Changes in serum KL-6 levels are associated with the development of chronic lung allograft dysfunction in lung transplant recipients.

Chronic lung allograft dysfunction (CLAD) remains a leading cause of death after lung transplantation. KL-6 is a reliable biomarker for various interstitial lung diseases and levels are increased in lung transplant recipients with versus without bronchiolitis obliterans syndrome. This study investigated whether changes in serum KL-6 levels over time were associated with CLAD. Twenty-one lung transplant recipients had serum KL-6 measured (NANOPIA®) at baseline and after 7 years. Changes in serum KL-6 levels from baseline were determined. Receiver operating characteristic curves and Kaplan-Meier analysis were used to test the predictive value of changes in serum KL-6 over time. The average increase in KL-6 in patients with CLAD was 15% versus a 28% decrease in non-CLAD patients (p = .042). An 11% decrease in serum KL-6 level was determined as the best cut-off value to be associated with the development of CLAD (86% sensitivity, 78% specificity). Kaplan-Meier analysis confirmed the association between this cut-off and the development of CLAD (log rank p = .013). In this small cohort, changes in serum KL-6 over time were associated with the development of CLAD after lung transplantation.

[Medical therapy of heart and lung diseases. Effects on the respective other organ]. / Medikamentöse Therapie von Herz- und Lungenerkrankungen. Effekte auf das jeweils andere Organ.

Many patients suffer from both heart and lung diseases. The choice of medical drugs should not only be driven by the clinical and prognostic effects on the target organ but should also be selected based on the effects on the respective other organ. Beta blockers and statins have both beneficial and harmful effects on the respiratory system. Angiotensin-converting enzyme (ACE) inhibitors and amiodarone can cause severe lung damage. Low-dose thiazides and calcium antagonists are first-line medications in hypertensive asthma patients but beta blockers should be avoided. Theophyline should be used with caution in patients with known cardiac disease. Glucocorticosteroids can cause cardiovascular symptoms while the phosphodiesterase inhibitor roflumilast appears to have no relevant cardiovascular side effects. Anticholinergic drugs have both favorable and unfavorable cardiovascular (side) effects. Short-acting beta-2 sympathomimetic drugs (SABA) and macrolides in particular can trigger arrhythmia and some SABAs are associated with a higher incidence of myocardial infarction. Detailed knowledge of the effects of drugs used for the treatment of lung and heart diseases on the respective other organ and the associated complications and long-term effects are essential in providing optimal medical care to the many patients who present with both respiratory and cardiovascular diseases.

[Is the Berlin questionnaire an appropriate diagnostic tool for sleep medicine in pneumological rehabilitation?]. / Ist der Berlin-Fragebogen ein geeignetes Instrument der schlafmedizinischen Diagnostik in der pneumologischen Rehabilitation?

BACKGROUND: The Berlin Questionnaire is an explorative tool of 13 questions designed to identify patients with obstructive sleep apnea. The questions are targeted toward key symptoms of snoring, apneas, daytime sleepiness, hypertension and overweight. METHODS: 153 patients undergoing pulmonary rehabilitation were screened for obstructive sleep apnea via i) ApneaLink (ResMed, Munich) and ii) the Berlin Questionnaire. The Epworth Sleepiness Scale (ESS) was administered to grade daytime sleepiness. Results of ApneaLink screening and questionnaires were prospectively compared. The Respiratory Disturbance Index (RDI) was used to compute predictive performance of the Berlin Questionnaire for obstructive sleep apnea. Results were also compared to previously published data from a primary care patient cohort. RESULTS: At a cut-off RDI=10/h, the Berlin Questionnaire had a sensitivity of 62.5 %, a specificity of 53.8 %, a positive predictive value of 38.4 %, a negative predictive value of 74.2 %, a positive likelihood ratio of 1.35 and a negative likelihood ratio of 0.69. At a cut-off RDI=15/h, the Berlin Questionnaire had a sensitivity of 67.2 %, a specificity of 52.8 %, a positive predictive value of 25.1 %, a negative predictive value of 84.7 %, a positive likelihood ratio of 1.42 and a negative likelihood ratio of 0.62. There was evidence that the participants of this study suffered from an increased daytime sleepiness (ESS=8.8 +/- 4.8). The study group was more likely to snore, have apneas (men 6.7 % more often, women 12.6 % more often) and suffer from daytime sleepiness (men 19.0 % more often, women 14.6 % more often) than the control group. Also, hypertension and overweight were more prevalent (men 6.1 % more often, women 11.1 % more often). CONCLUSIONS: The Berlin Questionnaire is a poor predictor of obstructive sleep apnea in a random group of patients undergoing pulmonary rehabilitation.

[Diaphragmatic weakness and its impact on respiratory function in primary myopathies]. / Einfluss der Zwerchfellschwäche auf die respiratorische Funktion bei primären Myopathien.

