The value of physical performance measurements alongside assessment of sarcopenia in predicting receipt and completion of planned treatment in non-small cell lung cancer: an observational exploratory study.

INTRODUCTION: The presence of muscle mass depletion is associated with poor outcomes and survival in cancer. Alongside muscle mass, assessment of muscle strength or physical performance is essential for the diagnosis of sarcopenia. Non-small cell lung cancer (NSCLC) is a prevalent form of cancer with high mortality, and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) is commonly used to assess patients' suitability for treatment. However, a significant proportion of patients with good PS are unable to complete multidisciplinary team (MDT)-planned treatment. Little is known about the ability of objective measurements of physical performance in predicting patients' ability to complete MDT-planned treatment and outcomes in NSCLC. OBJECTIVES: We sought to establish whether physical performance, utilising the short physical performance battery (SPPB), alongside muscle mass measurements, was able to predict receipt and completion of MDT-planned treatment, with a focus on chemotherapy in NSCLC. MATERIALS AND METHODS: Participants with NSCLC treated through a single lung cancer MDT and ECOG PS 0-2 were recruited and the following assessed: body composition [bioelectrical impedance (BIA) and whole body dual-energy X-ray absorptiometry (DXA) in a subset], physical performance (SPPB), PS and nutritional status. We recorded receipt and completion of chemotherapy, as well as any adverse effects, hospitalisations, and treatment delays. RESULTS: We included a total of 62 participants with NSCLC, and in 26 of these, the MDT-planned treatment was chemotherapy. Participants with earlier stage disease and weight loss of <10% were more likely to complete MDT-planned treatment (p < 0.001 and p < 0.05). Patients with a higher total SPPB score were more likely to complete more cycles of chemotherapy as well as the full course. Quicker gait speeds and sit-to-stand times were associated with completion of three or more cycles of chemotherapy (all p < 0.05). For every unit increase in SPPB score, there was a 28.2% decrease in adverse events, hospitalisations and delays of chemotherapy (incidence rate ratio 0.718, p = 0.001), whilst ECOG PS showed no correlation with these outcomes. CONCLUSION: Assessing physical performance by SPPB is quick and simple to do in clinical settings and may give better indication of likely chemotherapy treatment course completion than muscle mass alone and ECOG PS. In turn, this may identify specific targets for early functional intervention and impact on MDT decision-making and prudent use of resources.

Association of sarcopenia and observed physical performance with attainment of multidisciplinary team planned treatment in non-small cell lung cancer: an observational study protocol.

BACKGROUND: Non-small cell lung cancer (NSCLC) frequently presents in advanced stages. A significant proportion of those with reportedly good ECOG performance status (PS) fail to receive planned multidisciplinary team (MDT) treatment, often for functional reasons, but an objective decline in physical performance is not well described. Sarcopenia, or loss of muscle mass, is an integral part of cancer cachexia. However, changes in both muscle mass and physical performance may predate clinically overt cachexia, and may be present even with normal body mass index. Physical fitness for treatment is currently subjectively assessed by means of the PS score, which may be inadequate in predicting tolerance to treatment. This study aims to evaluate whether measuring physical performance and muscle mass at baseline in NSCLC patients, in addition to PS score, is able to predict commencement and successful completion of MDT-planned treatment. METHODS/DESIGN: This is a prospective, single-centre exploratory study of NSCLC patients attending a Rapid Access Lung Cancer clinic. Baseline data collected are (methods in brackets): physical performance (Short Physical Performance Battery), muscle mass (bioelectrical impedance ± dual energy x-ray absorptiometry), patient and physician-assessed PS (ECOG and Karnofsky), nutritional status and presence of cachexia. Longitudinal data consists of receipt and completion of MDT treatment plan. The primary outcome measure is commencement of MDT-planned treatment, and important secondary outcomes include successful completion of treatment, length of stay in surgical patients, and risk of chemotherapy- and radiotherapy-related side effects. DISCUSSION: A more comprehensive assessment of phenotype, particularly with regards to physical performance and muscle mass, will provide additional discriminatory information of patients' fitness for treatment. If positive, this study has the potential to identify targets for early intervention in those who are at risk of deterioration. This will subsequently enable optimisation of performance of patients with NSCLC, in anticipation of systemic treatment.

