[From "processing" and "fermentation" to oxidative metabolism]. / Über "Kochung" und "Gärung" zum oxidativen Stoffwechsel.

The theory of the four humors or humorism (Hippocrates of Kos) viewed disease as an imbalance of the humors. Galen of Pergamon further developed the theory by describing digestion as a sequence of chemical reduction processes that convert into the various humours. Theophrastus von Hohenheim attempted to overcome humorism in the 16th century and establish medicine on a natural-philosophical-alchemical basis. The era of empirical-experimental chemically oriented medicine began with "iatrochemistry" in the 17th century. Franciscus Sylvius' concept of disease is based on an imbalance of acidic and alkaline fermentation. It was Lazarro Spallanzani who understood the digestive processes in the stomach as a chemical dissolution of food. The discovery of oxygen and the process of oxidation by Lavoisier laid the foundation for our understanding the physiology of metabolism.

[The upper airway in obstructive sleep apnea patients is pathological even when awake]. / Der obere Atemweg bei OSA-Patienten ist auch im Wachzustand pathologisch.

Obstructive sleep apnea (OSA) is characterized by partial or complete obstruction of the pharyngeal airway. Anatomical factors can be distinguished from non-anatomical factors. Age and obesity are the main risk factors for OSA; however, approximately 50% of patients are not obese. In older patients (>60 years), the importance of obesity decreases. There is an increased prevalence of OSA among patients with normal weight. The effects of chronic intermittent hypoxemia, low-grade inflammation, increased sympathetic tone and mechanical stress contribute to a transformation of muscle fibers in the upper airway, resulting in reduced muscle mass and strength. Less frequently encountered non-anatomical factors include decreased muscle tone, increased arousal threshold, and altered sensitivity of CO2 chemoreceptors.

[Sleep disorders in patients with chronic tinnitus]. / Schlafstörungen bei Patienten mit chronischem Tinnitus.

Tinnitus has a lifetime prevalence of 25% in Germany. A common comorbidity in chronic cases are sleep disorders. The aims of this study were to detect sleep disorders and to identify possible associations with tinnitus parameters.Fifty patients with chronic tinnitus were recruited. The patients underwent audiometry, polysomnography, and completed standardised questionnaires on tinnitus and sleep behaviour.Data were available in 30 men and 9 women (age 50.2 ± 11 y, BMI 28.8 ± 4.4 kg/m²). The median duration of tinnitus was 36 (9; 120) months with a severity score of 2.00 (1.00; 3.00). The mean Tinnitus Questionnaire (TF) score was 43.6 ± 17.1, the Epworth Sleepiness Scale (ESS) score was 8.41 ± 4.27, the Pittsburgh Sleep Quality Index (PSQI) score was 9.21 ± 4.32, and the Screening Scale for Chronic Stress (SSCS) score was 58.13 ± 9.58.Sleep diagnoses included 18 cases of insomnia, 4 cases of RLS, and 11 cases of OSA. Patients with sleep comorbidities showed higher tinnitus severity, PSQI scores, and body weight compared to those without sleep disorders.Worse sleep quality was associated with higher tinnitus severity (p=0.038) and more disruptive tinnitus (p=0.03). Patients with subjectively highly disruptive tinnitus reported higher chronic stress scores. Tinnitus duration was correlated with OSA-severity (p=0.026).More than two-thirds of tinnitus patients showed sleep disorders as comorbidity. A sleep screening appears useful in cases of increased tinnitus severity. Whether CPAP therapy is helpful in reducing tinnitus symptoms could not be conclusively determined but deserves further attention.

[The search for the "node of life": breathing regulation]. / Die Suche nach dem "Knoten des Lebens" ­ die Atemregulation.

The article provides a historical overview of developments in the understanding of respiratory rhythm and its control mechanisms over the last two centuries. In the 19th century, a structure in the medulla oblongata was first described as the "node of life". In 1743, Taube discovered the carotid body, and in 1927 the Spaniard de Castro described its morphology and innervation. It was only with the work of father and son Heymans that the physiological and pharmacological significance of the carotid and aortic body was recognized. Today we understand that the generation and control of respiration are mediated by a complex neuronal network in the brainstem. Chemo-, mechano- and proprioreceptos convey information from blood, airways and muscles to the control centre. The respiratory centre integrates the afferent input from the receptors, the autonomic nervous system, the cardiovascular system, and voluntary input from the cerebral cortex to modulate the degree of respiratory activation of motoneurons and respiratory muscles.

