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.

In vivo efficacy of two heated humidifiers used during CPAP-therapy for obstructive sleep apnea under various environmental conditions.

STUDY OBJECTIVES: To investigate the humidification performance-defined as the maximum achievable absolute humidity in the CPAP tube-of two heated humidifier systems (HH) offered as CPAP accessories, as a function of ambient air conditions. DESIGN: In 48 patients undergoing CPAP treatment, temperature (T) and relative humidity (RH) in the distal CPAP tube system were measured, with and without either of the two heated humidifiers A (HH-A, n=23), or B (HH-B, n=25), until a steady state was achieved. At the same time, ambient T and RH in the examination room were recorded. T and RH were used to calculate the absolute humidity (AH). SETTING: University Hospital, Erlangen, Germany. PATICIPANTS: 48 patients with obstructive sleep apnea undergoing CPAP therapy. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Conditions in the examination room during measurement with the HH-A, T = 22.5+2.1 (16.4-26.0) degrees C and AH = 9.3+2.4 (5.3-13.9) g/m3 did not differ significantly from those prevailing during measurements with the HH-B, T = 22.9+1.9 (18.9-26.3) degrees C and AH = 9.9+2.8 (6.2-16.4) g/m3. The mean humidification performance (steady state AH with HH within the CPAP tube) of the HH-A was 23.5+2.9 (19.1-29.9) g/m3, that of the HH-B 26.8+3.9 (21.0-34.4) g/m3. CONCLUSIONS: Under the ambient conditions of humidity and temperature, commonly found in European and North American bedrooms, both HH demonstrate a high humidification performance that even falls within the range recommended for intubated patients. The difference between the two HH is small, and probably not clinical relevant. Thus, it would appear that both HH are suitable for the treatment of dry upper airways under CPAP therapy.

In vivo efficacy of heated and non-heated humidifiers during nasal continuous positive airway pressure (nCPAP)-therapy for obstructive sleep apnoea.

Upper airway dryness is a frequent side-effect of nasal continuous positive airway pressure therapy (nCPAP) in obstructive sleep apnoea (OSA). In this situation, heated or non-heated passover humidifiers are often added to the nCPAP-therapy. The efficacy of these two modes in terms of increasing the absolute humidity of the inspired air in vivo has so far not been established. The present investigation was therefore designed to compare various heated and non-heated passover humidifiers in terms of the their ability to increase the absolute humidity in the inspired air during nCPAP. In six healthy test individuals, nCPAP-therapy at pressures of 5 mbar and 10 mbar was simulated, and the relative humidity and temperature of the air within the tube at the junction between CPAP tube and mask were measured. In each test person, measurements were carried out both with and without the two heated (HC 100, Fischer&Paykel Inc., New Zealand and HumidAire, ResMed Ltd., Australia) and two non-heated (Oasis and Humidifier, both from Respironics Inc., U.S.A.) passover humidifiers under steady-state conditions. The absolute humidity was calculated from the relative humidity and temperature measurements. The mean (SD) absolute humidity (gm(-3)) in the steady-state was significantly (P<0.05 higher with each of the humidifiers than that calculated when no humidifier was used. The relevant figures were as follows: no humidifier: 10(-2) (1.8) gm(-3) (at 5 mbar)/9.8 (1.8) gm(-3) (at 10 mbar); Humidifier: 16.4 (0.97)/15.6 (1.26); Oasis: 17.3 (0.97)/ 16.7 (0.93); HC100: 26.5 (1.40)/26.2 (1.23); HumidAire: 31.8 (2.50)/30.9 (2.64). The mean increase in absolute humidity (in gm(-3)) with the aid of the heated humidifiers was 16.3 (5 mbar) gm(-3)/16.4 (10 mbar) gm(-3) with HC100 and 21.6/21.1 with HumidAire, and in both cases was clearly and significantly (P=0.028) higher in comparison with the non-heated humidifiers--6.2/5.8 with Humidifier and 7.2/6.9 with Oasis. In terms of the absolute humidity achieved within the CPAP tube system, the heated humidifiers were clearly superior to the non-heated humidifiers. These results were, however, obtained under laboratory conditions, and therefore cannot be translated unreservedly to the situation represented by long-term CPAP-treatment. Furthermore, it is possible that the smaller humidification capacity of the non-heated humidifiers may still suffice to meet the requirements of clinical use in terms of effectively preventing dry airways under CPAP treatment. This point, however, needs further investigation on the basis of long-term clinical studies.

Auto-CPAP therapy based on the forced oscillation technique.

