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

Balbi, B; Sangiorgi, C; Gnemmi, I; Ferrarotti, I; Vallese, D; Paracchini, E; Donne, LD; Corda, L; Baderna, P; Corsico, A; Carone, M; Brun, P; Cappello, F; Ricciardolo, FLM; Ruggeri, P; Mumby, S; Adcock, IM; Caramori, G; Di Stefano, D

doi:10.2147/COPD.S207203

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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, LTB4, 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 FEV1% 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. Keywords: alpha-1 antitrypsin deficiency, COPD, chronic airway inflammation, respiratory disability, sputum © 2019 Balbi et al.

Data di pubblicazione:	2019
Titolo:	Bacterial load and inflammatory response in sputum of alpha-1 antitrypsin deficiency patients with COPD
Autori:	Balbi B. SANGIORGI, Claudia Gnemmi I. Ferrarotti I. VALLESE, Davide Paracchini E. Donne L. D. Corda L. Baderna P. Corsico A. CARONE, MARCO Brun P. CAPPELLO, Francesco Ricciardolo F. L. M. Ruggeri P. Mumby S. Adcock I. M. Caramori G. Di Stefano D. mostra contributor esterni nascondi contributor esterni
Citazione:	Balbi B., Sangiorgi C., Gnemmi I., Ferrarotti I., Vallese D., Paracchini E., et al. (2019). Bacterial load and inflammatory response in sputum of alpha-1 antitrypsin deficiency patients with COPD. INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE, 14, 1879-1893.
Rivista:	INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Digital Object Identifier (DOI):	http://dx.doi.org/10.2147/COPD.S207203
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, LTB4, 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 FEV1% 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. Keywords: alpha-1 antitrypsin deficiency, COPD, chronic airway inflammation, respiratory disability, sputum © 2019 Balbi et al.
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