Impact of Panic Attacks on Bronchoconstriction and Subjective Distress in Asthma Patients With and Without Panic Disorder.

OBJECTIVE: Panic disorder (PD) is common among asthma patients and is associated with worse asthma outcomes. This may occur because of psychophysiological factors or cognitive/affective factors. This study evaluated the impact of panic attacks (PAs) on bronchoconstriction and subjective distress in people who have asthma with and without PD. METHODS: A total of 25 asthma patients (15 with PD who had a PA [PD/PA], 10 without PD who did not have a PA [no PD/no PA]) were recruited from an outpatient clinic. They underwent a panic challenge (one vital capacity inhalation of 35% carbon dioxide [CO2]) and completed the Panic Symptom Scale, the Subjective Distress Visual Analogue Scale, and the Borg Scale before and after CO2. Forced expiratory volume in 1 second was assessed pre- and post-CO2; respiratory (i.e., CO2 production, minute ventilation, tidal volume) was continuously recorded, and physiological measures (i.e., systolic and diastolic blood pressure [SBP/DBP]) were recorded every 2 minutes. RESULTS: Analyses adjusting for age, sex, and provocative concentration of methacholine revealed no significant differences between groups in forced expiratory volume in 1 second change after CO2 inhalation (F(1, 23) < 0.01, p = .961). However, patients with PD/PA reported more panic (F(1, 22) = 18.10, p < .001), anxiety (F(1, 22) = 21.93, p < .001), worry (F(1, 22) = 26.31, p < .001), and dyspnea (F(1,22) = 4.68, p = .042) and exhibited higher levels of CO2 production (F(1, 2843) = 5.89, p = .015), minute ventilation (F(1, 2844) = 4.48, p = .034), and tidal volume (F(1, 2844) = 4.62, p = .032) after the CO2 challenge, compared with patients with no PD/no PA. CONCLUSIONS: Results, presented as hypothesis generating, suggest that asthma patients with PD/PA exhibit increased panic-like anxiety, breathlessness, and a respiratory pattern consistent with hyperventilation that was not linked to statistically significant drops in bronchoconstriction.

Use of prediction equations to determine the accuracy of whole-body fat and fat-free mass and appendicular skeletal muscle mass measurements from a single abdominal image using computed tomography in advanced cancer patients.

Measurements of body composition using dual-energy X-ray absorptiometry (DXA) and single abdominal images from computed tomography (CT) in advanced cancer patients (ACP) have important diagnostic and prognostic value. The question arises as to whether CT scans can serve as surrogates for DXA in terms of whole-body fat-free mass (FFM), whole-body fat mass (FM), and appendicular skeletal muscle (ASM) mass. Predictive equations to estimate body composition for ACP from CT images have been proposed (Mourtzakis et al. 2008; Appl. Physiol. Nutr. Metabol. 33(5): 997-1006); however, these equations have yet to be validated in an independent cohort of ACP. Thus, this study evaluated the accuracy of these equations in estimating FFM, FM, and ASM mass using CT images at the level of the third lumbar vertebrae and compared these values with DXA measurements. FFM, FM, and ASM mass were estimated from the prediction equations proposed by Mourtzakis and colleagues (2008) using single abdominal CT images from 43 ACP and were compared with whole-body DXA scans using Spearman correlations and Bland-Altman analyses. Despite a moderate to high correlation between the actual (DXA) and predicted (CT) values for FM (rho = 0.93; p ≤ 0.001), FFM (rho = 0.78; p ≤ 0.001), and ASM mass (rho = 0.70; p ≤ 0.001), Bland-Altman analyses revealed large range-of-agreement differences between the 2 methods (29.39 kg for FFM, 15.47 kg for FM, and 3.99 kg for ASM mass). Based on the magnitude of these differences, we concluded that prediction equations using single abdominal CT images have poor accuracy, cannot be considered as surrogates for DXA, and may have limited clinical utility.

The abridged patient-generated subjective global assessment is a useful tool for early detection and characterization of cancer cachexia.

