Table 1.
Summary of Key Studies Investigating AECOPD Microbiology.
| Finding | Main Result(s) | Citation |
|---|---|---|
| NTHi proliferations cause AECOPD leading to hospitalisation. | NTHi was detected in the sputum of 70% patients in a large cohort study of 105 moderate (45%) and severe (40%) COPD patients (GOLD stage 2 - 3). During AECOPD, culture and PCR analysis revealed NTHi populations significantly proliferate compared to baseline. | (Wilkinson et al., 2017) |
| Streptococcus spp. and M. catarrhalis contribute to AECOPD. | Culture and PCR analysis of sputum revealed Streptococcus pneumoniae remained a dominant lung taxon during AECOPD (but proportions did decrease). M. catarrhalis proliferated during AECOPD. | (Wilkinson et al., 2017) |
| Viral interactions contribute to AECOPD and drive NTHi proliferation. | PCR showed increased co-infection of NTHi and HRV between exacerbation-state (29.2%) and stable state (9.1%) patients, with 46.5% patients having at least one HRV-positive exacerbation. | (Wilkinson et al., 2017) |
| Inoculation of 14 mild COPD (GOLD stage 2) patients with human rhinovirus (HRV) resulted in a 21% Haemophilus spp. proliferation driving a persistent infection. NTHi was detected in sputum by 16S rRNA pyrosequencing using the V3-V5 16S hypervariable regions. | (Molyneaux et al., 2013) | |
| NTHi proliferation is associated with AECOPD severity. | Microbiome analysis of 584 sputum samples from a cohort of 101 COPD patients with moderate (44.6%), severe (39.6) to very severe (15.8%) COPD (GOLD stage 2 – 4) showed that there was a significant increase in NTHi in patients with very severe COPD compared to moderate COPD. Microbiome sequencing was conducted using 16S rRNA Illumina sequencing, V4 hypervariable region. |
(Mayhew et al., 2018) |
| Overall, there were significant microbiome shifts during AECOPD over one year, across moderate, severe and very severe COPD patients, between stable and exacerbation states. NTHi proliferation was associated with exacerbation events. | (Mayhew et al., 2018) | |
| Pseudomonas aeruginosa causes AECOPD and prolongs hospitalisation. | Sputum culture and PCR analysis identified NTHi as most common bacteria (~24%) across 92 hospitalised AECOPD patients with mild (4.3%), moderate (19.5%), severe (10.8%) and very severe (65.2%) COPD (GOLD stage 1 – 4). However, NTHi was not significantly associated with hospitalisation duration. | (Nakou et al., 2014) |
| P. aeruginosa was detected by culture as the second most common species across 92 patients hospitalised (~14%) and was significantly associated with increased hospitalisation duration. | (Nakou et al., 2014) | |
| NTHi infections do not contribute to the COPD lung microbiome. | NTHi was not detected as part of the core microbiome in a small cohort of stable-state COPD patients. The microbiome was assessed using a terminal restriction fragment (TRF) length polymorphism and clone library analysis technique on bronchoalveolar lavage (BAL) samples from 9 stable state COPD patients with moderate (6/9) or severe (3/9) COPD (GOLD stage 2 - 3) compared to 9 healthy controls. | (Zakharkina et al., 2013) |
| NTHi infections do not contribute to AECOPD. | Haemophilus spp. were not identified as clinically important genera during AECOPD (0.7%). Pseudomonas spp. were also not clinically important (1.8%). In this study the sputum microbiota from a cohort of 9 patients with mild (1/9), moderate (3/9), and severe (5/9) COPD (GOLD stage 1 – 3) was analysed using 16S rRNA pyrosequencing and qPCR techniques. | (Jubinville et al., 2018) |
| Moraxella spp. and Streptococcus spp. contribute to severe AECOPD. | During exacerbation episodes, sputum samples from the 5 severe COPD patients (GOLD stage 3) showed increases of M. spp. and S. spp. in 90% and 88% patients, respectively. | (Jubinville et al., 2018) |
| AECOPD is associated with sputum microbiome shifts in Proteobacteria, Firmicutes or Bacteroidetes. | Between stable- and exacerbation-states, alpha-diversity analysis showed shifts in the proportion of Proteobacteria, Firmicutes and Bacteroidetes phyla. However, this dysbiosis was heterogeneous across patients. | (Jubinville et al., 2018) |
