[The experimental physiologist Carl Ludwig (1816-1895): Scientific genius - modest, selfless, unswerving!] / Der Experimentalphysiologe Carl Ludwig (1816­1895): Wissenschaftlicher Genius ­ uneitel, selbstlos, unbeirrbar!

Carl Ludwig was, besides Johannes Müller, one of the most prolific natural scientists of the 19th century. Carl Ludwig believed that the function of organs can be ascribed to the laws of physics and chemistry and that only through repeatable physiological experiments can hypotheses be verified. Ludwig has laid the technological foundations for experimental physiology. The "kymographion", (waves-recorder), the "stromuhr" and the blood gas pump are some of his developments that underline this fact. Together with his students he performed fundamental experiments to gain better understanding of renal physiology and pulmonary physiology, cardiovascular circulatory and innervation, as well as glandular secretion and the lymphatic system. For decades, Ludwig's two-volume textbook on the human physiology was standard work in scientific and experimental physiology. Many young scientists from all over the world ventured to Leipzig to be taught experimental physiology by Ludwig.

Time course of nocturnal cough and wheezing in children with acute bronchitis monitored by lung sound analysis.

Cough and wheezing are the predominant symptoms of acute bronchitis. Hitherto, the evaluation of respiratory symptoms was limited to subjective methods such as questionnaires. The main objective of this study was to objectively determine the time course of cough and wheezing in children with acute bronchitis. The impact of nocturnal cough on parent's quality of life was assessed as secondary outcome. In 36 children (2-8 years), the frequency of nocturnal cough and wheezing was recorded during three nights by automated lung sound monitoring. Additionally, parents completed symptom logs, i.e., the Bronchitis Severity Score (BSS), as well as the Parent-proxy Children's Acute Cough-specific Quality of Life Questionnaire (PAC-QoL). During the first night, patients had 34.4 ± 52.3 (mean ± SD) cough epochs, which were significantly reduced in night 5 (13.5 ± 26.5; p < 0.001) and night 9 (12.8 ± 28.1; p < 0.001). Twenty-two patients had concomitant wheezing, which declined within the observation period as well. All subjective parameters (BSS, Cough log and PAC-QoL) were found to be significantly correlated with the objectively assessed cough parameters.Conclusion: Long-term recording of cough and wheezing offers a useful opportunity to objectively evaluate the time course of respiratory symptoms in children with acute bronchitis. To assess putative effects of pharmacotherapy on nocturnal bronchitis symptoms, future studies in more homogeneous patient groups are needed. What is Known: • Cough and wheezing are the predominant symptoms of acute bronchitis. • There is a diagnostic gap in long-term assessment of these respiratory symptoms, which needs to be closed to optimize individual therapies. What is New: • Long-term recording of nocturnal cough and wheezing allows for objective evaluation of respiratory symptoms in children with acute bronchitis and provides a tool to validate the efficacy of symptomatic bronchitis therapies.

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.

Pilot study on nocturnal monitoring of crackles in children with pneumonia.

BACKGROUND: The clinical diagnosis of pneumonia is usually based on crackles at auscultation, but it is not yet clear what kind of crackles are the characteristic features of pneumonia in children. Lung sound monitoring can be used as a "longtime stethoscope". Therefore, it was the aim of this pilot study to use a lung sound monitor system to detect crackles and to differentiate between fine and coarse crackles in children with acute pneumonia. The change of crackles during the course of the disease shall be investigated in a follow-up study. PATIENTS AND METHODS: Crackles were recorded overnight from 22:00 to 06:00 h in 30 children with radiographically confirmed pneumonia. The data for a total of 28 800 recorded 30-s epochs were audiovisually analysed for fine and coarse crackles. RESULTS: Fine crackles and coarse crackles were recognised in every patient with pneumonia, but the number of epochs with and without crackles varied widely among the different patients: fine crackles were detected in 40±22% (mean±sd), coarse crackles in 76±20%. The predominant localisation of crackles as recorded during overnight monitoring was in accordance with the radiographic infiltrates and the classical auscultation in most patients. The distribution of crackles was fairly equal throughout the night. However, there were time periods without any crackle in the single patients so that the diagnosis of pneumonia might be missed at sporadic auscultation. CONCLUSION: Nocturnal monitoring can be beneficial to reliably detect fine and coarse crackles in children with pneumonia.

