The obstructive sleep apnea syndrome is typically associated with conditions known to increase insulin resistance as hypertension, obesity, and diabetes. We investigated whether obstructive sleep apnea itself is an independent risk factor for increased insulin resistance and whether continuous positive airway pressure (CPAP) treatment improves insulin sensitivity. Forty patients (apnea-hypopnea index > 20) were treated with CPAP. Before, 2 days after, and after 3 months of effective CPAP treatment, hyperinsulinemic euglycemic clamp studies were performed. Insulin sensitivity significantly increased after 2 days (5.75 +/- 4.20 baseline versus 6.79 +/- 4.91 micromol/kg.min; p = 0.003) and remained stable after 3 months of treatment. The improvement in insulin sensitivity after 2 days was much greater in patients with a body mass index less than 30 kg/m2 than in more obese patients. The improved insulin sensitivity after 2 nights of treatment may reflect a decreasing sympathetic activity, indicating that sleep apnea is an independent risk factor for increased insulin resistance. The effect of CPAP on insulin sensitivity is smaller in obese patients than in nonobese patients, suggesting that in obese individuals insulin sensitivity is mainly determined by obesity and, to a smaller extent, by sleep apnea.

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 at baseline 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 v30 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. Eur Respir J 2003; 22: 251-257 Obstructive sleep apnoea (OSA) is a common disorder affecting 2-4% of the adult population [1]. OSA is strongly associated with obesity. In a recent study involving 773 patients with OSA, only 6.5% had a normal body mass index (BMI), while 75.2% were obese (BMIo30 kg?m -2 ) [2]. Patients with OSA appear to be more likely to put on weight than equally obese subjects without OSA [3]. The mechanisms underlying this phenomenon remain obscure. Recently, a number of authors have speculated that changes in serum leptin levels or leptin-receptor insensitivity may be involved in the pathogenesis of progressive obesity in patients with OSA [4]. Leptin has been found to reduce appetite and simultaneously to increase respiratory drive in an animal model [5,6]. In humans, the situation may be expected to be more complicated. In recent studies, fasting leptin levels in patients with OSA decreased after initiation of continuous positive airways pressure (CPAP) treatment [7,8]. However, those leptin measurements were performed on awake individuals in the morning, when the respiratory situation was normalised, so that any linkage between leptin levels and respiratory effects is difficult in this setting. Furthermore, leptin levels are influenced by a multitude of factors, such as sex, body weight [9,10], the presence of hypertension, or specific medications impacting on leptin levels. Diurnal and ultradian variations in serum leptin levels are further factors complicating profound insights concerning significant respiratory effects [11][12][13].However, the finding that a hormone like leptin is able to cover a variety of biological functions, beyond its well-investigated role for the regulation of body weight and energy expenditure, also prompted the present aut...

Background: Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects with chemotherapy. Effects might be even stronger after immune-checkpoint-inhibitor (ICI) therapy. The purpose of this analysis was to evaluate the efficacy of ramucirumab plus docetaxel (R + D) as third-line treatment after failure of a first-line platinum-based chemotherapy and a second-line ICI treatment in patients with non-small-cell lung cancer (NSCLC) stage IV. Methods: Retrospective data were collected from 9 German thoracic oncology centers. Only patients who had received at least 1 cycle of third-line R + D were included. The numbers of cycles, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were investigated. Results: Sixty-seven patients met the criteria for inclusion. Third-line treatment with R + D achieved an ORR of 36% and a disease control rate (DCR) of 69%. Median PFS for third-line therapy was 6.8 months with a duration of response (DOR) of 10.2 months. A median OS of 29 months was observed from the start of first-line therapy with a median OS of 11.0 months from the start of third-line treatment. No unexpected toxicities occurred. Conclusion: R + D is a highly effective and safe third-line treatment after failure of second-line programmed cell death protein 1/programmed cell death-ligand 1 (PD1/PD-L1)-derived ICI therapy irrespective of NSCLC histology. As there may be synergistic effects of second- and third-line treatments, this sequence is a very suitable option for patients not treated with first-line ICI. In addition, R + D should continue to be investigated as a second-line treatment option after failure of chemotherapy plus ICI in the palliative first–line treatment.

Background-Auto-CPAP machines used in the treatment of obstructive sleep apnoea (OSA) are designed to vary the treatment pressure automatically in order always to apply the actually needed pressure. Consequently they should be able to achieve at least identical therapeutic effects as conventional constant pressure CPAP with a lower mean treatment pressure. The present study was designed to evaluate the therapeutic eYcacy and the treatment pressure of an auto-CPAP machine (REM+auto ® , SEFAM) in comparison with a conventional CPAP device. Methods-Following CPAP titration, 16 patients with OSA were allocated to receive conventional CPAP and auto-CPAP treatment under polysomnographic control in a randomised order. After each treatment the patients were asked to assess the therapy using a questionnaire; a vigilance test was also carried out and subjective daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). 2)). The vigilance test showed normal values after both treatments in all patients with no significant diVerences. The mean pressure during auto-CPAP treatment (8.1 (2.9) mbar), however, was significantly higher than that employed in conventional CPAP treatment (7.6 (2.7) mbar; mean diVerence 0.5 mbar; 95% CI 0.1 to 0.9 mbar; p<0.05). Conclusions-Auto-CPAP was equally as eVective as conventional CPAP with respect to therapeutic eYcacy. The aim of reducing the treatment pressure with auto-CPAP, however, was not achieved. (Thorax 1998;53:643-648) Results-The

