Sputum inflammatory cells in COPD patients classified according to GOLD 2011 guidelines

Bartoli, Maria Laura; Costa, Francesco; Malagrinò, Laura; Nieri, Dario; Antonelli, Sandra; Decusatis, Giovanna; Simone, Claudia De; Santerini, Sabrina; Cianchetti, Silvana; Latorre, Manuela; Vagaggini, Barbara; Paggiaro, Pier Luigi

doi:10.1183/13993003.00784-2015

Cited by 15 publications

(11 citation statements)

References 12 publications

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“…A similar analysis is required for CF. Mean NE activity is higher in adult CF than bronchiectasis and so the cut-offs used in our study should not be extrapolated to CF or other conditions such as COPD [48, 49]. We used NE >20 µg·mL −1 as a cut-off based on our prior publication [11], but we acknowledge that we cannot prove patients with lower levels of NE would not benefit from NE inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Personalised anti-inflammatory therapy for bronchiectasis and cystic fibrosis: selecting patients for controlled trials of neutrophil elastase inhibition

et al. 2019

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BackgroundNeutrophil elastase (NE) has been linked to lung neutrophil dysfunction in bronchiectasis and cystic fibrosis (CF), making NE inhibition a potential therapeutic target. NE inhibitor trials have given mixed result perhaps because not all patients have elevated airway NE activity.MethodsWe tested whether a single baseline sputum NE measurement or a combination of clinical parameters could enrich patient populations with elevated NE activity for “personalised medicine”. Intra- and interindividual variations of total and active NE levels in induced sputum from patients with CF or bronchiectasis were monitored over 14 days. Patients with established CF and bronchiectasis (n=5 per group) were recruited. NE was measured using three different methods: one total and two active NE assays. Subsequently, we analysed the association between clinical parameters and NE from a large bronchiectasis cohort study (n=381).ResultsAll three assays showed a high degree of day-to-day variability (0–233% over 14 days). There were strong correlations found between all assays (p<0.0001). Despite high day-to-day variability, patients could be stratified into “high” or “low” groups based on moderate cut-off levels. In the bronchiectasis cohort study, factors most associated with high sputum NE levels were: Pseudomonas aeruginosa infection (β-estimate 11.5, 95% CI −6.0–29.0), sputum colour (β-estimate 10.4, 95% CI 4.3–16.6), Medical Research Council dyspnoea score (β-estimate 6.4, 95% CI 1.4–11.4) and exacerbation history (β-estimate 3.4, 95% CI 1.4–5.3). Collectively, P. aeruginosa infection, sputum colour and exacerbation frequency provided the greatest specificity for “high” NE (98.7%, 95% CI 7.0–99.6%).ConclusionThese results show that patients with bronchiectasis and CF can be effectively divided into “high” or “low” groups, based on sputum NE assays or clinical inclusion criteria.

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Section: Discussionmentioning

confidence: 99%

Personalised anti-inflammatory therapy for bronchiectasis and cystic fibrosis: selecting patients for controlled trials of neutrophil elastase inhibition

et al. 2019

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“… 8 , 9 An observational study found that patients with higher sputum neutrophil percentages had a higher dyspnea score across different severities of COPD. 10 …”

Section: Introductionmentioning

confidence: 99%

Role of inflammatory cells in airway remodeling in COPD

Wang¹,

Xu²,

Meng³

et al. 2018

COPD

253

184

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COPD is characterized by chronic bronchitis, chronic airway obstruction, and emphysema, leading to a progressive and irreversible decline in lung function. Inflammation is central for the development of COPD. Chronic inflammation in COPD mainly involves the infiltration of neutrophils, macrophages, lymphocytes, and other inflammatory cells into the small airways. The contribution of resident airway structural cells to the inflammatory process is also important in COPD. Airway remodeling consists of detrimental changes in structural tissues and cells including airway wall thickening, epithelial metaplasia, goblet cell hypertrophy, and smooth muscle hyperplasia. Persistent airway inflammation might contribute to airway remodeling and small airway obstruction. However, the underlying mechanisms remain unclear. In this review, we will provide an overview of recent insights into the role of major immunoinflammatory cells in COPD airway remodeling.

