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Erschienen in: Lung 4/2014

01.08.2014

Neutrophil Elastase Gene Polymorphisms: Modulators of Response to Therapy in Childhood Bronchiectasis?

verfasst von: Aleksandra Nikolic, Katarina Milosevic, Srdjan Boskovic, Branimir Nestorovic

Erschienen in: Lung | Ausgabe 4/2014

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Abstract

Background

The aim of this study was to investigate polymorphisms in the promoter region of the neutrophil elastase (ELANE) gene as potential modulators of the therapeutic response in children with idiopathic bronchiectasis.

Methods

The study included 48 children between 5 and 17 years old who were diagnosed with idiopathic bronchiectasis based on high-resolution computed tomography of the thorax. In all patients therapy included administration of antibiotics, anti-inflammatory drugs, expectorants, and postural drainage. Response to therapy was evaluated by the change in FeNO levels before and after administration of therapy. The ELANE promoter region polymorphisms were analyzed by PCR-direct DNA sequencing.

Results

According to the predicted activity of ELANE genotypes, subjects were divided into two groups: low/intermediate activity (n = 18) and high activity (n = 30). Subjects in the group with high-activity genotype had higher initial FeNO levels and this difference was statistically significant (t = 2.906; p = 0.006). The difference between FeNO levels before and after therapy was also statistically significantly higher in children with high-activity genotype (t = 3.329; p = 0.002). Statistically significant correlation was observed between the change in FeNO levels and ELANE genotypes (r = 0.350; p = 0.015).

