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• W2083052532 abstract "The symptoms of asthma in a majority of patients can be fairly well controlled with modest doses of inhaled corticosteroids1Pauwels R.A. Pedersen S. Busse W.W. Tan W.C. Chen Y.Z. Ohisson S.V. et al.Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial.Lancet. 2003; 361: 1071-1076Abstract Full Text Full Text PDF PubMed Scopus (673) Google Scholar or a combination of inhaled corticosteroids and long-acting bronchodilators.2Pauwels R.A. Löfdahl C.G. Postma D.S. Tattersfield A.E. O'Byrne P. Barnes P.J. et al.Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group.N Engl J Med. 1997; 337: 1405-1411Crossref PubMed Scopus (1554) Google Scholar A small proportion of patients, estimated to be approximately 5% to 10% of all asthmatic patients, require very high doses of inhaled or ingested corticosteroids for asthma control. The reason for their relative steroid insensitivity might be multifactorial, varying from molecular mechanisms of glucocorticoid receptor kinetics,3Barnes P.J. Adcock I.M. Glucocorticoid resistance in inflammatory diseases.Lancet. 2009; 373: 1905-1917Abstract Full Text Full Text PDF PubMed Scopus (800) Google Scholar pharmacogenomics,4Weiss S.T. Litonjua A.A. Lange C. Lazarus R. Liggett S.B. Bleecker E.R. et al.Overview of the pharmacogenetics of asthma treatment.Pharmacogenomics J. 2006; 6: 311-326Crossref PubMed Scopus (86) Google Scholar a predominantly neutrophilic bronchitis,5Green R.H. Brightling C.E. Woltmann G. Parker D. Wardlaw A.J. Pavord I.D. Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids.Thorax. 2002; 57: 875-879Crossref PubMed Scopus (708) Google Scholar and airway smooth muscle responsiveness to steroids and bronchodilators.6Walker J.K. Penn R.B. Hanania N.A. Dickey B.F. Bond R.A. New perspectives regarding β(2)-adrenoceptor ligands in the treatment of asthma.Br J Pharmacol. 2011; 163: 18-28Crossref PubMed Scopus (83) Google Scholar The development of biomarkers that accurately identify the precise mechanism would be extremely useful for drug development to target the underlying pathophysiologic abnormality in these patients. The presence of eosinophils in the airway lumen, as identified based on quantitative sputum cell counts, is one of the predictors of response to corticosteroids.7Meijer R.J. Postma D.S. Kauffman H.F. Arends L.R. Koëter G.H. Kerstjens H.A. Accuracy of eosinophils and eosinophil cationic protein to predict steroid improvement in asthma.Clin Exp Allergy. 2002; 32: 1096-1103Crossref PubMed Scopus (94) Google Scholar The persistence of eosinophils in sputum despite high doses of corticosteroids is also a biomarker to select patients for treatment directed at TH cytokines, such as IL-5, which is involved in eosinophil maturation and differentiation.8Castro M. Mathur S. Hargreave F. Boulet L.P. Xie F. Young J. et al.Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study.Am J Respir Crit Care Med. 2011; 184: 1125-1132Crossref PubMed Scopus (593) Google Scholar, 9Nair P. Pizzichini M.M. Kjarsgaard M. Inman M.D. Efthimiadis A. Pizzichin E. Hargreave F.E. et al.Mepolizumab for prednisone-dependent asthma with sputum eosinophilia.N Engl J Med. 2009; 360: 985-993Crossref PubMed Scopus (1197) Google Scholar However, access to a laboratory and perceived difficulties in collecting and processing sputum might limit the widespread access and utility of this biomarker. Jia et al10Jia G. Erickson R.W. Choy D.F. Mosesova S. Wu L.C. Solberg O.D. et al.Periostin is a systemic biomarker of eosinophilic inflammation in asthmatic patients.J Allergy Clin Immunol. 2012; 130 (e10): 647-654Abstract Full Text Full Text PDF PubMed Scopus (494) Google Scholar report that levels of periostin, a matricellular protein that is partly regulated by IL-13,11Woodruff P.G. Boushey H.A. Dolganov G.M. Barker C.S. Yang Y.H. Donnelly S. et al.Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids.Proc Natl Acad Sci U S A. 2007; 104: 15858-15863Crossref PubMed Scopus (667) Google Scholar measured in serum might be a simple alternative to identify airway eosinophilia and therefore response to treatment directed at the TH2 pathway, specifically against IL-13.12Corren J. Lemanske R.F. Hanania N.A. Korenblat P.E. Parsey M.V. Arron J.R. et al.Lebrikizumab treatment in adults with asthma.N Engl J Med. 2011; 365: 1088-1098Crossref PubMed Scopus (1365) Google Scholar This conclusion was reached by demonstrating increased serum periostin levels in patients with airway luminal and tissue eosinophilia despite high doses of inhaled or ingested corticosteroids, correlations with blood and sputum eosinophilia, modest sensitivity and specificity using receiver operating characteristic curves, and repeatability over a 5-week observational period. Serum periostin measurements were more discriminatory than blood eosinophil, fraction of exhaled nitric oxide, and YKL-40 measurements to detect airway eosinophilia. Although these results are encouraging, one needs to be cautious about interpreting them and any extension of this interpretation to clinical practice. Although the airway epithelium can indeed be stimulated by IL-13 and IL-4 to secrete periostin,11Woodruff P.G. Boushey H.A. Dolganov G.M. Barker C.S. Yang Y.H. Donnelly S. et al.Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids.Proc Natl Acad Sci U S A. 2007; 104: 15858-15863Crossref PubMed Scopus (667) Google Scholar this protein is not specific to asthma or the airway epithelium. Periostin is a secreted protein that shares structural homology to the axon guidance protein FAS1 in insects and was originally named Osf2.13Horiuchi K. Amizuka N. Takeshita S. Takamatsu H. Katsuura M. Ozawa H. et al.Identification and characterization of a novel protein, Periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor beta.J Bone Miner Res. 1999; 14: 1239-1249Crossref PubMed Scopus (813) Google Scholar Periostin is particularly highly homologous to βig-h3, which promotes cell adhesion and spreading of fibroblasts13Horiuchi K. Amizuka N. Takeshita S. Takamatsu H. Katsuura M. Ozawa H. et al.Identification and characterization of a novel protein, Periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor beta.J Bone Miner Res. 1999; 14: 1239-1249Crossref PubMed Scopus (813) Google Scholar and epithelial14Sidhu S.S. Yuan S. Innes A.L. Kerr S. Woodruff P.G. Hou L. et al.Roles of epithelial cell-derived periostin in TGF-beta activation, collagen production, and collagen gel elasticity in asthma.Proc Natl Acad Sci U S A. 2010; 107: 14170-14175Crossref PubMed Scopus (336) Google Scholar and ovarian cells15Zhu M. Fejzo M.S. Anderson L. Dering J. Ginther C. Ramos L. et al.Periostin promotes ovarian cancer angiogenesis and metastasis.Gynecol Oncol. 2010; 119: 337-344Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar and the development of cardiac valves.16Litvin J. Blagg A. Mu A. Matiwala S. Montgomery M. Berretta R. et al.Periostin and periostin-like factor in the human heart: possible therapeutic targets.Cardiovasc Pathol. 2006; 15: 24-32Crossref PubMed Scopus (58) Google Scholar It is therefore not surprising that this protein has been demonstrated to be increased in patients with a number of conditions associated with increased cell division, cell turnover, invasion, and angiogenesis. Therefore periostin is increasingly recognized as a marker to predict the behavior of a number of cancers,17Kudo Y. Siriwardena B.S. Hatano H. Ogawa I. Takata T. Periostin: novel diagnostic and therapeutic target for cancer.Histol Histopathol. 2007; 22: 1167-1174PubMed Google Scholar such as colon, pancreas, bladder, thyroid, breast, lung, and gall bladder cancers, and other conditions associated with cellular hyperplasia and fibroblast proliferation that occur in pulmonary18Uchida M. Shiraishi H. Ohta S. Arima K. Taniguchi K. Suzuki S. et al.Periostin, a matricellular protein, plays a role in the induction of chemokines in pulmonary fibrosis.Am J Respir Cell Mol Biol. 2012; 46: 677-686Crossref PubMed Scopus (129) Google Scholar and renal fibrosis,19Sen K. Lindenmeyer M.T. Gaspert A. Eichinger F. Neusser M.A. Kretzler M. et al.Periostin is induced in glomerular injury and expressed de novo in interstitial renal fibrosis.Am J Pathol. 