Florian S. Fuchs

Leptin and ghrelin levels in patients with obstructive sleep apnoea: effect of CPAP treatment

Serum leptin and ghrelin levels were investigated in patients with obstructive sleep apnoea (OSA) syndrome before and during continuous positive airways pressure (CPAP) treatment and compared with body mass index (BMI)-matched controls without OSA. Male patients (n=30) with OSA (apnoea/hypopnoea index=58±16, BMI=32.6±5.3 kg·m−2) underwent CPAP treatment. Fasting leptin and ghrelin were measured atbaseline and 2 days, and in the case of leptin 2 months after initiation of treatment. Baseline plasma ghrelin levels were significantly higher in OSA patients than in controls. After 2 days of CPAP treatment, plasma ghrelin decreased in almost all OSA patients (n=9) to levels that were only slightly higher than those of controls (n=9). Leptin levels did not change significantly from baseline after 2 days of CPAP treatment, but were higher than in the control group. After 8 weeks, leptin levels decreased significantly, although the BMI of the patients showed no change. The decrease in leptin levels was more pronounced in patients with a BMI <30 kg·m−2. These data indicate that the elevated leptin and ghrelin levels are not determined by obesity alone, since they rapidly decreased during continuous positive airways pressure therapy.

The Effect of Continuous Positive Airway Pressure Treatment on Insulin Sensitivity in Patients with Obstructive Sleep Apnoea Syndrome and Type 2 Diabetes

Background: The obstructive sleep apnoea syndrome (OSA) is a frequent condition, as well as type 2 diabetes mellitus. Both diseases are characterized by insulin resistance. Objectives: The aim of this study was to establish whether OSA is an independent risk factor for increased insulin resistance in diabetics. For this purpose, we tested the hypothesis that the insulin sensitivity in patients with type 2 diabetes and OSA can be improved by 2 days or 3 months of continuous positive airway pressure (CPAP) treatment. Methods: In 9 obese patients with type 2 diabetes and OSA [apnoea/hypopnoea index 43.1 ± 21.3; body mass index (BMI) 37.3 ± 5.6 kg/m2] and good glycaemic control on oral antidiabetics or on diet alone (HbA1c 6.4 ± 0.7%), the insulin sensitivity index (ISI) was established by euglycaemic hyperinsulinaemic clamp tests at baseline, after 2 days and after 3 months of effective CPAP treatment. Results: ISI was unchanged after 2 days of CPAP treatment, but was significantly improved after 3 months (4.38 ± 2.94 vs. 2.74 ± 2.25 at baseline; p = 0.021), without any significant changes in BMI. Glycaemic control was unaffected after 3 months (HbA1c 6.3 ± 0.6%; not significant). Fasting leptin levels showed no significant changes. Conclusions: These results indicate that OSA itself is an independent risk factor for insulin resistance. This effect may be explained by the elevated sympathetic activity in OSA.

Review article: in vivo imaging by endocytoscopy.

Aliment Pharmacol Ther 2011; 33: 1183–1193

EGFR mutational status in a large series of Caucasian European NSCLC patients: data from daily practice.

Background:The prognosis of metastatic non-small cell lung cancer (NSCLC) is still poor. Activating epithelial growth factor receptor (EGFR) mutations are important genetic alterations with dramatic therapeutical implications. Up to now, in contrast to Asian populations only limited data on the prevalence of those mutations are available from patients with Caucasian and especially European ethnicity.Methods:In this multicentre study, 1201 unselected NSCLC patients from Southern Germany were tested in the daily clinical routine for EGFR mutation status.Results:Activating EGFR mutations were found in 9.8% of all tumours. Mutations in exons 18, 19 and 21 accounted for 4.2%, 61.9% and 33.1% of all mutations, respectively. Non-smokers had a significantly higher rate of EGFR mutations than smokers or ex-smokers (24.4% vs 4.2%; P<0.001). Non-lepidic-non-mucinous adenocarcinomas (G2) accounted for 45.5% of all activating EGFR mutations and 3.5% of all squamous cell carcinomas were tested positive. Thyroid transcription factor 1 protein expression was significantly associated with EGFR mutational status.Conclusion:These comprehensive data from clinical routine in Germany add to the knowledge of clinical and histopathological factors associated with EGFR mutational status in NSCLC.