[Why you should know the "nose cycle" as a pneumologist and sleep medicine specialist]. / Warum man auch als Pneumologe und Schlafmediziner den "Nasenzyklus" kennen sollte.

The nasal cycle refers to the anticyclic swelling and decongestion of the two nasal cavities that occur during the day and during sleep, while the overall nasal flow remains constant. The nasal cycle was first described by R. Kayser in 1895. Each cycle consists of a working phase and a subsequent resting phase, the purpose of which is the rehydration and regeneration of the mucosa. A nasal cycle occurs in about 70-90% of people. The duration of the phase is affected by age, body position, physical activity, mucociliary clearance and time of day. Typically, the cycle lengthens during sleep. Long-term rhinoflowmetry enables assessment of the circadian course of the alternating cyclic changes of the nasal mucosa.

[In commemoration of Adolf Kussmaul's 200th birthday: Describer of the Kussmaul Breathing and pioneer of endoscopy]. / Zum 200. Geburtstag von Adolf Kussmaul (1822­1902): Beschreiber der Kussmaul-Atmung und Wegbereiter der Endoskopie.

Adolf Kussmaul (1822-1902) studied medicine in Heidelberg. The name Kussmaul is known worldwide for the panarteritis nodosa, the pulsus paradoxus and the venous pulse in callous mediastinopericarditis as well as the high-frequency and deep breathing in diabetic ketoacidosis. Kussmaul was also a pioneer in the endoscopic diagnosis and treatment of diseases of the oesophagus and stomach. He had to close the medical practice he had started in 1850 in the black Forrest town of Kandern after three years, having developed health problems. Kussmaul's approach to his studies was clinical-scientific. In 1855, under the guidance of Virchow, he received his doctorate from the university of Würzburg. From 1859-1888 he held a chair in Erlangen, Freiburg and Strasbourg. He continued working as a physician after retirement at Heidelberg and wrote his memoirs "Jugenderinnerungen eines alten Arztes".

[Adherence to CPAP Three Months after Starting Therapy in 1078 Patients with Obstructive Sleep Apnea (OSA)]. / Therapieadhärenz drei Monate nach Einleitung einer nichtinvasiven CPAP-Therapie bei 1078 Patienten mit obstruktiver Schlafapnoe (OSA).

INTRODUCTION: Nocturnal Continuous Positive Airway Pressure (CPAP) is considered the gold standard treatment for obstructive sleep apnoea (OSA). The CPAP therapy is a long-term treatment but does come with few possible side effects. The adherence to the therapy is frequently suboptimal. In this paper, adherence to therapy was assessed and typical problems were classified. METHODS: 1078 OSA patients received CPAP therapy after a diagnostic polygraphy (PG) or polysomnography (PSG). Adherence to therapy was followed up three months after treatment induction. The following therapy adherence groups were defined: 1. correctly calibrated CPAP and good adherence, 2. CPAP non-acceptance, after initial use, 3. CPAP intolerance use due to side effects, 4. discontinuation due to lack of motivation/low rates of symptoms. 5. mask intolerance, 6. CPAP failure due to a lack of perceived treatment effect, 7. Change to another non-invasive ventilation method, 8. No control carried out. RESULTS: Out of 1078 OSA patients a therapy control was performed in 830 patients (77%). Of these, 450 patients (54.2%) were placed in group 1, 216 patients (26 %) in group 2, 71 patients (8.5 %) in group 3, 35 patients (4.2 %) in group 4, 14 patients (1.7 %) in group 5, 3 patients (0.4 %) in group 6 and 41 patients (4.9%) in group 7. A mild obstructive index, low CPAP pressure and, as a trend, a low Epworth-Sleepiness score were predictors of CPAP failure. No significant predictors could be shown for adherence to therapy. DISCUSSION: An effective treatment use of 54% after 3 months is a suboptimal result. Predictors of CPAP failure were parameters that indicated that the patient was less symptomatic prior to therapy. Despite a large patient cohort, neither anthropometric nor PSG-data provided any significant CPAP adherence predictors. Rather, experiences in the first nights of use could be decisive. CPAP devices offer comfort settings that have to be personalised to patients' needs and wants. A large selection of different mask shapes requires experience and training in patient-centred mask fitting. A three-month follow-up appointment seems too long to discuss therapy problems with the patient in a timely manner. Telemedical options or short-term telephone appointments should be considered.

