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Research questionThe assessment of cough frequency in clinical practice relies predominantly on the patient's history. Currently, objective evaluation of cough is feasible with bulky equipment during a brief time (i.e.hours up to 1 day). Thus, monitoring of cough has been rarely performed outside clinical studies. We developed a small wearable cough detector (SIVA-P3) that uses deep neural networks for the automatic counting of coughs. This study examined the performance of the SIVA-P3 in an outpatient setting.MethodsWe recorded cough epochs with SIVA-P3 over eight consecutive days in patients suffering from chronic cough. During the first 24 h, the detector was validated against cough events counted by trained human listeners. The wearing comfort and the device usage were assessed using a questionnaire.ResultsIn total, 27 participants (mean±sdage 50±14 years) with either chronic unexplained cough (n=12), COPD (n=4), asthma (n=5) or interstitial lung disease (n=6) were studied. During the daytime, the sensitivity of SIVA-P3 cough detection was 88.5±2.49% and the specificity was 99.97±0.01%. During the night-time, the sensitivity was 84.15±5.04% and the specificity was 99.97±0.02%. The wearing comfort and usage of the device was rated as very high by most participants.ConclusionSIVA-P3 enables automatic continuous cough monitoring in an outpatient setting for objective assessment of cough over days and weeks. It shows comparable sensitivity or higher sensitivity than other devices with fully automatic cough counting. Thanks to its wearing comfort and the high performance for cough detection, it has the potential for being used in routine clinical practice.

Zusammenfassung: Der Morbus Castleman ist eine seltene polyklonale, lymphoproliferative Erkrankung, bei der Mediatoren von Entzündungsreaktionen, v.a. Interleukin-6, eine wichtige pathophysiologische Rolle spielen. Zur Behandlung dieser Krankheit ist keine Standardtherapie etabliert. Wir berichten über den Fall einer 40-jährigen HIV-negativen Patientin mit primär pulmonaler Manifestation eines HHV-8-negativen, plasmazellreichen multizentrischen Morbus Castleman. Verschiedene Therapieversuche mit Immunmodulatoren wurden durchgeführt, bevor eine Behandlung mit dem Interleukin-6-Rezeptor-Antikörper Tocilizumab begonnen wurde. Seit 5Jahren ist der klinische Verlauf unter fortgesetzter Tocilizumabgabe stabil

Nicht das suchterzeugende Nikotin, sondern die unzähligen bei der Verbrennung von Tabak anfallenden Substanzen sind für die bekannten Gesundheitsschäden des Rauchens verantwortlich. Im Dampf von E-Zigaretten sind solche toxische Chemikalien nicht oder nur in Spuren nachweisbar. Deshalb kann davon ausgegangen werden, dass das Inhalieren von E-Zigaretten-Dampf für Erwachsene weitgehend unschädlich oder mit Sicherheit weniger schädlich als das Zigarettenrauchen ist. Zudem gibt es keine Daten, die belegen, dass E-Zigaretten bei Jugendlichen den Einstieg zum Rauchen von Zigaretten fördern. Der Konsum von E-Zigaretten mit nikotinhaltigen Liquids ist für stark nikotinabhängige Raucher, nach Scheitern einer strukturierten Raucher-entwöhnung eine Möglichkeit, um die Anzahl gerauchter Zigaretten zu reduzieren oder mit dem Rauchen aufzuhören. Weil die Diskussion um die E-Zigarette häufig emotional geführt und mit unbewiesenen Behauptungen hantiert wird, sollten sich Medizinalpersonen vorurteilslos über diese Art der Nikotin-Substitution informieren.

Objectives: We evaluated interactions between SERPINA1 PiMZ genotype, associated with intermediate α1-antitrysin deficiency, with outdoor particulate matter ≤10 μm (PM10), and occupational exposure to vapours, dusts, gases and fumes (VGDF), and their effects on annual change in lung function. Methods: Pre-bronchodilator spirometry was performed in 3739 adults of the Swiss Cohort Study on Air Pollution and Lung Disease in Adults (SAPALDIA) for whom SERPINA1 genotypes were available. At baseline in 1991, participants were aged 18-62 years; follow-up measurements were conducted from 2001 to 2003. In linear mixed regression models of annual change in lung function, multiplicative interactions were evaluated between PiMZ genotype (PiMM as reference) and change in PM10 (μg/m3), and VGDF exposure (high-level, low-level or no exposure as reference) during follow-up. Results: Annual declines in forced expiratory flow at 25-75% of forced vital capacity (FEF25-75%) (-82 mL/s, 95% CI -125 to -39) and forced expiratory volume in 1 s over forced vital capacity (FEV1/FVC) (-0.3%, 95% CI -0.6% to 0.0%) in association with VGDF exposure were observed only in PiMZ carriers (Pinteraction

Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular mortality. Endothelial dysfunction may underpin this association. This cross-sectional study aimed to determine the impact of airflow obstruction, systemic inflammation, oxidative stress, sympathetic activation, hypoxaemia and physical activity on endothelial function in COPD. In stable COPD patients, assessments of endothelial function by flow-mediated dilatation (FMD), cardiovascular risk (Pocock score), airflow obstruction (forced expiratory volume in 1 s (FEV1)), systemic inflammation (high-sensitivity C-reactive protein and interleukin-6), oxidative stress (malondialdehyde), sympathetic activation (baroreflex sensitivity), hypoxaemia (arterial oxygen tension), hypercapnia (arterial carbon dioxide tension ( P aCO2)), physical activity (steps per day) and exercise capacity (6-min walking distance) were performed. Associations between FMD and potential determinants were assessed in univariate and multivariate analyses. 106 patients (Global Initiative for Chronic Obstructive Lung Disease stage I/II 35%, stage III 25% and stage IV 40%) were included. In multivariate analysis FEV1 was positively associated with FMD, independent of other significant FMD determinants from univariate analysis (sex, smoking, combined inhaled long-acting β-adrenergic and steroid medication, heart rate, baroreflex sensitivity and P aCO2) and adjusted for potential confounders (cardiovascular risk and age). In addition, the FMD and FEV1 association was modified by physical activity. The findings of this study demonstrate that the severity of airflow obstruction is a significant determinant of endothelial function in patients with COPD. A high level of physical activity seems to have a favourable effect on this association. In COPD, the association between airflow obstruction and impaired endothelial function is modified by physical activity

