Sputum sample positivity for Haemophilus influenzae or Moraxella catarrhalis in acute exacerbations of chronic obstructive pulmonary disease: evaluation of association with positivity at earlier stable disease timepoints

Abstract

Background: Infection with Haemophilus influenzae (Hi) or Moraxella catarrhalis (Mcat) is a risk factor for exacerbation in chronic obstructive pulmonary disease (COPD). The ability to predict Hi- or Mcat-associated exacerbations may be useful for interventions developed to reduce exacerbation frequency.

Methods: In a COPD observational study, sputum samples were collected at monthly stable-state visits and at exacerbation during two years of follow-up. Bacterial species (Hi, Mcat) were identified by culture and quantitative PCR assay. Post-hoc analyses were conducted to assess: (1) first Hi- or Mcat-positive exacerbations given presence or absence of Hi or Mcat at the screening visit (stable-state timepoint); (2) first Hi- or Mcat-positive exacerbations given presence or absence of Hi or Mcat at stable timepoints within previous 90 days; (3) second Hi- or Mcat-positive exacerbations given presence or absence of Hi or Mcat at stable timepoints within previous 90 days. Percentages and risk ratios (RRs) with 95% confidence intervals were calculated.

Results: PCR results for analyses 1, 2 and 3 (samples from 84, 88 and 83 subjects, respectively) showed that the risk of an Hi- or Mcat-positive exacerbation is significantly higher if sputum sample was Hi- or Mcat-positive than if Hi- or Mcat-negative at previous stable timepoints (apart from Mcat in analysis 3); RRs ranged from 2.1 to 3.2 for Hi and 1.9 to 2.6 for Mcat.For all analyses, the percentage of Hi- or Mcat-positive exacerbations given previous Hi- or Mcat-positive stable timepoints was higher than the percentage of Hi- or Mcat-positive exacerbations if Hi- or Mcat-negative at previous stable timepoints. Percentage of Hi- or Mcat-positive exacerbations given previous Hi- or Mcat-negative stable timepoints was 26.3%-37.0% for Hi and 17.6%-19.7% for Mcat.

Conclusions: Presence of Hi or Mcat at a stable timepoint was associated with a higher risk of a subsequent Hi- or Mcat-associated exacerbation compared with earlier absence. However, a large percentage of Hi- or Mcat-associated exacerbations was not associated with Hi/Mcat detection at an earlier timepoint. This suggests that administration of an intervention to reduce these exacerbations should be independent of bacterial presence at baseline. Trial Registration https://clinicaltrials.gov/ ; NCT01360398, registered May 25, 2011.

Keywords: Bacterial identification; COPD; Culture; Exacerbation; Haemophilus influenzae; Moraxella catarrhalis; PCR; Vaccination.

Fig. 1

Plain language summary

Fig. 2

Positivity of first or second exacerbation by bacterial presence or absence at reference timepoint. Shown as percentage (95% CI) of samples that were positive for Haemophilus influenzae or Moraxella catarrhalis at first or second exacerbation given pathogen’s presence or absence at a the screening visit, b any stable visit within 90 days before the first exacerbation, or c any stable visit within 90 days before the second exacerbation (Full cohort, Year 1 and Year 2). 95% CI, 95% confidence interval; Culture +/− , H. influenzae- or M. catarrhalis-positive/negative by culture-based assay; PCR +/−, H. influenzae- or M. catarrhalis-positive/negative by PCR assay; p-value, p-value for difference between percentages, calculated by equality test between two independent proportions. Numbers in square brackets indicate the number of sputum samples positive at exacerbation/number positive or negative at reference timepoint

Fig. 3

Risk ratio values for Haemophilus influenzae presence at exacerbation. Shown as risk ratio for H. influenzae presence at first exacerbation, given H. influenzae presence or absence at a the screening visit or b any stable visit within 90 days before the first exacerbation. c Risk ratio for H. influenzae presence at second exacerbation given H. influenzae presence or absence at any stable visit within 90 days before the second exacerbation (Full cohort, Year 1 and Year 2). a p-value < 0.001 for culture and PCR; b p-value < 0.0001 for culture and PCR; c p-value < 0.001 for PCR. Other p-values not statistically significant. 95% CI, 95% confidence interval

Fig. 4

Risk ratio values for Moraxella catarrhalis presence at exacerbation. Shown as risk ratio for M. catarrhalis presence at first exacerbation, given M. catarrhalis presence or absence at a the screening visit or b any stable visit within 90 days before the first exacerbation. c Risk ratio for M. catarrhalis presence at second exacerbation, given M. catarrhalis presence or absence at any stable visit within 90 days before the second exacerbation (Full cohort, Year 1 and Year 2). a p-value = 0.03 for PCR; b p-value < 0.01 for PCR; c p-value = 0.03 for culture. Other p-values not statistically significant. 95% CI, 95% confidence interval