Social Contagion of Vasovagal Symptoms in Blood Donors: Interactions With Empathy.

BACKGROUND: Vasovagal reactions (VVRs) are commonly experienced in medical situations such as blood donation. Many believe that psychosocial contagion can contribute to the development of VVRs, but this is largely clinical lore. PURPOSE: The goal of the present investigation was to examine the physiological effects of observing another experience a reaction, focusing on the potential moderating effects of empathy. METHODS: This study was part of a randomized controlled trial of behavioral techniques on the prevention of VVRs in blood donors. The sample was composed of 530 healthy university students. Measures of symptoms were obtained with the Blood Donation Reactions Inventory (BDRI) and through observation. Physiological variables were measured using respiratory capnometry and a digital blood pressure monitor. The Affective and Cognitive Measure of Empathy was administered to 230 participants. RESULTS: Donors who witnessed another experiencing a reaction were more likely to spontaneously report symptoms during the blood draw, to be treated for a reaction, to score higher on the BDRI, and to exhibit smaller compensatory heart rate increases. Donors with higher affective empathy reported more symptoms, exhibited hyperventilation, and were more likely to be treated. Donors with higher cognitive empathy were less likely to require treatment if they witnessed a reaction. CONCLUSION: These results suggest that psychosocial contagion of physical symptoms can occur. The moderating effects of empathy differed depending on the subtype of empathy. Perhaps a better cognitive understanding of how other people are feeling functions as a coping response, whereas feeling sympathetic about others' distress increases one's own.

YAP-induced Ccl2 expression is associated with a switch in hepatic macrophage identity and vascular remodelling in liver cancer.

BACKGROUND & AIM: The development of hepatocellular carcinoma (HCC) is associated with the formation of communication networks leading to the recruitment of disease-modifying macrophages. However, how oncogenes in tumour cells control paracrine communication is not fully understood. METHODS: Transgenic mice with liver-specific expression of the constitutively active yes-associated protein (YAPS127A ) or an orthotopic implantation model served as tumour models. FACS-sorted F4/80+ /CD11bdim /CD146- /retinoid- macrophages from healthy and tumour-bearing livers were used for transcriptomic profiling. Expression data of 242 human HCCs and a tissue microarray consisting of 91 HCCs and seven liver tissues were analyzed. RESULTS: Screening of primary tumour cells expressing YAPS127A identified CC chemokine ligand 2 (Ccl2) as a macrophage chemoattractant, whose expression was regulated in a YAP/TEA domain family member 4 (TEAD4)-dependent manner. Ccl2 expression was associated with a loss of Kupffer cells (KCs) and an increase in immature macrophages (Mɸimm ) in hepatocarcinogenesis. Recruited Mɸimm were characterized by a lack of functional polarization (M0 signature) and high expression of the Ccl2 receptors C-C motif chemokine receptor 2 (Ccr2), C-X3-C motif chemokine receptor 1 (Cx3cr1) and pro-angiogenic platelet-derived growth factors (Pdgfa/Pdgfb). Mɸimm formed cellular clusters in the perivascular space, which correlated with vascular morphometric changes indicative for angiogenesis. In human HCCs, the M0 signature served as an identifier for poor clinical outcome and CCL2 correlated with YAP expression and vascular network formation. CONCLUSIONS: In conclusion, YAP/TEAD4-regulated Ccl2 associates with perivascular recruitment of unpolarized Mɸimm and may contribute to a proangiogenic microenvironment in liver cancer.

68Ga-FAPI-PET/CT improves diagnostic staging and radiotherapy planning of adenoid cystic carcinomas - Imaging analysis and histological validation.