Conclusion

Children with high-activity genotype had higher initial FeNO levels and showed better response to therapy than children with low/intermediate-activity genotypes.
Literatur
2.
3.
Zurück zum Zitat Chan SC, Shum DK, Ip MS (2003) Sputum sol neutrophil elastase activity in bronchiectasis: differential modulation by syndecan-1. Am J Respir Crit Care Med 168:192–198CrossRefPubMed Chan SC, Shum DK, Ip MS (2003) Sputum sol neutrophil elastase activity in bronchiectasis: differential modulation by syndecan-1. Am J Respir Crit Care Med 168:192–198CrossRefPubMed
4.
Zurück zum Zitat Schaaf B, Wieghorst A, Aries SP, Dalhoff K, Braun J (2000) Neutrophil inflammation and activation in bronchiectasis: comparison with pneumonia and idiopathic pulmonary fibrosis. Respiration 67:52–59CrossRefPubMed Schaaf B, Wieghorst A, Aries SP, Dalhoff K, Braun J (2000) Neutrophil inflammation and activation in bronchiectasis: comparison with pneumonia and idiopathic pulmonary fibrosis. Respiration 67:52–59CrossRefPubMed
5.
Zurück zum Zitat Mayer-Hamblett N, Aitken ML, Accurso FJ, Kronmal RA, Konstan MW, Burns JL, Sagel SD, Ramsey BW (2007) Association between pulmonary function and sputum biomarkers in cystic fibrosis. Am J Respir Crit Care Med 175:822–828PubMedCentralCrossRefPubMed Mayer-Hamblett N, Aitken ML, Accurso FJ, Kronmal RA, Konstan MW, Burns JL, Sagel SD, Ramsey BW (2007) Association between pulmonary function and sputum biomarkers in cystic fibrosis. Am J Respir Crit Care Med 175:822–828PubMedCentralCrossRefPubMed
6.
Zurück zum Zitat Döring G (1994) The role of neutrophil elastase in chronic inflammation. Am J Respir Crit Care Med 150:S114–S117CrossRefPubMed Döring G (1994) The role of neutrophil elastase in chronic inflammation. Am J Respir Crit Care Med 150:S114–S117CrossRefPubMed
7.
Zurück zum Zitat Weissmann G, Smolen JE, Korchak HM (1980) Release of inflammatory mediators from stimulated neutrophils. N Engl J Med 303:27–34CrossRefPubMed Weissmann G, Smolen JE, Korchak HM (1980) Release of inflammatory mediators from stimulated neutrophils. N Engl J Med 303:27–34CrossRefPubMed
8.
Zurück zum Zitat Takahashi H, Nukiwa T, Yoshimura K, Quick CD, States DJ, Holmes MD, Whang-Peng J, Knutsen T, Crystal RG (1988) Structure of the human neutrophil elastase gene. J Biol Chem 263:14739–14747PubMed Takahashi H, Nukiwa T, Yoshimura K, Quick CD, States DJ, Holmes MD, Whang-Peng J, Knutsen T, Crystal RG (1988) Structure of the human neutrophil elastase gene. J Biol Chem 263:14739–14747PubMed
9.
Zurück zum Zitat Saitoh H, Masuda T, Shimura S, Fushimi T, Shirato K (2001) Secretion and gene expression of secretory leukocyte protease inhibitor by human airway submucosal glands. Am J Physiol Lung Cell Mol Physiol 280:L79–L87PubMed Saitoh H, Masuda T, Shimura S, Fushimi T, Shirato K (2001) Secretion and gene expression of secretory leukocyte protease inhibitor by human airway submucosal glands. Am J Physiol Lung Cell Mol Physiol 280:L79–L87PubMed
10.
Zurück zum Zitat Verbanac KM, Heath EC (1986) Biosynthesis, processing, and secretion of M and Z variant human alpha 1-antitrypsin. J Biol Chem 261:9979–9989PubMed Verbanac KM, Heath EC (1986) Biosynthesis, processing, and secretion of M and Z variant human alpha 1-antitrypsin. J Biol Chem 261:9979–9989PubMed
11.
Zurück zum Zitat Stockley RA (1999) Neutrophils and protease/antiprotease imbalance. Am J Respir Crit Care Med 160:S49–S52CrossRefPubMed Stockley RA (1999) Neutrophils and protease/antiprotease imbalance. Am J Respir Crit Care Med 160:S49–S52CrossRefPubMed
12.
Zurück zum Zitat Taniguchi K, Yang P, Jett J, Bass E, Meyer R, Wang Y, Deschamps C, Liu W (2002) Polymorphisms in the promoter region of the neutrophil elastase gene are associated with lung cancer development. Clin Cancer Res 8:1115–1120PubMed Taniguchi K, Yang P, Jett J, Bass E, Meyer R, Wang Y, Deschamps C, Liu W (2002) Polymorphisms in the promoter region of the neutrophil elastase gene are associated with lung cancer development. Clin Cancer Res 8:1115–1120PubMed