Cancer cachexia (CC) is a syndrome characterized by wasting of lean body mass and fat, often driven by decreased food intake, hypermetabolism, and inflammation resulting in decreased lifespan and quality of life. Classification of cancer cachexia has improved, but few clinically relevant diagnostic tools exist for its early identification and characterization. The abridged Patient-Generated Subjective Global Assessment (aPG-SGA) is a modification of the original Patient-Generated Subjective Global Assessment, and consists of a four-part questionnaire that scores patients' weight history, food intake, appetite, and performance status. The purpose of this study was to determine whether the aPG-SGA is associated with both features and clinical sequelae of cancer cachexia. In this prospective cohort study, 207 advanced lung and gastrointestinal cancer patients completed the following tests: aPG-SGA, Edmonton Symptom Assessment System, handgrip strength, a complete blood count, albumin, apolipoprotein A and B, and C-reactive protein. Ninety-four participants with good performance status as assessed by the Eastern Cooperative Oncology Group Performance Status completed additional questionnaires and underwent body composition testing. Of these, 68 patients tested for quadriceps strength and completed a 3-day food recall. Multivariable regression models revealed that higher aPG-SGA scores (≥9 vs 0 to 1) are significantly associated (P<0.05) with the following: unfavorable biological markers of cancer cachexia, such as higher white blood cell counts (10.0 vs 6.7×10(9)/L; lower hemoglobin (115.6 vs 127.7 g/L), elevated C-reactive protein (42.7 vs 18.2 mg/L [406.7 vs 173.3 nmol/L]); decreased anthropometric and physical measures, such as body mass index (22.5 vs 27.1); fat mass (14.4 vs 26.0 kg), handgrip (24.7 vs 34.9 kg) and leg strength; an average 12% greater length of hospital stay; a dose reduction in chemotherapy; and increased mortality. Given its association with the main features of cancer cachexia and its ease of use, the aPG-SGA appears to be a useful tool for detecting and predicting outcomes of cancer cachexia. Additional research is required to determine what impact the aPG-SGA has on quality of care when used in the clinical setting.

Clinical impact of time of day on acute exercise response in COPD.

The purpose of this pilot study was to determine the impact of time of day on the acute response to incremental exercise in chronic obstructive pulmonary disease (COPD). Fourteen subjects (nine men) aged 71 ± 7 years with moderate to severe airflow obstruction (FEV1: 58 ± 13% predicted) followed a counterbalanced randomized design, performing three symptom-limited incremental cycling tests at 8:00, 12:00, and 16:00 hours on different days, each preceded by a spirometry. COPD medications were withdrawn prior to testing. No overall time effect was found for peak exercise capacity (p = 0.22) or pulmonary function (FEV1, p = 0.56; FVC, p = 0.79). However, a large effect size (f = 0.48) was observed for peak exercise capacity and several pulmonary function parameters. For peak exercise capacity, the average within-subject coefficient of variation was 5.5 ± 3.9% and the average amplitude of change was 7 ± 5W. Seven subjects (50%) showed diurnal changes at levels equal to or beyond the minimal clinically important difference for both peak exercise capacity and pulmonary function. In this sub-group, peak exercise capacity was greatest at 16:00 hours (p = 0.03, ƒ = 1.04). No systematic time-of-day effect on peak exercise capacity was obtained in COPD patients in the present pilot study. However, based on the observed effect size and on the average amplitude of change and within-subject variations seen across testing times, the guidelines recommendation that time of day be standardized for repeat exercise testing in COPD should be maintained.

Using continuous data tracking technology to study exercise adherence in pulmonary rehabilitation.

