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Purpose In this proof of principle study, we evaluated the diagnostic accuracy of the novel Nox BodySleepTM 1.0 algorithm (Nox Medical, Iceland) for the estimation of disease severity and sleep stages based on features extracted from actigraphy and respiratory inductance plethysmography (RIP) belts. Validation was performed against in-lab polysomnography (PSG) in patients with sleep-disordered breathing (SDB). Methods Patients received PSG according to AASM. Sleep stages were manually scored using the AASM criteria and the recording was evaluated by the novel algorithm. The results were analyzed by descriptive statistics methods (IBM SPSS Statistics 25.0). Results We found a strong Pearson correlation (r=0.91) with a bias of 0.2/h for AHI estimation as well as a good correlation (r=0.81) and an overestimation of 14 min for total sleep time (TST). Sleep efficiency (SE) was also valued with a good Pearson correlation (r=0.73) and an overestimation of 2.1%. Wake epochs were estimated with a sensitivity of 0.65 and a specificity of 0.59 while REM and non-REM (NREM) phases were evaluated a sensitivity of 0.72 and 0.74, respectively. Specificity was 0.74 for NREM and 0.68 for REM. Additionally, a Cohen’s kappa of 0.62 was found for this 3-class classification problem. Conclusion The algorithm shows a moderate diagnostic accuracy for the estimation of sleep. In addition, the algorithm determines the AHI with good agreement with the manual scoring and it shows good diagnostic accuracy in estimating wake-sleep transition. The presented algorithm seems to be an appropriate tool to increase the diagnostic accuracy of portable monitoring. The validated diagnostic algorithm promises a more appropriate and cost-effective method if integrated in out-of-center (OOC) testing of patients with suspicion for SDB.

Background In this study we tested the hypothesis that in patients with cystic fibrosis (pwCF) respiratory rate (RR) is associated with antibiotic treatment, exacerbation status, forced expiratory volume in one second (FEV1) and C-reactive protein (CRP). Methods Between June 2018 and May 2019, we consecutively enrolled pwCF who were referred to our hospital. We determined RR and heart rate (HR) by using the minimal-impact system VitaLog during the hospital stay. Furthermore, we performed spirometry and evaluated CRP. Results We included 47 patients: 20 with pulmonary exacerbation and 27 without. RR decreased in patients with exacerbation (27.5/min (6.0/min) vs. 24.4/min (6.0/min), p = 0.004) and in patients with non-exacerbation (22.5/min (5.0/min) vs. 20.9/min (3.5/min), p = 0.024). Patients with exacerbation showed higher RR than patients with non-exacerbation both at the beginning (p = 0.004) and at the end of their hospital stay (p = 0.023). During the hospital stay, HR did not change in the total cohort (66.8/min (11.0/min) vs. 66.6/min (12.0/min), p = 0.440). Furthermore, we did not find significant differences between patients with exacerbation and patients with non-exacerbation (67.0/min (12.5/min) vs. 66.5/min (10.8/min), p = 0.658). We observed a correlation of ρ = -0.36 between RR and FEV1. Moreover, we found a correlation of ρ = 0.52 between RR and CRP. Conclusion In pwCF requiring intravenous therapy, respiratory rate is higher at their hospital admittance and decreased by the time of discharge; it is also associated with C-reactive protein. Monitoring RR could provide important information about the overall clinical conditions of pwCF.

Background: Sleep-disordered breathing (SDB) and disturbed sleep are common, often underrecognized, comorbidities in people with cystic fibrosis (pwCF). Objectives: We studied the effect of CFTR triple combination therapy elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on sleep in pwCF. Method: This was a prospective, observational sleep study in clinically stable adult pwCF. All participants underwent overnight polysomnography (PSG), before (T0) and after (T1) initiation of CFTR modulator therapy with ELX/TEZ/IVA. In addition, pulmonary function tests, calculation of BMI, and sweat chloride testing were performed. Results: Twenty-nine pwCF (mean age 32 ± 8 years; 15 female) participated in the study. Mean time between T0 and T1 was 194 ± 21 days. Total sleep time (TST) was 298 ± 40 min, with decreased sleep efficiency (SE) (76 ± 109) and increased sleep latency (SL) (73 ± 38 min). Sleep stages for NREM (N1–3) and REM sleep were within the normal range. Nocturnal respiratory events mainly occur during REM sleep (T0: AHI REM 8.3 ± 9.0/h; ODI REM 9.4 ± 10.6/h), whereas the overall AHI was normal (3.6 ± 3.7/h). After initiation of ELX/TEZ/IVA, we saw significant improvements in ppFEV1 (p < 0.001) and BMI (p < 0.001) and a reduction in sweat chloride levels (p < 0.001). In parallel, there was a reduction in AHI (p = 0.003), ODI (p = 0.001), and nocturnal respiratory rate (p < 0.001), both in total, REM and NREM sleep. Neither TST, SL, SE, nor sleep architecture was influenced (all p > 0.05). Conclusions: Initiation of ELX/TEZ/IVA resulted in significant improvements in SDB in adult pwCF.

For early stage non-small cell lung cancer (NSCLC) retrospective data of functionally compromised patients undergoing segmentectomy showed equal outcomes for perioperative complications and quality of life (QoL) compared with lobectomy patients. However no prospectively randomized data comparing patients eligible for both procedures are available.We conducted a prospective, randomized, multicenter phase III trial and investigated perioperative complications and QoL in patients with NSCLC stage IA (7th edition) undergoing segmentectomy versus lobectomy. The EORTC Questionnaire Core-30 (QLQ C-30) supplemented by thirteen-item lung cancer-specific module (LC13) was assessed before surgery, at discharge, 6 weeks, 3, 6 and 12 months post-surgery.108 patients with verified or suspected NSCLC up to 2 cm diameter were enrolled, whereby 54 were assigned to lobectomy and 54 to segmentectomy. Due to nodal disease, tumor size and surgical reasons estimated during the operation, eight patients of the segmentectomy group received a lobectomy. In hospital and 90 days mortality was 0% in both groups. Perioperative complications were observed in 6 (11.3%) patients after segmentectomy and in 8 patients (14.8%) after lobectomy (p = 0.563), while the 90-day morbidity were 17% and 25.9% (9 and 14 patients), respectively (p = 0.452). Twelve months after surgery, there was a significant deterioration to the baselines of physical (p 0.001) and cognitive functioning (p = 0.025), dyspnea (p 0.001) and fatigue (p = 0.003) in the lobectomy group. Dyspnea showed a faster recovery in the segmentectomy compared to lobectomy group with statistical significance (p = 0.016 after 12 months).In patients with early-stage NSCLC, segmentectomy is associated with a statistically not significant lower perioperative morbidity and appears to provide a superior recovery in QoL compared with lobectomy patients.