BACKGROUND: Adenoid cystic carcinomas (ACCs) are rare epithelial tumors mostly situated in the head and neck region and characterized by infiltrative growth. The tumor stroma of ACCs includes cancer-associated fibroblasts (CAFs) expressing Fibroblast Activation Protein (FAP), a new target for positron emission tomography (PET) imaging. Here we describe the value of PET/ computed tomography (PET/CT) imaging using 68Ga-labelled FAP-Inhibitors (68Ga-FAPI-PET/CT) and their clinical potential for staging and radiotherapy planning in 12 ACC patients (7 primary, 5 recurrent). PATIENTS AND METHODS: Patients underwent contrast enhanced staging CT (ceCT) and magnetic resonance imaging (ceMRI) before 68Ga-FAPI - PET/CT. PET-scans were acquired 10, 60 and 180 minutes after administration of 150-250 MBq of 68Ga-labelled FAPI tracers. SUVmax and SUVmean values of ACCs and healthy organs were obtained using a 60% of maximum iso-contour. FAP and alpha smooth muscle actin (α-SMA) immunohistochemistry was performed in 13 cases (3 with and 10 without 68Ga FAPI-PET/CT). Staging and radiotherapy planning based on 68Ga-FAPI-PET/CT versus ceCT/MRI alone were compared. RESULTS: We observed elevated tracer uptake in all ACCs. Immunohistochemistry showed FAP-expressing CAFs in the tumor. Compared to conventional staging, 68Ga-FAPI-PET/CT led to upstaging in 2/12 patients and to detection of additional metastases in 3 patients, thus in total 42% of patients had their staging altered. Moreover, 68Ga-FAPI PET improved the accuracy of target volume delineation for radiotherapy, as compared to CT and MRI. CONCLUSION: 68Ga-FAPI-PET/CT is a promising imaging modality for ACC, increasing the accuracy of staging exams and radiotherapy planning volumes, as compared conventional to CT and MRI.

Gut Microbiome Directs Hepatocytes to Recruit MDSCs and Promote Cholangiocarcinoma.

Gut dysbiosis is commonly observed in patients with cirrhosis and chronic gastrointestinal disorders; however, its effect on antitumor immunity in the liver is largely unknown. Here we studied how the gut microbiome affects antitumor immunity in cholangiocarcinoma. Primary sclerosing cholangitis (PSC) or colitis, two known risk factors for cholangiocarcinoma which promote tumor development in mice, caused an accumulation of CXCR2+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). A decrease in gut barrier function observed in mice with PSC and colitis allowed gut-derived bacteria and lipopolysaccharide to appear in the liver and induced CXCL1 expression in hepatocytes through a TLR4-dependent mechanism and an accumulation of CXCR2+ PMN-MDSCs. In contrast, neomycin treatment blocked CXCL1 expression and PMN-MDSC accumulation and inhibited tumor growth even in the absence of liver disease or colitis. Our study demonstrates that the gut microbiome controls hepatocytes to form an immunosuppressive environment by increasing PMN-MDSCs to promote liver cancer. SIGNIFICANCE: MDSCs have been shown to be induced by tumors and suppress antitumor immunity. Here we show that the gut microbiome can control accumulation of MDSCs in the liver in the context of a benign liver disease or colitis.See related commentary by Chagani and Kwong, p. 1014.This article is highlighted in the In This Issue feature, p. 995.

Circulating levels of soluble urokinase plasminogen activator receptor predict outcome after resection of biliary tract cancer.