Autoadjusting CPAP devices (APAP) are designed to continuously adjust the positive pressure to the required levels, and thus increase treatment quality and patient compliance. The results of APAP treatment strongly depend on the control mechanism of the respective APAP device. In agreement with other working groups, we have recently shown that the forced oscillation technique (FOT) is capable of detecting incipient upper airway obstruction prior to physiological reactions such as the onset of increasing esophageal pressure swings or microarousals. Therefore we studied efficacy and acceptance of a novel APAP device controlled exclusively by FOT. 100 consecutive patients with OSAS confirmed by polysomnography (mean AHI 47.9 +/- 22.6) and daytime sleepiness (Epworth sleepiness scale, ESS 12.6 +/- 3.9) were randomized to either APAP treatment (n = 50) or conventional CPAP treatment (n = 50). Polysomnographies were performed at the second treatment night and subjective sleepiness (modified ESS) was established in the morning. The respiratory disturbance was largely normalized in both treatment groups in the second treatment night (AHI 4.7 +/- 5.3 vs. 3.7 +/- 3.4; n.s.). Both groups showed largely improved sleep profiles and had markedly reduced ESS-scores (6.6 +/- 3.6 vs. 7.0 +/- 3.4; n.s.). The mean treatment pressure during APAP was significantly lower than during CPAP treatment (6.0 +/- 2.0 vs. 9.0 +/- 1.8 mbar; p < 0.001). There were no significant differences between APAP and CPAP treatment in any parameter of efficacy or acceptance. APAP treatment with this device controlled exclusively by FOT is well accepted by the patients and permits an adequate treatment of OSAS without the need for invidiual CPAP titration.

Melatonin and omentin: influence factors in the obstructive sleep apnoea syndrome?

The incidence of the obstructive sleep apnoea syndrome (OSAS) is rising as it is often associated with obesity. Actually, the adipose tissue is working as an endocrine organ with complex interactions. Recently, many adipokines such as omentin-1 were discovered. The role of omentin-1 in the pathogenesis of OSAS has not been clearly determined. Melatonin has a known influence on the sleep and wake rhythm. The data on the involvement of melatonin in OSAS are rare. Therefore we evaluated the changes in plasma levels of omentin-1 and melatonin before and after continuous positive airway pressure (CPAP) therapy in OSA patients. 10 patients with newly diagnosed OSAS were included in the study. They underwent diagnostic polysomnography with blood drawings in a 2 hour interval for 24 hours. In the second night sufficient CPAP therapy was established. After three months of CPAP therapy the measurements were repeated. As controls 10 healthy volunteers were recruited. The same blood analysis and a polygraphic measurement were made and compared with the patients. OSA patients showed significantly higher omentin-1 plasma levels (17.22±13.94 versus 9.24±4.85 ng/ml, p<0.05). After three months of therapy the plasma levels of omentin-1 decreased toward the values observed in the controls at 8.00 a.m. Melatonin showed the usual peak at 2.00 a.m. in the volunteer group. OSA patients showed a later peak of melatonin at 6.00 a.m. which returned to 2.00 a.m. after CPAP therapy. We conclude that omentin as well as melatonin seem to be involved in pathogenesis of OSAS. To what exent, further studies will have to face that question.

Review article: in vivo imaging by endocytoscopy.

BACKGROUND: Endocytoscopy (EC) enables in vivo microscopic imaging at 1400-fold magnification, thereby allowing the analysis of mucosal structures at the cellular level. In contrast to fluorescence imaging with confocal laser endomicroscopy which allows analysis of mucosal structures up to 250 µm in depth, EC is based on the principle of contact light microscopy and only allows visualisation of the very superficial mucosal layer. AIM: To systematically review the feasibility and diagnostic yield of EC for in vivo diagnosis of diseases. METHODS: A systematic search of the literature on diagnostic interventions in the gastrointestinal tract using EC was performed by searches in MEDLINE, Current Contents, PubMed, cross-references and references from relevant articles using the search terms 'endocytoscopy', 'endocytoscope', 'magnification endoscopy', 'endocytoscopic imaging', 'virtual histology' and 'optical biopsy'. Only full manuscripts and case reports published in English were included. RESULTS: Overall twenty-nine relevant reports were identified. EC was feasible to detect oesophageal squamous cell cancer with sensitivity, specificity and accuracy of 95%, 84% and 82%, respectively. Moreover, EC reached excellent sensitivity and specificity for in vivo diagnosis of colon polyps (91% and 100%, respectively). Other diagnostic applications of EC included diagnosis of Barrett's oesophagus, Helicobacter pylori, coeliac disease and small cell lung cancer. No serious complications of EC have yet been reported. CONCLUSIONS: Endocytoscopy is a safe and effective new endoscopic imaging technique to obtain in vivo histology and guided biopsies with high diagnostic accuracy. Therefore, endocytoscopy has the potential to facilitate both diagnosis and patient management.

[69 year-old patient with opaque hemithorax on the right side]. / 69-jähriger Patient mit weissem Hemithorax rechts.

Liposarcomas are the most common sarcomas in adults. Mediastinal occurrence is very rare. We report on a 69 year-old man with a huge tumor in the right pleural cavity leading to a complete atelectasis of the right lung. The tumor could be completely resected. Histology showed a well-differentiated liposarcoma of the mediastinum. One year after resection there was no evidence for local recurrence or metastatic spread.

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 > or =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.

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.

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.

