How the Brain, Not Just Lung Function, Affects Patient-Perceived COPD Level

by U.S. Medicine

May 31, 2017

By Brenda L. Mooney

Test results are only one part of the calculation on how sick patients are with chronic obstructive pulmonary disease. Psychosocial symptoms also play a big role, so that for some veterans with dire views of their illness, systemic biomarkers of inflammation don’t necessarily bear that out.

SAN ANTONIO—As the old saying goes, you treat the patient not just the disease.

That might be especially the case with chronic obstructive pulmonary disease (COPD). A study conducted at three clinical sites, including the Texas Health Science Center at San Antonio/South Texas Veterans Health Care System and the VA Puget Sound Health Care System, sought to determine how psychological symptoms—not just physical manifestations—affected how patients viewed their illness.

The study, published in BMC Pulmonary Medicine, also included non-VA participants from the University of Washington healthcare system in Seattle.1

The Kaiser Permanente-led researchers focused on three physical symptoms—dyspnea, fatigue and pain—and two psychological symptoms—depression and anxiety—in 302 patients with moderate to severe COPD.

To do that, they used baseline data from a longitudinal observational study of depression in COPD. Also included were systemic inflammatory markers included IL1, IL8, IL10, IL12, IL13, INF, GM-CSF, TNF-α, with levels greater than the 75th percentile considered high, and C-reactive protein (CRP), with levels greater than 3 mg/L considered high.

Ultimately, the researchers settled on a four-class model for sorting the patients:

  • low physical and psychological symptoms (26%, Low-Phys/Low-Psych);
  • low physical but moderate psychological symptoms (18%, Low-Phys/Mod Psych);
  • high physical but moderate psychological symptoms (25%, High-Phys/Mod Psych), and
  • high physical and psychological symptoms (30%, High-Phys/High Psych).

While unadjusted analyses showed associations between symptom class with high levels of IL7, IL-8 and CRP, in the adjusted model, participants with a high CRP level were less likely to be in the High-Phys/Mod-Psych class compared to the Low-Phys/Low-Psych, odds ratio (OR) 0.41, and Low-Phys/Mod-Psych classes, OR 0.35. At the same time, elevated CRP was associated with in increased odds of being in the High-Phys/High-Psych compared to the High-Phys/Mod-Psych class, OR 2.22.

The researchers were surprised by some of the results, which indicated that younger age, having at least a college education, oxygen use and depression history increased the chance that patients would end up in the higher symptom classes.

“We were puzzled with the college education link and don’t have a very good explanation for it,” corresponding author Huong Q. Nguyen, PhD, of Kaiser Permanente Southern California, told U.S. Medicine. “What stands out with the higher symptom class is that patients tended to be younger and did not have worse airflow limitation compared to the other classes despite the higher physical symptoms. Many of these patients had a history of depression well before they were diagnosed with COPD. We know that the experience and report of physical symptoms is shaped by a multitude of factors beyond biological processes, including psychosocial-environmental influences.”

Noting that the four distinct symptom classes are based on five commonly co-occurring physical and psychological symptoms, study authors emphasized that systemic biomarkers of inflammation were not associated with symptom class.

“Patients may present with different symptom clusters that potentially warrant different approaches to therapy,” Nguyen noted. “The symptom classes we found in our study need to be replicated in other larger samples that have a balanced gender representation. If these classes are confirmed, further work is then needed to test therapies tailored to the classes to determine if indeed the classifying patients into symptom classes has any clinical utility. It appears that patients in the high symptom class may need concurrent medical and behavioral management to address their high physical and psychological symptoms.”

The COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE) study followed patients for two years to pinpoint the biological causes and functional consequences of depression. As a follow-up, this report is a cross-sectional descriptive analysis of data from 302 patients collected at entry to CASCADE.

Participants were recruited from queries of medical records and pulmonary function tests, chest clinics from the three medical centers, a research database maintained by the investigators, pulmonary rehabilitation programs, “better breather” groups, community pulmonary practices, advertisements, study website and other referrals.

To be included, patients had to meet the following criteria:

  • Clinical diagnosis of COPD;
  • Post-bronchodilator forced expiratory volume in one second to forced vital capacity ratio (FEV1/FVC) < 70%;
  • Moderate to very severe disease with an FEV1 < 80%;
  • Age younger than 40 years;
  • Current or past cigarette smoking (>10 pack-years);
  • Stable disease with no acute exacerbations of COPD in the past 4 weeks; and
  • Ability to speak, read and write English.

