Kirsten Lehmann’s research while affiliated with QIAGEN and other places

Background: Dyspnea is the impairing cardinal symptom in COPD, but the underlying brain mechanisms and their relationships to clinical patient characteristics are widely unknown. This study compared neural responses to the perception and anticipation of dyspnea between patients with stable moderate-to-severe COPD and healthy controls. Moreover, associations between COPD-specific brain activation and clinical patient characteristics were examined. Methods: During functional magnetic resonance imaging, dyspnea was induced in patients with stable moderate-to-severe COPD (n = 17) and healthy control subjects (n = 21) by resistive-loaded breathing. Blocks of severe and mild dyspnea were alternating, with each block being preceded by visually cued anticipation phases. Results: During the perception of increased dyspnea, both patients and controls showed comparable brain activation in common dyspnea-relevant sensorimotor and cortico-limbic brain regions. During the anticipation of increased dyspnea, patients showed higher activation in hippocampus and amygdala than controls which was significantly correlated with reduced exercise capacity, reduced health-related quality of life, and higher levels of dyspnea and anxiety. Conclusions: This study suggests that patients with stable moderate-to-severe COPD show higher activation in emotion-related brain areas than healthy controls during the anticipation, but not during the actual perception of experimentally induced dyspnea. These brain activations were related to important clinical characteristics and might contribute to an unfavorable course of the disease via maladaptive psychological and behavioral mechanisms.

Patients with COPD suffer from chronic dyspnea. Previous studies on the neural mechanisms underlying dyspnea perception were investigated in healthy volunteers only. We tested whether COPD patients compared to healthy controls show different neural responses while anticipating and perceiving dyspnea, and whether neural responses correlate with disease-specific characteristics. Using functional magnetic resonance imaging, 17 stable outpatients with moderate-to-severe COPD were compared with 21 matched controls. Conditions of baseline and inspiratory resistive load-induced dyspnea were repeatedly presented for 24s in alternating order. Each trial was preceded by a 6s anticipation phase, being signalled by specific cues . After each trial subjects provided Borg ratings of perceived dyspnea unpleasantness and intensity. Patients and controls showed comparable ratings of dyspnea unpleasantness and intensity. During dyspnea perception, patients and controls showed comparable activations in sensorimotor and limbic brain regions with known relevance for dyspnea perception. For dyspnea anticipation, patients showed greater neural activation in fear-related brain areas, such as hippocampus and amygdala, when compared to controls. In patients, disease duration and symptom level were positively correlated with neural activity in the amygdala, anterior cingulate, and prefrontal cortex. The present findings suggest that chronic exposure to dyspnea in COPD patients affects mainly neural responses during the anticipation of dyspnea. Correlations between neural activity and disease-specific characteristics might be related to the development of dyspnea-related fear/anxiety, or mirror the neural effort for emotional regulation and control.

Patients with Chronic Obstructive Pulmonary Disease (COPD) suffer from chronic dyspnea, which is commonly perceived as highly aversive and threatening. Moreover, COPD is often accompanied by disease-specific fears and avoidance of physical activity. However, little is known about structural brain changes in COPD patients and respective relations with disease duration and disease-specific fears. This study investigated structural brain changes in COPD patients and their relation with disease duration, fear of dyspnea, and fear of physical activity. We used voxel-based morphometric analysis of MRI images to measure differences in generalized cortical degeneration and regional gray matter between 30 patients with moderate-to-severe COPD and 30 matched healthy control subjects. Disease-specific fears were assessed by the COPD anxiety questionnaire. COPD patients showed no generalized cortical degeneration, but decreased gray matter in posterior cingulate cortex (whole brain analysis) as well as in anterior and mid cingulate cortex, hippocampus, and amygdala (regions-of-interest analyses). Patients' reductions in gray matter in anterior cingulate cortex were negatively correlated with disease duration, fear of dyspnea, and fear of physical activity. Mediation analysis revealed that the relation between disease duration and reduced gray matter of the anterior cingulate was mediated by fear of physical activity. COPD patients demonstrated gray matter decreases in brain areas relevant for the processing of dyspnea, fear, and antinociception. These structural brain changes were partly related to longer disease duration and greater disease-specific fears, which might contribute to a less favorable course of the disease.

  Comorbid anxiety is highly prevalent in Chronic Obstructive Pulmonary Disease (COPD), and it is related to increased morbidity and mortality. It has consistently been found that social comparison has substantial impact on mood. However, despite the strong social component of pulmonary rehabilitation, the effect of social comparison processes on anxiety has not been explored in this context.   Participants were 43 COPD patients enrolled in a 3-week pulmonary rehabilitation programme. We tested in a longitudinal design the relationship between social comparison and assimilation and contrast at the beginning of rehabilitation and anxious mood at the end of the programme.   Using moderator analysis, we tested whether perceived similarities and differences to upward and downward social comparison standards influence the relationship between comparison direction at the beginning of the programme and anxious mood at the end of the programme.   The relationship between social comparison at the start of rehabilitation and anxious mood at the end of the programme was dependent on assimilation and contrast to upward and downward standards. Downward assimilation and upward contrast were related to a stronger relationship of upward and downward social comparison and anxious mood.   This study demonstrates the important role of social comparison focus in moderating beneficial effects of pulmonary rehabilitation. Downward assimilation and upward contrast might be important targets in reducing anxiety in pulmonary rehabilitation.

Anxiety and depression are prevalent comorbidities in COPD and are related to a worse course of disease. The present study examined the impact of anxiety and depression on functional performance, dyspnea, and quality of life (QoL) in patients with COPD at the start and end of an outpatient pulmonary rehabilitation (PR) program. Before and after PR, 238 patients with COPD (mean FEV(1) % predicted = 54, mean age = 62 years) underwent a 6-min walking test (6MWT). In addition, anxiety, depression, QoL, and dyspnea at rest, after the 6MWT, and during activities were measured. Except for dyspnea at rest, improvements were observed in all outcome measures after PR. Multiple regression analyses showed that before and after PR, anxiety and depression were significantly associated with greater dyspnea after the 6MWT and during activities and with reduced QoL, even after controlling for the effects of age, sex, lung function, and smoking status. Moreover, before and after PR, anxiety was related to greater dyspnea at rest, whereas depression was significantly associated with reduced functional performance in the 6MWT. This study demonstrates that anxiety and depression are significantly associated with increased dyspnea and reduced functional performance and QoL in patients with COPD. These negative associations remain stable over the course of PR, even when improvements in these outcomes are achieved during PR. The results underline the clinical importance of detecting and treating anxiety and depression in patients with COPD.