Evaluation of a Portable Recording Device (Somnocheck®) for Use in Patients with Suspected Obstructive Sleep Apnoea

Background: Portable recording devices for the diagnosis of obstructive sleep apnoea (OSA) should be carefully evaluated before being used on a routine basis in out-patients. Objective: This study was designed to evaluate the diagnostic accuracy of the new portable recording device, Somnocheck® (SC). Methods: Nocturnal polysomnographies (PSG) and SC recordings were performed simultaneously in the sleep laboratory in 51 patients with suspected OSA, and were analysed manually by a blinded investigator. Results: The apnoea/hypopnoea index (AHI) obtained by manual SC analysis correlated closely with that obtained by PSG (r = 0.98), but the correlation with AHI obtained by automatic SC analysis was markedly lower (r = 0.83). When an AHI ≧10 was defined as indicative of OSA, the sensitivity of manual SC analysis was 0.97 and its specificity 1.00. The sensitivity of automatic analysis was 0.83 and its specificity 0.95. Conclusions: In this experimental setting, the SC showed a very high diagnostic accuracy for the diagnosis of OSA and was able to define its severity precisely. The diagnostic accuracy of manual analysis was found to be superior to that of automatic analysis. Considering the results of this technical evaluation, the SC may also be expected to work reliably when it is used in an ambulatory setting.

Confocal laser endomicroscopy for diagnosing lung cancer in vivo

Confocal laser endomicroscopy is a novel endoscopic technique that may allow imaging of living cells in lung tissue in vivo. We assessed the potential of this technique for the detection of histology during screening bronchoscopy for lung cancer. 32 patients with suspected malignancies underwent bronchoscopy with endomicroscopy using acriflavine hydrochloride. Standardised areas and localised lesions were analysed by in vivo confocal imaging during bronchoscopy and biopsies were taken. Confocal images were graded and correlated prospectively with conventional histology from biopsies. Acriflavine hydrochloride yielded high-quality confocal images and strongly labelled airway epithelial cells. No side-effects were noted. 75 522 confocal images from 56 different locations were compared prospectively with histological data from biopsy specimens. Endomicroscopy allowed subsurface imaging with detailed analysis of cellular and subcellular structures. Neoplastic changes could be predicted with high accuracy (sensitivity 96.0%, specificity 87.1%, accuracy 91.0%). Confocal laser endomicroscopy with acriflavine is a novel diagnostic tool for the analysis of living cells during bronchoscopy and permits virtual histology of neoplastic changes in the airways with high accuracy. This technique may enable the rapid diagnosis of neoplasia during ongoing endoscopy in patients with suspected lung cancer.

Initiation of CPAP therapy for OSA: does prophylactic humidification during CPAP pressure titration improve initial patient acceptance and comfort?

Background: Heated humidifiers (HH) enable effective treatment of upper airway dryness during nasal continuous positive airway pressure (nCPAP) therapy for obstructive sleep apnoea (OSA), but the role of prophylactic use of HH during the initiation of nCPAP treatment has not been studied so far. Objectives: The aim of the present study was to investigate whether prophylactic HH during the initiation of CPAP would result in improved initial patient comfort and acceptance. Methods: In 44 consecutive, previously untreated OSA patients with no history of upper airway dryness, CPAP titration with and without HH was performed on two consecutive nights in a randomised order. The patients were interviewed after each treatment night in order to establish the comfort of the treatment, and, after the second treatment, they were asked which of the two nights they considered more pleasant, and which treatment they would prefer for long-term use. Results: Following CPAP titration with HH, 32 patients (73%) claimed to have had a better night’s sleep than usual (i.e. without CPAP treatment) compared with 33 patients (75%) saying the same following CPAP treatment without HH. For 21 patients (47.7%) treatment with HH was more pleasant, 23 (52.3%) saw no difference or said that treatment without HH was more pleasant. Nineteen patients (43.2%) gave preference to treatment with HH for long-term use, while 25 patients (56.8%) had no preference or said they would prefer treatment without HH. Conclusions: The use of HH during the initiation phase of CPAP treatment was associated neither with an initial improvement in comfort nor with greater initial treatment acceptance.