[Negative-pressure pulmonary edema and alveolar hemorrhage are potentially life-threatening complications of upper airway obstruction]. / "Negativdruck-Lungenödem" und "alveoläre Hämorrhagie" als Komplikationen einer oberen Atemwegsobstruktion.

Negative pressure pulmonary edema and alveolar hemorrhage are potentially life-threatening complications after relief of upper airway obstruction. The laryngeal-pharyngeal obstruction results in high negative intrapleural pressures. The increased intrapleural pressures affect the integrity of the alveolo-capillary membrane due to various factors. This review describes clinical symptoms, etiologic factors, pathophysiology and treatment strategies associated with each of these factors. The aim of this review is to equip clinicians with the knowledge base necessary to identify patients at increased risk for negative pressure pulmonary edema and alveolar hemorrhage.

[Langhans' or Langerhans' cells? - The problem of the eponym]. / Langhans'sche oder Langerhans'sche Zellen? ­ Das Problem des Eponyms.

There is frequent confusion between Theodor Langhans (1839-1915) and Paul Langerhans (1847-1888) in the literature. Theodor Langhans was a German pathologist who discovered and described the "giant cells" with nuclei close to the outer membrane of the tubercles. Today, these cells are called "Langhans' giant cells". The eponym "Langerhans' cells" refers to dendritic cells in the stratum spinosum of the epidermis. Paul Langerhans described these cells for a competition organised by the Berlin Medical Faculty when he was still a student. Most doctors know Paul Langerhans through the first description of the "Langerhans' islet cells" of the pancreas. Langerhans died of tuberculosis at the age of 40 after a long exile on the island of Madeira.

Acoustic Monitoring of Night-Time Respiratory Symptoms in 14 Patients with Exacerbated COPD Over a 3- Week Period.

Introduction: In clinical practice, wheezing and coughing represent a worsening of the respiratory situation of COPD patients and should be monitored long-term during and after an Acute Exacerbation of COPD (AECOPD) to observe the therapy. We investigated if overnight monitoring of wheezing and coughing is feasible during AECOPD and whether automatic long - term monitoring enables an objective assessment during and after an AECOPD. Methods: In 14 patients (age: 56-80 years) with pre-existing COPD (stages B-D) nighttime wheezing and coughing events were monitored for a period of three weeks. The portable LEOSound® monitor recorded three nights into AECOPD (nights 1, 3 and 6) during the hospital stay, and the 20th night post- AECOPD ambulatory. Before each recording the subjective symptom severity was assessed by a COPD Assessment Test (CAT) and a Modified British Medical Research Council (MMRC) dyspnoea index questionnaire. Results: In all 14 patients, lung sounds were recorded in good quality during each of the 4 recording nights. Wheezing ranged between 5% and 90% (79 -539.5 minutes) of the recording time on the first night. All patients showed some coughs, in four patients coughing was particularly pronounced and largely receding over the total investigation period. As group, the percentages of wheezing and the number of coughs did not show significant differences between the four recording times. The CAT scores (p<0.001) declined over the course of investigation period, suggesting a subjective improvement of symptoms. Conclusion: The observational study showed that standardized long-term recording can be performed in high-quality during acute COPD exacerbation as it does not require the patient's cooperation. The good-quality data of coughs and wheezing were analyzed qualitatively and quantitatively. The long-term presentation of respiratory symptoms during an AECOPD offers the opportunity to evaluate factors that influence exacerbations and therapeutic approaches.

[The bronchial arteries: a small but vital contribution to lung perfusion after lung transplantation]. / Die Bronchialarterien ­ ein kleiner, aber lebenswichtiger Beitrag zur Lungenperfusion nach Lungentransplantation.

