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

Int J Chron Obstruct Pulmon Dis. 2019 Aug 21;14:1879-1893. doi: 10.2147/COPD.S207203. eCollection 2019.

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: COPD; alpha-1 antitrypsin deficiency; chronic airway inflammation; respiratory disability; sputum.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Bacteria / genetics
  • Bacteria / isolation & purification*
  • Bacteria / pathogenicity
  • Bacterial Load
  • Case-Control Studies
  • Female
  • Host-Pathogen Interactions
  • Humans
  • Inflammation Mediators / analysis*
  • Lung / immunology*
  • Lung / microbiology*
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / etiology*
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Pulmonary Disease, Chronic Obstructive / microbiology
  • Risk Factors
  • Smoking / adverse effects*
  • Sputum / immunology
  • Sputum / microbiology
  • alpha 1-Antitrypsin Deficiency / complications*
  • alpha 1-Antitrypsin Deficiency / diagnosis
  • alpha 1-Antitrypsin Deficiency / immunology
  • alpha 1-Antitrypsin Deficiency / microbiology

Substances

  • Inflammation Mediators