Prediction Equations Underestimate Resting Energy Expenditure in Patients With End-Stage Cystic Fibrosis.

BACKGROUND: Resting energy expenditure (REE) is increased in patients with cystic fibrosis (CF) with end-stage lung disease due to chronic inflammation and pulmonary infections. After lung transplantation (LTx), energy expenditure is expected to be lower because inflammation will decrease. We assessed the agreement between measured and predicted REE in pre-LTx CF and post-LTx patients with CF and differences in REE in pre-LTx CF and post-LTx patients with CF in a cross-sectional study. METHODS: Included were 12 pre-LTx patients with CF (9 women; median age 31.6 years; interquartile range [IQR], 23.3-40.0) and 12 patients with CF within 2 years after LTx (6 women; median age 33.5 years; IQR, 22.3-40.3). REE was measured in a fasted state using indirect calorimetry. Values were compared with predicted REE calculated by formulas of Harris-Benedict (1919 and 1984), Schofield, and the World Health Organization (1985). A calculated REE between 90% and 110% of REE measured was considered adequate. RESULTS: Prediction equations underestimate REE in at least 75% of pre-LTx and 33% of post-LTx patients with CF. Mean (SD) REE measured by indirect calorimetry was 1735 (251) kcal pre-LTx and 1650 (235) kcal post-LTx ( P = .40). REE expressed per kilogram of fat-free mass (FFM) was 40.5 kcal/kg in pre-LTx patients with CF, which was higher than the 34.3 kcal/kg in post-LTx patients with CF ( P = .01). CONCLUSIONS: Prediction equations underestimate REE in patients with end-stage CF. REE per kg of FFM is lower post-LTx than pre-LTx in patients with CF. Measurement of REE is recommended for patients with CF, especially pre-LTx, to optimize energy requirements for improving nutrition status.

Body Weight and Body Mass Index in Patients with End-Stage Cystic Fibrosis Stabilize After the Start of Enteral Tube Feeding.

BACKGROUND: Enteral tube feeding (ETF) is widely used in patients with cystic fibrosis (CF) and end-stage lung disease, but previous studies have been limited to investigating whether ETF improves outcomes in patients with moderately or mildly impaired pulmonary function. OBJECTIVE: This study investigated body weight, body mass index (BMI; calculated as kg/m2), pulmonary function, and the presence of CF-related diabetes before and after the start of ETF. DESIGN: This was a retrospective observational study. PARTICIPANTS/SETTING: Data from 26 adult patients in an outpatient setting who had end-stage CF (19 women) and had been using ETF for at least 6 months between 2000 and 2014 were analyzed. MAIN OUTCOME MEASURES: Body weight, BMI, pulmonary function (forced expiratory volume in 1 second as percent of predicted) and incidence of CF-related diabetes from 6 months before to 6 months after starting ETF. STATISTICAL ANALYSES PERFORMED: Time effects were tested with one-way analysis of variance for data that were normally distributed and the Friedman test for non-parametric data. Correlations were tested with Pearson's r or Spearman's ρ, depending on the distribution of the data. RESULTS: Mean body weight increased by 3.5 kg (95% CI 2.2 to 4.8 kg) after patients started ETF. In women, mean BMI decreased by 0.7 in the 6 months before the start of ETF (P<0.05) and increased by 1.4 in the 6 months thereafter (P<0.05). In men, BMI changes were similar (-0.8 and +1.1), but not statistically significant. Forced expiratory volume in 1 second as percent of predicted significantly decreased in time from a median of 28% to 26% at the start of ETF to 25% after 6 months (P=0.0013), with similar trends in women and men. There was no correlation between changes in weight and lung function. CF-related diabetes was already present in 12 patients and developed in 1 more patient after the start of ETF. CONCLUSIONS: ETF improved body weight and BMI but not pulmonary function in 26 patients with end-stage CF. Clinical outcomes were similar in women and men, but the sample size of men was too small to determine statistical significance.

Pretransplant HRCT Characteristics Are Associated with Worse Outcome of Lung Transplantation for Cystic Fibrosis Patients.

OBJECTIVES: Peri- and postoperative complications diminish the outcome of lung transplantation (LTx) in patients with cystic fibrosis (CF). We hypothesized that the degree of pathological findings on pre-LTx high resolution computed tomography (HRCT) is associated with higher morbidity and mortality in CF. METHODS: All our CF patients undergoing LTx between 2001 and 2011 were included. HRCT examinations were evaluated according to a scoring system for pulmonary disease in CF patients, the Severe Advanced Lung Disease (SALD) score and for pleural involvement. RESULTS: Fifty-three patients were included. Dominant infectious/inflammatory disease according to the SALD score was observed in 10 patients (19%). Five (50%) of those patients died within one week after LTx, compared to 2 (5%) patients without dominant infectious/inflammatory disease (p<0.001). This difference in survival percentage remained also significant in multivariate analysis. Patients with infectious/inflammatory disease received more packed red blood cells; 26 versus 8 in the first week (p<0.001). Pleural thickening was associated with higher requirement (10 units) for blood transfusion during LTx, compared to patients with normal pleura (4 units). CONCLUSIONS: The analysis of HRCT in CF patients according to the SALD score showed that dominant infectious/inflammatory disease is associated with a higher mortality after LTx. If confirmed in other studies, HRCT might aid estimation of surgical risk in some adult CF patients.