Randomised experimental evaluation of a social media campaign to promote COVID-19 vaccination in Nigeria.

Background: The coronavirus disease 2019 (COVID-19) pandemic has challenged public health and behaviour change programmes, and has led to the development of innovative interventions and research. In low -and middle-income countries (LMICs) such as Nigeria, new strategies to promote vaccination, increase pro-vaccination social norms, and reduce vaccine hesitancy have been deployed through social media campaigns and evaluated using digital media platforms. Methods: We conducted two randomised experimental evaluations of social media content designed to promote COVID-19 vaccination and to complement research on a nationwide vaccination promotion campaign in Nigeria run in 2022. We conducted two studies in March and August 2022 among Nigerians drawn from 31 states that had not been targeted in the aforementioned nationwide campaign. We randomised the participants to either receive the pro-vaccination social media campaign or not and collected data at pre- and post-test time points to evaluate psychosocial predictors of vaccination and vaccination outcomes following the Theory of Change based on Diffusion of Innovations; the Social Norms Theory, and the Motivation, Opportunity, Ability (MOA) framework. Data were collected through a novel intervention delivery and data collection platform through social media. Results: We found that pro-vaccination social norms and vaccination rates increased, while vaccine hesitancy decreased among participants randomised to the social media intervention study arm. Conclusions: Social media campaigns are a promising approach to increasing vaccination at scale in LMICs, while social norms are an important factor in promoting vaccination, which is consistent with the Social Norms Theory. This study demonstrates the capability and potential of new social media-based data collection techniques. We describe implications for future vaccination campaigns and identify future research priorities in this area. Registration: Pan African Clinical Trial Registry: PACTR202310811597445.

Development and Evaluation of an Index to Measure the Ability to Get Vaccinated for COVID-19.

The COVID-19 pandemic has been an historic challenge to public health, and to behavior change programs. There have been challenges in promoting vaccination in LMICs, including Nigeria. One important hypothesis deserving consideration is the ability to obtain vaccination as a potential barrier to vaccination uptake. The MOA (motivation, opportunity, and ability) framework, as illustrated by multiple theories such as COM-B, EAST, and the Fogg model, is a primary theoretical basis for the evaluation of this ability as a factor in vaccination uptake. There is little research on measuring the ability to get vaccinated in LMICs, including on the role of all of the MOA framework. The aim of this study was to develop and evaluate an ability factors index measured through social media-based data collected in Nigeria in late 2021 and early 2022. We present findings from an online survey of 8574 Nigerians and highlight new social media-based data collection techniques in this research. This study found that a new ability factors index comprising 12 items was associated with vaccine uptake independent of measures capturing other components of the MOA framework. This index may serve as a valuable research instrument for future studies. We conclude that a person's perceived ability to get vaccinated, measured by a newly validated index, is related to vaccination uptake and hesitancy, and that more research should be conducted in this area.

Assessing digital advertising exposure using a virtual experimental protocol.

Introduction: The rapid increase in online public education campaigns underscores the need for a better understanding of the effects of exposure to digital advertising and targeted individual-level outcomes. The goal of this study is to develop a virtual experimental protocol to evaluate the dose-response effects of individual-level exposure to digital video ads on campaign outcomes in a naturalistic online browsing context. Methods: Young adults aged 18-24 years (n = 221) completed three 5 min viewing sessions on a realistic mock-up of the YouTube mobile app over a period of 2 weeks, followed by a 10-min survey after the third session. Participants were randomized to view between 0 and 6 exposures of ads from an e-cigarette prevention campaign; respondents viewed a total of 2 ads per session, with 0 to 2 of those ads being non-skippable digital video ads from the campaign and/or a dummy ad. The video ads played prior to short YouTube videos. Outcomes measured were self-reported ad recognition, frequency of ad exposure, and main message knowledge. Results: This study demonstrates a rapidly accessible virtual experimental protocol for evaluating the dose-response effects of digital advertising and individual-level outcomes. Five digital exposures of non-skippable video ads delivered via this platform over a 2-week period generated the highest ad recognition when there were up to six exposures. Higher exposure levels may be needed for message knowledge and ad-content-related effects. Conclusion: This protocol can be extended to investigate dose-response effects and mechanisms of action of individual-level exposure to digital advertising for multiple campaign outcomes, including changes in knowledge, attitudes, and beliefs. Findings can inform evidence for adequate levels of digital exposure in public education campaigns.

