Sputum Neutrophil Elastase and Its Relation to Pediatric Bronchiectasis Severity: A Cross-sectional Study

Overview

Journal Health Sci Rep

Specialty General Medicine

Date 2022 May 5

PMID 35509417

Authors

Heba A Ali

Eman M Fouda

Mona A Salem

Marwa A Abdelwahad

Heba H Radwan

Affiliations

Soon will be listed here.

Abstract

Background And Aims: Sputum neutrophil elastase (NE) is a marker of neutrophilic airway inflammation in bronchiectasis. Yet, not much is known about its role in pediatric bronchiectasis severity. This study aimed to assess the sputum NE value as a biomarker of clinical and radiological severity in pediatric bronchiectasis.

Methods: This was a cross-sectional study assessing sputum NE in a total of 50 bronchiectasis patients under the age of 18 years-30 patients with cystic fibrosis (CF) and 20 patients with non-CF bronchiectasis were included. Bronchiectasis severity was assessed using Shwachman-Kulczycki (SK) score, CF-ABLE score, and CF risk of disease progression score, among CF patients, and bronchiectasis severity index (BSI) and FACED criteria among non-CF bronchiectasis patients, associations between sputum NE and bronchiectasis severity were assessed in both patient groups.

Results: Sputum NE was directly correlated with C-reactive protein ( = 0.914, < 0.001), ( = 0.786, < 0.001), frequency of exacerbations ( = 0.852, < 0.001) ( = 0.858, < 0.001), exacerbations severity ( = 0.735, = 0.002), ( = 0.907, < 0.001), and the number of hospital admissions ( = 0.813, < 0.001), ( = 0.612, 0.004) in the last year among CF, and non-CF bronchiectasis patients, respectively. Additional linear correlations were found between sputum NE, CF risk of disease progression score ( < 0.001), CF-ABLE score ( < 0.001), and lower forced expiratory volume 1% of predicted (= 0.017; = -0.8) among CF patients. Moreover, sputum NE was positively correlated with the neutrophil count ( = 0.018), and BSI severity score ( = 0.039; = 0.465) among non-CF bronchiectasis patients.

Conclusions: Sputum NE may be considered a good biomarker of bronchiectasis severity in both CF and non-CF bronchiectasis patients, as confirmed by the exacerbations rate, CF risk of disease progression, and BSI scores.

Citing Articles

Targeting neutrophil serine proteases in bronchiectasis.

Chalmers J, Mall M, Chotirmall S, ODonnell A, Flume P, Hasegawa N Eur Respir J. 2024; 65(1).

PMID: 39467608 PMC: 11694565. DOI: 10.1183/13993003.01050-2024.

Neutrophil serine proteases in cystic fibrosis: role in disease pathogenesis and rationale as a therapeutic target.

Mall M, Davies J, Donaldson S, Jain R, Chalmers J, Shteinberg M Eur Respir Rev. 2024; 33(173).

PMID: 39293854 PMC: 11409056. DOI: 10.1183/16000617.0001-2024.

Endotypes of Paediatric Cough-Do They Exist and Finding New Techniques to Improve Clinical Outcomes.

OFarrell H, Kok H, Goel S, Chang A, Yerkovich S J Clin Med. 2024; 13(3).

PMID: 38337450 PMC: 10856076. DOI: 10.3390/jcm13030756.

Substrate-dependent metabolomic signatures of myeloperoxidase activity in airway epithelial cells: Implications for early cystic fibrosis lung disease.

Kim S, Shapiro J, Cottrill K, Collins G, Shanthikumar S, Rao P Free Radic Biol Med. 2023; 206:180-190.

PMID: 37356776 PMC: 10513041. DOI: 10.1016/j.freeradbiomed.2023.06.021.

Bacteriophage: A new therapeutic player to combat neutrophilic inflammation in chronic airway diseases.

Laucirica D, Stick S, Garratt L, Kicic A Front Med (Lausanne). 2023; 9:1069929.

PMID: 36590945 PMC: 9794625. DOI: 10.3389/fmed.2022.1069929.

References

De Boeck K, Derichs N, Fajac I, de Jonge H, Bronsveld I, Sermet I . New clinical diagnostic procedures for cystic fibrosis in Europe. J Cyst Fibros. 2011; 10 Suppl 2:S53-66. DOI: 10.1016/S1569-1993(11)60009-X. View

Al-Saleh S, Dell S, Grasemann H, Yau Y, Waters V, Martin S . Sputum induction in routine clinical care of children with cystic fibrosis. J Pediatr. 2010; 157(6):1006-1011.e1. DOI: 10.1016/j.jpeds.2010.06.001. View

Sagel S, Kapsner R, Osberg I . Induced sputum matrix metalloproteinase-9 correlates with lung function and airway inflammation in children with cystic fibrosis. Pediatr Pulmonol. 2005; 39(3):224-32. DOI: 10.1002/ppul.20165. View