Patients with type 2 diabetes mellitus failing on oral agents and starting once daily insulin regimen; a small randomized study investigating effects of adding vildagliptin.

BACKGROUND: The addition of a DDP4-inhibitor to existing insulin therapy reduces HbA1c. However, no data exist about the addition of these agents at the beginning of insulin treatment in type 2 diabetes while this could especially be interesting because it is during this period that considerable residual beta cell function is still present. The benefit of such a strategy could be a lower insulin dose required for glycemic control. The hypothesis of our study was that adding a DPP4-inhibitor at the beginning of insulin treatment could lead to less exogenous insulin requirement, a reduction of hyperinsulinemia and side effects (hypoglycemia and weight gain), less glucose variability and improvement of insulin and glucagon dynamics during a mixed meal test. RESULTS: In this small clinical trial (trial registration NTR2022) 9 patients were randomized to receive vildagliptin and 6 to receive placebo in addition to start of once daily insulin treatment. Unfortunately, due to a difficult inclusion, the preset sample size of 40 patients could not be met. Median units of insulin at the end of the study was 47 U in the placebo group and 34 U in the vildagliptin group. Median glycemic variability (SD) at the end of study was 2.1 in the placebo group and 1.5 in the vildagliptin group. Median weight gain at the end of study was 3 kg in the placebo and 0.5 kg in the vildagliptin group. Occurrence of hypoglycemia was low in both groups. Insulin, C-peptide, glucose and glucagon levels were comparable during mixed meal tests. CONCLUSIONS: This small randomized study did not have sufficient power to detect effects of the addition of vildagliptin to the start of once daily long-acting insulin. However in our opinion adding a DPP4-inhibitor, especially in this group remains a very interesting approach. This study could be used as a guidance for larger studies that are required to investigate the effects of this intervention on insulin requirements, glycemic variability, hypoglycemia and weight gain.

[Domperidone and the risk of sudden cardiac death]. / Domperidon en het risico op acute hartdood.

Domperidone is an antiemetic drug with relatively few side-effects. In the Netherlands, domperidone is available over the counter. Recently, discussion on the safety of domperidone has arisen because an association with sudden cardiac death has been suggested. We performed a systematic literature search to investigate whether these concerns can be justified. Three out of four case-control studies found statistically significant increased odds ratios for sudden cardiac death when using domperidone. A dose-response relationship was described in one study. Results may be influenced by several confounders. We conclude that there is a relationship between domperidone use and sudden cardiac death at doses of more than 30 mg per day. We recommend that the indication be weighed up properly, that domperidone be provided only on prescription, and dose advice be given. At a dose of 30 mg per day, domperidone can be prescribed safely.

Pulmonary hypertension is a mild comorbidity in end-stage cystic fibrosis patients.

BACKGROUND: This study investigated the prevalence of pulmonary hypertension (PH) in cystic fibrosis (CF) patients awaiting lung transplantation (LTx) and its influence on survival. We also explored the feasibility of using echocardiography as a first assessment for diagnosing PH. METHODS: The study included 93 CF patients (46 women [50%]) evaluated for LTx between 2001 and 2010. Median age was 29 years. PH was defined as a mean pulmonary artery pressure (mPAP) measured by right heart catheterization (mPAP(cath)) of ≥ 25 mm Hg with a wedge pressure of ≤ 15 mm Hg. Echocardiographic results were divided into 3 categories based on current guidelines as "unlikely," "possible," or "likely" to have PH. RESULTS: In 23 patients (25%) the mPAP(cath) was between 25 and 35 mm Hg, and 1 (1%) had severe PH (mPAP(cath) of ≥ 35 mm Hg). PH did not influence survival after enlistment (p = 0.7) and after LTx (p = 0.8). For 62 patients (67%), the sPAP(echo) could be measured, and PH was unlikely in 24 (39%). In another 19 patients (20%), PH was unlikely based on the absence of tricuspid regurgitation. The negative-predictive value (NPV) of measuring PH by echocardiography was 88% in whom PH was estimated to be unlikely (n = 43); whereas in 24 patients with a measurable low sPAP(echo), the NPV was 96%. CONCLUSIONS: PH exists in 26% of end-stage CF patients and has no effect on survival on the waiting list for LTx or after LTx. Echocardiography might be used as the first tool to rule out PH, showing a NPV of 88%.