Neutrophil elastase in bronchiectasis

Gramegna, Andrea; Amati, Francesco; Terranova, Leonardo; Sotgiu, Giovanni; Tarsia, Paolo; Miglietta, Daniela; Calderazzo, Maria Adelaide; Aliberti, Stefano; Blasi, Francesco

doi:10.1186/s12931-017-0691-x

Cited by 94 publications

(81 citation statements)

References 88 publications

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“…Bronchiectasis has also been associated with AATD, with the mechanistic link of incompletely opposed neutrophil elastase activity [25]. There is concrete evidence of a direct impact of neutrophil elastase on bronchiectasis disease progression through effects on ciliated epithelium, mucus production, emphysema development and inactivation of the immune response [26]. However, whether bronchiectasis comes from a primary mechanism of the disease or is the result of recurrent respiratory infection is still matter of debate [27].…”

Section: Bronchiectasismentioning

confidence: 99%

α₁-Antitrypsin deficiency and chronic respiratory disorders

et al. 2020

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α1-antitrypsin deficiency (AATD) is a hereditary disorder associated with a risk of developing liver disease and pulmonary emphysema, and other chronic respiratory disorders (mainly asthma and bronchiectasis); Z variant is the commonest deficient variant of AAT. Determining AAT concentration in serum or plasma and identifying allelic variants by phenotyping or genotyping are fundamental in the diagnosis of AATD. Initial evaluation and annual follow-up measurement of lung function, including post-bronchodilator forced expiratory volume in 1 s and gas transfer inform on disease progression. Lung densitometry is the most sensitive measure of emphysema progression, but must not be use in the follow-up of patients in routine clinical practice. The exogenous administration of purified human serum-derived AAT is the only approved specific treatment for AATD in PiZZ. AAT augmentation therapy is not recommended in PiSZ, PiMZ or current smokers of any protein phenotype, or in patients with hepatic disease. Lung volume reduction and endoscopic bronchial valve placement are useful in selected patients, whereas the survival benefit of lung transplant is unclear. There are several new lines of research in AATD to improve the diagnosis and evaluation of the response to therapy and to develop genetic and regenerative therapies and other treatments.

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Section: Bronchiectasismentioning

confidence: 99%

α₁-Antitrypsin deficiency and chronic respiratory disorders

et al. 2020

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“…The predominant immune cells seen histologically in bronchiectasis are: (i) neutrophils (principally in the airway lumen), supporting a role for neutrophil‐derived proteases (found in high levels in sputum from bronchiectasis patients) in driving bronchial wall damage; (ii) macrophages; and (iii) lymphocytes (predominantly CD4+ cells). Recent work has implicated IL‐17‐secreting lymphocytes (Th17 cells and NK cells) in driving neutrophil recruitment as well as mucus hypersecretion.…”

Section: Pathophysiological Mechanisms In Established Diseasementioning

confidence: 87%

Pathophysiology, causes and genetics of paediatric and adult bronchiectasis

Bush

Floto

2019

Respirology

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Bronchiectasis has historically been considered to be irreversible dilatation of the airways, but with modern imaging techniques it has been proposed that 'irreversible' be dropped from the definition. The upper limit of normal for the ratio of airway to arterial development increases with age, and a developmental perspective is essential. Bronchiectasis (and persistent bacterial bronchitis, PBB) is a descriptive term and not a diagnosis, and should be the start not the end of the patient's diagnostic journey. PBB, characterized by airway infection and neutrophilic inflammation but without significant airway dilatation may be a precursor of bronchiectasis, and there are many commonalities in the microbiology and the pathology, which are reviewed in this article. A high index of suspicion is essential, and a history of chronic wet or productive cough for more than 4-8 weeks should prompt investigation. There are numerous underlying causes of bronchiectasis, although in many cases no cause is found. Causes include post-infectious, especially after tuberculosis, adenoviral or pertussis infection; aspiration syndromes; defects in host defence, which may solely affect the airways (cystic fibrosis, not considered in this review, and primary ciliary dyskinesia); and primary ciliary dyskinesia or be systemic, such as common variable immunodeficiency; genetic syndromes; and anatomical defects such as intraluminal airway obstruction (e.g. foreign body), intramural obstruction (e.g. complete cartilage rings) and external airway compression (e.g. by tuberculous lymph nodes). Identification of the underlying cause is important, because some of these conditions have specific treatments and others genetic implications for the family.