Mayer-Hamblett N, Aitken M, Accurso F, Kronmal R, Konstan M, Burns J . Association between pulmonary function and sputum biomarkers in cystic fibrosis. Am J Respir Crit Care Med. 2007; 175(8):822-8. PMC: 2720115. DOI: 10.1164/rccm.200609-1354OC. View

Roghanian A, Drost E, MacNee W, Howie S, Sallenave J . Inflammatory lung secretions inhibit dendritic cell maturation and function via neutrophil elastase. Am J Respir Crit Care Med. 2006; 174(11):1189-98. DOI: 10.1164/rccm.200605-632OC. View

Gramegna A, Amati F, Terranova L, Sotgiu G, Tarsia P, Miglietta D . Neutrophil elastase in bronchiectasis. Respir Res. 2017; 18(1):211. PMC: 5735855. DOI: 10.1186/s12931-017-0691-x. View

Suter S, Schaad U, Tegner H, Ohlsson K, Desgrandchamps D, Waldvogel F . Levels of free granulocyte elastase in bronchial secretions from patients with cystic fibrosis: effect of antimicrobial treatment against Pseudomonas aeruginosa. J Infect Dis. 1986; 153(5):902-9. DOI: 10.1093/infdis/153.5.902. View

McCarthy C, Dimitrov B, Meurling I, Gunaratnam C, McElvaney N . The CF-ABLE score: a novel clinical prediction rule for prognosis in patients with cystic fibrosis. Chest. 2012; 143(5):1358-1364. DOI: 10.1378/chest.12-2022. View

OConnor C, Gaffney K, Keane J, Southey A, Byrne N, OMahoney S . alpha 1-Proteinase inhibitor, elastase activity, and lung disease severity in cystic fibrosis. Am Rev Respir Dis. 1993; 148(6 Pt 1):1665-70. DOI: 10.1164/ajrccm/148.6_Pt_1.1665. View

10.

Ancliff P, Gale R, Watts M, Liesner R, Hann I, Strobel S . Paternal mosaicism proves the pathogenic nature of mutations in neutrophil elastase in severe congenital neutropenia. Blood. 2002; 100(2):707-9. DOI: 10.1182/blood-2002-01-0060. View

11.

SHWACHMAN H, KULCZYCKI L . Long-term study of one hundred five patients with cystic fibrosis; studies made over a five- to fourteen-year period. AMA J Dis Child. 1958; 96(1):6-15. DOI: 10.1001/archpedi.1958.02060060008002. View

12.

Ali H, Fouda E, Salem M, Abdelwahad M, Radwan H . Sputum neutrophil elastase and its relation to pediatric bronchiectasis severity: A cross-sectional study. Health Sci Rep. 2022; 5(3):e581. PMC: 9059204. DOI: 10.1002/hsr2.581. View

13.

Chang A, Bell S, Torzillo P, King P, Maguire G, Byrnes C . Chronic suppurative lung disease and bronchiectasis in children and adults in Australia and New Zealand Thoracic Society of Australia and New Zealand guidelines. Med J Aust. 2015; 202(1):21-3. DOI: 10.5694/mja14.00287. View

14.

Goeminne P, Vandooren J, Moelants E, Decraene A, Rabaey E, Pauwels A . The Sputum Colour Chart as a predictor of lung inflammation, proteolysis and damage in non-cystic fibrosis bronchiectasis: a case-control analysis. Respirology. 2013; 19(2):203-210. DOI: 10.1111/resp.12219. View

15.

Chalmers J, Smith M, McHugh B, Doherty C, Govan J, Hill A . Short- and long-term antibiotic treatment reduces airway and systemic inflammation in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2012; 186(7):657-65. DOI: 10.1164/rccm.201203-0487OC. View

16.

Chalmers J, Moffitt K, Suarez-Cuartin G, Sibila O, Finch S, Furrie E . Neutrophil Elastase Activity Is Associated with Exacerbations and Lung Function Decline in Bronchiectasis. Am J Respir Crit Care Med. 2016; 195(10):1384-1393. PMC: 5443898. DOI: 10.1164/rccm.201605-1027OC. View

17.

Fuchs H, Borowitz D, Christiansen D, Morris E, Nash M, Ramsey B . Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group. N Engl J Med. 1994; 331(10):637-42. DOI: 10.1056/NEJM199409083311003. View

18.

Khan T, Wagener J, Bost T, Martinez J, Accurso F, Riches D . Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med. 1995; 151(4):1075-82. DOI: 10.1164/ajrccm/151.4.1075. View

19.

Guan W, Gao Y, Xu G, Lin Z, Tang Y, Gu Y . Sputum matrix metalloproteinase-8 and -9 and tissue inhibitor of metalloproteinase-1 in bronchiectasis: clinical correlates and prognostic implications. Respirology. 2015; 20(7):1073-81. DOI: 10.1111/resp.12582. View

20.

Sly P, Brennan S, Gangell C, de Klerk N, Murray C, Mott L . Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening. Am J Respir Crit Care Med. 2009; 180(2):146-52. DOI: 10.1164/rccm.200901-0069OC. View