2011; 179: 1756-1767Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar pulmonary hypertension, and dermatitis. The protein is also expressed in the epithelium of the gastrointestinal tract in patients with eosinophilic gastroenteritis,20Blanchard C. Mingler M.K. McBride M. Putnam P.E. Collins M.H. Chang G. et al.Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses.Mucosal Immunol. 2008; 1: 289-296Abstract Full Text Full Text PDF PubMed Scopus (227) Google Scholar and this might be a reflection of the upregulated IL-13 activity seen in patients with this condition. Although there is no dispute that periostin promotes eosinophilic inflammation in response to TH2 cytokines,21Masuoka M. Shiraishi H. Ohta S. Suzuki S. Arima K. Aoki S. et al.Periostin promotes chronic allergic inflammation in response to Th2 cytokines.J Clin Invest. 2012; 122: 2590-2600Crossref PubMed Scopus (306) Google Scholar the precise role of periostin in asthmatic patients is still unresolved. It has also been reported to protect against allergen-induced hyperresponsiveness.22Gordon E.D. Sidhu S.S. Wang Z.E. Woodruff P.G. Yuan S. Solon M.C. et al.A protective role for periostin and TGF-β in IgE-mediated allergy and airway hyperresponsiveness.Clin Exp Allergy. 2012; 42: 144-155Crossref PubMed Scopus (81) Google Scholar Overall, our current understanding of periostin is that it is upregulated in adult tissues under a number of diverse adverse conditions, including tissue injury, stress, or both, that might not always be dependent on a TH2 immune response. However, this should not deter clinicians from using this biomarker to direct anti-TH2 therapies in patients with eosinophilic asthma if there is convincing evidence that this protein is specific for airway eosinophilia and that patients with high levels of periostin respond favorably to such therapies. Although an arbitrary level of 25 ng/mL had a positive predictive value of 93% and a negative predictive value of 37% for sputum (≥3%) or tissue (≥22/mm2) eosinophilia to identify an “eosinophilic phenotype,” it is not currently known whether this is influenced by current dose of corticosteroids or by the severity of asthma. In other words, the changes in periostin levels or its responsiveness have not been evaluated with an increase or a downtitration of steroids in a placebo-controlled randomized trial. The measurement properties of serum periostin are not known in other conditions associated with eosinophilic bronchitis, such as nonasthmatic cough, chronic hyperplastic rhinosinusitis, or smoker's bronchitis, that might be associated with eosinophilic bronchitis. Finally, the treatment effects of an anti–IL-13 mAb in those patients with high periostin levels were modest and not sustained over the 23-week treatment period.12Corren J. Lemanske R.F. Hanania N.A. Korenblat P.E. Parsey M.V. Arron J.R. et al.Lebrikizumab treatment in adults with asthma.N Engl J Med. 2011; 365: 1088-1098Crossref PubMed Scopus (1365) Google Scholar Although sputum eosinophil counts are an accurate reflection of a TH2-dominant mechanism in those asthmatic patients whose symptoms are uncontrolled on high doses of corticosteroids, a simple blood test to accurately predict response to treatment with biologic agents would be ideal and potentially clinically very useful. Periostin shows promise, particularly in patients with severe asthma, but it remains to be seen whether it will serve that purpose. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patientsJournal of Allergy and Clinical ImmunologyVol. 130Issue 3PreviewEosinophilic airway inflammation is heterogeneous in asthmatic patients. We recently described a distinct subtype of asthma defined by the expression of genes inducible by TH2 cytokines in bronchial epithelium. This gene signature, which includes periostin, is present in approximately half of asthmatic patients and correlates with eosinophilic airway inflammation. However, identification of this subtype depends on invasive airway sampling, and hence noninvasive biomarkers of this phenotype are desirable. Full-Text PDF" @default.
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• W2083052532 title "Serum periostin as a marker of TH2-dependent eosinophilic airway inflammation" @default.
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