Allergic rhinitis: a disease remodeling the upper airways?

The nasal and bronchial mucosa present similarities and differences. Remodeling is defined as "model again or differently, reconstruct" and is present in the airways of most if not all asthmatic patients. Even though inflammation is similar in allergic rhinitis and asthma, the pathologic extent of nasal remodeling in patients with rhinitis seems to be far less extensive than that in the bronchi of asthmatic patients. Epithelial damage is only minimal, and the reticular basement membrane does not appear to be largely pseudothickened. Moreover, the demonstration of fibrogenic growth factors in the nasal mucosa of patients with allergic rhinitis is lacking because of the paucity of studies. The reasons why remodeling appears to be less extensive in the nasal mucosa than in the bronchial mucosa are still unclear, but 2 hypotheses can be put forward. On one hand, the cytokine production of smooth muscle cells might partly explain differences in remodeling of the 2 sites of the airways. On the other hand, the genes of the embryologic differentiation might persist in the nose and bronchi or might be re-expressed in asthma and rhinitis. Because the nose is of ectodermal origin and the bronchi of endodermal origin, these genes might also govern remodeling patterns. More studies are urgently required to better characterize nasal remodeling in patients with rhinitis. A better understanding of nasal and bronchial remodeling might help to identify new pathways and new therapeutic strategies to reduce long-term remodeling in asthma.

Effects of inhaled corticosteroids, leukotriene receptor antagonists, or both, plus long-acting beta2-agonists on asthma pathophysiology: a review of the evidence.

Chronic inflammation and smooth muscle dysfunction are consistent features of asthma, and are responsible for disease progression and airway remodelling. The development of chronic airway inflammation depends upon the recruitment and activation of inflammatory cells and the subsequent release of inflammatory mediators, including cytokines. Cellular and histological evaluation of drugs with anti-inflammatory activity, such as inhaled corticosteroids (ICSs), is achieved by analysing samples of lung tissue or biological fluids, obtained by techniques such as bronchial biopsy, bronchoalveolar lavage and sputum induction. These provide valuable information on the inflammatory processes occurring in the lung, although not all are equal in value. The beneficial effects of ICSs in asthma treatment are a consequence of their potent and broad anti-inflammatory properties. Furthermore, there have been promising results indicating that ICSs can reverse some of the structural changes that contribute to airway remodelling. Long-acting beta2-agonists (LABAs) added to ICSs provide greater clinical efficacy than ICSs alone, suggesting the possibility of complementary activity on the pathophysiological mechanisms of asthma: inflammation and smooth muscle dysfunction. Leukotrienes play a part in the pathogenesis of asthma. Leukotriene receptor antagonists (LTRAs) directly inhibit bronchoconstriction and may have some anti-inflammatory effects, although the extent to which inhibiting one set of inflammatory mediators attenuates the inflammatory response is questionable. In concert with their effect on a broad variety of inflammatory mediators and cells, treatment with ICSs (including ICSs and LABAs) results in superior control of the pathophysiology of asthma and superior clinical efficacy as assessed by the greater improvements in pulmonary function and overall control of asthma compared with LTRAs.

Circulating hematopoietic progenitor cells in runners.

Because endurance exercise causes release of mediators and growth factors active on the bone marrow, we asked whether it might affect circulating hematopoietic progenitor cells (HPCs) in amateur runners [n = 16, age: 41.8 +/- 13.5 (SD) yr, training: 93.8 +/- 31.8 km/wk] compared with sedentary controls (n = 9, age: 39.4 +/- 10.2 yr). HPCs, plasma cortisol, interleukin (IL)-6, granulocyte colony-stimulating factor (G-CSF), and the growth factor fms-like tyrosine kinase-3 (flt3)-ligand were measured at rest and after a marathon (M; n = 8) or half-marathon (HM; n = 8). Circulating HPC counts (i.e., CD34(+) cells and their subpopulations) were three- to fourfold higher in runners than in controls at baseline. They were unaffected by HM or M acutely but decreased the morning postrace. Baseline cortisol, flt3-ligand, IL-6, and G-CSF levels were similar in runners and controls. IL-6 and G-CSF increased to higher levels after M compared with HM, whereas cortisol and flt3-ligand increased similarly postrace. Our data suggest that increased HPCs reflect an adaptation response to recurrent, exercise-associated release of neutrophils and stress and inflammatory mediators, indicating modulation of bone marrow activity by habitual running.