13.
Zurück zum Zitat Park JY, Chen L, Lee J, Sellers T, Tockman MS (2005) Polymorphisms in the promoter region of neutrophil elastase gene and lung cancer risk. Lung Cancer 48:315–321PubMedCentralCrossRefPubMed Park JY, Chen L, Lee J, Sellers T, Tockman MS (2005) Polymorphisms in the promoter region of neutrophil elastase gene and lung cancer risk. Lung Cancer 48:315–321PubMedCentralCrossRefPubMed
14.
Zurück zum Zitat Weinrauch Y, Drujan D, Shapiro SD, Weiss J, Zychlinsky A (2002) Neutrophil elastase targets virulence factors of enterobacteria. Nature 417:91–94CrossRefPubMed Weinrauch Y, Drujan D, Shapiro SD, Weiss J, Zychlinsky A (2002) Neutrophil elastase targets virulence factors of enterobacteria. Nature 417:91–94CrossRefPubMed
15.
Zurück zum Zitat Pasteur MC, Bilton D, Hill AT, British Thoracic Society Bronchiectasis non-CF Guideline Group (2010) British Thoracic Society guideline for non-CF bronchiectasis. Thorax 65(Suppl 1):i1–i58CrossRefPubMed Pasteur MC, Bilton D, Hill AT, British Thoracic Society Bronchiectasis non-CF Guideline Group (2010) British Thoracic Society guideline for non-CF bronchiectasis. Thorax 65(Suppl 1):i1–i58CrossRefPubMed
16.
Zurück zum Zitat Manna A, Caffarelli C, Varini M, Povesi Dascola C, Montella S, Maglione M, Sperlì F, Santamaria F (2012) Clinical application of exhaled nitric oxide measurement in pediatric lung diseases. Ital J Pediatr 38:74PubMedCentralCrossRefPubMed Manna A, Caffarelli C, Varini M, Povesi Dascola C, Montella S, Maglione M, Sperlì F, Santamaria F (2012) Clinical application of exhaled nitric oxide measurement in pediatric lung diseases. Ital J Pediatr 38:74PubMedCentralCrossRefPubMed
17.
Zurück zum Zitat Habib SS (2008) Exhaled nitric oxide: an emerging marker of inflammation in respiratory diseases. Saudi Med J 29:1697–1702PubMed Habib SS (2008) Exhaled nitric oxide: an emerging marker of inflammation in respiratory diseases. Saudi Med J 29:1697–1702PubMed
18.
Zurück zum Zitat Dweik RA, Boggs PB, Irvin CG, Leigh MW, Erzurum SC, Lundberg JO, Olin AC, Taylor DR, American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications (2011) An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med 184:602–615PubMedCentralCrossRefPubMed Dweik RA, Boggs PB, Irvin CG, Leigh MW, Erzurum SC, Lundberg JO, Olin AC, Taylor DR, American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications (2011) An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med 184:602–615PubMedCentralCrossRefPubMed
19.
Zurück zum Zitat Angrill J, Agustí C, De Celis R, Filella X, Rañó A, Elena M, De La Bellacasa JP, Xaubet A, Torres A (2001) Bronchial inflammation and colonization in patients with clinically stable bronchiectasis. Am J Respir Crit Care Med 164:1628–1632CrossRefPubMed Angrill J, Agustí C, De Celis R, Filella X, Rañó A, Elena M, De La Bellacasa JP, Xaubet A, Torres A (2001) Bronchial inflammation and colonization in patients with clinically stable bronchiectasis. Am J Respir Crit Care Med 164:1628–1632CrossRefPubMed
20.
Zurück zum Zitat Ergan Arsava B, Cöplü L (2011) Does airway colonization cause systemic inflammation in bronchiectasis? Tuberk Toraks 59:340–347CrossRefPubMed Ergan Arsava B, Cöplü L (2011) Does airway colonization cause systemic inflammation in bronchiectasis? Tuberk Toraks 59:340–347CrossRefPubMed
21.
Zurück zum Zitat Foley SC, Hopkins NO, Fitzgerald MX, Donnelly SC, McLoughlin P (2007) Airway nitric oxide output is reduced in bronchiectasis. Respir Med 101:1549–1555CrossRefPubMed Foley SC, Hopkins NO, Fitzgerald MX, Donnelly SC, McLoughlin P (2007) Airway nitric oxide output is reduced in bronchiectasis. Respir Med 101:1549–1555CrossRefPubMed