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“…The test is semi-quantitative and shows a good correlation with neutrophil elastase activity measured by immunoassay. Neutrophil elastase activity is an established biomarker of bronchiectasis as well as being associated with risk of exacerbations, airway infection status and lung function decline in other conditions such as cystic fibrosis [16]. Implementation of sputum biomarkers into clinical practice are limited by the requirement to process sputum via centrifugation and the design of traditional assays for neutrophil elastase, which are typically based on the cleavage of chromogenic substrates.…”

Section: Discussionmentioning

confidence: 99%

“…Neutrophil elastase activity is a leading candidate for a bronchiectasis biomarker [13]. The relationship between sputum neutrophil elastase activity and airway infection has been known for more than two decades and studies demonstrate that neutrophil elastase may directly impact on bronchiectasis disease progression through effects of ciliated epithelium, mucus production, emphysema development and inactivation of the immune response [14][15][16]. A systematic review of clinical studies in bronchiectasis identified 31 studies and found that higher neutrophil elastase activity in sputum was associated with sputum colour, P. aeruginosa infection, airway bacterial load, disease severity, forced expiratory volume in 1 s (FEV1) symptoms and long-term risk of exacerbations and lung function decline [16].…”

Section: Introductionmentioning

confidence: 99%

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A point-of-care neutrophil elastase activity assay identifies bronchiectasis severity, airway infection and risk of exacerbation

et al. 2019

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IntroductionNeutrophil elastase activity in sputum can identify patients at high risk of airway infection and exacerbations in bronchiectasis. Application of this biomarker in clinical practice is limited, because no point-of-care test is available. We tested whether a novel semi-quantitative lateral flow device (neutrophil elastase airway test stick – NEATstik®) can stratify bronchiectasis patients according to severity, airway infection and exacerbation risk.MethodsSputum samples from 124 patients with stable bronchiectasis enrolled in the UK and Spain were tested using the NEATstik®, which scores neutrophil elastase concentration from 0 (<8 µg·mL−1 elastase activity) to 10 (maximum detectable neutrophil elastase activity). High neutrophil elastase activity was regarded as a NEATstik® grade >6. Severity of disease, airway infection from sputum culture and exacerbations over the 12 months were recorded. An independent validation was conducted in 50 patients from Milan, Italy.Measurements and main resultsPatients had a median age of 69 years and forced expiratory volume in 1 s (FEV1) 69%. High neutrophil elastase activity was associated with worse bronchiectasis severity using the bronchiectasis severity index (p=0.0007) and FEV1 (p=0.02). A high NEATstik® grade was associated with a significant increase in exacerbation frequency, incident rate ratio 2.75 (95% CI 1.63–4.64, p<0.001). The median time to next exacerbation for patients with a NEATstik® grade >6 was 103 days compared to 278 days. The hazard ratio was 2.59 (95% CI 1.71–3.94, p<0.001). Results were confirmed in the independent validation cohort.ConclusionsA novel lateral flow device provides assessment of neutrophil elastase activity from sputum in minutes and identifies patients at increasing risk of airway infection and future exacerbations.

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Neutrophil elastase in bronchiectasis

Cited by 94 publications

References 88 publications

α₁-Antitrypsin deficiency and chronic respiratory disorders

α₁-Antitrypsin deficiency and chronic respiratory disorders

Pathophysiology, causes and genetics of paediatric and adult bronchiectasis

A point-of-care neutrophil elastase activity assay identifies bronchiectasis severity, airway infection and risk of exacerbation

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Neutrophil elastase in bronchiectasis

Cited by 94 publications

References 88 publications

α1-Antitrypsin deficiency and chronic respiratory disorders

α1-Antitrypsin deficiency and chronic respiratory disorders

Pathophysiology, causes and genetics of paediatric and adult bronchiectasis

A point-of-care neutrophil elastase activity assay identifies bronchiectasis severity, airway infection and risk of exacerbation

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α₁-Antitrypsin deficiency and chronic respiratory disorders

α₁-Antitrypsin deficiency and chronic respiratory disorders