Blood supply to the lungs is carried out by the pulmonary and bronchial-arterial system. The bronchial-arterial vessels are involved in supplying the small airways all the way up to the terminal bronchioles. The bronchial-arterial system is also necessary for the regulation of airway temperature, humidity and mucociliary clearance. Chronic ischaemia of the small airways due to damage or injury to bronchial arterial supply increases the risk of fibrosis of the small airways (bronchiolitis obliteration), especially in lung transplantation (LTx). Although survival after LTx has improved over time, it is, with a 5-year survival rate of only 50 to 60%, still significantly worse than that of other organ transplants. It is likely that bronchial arterial revascularisation at the time of LTx plays an important transplant-preserving function.

[The Inventor of the "Triage": Dominique-Jean Larrey (1766-1842), Napoleon's Chief Military Doctor]. / Der Erfinder der "Triage" ­ Dominique-Jean Larrey (1766­1842), Napoleons oberster Militärchirurg.

During the reign of Emperor Napoleon I, Dominique-Jean Larrey (1766-1842) was chief surgeon in the French army. He has become known as the father of modern military surgery and for the development of the "triage system". Larrey was an outstanding and dedicated physician who provided medical care not only to his own troops but also to those of the enemy. Without reliable analgesia and anaesthesia, speed and skill were the most salient characteristics of a surgeon at that time. Against the opposition of the administration, Larrey is credited with the introduction of first-aid on the battlefield as well as a quick rescue of the wounded with the help of the so-called "flying ambulances". He was considered the soldiers' greatest friend.

[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.

Validation of the LEOSound® monitor for standardized detection of wheezing and cough in children.

BACKGROUND: A hallmark of many respiratory conditions is the presence of nocturnal symptoms. Nevertheless, especially in children there is currently still a huge diagnostic gap in detecting nighttime symptoms, which leads to an underestimation of the frequency in clinical practise. METHODS: We evaluated the clinical applicability and determined the formal test characteristics of the LEOSound ® system, a device for digital long-time recording and automated detection of acoustic airway events. Airway sounds were recorded overnight in 115 children and adolescents (1-17 years) with and without respiratory conditions. The automated classification for "cough" and "wheezing" was subsequently validated against the manual acoustic reassessment by an expert physician. RESULTS: The general acceptance was good across all age groups and a technically successful recording was obtained in 98 children, corresponding to 92,976 sound epochs (à 30 s) or a total of 774 h of lung sounds. We found a sensitivity of 89% and a specificity of 99% for the automated detection of cough. For detection of wheezing, sensitivity and specificity were both 98%. The cough index and the wheeze index (events per hour) of individual patients showed a strong positive correlation (cough: rS = 0.85, wheeze: rS = 0.95) and a sufficient agreement of the two assessment methods in the Bland-Altman analysis. CONCLUSION: Our data show that the LEOSound® is a suitable device for standardized detection of cough and wheezing and hence a promising diagnostic tool to detect nocturnal respiratory symptoms, especially in children. However, a validation process to reduce false positive classifications is essential in clinical routine use.

[Adherence to CPAP Three Months after Starting Therapy in 1078 Patients with Obstructive Sleep Apnea (OSA)]. / Therapieadhärenz 3 Monate nach Einleitung einer nichtinvasiven CPAP-Therapie bei 1078 Patienten mit obstruktiver Schlafapnoe (OSA).

