Background Prevalence and load of airway bacteria in stable and exacerbated chronic obstructive pulmonary disease (COPD) has been previously studied using microbiological culture. Molecular techniques, such as quantitative PCR (qPCR), may be more informative. Methods In this study, 373 sputum samples from 134 COPD outpatients were assessed for prevalence and load of typical airway bacteria (Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis) by multiplex qPCR, with 176 samples analysed for atypical bacteria. Paired stable and exacerbation typical bacteria data were compared in 52 patients. We compared routine culture with qPCR in 177/373 samples. Results Typical bacteria were more prevalent in exacerbation than stable-state paired samples: 30/52 (57.7%) vs. 14/52 (26.9%); p¼0.001. In patients who were bacteria-positive at both time points, mean (61 SEM) load was significantly higher at exacerbation than stable state ( vs. cfu/ml), constituting a 20-fold increase (p¼0.011). qPCR was more discriminatory at detecting typical bacteria than microbiological culture (prevalence 59.3% vs. 24.3%; p<0.001). At stable state, higher airway bacterial load correlated with more severe airflow limitation (FEV 1 % predicted) (r¼À0.299; p¼0.033) and higher inhaled corticosteroid dosage (r¼0.382; p¼0.008). Mean C-reactive protein was higher in bacterial-associated exacerbations (35.0 Vs 25.1 mg/L; p¼0.032). Conclusions Airway bacterial prevalence and load increase at COPD exacerbations and are an aetiological factor. qPCR is more discriminatory than culture, identifying higher airway bacterial prevalence. Exacerbations associated with bacterial detection showed a higher mean C-reactive protein level. In the stable state, airway bacterial load is related to more severe airflow limitation and higher inhaled corticosteroid dosage used.

The CAT provides a reliable score of exacerbation severity. Baseline CAT scores are elevated in frequent exacerbators. CAT scores increase at exacerbation and reflect severity as determined by lung function and exacerbation duration.

Frequent COPD exacerbators have greater arterial stiffness than infrequent exacerbators. Arterial stiffness rises acutely during COPD exacerbations, particularly with airway infection. Increases in arterial stiffness are related to inflammation, and are slow to recover. Myocardial injury is common and clinically significant during COPD exacerbations, particularly in those with underlying ischemic heart disease.

Human rhinovirus (HRV) infection is an important trigger of exacerbations of chronic obstructive pulmonary disease (COPD) but its role in determining exacerbation frequency phenotype or the time-course of HRV infection in naturally occurring exacerbations is unknown.Sputum samples from 77 patients were analysed by real-time quantitative PCR for both HRV (388 samples), and Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis (89 samples). Patients recorded worsening of respiratory symptoms on daily diary cards, from which exacerbations were identified.HRV prevalence and load at exacerbation presentation were significantly higher than in the stable state (prevalence 53.3% versus 17.2%, respectively; p,0.001) but 0% by day 35 post-exacerbation. HRV load was higher in patients with cold symptoms (p50.046) or sore throats (p50.006) than those without. 73% of bacterium-negative but HRV-positive exacerbations were bacterium-positive by day 14. Patients with HRV detected at exacerbation had a higher exacerbation frequency (interquartile range) of 3.01 (2.02-5.30) per year compared with patients without HRV (2.51 (2.00-3.51)) (p50.038).HRV prevalence and load increased at COPD exacerbation, and resolved during recovery. Frequent exacerbators were more likely to experience HRV infection. Secondary bacterial infection is common after HRV infection, and provides a possible mechanism for exacerbation recurrence and a potential target for novel therapies. @ERSpublications Increased HRV prevalence and load are aetiological factors in natural COPD exacerbations and frequent exacerbations