Systematic Review of Peer-Reviewed Literature on Global Condom Promotion Programs.

Background: Globally, 1.7 million people were newly infected with HIV in 2018. Condoms are inexpensive, cost-effective, reduce HIV/STI incidence, morbidity, mortality, and unintended pregnancies, and result in health care cost savings. Given the rapid increase in at-risk adolescent and young adult (AYA) populations in countries with high HIV/STI prevalence as well as the reductions in donor support, promoting consistent condom use remains crucial. We synthesized all peer-reviewed literature on condom promotion programs with a focus on promotion in low and lower middle income (LMIC) countries and with AYA users. Methods: We systematically reviewed the published literature. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methods, we identified 99 articles published between 2000-2019. Results: Condom promotion programs were generally effective in changing attitudes, social norms, and beliefs in favor of condom use, and 85% demonstrated positive effects on multiple condom use measures. Programs targeting AYA were at least equally as effective as those targeting others and often showed greater use of best practices, such as mass media (66%) and audience segmentation (31%). We also saw differences between programs in the intervention strategies they used and found greater effects of marketing strategies on AYA compared to the overall sample. Conclusion: Condoms remain essential to prevention, and donor support must be maintained to combat the HIV/STI epidemic.

Absolute standardisation and determination of the half-life and gamma emission intensities of 89Zr.

An absolute standardisation of 89Zr was performed alongside determination of gamma emission intensities and half-life. The collected data were evaluated alongside complementary works from previous publications and new recommended nuclear data values are presented including a new evaluated T1/2 = 78.361(25) h and new absolute intensities for gamma transitions resulting from its decay to 89Y. Dial settings for commercially available radionuclide calibrators are also presented and show a relative difference of approximately 3% compared to previously published values.

CATS II Long-term Anthropometric and Metabolic Effects of Maternal Sub-optimal Thyroid Function in Offspring and Mothers.

CONTEXT AND OBJECTIVES: The Controlled Antenatal Thyroid Screening Study I (CATS-I) was a randomized controlled trial investigating the effects of levothyroxine therapy for suboptimal gestational thyroid function (SGTF), comparing outcomes in children of treated (SGTF-T) with untreated (SGTF-U) women during pregnancy. This follow-up study, CATS-II, reports the long-term effects on anthropometric, bone, and cardiometabolic outcomes in mothers and offspring and includes a group with normal gestational thyroid function (NGTF). DESIGN & PARTICIPANTS: 332 mothers (197 NGTF, 56 SGTF-U, 79 SGTF-T) aged 41.2±5.3 years (mean±SD) and 326 paired children assessed 9.3±1.0 years after birth for (i) body mass index (BMI); (ii) lean, fat, and bone mass by dual-energy X-ray absorptiometry; (iii) blood pressure, augmentation index, and aortic pulse-wave-velocity; and (iv) thyroid function, lipids, insulin, and adiponectin. The difference between group means was compared using linear regression. RESULTS: Offspring's measurements were similar between groups. Although maternal BMI was similar between groups at CATS-I, after 9 years (at CATS-II) SGTF-U mothers showed higher BMI (median [interquartile ratio] 28.3 [24.6-32.6] kg/m2) compared with NGTF (25.8 [22.9-30.0] kg/m2; P = 0.029), driven by fat mass increase. At CATS-II SGTF-U mothers also had higher thyroid-stimulating hormone (TSH) values (2.45 [1.43-3.50] mU/L) than NGTF (1.54 [1.12-2.07] mU/L; P = 0.015), since 64% had never received levothyroxine. At CATS-II, SGTF-T mothers had BMI (25.8 [23.1-29.8] kg/m2, P = 0.672) and TSH (1.68 [0.89-2.96] mU/L; P = 0.474) values similar to NGTF mothers. CONCLUSIONS: Levothyroxine supplementation of women with SGTF did not affect long-term offspring anthropometric, bone, and cardiometabolic measurements. However, absence of treatment was associated with sustained long-term increase in BMI and fat mass in women with SGTF.