Pulmonary rehabilitation (PR) is an important component in the management of respiratory diseases. The effectiveness of PR is dependent upon adherence to exercise training recommendations. The study of exercise adherence is thus a key step towards the optimization of PR programs. To date, mostly indirect measures, such as rates of participation, completion, and attendance, have been used to determine adherence to PR. The purpose of the present protocol is to describe how continuous data tracking technology can be used to measure adherence to a prescribed aerobic training intensity on a second-by-second basis. In our investigations, adherence has been defined as the percent time spent within a specified target heart rate range. As such, using a combination of hardware and software, heart rate is measured, tracked, and recorded during cycling second-by-second for each participant, for each exercise session. Using statistical software, the data is subsequently extracted and analyzed. The same protocol can be applied to determine adherence to other measures of exercise intensity, such as time spent at a specified wattage, level, or speed on the cycle ergometer. Furthermore, the hardware and software is also available to measure adherence to other modes of training, such as the treadmill, elliptical, stepper, and arm ergometer. The present protocol, therefore, has a vast applicability to directly measure adherence to aerobic exercise.

Metabolic, nutritional and inflammatory characteristics in elderly women with advanced cancer.

OBJECTIVE: Few studies have focused on the metabolic profiling of patients with advanced cancer and the relationship with nutritional and inflammatory characteristics, which have important diagnostic, treatment and prognostic implications, particularly in the elderly. Our objective was to determine differences in energy expenditure during rest and activity, body composition, nutrition, and inflammatory markers between healthy elderly females and those with advanced cancer. MATERIALS AND METHODS: Twenty elderly (74.8±6.7years) females (9 with solid malignancies, 11 healthy) were evaluated for energy expenditure using indirect calorimetry at rest and throughout a 6-min walk test (6MWT). Body composition (dual-energy x-ray absorptiometry); nutritional intake (3-day 24-h food recall); and markers of nutrition and inflammation (complete blood count, albumin and C-reactive protein) were also measured. RESULTS: Compared to healthy controls, patients with cancer had similar energy expenditures, but significantly lower (p<0.05) respiratory quotients at rest. During the 6MWT, the group with cancer walked shorter distances at slower speeds (p<0.001), consumed less oxygen (p<0.05), and trended toward an increased oxygen cost while walking. The patients with cancer ingested fewer calories and presented with higher levels of inflammatory markers (p<0.05). No differences in body composition were observed. CONCLUSION: Early signs of cachexia (i.e. reduced caloric intake, inflammation and greater fat metabolism) may be present in older patients with cancer, along with poorer levels of functional capacity, compared to healthy controls. Timely recognition of these signs may allow therapeutic interventions to better prevent or delay nutritional and functional demise in elderly patients with cancer.

Is IL-6 the best pro-inflammatory biomarker of clinical outcomes of cancer cachexia?

BACKGROUND & AIMS: Despite the descriptive presence of cancer cachexia (CC) in clinical practice, the underlying mechanisms and diagnostic definition have not been clearly identified. Recent work, attempting to establish diagnostic and staging criteria for CC, has identified IL-6 as a biomarker. This study aimed to investigate the clinical relevance of plasma levels of four pro-inflammatory cytokines (IL-6, IL-1ß, IL-8 and TNF-α) in advanced cancer patients (ACP) to further establish their potential in the diagnostic definition of CC. METHODS: Blood was obtained from 83 ACP (47 male and 36 female, aged 34-85 years) and analyzed for white blood cells, lymphocytes, C-reactive protein, albumin and cytokines. Subjects completed questionnaires to establish weakness, loss of appetite, fatigue, quality of life and weight loss; completed tests to determine strength, body composition and sarcopenia; and consented to chart review to calculate survival and total days admitted to hospital. RESULTS: This study shows that, in ACP, IL-1ß is better associated with clinical features of the cachectic condition, such as weakness, loss of appetite, weight loss and sarcopenia, than IL-6. CONCLUSION: IL-6 may not best represent the clinical correlates of CC in ACP. Additional cytokines should be considered in the definition of this condition.

Male hypogonadism associated with advanced cancer: a systematic review.