OBJECTIVES Persistent lymph nodes infiltration after neoadjuvant treatment remains a controversial topic in the treatment of stage III non-small-cell lung cancer (NSCLC). The aim of this study is to identify subgroups with persistent N2 disease, who could experience survival benefit from the addition of surgery. METHODS A retrospective mono-institutional study was conducted to analyse all patients with a final histopathology of NSCLC and persistent mediastinal disease after induction chemotherapy or chemoradiotherapy and surgery from January 1998 to June 2015. RESULTS A total of 145 patients (93 men, 52 women) fulfilled the inclusion criteria. The median age was 60 years (range 38–78). A total of 82 (56.5%) patients received a lobectomy, 48 (33.1%) a pneumonectomy, 11 (7.6%) a bilobectomy and 4 (2.6%) an anatomical segmentectomy; 128 (88.3%) were completely resected (R0). Operative mortality was 2.6% (4 patients), and morbidity was 35.2% (51 patients). Overall survival at 5 years was 47.3% (n = 19) for single N2 (skip), 30.2% (n = 16) for single N2 and N1 lymph nodes and under 5% (n = 1) for multiple mediastinal stations disease. Overall survival at 5 years after lobectomy/bilobectomy was not statistically different than after pneumonectomy (33.5% vs 20.5%, P = 0.082). Disease-free survival at 5 years was 30.6% (n = 6) for ypN2a1, 23.4% (n = 7) for ypN2a2 and under 5% (n = 1) for ypN2b status. CONCLUSIONS Lobectomy or bilobectomy has to be taken into account as a potentially curative option with promising long-term results for patients after induction treatment and persistent single-station N2 involvement (skip or additionally N1 status). Trial registry number 14-6138-BO.

Thymic epithelial tumors are the most common mediastinal tumors. Surgery is the mainstay of treatment and complete resection provides the best survival rate. However, advanced tumors often require multimodality treatment and thus we analyzed the prognostic potential of routine circulating biomarkers that might help to risk-stratify patients beyond tumor stage and histology. Preoperative values for white blood cell count (WBC), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were analyzed in 220 thymic epithelial tumor patients operated between 1999 and 2018. Increased CRP levels (>1 mg/dl) were significantly more often measured in thymic carcinoma and neuroendocrine tumors when compared to thymoma. LDH serum activity was higher in thymic neuroendocrine tumors when compared to thymoma or thymic carcinoma. The median disease specific survival was significantly longer in thymoma cases than in thymic carcinoma and neuroendocrine tumors. Increased preoperative LDH level (>240 U/L) associated with shorter survival in thymus carcinoma (HR 4.76, p = 0.0299). In summary, higher CRP associated with carcinoma and neuroendocrine tumors, while LDH increased primarily in neuroendocrine tumors suggesting that biomarker analysis should be performed in a histology specific manner. Importantly, preoperative serum LDH might be a prognosticator in thymic carcinoma and may help to risk stratify surgically treated patients in multimodal treatment regimens.

Cognitive functioning after transplantation, which could influence medication compliance and independence, has not been well studied. This study investigated cognitive impairment after lung transplantation. Patients undergoing bilateral transplant between March 2013 and October 2015 underwent comprehensive neuropsychological assessment at 60.1 ± 44.1 months post-transplantation: verbal memory (Auditory-Verbal Learning Test, digit span forward), visual memory (Corsi Block-Tapping Test forward, Benton Visual Retention Test), concentration/speed of processing/attention (D2 Test of Attention, Trail Making Test (TMT) A, Grooved Pegboard), and executive functioning (TMT B, Stroop Color-Word Test, semantic and phonematic verbal fluency, digit span backward, Corsi Block-Tapping Test backward). Mean scores were compared with a normative dataset using a one-sample t-test. A cognitive domain was judged impaired if the score on two or more domain-specific tests was greater than one standard deviation below the normative dataset age range mean. Of 124 lung transplant recipients (51% male, 54.3 ± 9.0 years), 70% showed cognitive impairment in one or more domains. Executive function was most often impaired (78% of recipients not within the age range) followed by verbal memory impairment (72% not within the age range). Cognitive function reductions were largely independent of age, gender, education, immunosuppressive medications, and time since transplantation. The findings show that cognitive impairment is common after lung transplantation and should be subject to rehabilitation and psychological resilience strategies.

Patients with cystic fibrosis (CF) are highly susceptible to infection and colonization of pulmonary epithelia. Repeated and chronic infections may affect disease course and efficacy of host immune protection. Higher Interleukin (IL)-7 serum levels, indicating impaired T-cell response to IL-7, have been described for chronic viral and mycobacterial infections.Time course measures of IL-7 serum concentrations in patients with CF (n = 164; n = 78 for the second time point) and healthy controls (n = 60) were done. CF patients were characterized for disease severity parameters as well as infection status and association with IL-7 serum levels was determined.CF patients had significantly higher IL-7 serum concentrations as compared to healthy controls (9.79 pg/ml, IQR 6.76-13.6 versus 4.55 pg/ml, IQR 2.76-9.51, p .001). IL-7 serum levels were negatively correlated with individual CF patient's BMI (r = -0.19, p = .021) and a tendency of increased IL-7 levels in Staphylococcus aureus infected CF patients was found. Linear regression of multiple parameters revealed significant negative correlation of FEV1High IL-7 serum levels were found in CF patients and correlated with impaired lung function during CF disease course. As a candidate biomarker of T-cell dysfunction, higher IL-7 serum level may also indicate worsened immune competence of patients with CF.

