to evaluate level and type of airway inflammation, measurement of exhaled nitric oxide (eNO) and ENT visit. Asthma control was evaluated according to GINA guidelines and by Asthma Control Test (ACT) questionnaire, quality of life by Asthma Quality of Life Questionnaire (AQLQ). The percentage of patients with uncontrolled asthma according GINA guidelines was high: 46.9%. The prevalence of obesity and nasal polyps was 34.4% and 32.8% respectively. Obese asthmatics had a similar functional data than non-obese (pre-BD FEV1 77.7±23.5 vs 77.9±14.8), but worse asthma control (ACT score: 16 (7-25) vs 21 (10-25), p<0.05; poorly controlled according GINA guidelines: 71,4% vs 34,9%, p<0.05) and quality of life index (AQLQ score: 4.5 (3.0-6.2) vs 5.1 (2.7-6.7), p<0.05), as well as a trend to have lower sputum eosinophilia (6.6 (0-71.2) vs 17.6 (0-95.6), p=0,07), with no-difference in asthma treatment. Asthmatics with chronic rhinosinusitis and nasal polyps showed similar asthma control and quality of life index than asthmatics without nasal polyps, but worse spirometry (FEV1 71.1±16.7 vs 81.0±17.3, p<0.05) and higher sputum eosinophilia (29.8 (0.4-95.6) vs 8.5 (0-84.1), p<0.05). In a multivariate analysis taking into account age, sex, FEV1 (% of predicted), obesity, nasal polyps and sputum eosinophilia, only the obesity predicted the lack of asthma control (OR: 5.6, CI: 1.4-22.8 p=0.01). We concluded that in patients with severe asthma, nasal polyposis is associated with increased eosinophilic airway inflammation and with worse lung function, but has less impact on asthma control and quality of life than obesity.

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Dott.ssa Federica Novelli

Graduated in Medicine and Surgery at the University of Parma (2005) and post-graduated in Respiratory Medicine at the University of Pisa (2009). Since 2011 holder of a research grant on “Phenotyping of asthma” and currently PhD in Physiopathology and Clinical of Cardiovascular and Respiratory Diseases at the University of Pisa on severe asthma. Author and co-author of several abstracts presented in national and international congresses and of 11 papers published on international peer-review journals.