BackgroundThe obstructive sleep apnoea syndrome (OSAS) is conventionally treated by continuous positive airway pressure set at a fixed level (fCPAP). Automatic mask pressure adjustment (autoCPAP) is increasingly used during home therapy. We investigated whether autoCPAP is equivalent to fCPAP in improving sleepiness in patients with OSAS in the long-term.MethodsIn this multicentre equivalence trial, 208 patients with OSAS, with median Epworth sleepiness score (ESS) 13, apnoea/hypopnoea index 48.4/hour, were randomised to treatment with autoCPAP (5–15 mbar) or fCPAP (pressure set at the 90th percentile applied by autoCPAP during 2–4 weeks adaptation). Coprimary outcomes were changes in subjective and objective sleepiness from baseline to 2 years after treatment. Equivalence ranges were ±2 points in ESS and ±3 min sleep resistance time evaluated by recording responses to light signals.ResultsAt 2 years, in the intention to treat analysis, the reduction in sleepiness versus pretreatment baseline was similar in patients using autoCPAP (n=113, mean ESS-change −6.3, 95% CI −7.1 to −5.5; sleep resistance time +8.3 min, +6.9 to +9.7) and fCPAP (n=95, mean ESS-change −6.2, 95% CI −7.0 to −5.3; sleep resistance time +6.3 min, +4.7 to +7.8). The 95% CI of difference in ESS-reduction between autoCPAP and fCPAP was −0.9 to +1.4 and the 95% CI of difference in increase in sleep resistance time was −2.6 to +1.0 min. Blood pressure reduction and OSAS-related costs were similar between groups.ConclusionsAutoCPAP and fCPAP are equivalent within prespecified ranges in improving subjective and objective sleepiness in patients with OSAS over the course of 2 years. Costs of these treatments are similar.Trial registration numberClinicalTrials.gov NCT00280800.

Objectives: To prospectively assess the impact of sinogram-affirmed iterative reconstruction (SAFIRE) on image quality of nonenhanced low-dose lung CT as compared to filtered back projection (FBP). Methods: Nonenhanced low-dose chest CT (tube current-time product: 30mAs) was performed on 30 patients at 100kVp and on 30 patients at 80kVp. Images were reconstructed with FBP and SAFIRE. Two blinded, independent readers measured image noise; two readers assessed image quality of normal anatomic lung structures on a five-point scale. Radiation dose parameters were recorded. Results: Image noise in datasets reconstructed with FBP (57.4 ± 15.9) was significantly higher than with SAFIRE (31.7 ± 9.8, P

Rationale α1-Antitrypsin (AAT) deficiency is one of the commonest rare respiratory disorders worldwide. Diagnosis, assessment of risk for developing chronic obstructive pulmonary disease (COPD), and management of replacement therapy require the availability of precise and updated ranges for protein serum levels. Objective This paper aims to provide ranges of serum AAT according to the main genotype classes in the general population. Methods The authors correlated mean AAT serum levels with the main SERPINA1 variants (M1Ala/M1Val (rs6647), M3 (rs1303), M2/M4 (rs709932), S (rs17580) and Z (rs28929474)) in 6057 individuals enrolled in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) cohort. Results The following ranges (5th–95th percentile) of AAT were found in the serum (g/litre): 1.050–1.640 for PI*MM, 0.880–1.369 for PI*MS, 0.730–1.060 for PI*SS, 0.660–0.997 for PI*MZ and 0.490–0.660 for PI*SZ. There was very little overlap in AAT serum levels between genotype classes generally not believed to confer an enhanced health risk (MM and MS) and those associated with an intermediate AAT deficiency and a potentially mildly enhanced health risk (SS, MZ). Conclusion This work resulted in three important findings: technically updated and narrower serum ranges for AAT according to PI genotype; a suggestion for a population-based ‘protective threshold’ of AAT serum level, used in decision-making for replacement therapy; and more precise ranges framing the intermediate AAT deficiency area, a potential target for future primary prevention.

Background and objective: COPD is associated with impaired health-related quality of life (HRQL) and cardiac autonomic dysfunction. Data describing the association between these factors in patients with COPD are mostly lacking. The objective of this study was to evaluate whether there is an association between cardiac autonomic dysfunction and HRQL in COPD. Methods: We studied 60 patients with COPD (37 women, mean (SD) age 65.20 (7.73) years, FEV1 % pred. 46.58 (18.53) %) and measured HRQL, as assessed by the Chronic Respiratory Disease Questionnaire, and cardiac autonomic dysfunction, as assessed by heart rate variability (HRV). Analysis of HRV was performed using a Holter-ECG device during a recording period of 5 min. To evaluate a possible association between these factors, univariate and multivariate analyses were used. Results: There was a significant correlation between Chronic Respiratory Disease Questionnaire total score and both variables of HRV reflecting parasympathetic tone; root mean square successive difference of RR intervals (rMSSD) (r = 0.34, P = 0.012) and the density of the beat-to-beat oscillation in the N-N interval of HRV in the high-frequency band (HF power) (r = 0.35, P = 0.01). In a multivariate analysis rMSSD was found to be independently associated with HRQL after correcting for FEV1, carbon monoxide transfer coefficient (DLCO), 6MWD and CRP. Conclusions: Resting parasympathetic tone, as measured by HRV, is independently associated with HRQL, which emphasizes the role of cardiac autonomic dysfunction on HRQL in patients with COPD.