Pattern of COPD symptom classes based on normalized symptom scores. *Z-scores on Y-axis; higher z-scores indicate worse symptoms. Class 1 (diamond): Low physical and low psychological symptom burden (Low-Phys/Low-Psych); 26%. Class 2 (square): Low physical and moderate psychological symptom burden (Low-Phys/Mod-Psych); 18%. Class 3 (triangle): High physical and moderate psychological symptom burden (High-Phys/Mod-Psych); 25%. Class 4 (circle): High physical and high psychological symptom burden (High- Phys/High-Psych); 30% Source: Symptom profiles and inflammatory markers in moderate to severe COPD. BMC Pulm Med. 2016 Dec 3;16(1):173

The study found patients in the higher symptom classes were more likely to be younger, female and have lower income. For those in the higher symptom class, the six-minute walk test distance was lower and oxygen use was more common. No difference was detected, however in FEV1 % predicted, BMI or number of comorbidities across the four symptom classes.

Effect of Early Depression

Other factors appeared to come into play, according to the report. For example, patients who had their first depression episode before age 40 were more likely to be in the highest symptom class.

In terms of inflammatory markers, meanwhile, 18-36% of patients had cytokine levels greater than the 75th percentile across symptom classes and, for CRP, a higher percentage (31-60%) had levels greater than 3mg/L. Only CRP was different across groups, followed marginally by IL-7 or IL-8, study authors pointed out.

“Only CRP was significantly associated with symptom class, where patients with a high CRP level were less likely to be in the High-Phys/Mod-Psych class compared to both the Low-Phys/Low-Psych (OR: 0.41, 95% CI 0.19, 0.90) and Low-Phys/Mod-Psych classes (OR: 0.35, 95% CI 0.16, 0.78),” study authors wrote. “Interestingly, elevated CRP was associated with increased odds of being in the High-Phys/High-Psych symptom class compared to the High-Phys/Mod-Psych class (OR: 2.22, 95% CI 1.08, 4.58).”

The articles described how socio-demographic and disease severity characteristics were associated with symptom class. Age was among those, with older age generally associated with a lower risk of being in the higher symptom classes compared to younger age, OR 0.87 to 0.94. Other specific findings include:

  • Having a college education was associated with a two- to fourfold odds of being in a higher symptom class compared to those with lower symptom levels (OR: 2.71 to 4.33).
  • Oxygen use was associated with higher odds of membership in the High-Phys/High-Psych compared to both the Low-Phys/Low-Psych (OR: 3.18, 95%CI 1.21, 8.36) and the Low-Phys/Mod-Psych (OR: 3.41, 95% CI 1.29, 9.01) symptom classes.
  • Patients with a depression history had two to six times the odds of being in the High-Phys/Mod-Psych or High-Phys/High-Psych symptom classes compared to being in the Low-Phys/Low-Psych or Low-Phys/Mod-Psych classes (OR: 2.66 to 6.55).
  • Gender, living situation, smoking status, six-minute walk test performance, FEV1% predicted, BMI or number of comorbidities did not differ much across the four symptom classes.

“Systemic inflammation as measured by 14 serum biomarkers did not appear to have any consistent relationship with these empirically identified symptom classes with the exception of CRP,” researchers pointed out.

“The observation of a distinct class of patients who have high physical but only moderate levels of psychological symptoms challenge the common notion that physical and psychological symptoms are tightly coupled in patients with COPD,” they added. “Confirmation of such a symptom cluster in other COPD cohorts is needed.”

“Patients may present with different symptom clusters that potentially warrant different approaches to therapy” Nguyen suggested. “The symptom classes we found in our study need to be replicated in other larger samples that have a balanced gender representation. If these classes are confirmed, further work is then needed to test therapies tailored to the classes to determine if indeed the classifying patients into symptom classes has any clinical utility. It appears that patients in the high symptom class may need concurrent medical and behavioral management to address their high physical and psychological symptoms.”

Study authors pointed to a subgroup of “young COPD patients with a long-standing depression history who need more intensive and integrative management of both their mental and physical health.”

Those findings are likely to take on greater significance in the future. A study last year found that the rate of COPD increased from 0.31% to 0.55% among the more than 760,000 veterans who served in Iraq or Afghanistan and received VA health care from 2003 and 2011.

Authors of the report, which appeared in Military Medicine, said the findings “may suggest a link between deployment exposures and increased diagnoses of chronic lung disease in [Iraq and Afghanistan Veterans].”2

  1. Nguyen HQ, Herting JR, Pike KC, Gharib SA, Matute-Bello G, Borson S, Kohen R, Adams SG, Fan VS. Symptom profiles and inflammatory markers in moderate to severe COPD. BMC Pulm Med. 2016 Dec 3;16(1):173. PubMed PMID: 27914470; PubMed Central PMCID: PMC5135800.
  2. Pugh MJ, Jaramillo CA, Leung KW, Faverio P, Fleming N, Mortensen E, Amuan ME, Wang CP, Eapen B, Restrepo M, Morris MJ. Increasing Prevalence of Chronic Lung Disease in Veterans of the Wars in Iraq and Afghanistan. Mil Med. 2016 May;181(5):476-81. doi: 10.7205/MILMED-D-15-00035. PubMed PMID: 27136656.

 


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