Design and Feasibility of a Text Messaging Intervention to Prevent Indoor Tanning Among Young Adult Women: A Pilot Study.

BACKGROUND: Although skin cancer is largely preventable, it affects nearly 1 of 5 US adults. There is a need for research on how to optimally design persuasive public health indoor tanning prevention messages. OBJECTIVE: The objective of our study was to examine whether framed messages on indoor tanning behavioral intentions delivered through short message service (SMS) text messaging would produce (1) positive responses to the messages, including message receptivity and emotional response; (2) indoor tanning efficacy beliefs, including response efficacy and self-efficacy; and (3) indoor tanning risk beliefs. METHODS: We conducted a pilot study of indoor tanning prevention messages delivered via mobile phone text messaging in a sample of 21 young adult women who indoor tan. Participants completed baseline measures, were randomly assigned to receive gain-, loss-, or balanced-framed text messages, and completed postexposure outcome measures on indoor tanning cognitions and behaviors. Participants received daily mobile phone indoor tanning prevention text messages for 1 week and completed the same postexposure measures as at baseline. RESULTS: Over the 1-week period there were trends or significant changes after receipt of the text messages, including increased perceived susceptibility (P<.001), response efficacy beliefs (P<.001), and message receptivity (P=.03). Ordinary least squares stepwise linear regression models showed an effect of text message exposure on self-efficacy to quit indoor tanning (t6=-2.475, P<.02). Ordinary least squares linear regression including all measured scales showed a marginal effect of SMS texts on self-efficacy (t20=1.905, P=.08). Participants endorsed highly favorable views toward the text messaging protocol. CONCLUSIONS: This study supports this use of mobile text messaging as an indoor tanning prevention strategy. Given the nature of skin cancer risk perceptions, the addition of multimedia messaging service is another area of potential innovation for disseminating indoor tanning prevention messages.

Natural and synthetic flavonoid modulation of TRPC5 channels.

BACKGROUND AND PURPOSE: The TRPC5 proteins assemble to create calcium-permeable, non-selective, cationic channels. We sought novel modulators of these channels through studies of natural products. EXPERIMENTAL APPROACH: Intracellular calcium measurements and patch clamp recordings were made from cell lines. Compounds were generated by synthetic chemistry. KEY RESULTS: Through a screen of natural products used in traditional Chinese medicines, the flavonol galangin was identified as an inhibitor of lanthanide-evoked calcium entry in TRPC5 overexpressing HEK 293 cells (IC50 0.45 µM). Galangin also inhibited lanthanide-evoked TRPC5-mediated current in whole-cell and outside-out patch recordings. In differentiated 3T3-L1 cells, it inhibited constitutive and lanthanide-evoked calcium entry through endogenous TRPC5-containing channels. The related natural flavonols, kaempferol and quercetin were less potent inhibitors of TRPC5. Myricetin and luteolin lacked effect, and apigenin was a stimulator. Based on structure-activity relationship studies with natural and synthetic flavonols, we designed 3,5,7-trihydroxy-2-(2-bromophenyl)-4H-chromen-4-one (AM12), which inhibited lanthanide-evoked TRPC5 activity with an IC50 of 0.28 µM. AM12 also inhibited TRPC5 activity evoked by the agonist (-)-Englerin A and was effective in excised outside-out membrane patches, suggesting a relatively direct effect. It inhibited TRPC4 channels similarly, but its inhibitory effect on TRPC1-TRPC5 heteromeric channels was weaker. CONCLUSIONS AND IMPLICATIONS: The data suggest that galangin (a natural product from the ginger family) is a TRPC5 inhibitor and that other natural and synthetic flavonoids contain antagonist or agonist capabilities at TRPC5 and closely related channels depending on the substitution patterns of both the chromone core and the phenyl ring.

