[The Road to Discovery of the Pulmonary Gas Exchange - From the "Phlogiston-" to the "Oxygen Theory"]. / Der Weg zur Entdeckung des pulmonalen Gasaustausches.

The discovery of oxygen and pulmonary gas exchange was a major advancement in our understanding of breathing. For centuries it was believed that the lungs were primarily necessary to cool the heart or to "refine" the blood. Richard Lower (1631-1691) observed that the blood had a different colour before and after passage through the lung. His assumption was that breathing must have been added a special substance to the blood. Georg Ernst Stahl (1660-1734) formulated a fire substance "phlogiston" (phlox = flame) with his phlogiston theory. He postulated that phlogiston is contained in all combustible substances and escapes when burned. John Mayow (1641-1679) recognised that about one fifth of the breathing gas is important for the breathing process. He called the gas "spiritus nitro aerius". Oxygen was first discovered in the early 1770 s by the Swedish-German pharmacist Carl Wilhelm Scheele (1742-1786) and the English chemist Joseph Priestley (1733-1804) - independently of each other. Antoine-Laurent Lavoisier (1743-1794) recognised oxygen as element and for the first time described the oxidation process accurately.

High Plasma Cystine Levels Are Associated with Blood Pressure and Reversed by CPAP in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) independent of obesity (OBS) imposes severe cardiovascular risk. To what extent plasma cystine concentration (CySS), a novel pro-oxidative vascular risk factor, is increased in OSA with or without OBS is presently unknown. We therefore studied CySS together with the redox state and precursor amino acids of glutathione (GSH) in peripheral blood mononuclear cells (PBMC) in untreated male patients with OSA (apnea-hypopnea-index (AHI) > 15 h-1, n = 28) compared to healthy male controls (n = 25) stratifying for BMI ≥ or < 30 kg m-2. Fifteen OSA patients were reassessed after 3-5-months CPAP. CySS correlated with cumulative time at an O2-saturation <90% (Tu90%) (r = 0.34, p < 0.05) beside BMI (r = 0.58, p < 0.001) and was higher in subjects with "hypoxic stress" (59.4 ± 2.0 vs. 50.1 ± 2.7 µM, p < 0.01) defined as Tu90% ≥ 15.2 min (corresponding to AHI ≥ 15 h-1). Moreover, CySS significantly correlated with systolic (r = 0.32, p < 0.05) and diastolic (r = 0.31, p < 0.05) blood pressure. CPAP significantly lowered CySS along with blood pressure at unchanged BMI. Unexpectedly, GSH antioxidant capacity in PBMC was increased with OSA and reversed with CPAP. Plasma CySS levels are increased with OSA-related hypoxic stress and associated with higher blood pressure. CPAP decreases both CySS and blood pressure. The role of CySS in OSA-related vascular endpoints and their prevention by CPAP warrants further studies.

[Control of Respiratory Symptoms During Sleep in Patients with Stable Bronchial Asthma]. / Nächtliche Symptomkontrolle bei Patienten mit stabilem Asthma bronchiale.

INTRODUCTION: Awareness of respiratory symptoms during day- and night-time is important for asthma control. Acoustic long-term recording offers a possibility to monitor symptoms objectively. In this prospective observational study frequency of night-time cough and wheezing was evaluated in patients with stable asthma. METHODS: Night-time cough and wheezing were monitored by LEOSound lung sound monitor in 40 patients with stable asthma. Patients did not complain of respiratory problems during day- and nighttime, asthma control test was 23 points on average. FEV1 was 84 ±â€Š15 %; MEF 50 71 ±â€Š27 % and Rtot 0,48 ±â€Š0,18 kPas/l. The age of the patients was 35 ±â€Š11 years. All patients had an antiobstructive and/or anti-inflammatory medication. The present study focuses on description of frequency, severity and characteristics of night-time symptoms like cough and wheezing in patients with stable asthma and tries to depict differences in patients who present cough or wheezing. RESULTS: Wheezing was monitored in 2 of the 40 patients. In the first patient duration of wheezing was 19 min, in the second 55 min. Lung function in patient 1 showed a moderate bronchial obstruction, he was still smoking. Patient 2 was a non-smoker with a significant bronchial obstruction (FEV1 49 %; MEF 50 27 % and Rtot 0,52 kPas/l). In 26 patients there was no coughing, 14 patients had 4 ±â€Š3 (2 - 13) cough epochs during the night. By dividing the collective in two groups differentiated by the presence of cough/ no cough we found no significant differences regarding lung function and ACT-scores. Both patients with night-time wheezing presented low ACT- Scores (20 and 21 points). CONCLUSIONS: Nocturnal wheezing and cough episodes were detectable in 2 respectively 14 patients with stable asthma. Long-term recording of normal and adventitious breath sounds offers a practical opportunity to evaluate night-time cough and wheezing objectively.