Male hypogonadism is commonly diagnosed on the basis of subphysiological concentrations of androgen hormones, and is associated with many symptoms present in advanced cancer. Androgen deficiency might be an important cause of muscle wasting in both cancer cachexia and sarcopenia. We did a systematic review of the clinical association of male hypogonadism in advanced cancer. We searched PubMed, Medline, and Embase for publications on the relation between male hypogonadism and functional status, nutritional status, body composition, symptoms, and quality of life in patients with advanced cancer. Of 381 publications identified, six original articles were included. We found no definitive association between nutritional, functional, or quality-of-life characteristics and male hypogonadism. Possible associations between male hypogonadism and weight loss, low albumin, low-body cell mass index, low-peripheral fat and muscle mass, higher inflammation, higher pain, higher opioid consumption, worse scores for anxiety, depression, and emotional and functional well-being need to be confirmed by better designed studies. There is no clear epidemiological data to indicate whether male hypogonadism is independently associated with clinical and biological sequelae of cancer cachexia, such as higher inflammation, fatigue, and body wasting. Standardised kits sensitive to low concentrations of free-testosterone or bioavailable testosterone are needed to diagnose androgen deficiency in women. A clearer epidemiology of androgen deficiencies in advanced cancer will help determine which patients should receive testosterone-replacement therapy for alleviating cancer cachexia symptoms and improving quality of life.

Cancer-related fatigue: the impact of skeletal muscle mass and strength in patients with advanced cancer.

BACKGROUND: Although exertional fatigue is directly and negatively related to skeletal muscle mass and strength, it is currently unknown if these variables are associated with cancer-related fatigue (CRF). Therefore, the purpose of this study was to determine if CRF is associated with measures of appendicular lean muscle mass and strength in advanced cancer patients (ACP). METHODS AND RESULTS: Eighty-four patients (48 men, 36 women aged 61.6 ± 13.2 year) newly diagnosed (≤6 months) with inoperable (Stages III-IV) gastrointestinal or non-small cell lung cancer participated in this study. All patients completed the Brief Fatigue Inventory (BFI). Handgrip (HGS) and quadriceps (QS) strength were assessed using isometric and isokinetic dynamometry, respectively. Skeletal muscle mass index (SMMI) was calculated from the appendicular lean mass measured via dual-energy X-ray absorptiometry divided by body height squared. Univariate analysis showed BFI to be significantly associated with body mass index, weight loss, anemia, hypoalbuminemia, activity level, pain, depression, and sarcopenia along with SMMI, HGS, and QS. HGS (r = -0.34; p = 0.018), QS (r = -0.39; p = 0.024), and SMMI (r = -0.60; p < 0.001) were negatively correlated with BFI total scores in men but not in women. When adjusted for sex, age, diagnosis, survival, along with the above characteristics, multivariate analyses showed that BFI scores were negatively associated with HGS (B = -0.90; 95% CI -1.5:-0.3), QS (-0.2; -0.3:-0.01), and SMMI (-7.5; -13.0:-2.0). There was a significant sex × SMMI interaction (10.8; 1.2:20.5), where BFI decreased with increasing SMMI in men, but did not change with SMMI in women. CONCLUSION: These results suggest that in ACP, CRF is related to muscle mass and strength, which may provide targets for future interventions.

Relationship between angiotensin-converting enzyme gene polymorphism and body composition, functional performance, and blood biomarkers in advanced cancer patients.

PURPOSE: Nutritional and functional outcome measures have been shown to vary in patients with chronic diseases according to the polymorphic alleles of angiotensin-converting enzyme (ACE), but little is known about the associations between ACE gene polymorphism (ACEGP) and the components of body composition, strength, and selected blood markers in advanced cancer patients (ACP). EXPERIMENTAL DESIGN: Data were collected from an inception cohort of 172 newly diagnosed ACP with gastrointestinal and non-small cell lung cancer. ACEGP status was defined by the presence of one of the following three combinations of alleles: insertion/insertion, insertion/deletion, and deletion/deletion. Body composition measurements using Dual-energy X-ray Absorptiometry comprised of the following: total fat mass, percent body fat, lean body mass, and appendicular lean mass. Body mass index; handgrip force by Jamar dynamometry; subjective recording of nutrition and performance status as per patient-generated subjective global assessment; cell blood count and differential, serum albumin, ACE, and C-reactive protein were also recorded. RESULTS: Multiple regression analysis, controlling for gender, age, diagnosis, treatments (radio/chemo), survival, and medication use (ACE inhibitors, anti-inflammatories, statins) revealed the following significant (P

Precision and reliability of strength (Jamar vs. Biodex handgrip) and body composition (dual-energy X-ray absorptiometry vs. bioimpedance analysis) measurements in advanced cancer patients.