Objective To evaluate two standard procedure-specific pain regimens and to assess independent predictors for higher pain intensity after thoracic surgery. Methods Patients received either oral opioid analgesia (Opioid Group) or epidural analgesia and were then bridged to systemic opioid analgesia (EDA + O Group) in this retrospective observational study. Medical history, discharge letters, anesthetic protocols, and pain protocols were evaluated in 621 patients after open thoracotomy and assessed with a stepward back elimination in a multivariate logistic regression model. Results Data of 621 thoracotomies in 2014 were analyzed, 309 patients in the Opioid Group and 312 patients in the EDA + O Group. Pain scores at rest and on coughing were significantly lower in the EDA + O Group on postoperative days (PODs) 1-4 (P

Background The resection of the tracheobronchial bifurcation with complete preservation of lung parenchyma remains a challenge owing to the limited indications for surgery, anesthesiologic management, operative technique, and postoperative course. The aim of this retrospective study was to evaluate factors influencing the perioperative course and long-term survival. Methods Between 1989 and 2014, 19 patients underwent a resection of the distal trachea and carina with complete preservation of lung tissue, 16 for malignant tumors (7 adenoid cystic carcinomas, 3 carcinoid tumors, 3 mucoepidermoid tumors, 2 squamous cell carcinomas, and 1 small cell carcinomas), 2 for inflammatory stenosis, and 1 after a complex traumatic rupture. Results Surgical approach was posterolateral thoracotomy in 17 patients and median sternotomy in 2. In 16 patients, end-to-end anastomosis was performed, and in 3 patients, combined end-to-end and side-to-end anastomosis were performed. The operative mortality was 0%, the perioperative complication rate was 26.3%. Six patients with adenoid cystic carcinoma and all patients with lung carcinoma received adjuvant radiotherapy; only 1 patient with small cell lung cancer had chemotherapy before surgery. Long-term results are excellent in patients with benign disease, typical and atypical carcinoid tumor, mucoepidermoid carcinoma, and in most patients with adenoid cystic carcinoma. Two patients with lung cancer died 28 and 45 months after surgery, and 1 patient with adenoid cystic carcinoma died 75 months after surgery. Conclusions Resection of the tracheobronchial bifurcation with complete preservation of lung indicated for selected patients with local tumor growth at the distal trachea and carina provides low perioperative mortality and complications and results in long-term survival rates.

To evaluate postoperative pain intensity and length of hospital stay after open or robotic thoracic surgery in a standardized postoperative pain therapy setting. In the present retrospective (oberservation period: January 2015 until January 2016) study we matched data of 38 patients with robotic thoracic surgery ("robotic patients"; age: 62.2 years, male gender: 42.1%) with 38 patients with open thoracic surgery ("open patients"; age: 62.5 years, male gender: 42.1%). Power analysis indicated that 36 patients per group would be required. 68% of all patients received an epidural catheter, and 32% a systemic opioid based analgesia. Postoperative pain intensity in "robotic patients" was lower at rest on postoperative day 3–5 compared to "open patients" (NRS POD 3 robotic surgery 0.5±1.0 vs. open surgery 1.0±1.6, p = 0.04; NRS POD 4 robotic surgery 0,5 ± 1.0 vs. open surgery 1.1±1.3, p=0.04; NRS POD 5 robotic surgery 0.7 ± 1.0 vs. open surgery 1.5±1.5, p=0.003). Chest tube duration was shorter in "robotic patients" (2.9 ± 2.0 days vs. 4.9 ± 2.2 days; p < 0.001). Moreover, length of hospital stay was shorter in "robotic patients" than in "open patients" (6.9 days vs. 8.0 days; p = 0.02). There was no significant difference in postoperative opioid consumption between the groups. Nearly 95% of patients were discharged home with an oral opioid in both groups. Patients after robotic pulmonary resection experience lower postoperative pain and are discharged earlier from hospital than patients after open thoracic surgery. Study limitations: The study design is retrospectively.

In this study, we assessed the diagnostic accuracy of the device VitaLog (SWG Sportwerk GmbHCo. KG, Dortmund, Germany) for estimation of respiratory rate (RR) variability.VitaLog is a minimal-contact biomotion device that is placed under the mattress topper. It senses respiratory effort and body movement using a piezoelectric sensor. Diagnostic accuracy was determined in 103 patients referred to our sleep laboratory for suspected sleep-disordered breathing (SDB). SDB was defined by AHI ≥ 15/h. Results provided by VitaLog were compared with nasal flow measurement obtained by polysomnography (PSG).Diagnostic accuracy of VitaLog was excellent. We obtained a correlation of r = 0.99 and a bias of 0.2 cycles per minute (cpm) between VitaLog and PSG-provided nasal flow. Detection RR variability worked nearly identically in patients with and without SDB.VitaLog is an appropriate method for determination of RR variability based on a minimal-contact biomotion sensor. This device is easy to handle, available at low cost, and suitable for long-term monitoring in the hospital or at home.

Bilateral lung transplantation results in complete denervation of the lung and might impair hypercapnic ventilatory response (HCVR). However, experimental and clinical findings are scarce and conflicting. Therefore, this study investigated the relationship between HCVR and exercise capacity after long-term bilateral lung transplantation.This cross-sectional analysis enrolled 46 bilateral lung transplant recipients between October 2011 and July 2012 who underwent cardiopulmonary exercise testing to evaluate maximum workload, and carbon dioxide (CO2) rebreathing. CO2 rebreathing was also evaluated in 35 control subjects.In lung transplant recipients age was 54 ± 11 years, body mass index (BMI) 25.4 ± 4.1 kg/m(2), and time after transplantation 4.5 ± 2.5 years (range 9 months to 10 years). Controls were aged 41 ± 12 years and had a BMI of 24.9 ± 4.0 kg/m(2). There were significant differences between lung transplant recipients and controls in forced expiratory volume in 1 s (76 ± 22 vs. 94 ± 12 % predicted, p 0.001) and inspiratory vital capacity (91 ± 20 vs. 105 ± 14 % predicted, p = 0.001). Blood gases did not differ significantly in patients versus controls. HCVR in lung transplant recipients was 1.44 ± 1.07 L/min/mmHg compared with 2.09 ± 1.14 L/min/mmHg in controls (p = 0.001). Exercise capacity in lung transplant recipients (73 ± 24 W) was 49 % predicted. Linear regression analysis showed that exercise capacity was significantly associated with HCVR. A 1 L/min/mmHg decrease in HCVR decreased exercise capacity by 50 W.HCVR is reduced in long-term bilateral lung transplant recipients and this might explain the observed impairment of exercise capacity.