Hidden depletion of fat-free mass and bone mineral density in adults with cystic fibrosis.

BACKGROUND: Weight loss is associated with reduced survival in patients with cystic fibrosis (CF). OBJECTIVE: We hypothesized that some adult patients with a normal body mass index (BMI) have evidence of hidden fat-free mass (FFM) and bone mineral density (BMD) depletion that is linked to more severe disease. DESIGN: Fat mass (FM), FFM, and BMD were determined by dual-energy x-ray absorptiometry (DXA) and by bioelectric impedance in 56 adults in clinically stable condition and 20 age-matched healthy subjects. FM index and FFM index (FFMI) [kilograms per meter squared] of the right arm, leg, and trunk (ratio to height squared) were calculated. Lung function, including the maximum inspiratory pressure (MIP) and sustained MIP (SMIP), physical activity, serum C-reactive protein (CRP) and the number of exacerbations in the previous year were recorded. RESULTS: Patients had a lower total FFM than healthy subjects (p < 0.01), while FM was similar. Of the 56 patients, 30 patients had a normal BMI, of which 12 patients had a low FFM (hidden loss) by DXA. The right arm, leg, and trunk FFMI and BMD at hip sites were less in these patients than in those with a normal BMI and normal FFM (all p < 0.01). This group had a lower FEV(1), SMIP, more frequent exacerbations, and greater circulating CRP (all p < 0.05). CONCLUSIONS: In adults with CF, apparent or hidden loss of FFM, rather than weight loss, was related to overall disease severity. Hidden depletion of FFM was associated with increased loss of BMD and systemic inflammatory activity.

Mass media health communication campaigns combined with health-related product distribution: a community guide systematic review.

CONTEXT: Health communication campaigns including mass media and health-related product distribution have been used to reduce mortality and morbidity through behavior change. The intervention is defined as having two core components reflecting two social marketing principles: (1) promoting behavior change through multiple communication channels, one being mass media, and (2) distributing a free or reduced-price product that facilitates adoption and maintenance of healthy behavior change, sustains cessation of harmful behaviors, or protects against behavior-related disease or injury. EVIDENCE ACQUISITION: Using methods previously developed for the Community Guide, a systematic review (search period, January 1980-December 2009) was conducted to evaluate the effectiveness of health communication campaigns that use multiple channels, including mass media, and distribute health-related products. The primary outcome of interest was use of distributed health-related products. EVIDENCE SYNTHESIS: Twenty-two studies that met Community Guide quality criteria were analyzed in 2010. Most studies showed favorable behavior change effects on health-related product use (a median increase of 8.4 percentage points). By product category, median increases in desired behaviors ranged from 4.0 percentage points for condom promotion and distribution campaigns to 10.0 percentage points for smoking-cessation campaigns. CONCLUSIONS: Health communication campaigns that combine mass media and other communication channels with distribution of free or reduced-price health-related products are effective in improving healthy behaviors. This intervention is expected to be applicable across U.S. demographic groups, with appropriate population targeting. The ability to draw more specific conclusions about other important social marketing practices is constrained by limited reporting of intervention components and characteristics.

Body composition in children with type 1 diabetes in the first year after diagnosis: relationship to glycaemic control and cardiovascular risk.

