The Relationship between Airways Inflammation and Asthma Severity

Abstract

In order to investigate the relationship between airways inflammation and disease severity, and improve the understanding of persistent asthma, 74 asthmatics, with disease severity ranging from intermittent, to mild to moderate and severe persistent (classified according to the Global Initiative for Asthma [GINA] guidelines), and 22 nonatopic control subjects were studied using the method of induced sputum. Sputum was analyzed for total and differential cell counts concentrations of albumin, and levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), and tryptase, inflammatory mediators reflecting eosinophil, neutrophil, and mast cell activation. Asthma severity (assessed by FEV(1), peak expiratory flow [PEF] variability, and daily symptom scores) and methacholine airways responsiveness were related to sputum eosinophilia and ECP. In addition, sputum neutrophilia and MPO levels correlated, albeit weakly, with PEF variability and symptom scores, respectively. Tryptase concentrations were raised in mild to moderate asthmatics. Albumin concentrations were significantly raised across the spectrum of asthma severity and correlated with those of tryptase and ECP. Despite treatment with either high doses of inhaled corticosteroids or oral corticosteroids, prominent eosinophilic inflammation with raised ECP was noted. This study points to persistent, disease severity-related airways inflammation in asthma, involving eosinophils, mast cells, and neutrophils, which is evident despite treatment with corticosteroids.

Th17 cells: new players in asthma pathogenesis

“…These phenotypes, including allergic asthma, severe steroid-resistant asthma, asthma associated with obesity, induced by exercise, exposure to air pollutants or to aspirin, are characterized by different cellular networks supporting the chronic inflammation. The role of Th2 lymphocytes and eosinophils infiltrating the lung in the pathogenesis of the allergic form of the disease is supported by several evidences (3), and more recently, it has been suggested that Th17 lymphocytes and neutrophils could be involved in nonatopic (70) and in steroid-resistant (87) asthma. The definition of different asthma phenotypes is crucial for redirecting the therapeutic approach, which in future will be hopefully personalized for each patient.…”

“…In those patients with asthma in which inflammation is nonatopic, non-IgE-dependent, and noneosinophilic, airway neutrophilia is correlated with asthma severity, suggesting a major role for neutrophils, at least in this subset of patients with asthma (70,71). Neutrophilic inflammation has also been described in sudden-onset fatal asthma and neutrophil numbers are highly elevated in status asthmaticus (72), thus suggesting a possible role for these cells in severe and fatal asthma.…”

Mouse models of asthma: a comparison between C57BL/6 and BALB/c strains regarding bronchial responsiveness, inflammation, and cytokine production

“…In humans, no significant correlation was found between the degree of airway responsiveness and sputum inflammatory cells, which are two major features of asthma [4][5][6]. Concurrently, different strains of mice exhibit various degrees of airway responsiveness and inflammation despite identical sensitization and airway challenge with an allergen [7,8].…”

Health care resource utilization and characteristics of patients with eosinophilic asthma in secondary health care in Finland

“…Elevated eosinophil counts in blood and sputum is associated with disease severity [13,14]. As early as 1975, Horn et al [15] observed that increased blood eosinophil counts correlate with increasing airway obstruction in patients undergoing a pulmonary function test.…”