Nontuberculous mycobacterium (NTM) species are mycobacterial species other than those belonging to the Mycobacterium tuberculosis complex and M. leprae. NTM are generally free-living organisms that are ubiquitous in the environment. Pulmonary disease, especially in older persons with and without underlying lung disease, is caused primarily by M. avium complex (MAC) and M. kansasii. The symptoms and signs of MAC lung disease are variable and not specific, but include cough, malaise, weakness, dyspnoea, chest discomfort and occasionally hemoptoe. Two major clinical presentations include disease in those with underlying lung disease, primarily white, middle-aged or elderly men - often alcoholics and/or smokers with underlying chronic obstructive lung disease, patients in whom MAC develops in areas of prior bronchiectasis, and patients with cystic fibrosis; and those without known underlying lung disease, including non-smoking women over age 50 who have interstitial patterns on chest radiography. M. kansasii infections are endemic in cities with infected tap water. Symptoms of the M. kansasii lung disease resemble to tuberculosis. M. abszessus is the most pathogenic rapid growing Mycobacterium which causes pulmonary infection. The American Thoracic Society and Infectious Disease Society of America's diagnostic criteria for nontuberculous mycobacterial pulmonary infections include both imaging studies consistent with pulmonary disease and recurrent isolation of mycobacteria from sputum or isolated from at least one bronchial wash in a symptomatic patient. For treatment of MAC lung disease we recommend depending on severity and susceptibility testing a three to four drug treatment with a macrolide, rifampicin and ethambutol and for M. kansasii a treatment with Isoniazid, rifampicin and ethambutol. Surgical management only plays a role in rare and special cases. Treatment should be continued until sputum cultures are consecutively negative for at least one year.

Rationale: To establish a new approach to investigate the physiological effects of obstructive sleep apnea (OSA), and to evaluate novel treatments, during a period of continuous positive airway pressure (CPAP) withdrawal. Objectives: To determine the effects of CPAP withdrawal. Methods: Forty-one patients with OSA and receiving CPAP were randomized to either CPAP withdrawal (subtherapeutic CPAP), or continued CPAP, for 2 weeks. Polysomnography, sleepiness, psychomotorperformance, endothelial function, blood pressure (BP), heart rate (HR), urinary catecholamines, blood markers of systemic inflammation, and metabolism were assessed. Measurements and Main Results: CPAP withdrawal led to arecurrence of OSA within a few days and a return of subjective sleepiness, but was not associated with significant deterioration of psychomotor performance within 2 weeks. Endothelial function, assessed by flow-mediated dilatation, decreased significantly in the CPAP withdrawal group compared with therapeutic CPAP (mean difference in change, -3.2%; 95% confidence interval [CI], -4.5, -1.9%; P < 0.001). Compared with continuing CPAP, 2 weeks of CPAP withdrawal was associated with a significant increase in morning systolic BP (mean difference in change, 18.5 mm Hg; 95% CI, +1.7, +15.3 mm Hg; P=0.016), morning diastolic BP (mean difference in change, +6.9 mm Hg; 95% CI, +1.9, +11.9 mm Hg; P =0.008), and morning HR (mean difference in change, +6.3 bpm, 95% CI, +0.4, +12.2 bpm; P = 0.035). CPAP withdrawal was associated with an increase in urinary catecholamines but did not lead to an increase in markers of systemic inflammation, insulin resistance, or blood lipids. Conclusions: CPAP withdrawal usually leads to a rapid recurrence of OSA, a return of subjective sleepiness, andis associated with impaired endothelial function, increased urinary catecholamines, blood pressure, and heart rate. Thus the proposed study model appears to be suitable to evaluate physiological and therapeutic effects in OSA. Clinical trial registered with www.controlled-trials.com (ISRCTN 93153804). Copyright ©2011 by the American Thoracic Society.

Objectives: To establish the value of the main pulmonary artery (MPA) diameter assessed from unenhanced computer tomography (CT) scans used for attenuation correction (AC) of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to predict pulmonary hypertension (PHT). Background: In contrast-enhanced chest CT scans an MPA diameter of 29mm or greater is an established predictor of PHT. However, it is unknown, whether measurements from an unenhanced CT scan for AC may be used as predictor of PHT. Methods: 100 patients underwent SPECT MPI for assessment of coronary artery disease. PHT was defined as a right ventriculo-atrial gradient of 30mm Hg or greater by Doppler echocardiography. We compared MPA diameter from CT to SPECT findings (right ventricular hypertrophy/enlargement, septal wall motion abnormality/perfusion defect, and D-shape) to determine the best predictor of PHT. Results: PHT was found in 37 patients. An MPA diameter of 30mm or greater yielded a sensitivity, specificity, accuracy, positive, and negative predictive value of 78%, 91%, 86%, 83%, and 88%, respectively. This yielded an area under the ROC curve of 0.85. Conclusions: MPA diameter from low-dose unenhanced multi-slice CT reliably predicts PHT, providing an important added clinical value from AC for SPECT MPI

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a life-threatening disease as rupture of the aneurysm is associated with high mortality. The likelihood that an AAA will rupture is particularly influenced by the diameter of the aneurysm and the rate of expansion; the reasons for fast expansion are largely unknown. Applanation tonometry (APT) can predict outcome in certain cardiovascular diseases by measuring arterial stiffness (augmentation index, AIx) and central aortic blood pressure (CABP). We tested the hypothesis that AIx and CABP would be higher in patients with fast-progressing AAA. METHODS: We performed APT and peripheral blood pressure measurements in 114 patients with AAA (11 women) with a mean ± SD age of 67.4±6.1 years. Annual AAA progression rate was determined by ultrasound. Patients were grouped into fast progressors (progression ≥2 mm/year) and slow progressors (progression

The aim of the present study was to measure age-specific prevalence of airflow obstruction in Switzerland in smokers and never-smokers using pulmonary function tests and respiratory symptoms from 6,126 subjects participating in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults. The lower limit of normal of the forced expiratory volume in 1 s/forced vital capacity ratio was used to define airflow obstruction. Severity of airflow obstruction was graded according to the recommendations of the Global Initiative for Chronic Obstructive Lung Disease. Prevalence of airflow obstruction ranged from 2.5% in subjects aged 30-39 yrs to 8.0% in those aged >/= 70 yrs. In multivariate analysis, age (OR 2.8, >/= 70 yrs versus 30-39 yrs), smoking (OR 1.8) and asthma (OR 6.7) were associated with airflow obstruction. Never-smokers constituted 29.3% of subjects with airflow obstruction. Never-smokers with airflow obstruction were younger, more likely to be male and reported asthma more frequently than obstructive smokers. Obstructive smokers and never-smokers had similar level of symptoms and quality of life impairment. The prevalence of airflow obstruction in Switzerland is similar to other developed countries. Never-smokers account for a third of the prevalence, which is higher proportion than elsewhere. Airflow obstruction in never-smokers deserves attention because of its frequency and its similar health impact to that in smokers.