INTRODUCTION: Rapid weight gain is often observed following initiation of insulin therapy in children with type 1 diabetes mellitus (T1DM) and girls are particularly at risk of becoming overweight. The authors evaluated body composition changes in children during the first year after diagnosis and related this to markers of cardiovascular risk. METHODS: Body mass index (BMI) and body composition measured by whole body dual energy x-ray absorptiometry (DEXA) were assessed in 30 patients (18 boys) with T1DM 3-10 days after diagnosis, 6 weeks later and at 1 year, and on two occasions 1 year apart in 14 controls (8 boys). Cardiovascular risk markers were assessed in T1DM subjects at 1 year. RESULTS: T1DM subjects had lower BMI SD scores (SDS) at diagnosis than controls (mean (SD) BMI SDS -0.67 (1.34) vs 0.20 (1.14), p<0.05) and reduced percentage body fat (20.3% (4.6) vs 24.5% (7.7), p<0.05). T1DM subjects normalised their body composition at 6 weeks and this was maintained 1 year later. Girls with diabetes were thinner than boys at diagnosis (BMI SDS -1.64 (1.02) vs -0.02 (1.17), p<0.05) and at 1 year (BMI SDS -0.58(0.9) vs 0.65 (0.98), p<0.05). Girls had higher glycated haemoglobin (HbA1c) (8.8% (1.2) vs 7.8% (1.0), p<0.05), insulin dose (1.01 (0.30) vs 0.82 (0.18) U/kg/day, p=0.04), total cholesterol (4.30 (0.45) vs 3.79 (0.50) mmol/l, p<0.05) and high-density lipoprotein (2.62 (0.53) vs 2.02 (0.37) mmol/l). High sensitivity C reactive protein and fibrinogen were in the normal range and there were no differences between genders. DISCUSSION: Insulin deficiency at diagnosis of diabetes causes a catabolic state that is predominantly lipolytic. Body composition normalises within 6 weeks of treatment, though girls remain thinner than boys both at diagnosis and 1 year thereafter, in contrast to published findings. Despite girls being prescribed a larger insulin dose, their HbA1c and cholesterol levels are higher at 1 year suggesting increased insulin resistance and cardiovascular risk.

Arterial stiffness and osteoporosis in chronic obstructive pulmonary disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular events and osteoporosis. Increased arterial stiffness is an independent predictor of cardiovascular disease. OBJECTIVES: We tested the hypothesis that patients with COPD would have increased arterial stiffness, which would be associated with osteoporosis and systemic inflammation. METHODS: We studied 75 clinically stable patients with a range of severity of airway obstruction and 42 healthy smoker or ex-smoker control subjects, free of cardiovascular disease. All subjects underwent spirometry, measurement of aortic pulse wave velocity (PWV) and augmentation index, dual-energy X-ray absorptiometry, and blood sampling for inflammatory mediators. MEASUREMENTS AND MAIN RESULTS: Mean (SD) aortic PWV was greater in patients, 11.4 (2.7) m/s, than in control subjects, 8.95 (1.7) m/s, p < 0.0001. Inflammatory mediators and augmentation index were also greater in patients. Patients with osteoporosis at the hip had a greater aortic PWV, 13.1 (1.8) m/s, than those without, 11.2 (2.7) m/s, p < 0.05. In patients, aortic PWV was related to age (r = 0.63, p < 0.0001) and log(10) IL-6 (r = 0.31, p < 0.01), and inversely to FEV(1) (r = -0.34, p < 0.01). The strongest predictors of aortic PWV in all subjects were age (p < 0.0001), percent predicted FEV(1) (p < 0.05), mean arterial pressure (p < 0.05), and log(10) IL-6 (p < 0.05). CONCLUSIONS: Increased arterial stiffness was related to the severity of airflow obstruction and may be a factor in the excess risk for cardiovascular disease in COPD. The increased aortic PWV in patients with osteoporosis and the association with systemic inflammation suggest that age-related bone and vascular changes occur prematurely in COPD.

Body composition of long-term survivors of acute lymphoblastic leukaemia.

