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.

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.

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.

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.

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.