Das obstruktive Schlafapnoe-Syndrom (OSAS) ist eine hochprävalente, schlaf-assoziierte Atmungsstörung, welche mit Hypopnoen/Apnoen, Aufwachreaktionen sowie erhöhter Tagesmüdigkeit einhergeht. Die Effekte des OSAS beinhalten unter anderem auch gefässschädigende Wirkungen, weshalb angenommen wird, dass das OSAS ein unabhängiger kardiovaskulärer Risikofaktor ist. Ein kausaler Zusammenhang zwischen dem OSAS und kardiovaskulären Erkrankungen wurde allerdings bisher nur für die arterielle Hypertonie und für die Herzinsuffizienz bewiesen. Die Evidenz dafür, dass das OSAS auch bei der Entstehung des Herzinfarkts oder Schlaganfalls eine Rolle spielt und eine OSAS-Therapie die kardiovaskuläre Morbidität und Mortalität reduziert, ist bisher noch limitiert. Die Ergebnisse von mehreren laufenden internationalen Multizenter-Studien, welche den Effekt der OSAS-Therapie auf kardiovaskuläre Ereignisse und die Mortalität untersuchen, werden deshalb mit grossem Interesse erwartet.

BACKGROUND: Understanding the prognostic meaning of early stages of chronic obstructive pulmonary disease (COPD) in the general population is relevant for discussions about underdiagnosis. To date, COPD prevalence and incidence have often been estimated using prebrochodilation spirometry instead of postbronchodilation spirometry. In the SAPALDIA (Swiss Study on Air Pollution and Lung Disease in Adults) cohort, time course, clinical relevance and determinants of severity stages of obstruction were investigated using prebronchodilator spirometry. METHODS: Incident obstruction was defined as an FEV(1)/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio ≥ 0.70 at baseline and

Background: Pulmonary hypertension (PH) is prognosti- cally important in chronic obstructive pulmonary disease (COPD). Since PH only weakly correlates with hypoxemia, other factors must play a role. Objective: To investigate whether polymorphisms of the serotonin transporter (5HTT), serotonin-2a receptor (5HTR2a) and endothelial nitric oxide synthetase (eNOS) are related to PH in COPD. Methods: In 59 COPD patients who underwent right heart catheterization, 6-min walking distance, NYHA functional class, pulmonary function tests, blood gases and 5HTT, 5HTR2a and eNOS (4ab and T298C) polymorphisms were determined. Results: Forty-nine COPD patients in NYHA functional class III–IV were included. Ten were excluded due to comorbid causes of PH (mainly chronic thromboembolic). PH (mPAP ≧25 mm Hg) was present in 55% and usually mild, but out of proportion (mPAP ≧40 mm Hg) in 12%. Patients with PH had significantly higher frequencies of the 5HTT-L-allele (52%) compared to individuals without PH (36%), and LL homozygote patients had more severe PH. In patients with out-of-proportion PH, the L-allelic frequency was even 75%. We found no association of 5HTR2a and eNOS polymorphism with PH in COPD. Conclusions: In this COPD cohort we confirm that PH is frequent and usually mild, but out of proportion in a subgroup. We found a significant association of the L-allelic variant of 5HTT with PH overall and especially in out-of-proportion PH. These findings may point towards a role of the serotonin system in COPD-PH and warrant further studies.

Caveolin-1 is a regulator of both intracellular calcium homeostasis and endothelial nitric oxide synthase and may play a pathogenetic role in pulmonary hypertension. In the present study, we aimed to investigate the correlations between pulmonary hemodynamics and vessel morphology including the expression of Caveolin-1 in pulmonary arterioles from patients with chronic obstructive pulmonary disease (COPD) who underwent lung-volume reduction surgery. Staining and subsequent analysis was performed on paraffin-embedded lung tissue from COPD patients (n = 12). Pulmonary arteries with an external diameter of 100-500microm were analysed. Immunhistochemistry with antibodies against caveolin-1 was performed and intensity was assessed. Morphometric data were obtained by using computer-assisted imaging software. The findings were quantified and correlated to hemodynamic data obtained by right-heart catheterization. In COPD patients with pulmonary hypertension (n = 5), the expression of caveolin-1 within the medial smooth muscle cell layer was found to be increased, whereas the intimal caveolin-1 was more prominently expressed in COPD patients with normal pulmonary pressures (n = 7). The ratio between these expression patterns was positively correlated to the mean pulmonary artery pressure. Similar findings were observed for the ratio between intimal and medial thickness as well as for the expression of smooth muscle actin (SMA).Taken together, the expression of caveolin-1 within medial smooth muscle cells of pulmonary arteries in patients with COPD is associated with pulmonary hypertension. Our results thus emphasize a potential novel player in the pathogenesis of COPD-associated pulmonary hypertension.