BACKGROUND & AIMS: Surgical resection is the only potentially curative therapy for patients with biliary tract cancer (BTC), but 5-year survival rates after tumor resection have remained below 30%, corroborating the need for better stratification tools to identify the ideal surgical candidates. The soluble urokinase plasminogen activator receptor (suPAR) represents a mediator of inflammation and has been associated with distinct types of cancer. In this study, we evaluated a potential role of suPAR as a novel biomarker in patients undergoing BTC resection. METHODS: Tumor expression of uPAR was analyzed by immunohistochemistry in 108 BTC samples. Serum levels of suPAR were analyzed by ELISA in a training and validation cohort comprising a total of 117 patients with BTC and 76 healthy controls. RESULTS: High tumoral uPAR expression was associated with an adverse outcome after BTC resection. Accordingly, circulating levels of suPAR were significantly elevated in patients with BTC compared to healthy controls, as well as in patients with primary sclerosing cholangitis. Using a small training set, we established an optimal prognostic suPAR cut-off value of 3.72 ng/ml for patients with BTC. Importantly, preoperative suPAR serum levels above this cut-off value were associated with significantly impaired overall survival in both the training and validation cohort. Multivariate Cox-regression analysis including various clinicopathological parameters such as tumor stage, markers of inflammation and organ dysfunction, as well as tumor markers, revealed circulating suPAR levels as an independent prognostic marker following BTC resection. Finally, high preoperative suPAR levels were indicative of acute kidney injury after tumor resection. CONCLUSION: Circulating suPAR represents a previously unrecognized biomarker in patients with resectable BTC, which might help to preoperatively identify the ideal candidates for liver surgery. LAY SUMMARY: Surgical resection represents the only curative treatment option for patients with biliary tract cancer, but not all patients benefit to the same extent in terms of overall survival. Here, we provide evidence that serum levels of an inflammatory mediator (suPAR) are indicative of a patient's postoperative outcome and might thus help to identify the ideal surgical candidates.

Hyperventilation as a Predictor of Blood Donation-Related Vasovagal Symptoms.

OBJECTIVE: Most of the research on vasovagal reactions has focused on the contributions of cardiovascular activity to the development of symptoms. However, other research suggests that additional mechanisms like hyperventilation may contribute to the process. The goal of the present investigation was to examine the influences of cardiovascular and respiratory variables on vasovagal symptoms. METHODS: This study was part of a randomized controlled trial investigating the effects of behavioral techniques on the prevention of vasovagal reactions in blood donors. Data from the no-treatment control group were analyzed. The final sample was composed of 160 college and university students. Observational and self-report measures of symptoms were obtained. Physiological variables were measured mainly using respiratory capnometry. RESULTS: Although respiration rate remained stable throughout donation, change in end-tidal carbon dioxide was associated with requiring treatment for a reaction during donation (odds ratio = 0.57, 95% confidence interval [CI] = 0.41 to 0.79, p = .001) and self-reported symptoms measured in the postdonation period using the Blood Donation Reactions Inventory (ß = -0.152, 95% CI = -0.28 to -0.02, t = -2.32, p = .022). Individuals with higher levels of predonation anxiety displayed larger decreases in end-tidal carbon dioxide throughout the procedure (F(2,236) = 3.64, p = .043, ηp = 0.030). Blood Donation Reactions Inventory scores were related to changes in systolic (ß = -0.022, 95% CI = -0.04 to -0.004, t = -2.39, p = .019) and diastolic blood pressure (ß = -0.038, 95% CI = -0.06 to -0.02, t = -4.03, p < .001). CONCLUSIONS: Although the vasovagal reaction has traditionally been viewed as a primarily cardiovascular event, the present results suggest that hyperventilation also plays a role in the development of vasovagal symptoms.

High baseline soluble urokinase plasminogen activator receptor (suPAR) serum levels indicate adverse outcome after resection of pancreatic adenocarcinoma.

Surgical resection represents the only potentially curative therapy for patients with pancreatic adenocarcinoma (PDAC), an aggressive malignancy with a very limited 5-year survival rate. However, even after complete tumor resection, many patients are still facing an unfavorable prognosis underlining the need for better preoperative stratification algorithms. Here, we explored the role of the secreted glycoprotein soluble urokinase plasminogen activator receptor (suPAR) as a novel circulating biomarker for patients undergoing resection of PDAC. Serum levels of suPAR were measured by enzyme-linked immunosorbent assay (ELISA) in an exploratory as well as a validation cohort comprising a total of 127 PDAC patients and 75 healthy controls. Correlating with a cytoplasmic immunohistochemical expression of uPAR in PDAC tumor cells, serum levels of suPAR were significantly elevated in PDAC patients compared to healthy controls and patient with PDAC precursor lesions. Importantly, patients with high preoperative suPAR levels above a calculated cutoff value of 5.956 ng/ml showed a significantly reduced overall survival after tumor resection. The prognostic role of suPAR was further corroborated by uni- and multivariate Cox-regression analyses including parameters of systemic inflammation, liver and kidney function as well as clinico-pathological patients' characteristics. Moreover, high baseline suPAR levels identified those patients particularly susceptible to acute kidney injury and surgical complications after surgery. In conclusion, our data suggest that circulating suPAR represents a novel prognostic marker in PDAC patients undergoing tumor resection that might be a useful addition to existing preoperative stratification algorithms for identifying patients that particularly benefit from extended tumor resection.