Important deteriorations in body composition and strength occur and need to be accurately measured in advanced cancer patients (ACPs). The aim of this study was to establish the relationship between a single-frequency bioimpedance analyzer (BIA) and the dual-energy X-ray absorptiometer (DXA), as well as the Jamar handgrip dynometer and the Biodex handgrip attachment, and to determine the precision of each of these instruments in ACPs. Eighty-one ACPs with non-small-cell lung cancer and gastrointestinal cancer were recruited from the McGill University Health Centre (Montreal, Que.). Consecutive paired measurements, with repositioning between measurements, were obtained for total-body DXA, BIA, Biodex handgrip, and BIA plus Jamar handgrip. The total-body percent coefficient of variation (%CV) for the BIA and DXA were 1.34 and 1.56 for fat mass (FM), respectively, and 0.42 and 0.72 for fat free mass (FFM), respectively. The %CV for the Jamar and Biodex handgrips were 6.3 and 16.7, respectively. Bland-Altman plots were used to characterize the limits of agreement between DXA and BIA for FM (4.60 +/- 7.80 (-3.19 to 12.39) kg) and FFM (-1.87 +/- 7.16 (-9.03 to 5.29) kg). Both DXA and BIA demonstrate good short-term precision in ACPs. However, given its poor accuracy, it remains to be determined if BIA can be used to monitor ACPs for changes in total-body tissue composition as a function of time, whether for observation or response to treatment. Furthermore, because of wide limits of agreement, the DXA and BIA cannot be used interchangeably in research or clinical settings. The Jamar handgrip dynamometer shows more consistency than the Biodex handgrip attachment in ACPs, and should therefore be the preferred measure of changes in strength over time.

Female boxers have high bone mineral density despite low body fat mass, high energy expenditure, and a high incidence of oligomenorrhea.

Low body fat mass and menstrual irregularities have been associated with low bone mineral density (BMD). The aim of this study was to compare the relation between BMD, lean body mass, fat mass, physical activity energy expenditure (PAEE), and menstrual status in female boxers and in physically active females with low (C1) or average (C2) fat mass. Boxers (n = 11) and controls (C1, n = 16; C2, n = 17), aged 18-38 years, were assessed for BMD and body composition with dual-energy X-ray absorptiometry. Menstrual status and PAEE were determined from questionnaires. There was no difference in anthropometric measurements between boxers and C1 subjects, except that boxers had higher arm lean mass. However, both boxers and C1 subjects had a lower percentage of fat (p < 0.001) than C2 subjects (boxers, 14.6% +/- 2.0; C1, 15.5% +/- 4.2; C2, 25.8% +/- 3.4%), and boxers had a higher (p = 0.002) lean body mass index (lean body mass/height2, where lean body mass is measured in kilograms and height is measured in metres) than C2 subjects. The PAEE of boxers was higher (p < 0.007) than that of controls (boxers, 5748 +/- 2284 ; C1, 2966 +/- 2258 ; C2, 2714 +/- 1722 kcal.week-1). Oligomenorrhea was more common in boxers than in C1 and C2 subjects (boxers, 54.6%; C1, 18.8%; C2, 35.3%). Arm, leg, and spine BMD were higher (p < 0.008) in boxers than in C1 subjects, and arm BMD was higher in boxers than in C2 subjects. BMD Z scores were also higher (p < 0.05) in boxers (boxers, 1.1+/- 0.8, C1, 0.1 +/- 0.7; C2: 0.3 +/- 1.1). High BMD in boxers, despite low fat mass, high PAEE, and an increased incidence of oligomenorrhea suggest that boxing has a positive effect on BMD.