Die Bildgebung des Thorax hat in den letzten zwanzig Jahren grose Fortschritte gemacht. Das Thorax-Rontgenbild bleibt eine der wichtigsten diagnostischen Zusatzuntersuchungen im medizinischen Alltag. Die Wahl einer geeigneten weiterfuhrenden Spezialuntersuchung richtet sich nach der im Vordergrund stehenden diagnostischen Fragestellung. Grundkenntnisse der einzelnen Verfahren erleichtern die diagnostische Entscheidungsfindung und eine gemeinsame Terminologie fordern die Kommunikation zwischen Auftraggeber und Radiologen. Die heute gebrauchlichen Verfahren zeichnen sich nicht nur durch eine hohere Sensitivitat und Spezifitat gegenuber fruheren Untersuchungstechniken aus, sie sind auch mit einer deutlichen geringeren Belastung fur den Patienten verbunden. = Imaging of the chest made considerable progress over the past twenty years. Nevertheless, a chest X-ray remains one of the most informative and hence frequently used diagnostic procedures in daily medical practice. The choice of additional imaging techniques has to be based on pertinent differential diagnostic considerations. Basic knowledge of the various radiological techniques facilitates and improves the diagnostic process and a common terminology enhances the communication between the clinician and the radiologist. Modern radiological procedures are less invasive as compared to some historical procedures, are well tolerated by the patients and have a high sensitivity and specificity.

Lung densitometry in drug evaluation trials can be confounded by changes in inspiration levels between computed tomography (CT) scans, limiting its sensitivity to detect changes over time. Therefore our aim was to explore whether the sensitivity of lung densitometry could be improved by correcting the measurements for changes in lung volume, based on the estimated relation between density (as measured with the 15th percentile point) and lung volume. We compared four correction methods, using CT data of 143 patients from five European countries. Patients were scanned, generally twice per visit, at baseline and after 2.5 years. The methods included one physiological model and three linear mixed-effects models using a volume-density relation: (1) estimated over the entire population with one scan per visit (model A) and two scans per visit (model B); and (2) estimated for each patient individually (model C). Both log-transformed and original volume and density values were evaluated and the differences in goodness-of-fit between methods were tested. Model C fitted best (P < 0.0001, P < 0.0001, and P = 0.064), when two scans were available. The most consistent progression estimation was obtained between sites, when both volume and density were log-transformed. Sensitivity was improved using repeated CT scans by applying volume correction to individual patient data. Volume correction reduces the variability in progression estimation by a factor of two, and is therefore recommended.

Asthma ist eine haufige Erkrankung mit erheblichen gesundheitlichen und gesundheitsokonomischen Konsequenzen. In den Richtlinien wurde Asthma bisher nach dem Schweregrad basierend auf Symptomen, Ausmas der Obstruktion und Variabilitat in vier Subgruppen (intermittierend, chronisch leicht, chronisch mittelschwer und chronisch schwer) eingeteilt. In den neuen GINA (Global Initiative for Asthma) Richtlinien wird das Erreichen einer guten Asthmakontrolle als das wichtigste Ziel im Management dieser Erkrankung genannt. Statt des Schweregrades wird das periodisches Erheben der Asthmakontrolle empfohlen und das Mas der Asthmakontrolle in kontrolliert, teilweise kontrolliert oder unkontrolliert eingeteilt. Eine gute Asthmakontrolle zu erreichen und aufrechtzuerhalten ist ein komplexer Langzeitprozess und die Bemuhungen sollten sich auf folgende vier Bereiche konzentrieren: ( 1.) Diagnose und sorgfaltige Erhebung der Krankheitsaktivitat, (2.) Adaquate Pharmakotherapie mit Evaluation des Ansprechens auf die Therapie, (3.) regelmasige klinische Kontrollen und (4.) Schulung der Patienten. Diese Arbeit bietet einen Uberblick uber die Pharmakotherapie im Kontext der Asthmakontrolle. = Asthma is a common, chronic inflammatory airway disease associated with prominent health and economic consequences. In the first National Heart Lung and Blood Institute (NHLBI) and Global Initiative for Asthma (GINA) guidelines the level of symptoms and airflow limitation and its variability subdivided asthma by severity into four subcategories (intermittent, mild persistent, moderate persistent, and severe persistent). In the new GINA guidelines asthma control is emphasized as a main goal and a periodic assessment of asthma control is recommended. The three subcategories are controlled, partly controlled and uncontrolled asthma. The achievement and maintenance of asthma control is a long-term process with focus on: (1.) diagnosis and objective evaluation of disease activity, (2.) Adequate pharmacotherapy and re-evaluation of response to therapy, (3.) regular follow up, and (4.) self-management education. This article presents an overview on pharmacotherapy for adult asthmatics, with emphasise on the importance of achieving and to maintain control.

Die Schleimhäute des oberen und unteren Respirationstrakts bilden eine funktionelle Einheit. Es verwundert deshalb nicht, dass sie im Rahmen von Systemerkrankungen zwar ähnlich reagieren, entsprechend ihren anatomischen und funktionellen Gegebenheiten aber unterschiedliche Symptome verursachen («United Airways»). Die häufigsten akut verlaufenden Entzündungen der oberen und unteren Atemwege sind durch Viren verursacht und verlaufen bei sonst gesunden Personen selbstlimitierend. Allergische oder nicht-allergische Rhinosinusitide und Bronchialasthma sind die häufigsten chronischen Atemwegserkrankungen. Diese Erkrankungen manifestieren sich häufig konsekutiv oder gleichzeitig, was bei Diagnostik und Therapie zu berücksichtigen ist.

Background: Periodic whole body acceleration in the spinal axis (pGz) applied by a motion platform is a novel treatment modality that induced endothelial nitric oxide release into the circulation of animals, healthy subjects and patients with inflammatory diseases during single treatment sessions in previous studies. We hypothesized that patients with advanced arteriosclerotic diseases who are not candidates for a surgical intervention would clinically benefit from repeated pGz treatments over several weeks through improvement of endothelial function. Patients and methods: 11 patients, 5 men (37 to 71y) with stable ischemic heart disease, LVEF < 35%, NYHA stage > II, and 6 patients (51 to 83y, 1 woman) with intermittent leg claudication, Fontaine stage II, were enrolled after optimization of pharmacological therapy. PGz was applied for 40 min, 5 days/week during 5 weeks. Quality of life (SF-36 questionnaire), exercise performance, and endothelial function were assessed at baseline, during the treatment period, and 4 weeks after discontinuation of pGz. Results: PGz was well tolerated. In heart failure paitents, pGz therapy improved quality of life, increased 6 min walking distance by a mean ± SE of 105 ± 24 m, and improved postischemic skin hyperemia (p < .05 in all instances). In 4 of 6 patients with intermittent claudication, quality of life, treadmill walking distance and post-ischemic skin hyperemia improved with pGz therapy (p < .05). Four weeks after discontinuation of pGz, most therapeutic effects had vanished in both patient groups. Conclusions: In patients with severe heart failure and with leg claudication who remain symptomatic despite maximal medical therapy and who were not candidates for surgery, periodic acceleration applied over several weeks improved quality of life and exercise capacity. The clinical benefits appear to be mediated through improved endothelial function.