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“… 1–3 Sputum eosinophilia (>3% non-squamous cells) has been observed in approximately one-third of patients during an exacerbation, 3 and sputum eosinophil counts are associated with COPD severity. 4 , 5 Sputum eosinophils can also identify patients more likely to respond to corticosteroid treatment. 1 , 6 …”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] Sputum eosinophilia (>3% nonsquamous cells) has been observed in approximately onethird of patients during an exacerbation, 3 and sputum eosinophil counts are associated with COPD severity. 4,5 Sputum eosinophils can also identify patients more likely to respond to corticosteroid treatment. 1,6 Blood eosinophil counts correlate positively with sputum eosinophil counts, with counts of <2% (equivalent to approximately <150 cells/µL) 7 having a high negative predictive value in stable and exacerbating COPD.…”

Section: Introductionmentioning

confidence: 99%

Mepolizumab for Eosinophil-Associated COPD: Analysis of METREX and METREO

Pavord¹,

Bafadhel²,

Sciurba³

et al. 2021

COPD

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Background A pre-specified meta-analysis of individual patient data from the 52-week METREX and METREO trials, which investigated mepolizumab for chronic obstructive pulmonary disease (COPD) in patients with blood eosinophil counts ≥150 cells/µL (screening) or ≥300 cells/µL (prior year) and frequent exacerbations, enables more robust characterization of mepolizumab efficacy in COPD and exploration of the relationship between blood eosinophil count and treatment responses. Methods In METREX (117106/NCT02105948) and METREO (117113/NCT02105961), randomized patients received mepolizumab or placebo added to existing inhaled corticosteroid (ICS)–based triple maintenance therapy. The annual rate of moderate/severe exacerbations (primary endpoint) was compared between subcutaneous (SC) mepolizumab 100 mg versus placebo (primary comparison of interest) and all doses (100 mg and 300 mg SC) versus placebo in patients with blood eosinophil counts ≥150 cells/µL at screening or ≥300 cells/µL in the prior year. Secondary/other endpoints included time to first moderate/severe exacerbation, exacerbations leading to emergency department visit/hospitalization and health-related quality of life (HRQoL). A predictive model of the relationship between screening blood eosinophil counts and exacerbation rates included data from all randomized patients. Results In total, 1510 patients were randomized in METREX and METREO and 1136 patients were included in the pre-specified meta-analysis. From the meta-analysis, mepolizumab 100 mg SC significantly reduced annual moderate/severe exacerbation rates versus placebo by 18% (rate ratio: 0.82; 95% confidence interval: 0.71, 0.95; p=0.006) and delayed time to first moderate/severe exacerbation (hazard ratio: 0.80 [0.68, 0.94]; p=0.006). Mepolizumab 100 mg SC versus placebo numerically reduced exacerbations leading to ED visits/hospitalization and improved HRQoL. A modelling approach demonstrated increasing efficacy for moderate/severe exacerbations with increasing screening blood eosinophil count; this relationship was more pronounced for exacerbations requiring oral corticosteroids (post hoc). The all-doses comparison had similar results. Conclusion Mepolizumab reduces exacerbations in patients with eosinophil-associated COPD. Results suggest that blood eosinophil counts (≥150 cells/µL at screening or ≥300 cells/µL in the prior year) allow for identification of patients with COPD who experience exacerbations while treated with maximal ICS-based triple maintenance therapy who are likely to benefit from mepolizumab.

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Sputum inflammatory cells in COPD patients classified according to GOLD 2011 guidelines

Cited by 15 publications

References 12 publications

Personalised anti-inflammatory therapy for bronchiectasis and cystic fibrosis: selecting patients for controlled trials of neutrophil elastase inhibition

Personalised anti-inflammatory therapy for bronchiectasis and cystic fibrosis: selecting patients for controlled trials of neutrophil elastase inhibition

Role of inflammatory cells in airway remodeling in COPD

Mepolizumab for Eosinophil-Associated COPD: Analysis of METREX and METREO

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