| M. catarrhalis infection is responsible for a subset of AECOPD but infection is cleared following immune response. | M. catarrhalis is estimated to cause 10% AECOPD. M. catarrhalis was detected by sputum culture in a prospective cohort study involving 104 COPD patients with 3009 clinic visits over 81 months. 560 visits occurred during exacerbation episodes and 2449 visits occurred during clinically stable periods. M. catarrhalis was detected in the sputum of 50 patients with 47.5% presenting with AECOPD. Immunoassays showed that patients cleared M. catarrhalis infections efficiently and molecular typing techniques showed that reacquisition of the same strain was rare, demonstrating development of strain-specific protection. | (Murphy et al., 2005) |
| Interspecific co-colonisation interactions exist in COPD patients. | A prospective cohort study involving monthly sputum cultures from 181 COPD patients exhibiting chronic bronchitis with 8843 clinic visits over 4.5 years revealed NTHi was the most common bacteria isolated (14.4%) and colonisation was positively correlated with S. pneumoniae. Co-colonisation correlation was consistent between stable-state and exacerbation states. | (Jacobs et al., 2018) |
| Lung tissue microbiota shifts in very severe COPD patients compared to smoker and non-smoker controls. | There is a reduction in diversity in severe COPD patients which also correlates with alveolar destruction. Bacterial DNA was isolated from lung tissue from 8 very severe COPD (GOLD stage 4) patients undergoing lung transplantation. Bacterial communities were analysed using qPCR amplification of 16S rRNA hypervariable region V2 and terminal restriction fragment length polymorphism analysis and pyrotag sequencing. | (Sze et al., 2012) |
| Bronchial wash microbiota shifts in COPD patients compared to smoker and non-smoker controls. | COPD is associated with a reduction in microbial diversity compared to smoking and non-smoking healthy controls, highlighting a microbial cause for COPD. The microbiome of bronchial wash samples in 18 clinically stable COPD patients with mild to severe (GOLD 1 – 3) airflow obstruction was significantly different to 8 healthy smokers and 3 non-smoker controls, detected by culture and Illumina MiSeq sequencing. |
(Einarsson et al., 2016) |
| Lung microbiota does not shift during AECOPD and there does not account for exacerbation events. | Whilst dominant bacteria cultured from COPD patient sputum have included P. aeruginosa and H. influenzae, there were no significant microbiota changes before and after exacerbations. Overall microbial load and community composition remained stable following antibiotic treatment for AECOPD. Microbiota was analysed using anaerobic culture and 16S rDNA pyrosequencing of sputum from 40 patients with mild (17/40), moderate (17/40) or severe (6/40) COPD (GOLD stage 1 – 3). | (Tunney et al., 2013) |
| In a longitudinal study analysing the microbiome of 476 sputum samples from 87 patients with mild (1/87), moderate (35/87), severe (32/87) and very severe (19/87) COPD (GOLD stage 1 – 4) patients, Streptococcus, Haemophilus, Moraxella and Pseudomonas accounted for 41.1%, 18.9%, 5.6% and 4.4%, respectively, of the total 366 genera and showed no statistically significant differences in composition before and during exacerbation. Sputum microbiota was analysed 16S rRNA pyrosequencing using the V3-V5 hypervariable region. | (Wang et al., 2016) | |
| Dominant COPD lung microbiota are shared with healthy lung microbiota. | PCR amplification and 16S rRNA pyrosequencing of stable state sputum, bronchial aspirate, bronchoalveolar lavage and bronchial mucosa samples from 8 patients with moderate COPD (GOLD stage 3) showed 60% of the microbiota was dominated by genera shared with the healthy lung microbiota, including Streptococcus, Prevotella, Moraxella, Haemophilus, Acinetobacter, Fusobacterium, and Neisseria . | (Cabrera-Rubio et al., 2012) |
GOLD, Global Initiative for Chronic Obstructive Lung Disease.