INTRODUCTION: Nocturnal Continuous Positive Airway Pressure (CPAP) is considered the gold standard treatment for obstructive sleep apnoea (OSA). The CPAP therapy is a long-term treatment but does come with few possible side effects. The adherence to the therapy is frequently suboptimal. In this paper, adherence to therapy was assessed and typical problems were classified. METHODS: 1078 OSA patients received CPAP therapy after a diagnostic polygraphy (PG) or polysomnography (PSG). Adherence to therapy was followed up three months after treatment induction. The following therapy adherence groups were defined: 1. correctly calibrated CPAP and good adherence, 2. CPAP non-acceptance, after initial use, 3. CPAP intolerance use due to side effects, 4. discontinuation due to lack of motivation/low rates of symptoms. 5. mask intolerance, 6. CPAP failure due to a lack of perceived treatment effect, 7. Change to another non-invasive ventilation method, 8. No control carried out. RESULTS: Out of 1078 OSA patients a therapy control was performed in 830 patients (77 %). Of these, 450 patients (54.2 %) were placed in group 1, 216 patients (26 %) in group 2, 71 patients (8.5 %) in group 3, 35 patients (4.2 %) in group 4, 14 patients (1.7 %) in group 5, 3 patients (0.4 %) in group 6 and 41 patients (4.9 %) in group 7. A mild obstructive index, low CPAP pressure and, as a trend, a low Epworth- Sleepiness score were predictors of CPAP failure. No significant predictors could be shown for adherence to therapy. DISCUSSION: An effective treatment use of 54 % after 3 months is a suboptimal result. Predictors of CPAP failure were parameters that indicated that the patient was less symptomatic prior to therapy. Despite a large patient cohort, neither anthropometric nor PSG-data provided any significant CPAP adherence predictors. Rather, experiences in the first nights of use could be decisive. CPAP devices offer comfort settings that have to be personalised to patients' needs and wants. A large selection of different mask shapes requires experience and training in patient-centred mask fitting. A three-month follow-up appointment seems too long to discuss therapy problems with the patient in a timely manner. Telemedical options or short-term telephone appointments should be considered.

Predisposing factors of daytime sleepiness in obese OSA patients.

Excessive daytime sleepiness is a common symptom in obese patients with obstructive sleep apnea. We investigated predisposing factors of excessive daytime sleepiness by comparing obese non-sleepy with sleepy patients with obstructive sleep apnea. Excessive daytime sleepiness was determined by the Epworth Sleepiness Scale in 43 patients (34 men and 9 women) with obstructive sleep apnea (apnea-hypopnea index ≥ 15 events per hr) and obesity (body mass index ≥ 30 kg m-2 ). Two subgroups were formed with (Epworth Sleepiness Scale ≥ 11) and without (Epworth Sleepiness Scale < 11) excessive daytime sleepiness. The concept of excessive daytime sleepiness was compared with other established daytime performance tests (Stanford Sleepiness Scale, Multiple Sleep Latency Test, Pupillographic Sleepiness Test, Marburger Vigilance test). Associations were calculated between excessive daytime sleepiness and demographic, metabolic and polysomnographic data. We included 19 sleepy patients (mean Epworth Sleepiness Scale score 15.2) and 24 non-sleepy patients (mean Epworth Sleepiness Scale score 5.8). Epworth Sleepiness Scale was negatively correlated with age and morning cortisol. Epworth Sleepiness Scale was positively correlated with body mass index, Stanford Sleepiness Scale, Beck's Depression Inventory and Marburger Vigilance test. Sleepy obese patients were significantly younger (mean 49.1 years), showed lower morning cortisol level (mean 9.41 µg L-1 ) and a trend to higher body mass index (mean 37.5 kg m- ²) compared with non-sleepy obese patients (mean: 59.3 years, 5.7 µg L-1 , 34.6 kg m- ², respectively). Many different excessive daytime sleepiness phenotypes are probably enclosed in obese patients with obstructive sleep apnea. Epworth Sleepiness Scale scores were best reflected by the objective Marburger Vigilance test results. The objective test can be particularly useful in cohorts where subjective reports are unreliable and operational readiness is paramount. Sleepy and non-sleepy obese patients with obstructive sleep apnea were similar in all polysomnographic parameters. Sleepy patients were younger, heavier and showed lower morning cortisol levels than non-sleepy patients.

Computer based sleep recording and analysis.

Sleep analysis is based on polysomnography. Modern polysomnographic systems are computer based. Visual and automatic analysis of sleep and respiration is supported by most computer based systems. Four functions can be distinguished in computer based polysomnography: recording, documentation during the recording, automatic and visual analysis and report generation. This review compiles the minimal requirements for digital sleep recording, documentation, analysis and reporting. The basic principles of automatic sleep analysis are reported. The requirements and the basic principles for the analysis of non-electroencephalography (EEG) signals, such as respiration, snoring, oxygen saturation, electrocardiography (ECG) and options are reported. New developments in sleep EEG processing are discussed to enlighten how computer based sleep analysis can add quantative parameters to the rules for visual sleep staging established by Rechtschaffen and Kales 30 years ago. This helps to extend our understanding of sleep.