Pathogenesis of Small Airways in Asthma

Abstract

Asthma is a lung disease characterized by inflammation and remodeling of the airways. It is now widely accepted that airway inflammation and remodeling occur not only in the central airways but also in the small airways and even in the lung parenchyma. Inflammation of the distal lung can be observed even in mild asthmatics with normal or noncompromised lung function. Moreover, the small airways and the lung parenchyma can produce many Th2 cytokines and chemokines involved in initiation and perpetuation of the inflammatory process. In addition, the distal parts of the bronchial tree have been recognized as a predominant site of airflow obstruction in many asthmatics. In fact, the inflammation at this distal site has been described as more severe when compared to the large airway inflammation, and evidence of remodeling in the lung periphery is emerging. Recognition of asthma as a disease of the entire respiratory tract has an important clinical significance, highlighting the need to also consider the distal lung as a target in any therapeutic strategy for effective treatment of this disease.

Serum bilirubin is associated with lung function in a Swiss general population sample

“…The significant associations with FEF25-75% and FEV1/FVC might point to an inverse relationship with small airway obstruction. Due to their large surface area, small airways are an important compartment of chronic respiratory disease development [26,27], where subclinical changes often manifest first, and accordingly, strongest associations presented at this site in our general population sample. Smoking adjustment decreased association estimates considerably, which was expected given its known inverse relationship with lung function and serum bilirubin, resulting in positive confounding of the bilirubin lung function association.…”

Treating the Small Airways

“…From the previous articles in this current Thematic Review Series in Respiration , the authors have described that pathological, immunological and structural abnormalities occur in the small airways of patients with asthma and chronic obstructive pulmonary disease (COPD); that these abnormalities contribute to the physiological observations of the small airways being the major site of airflow limitation, and that small airways are involved in the clinical expression of these diseases [1,2,3]. Involvement of the small airways has been observed not only in patients with severe asthma [4], but also in those with mild disease [5,6] and in patients with nocturnal and exercise-induced asthma [7,8,9].…”

Lung Pathologies in a Chronic Inflammation Mouse Model Are Independent of Eosinophil Degranulation

“…A hallmark feature of chronic allergic severe asthma is the extensive deposition and extracellular accumulation of eosinophil secondary granule proteins in lung tissue and airways (28; reviewed in References 26,29,30). Moreover, the release of major basic protein-1 (MBP-1), eosinophil peroxidase (EPX), eosinophilderived neurotoxin (EDN), and eosinophil cationic protein (ECP) have been suggested to mediate cell killing and tissuedamaging events occurring in the lung as part of the late phase response to allergen provocation (31; reviewed in Reference 32).…”