Description of nighttime cough epochs in patients with stable COPD GOLD II-IV.

PURPOSE: Chronic cough is one of the main symptoms of COPD. Ambulatory objective monitoring provides novel insights into the determinants and characteristics of nighttime cough in COPD. MATERIALS AND METHODS: Nighttime cough was monitored objectively by LEOSound lung sound monitor in patients with stable COPD II-IV. In 30 patients, with 10 patients in each stage group, nighttime cough was analyzed for epoch frequency, epoch severity (epoch length and coughs per epoch), and pattern (productive or nonproductive). RESULTS: Cough was found in all patients ranging from 1 to 294 events over the recording period. In 29 patients, cough epochs were monitored, ranging from 1 to 75 epochs. The highest amount of cough epochs was found in patients with COPD stage III. Active smokers had significantly more productive cough epochs (61%) than nonsmokers (24%). CONCLUSION: We found a high rate of nighttime cough epochs in patients with COPD, especially in those in stage III. Productive cough was predominantly found in patients with persistent smoking. LEOSound lung sound monitor offers a practical and valuable opportunity to evaluate cough objectively.

Long-term Recording of Night-Time Respiratory Symptoms in Patients with Stable COPD II-IV.

INTRODUCTION: Night-time respiratory symptoms have a considerable impact on sleep and life quality in patients with chronic obstructive pulmonary disease (COPD). Lack of awareness of night-time symptoms can lead to worsened COPD control. Automated long-term monitoring of respiratory symptoms with LEOSound enables assessment of nocturnal wheezing and cough. METHODS: In this observational study we investigated the prevalence and severity of cough and wheezing in patients with stable COPD [Global Initiative for Chronic Obstructive Lung Disease (GOLD) II-IV] disease for two consecutive nights with the LEOSound system. 48 patients (30 males, 63%) were eligible for inclusion, median age was 67 years, and body mass index (BMI) was 25.3 kg/m2. RESULTS: In 15 out of 48 patients (31%), we found wheezing periods for at least 10-minute duration. Wheezing periods >30 minutes were monitored in seven patients and wheezing periods >60 minutes were monitored in three patients. The maximum duration of wheezing was 470 minutes in one patient with COPD II. The median wheezing rate differed between the COPD stages and between active and non-active smokers. Cough was found in 42 patients (87.5%) with a range of 1-326 events. The cough-period-index in night one was 0.83 n/hour (P25:0.33||P75: 2.04) and night two 0.97 n/hour (P25:0.25||P75: 1.9). Most of the cough events were non-productive with a median of 0.86. CONCLUSIONS: Night-time symptoms are common in COPD patients. LEOSound offers an opportunity to evaluate objectively night-time symptoms like wheezing and cough in patients with COPD which remain otherwise unnoticed. We found a high incidence of night-time wheezing in these patients, which was related to persistant smoking.

Age-related differences in skeletal muscle microvascular response to exercise as detected by contrast-enhanced ultrasound (CEUS).

BACKGROUND: Aging involves reductions in exercise total limb blood flow and exercise capacity. We hypothesized that this may involve early age-related impairments of skeletal muscle microvascular responsiveness as previously reported for insulin but not for exercise stimuli in humans. METHODS: Using an isometric exercise model, we studied the effect of age on contrast-enhanced ultrasound (CEUS) parameters, i.e. microvascular blood volume (MBV), flow velocity (MFV) and blood flow (MBF) calculated from replenishment of Sonovue contrast-agent microbubbles after their destruction. CEUS was applied to the vastus lateralis (VLat) and intermedius (VInt) muscle in 15 middle-aged (MA, 43.6±1.5 years) and 11 young (YG, 24.1±0.6 years) healthy males before, during, and after 2 min of isometric knee extension at 15% of peak torque (PT). In addition, total leg blood flow as recorded by femoral artery Doppler-flow. Moreover, fiber-type-specific and overall capillarisation as well as fiber composition were additionally assessed in Vlat biopsies obtained from CEUS site. MA and YG had similar quadriceps muscle MRT-volume or PT and maximal oxygen uptake as well as a normal cardiovascular risk factors and intima-media-thickness. RESULTS: During isometric exercise MA compared to YG reached significantly lower levels in MFV (0.123±0.016 vs. 0.208±0.036 a.u.) and MBF (0.007±0.001 vs. 0.012±0.002 a.u.). In the VInt the (post-occlusive hyperemia) post-exercise peaks in MBV and MBF were significantly lower in MA vs. YG. Capillary density, capillary fiber contacts and femoral artery Doppler were similar between MA and YG. CONCLUSIONS: In the absence of significant age-related reductions in capillarisation, total leg blood flow or muscle mass, healthy middle-aged males reveal impaired skeletal muscle microcirculatory responses to isometric exercise. Whether this limits isometric muscle performance remains to be assessed.