[Franciscus Sylvius: A Life for Clinic, Research, Teaching And a Little Gin]. / Franciscus Sylvius: Ein Leben für Klinik, Forschung, Lehre und ein bisschen Gin.

Franciscus Sylvius, latinized from Franz de le Boë (*15 March 1614 in Hanau; † 14 November 1672 in Leiden), was a Hessian-Dutch physician, anatomist, and natural scientist of Flemish descent. He was an important clinician and iatrochemist, and is considered the founder of scientifically oriented medicine and clinical chemistry. Sylvius introduced the concept of affinity and dealt with digestive processes and body fluids. He was one of the leading exponents of the concept of blood circulation developed by William Harvey. As the person responsible for practical medicine in Leiden, Sylvius established bedside teaching as part of the medical curriculum, and he introduced his students to clinical medicine in an experimental way, both contrary to the rules of the time. He was also interested in pharmacology, herbalism and botany. For heartburn and digestive disorders, Sylvius mixed juniper berries, herbs and alcohol to create a medicine. According to legend, Sylvius marketed this medicine as Genever, for which the name Gin was later adopted in the British Isles, but not only used for medical purposes. Accordingly, the city of birth of Sylvius today calls itself a "birthplace of gin".

Disease control in patients with asthma and respiratory symptoms (wheezing, cough) during sleep.

INTRODUCTION: The Global Initiative for Asthma (GINA)-defined criteria for asthma control include questions about daytime symptoms, limitation of activity, nocturnal symptoms, need for reliever treatment and patients' satisfaction. Patients with nocturnal symptoms like wheezing and cough often suffer from lower sleep quality and impaired daytime performance. The lack of an appropriate method for standardized and objective monitoring of respiratory symptoms leads to difficulties in asthma management. The aim of this study is to present a new method for automated wheeze and cough detection during sleep and to assess the actual level of asthma control by the Asthma Control Test (ACT). METHODS: Respiratory symptoms like wheezing and cough were recorded with the LEOSound-Monitor for one night in 55 asthmatic patients in their individual domestic setting. Patients were asked to assess their level of asthma subjectively with the ACT. The study consisted of 37 women and 18 men, with a mean age of 41 years, and a mean BMI of 27 kg/m2. Most of the patients had been taking an ICS/LABA combination and would resort to a SABA as their rescue medication. RESULTS: 60% of the participants were classed as having controlled, and 40% were classed as having partially- or uncontrolled asthma. During sleep wheezing was found in 8 of the 55 asthma patients (14.5%) and coughing was found in 30 patients (54.5%). The median ACT score in wheezing-patients was 14, while in non-wheezing patients it was 21. Uncontrolled asthma was found in 6 of the 8 wheezing-patients. Coughing versus non-coughing patients did not show a significant difference in the ACT-score (20, 22 respectively). CONCLUSION: Wheezing is a sign of uncontrolled asthma. The ACT-score in wheezing patients is worse compared to patients without wheezing. LEOSound proofed to be a useful tool in providing an objective evaluation of respiratory symptoms, like coughing and wheezing. In clinical practice, this may allow an improvement in asthma therapy.

[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.

Estimation of respiratory flow by means of normal lung sound.

The respiratory flow is a good indicator of sleep-related breathing disorders. Common praxis is to use a pneumotachograph as the golden standard for flow measurement. However, it does not have to be necessarily the best possible test device for long-term condition, because the device is very uncomfortable and rarely suitable for measurement during sleep. A computer-based method to determine the respiratory flow, called ThorAKUSTIK, yielded a highly positive correlation between the calculated flow out of the tracheal breath sound and a measured flow signal. In order to avoid noise interference due to a breath-mask or a pneumotachograph, in this study we applied the ThorAKUSTIK-method to lung sound which was measured at the back of 18 subjects and investigated the correlation between the calculated flow and the measured flow by a pneumotachograph. The new method showed a highly positive correlation (r = 0.89 and 0.90). Additionally we examined the use of an accelerometer signal to distinguish between inspiration and expiration. In this case we got high correlation coefficients of r = 0.87 and 0.88 between the calculated and measured airflow as well.