BACKGROUND: Long-term quality of life is of growing importance in children previously treated for malignancy. Obesity defined indirectly from indices of height and weight, has been described in long-term survivors of acute lymphoblastic leukaemia (ALL) and hypothesised to be a consequence of previous cranial irradiation. PROCEDURE: In this study, measures of whole and regional body composition using skinfold and dual energy X-ray absorptiometry (DEXA) measurements have been made in 35 long-term survivors of ALL who had received cranial irradiation and chemotherapy. To assess the influence of cranial irradiation, results were compared with those obtained in 21 children treated for other malignancies, who received chemotherapy alone and with 31 healthy sibling controls. RESULTS: Girls treated for ALL were significantly fatter than those treated for other malignancies or healthy control siblings whether measured by skinfold thickness (median (range) 37.4% (17.9-41.3) vs. 24.6% (19.1-35.0) and 28.8% (19.6-43.1), respectively, P<0.01) or DEXA (33.5% (20.5-42.8) vs. 25.5% (16.5-31.0) and 24.5% (18.8-53.6), respectively, P<0.01). Boys treated for ALL were not significantly fatter than boys in the other two groups. Measures of whole body percent fat derived from DEXA were persistently less than those derived from skinfold measurements with a mean (95% CI) difference of 2.4% (1.7-3.1, P<0.001) for all groups combined. In ALL survivors, using regression equations for skinfold thicknesses derived from controls with DEXA as the 'gold standard' method, fat mass was significantly overestimated. CONCLUSION: Female survivors of ALL are significantly fatter than those of other malignancies and healthy sibling controls. Caution should be observed in the application of published equations, derived from the normal population, for the calculation of body composition in children treated for ALL. The mechanism of onset of obesity remains unclear, but is probably multifactorial and related to previous cranial irradiation.

Associated loss of fat-free mass and bone mineral density in chronic obstructive pulmonary disease.

We hypothesized that in patients with chronic obstructive pulmonary disease, loss of fat-free mass (FFM) and loss of bone mineral density (BMD) were related to (1) each other and may be clinically inapparent, (2) urinary markers of cellular and bone collagen protein breakdown, and (3) severity of lung disease. Eight-one patients and 38 healthy subjects underwent dual-energy X-ray absorptiometry to determine body composition and BMD. Urinary protein breakdown markers, inflammatory mediators, and their soluble receptors were determined. Thirty-three patients had a low fat-free mass index (kg/m(2)), 17 of whom had a normal body mass index. Thirty-two percent of patients (13% of healthy subjects) had osteoporosis at the hip or lumbar spine. The marker of cellular protein breakdown was elevated in patients and related to lung disease severity and body composition. The marker of bone collagen breakdown was greater in patients with osteoporosis. Inflammatory mediators were elevated in patients. Loss of FFM and loss of BMD were related, occurred commonly, and could be subclinical in patients with chronic obstructive pulmonary disease. Loss of both was greatest with severe lung disease. Increased excretion of cellular and bone collagen protein breakdown products in those with low FFM and BMD indicates a protein catabolic state in these patients.

Pulmonary function, body composition, and protein catabolism in adults with cystic fibrosis.

Increased survival in cystic fibrosis (CF) is associated with bone thinning and fat-free mass (FFM) loss. We hypothesized that the severity of lung disease would be associated with increased protein catabolism and systemic inflammatory status in clinically stable patients. Forty adults with CF and 22 age-matched healthy subjects were studied. Body composition was determined by dual-energy X-ray absorptiometry. Urinary pseudouridine (PSU), a marker of protein breakdown, and cross-linked N-telopeptides of type I collagen (NTx), a marker of bone connective tissue breakdown, serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and their soluble receptors were measured. A 3-d food intake diary revealed 21 patients had a low energy intake. Excretion of PSU (p = 0.019) and NTx (p < 0.01) was increased in patients and was inversely related to FEV(1); PSU (r = - 0.53, p = 0.001) and NTx (r = - 0.43, p < 0.01). Increased excretion of PSU and NTx (p < 0.05 for both) was also related to a low FFM. All inflammatory mediators were greater in patients and were related to PSU and NTx. Clinically stable adults were catabolic with both cellular and connective tissue protein breakdown, which was related to lung disease severity, systemic inflammation, and body composition.