Reduced human beta-defensin-2 levels associated with COPD exacerbations

14th April 2023

Lowered levels of human beta-defensin-2 levels have been linked to exacerbations in patients with chronic obstructive pulmonary disease

Chinese researchers have identified that lower levels of human beta-defensin-2 are significantly associated with an increased risk of a disease exacerbation in patients with chronic obstructive pulmonary disease (COPD).

Human beta-defensin 2 (hBD-2) has antimicrobial activity and is elevated in distal airways of COPD patients and may be involved in pathogenesis of the disease. Moreover, hBD2 has been shown to be reduced in the central airways of current smokers with COPD. Since human beta-defensin-2 levels are reduced in smokers with COPD, in the current study, researchers speculated on the association between hBD2 levels and disease exacerbations in COPD. In trying to establish the nature of the relationship between hBD2 and disease exacerbations, the researchers recruited patients with COPD and compared sputum levels with healthy controls. Levels of hBD2 were measured at baseline in the two groups and then after 12 and 24 months and compared. In a further analysis, researchers also compared human beta-defensin-2 levels among COPD patients who either had, or did not have, at least one symptom aggravation or disease exacerbation, over the next 2 years.

Human beta-defensin-2 levels and COPD exacerbations

A total of 203 COPD patients with a mean baseline age of 64.7 years (82% male) were compared to 51 controls who were younger (mean age = 59.5 years).

At baseline, there were no significant differences in the sputum and serum hBD-2 levels between COPD and control patients, although levels were actually slightly lower among COPD patients (2152.5 vs 1716.9 pg/mL, p = 0.057). However, when turning to COPD patients who had at least one symptom aggravation over the next 2 years, hBD2 levels were significantly lower in those who experienced an exacerbation (p = 0.001). Interestingly, sputum hBD-2 levels were not significantly different between COPD patients without an exacerbation and health controls (p = 0.626).

Using regression analysis, the researchers showed that low hBD-2 level (< 1000 pg/mL) was significantly associated with exacerbations and patients with such levels more likely to experience exacerbations over the next 12 months (p = 0.001).

They concluded that the risk of exacerbations in patients with COPD are more likely to occur when they had lower sputum hBD-2 levels, adding that these findings had important implications for future therapies for COPD.

Citation
Feng S et al. Low human beta-defensin-2 levels in the sputum of COPD patients are associated with the risk of exacerbations. BMC Pulm Med 2023

RAS inhibitor use reduces exacerbations and mortality in COPD

RAS inhibitor use in chronic obstructive pulmonary disease patients is linked to a reduced risk of acute exacerbations and mortality

Danish researchers have found that use of drugs affecting the renin-angiotensin-system (RAS) is associated with a lower risk of both acute exacerbations and death in patients with chronic obstructive pulmonary disease (COPD).

COPD remains a major public health problem with one analysis finding that globally in 2019, there were 212.3 million cases and which accounted for 3.3 million deaths. In addition, COPD is characterised not only by local pulmonary, but also by systemic inflammation which promotes the development of extra-pulmonary and cardiovascular co-morbidities. Although traditionally used in the management of hypertension, there is emerging evidence that RAS inhibitors such as angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) also have potential benefits in COPD patients. In fact, evidence from a retrospective analysis suggest that RAS inhibitors have dual cardiopulmonary protective properties, reducing the risk of myocardial infarction as well as COPD-related hospitalisation.

In the current study, the Danish researchers hypothesised that the use of RAS inhibitors could reduce the incidence of acute exacerbations of COPD as well as mortality in those with severe disease. Adopting a propensity-score matching approach, the team matched COPD patients prescribed a RAS drug with a similar cohort of COPD patients given bendroflumethiazide as an active comparator. The primary outcome was severe acute exacerbations of COPD within 12 months after study entry or death in the same period.

RAS inhibitor use and COPD outcomes

A total of 3029 patients with a median age of 72 years (69.1% female) and prescribed either an ACEi or ARB and propensity matched to a similar number prescribed bendroflumethiazide.

The use of either an ACEi or ARB was associated with a 14% lower risk of exacerbations or death compared to those using bendroflumethiazide (hazard ratio, HR = 0.86, 95% CI 0.78 – 0.95). This reduced risk was also evident in a sensitivity analysis of the propensity-score-matched population (HR = 0.89, 95% CI 0.83 – 0.94) and in an adjusted Cox proportional hazards model (HR = 0.93, 95% CI 0.89- 0.98).

The authors concluded that use of RAS inhibitor treatment lowered the risk of both acute exacerbations and death in those with COPD. However, they added the caveat that while there is a biologically plausible explanation for this finding, randomised controlled trials were needed to confirm this effect, given the observational nature of their study.

Citation
Vilstrup F et al. Renin-angiotensin-system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease: a nationwide registry study. BMJ Open Respir Res 2023