22.
Zurück zum Zitat Tsang KW, Leung R, Fung PC, Chan SL, Tipoe GL, Ooi GC, Lam WK (2002) Exhaled and sputum nitric oxide in bronchiectasis: correlation with clinical parameters. Chest 121:88–94CrossRefPubMed Tsang KW, Leung R, Fung PC, Chan SL, Tipoe GL, Ooi GC, Lam WK (2002) Exhaled and sputum nitric oxide in bronchiectasis: correlation with clinical parameters. Chest 121:88–94CrossRefPubMed
23.
Zurück zum Zitat Shoemark A, Devaraj A, Meister M, Ozerovitch L, Hansell DM, Wilson R (2011) Elevated peripheral airway nitric oxide in bronchiectasis reflects disease severity. Respir Med 105:885–891CrossRefPubMed Shoemark A, Devaraj A, Meister M, Ozerovitch L, Hansell DM, Wilson R (2011) Elevated peripheral airway nitric oxide in bronchiectasis reflects disease severity. Respir Med 105:885–891CrossRefPubMed
24.
Zurück zum Zitat Cho YJ, Lim HJ, Park JS, Lee JH, Lee CT, Yoon HI (2013) Measurement of fractional exhaled nitric oxide in stable bronchiectasis. Tuberc Respir Dis (Seoul) 74:7–14CrossRef Cho YJ, Lim HJ, Park JS, Lee JH, Lee CT, Yoon HI (2013) Measurement of fractional exhaled nitric oxide in stable bronchiectasis. Tuberc Respir Dis (Seoul) 74:7–14CrossRef
25.
Zurück zum Zitat Kharitonov SA, Barnes PJ (2000) Clinical aspects of exhaled nitric oxide. Eur Respir J 16:781–792CrossRefPubMed Kharitonov SA, Barnes PJ (2000) Clinical aspects of exhaled nitric oxide. Eur Respir J 16:781–792CrossRefPubMed
26.
Zurück zum Zitat Kawabata K, Hagio T, Matsuoka S (2002) The role of neutrophil elastase in acute lung injury. Eur J Pharmacol 451:1–10CrossRefPubMed Kawabata K, Hagio T, Matsuoka S (2002) The role of neutrophil elastase in acute lung injury. Eur J Pharmacol 451:1–10CrossRefPubMed
27.
Zurück zum Zitat Smallman LA, Hill SL, Stockley RA (1984) Reduction of ciliary beat frequency in vitro by sputum from patients with bronchiectasis: a serine proteinase effect. Thorax 39:663–667PubMedCentralCrossRefPubMed Smallman LA, Hill SL, Stockley RA (1984) Reduction of ciliary beat frequency in vitro by sputum from patients with bronchiectasis: a serine proteinase effect. Thorax 39:663–667PubMedCentralCrossRefPubMed
28.
Zurück zum Zitat Tsang KW, Tan KC, Ho PL, Ooi GC, Khong PL, Leung R, Mak JC, Tipoe GL, Ko C, Lam WK (2004) Exhaled nitric oxide in bronchiectasis: the effects of inhaled corticosteroid therapy. Int J Tuberc Lung Dis 8:1301–1307PubMed Tsang KW, Tan KC, Ho PL, Ooi GC, Khong PL, Leung R, Mak JC, Tipoe GL, Ko C, Lam WK (2004) Exhaled nitric oxide in bronchiectasis: the effects of inhaled corticosteroid therapy. Int J Tuberc Lung Dis 8:1301–1307PubMed
29.
Zurück zum Zitat Gorrini M, Lupi A, Viglio S, Pamparana F, Cetta G, Iadarola P, Powers JC, Luisetti M (2001) Inhibition of human neutrophil elastase by erythromycin and flurithromycin, two macrolide antibiotics. Am J Respir Cell Mol Biol 25:492–499CrossRefPubMed Gorrini M, Lupi A, Viglio S, Pamparana F, Cetta G, Iadarola P, Powers JC, Luisetti M (2001) Inhibition of human neutrophil elastase by erythromycin and flurithromycin, two macrolide antibiotics. Am J Respir Cell Mol Biol 25:492–499CrossRefPubMed
30.
Zurück zum Zitat Shinkai M, Rubin BK (2005) Macrolides and airway inflammation in children. Paediatr Respir Rev 6:227–235CrossRefPubMed Shinkai M, Rubin BK (2005) Macrolides and airway inflammation in children. Paediatr Respir Rev 6:227–235CrossRefPubMed
Metadaten
Titel
Neutrophil Elastase Gene Polymorphisms: Modulators of Response to Therapy in Childhood Bronchiectasis?
verfasst von
Aleksandra Nikolic
Katarina Milosevic
Srdjan Boskovic
Branimir Nestorovic
Publikationsdatum
01.08.2014
Verlag
Springer US
Erschienen in
Lung / Ausgabe 4/2014
Print ISSN: 0341-2040
Elektronische ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-014-9596-3

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