[A humidification system for CPAP therapy in obstructive sleep apnea--evaluation of the effectiveness in changing climatic environmental conditions]. / Ein Befeuchtersystem für die CPAP-Therapie bei obstruktiver Schlafapnoe--Evaluierung der Leistungsfähigkeit bei wechselnden klimatischen Umgebungsbedingungen.

OBJECTIVE: Upper airway dryness is a frequent side-effect of nasal continuous positive airway pressure (nCPAP) therapy in obstructive sleep apnoea syndrome (OSA). In this situation, heated humidification is often used. Therefore, the present study aimed to investigate the humidification performance--defined as the maximum achievable humidity in the tube system of the CPAP device--of a heated humidifier (HH) offered as CPAP accessories, as a function of ambient air conditions (humidity and temperature). PATIENTS AND METHODS: In 30 patients (22 male, 8 female, mean age 56.4 +/- 11.7 years) with OSA undergoing CPAP treatment, temperature (T) and relative humidity (RH) in the CPAP tube system were measured, with and without the HH Somnowave, until a steady state was achieved. At the same time, ambient T and RH in the examination room were recorded. T and RH were used to calculate the absolute humidity (AH). RESULTS: The conditions of the examination room during the examination nights were as follows: T = 21.9 +/- 2.8 degrees C (15.2-26.9), RH 46.5 +/- 11.9% (21.7-69.1) and AH 9.2 +/- 3.2 g/m3 (3.7-16.7). The steady state AH without HH was 9.6 +/- 3.0 g/m3 (4.1-15.4), that with HH (humidification performance) 23.2 +/- 2.8 g/m3 (19.1-29.9) (p < 0.001). CONCLUSION: Under the ambient conditions of humidity and temperature, commonly found in European bedrooms, the HH demonstrate a high humidification performance. Thus, it would appear that the HH is suitable for the treatment of dry upper airways under nCPAP therapy.

Reproducibility of a standardized titration procedure for the initiation of continuous positive airway pressure therapy in patients with obstructive sleep apnoea.

BACKGROUND: Manual titration of continuous positive airway pressure (CPAP) under polysomnographic control is the method most commonly employed to establish the minimal effective pressure (P(eff)) for the treatment of the obstructive sleep apnoea syndrome (OSA). To date, however, the reproducibility of P(eff) titrated in this way has not been investigated in any detail. OBJECTIVES: The present study aims to establish the reproducibility of P(eff) determined by manual titrations of CPAP under polysomnographic control in the sleep lab. METHODS: In a group of 50 patients (5 women), with a mean (SD) apnoea-hypopnoea index of 39.3 (21.8), apnoea index of 28.1 (20.9) and oxygen desaturation index of 39.3 (22.6), with newly diagnosed OSA, manual titration of CPAP was performed on two consecutive nights using the following standard titration protocol: starting at 4 mbar, CPAP was increased by steps of 1 mbar at intervals of at least 5 min, until no signs of airway obstruction could be seen, and arousals were no longer elicited. When no airway obstruction was detected over a period of 30 min, the pressure was lowered once during the night in steps of 1 mbar at intervals of at least 10 min, until obstructive events reappeared, whereupon the pressure was again increased as described above, until, once more, no signs of airway obstruction and no arousals occurred. The second titration was carried out in a blind manner, that is the lab technician did not know the results of the first pressure titration. RESULTS: The mean (SD) P(eff) for all titrations was 8.1 mbar (2.9). A high level of correlation was found between the P(eff) titrated on the first night and that titrated on the second night (Spearman correlation coefficient = 0.89). In a few individual cases, however, differences of up to 3 mbar were found between P(eff) on the first night and P(eff) on the second night. On average, the P(eff) measured on the second night was 0.5 mbar (SD = 1.3, range: -2.0 to 3.0 mbar) higher than that of the first night. CONCLUSIONS: With standardization of the manual titration of CPAP, P(eff) is readily reproducible. In individual cases, however, a difference of as much as 3.0 mbar between the two titrations is possible.

Sensitivity of a simplified forced oscillation technique for detection of upper airway obstruction.

The sensitivity of a simplified variant of forced oscillation technique (FOT) was studied for assessment of dynamic upper airway obstruction during nasal continuous positive airway pressure (nCPAP) therapy for obstructive sleep apnoea (OSA). The airway impedance P[FOT] was measured by FOT and the oesophageal pressure (P(oes)) was recorded during stable stage II sleep in 11 patients with OSA. The CPAP level was initially set high enough to completely abolish upper airway obstruction. To induce gradually increasing upper airway re-obstruction, the CPAP pressure was then lowered stepwise. Thirty six such manoeuvres were analysed, blind, to define the first inspiration at which upper airway re-obstruction was detectable by analysis of P[FOT](t(FOT)) and by P(oes)(t(oes)), respectively. On seven occasions t(FOT) and t(oes) occurred together, in the remaining 29 cases t(FOT) preceded t(oes) with a mean latency of 6.0+/-7.7 (0-32) breath cycles. In no case did t(oes) preceed t(FOT). FOT is a highly sensitive tool for the assessment of incipient upper airway obstruction during nCPAP therapy.

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 x 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 <30 kg x 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.