Background: Chemotherapy plus immune-checkpoint inhibitor (CTx+ICI) therapy has become the preferred 1st line treatment in patients with metastatic NSCLC without oncogenic driven mutations.However, the optimal subsequent 2nd line treatment is not defined and several alternatives exist. The purpose of this analysis was to evaluate the efficacy of 2nd line docetaxel plus ramucirumab (D+R) initiated after failure of 1st line CTx+ICI.Methods: Retrospective data were collected during routine care from German thoracic oncology centers.Only patients who had received at least one course of 2nd line D+R were included. ORR, PFS, OS and numbers of courses of D+R were investigated with PFS after initiation of D+R being the primary endpoint.Results: Seventy-seven patients met the inclusion criteria. 2nd line treatment with D+R achieved an ORR and DCR of 32.5% and 62.4%, respectively. Median PFS for 2nd line therapy was 3.9 months with a DOR of 6.4 months. Median OS of 15.5 and 7.5 months were observed from the start of 1st line therapy and 2nd line treatment, respectively. No unexpected toxicities occurred. Presence of KRAS mutations was associated with significantly worse median PFS to D+R (2.8 vs. 4.5 months in wild-type cases; P=0.021) and was an independent predictor of inferior PFS in multivariate analysis.Conclusions: D+R is an effective and safe 2nd line treatment after failure of 1st line CTx+ICI irrespective of NSCLC histology. However, patients with a KRAS mutation did not benefit from D+R in terms of PFS

Upper airway dryness is a frequent side-effect of nasal continuous positive airway pressure (nCPAP) therapy in obstructive sleep apnoea (OSA). In this situation, heated humidification is often used. Alternatively, oily nose drops are frequently applied to relieve dryness. The present study aimed to investigate the efficacy of a heated humidifier in comparison with oily nose drops. Twenty-four OSA patients complaining of serious nCPAP-related upper airway dryness were randomized to 6 weeks of treatment either with heated humidification (HC 100, Fischer & Paykel, Inc., Auckland, New Zealand) or oily nose drops (Colda-Stop, Desitin, Inc., Germany). The patients completed questionnaires on the degree and frequency of upper airway dryness, compliance with nCPAP, intention to terminate nCPAP and comfort during the nCPAP therapy. All 12 patients treated with heated humidification improved in terms of the degree and frequency of upper airway dryness, and reported greater comfort when using the nCPAP device. All patients in the heated humidification group intending to terminate nCPAP therapy because of upper airway dryness persisted with nCPAP on addition of humidification. In contrast, only five out of 12 patients (42%) in the oily nose drops group reported their degree of upper airway dryness to be improved (P = 0.003), only three patients (25%) reported an improvement in the frequency of upper airway dryness (P < 0.001), and only five patients (42%) reported greater comfort when using the nCPAP device with oily nose drops (P < 0.001). In the group using oily nose drops none of the three patients who intended to terminate nCPAP therapy persisted with nCPAP. Heated humidification is highly effective and superior to oily nose drops in reducing the symptoms of upper airway dryness during nCPAP.

The prognostic role of estrogen receptors in lung cancer is not validated. Results from patients with early stage non-small lung cancer patients indicate a prognostic role of estrogen receptor 1 (ESR1) mRNA expression in these patients. Automated RNA extraction from paraffin and RT-quantitative PCR was used for evaluation of tumoral ESR1 and progesterone receptor (PGR) mRNA expression. The test cohort consisted of 31 patients with advanced or metastatic non-small cell lung cancer (NSCLC) patients, treated in a first-line registry trial. For validation, 53 patients from a randomized multicentre first-line study with eligible tumor samples were evaluated. There was no significant correlation of ESR1 expression with clinical characteristics. ESR1 high expression was of significant positive prognostic value in the training set with a median overall survival (OS) of 15.9 versus 6.2 months for high versus low ESR1 expression patients (p 5 0.0498, HR 0.39). This could be confirmed in the validation cohort with a median OS of 10.9 versus 5.0 months in ESR1 high versus low patients, respectively (p 5 0.0321, HR 0.51). In the multivariate analysis adjusted for histological subtype, gender, age and performance status, ESR1 expression remained an independent prognostic parameter for survival in both cohorts. In contrast to ESR1, PGR expression was not able to separate prognostic groups or to predict outcome significantly (for OS; p 5 0.94). Our study shows that ESR1 mRNA as assessed by qPCR represents a reliable method for detecting ESR1 expression in NSCLC and that ESR1 expression is an independent prognostic factor in metastatic NSCLC.In advanced non-small cell lung cancer (NSCLC), encouraging efforts were achieved in the last years towards individualized and targeted therapies by identification of driver mutations and predictive biomarkers. Meanwhile, EGFR tyrosine kinase inhibitors are standard of care in patients with activating epidermal growth factor receptor (EGFR) mutations, 1,2 leading to significant increase in response rates, quality of life and progression-free survival (PFS) by improvement of side effects. Recently, EML4-ALK translocations were identified in a small subset of patients with adenocarcinoma of the lung, and this lead to approval of crizotinib, a drug targeting this translocation, in a very short period of time.3 Nevertheless, despite this encouraging development in targeted therapies, for the majority of patients yet there are no approved targetable genetic alterations identified. Therefore, it is of utmost importance to identify new targets for individualized therapy in metastatic lung cancer. The estrogen receptor (ER) is a prototype of a predictive biomarker and its expression in breast cancer is an established guide for antihormonal anticancer treatment. In lung cancer, the sex hormone receptor family is far less extensively explored. However, there are clinical data that give hints about an involvement in this entity as well. Fu et al.4 could demonstrate that significantly more pre-menopausa...

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.