In patients with airflow limitation caused by cigarette smoking, lung density measured by computed tomography is strongly correlated with quantitative pathology scores of emphysema, but the ability of lung densitometry to detect progression of emphysema is disputed. We assessed the sensitivity of lung densitometry as a parameter of disease progression of emphysema in comparison to FEV(1) and gas transfer. At study baseline and after 30 months we measured computed tomography (CT)-derived lung density, spirometry and carbon monoxide diffusion coefficient in 144 patients with chronic obstructive pulmonary disease (COPD) in five different centers. Annual change in lung density was 1.31 g/L/year (CI 95%: -2.12 to -0.50 HU, p=0.0015, 39.5 mL/year (CI 95%: -100.0-21.0 mL, p=0.2) for FEV(1) (-39.5 mL) and 24.3 micromol/min/kPa/L/year for gas transfer (CI 95%: -61.0-12.5 micromol/min/kPa/L/year, p=0.2). Signal-to-noise ratio (mean change divided by standard error of the change) for the detection of annual change was 3.2 for lung densitometry, but 1.3 for both FEV(1) and gas diffusion. We conclude that detection of progression of emphysema was found to be 2.5-fold more sensitive using lung densitometry than by using currently recommended lung function parameters. Our results support CT scan as an efficacious test for novel drugs for emphysema.

Objective: Solitary fibrous tumours of the pleura (SFTP) are rare and can histologically be differentiated into benign and malignant forms. The aim of this study is to present new cases, and discuss up-to-date preoperative examinations, the role of video-assisted thoracic surgery and longterm outcome. Methods: Between 1993 and 2006, 27 SFTPs were diagnosed (14 females, mean age SD, 62.3 9.6 years) at our institution. Medicalrecordswere reviewed,and follow-up was obtained byrepeated examinations orcontactwith generalpractitioners.Results:SFTPswere associated with symptoms in 63% of all cases. In the six patients in which positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) was performed preoperatively, malignant lesions were all found to be positive. Complete resection was achieved by video-assisted thoracic surgery in 15 and anterolateral thoracotomy in 12 patients. Mean hospital stay was shorter for patients operated by video-assisted thoracic surgery compared to thoracotomy, 4.5 (range 3—6) versus 7.5 (range 4—25) days, respectively (p < 0.01). Histology revealed 17 benign and 10 malignant SFTP. Mean SD tumour diameter of malignant SFTPs was larger than in benign forms, 11.9 7.1 versus 6.1 3.5 cm, respectively (p < 0.01). Tumour recurrence was recognised in four patients with malignant SFTPs at a median time interval after surgery of 38 (range 6—122) months, two late deaths occurred resulting from tumour recurrences. Conclusions: SFTPs can be treated minimally invasively by video-assisted thoracic surgery with short hospital stay. Large SFTPs with increased FDG-uptake have a high likelihood for malignancy. Long-term follow-up is mandatory in malignant SFTPs because of late recurrences associated with death. # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Non-compliance is one of the crucial problems impairing outcome after transplantation. Fourteen lung transplant recipients were interviewed about their thoughts regarding transplant-related topics. Compliance was assessed by doctors. The psychological processing was investigated by content analysis. Highly compliant patients perceived more advantages by transplantation. In contrast, low-compliant patients reported either an emotional distance to the lung or a closer relationship to the donor. Furthermore, they showed a contradictory relationship to the medical staff. There are some indications that perception of advantages by transplantation is crucial to compliance. This experience takes place in the context of a good staff – patient relationship. Emotional distance to the lung or nearness to the donor are further contributing factors of non-compliance.

Background Rituximab (RTX), a B-cell depleting monoclonal antibody is increasingly used in several antibody-mediated diseases. It has been reported to cause pulmonary toxicity, though mainly during polychemotherapy of malignant lymphoma. Prospective data on RTX-induced pulmonary complications in patients with rheumatoid arthritis (RA) are lacking. Methods and methods Serial spirometries and measurements of diffusion capacity of the lung for carbon monoxide (DLCO) in patients with RA before and 2, 4, 8, and 26 weeks after treatment with RTX were performed. A reduction from baseline of forced vital capacity (FVC) of ≥10%, or ≥15% of DLCO was defined as indicative for pulmonary toxicity. Results Thirty-three patients (mean (SD) age 59 (12) years, 27% males) were included. Mean (SD) FVC predicted and DLCO predicted at baseline were 108% (18%) and 88% (18%), respectively. In contrast to FVC, DLCO showed a progressive decline during follow-up with a maximum reduction of 6.1% (95%CI 2.5%, 9.7%; p = 0.001) at 26 weeks compared with baseline. After 26 weeks, 22% of the patients had a ≥15% DLCO decline. None of the patients reported increased dyspnea during follow-up. Risk factors for pulmonary function changes after treatment with RTX were cigarette smoking, repeated administration of the drug, and co-medication with Prednisone. Conclusion Although no cases of symptomatic lung injury were observed, the progressive DLCO decline seems to indicate the presence of subclinical RTX-induced pulmonary toxicity.