The prevalence of sleep-disordered breathing (SDB) after lung transplantation (LTX) is high. It is well-established that SDB is associated with decreased health-related quality of life (HRQoL), but the impact of SDB on exercise capacity is less clear. In this study we investigated HRQoL and exercise capacity in LTX recipients with or without SDB. In addition, we also investigated associations between sleep parameters and both HRQoL and exercise capacity. There were 53 stable LTX recipients (age 18 years, 31 males, time from LTX 9-120 months) enrolled into the study. They all underwent polysomnography examination. HRQoL was assessed using the Short Form-36 (SF-36). Exercise capacity was measured using the 6-min walk test and cardiopulmonary exercise testing (CPET). We found inverse correlations between severity of SDB and both the predicted maximal workload (r = 0.24, p = 0.04) and maximal oxygen uptake (r = -0.26, p = 0.03) during CPET. Relative oxygen uptake positively correlated with sleep efficiency (r = 0.27, p = 0.03). SF-36 scores did not differ between patients with and without SDB, and were not significantly associated with SDB parameters. In conclusion, the presence of SDB is associated with a slight reduction in maximal exercise capacity in LTX recipients, and there is no appreciable relationship between SDB and HRQoL.

Background Thymic epithelial and neuroendocrine carcinomas are rare malignancies, and only a few prognosticators are defined. Surgery is the mainstay of treatment, and complete resection contributes to superior outcome. Systematic lymph node dissection is not routinely performed in thymic malignancies. The aim of this study was to assess the impact of histologically confirmed lymph node metastases on the outcome after thymectomy. Methods We identified 53 patients with thymic epithelial or neuroendocrine carcinomas who underwent surgical resection at our center between 1999 and 2016. The clinical follow-up was retrospectively collected, and the impact of clinicopathologic factors on overall survival was analyzed. Results Ninety-one percent of the patients were treated taking a multimodal approach. Median overall survival was 11.3 years. Lymph node metastases were identified in 16 patients (30.2%; 11 pN1 and 5 pN2). Lymph node metastasis was associated with inferior overall survival (hazard ratio [HR] 3.03, 95% confidence interval [CI]: 1.03 to 8.87, p = 0.044). Masaoka-Koga stage (4 versus 1 to 3) was another significant prognosticator (HR 7.01, 95% CI: 2.52 to 19.50, p = 0.0002). Organ metastases were present in 18 patients at the time of thymectomy and were associated with inferior outcome (HR 5.8, 95% CI: 2.04 to 16.79, p = 0.001). Conclusions This retrospective, single-center analysis demonstrates a high rate of lymph node metastasis in resectable thymic neuroendocrine tumors or carcinomas. Positive lymph nodes are associated with an inferior outcome. Prospective studies are warranted to explore whether this outcome can be improved by systematic lymphadenectomy and adjuvant therapies. Nevertheless, lymphadenectomy provides optimal staging and should be a routine part of surgery for patients with thymic malignancies.

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.

BACKGROUND: Dental status has been implicated in several systemic inflammatory diseases and is a potential focus for systemic infections. Therefore, most lung-transplant centers have recommendations regarding pre-transplant dental care and follow-up, but there are no official clinical guidelines. To date there is little information on oral health status in lung transplant (LTx) recipients. The aim of this study was to systematically assess oral health status in LTx recipients. OBJECTIVES: The aim of this study was to assess oral health status, including periodontal disease, oral health behavior, and awareness of the need for good oral health after LTx. METHODS: LTx recipients were recruited during follow-up outpatient visits at a university clinic transplant unit. Oral health status was quantified using the count of Decayed, Missing and Filled Teeth (DMF-T) and the grade of periodontal disease was measured by probing depth. Patients' oral health behavior was assessed using a questionnaire. RESULTS: Seventy-three patients were included at 5.8±3.4 years after lung transplantation. The mean DMF-T was 21.9±5.5. Patients with cystic fibrosis as the indication for transplantation had a significantly lower DMF-T than patients with chronic obstructive pulmonary disease as the transplant indication. Of the 66 patients with teeth, 97% had moderate or severe periodontal disease. The prevalence of moderate or severe periodontal disease was significantly higher in LTx recipients (mean age 55.9 years) compared with older individuals (age 65-74 years) from the German general population (p

There is increasing evidence that sleep disorders are associated with cognitive decline. We, therefore, examined the cross-sectional association of sleep-disordered breathing (SDB), sleep quality, and three types of sleep complaints (difficulties initiating sleep, difficulties maintaining sleep, and early morning awakening) with mild cognitive impairment (MCI) and its subtypes. A group of 1,793 participants (51% men; 63.8 ± 7.5 years) of the population-based Heinz Nixdorf Recall study (total sample n = 4,157) received a screening for SDB and self-report measures of sleep complaints. Group comparisons were used to compare performances among five cognitive subtests. Multivariate logistic regression models were calculated to determine the association of MCI (n = 230) and MCI subtypes (amnestic MCI, n = 120; non-amnestic MCI, n = 110) with SDB severity levels, poor sleep quality, and sleep complaints. Severe SDB (apnea-hypopnea index ≥30/h, n = 143) was not associated with MCI, amnestic MCI, or non-amnestic MCI. Poor sleep quality was associated with MCI (Odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.02-2.03; fully adjusted) as well as frequently reported difficulties initiating sleep (OR = 1.94, 1.20-3.14), difficulties maintaining sleep (OR = 2.23, 1.27-4.63), and early morning awakening (OR = 2.30, 1.32-4.00). Severe difficulties initiating sleep (OR = 2.23, 1.21-4.13) and early morning awakening (OR = 2.88, 1.45-5.73) were solely associated with the amnestic MCI subtype, whereas, severe difficulties maintaining sleep (OR = 3.84, 1.13-13.08) were associated with non-amnestic MCI. Our results suggest that poor sleep quality, rather than SDB, is associated with MCI. The selective association of difficulties initiating sleep and early morning awakening with amnestic MCI and of difficulties maintaining sleep with non-amnestic MCI might serve as a marker to improve diagnostic accuracy in the earliest stages of cognitive impairment and will be further investigated in our longitudinal examination.

