By Ves Dimov, MD
Allergist/Immunologist, Assistant Professor of Medicine and Pediatrics
University of Chicago
Web Content Editor, WAO Small Airways Working Group
Posted: 7 June 2012
Chitinase 3-like 1 protein (YKL-40) increases bronchial smooth muscle remodeling in asthma
Chitin (C8H13O5N) is a long-chain polymer of a glucose derivative. It is the main component of the cell walls of fungi, the exoskeletons of arthropods, such as crustaceans (crab, lobster and shrimp) and insects, including ants, beetles, etc. The English word "chitin" was derived from the Latin word "chitōn", meaning mollusk. Chitinases are digestive enzymes that break down glycosidic bonds in chitin.
Bronchial remodeling, including increased bronchial smooth muscle (BSM) mass, contributes to bronchial obstruction in asthma. A role of the chitinase 3-like 1 protein (YKL-40) has been evoked in asthma.
This study from France enrolled 40 patients with asthma. Bronchial specimens were obtained by fiberoptic bronchoscopy or lobectomy, and cell proliferation was assessed. The involvement of protease activated receptor (PAR)-2 and YKL-40 was analyzed in both asthmatics and controls.
YKL-40 increased BSM cell proliferation and migration through PAR-2 dependent mechanisms. YKL-40 epithelial expression was correlated with smooth muscle mass in asthma.
This study suggests that YKL-40 promotes smooth muscle cell proliferation and migration through a PAR-2–dependent mechanism.
Bara I, Ozier A, Girodet P-O, Carvalho G, Cattiaux J et al. Role of YKL-40 in bronchial smooth muscle remodeling in asthma. American Journal of Respiratory and Critical Care Medicine 2012; 185(7): 715-722. (doi: 10.1164/rccm.201105-0915OC)
A cicada sheds its chitinous exoskeleton. Image source: Wikipedia, Creative Commons "Attribution ShareAlike 2.0 France" License.
Febrile respiratory illnesses in infancy and atopy are major risk factors for asthma
This study from Australia included 147 children at high atopic risk who were followed from birth to age 10 years. Atopy was measured by skin prick tests at 6 months, and 2 and 5 years. History of wheeze and doctor-diagnosed eczema and asthma was collected regularly until 10 years of age.
At 10 years, 60% of the cohort was atopic, 26% had eczema, 18% asthma and 20% persistent wheeze. Thirty-six percent experienced at least one lower respiratory infection (LRI) associated with fever and/or wheeze in first year of life.
Children who had wheezy or, in particular, febrile LRI in infancy and were atopic by 2 years, were much more likely to have persistent wheeze (RR 3.51) and current asthma (RR 4.92) at 10 years.
Severe viral respiratory infections in infancy and early atopy are risk factors for persistent wheeze and asthma. The strongest marker of the asthmatogenic potential of early life infections was concurrent fever. The study conclusions are interesting especially in the light of the recent hypothesis that implicates acetaminophen (paracetamol) in the etiology of pediatric asthma. Many children with febrile respiratory illness receive acetaminophen (paracetamol) as symptomatic therapy which may aggravate or confound their risk profile.
Kusel MMH, Kebadze T, Johnston SL, Holt PG, Sly PD. Febrile respiratory illnesses in infancy and atopy are risk factors for persistent asthma and wheeze. European Respiratory Journal 2012; 39(4): 876-882.
Untangling asthma phenotypes and endotypes
Asthma phenotypes have been developed to address the complexities of the disease. A phenotype covers the clinical properties of the disease, but does not show the relationship to disease etiology and pathophysiology.
Different pathogenetic mechanisms might cause similar asthma symptoms and might be operant in a certain phenotype. These mechanisms are addressed by the term ‘endotype’. Endotypes should link key pathogenic mechanisms with the asthma phenotype. The identification of molecular biomarkers for individual pathogenic mechanisms underlying phenotypes is important. The accurate endotyping may predict treatment response.
Agache I, Adkis C, Jutel M, Virchow JC. Untangling asthma phenotypes and endotypes. Allergy, 2012 (doi: 10.1111/j.1398-9995.2012.02832.x) Published online before print.
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Posted: 7 June 2012