Two oxidative stress biomarkers were linked to high vs. low perceived stress.

Former smokers with COPD reporting higher perceived stress had poorer scores on respiratory health assessments, according to results published in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation.

"These findings show that perceived stress that often results from psychosocial stressors plays a role in the manifestation of disease," Obiageli Offor, MD, MPH, pulmonary and critical care fellow at Johns Hopkins University, told Healio.

"Our findings are a reminder that as clinicians, we should inquire about our patients' psychosocial health as it impacts disease pathogenesis in ways that we are still working to fully understand," Offor said.

In this study, Offor and colleagues analyzed 99 adults (mean age, 66.4 years; 55.6% women; 57% Black) with COPD, former smoker status and low-income area residence from the Comparing Urban and Rural Effects of Poverty on COPD (CURE COPD) study to determine if perceived stress, measured via the Perceived Stress Scale (PSS) at baseline, 3 months and 6 months, is linked to respiratory symptoms and elevated odds for exacerbations.

Researchers also collected several biomarkers -- urine 11-dehydro-thromboxane B2 (11dTxB2) for platelet activation; urine thiobarbituric acid reactive substances (TBARS), 8-hydreoxyguanosine and 8-isoprostane for oxidative stress; and inflammation -- to examine whether any are linked to perceived stress.

Using baseline measurements, 52 patients had low perceived stress (PSS 0-13), 45 patients had moderate perceived stress (PSS 14-26) and two patients had high perceived stress (PSS 27-40). At baseline, 3 months and 6 months, researchers reported a median PSS score of 13 in the total cohort.

Those with moderate vs. low perceived stress had differences in several measures of respiratory symptoms that signaled poorer outcomes, according to the study:

Based on the above mean differences, only the CAT met/passed the minimum clinically important difference (MCID) of two. Notably, the study highlighted that there is no MCID definition for ECSC.

The difference in each of these scores was even greater when researchers assessed high vs. low perceived stress:

For all measures except ECSC, the mean difference went over the MCID defined for each test/questionnaire, according to the study.

When divided based on COPD severity (mild-moderate and severe), researchers reported links between moderate perceived stress and heightened scores on the SGRQ, CAT, ECSC and CCQ in patients with severe COPD. Similarly, increased scores for each of the above tests/questionnaires were linked to high perceived stress in the severe COPD group.

In contrast, only high perceived stress was linked to heightened scores in patients with mild-moderate COPD, and this was found for the SGRQ, CAT and CCQ, according to the study.

"We found that perceived stress is related to worse respiratory outcomes, especially in individuals with more severe COPD," Offor told Healio. "This finding was independent of other psychosocial factors such as symptoms of depression or anxiety, supporting our initial hypothesis for this study, which highlights that perceived stress has a significant impact in COPD."

Researchers further found that the likelihood for a moderate/severe COPD exacerbation over 12 months was heightened with high vs. low perceived stress (OR = 4.15; 95% CI, 1.28-13.47).

In terms of biomarkers, there was a link between high perceived stress and two of the studied oxidative stress biomarkers vs. low perceived stress. These were lower TBARS (beta = -25.5%; 95% CI, -43.8% to -1.2%) and higher 8-isoprostane (beta = 40.1%; 95% CI, 11.5%-76%), according to the study.

Breaking down the study population by COPD severity revealed a link between moderate perceived stress and increased 11dTxB2 in patients with mild-moderate COPD (beta = 20.1%; 95% CI, 3.1%-40%).

Researchers additionally observed a link between high perceived stress and this biomarker (beta = 52.9%; 95% CI, 22.1%-91.6%) in the same COPD severity group, which was also found to have a link between high stress and increased 8-isoprostane (beta = 59.4%; 95% CI, 20.6%-110.8%).

"It was notable that in COPD, unlike in other chronic diseases, there were no significant relationships between perceived stress and common blood markers of inflammation," Offor told Healio. "Instead, we found that other more specific biologic mechanisms -- platelet activation and oxidative stress -- may be more relevant in COPD."

"Further studies that look at specific psychosocial factors that contribute to perceived stress but can be directly intervened on, such as social isolation, cost of medications and neighborhood-level factors, will enrich our understanding of this important topic," Offor said. "Studies that evaluate other biologic mechanisms that are potential therapeutic targets, such as the neuroendocrine stress response, will expand our understanding of the impact of psychosocial factors on disease biology."