Not nicotine, but an abundant amount of toxic chemicals produced by the combustion of tobacco are the cause of well-known health problems. E-cigarette vapor contains no or only minimal quantities of potentially harmful substances. Hence it can be assumed that vaping in adults is much less harmful than smoking of cigarettes. Furthermore, no data exist that e-cigarettes will encourage youngsters to become cigarette smokers. E-cigarette vaping has the potential to reduce the daily number of cigarettes smoked or facilitates cessation of smoking in heavily nicotine-dependent smokers, who keep on smoking despite a structured smoking cessation program. Health professionals should be aware of this type of nicotine substitution, since the controversial discussion is often emotional and not evidence-based.

Bronchial hyperresponsiveness (BHR) is a common feature of asthma. However, BHR is also present in asymptomatic individuals and its clinical and prognostic significance is unclear. We hypothesised that BHR might play a role in the development of chronic obstructive pulmonary disease (COPD) as well as asthma.In 1991 respiratory symptoms and BHR to methacholine were evaluated in 7126 of the 9651 participants in the SAPALDIA cohort study. Eleven years later 5825 of these participants were re-evaluated, of whom 4852 performed spirometric tests. COPD was defined as an FEV1/FVC ratio of0.70.In 1991 17% of participants had BHR, of whom 51% were asymptomatic. Eleven years later the prevalence of asthma, wheeze, and shortness of breath in formerly asymptomatic subjects with or without BHR was, respectively, 5.7% v 2.0%, 8.3% v 3.4%, and 19.1% v 11.9% (all p0.001). Similar differences were observed for chronic cough (5.9% v 2.3%; p = 0.002) and COPD (37.9% v 14.3%; p0.001). BHR conferred an adjusted odds ratio (OR) of 2.9 (95% CI 1.8 to 4.5) for wheezing at follow up among asymptomatic participants. The adjusted OR for COPD was 4.5 (95% CI 3.3 to 6.0). Silent BHR was associated with a significantly accelerated decline in FEV1 by 12 (5-18), 11 (5-16), and 4 (2-8) ml/year in current smokers, former smokers and never smokers, respectively, at SAPALDIA 2.BHR is a risk factor for an accelerated decline in FEV1 and the development of asthma and COPD, irrespective of atopic status. Current smokers with BHR have a particularly high loss of FEV1.

A recently introduced, multidimensional index called BODE (body mass index [BMI], degree of airflow obstruction assessed by spirometry, grade of dyspnea, and exercise capacity), quantified by 6-min walking distance (6MWD), has excellent predictive power with respect to outcome in COPD. We investigated whether the BODE index is able to predict survival after lung volume reduction surgery (LVRS).Retrospective study.Tertiary university hospital.One hundred eight-six COPD patients (76 women) with severe emphysema (mean +/- SD age, 64 +/- 8 years; mean FEV(1), 28 +/- 8% of predicted).Bilateral thoracoscopic LVRS.BMI, pulmonary function, 6MWD, and the modified Medical Research Council dyspnea score were assessed before and 3 months after LVRS, and the BODE index was calculated. The patients were followed up with respect to survival for a median time of 40 months (range, 3 to 116 months) after surgery. The mean BODE index decreased from 7.2 +/- 1.6 preoperatively to 4.0 +/- 2.0 at 3 months after LVRS (p0.001). The postoperative but not the preoperative BODE correlated with survival, although preoperative patient characteristics were comparable between short-term (5 years) and long-term (5 years) survivors. A decrease to a lower BODE score class was associated with a reduced mortality (hazard ratio, 0.497, 95% confidence interval, 0.375 to 0.659; p0.001). The C statistic for the ability of the BODE index to predict the risk of death was larger (0.74) than that for the FEV(1) (0.63), the degree of dyspnea (0.64), or the 6MWD (0.62).The postoperative BODE index is a powerful predictor of survival in COPD patients after LVRS.

We report a 57-year-old female with severe airway obstruction who underwent resection of a tumor of unknown dignity during lung volume reduction surgery. The nodule consisted of a well-differentiated neuroendocrine tumor (carcinoid), and severe chronic obstructive lung disease was due to diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, a very rare cause of obliterative bronchiolitis. Radionuclide ablative therapy of the neuroendocrine tissue was considered but not found to be feasible due to a low lung/background ratio of the radiotracer.

Objectives Treatment of obstructive sleep apnea syndrome (OSA) is often delayed because polysomnography, the recommended standard diagnostic test, is not readily available. We evaluated whether the diagnosis of sleep apnea could be inferred from the response to a treatment trial with nasal continuous positive airway pressure (CPAP). Design Study on diagnostic accuracy. Setting Sleep-disorders clinic of a university hospital. Patients Seventy-six sleepy snorers consecutively referred for sleep apnea evaluation. Interventions CPAP treatment trial over 2 weeks as an initial diagnostic test in comparison with polysomnography, and treatment success over ≥ 4 months. Measurements and results The main outcome was diagnostic accuracy of the CPAP trial. The trial result was positive if the patient had used CPAP for > 2 h per night and wished to continue therapy. This suggested sleep apnea. The trial was evaluated in terms of predicting an obstructive apnea/hypopnea index (AHI) > 10/h during polysomnography performed for validation, and in terms of identifying sleep apnea patients treated successfully over ≥ 4 months. Forty-four of 76 patients (58%) had sleep apnea as confirmed by an AHI > 10/h. The CPAP trial predicted sleep apnea with a sensitivity of 80%, a specificity of 97%, and positive and negative predictive values of 97% and 78%, respectively. In 35 of 76 sleep apnea patients (46%) with positive CPAP trial results, polysomnography could have been avoided. These patients were prescribed long-term CPAP therapy. After 4 months, 33 of 35 patients (94%) still used CPAP, and their symptoms remained improved. These patients were identified by the CPAP trial with positive and negative predictive values of 92% and 100%, respectively. Conclusions In a selected population, a CPAP trial may help to diagnose OSA, to identify patients who benefit from CPAP, and to reduce the need for polysomnography.

