Alvesco

Small airways in asthma

The small airways (<2mm diameter) account for the vast majority (98.9%) of lung volume1 and cross-sectional area (Figure 1) and play a large part in the pathogenesis of asthma.2  The reactivity of the small airways to both specific and nonspecific allergens is increased in asthmatic patients compared with normal subjects3  and in mild asthma, peripheral resistance can be several times higher than in normal subjects.4,5  Small airway inflammation is also associated with nocturnal asthma.6

12 fig 1Small airway lung volume
Figure 1: The small airways make up the majority of lung volume

Most clinical measures of asthma detect inflammation and airway obstruction in the larger airways. However, the inflammatory processes associated with the small airways may be more severe (Figure 2)7 and these airways may also have an increased contractile response compared to larger airways.8 Read more on Asthma pathophysiology.

12 fig 2Eosinophils in small airways

Figure 2: Immunocytochemical cell markers in airways <2 mm and >2 mm in diameter from patients with asthma.7

Reproduced with permission from Elsevier. 


A number of pathophysiological changes occur in the small airways of the asthmatic lung. Large numbers of immune cells and inflammatory mediators can accumulate in the small airways; eosinophils in particular are more numerous in the small airways than in the large airways of asthma patients (Figure 2).7 Airway remodelling is characteristic in the large airways of asthma patients, but chronic inflammation also thickens the walls of the small airways (Figure 3).2,9

12 fig 3Small airway remodeling
Figure 3: Small airway of a patient with severe asthma showing features of remodelling2
Reproduced with permission from Wiley & Sons.

Small airways and asthma control

Inflammation and structural remodelling in the small airways can have a considerable impact on patients with asthma, as the degree of small airway inflammation correlates with asthma control. An elevated alveolar nitric oxide (NO) concentration is significantly associated with a lack of asthma control in mild asthma, whereas bronchial NO is not.10 This suggests that abnormalities in the small airways are an important clinical consideration even in the mildest forms of the disease.

Therefore an assessment of the degree of small airway inflammation and remodelling may be important in the diagnosis of asthma.

Learn more about how to reach the small airways and reduce inflammation in the lung periphery with Alvesco®.

References
  1. Virchow JC. [Asthma--a small airway disease: concepts and evidence]. Pneumologie 2009;63 Suppl 2:S96-101.
  2. Contoli M, Bousquet J, Fabbri LM, et al. The small airways and distal lung compartment in asthma and COPD: a time for reappraisal. Allergy 2010;65:141-51.
  3. Wagner EM, Bleecker ER, Permutt S, et al. Direct assessment of small airways reactivity in human subjects. Am J Respir Crit Care Med 1998;157:447-52.
  4. Hyde DM, Hamid Q and Irvin CG. Anatomy, pathology, and physiology of the tracheobronchial tree: emphasis on the distal airways. J Allergy Clin Immunol 2009;124:S72-S77.
  5. Wagner EM, Liu MC, Weinmann GG, et al. Peripheral lung resistance in normal and asthmatic subjects. Am Rev Respir Dis 1990;141:584-8.
  6. Kraft M, Pak J, Martin RJ, et al. Distal lung dysfunction at night in nocturnal asthma. Am J Respir Crit Care Med 2001;163:1551-6.
  7. Hamid Q, Song Y, Kotsimbos TC, et al. Inflammation of small airways in asthma. J Allergy Clin Immunol 1997;100:44-51.
  8. Mitchell HW, Cvetkovski R, Sparrow MP, et al. Concurrent measurement of smooth muscle shortening, lumen narrowing and flow to acetylcholine in large and small porcine bronchi. Eur Respir J 1998;12:1053-61.
  9. Carroll N, Elliot J, Morton A, et al. The structure of large and small airways in nonfatal and fatal asthma. Am Rev Respir Dis 1993;147:405-10.
  10. Scichilone N, Battaglia S, Taormina S, et al. Alveolar nitric oxide and asthma control in mild untreated asthma. J Allergy Clin Immunol 2013;131:1513-7.

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