Respiration and applied tension strategies to reduce vasovagal reactions to blood donation: A randomized controlled trial.

BACKGROUND: Whether produced by breathing too fast or too deeply, hyperventilation is common in stressful situations and may contribute to blood donation-related vasovagal symptoms. The effects of some previously tested interventions for vasovagal symptoms, for example, applied tension (AT), may be related to reduction of hyperventilation. More targeted breathing techniques might be useful. STUDY DESIGN AND METHODS: This was a randomized controlled trial comparing the effects of AT, a slow, shallow "anti-hyperventilation" breathing technique previously tested in phobic individuals (respiration control [RESP]), the combination of AT and RESP, and no intervention on blood donors participating in university clinics. A total of 547 eligible donors were assigned randomly to one of these four groups. Observational, self-report, and physiologic measures (primarily via respiratory capnometry) were obtained. RESULTS: Although both RESP and AT had some positive impact on blood donation outcome, the effects of RESP were more numerous, albeit limited primarily to donors who had less general fear of medical procedures. For example, lower-fear donors assigned to practice RESP had significantly lower Blood Donation Reaction Inventory scores and were significantly less likely to require treatment for symptoms than no-treatment individuals. In general, RESP led to a significant decrease in respiration rate, though it did not influence end-tidal CO2 , a more precise measure of hyperventilation. CONCLUSION: While the mechanisms remain somewhat unclear and the interventions did not benefit more fearful, higher-risk donors, respiration control is a promising additional approach to reducing vasovagal symptoms.

Towards an assessment of perceived COPD exacerbation triggers: Initial development and validation of a questionnaire.

BACKGROUND AND OBJECTIVE: Prevention of exacerbations in chronic obstructive pulmonary disease (COPD) is important to decrease overall declines in functioning and improve quality of life. The present study sought to develop a psychometrically valid measure of perceived triggers of exacerbations in COPD patients, the COPD Exacerbation Trigger Inventory (CETI). METHODS: Participants (n = 192) were recruited through local clinics and online to complete surveys of the CETI, demographic information, disease-specific information and the COPD Assessment Test (CAT). The CETI included a free response section on patients' individual top triggers, combined with ratings of their controllability. RESULTS: Exploratory principal component analyses identified a stable 5-factor structure (33 items), from which trigger subscales for weather/climate, air pollution/irritants, exercise, infection/illness and psychological factors were formed (internal consistency Cronbach's α = 0.90-0.94). Trigger factors were associated with COPD functional status, exacerbation frequency and healthcare utilization. Participants found personal triggers related to dust, air pollution, smoking and physical activity to be the most easily controlled, whereas those related to psychological factors, climate, infection, respiratory symptoms and sleep to be more difficult to control. Greater perceived controllability of triggers was associated with lower CAT scores, indicating better health status and less impact of the disease on functioning. CONCLUSION: The CETI is a psychometrically valid measure of perceived exacerbation triggers in patients with COPD. Perceived triggers are associated with clinical outcomes. Assessment of trigger classes and their controllability may prove useful in both research and clinical settings with COPD patients and to further our knowledge in prevention and disease management.

The multikinase inhibitor regorafenib decreases angiogenesis and improves portal hypertension.