Pulmonary metastasectomy has gained the status of a standard treatment for oligometastases of various primaries. Given that the consequences for quality of life (QoL) remain unclear, we initiated this study to characterize the therapy-induced effects of pulmonary metastasectomy on QoL.From 2008 to 2010, patients scheduled for metastasectomy were prospectively evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) and the lung cancer module (LC13) questionnaire and again 3 months later. We analyzed QoL changes over time and looked for sex-specific and age-specific (70 versus70 years) differences.A total of 126 cases were analyzed. The median age of the 73 male and 53 female patients was 59.2 years (range, 24.2 to 83.9). There was no significant change between preoperative and postoperative QoL values for emotional, cognitive, and social functioning. Significant deterioration of QoL items was found for physical functioning (-11.0; p0.001), role functioning (-16.4; p0.001), fatigue (11.1; p0.001), pain (15.0; p0.001), and dyspnea (16.9; p0.001). There were no differences between sexes concerning preoperative and postoperative scores. Younger patients (70 years) had more preoperative symptoms (1.9; p = 0.03) and a worse function (2.2; p = 0.04). A tendency was found for decreased global QoL (-6.0; p = 0.08) in the older age group (70 years) after metastasectomy.Pulmonary metastasectomy can be offered every patient with a chance of cure or prolongation of life because the anticipated midterm changes in QoL are of moderate clinical importance, and the change in global health-related QoL is trivial.

Recent studies found that the non-contact screening device SleepMinder (ResMed Sensor Technologies, Dublin, Ireland) detects sleep-disordered breathing (SDB) with high diagnostic accuracy in cohorts suspected of this disorder. However, it was reported that in patients with periodic limb movement in sleep (PLMS), this non-contact device overestimates the apnea-hypopnea index (AHI). We aimed to overcome this limitation by introducing the novel sleep disorder index (SDI) which is sum of the AHI and the period limb movement index (PLMI). Between January 2011 and December 2013, we studied a mixed cohort of 57 patients (31 OSA, 19 PLMS). The easy-to-use non-contact device emits a very weak electromagnetic radiation and detects body movement by measuring the Doppler effect. We interpreted the device-generated movement index as the SDI and validated the diagnostic accuracy against simultaneous application of the gold-standard polysomnography (PSG). We found that the SDI of the non-contact device correlated well with the sum of AHI and PLMI derived from PSG (r = 0.79, p = 0.01). For PSG-derived SDI cutoff ≥ 15/h, we obtained a sensitivity of 92.2% and a specificity of 95.8%. Positive likelihood ratio was 23.3 and negative likelihood ratio 0.03. The studied non-contact screening device detects accurately the combination of the sleep disorders SDB and/or PLM. However, further testing is required in order to specify the nature of the underlying sleep disorder. At the current stage of algorithm development, the clinical strength is that the studied non-contact device can be used as a rule-out screening device for SDB and PLM.

Background. Chronic post-thoracotomy pain (CPP) has a high incidence. However, less is known about risk factors and the influence of different analgesia therapies. Methods. In this prospective cohort study, patients either received standardized epidural analgesia or began an oral analgesic protocol with controlled-release oxycodone immediately postoperatively. Patients answered a baseline questionnaire on the day before surgery and a follow-up questionnaire six months postoperatively. The questionnaire included Short-Form 12, the Neuropathic Pain Scale, and descriptive questions for CPP. Pain protocols of all patients were examined. Logistic regression was used to analyze the risk factors related to CPP. Results. One hundred seventy-four patients were enrolled; data of 131 patients were available after the six-month follow-up period. Fifty-one patients (39%) had CPP six months postoperatively. Of these, more than 80% had impaired daily activity or ability to work, or reported sleeping disturbance due to CPP. The strongest predictive factors for the development of CPP were: thoracic pain for three months preoperatively (odds ratio [OR] = 3.54, 95% confidence interval [CI] = 1.69–7.40, P = 0.001), thoracic pain for 12 months preoperatively (OR = 2.73, 95% CI = 1.28–5.83, P = 0.009), and higher pain scores at rest in the first five postoperative days compared with patients without CPP (OR = 1.79, 95% CI = 1.24–2.57, P = 0.002). Neuropathic pain was present in 4.8% of patients. Patients with CPP had a reduced physical ( P = 0.005) and mental health status ( P = 0.03) six months after surgery compared with patients without CPP. Conclusions. Preoperative thoracic pain and higher pain scores in the first five postoperative days seem to be the strongest risk factors for the development of CPP. CPP patients reported poorer mental and physical health before and six months after surgery.

INTRODUCTION Patients after lung transplantation (LuTx) were found to present oral health deficiencies. The investigation of potentially underlying or influencing factors appears to be of clinical relevance. OBJECTIVES Aim of this study was to evaluate the oral health related quality of life (OHRQoL) in a group of patients after LuTx and compare this to a healthy control group (HC). Furthermore, the influence of dental and periodontal condition, as well as specific factors like immunosuppression, time after LuTx and causal underlying disease should be investigated. METHODS The OHRQoL was assessed using the German short form of the Oral Health Impact Profile (OHIP G14). Dental examination included the decayed (D-), missing (M-), and filled (F-) teeth index (DMF-T). Periodontal condition was classified based on clinical attachment loss and/or pocket depth as no/mild or moderate/severe periodontitis. STATISTICAL ANALYSIS Mann-Whitney-U-test, Kruskal-Wallis test (P

Introduction: There is only limited quantitative information on the association between intake of sleep disturbing drugs and nocturnal sleep disturbances. Information on sleep disturbing effects of drugs mostly derives from clinical trials with highly selected patient collectives. As these patient collectives[for full text, please go to the a.m. URL], GMDS 2015; 60. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V. (GMDS)