Leptin, Obestatin and Apelin levels in patients with obstructive sleep apnoea syndrome

Summary Background Recent studies suggest that adipose tissue hormones are involved in the pathogenesis of obstructive sleep apnoea syndrome (OSAS). The role of leptin, obestatin and apelin still needs to be established. Material/Methods Ten patients with newly diagnosed OSAS (AHI >10/h and ESS >10 points) were enrolled in the study as well as ten healthy volunteers as controls. All underwent measurements for Leptin, Obestatin and Apelin in four hour intervals during diagnostic polysomnography for 24 h and the patients also three months after onset of CPAP treatment. Furthermore the HOMA-index and body composition were quantified. Results Plasma apelin levels in the patients decreased under CPAP therapy, but showed no significant difference in patients and volunteers. We found a positive correlation to AHI, BMI in the therapy group at all observation points. Leptin plasma levels were higher in the patient group and decreased after onset of CPAP therapy. Leptin plasma levels were positively correlated to the BMI, min. 02 and AHI in the patient group before therapy. Plasma obestatin levels did not differ significantly in these three observation groups, but were partly correlated to AHI and weight in the newly diagnosed OSAS group. Conclusions In agreement with previous investigations, we could demonstrate a difference in leptin plasma levels between healthy volunteers and patients with newly diagnosed OSAS. Apelin decreases under CPAP therapy, but not significantly. Obestatin remains unchanged after onset of CPAP. We further found a linkage between leptin plasma levels and BMI, AHI and weight in the untreated patient group.

An auto-continuous positive airway pressure device controlled exclusively by the forced oscillation technique

The forced oscillation technique (FOT) has been demonstrated to be a very sensitive tool for the assessment of upper airway obstruction during nasal continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA). The present study was designed to evaluate the therapeutic efficacy of a novel auto-CPAP device based exclusively on the FOT. Following manual CPAP titration, 18 patients with OSA (mean apnoea/hypopnoea index (AHI) 48.0+/-28.1) were allocated to conventional CPAP and auto-CPAP treatment under polysomnographic control in randomized order. The patients were asked to assess their subjective daytime sleepiness using the Epworth Sleepiness Scale (ESS). The mean AHI during auto-CPAP treatment was 3.4+/-3.4 and was comparable with that obtained during conventional CPAP treatment (4.2+/-3.6). The analysis of sleep architecture, the arousal index (6.6+/-2.1 versus 7.3+/-4.4) or the ESS (5.6+/-1.8 versus 7.3+/-4.4) did not reveal any significant differences. However, the mean CPAP pressure during auto-CPAP treatment (0.84+/-0.26 kPa) and in particular the pressure applied in the lateral body position (0.74+/-0.35 kPa), was significantly lower than that employed in conventional CPAP treatment (0.93+/-0.16 kPa, both comparisons: p<0.05). The auto-continuous positive airway pressure device proved equally as effective as conventional continuous positive airway pressure. However, the mean treatment pressure was significantly reduced, especially when patients were sleeping in the lateral position.

Fluorescein-Aided Confocal Laser Endomicroscopy of the Lung

Background: There are only few reports about confocal laser endomicroscopy (CLE) for pulmonary imaging. In these studies, in contrast to gastrointestinal endoscopy, CLE was performed without fluorescein. Objectives: The aim of the present study was to evaluate the value of fluorescein usage for CLE of the lung. Methods: Fluorescein-aided CLE was performed in 15 consecutively recruited patients and in 4 young healthy volunteers with a miniprobe during flexible bronchoscopy. Before and after intravenous administration of fluorescein, central airways and alveolar structures were evaluated. Results: Fluorescein administration did not permit imaging of epithelial cells in the central airways. In the lung periphery, alveolar walls and partially macrophages could be seen in native imaging, as expected. After administration of fluorescein, alveoli were almost filled with foam in areas with normal lung tissue. The origin of this foam was shown to be artificial. Furthermore, in patients with pathologies of the lung parenchyma, dark neoplastic and inflammatory cells adjacent to the alveolar walls were identified. No relevant side effects of fluorescein administration could be observed. Conclusions: Fluorescein-aided CLE of the lung appeared to be safe and well tolerated. While the lack of staining of cells in the central airways was a major limitation, it permitted analysis of the lung interstitium and alveolar space and thus emerges as a new approach for the in vivo analysis of interstitial lung diseases.