BACKGROUND AND AIMS: Angiogenesis is critically involved in the development of liver fibrosis, portal hypertension (PHT) and hepatocellular carcinoma (HCC). Regorafenib is a novel second-line therapy for HCC, but might also be beneficial in fibrosis and PHT even in absence of HCC. This study investigated the effects of regorafenib in experimental models without HCC. METHODS: Fibrosis (in vivo and in vitro), inflammation, liver damage (aminotransferases), angiogenesis (matrigel implantation) and in vivo systemic and portal hemodynamics were assessed in different mouse and rat models (bile duct ligation, CCl4, partial portal vein ligation) after acute and chronic treatment with regorafenib. RESULTS: Long-term treatment with regorafenib improved portal hypertension most likely due to blunted angiogenesis, without affecting fibrosis progression or regression. Interestingly, acute administration of regorafenib also ameliorated portal hemodynamics. Although regorafenib treatment led to hepatotoxic side effects in long-term treated fibrotic animals, in partial portal vein ligated rats, no liver toxicity due to regorafenib was observed. DISCUSSION: Regorafenib might be especially suitable as therapy in patients with PHT and preserved liver function.

Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells.

Primary liver tumors and liver metastasis currently represent the leading cause of cancer-related death. Commensal bacteria are important regulators of antitumor immunity, and although the liver is exposed to gut bacteria, their role in antitumor surveillance of liver tumors is poorly understood. We found that altering commensal gut bacteria in mice induced a liver-selective antitumor effect, with an increase of hepatic CXCR6+ natural killer T (NKT) cells and heightened interferon-γ production upon antigen stimulation. In vivo functional studies showed that NKT cells mediated liver-selective tumor inhibition. NKT cell accumulation was regulated by CXCL16 expression of liver sinusoidal endothelial cells, which was controlled by gut microbiome-mediated primary-to-secondary bile acid conversion. Our study suggests a link between gut bacteria-controlled bile acid metabolism and liver antitumor immunosurveillance.

Dynamic plasticity of macrophage functions in diseased liver.

Liver macrophages attract increasing interest due to their crucial roles in homeostasis and hepatic diseases. Recent findings in mice and man suggest a remarkable phenotypic and functional diversity of liver macrophages. Kupffer cells, the subset of tissue resident macrophages with sentinel functions in liver, mainly arise from embryogenic precursors, whereas in injury, liver tissue is engrafted by monocyte-derived macrophages. Both principal macrophage populations respond to local or systemic signals and have substantial effects on reduction as well as aggravation of hepatic diseases. Despite contrasting functions of heterogeneous macrophage subsets in disease progression and regression, they may provide promising targets for novel therapeutic interventions in hepatology. Areas of intense research include their multifaceted roles in metabolic diseases (non-alcoholic steatohepatitis, NASH), fibrosis or liver cancer (hepatocellular or cholangiocellular carcinoma, HCC or CCA). We discuss recent findings on the origin, diversity and functional plasticity of liver macrophages in homeostasis and hepatic disease conditions.

Exhaled nitric oxide and vascular endothelial growth factor as predictors of cold symptoms after stress.

OBJECTIVE: Prior research has demonstrated that psychosocial stress is associated with respiratory infections. Immunologic, endocrine, and cardiovascular predictors of such infections have been explored with varying success. We therefore sought to study the unexplored role of airway mucosal immunity factors, nitric oxide (NO) and vascular endothelial growth factor (VEGF). NO is secreted by airway epithelial cells as part of the first line of defense against bacteria, viruses, and fungi. VEGF is expressed by mast cells in respiratory infections and recruits immune cells to infected sites, but in excess lead to vulnerability of the airway epithelium. METHODS: In this proof-of-concept study we measured exhaled NO, exhaled breath condensate (EBC) VEGF, salivary VEGF, and salivary cortisol in 36 students undergoing final academic examinations at three occasions: a low-stress baseline during the term, an early phase of finals, and a late phase of finals. Participants also reported on cold symptoms at these time points and approximately 5 and 10days after their last academic examination. RESULTS: Higher baseline NO was associated with fewer cold symptoms after stress, whereas higher baseline VEGF in EBC and saliva were associated with more cold symptoms after stress. Perceived stress at baseline as well as salivary VEGF and cortisol late in the finals also contributed to the prediction of later cold symptoms. CONCLUSION: Basal levels of NO and VEGF may inform about mucosal immunocompetence and add to preventative treatments against airway infections from periods of stress in daily life.