The aim of this study was to assess the validity of an artificial neural network based on flow-related spectral entropy as a diagnostic test for obstructive sleep apnoea and Cheyne-Stokes respiration. A data set of 37 subjects was used for spectral analysis of the airflow by performing a fast Fourier transform. The examined intervals were divided into epochs of 3 min. Spectral entropy S was applied as a measure for the spread of the related power spectrum. The spectrum was divided into several frequency areas with various subsets of spectral entropy. We studied 11 subjects with obstructive apnoeas (n = 267 epochs), 10 subjects with obstructive hypopnoeas (n = 80 epochs), 11 subjects with Cheyne-Stokes respiration (n = 253 epochs) and 5 subjects with normal breathing in non-REM sleep (n = 174 epochs). Based on spectral entropy an artificial neural network was built, and we obtained a sensitivity of 90.2% and a specificity of 90.9% for distinguishing between obstructive apnoeas and Cheyne-Stokes respiration, and a sensitivity of 91.3% and a specificity of 94.6% for discriminating between obstructive hypopnoeas and normal breathing in non-REM sleep. This resulted in an accuracy of 91.5% for identifying flow patterns of obstructive sleep apnoea, Cheyne-Stokes respiration and normal breathing in non-REM sleep. It is concluded that the use of an artificial neural network relying on spectral analysis of the airflow could be a useful method as a diagnostic test for obstructive sleep apnoea and Cheyne-Stokes respiration.

The resection of pulmonary metastases is associated with a loss of lung function. The amount of functional impairment after bilateral metastasectomy remains unclear. Because only around 35% of those patients may expect long-term survival, it is important to preserve enough pulmonary function for an adequate quality of life. This analysis of 31 bilaterally operated patients was performed to describe the amount of pulmonary function loss.This is a post-hoc subanalysis and comparison of a population that was published before. All pulmonary metastasectomies were performed through an anteroaxillary thoracotomy in all patients. Resections were performed with staplers, electrocautery, or laser. All patients had pulmonary function tests (PFTs) preoperative and after 3 months at the follow-up visit, including spirometry, diffusing capacity of lung for carbon monoxide (Dlco) and blood gases. Of the 31 bilaterally operated cases, 15 had additional PFTs after each staged operation before discharge from hospital.Altogether, 271 nodules (median 7, mean 8.2) were removed from the 31 patients with a lobectomy in 2, a segmentectomy in 8, and multiple wedge resections in 21 patients, with this being the largest resection. The mean loss of pulmonary function at follow-up visit was forced vital capacity (FVC) - 15.2%, total lung capacity (TLC) - 13.8%, forced expiratory volume in 1 second (FEV1) - 16.3%, and Dlco - 10.3%, all of which were significant (p = 0.001). The 15 patients with PFTs after each operation showed a stepwise decrease of volume parameters and Dlco with deepest values after the second surgery of around - -40% from preoperative values. At this time, Po 2 was also significantly reduced by 10 mm Hg (p = 0.01). Comparing the bilateral group with 86 patients after unilateral metastasectomy, we found significantly more nodules removed in the bilateral group (8.2 vs. 3.1; p 0.001) and that the loss of volume parameters was twice that of the unilateral group after metastasectomy. Dlco impairment did not differ between the groups (- 10.3 vs. - 9.5%; p = 0.868) after 3 months.Midterm pulmonary function impairment after bilateral pulmonary metastasectomy is 15% of spirometry values and 10% of Dlco. Reduction of spirometry values is almost twice compared with the group after unilateral surgery. Early functional loss after the second intervention causes FVC, TLC, and FEV1 reduction of around 40% and is associated with lower Po 2 (- 10 mm Hg). Therefore, bilateral metastasectomy can be offered to patients who do not have greater pulmonary limitations.

Background Large cell neuroendocrine carcinoma (LCNEC) is an uncommon tumor of the lung and represents approximately 3% of all lung cancers. LCNEC displays biological behaviors resembling those of small cell lung carcinomas and features of high-grade neuroendocrine tumors. LCNEC of the lung are considered aggressive. Reported prognoses are heterogeneous, and the optimum treatment remains undefined. Methods We conducted a retrospective study of all patients who were treated for LCNEC in our Department of Thoracic Surgery between May 2005 and December 2013. Primary outcomes of interest were patient survival and prognostic factors. Kaplan-Meier analysis was performed to determine the significant predictors of overall survival. Results Within the prescribed period, 127 patients were treated for LCNEC, and 125 underwent surgical resection with curative intent. Induction chemotherapy or radiochemotherapy was given to 9 patients, and 63 patients received postoperative chemotherapy. Complete resection was achieved in 99.2%. The overall 1-, 3- and 5-year survival rates were 83.7%, 63.2%, and 53.8% of all patients, and the 5-year survival in patients at stages I, II, and III was 64.5%, 40%, and 29.7%. There was a significant survival difference at 5 years between pT1/2 (58.5%) and pT3 tumors (22.4%; p = 0.043) and for patients with lymphatic involvement (L0 vs L1, p = 0.001; pN1 or pN2 vs pN0, p = 0.04). Conclusions Surgical treatment can achieve satisfactory results in early tumor stages, which are comparable with other non-small cell lung cancers, with a low perioperative mortality rate.

Scarce evidence suggests that ambient air pollution and temperature might play a role in incidence and severity of sleep disordered breathing (SDB). We investigated the association of short-term exposure to fine particulate matter (particles with a 50% cut-off aerodynamic diameter of 10 μm (PM10)), ozone and temperature with SDB in the general population.Between 2006 and 2008, 1773 participants (aged 50–80 years) of the Heinz Nixdorf Recall study underwent screening for SDB, as defined by the apnoea–hypopnoea index (AHI). We assessed daily exposure to PM10, ozone, temperature and humidity. We used multiple linear regression to estimate associations of daily PM10, ozone levels and temperature on the day of screening, adjusting for relative humidity, season, age, sex, body mass index, education, smoking habits, alcohol consumption and physical activity.In the study population, the mean±sdAHI was 11.2±11.4 events·h−1. Over all seasons, an interquartile range increase in temperature (8.6°C) and ozone (39.5 µg·m−3) was associated with a 10.2% (95% CI 1.2–20.0%) and 10.1% (95% CI 2.0–18.9%) increase in AHI, respectively. Associations for temperature were stronger in summer, yielding a 32.4% (95% CI 0.0–75.3%) increase in AHI per 8.6°C (p-value for season–temperature interaction 0.08). We observed that AHI was not associated with PM10.This study suggests that short-term variations in ozone concentration and temperature are associated with SDB.