[Is daytime sleepiness a sufficient predictor of sleep-disordered breathing during pre-anesthesia consultation?]. / "Tagesschläfrigkeit" als Prädiktor für schlafbezogene Atmungsstörungen (SBAS)--ist eine präoperative Evaluation sinnvoll?

BACKGROUND: Sleep-disordered breathing (SDB) is associated with increased rate of perioperative complications. Daytime sleepiness is a frequent symptom of SDB. Thus, aim of the present study was to evaluate whether preoperative assessment of daytime sleepiness would be eligible for sufficient prediction of SDB. METHODS: Patients before scheduled surgery were prospectively recruited and asked to answer a standardized sleep questionnaire (Epworth Sleepiness Scale; ESS). The night before surgery, sleep polygraphy was performed and the oxygen desaturation index 4% (ODI 4%) was calculated. RESULTS: Data of 363 patients (190 men and 173 women) were finally analyzed. Regarding risk assessment, 42 patients had ASA grade 1, 192 patients had ASA grade 2, 123 patients had ASA grade 3 and 6 patients had ASA grade 4. Mean Body Mass Index was 27.9 ± 5.1 kg/m2, mean age was 59.2 ± 13.3 years and mean ESS score was 5.7 ± 3.4. Clinical relevant daytime sleepiness (ESS ≥ 11) was found in 32 patients (9%). In 11 patients (34%) with ESS ≥ 11, ODI 4% ≥ 5/h was calculated whereas in 21 patients with ESS ≥ 11 (66%), ODI 4% < 5/h was found. Odds ratio between ODI 4% ≥ 5/h and ESS ≥ 11 was 0.919 (CI 0.85-0.99, p = 0.038). CONCLUSION: In non-obese patients, daytime sleepiness is a rare event and is not associated with SDB. Thus, daytime sleepiness is not eligible for the preoperative SDB screening.

[Sleep disordered breathing and nonsustained ventricular tachycardia in patients with chronic heart failure]. / Schlafbezogene Atmungsstörungen und maligne ventrikuläre Arrhythmien bei Patienten mit chronischer Herzinsuffizienz.

BACKGROUND: Patients with chronic heart failure (CHF) have a high incidence of sleep disordered breathing (SDB). It is assumed that patients with the combination of CHF and SDB have more ventricular couplets and nonsustained ventricular tachycardia (NSVT) than patients without SDB. METHODS: In 63 patients, 49 men and 14 women with chronic heart failure (EF < 45%), all-night polysomnography and long-term-ECG were performed. Mean age was 59 ± 15 years, mean BMI 27 ± 5 kg/m(2). 56% had an ischemic, 44% a nonischemic heart disease. 51% had heart insufficiency classification NYHA III. RESULTS: 42 of the 63 patients (67%) had sleep disordered breathing (SDB) with an AHI ≥5/h. In 24 patients (38%) SDB was central, in 18 (29%) obstructive. More patients with SDB than patients without SDB had NSVT (50% vs. 19%). Nocturnal frequency of NSVT in patients with SDB was about twice as high as the rate observed during daytime (0.48/h vs. 0.21/h). In patients without SDB there was no relevant difference between day and night (0.23/h vs. 0.21/h). AHI correlated with NSVT (r = 0.329, p < 0.01). Day/night comparison of couplets was 2.3/h vs. 1.9/h in SDB patients and 2.0/h vs. 1.6/h in patients without SDB. CONCLUSIONS: Patients with chronic heart failure have a high prevalence of SDB. The combination of CHF and SDB predisposes for nocturnal malignant ventricular arrhythmias.