Sympathetic and parasympathetic cardiac responses to phobia-relevant and disgust-specific emotion provocation in blood-injection-injury phobia with and without fainting history.

The autonomic regulation in blood-injection-injury (BII) phobia has received particular attention due to the unique link between fear and fainting in this anxiety disorder. However, systematic exploration of sympathetic and parasympathetic cardiac activity during exposure to phobia-relevant emotional stimuli has remained rare and inconclusive, including with regard to disgust, a frequent response to BII stimuli. Existing studies using respiratory sinus arrhythmia (RSA) as a noninvasive index of parasympathetic cardiac activity also have not accounted sufficiently for effects of respiration. We compared 60 participants with BII phobia (27 with and 33 without history of loss of consciousness) and 20 healthy controls during emotion induction with films, including a disgust and a BII-relevant surgery film. Cardiorespiratory activity was measured continuously, with RSA (controlled for respiration) and T-wave amplitude (TWA; as a noninvasive index of sympathetic cardiac activity) extracted. Significant increases in RSA during the surgery film were observed for participants with a history of loss of consciousness compared to others, but controlling for respiration eliminated these differences. Sympathetic effects with heart rate accelerations, which were most pronounced for the disgust film, did not differentiate groups. However, substantial increases in RSA and TWA, suggesting parasympathetic excitation and sympathetic withdrawal, were observed in five participants that became presyncopal during the surgery film. Thus, parasympathetic excitation and sympathetic withdrawal appear to be cardinal autonomic features in BII phobia, but larger studies of participants reaching presyncopal states in BII-relevant stimulus exposure are needed to consolidate these findings.

A novel biomarker associated with distress in humans: calcium-binding protein, spermatid-specific 1 (CABS1).

Calcium-binding protein spermatid-specific 1 (CABS1) is expressed in the human submandibular gland and has an anti-inflammatory motif similar to that in submandibular rat 1 in rats. Here, we investigate CABS1 in human saliva and its association with psychological and physiological distress and inflammation in humans. Volunteers participated across three studies: 1) weekly baseline measures; 2) a psychosocial speech and mental arithmetic stressor under evaluative threat; and 3) during academic exam stress. Salivary samples were analyzed for CABS1 and cortisol. Additional measures included questionnaires of perceived stress and negative affect; exhaled nitric oxide; respiration and cardiac activity; lung function; and salivary and nasal inflammatory markers. We identified a CABS1 immunoreactive band at 27 kDa in all participants and additional molecular mass forms in some participants. One week temporal stability of the 27-kDa band was satisfactory (test-retest reliability estimate = 0.62-0.86). Acute stress increased intensity of 18, 27, and 55 kDa bands; 27-kDa increases were associated with more negative affect and lower heart rate, sympathetic activity, respiration rate, and minute ventilation. In both acute and academic stress, changes in 27 kDa were positively associated with salivary cortisol. The 27-kDa band was also positively associated with VEGF and salivary leukotriene B4 levels. Participants with low molecular weight CABS1 bands showed reduced habitual stress and negative affect in response to acute stress. CABS1 is readily detected in human saliva and is associated with psychological and physiological indicators of stress. The role of CABS1 in inflammatory processes, stress, and stress resilience requires careful study.

Airway reactivity in response to repeated emotional film clip presentation in asthma.

Emotional stimuli elicit airway constriction in individuals with asthma and in healthy individuals, but little is known about effects of repeated stimulation. We therefore explored the effect of repeated emotion induction on respiratory resistance (Rrs) using unpleasant, high-arousal surgery films and investigated effects of respiration and emotional reactivity. Twenty-six participants (13 with asthma) watched a series of 12 short, 45-s surgery films followed by 2-min recovery periods. Rrs assessed with impulse oscillometry was significantly elevated during films in both groups compared to baseline and recovered quickly after that. No habituation of airway responses occurred. Rrs was higher in participants who felt more aroused and less in control when watching the films. Changes in Rrs remained significant when controlling for changes in respiration or emotional experience. Thus, although unpleasant stimuli lead to elevated Rrs, airway obstruction is not exacerbated with repeated stimulation due to a fast return to baseline after stimulation.

