Bacterial load and inflammatory response in sputum of alpha-1 antitrypsin deficiency patients with COPD

Bruno Balbi, Claudia Sangiorgi, Isabella Gnemmi, Ilaria Ferrarotti, Davide Vallese, Elena Paracchini, Lorena Delle Donne, Luciano Corda, Paolo Baderna, Angelo Corsico, Mauro Carone, Paola Brun, Francesco Cappello, Fabio Lm Ricciardolo, Paolo Ruggeri, Sharon Mumby, Ian M Adcock, Gaetano Caramori, Antonino Di Stefano

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Airway inflammation may drive the progression of chronic obstructive pulmonary disease (COPD) associated with alpha-1 antitrypsin deficiency (AATD), but the relationship between airway microbiota and inflammation has not been investigated. METHODS: We studied 21 non-treated AATD (AATD-noT) patients, 20 AATD-COPD patients under augmentation therapy (AATD-AT), 20 cigarette smoke-associated COPD patients, 20 control healthy smokers (CS) and 21 non-smokers (CON) with normal lung function. We quantified sputum inflammatory cells and inflammatory markers (IL-27, CCL3, CCL5, CXCL8, LTB(4), MPO) by ELISA, total bacterial load (16S) and pathogenic bacteria by qRT-PCR. RESULTS: AATD-AT patients were younger but had similar spirometric and DLCO values compared to cigarette smoke-associated COPD, despite a lower burden of smoking history. Compared to cigarette smoke-associated COPD, AATD-noT and AATD-AT patients had lower sputum neutrophil levels (p=0.0446, p=0.0135), total bacterial load (16S) (p=0.0081, p=0.0223), M. catarrhalis (p=0.0115, p=0.0127) and S. pneumoniae (p=0.0013, p=0.0001). Sputum IL-27 was significantly elevated in CS and cigarette smoke-associated COPD. AATD-AT, but not AATD-noT patients, had IL-27 sputum levels (pg/ml) significantly lower than COPD (p=0.0297) and these positively correlated with FEV(1)% predicted values (r=0.578, p=0.0307). CONCLUSIONS: Compared to cigarette smoke-associated COPD, AATD-AT (COPD) patients have a distinct airway inflammatory and microbiological profile. The decreased sputum bacterial load and IL-27 levels in AATD-AT patients suggests that augmentation therapy play a role in these changes.
Original languageEnglish
Pages (from-to)1879-1893
Number of pages15
JournalInternational journal of chronic obstructive pulmonary disease
Volume14
DOIs
Publication statusPublished - Aug 21 2019

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Keywords

  • *COPD
  • *alpha-1 antitrypsin deficiency
  • *chronic airway inflammation
  • *respiratory disability
  • *sputum

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