BACKGROUND: Diaphragmatic weakness (DW) is a potential manifestation of primary myopathies. Prevalence and impact on respiratory function have not been defined. METHODS: Respiratory function (inspiratory vital capacity, IVC; maximal inspiratory muscle pressure, PImax; respiratory muscle effort, P (0.1)/PImax) and polysomnography/nocturnal capnometry (PtcCO(2)) was analysed in 49 patients with primary myopathies. DW was defined as > 25 % drop of IVC upon shift from upright to supine position. RESULTS: 19/54 (35 %) of patients, mostly AMD (68 %) and DMD (42 %) had DW. Restrictive ventilatory defect was moderate (IVC 37.2 +/- 26.2 %) in patients with and without DW (IVC 46 +/- 26 %, p = n. s.). DW caused a -33 %, respective - 25 %, supine drop of IVC and PImax, resulting in severe restriction in supine position (IVC (supine) 24.9 +/- 19.1 %, PImax (supine) 2.0 +/- 1.0 kPa, P (0.1)/PImax (supine) 19.9 +/- 12,8 %). All patients with DW and 75 % without had sleep-disordered breathing. This was significantly more severe in DW: 90 % (vs 17 % without DW) had continuous nocturnal hypoventilation (PtcCO(2) 62 +/- 2 mm Hg), 70 % (vs 18 % without DW) had combined nocturnal and diurnal hypercapnic respiratory failure (PaCO(2) 54,7 +/- 11.8 mm Hg). DW was an independent risk factor for sleep disordered breathing, for nocturnal and diurnal respiratory failure (r = 0.95, p < 0,05). Predictive thresholds thereof were accurate and identical to previously determined only for supine function data. CONCLUSION: DW is common in primary myopathies and predictive of nocturnal and diurnal respiratory failure. Supine respiratory function tests are necessary for clinical diagnosis and respiratory risk stratification.

[Validation of microMESAM as screening device for sleep disordered breathing]. / Validierung von microMESAM als Screeningsystem für schlafbezogene Atmungsstörungen.

INTRODUCTION: Polysomnography (PSG) is considered the gold standard in the diagnosis of sleep disordered breathing (SDB). Because of costs and labor-intensity it is, however, performed last in graded diagnostic protocols that often involve respiratory pressure measurements via nasal canula as an alternative sensitive method for SDB detection. MicroMESAM, a newly developed screening device based on this method, allows automated analysis of apnoeas, hypopnoeas and snoring. AIM AND METHODS: To validate the device, we first compared signal quality of MicroMESAM flow-time curves with those generated by a pneumotachograph. Then, in 50 patients suspected of having obstructive sleep apnoea, we compared MicroMESAM-generated automated analysis with manually scored results of simultaneously collected PSG data. RESULTS: MicroMESAM-generated flow-time curves correspond with pneumotachograph-generated curves in 95% of respiratory events, resulting in less 4 +/- 2% difference in respective area under the curves. MicroMESAM and PSG generated numbers of apnoeas (r = 0.99) and hypopnoea (r = 0.81), as well as AHI (r = 0.98) correlated highly, displaying mean differences in AHI of 3.8, and in 1.96 sigma interval of + 11.1 to - 3.5/h. Sensitivities and specificities for SDB were 97.3%, respective 46% at SDB-defining AHI of 5, and 100%, respective 87.5%, at SDB-defining AHI of 10. SUMMARY: MicroMESAM-generated flow-time curves correspond well with pneumotachograph generated curves, producing automated AHIs that are highly sensitive in detecting SDB. MicroMESAM, therefore, is suitable as a screening device for SDB.

Air-wood coupling and the Swiss-cheese violin.

Some problems with the conventional formalism for describing the coupling of fluid vibrations to those of an enclosing shell are examined. An alternative ("dynamic") basis for expanding the normal modes, in which the "pure shell modes" include incompressible motion of the fluid, is proposed. This new approach is applied to Hutchins's "Swiss-cheese violin," the behavior of whose air modes for the case of a rigid shell have been calculated by Shaw. Measurements are presented of various response functions of this instrument as a function of both frequency and the number of open rib holes. These results show the predicted "mode veering" behavior, and can be easily matched to theory with the assumption of plausible parameters.

Nature of the lip reed.

Reed instruments have been categorized into two families since Helmholtz: the "striking inward" and the "striking outward" reeds. In an attempt to clarify the question to which family the lips of the brass player belong, a Helmholtz resonator with active feedback was used as a single-mode brass instrument and the playing frequencies generated by three trumpet players were measured. By adjusting the gain and the phase in the feedback loop, the resonant frequency and the quality factor of the resonator can be varied. The acoustic impedance at the mouthpiece is measured by a novel method without removing the play's lips. The results show that with extreme efforts the players can generated playing frequencies both lower and higher than the corresponding air column resonance, but that the playing frequency under normal playing conditions (the "most comfortable note") is almost always higher than the corresponding air column resonance. This supports the view that human lips function as "striking outward" reeds.

[Medium high-dose estrogen/gestagen sequential therapy in constitutional stature. The results of a 10-year pediatric gynecological follow-up observation]. / Mittelhochdosierte Estrogen/Gestagen-Sequentialtherapie bei konstitutionellem Hochwuchs. Ergebnisse einer 10jährigen gynäkologisch-pädiatrischen Nachbeobachtung.

We report about results of growth-inhibiting treatment in Magdeburg between 1976-1986. In 57 girls closed treatment was studied. Side effects are small. The functional state of the hypothalamo-pituitary axis experienced no negative influence.