To assess the clinical efficacy of controlled-release oxycodone for postoperative analgesia after video-assisted thoracic surgery (VATS) or thoracoscopy.Pain therapy is standardized in our thoracic center throughout the complete postoperative stay. Patients receive immediately postoperative standardized oral analgesic protocol with controlled-released oxycodone (Oxy Group) or oxycodone with naloxone (Targin Group) and nonopioid every 6 h. We switched the opioid protocol from controlled-release oxycodone to Targin in January 2012. All patients are visited daily by a pain specialist throughout the whole stay.Data of 788 patients undergoing VATS (n = 367) or thoracoscopy (n = 421) during January 2011 until March 2013 were analyzed. In VATS, patients with Targin had higher pain scores at rest (p 0.02) and on coughing (p 0.001) than patients with oxycodone alone and more patients with Targin were dismissed with oral opioid dose than patients with oxycodone alone (p 0.001). No differences in pain scores on POD 5 and 6, or in length of hospital stay, incidence of nausea, time to first dejection or opioid dose after dismission were found between controlled-release oxycodone and Targin. After conventional thoracoscopy, 209 patients received controlled-release oxycodone and 212 Targin. Patients with Targin had higher pain scores at rest (p 0.004) and on coughing (p 0.01) than patients with oxycodone alone and more patients with Targin were dismissed with oral opioid dose than patients with oxycodone alone (p 0.004). There were no differences in pain scores on POD 5 and 6, or in length of hospital stay, incidence of nausea, time to first dejection or opioid dose after dismission.Oral opioid analgesia with controlled-release oxycodone is an effective postoperative regimen after VATS and thoracoscopies. Our retrospective data indicate that Targin might be less effective analgesic than oxycodone after VATS and thoracoscopies with no improvement in bowel function in the immediate postoperative period.The study design is retrospective in nature.

Background To assess the protocols of epidural analgesia versus systemic opioid-based analgesia retrospectively in 1555 thoracotomies in our thoracic centre during 2011–2013. Methods Pain therapy is aggressive and standardized in our thoracic centre thoughout the complete postoperative stay. Patients receive either standardized epidural analgesia with ropivacaine + sufentanil 4–8 mls/h (500 mls bag) and are bridged when the epidural bag is finished to a standardized controlled-release oxycodone protocol with non opioid every 6 hours (EDA Group), or patients receive immediately postoperative standardized oral analgesic protocol with controlled-released oxycodone and non opioid every 6 h (Opioid Group). All patients are visited daily by a pain specialist throughout the whole stay. Results Data of 1555 thoracotomies from 2011-2013 were analysed, 838 patients in the EDA Group and 717 patients in the Opioid Group. There was no difference with regard to sex or age between groups. 7.5% of patients in the EDA Group and 13% in the Oxy Group had a preexisting pain therapy (p = 0.001). In the EDA Group epidural analgesia was performed for 4.6 ± 1.5 days. Length of hospital stay was the same in both groups (EDA: 9.9.6 ± 4.9 vs Opioid: 9.6 ± 5.8 days). 84.7% of patients in the EDA Group and 79.1% of patients of the Oxy Group were dismissed with oral opioid (p < 0.004). When patients were dismissed with opioid medication patients in the EDA Group were dismissed with higher oxycodone opioid doses than patients in the Opioid Group (29.5 ± 15.2 mg vs 26.9 ± 15.2 mg, p = 0.01). There was no difference with regard to dejection time between the two groups (EDA: 3.8 ± 2.2 days vs Opioid: 3.7 ± 1.6 days, n.s.). Conclusion We first present data monitoring postoperative analgesic protocols after thoracotomies throughout the whole stay in hospital until dismission. Our retrospective data indicate that patients with epidural analgesia stay as long in hospital as patients with systemic opioid based therapy. Patients with initial epidural analgesia are dismissed with higher oxycodone opioid doses than patients with initial opioid based postoperative analgesia. We found no difference in recovery of bowel function. Study limitations The study design is retrospectively and results might be biased.

Background: To assess prospectively the incidence of chronic and neuropathic pain in patients undergoing anteroaxillary thoracotomy with postoperative epidural analgesia or controlled-release oxycodone pain regimen. Methods: 77 patients who underwent anteroaxillary thoracotomy were enrolled in our observational study. 40 patients received postoperatively a standardized oral analgesic protocol with controlled-release oxycodone and IV non opioid (CRO Group), and 37 patients received epidural analgesia with ropivacaine 0.1% + 1 μg/ml sufentanil (EDA Group) and IV non opioid. The painDETECT questionnaire was completed from the patients with one of the authors (JL) on the 7th postoperative day and six months postoperatively. Results: The data of 60 patients were eligible for statistical analysis, 28 patients in the CRO Group and 32 patients in the EDA Group. 17 patients did not reach the 6-months follow-up interval (12 drop outs in the CRO Group and 5 drop outs in the EDA Group). 79% percent of patients in the CRO Group and 74% percent of patients in the EDA Group had a numeric rating scale score (NRS) = 0 after 6 months. 22% percent of patients in the CRO Group and 16% percent of patients in the EDA Group experienced a NRS 1–3 6-months postoperatively. No patient in the CRO Group and 9% percent of patients in the EDA Group had 6-months postoperatively a NRS 4–6. Neither in the CRO Group nor in the EDA Group we could detect a neuropathic pain 6 months postoperatively corresponding to a painDETECT score > 18. Overall, with regard to NRS, there was no statistical difference between the two groups (p = 0.13). 90% percent of patients in the CRO Group and 90% percent of patients in the EDA Group showed 6-months postoperatively a painDETECT score < 13 (definitely no neuropathic pain), and 9% percent in the EDA Group and 11% in the CRO Group had a 6-months painDETECt score 13–18 (p = not significant). Conclusion: These pilot data indicate that epidural analgesia is not superior to systemic postoperative analgesia with regard to preventing chronic or neuropathic pain after thoracotomy.