The objectives of this study were to investigate whether computed tomography (CT) densitometry can be applied consistently in different centers; and to evaluate the reproducibility of densitometric quantification of emphysema by assessment of different sources of variation, ie, intersite, interscan and inter- and intraobserver variability, in comparison with intersubject variability.In 5 different hospitals, 119 patients with emphysema were scanned using standardized protocols. In each site, an observer performed a quantitative densitometric analysis (including blood recalibration) on the corresponding patient group (n=23-25) and one observer analyzed the entire group of 119 patients. After several months, the latter observer analyzed all data for a second time. Subsequently, different sources of variation were assessed by variance component analysis with and without volume correction of the data.Inter- and intraobserver variability marginally contributes to the total variability (0.001%). The interscan variability was 0.02% of the total variation after application of volume correction. The intersite variability was 48% as a result of one deviating CT scanner. Air recalibration normalized deviating air densities in CT scanners. Within sites, the intersubject variability ranged between 93% and 99% based on the analysis of 2 subsequent CT scans of the patients.Almost all variability in the density measurement of emphysema originates from differences between scanners and from differences in severity of emphysema between patients. Lung densitometry with multislice CT scanners is a highly reproducible measurement, especially if corrected for lung volume, because this reduces interscan variability.

Duchenne muscular dystrophy (DMD) leads to progressive, generalized paresis, and to respiratory failure in the second decade of life. The assumption that severe physical disability precludes an acceptable quality of life is common, but has not been specifically evaluated in DMD.The purpose of this study was to investigate the quality of life in relation to physical disability, pulmonary function, and the need for assisted ventilation in DMD.In 35 patients with DMD, aged 8-33 yr, we assessed physical disability by a score ranging from 9 (no disability) to 80 (complete dependence on care and technical aids), pulmonary function, and health-related quality of life by Short-Form 36 of the medical outcome questionnaire.All patients required a wheelchair and help for dressing and eating. Fourteen patients were on long-term noninvasive positive-pressure ventilation. In ventilated patients, mean +/- SD FVC was 12 +/- 10 % predicted, and the physical disability score was 65 +/- 7. Corresponding values in spontaneously breathing patients were 48 +/- 25 % predicted, and 51 +/- 7, respectively (p0.05 for both comparisons between groups). Short-Form 36 physical function scores were massively reduced in both groups (1 +/- 2, and 0 +/- 0, respectively), but vitality, role-emotional, social function, and mental health scores were nearly normal (67-98), and did not differ between groups.Quality of life in DMD is not correlated with physical impairment nor the need for noninvasive positive-pressure ventilation. The surprisingly high quality of life experienced by these severely disabled patients should be taken into consideration when therapeutic decisions are made.

Transtracheal insufflation of oxygen-enriched air at a high flow rate has been proposed to support ventilation. The purpose of this study was to investigate the physiologic effects of high-flow insufflation unobtrusively with a respiratory inductive plethysmograph in patients with chronic respiratory failure. Using a respiratory inductive plethysmograph also permitted monitoring of end-expiratory lung volume, and respiratory variables could be quantified independently of the tracheal bias flow.Prospective randomized comparison of low-flow vs high-flow transtracheal insufflation.Pulmonary division of a tertiary teaching hospital.Fourteen spontaneously breathing outpatients with chronic hypoxemic respiratory failure carrying a transtracheal catheter for long-term oxygen therapy.Oxygen-enriched air (fraction of inspired oxygen, 0.37) at 15 L/min and oxygen at 1.5 L/min were transtracheally administered for 1 h each. The breathing pattern and the end-expiratory lung volume were monitored by inductive plethysmography along with pulse oximetry and transcutaneous PCO2. Arterial blood gases were also analyzed at the end of the hour of both low-flow and high-flow insufflation.High-flow insufflation decreased the mean (+/- SEM) minute ventilation (Ve) by 20% from 8.37 +/- 0.49 to 6.66 +/- 0.57 L/min, the mean respiratory rate from 19.2 +/- 0.9 to 15.7 +/- 1.0 breaths/min, while mean expiratory time increased from 2.0 +/- 0.1 to 2.8 +/- 0.2 s, and end-expiratory lung volume decreased by 0.55 +/- 0.15 L compared to low-flow oxygen insufflation (p0.05 for all comparisons). Mean arterial and transcutaneous PCO2 decreased from 45 +/- 1 to 43 +/- 1 mm Hg and from 54 +/- 2 to 53 +/- 2 mm Hg, respectively (p0.05 in both instances), while arterial PaO2 and oxygen saturation did not change.High-flow transtracheal insufflation of oxygen-enriched air assists ventilation by reducing Ve without compromising gas exchange and by reducing end-expiratory lung volume, possibly through the reversal of dynamic hyperinflation.

We evaluated the efficacy of two different continuous positive airway pressure devices with automatic mask pressure adjustment (autoCPAP) in comparison with fixed CPAP in treating obstructive sleep apnea syndrome in 29 patients. The mean (+/- SE) apnea-hypopnea index was 46 +/- 4 per hour and the Epworth score was 14.2 +/- 0.7. Patients were treated over three consecutive 1-month periods with three regimens in random order: an autoCPAP device responding to apnea-hypopnea and snoring, another autoCPAP device responding to snoring and changes in flow contour, and fixed CPAP at the 90th pressure percentile titrated by autoCPAP over 2 weeks. Allowed pressure in the autoCPAP mode was 4 to 15 cm H2O. At the end of each treatment period, symptoms, quality of life, vigilance, and nocturnal breathing disturbances were evaluated. All three treatment modalities improved symptoms, quality-of-life domains, and apnea-hypopnea index significantly and to a similar degree. Mean (+/- SE) maintenance-of-wakefulness time increased by 4.5 +/- 1.8, 6.0 +/- 1.5, and 6.1 +/- 1.4 minutes with DeVilbiss AutoAdjust LT, AutoSet T, and fixed-pressure CPAP, respectively (p0.001 vs. baseline, p=not significant for comparisons among the three modalities). We conclude that both autoCPAP devices were equally effective as fixed-pressure CPAP in improving major outcomes during short-term therapy of sleep apnea.