Effects of academic exam stress on nasal leukotriene B4 and vascular endothelial growth factor in asthma and health.

OBJECTIVE: To examine the effect of final exam stress on the concentrations of leukotriene B4 (LTB4) and vascular endothelial growth factor (VEGF) in the upper airways among healthy and asthmatic individuals. METHOD: Nasal samples were collected from 12 individuals with asthma and 23 healthy controls early and late in a final exam period, and during a low-stress period in the semester. We determined LTB4 and VEGF concentrations using Enzyme-Linked Immunoassays. RESULTS: Mixed effects analysis of variance models showed that asthmatic participants with allergies in contrast to healthy individuals experienced a decrease in nasal LTB4 during the final exam period as compared to mid-semester (low stress period). There were no significant changes in nasal VEGF across the observation period. Changes in nasal LTB4 and VEGF were not associated with salivary cortisol, exhaled nitric oxide, or spirometric lung function. CONCLUSIONS: Our results suggest that nasal LTB4 concentrations change in periods of psychological stress for asthmatic individuals with allergies.

Cardiovascular activity in blood-injection-injury phobia during exposure: evidence for diphasic response patterns?

Exposure to feared stimuli in blood-injection-injury (BII)-phobia is thought to elicit a diphasic response pattern, with an initial fight-flight-like cardiovascular activation followed by a marked deactivation and possible fainting (vasovagal syncope). However, studies have remained equivocal on the importance of such patterns. We therefore sought to determine the prevalence and clinical relevance of diphasic responses using criteria that require a true diphasic response to exceed cardiovascular activation of an emotional episode of a negative valence and to exceed deactivation of an emotionally neutral episode. Sixty BII-phobia participants and 20 healthy controls were exposed to surgery, anger and neutral films while measuring heart rate, blood pressure, respiratory pattern, and end-tidal partial pressure of carbon dioxide (as indicator of hyperventilation). Diphasic response patterns were observed in up to 20% of BII-phobia participants and 26.6% of healthy controls for individual cardiovascular parameters. BII-phobia participants with diphasic patterns across multiple parameters showed more fear of injections and blood draws, reported the strongest physical symptoms during the surgery film, and showed the strongest tendency to hyperventilate. Thus, although only a minority of individuals with BII phobia shows diphasic responses, their occurrence indicates significant distress. Respiratory training may add to the treatment of BII phobia patients that show diphasic response patterns.

Psychosocial factors and behavioral medicine interventions in asthma.

OBJECTIVE: This review examines the evidence for psychosocial influences in asthma and behavioral medicine approaches to its treatment. METHOD: We conducted a systematic review of the literature on psychosocial influences and the evidence for behavioral interventions in asthma with a focus on research in the past 10 years and clinical trials. Additional attention was directed at promising new developments in the field. RESULTS: Psychosocial factors can influence the pathogenesis and pathophysiology of asthma, either directly through autonomic, endocrine, immunological, and central nervous system mechanisms or indirectly through lifestyle factors, health behaviors, illness cognitions, and disease management, including medication adherence and trigger avoidance. The recent decade has witnessed surging interest in behavioral interventions that target the various pathways of influence. Among these, self-management training, breathing training, and exercise or physical activation programs have proved particularly useful, whereas other essential or promising interventions, such as smoking cessation, dietary programs, perception and biofeedback training, and suggestive or expressive psychotherapy, require further, more rigorous evaluation. Given the high comorbidity with anxiety and mood disorders, further evaluation of illness-specific cognitive behavior therapy is of particular importance. Progress has also been made in devising community-based and culturally tailored intervention programs. CONCLUSION: In concert with an essential medication treatment, behavioral medicine treatment of asthma is moving closer toward an integrated biopsychosocial approach to disease management.