Background Accumulating evidence suggests a role of obstructive sleep apnoea (OSA) as a risk factor for coronary atherosclerosis. This study aimed i) to assess the prevalence of OSA in the general population and ii) to analyse the association of this disorder with traditional cardiovascular disease risk factors and subclinical coronary atherosclerosis. Methods In a cross-sectional analysis of the Heinz Nixdorf Recall study a subgroup of 1604 subjects (791 men, age 50–80 years) underwent OSA screening. Furthermore, coronary artery calcium (CAC) was measured. OSA was defined as apnoea-hypopnoea index (AHI) ≥ 15/h. Results OSA was observed in 29.1% of men and 15.6% of women. In a multiple linear regression analysis adjusted for risk factors AHI was associated with CAC in men aged ≤65 years (estimated log-transformed increase of CAC = 0.25, 95% confidence interval (CI) = −0.001–0.50, p = 0.051) and in women of any age (estimated log-transformed increase = 0.23, 95% CI = 0.04–0.41, p = 0.02). Doubling of the AHI was associated with a 19% increase of CAC in men aged ≤65 years and with a 17% increase in women of any age. Conclusions In the general population aged ≥50 years OSA is associated with subclinical atherosclerosis in men aged ≤65 years and in women of any age, independent of traditional cardiovascular risk factors.

Objectives Pulmonary sarcomatoid carcinoma (PSC) is a rare histological subtype of non-small cell lung cancer and comprises a diagnostically and therapeutically challenging group of tumours. We explored the clinicopathological features and prognostic factors of this tumour. Methods We conducted a retrospective study of all patients who were treated for PSC in the Department of Thoracic Surgery between May 2005 and December 2014. Primary outcomes of interest were patient survival and prognostic factors. Results A total of 58 patients were treated for sarcomatoid carcinoma within the described period and 46 patients underwent surgical resection with curative intent. The mean follow-up period was 30 months. Of the operated patients, 21.7% had pathological stage I disease, and 78.3% had more advanced disease. There were 25 carcinosarcomas, 10 pleomorphic carcinomas, 7 spindle cell carcinomas, 3 giant cell carcinomas and 1 pulmonary blastoma. Overall 5-year survival of the operated patients was 28.7%. A total of 28 patients experienced recurrence and died cancer-related. Our analysis revealed that tumour size, gender, histological entity, lymphatic vessel invasion (L1) and vascular invasion (V1) did not influence survival. There was a trend for decreased survival in older patients (>65 years). Conclusions Surgical treatment can achieve satisfactory results with low perioperative mortality, but the overall prognosis even with multimodality concepts and in earlier tumour stages is worse compared to other types of non-small cell lung cancer.

Background Several studies have analysed adherence to continuous positive airway pressure (CPAP) therapy but little is known on the effects of age and gender. Methods Data from 4281 patients with obstructive sleep apnea (OSA) treated with CPAP (S8, ResMed, Sydney, Australia) were analysed, including apnea–hypopnea index (AHI), mask pressure, leakage, period of use (hours of use/night), and efficiency (days of use/total days). Patterns of use and treatment efficacy were compared between different age groups and genders. Results Average numbers of days used per week (range of the subgroups 5.8±1.6 to 6.3±1.2days/week) and period of use (range 363±88 to 395±120min) increased with age. Residual AHI CPAP (range 4.8±3.4 to 11.1±9.0/h), leakage (range 0.09±0.11 to 0.27±0.32l/s) increased significantly with age. Males had statistically significantly higher average hours of use (377±94 vs. 370±96min), AHI CPAP (6.4±4.9 vs. 5.4±4.5/h), mask pressure (8.8±2.0 vs. 8.4±1.9cm H 2 O), and leakage (0.13±0.16 vs. 0.11±0.15l/s) than females. Conclusion Adherence to therapy is high and therapeutic efficacy is excellent in long-term CPAP users. Adherence is both age- and gender-dependent, but the differences are small and not clinically relevant.

ApneaLink is a novel single-channel screening device for sleep apnea detection which is based on pressure-transduced measurement of oronasal airflow, summarised as respiratory disturbance index per hour of recording time (RDI(ApneaLink)). We tested ApneaLink's diagnostic performance in a patient population with high prevalence of sleep apnea.ApneaLink was applied simultaneously with in-laboratory polysomnography (PSG) (n = 102, 24 female, age 54.7 years) and sequentially with PSG in the unattended home setting (n = 131, 37 female, age 59.1 years). Predictive values were computed for apnea-defining thresholds of apnea-hypopnea index (AHI)or= 5/h,or=10/h,or=15/h. Night-to-night variability (NNV) was assessed over three consecutive nights (n = 55, 10 female, age 48.9 years).RDI(ApneaLink) correlated well with apnea-hypopnea index on PSG (PSG(AHI)) on simultaneous (r = 0.98, bias -0.7) and unattended home application (r = 0.95, bias -0.6). Predictive values were highest at AHIor= 10/h (in-laboratory: sensitivity 91.1%, specificity 87.5%, LR+ (positive likelihood ratio) 7.4, LR- 0.1; home: sensitivity 80%, specificity 85.5%, LR+5.5, LR- 0.2). NNV was low (V = 0.58 +/- 0.44, range 0-1.69).ApneaLink is an accurate screening tool for sleep apnea in a population with high prevalence of the disorder.

Background Tacrolimus (TAC) dosing in lung transplantation is traditionally based on blood trough levels (C0). The best sampling strategy for the estimation of total drug exposure (area-under-the-curve [AUC]) has not been determined. Methods Thirty-one 12-hour pharmacokinetic profiles were studied in 15 patients (8 men and 7 women, 42.0 ± 13 years) post-bilateral lung transplantation (7.3 ± 3.7 months; range, 3–18 months). Twelve-hour AUC (AUC 0–12 ) was calculated by trapezoidal rule. Relationships between individual concentration points or abbreviated kinetics (2–4 concentration points) and AUC 0–12 were determined by linear regression analysis ( R 2 ; absolute prediction error [APE]). Results Pharmacokinetic profiles showed high variability, particularly in the absorption phase. AUC was 221 ± 47.2 ng/ml (range, 156–329.3 ng/ml) at C0 10 to 15 ng/ml and was independent of TAC dose ( R 2 = 0.002). C0 was poorly predictive of AUC 0–12 ( R 2 = 0.64; APE, 16.1% ± 10.9%; range, 1.4%–37.8%). The predictive performance for AUC 0–12 was highest with abbreviated kinetics using 4 (C0/C2/C3/C4: R 2 = 0.99; APE, 2.6% ± 2.0%; range, 0.1%–7%) or 3 concentration points (C0/C2/C4: R 2 = 0.98; APE, 2.6% ± 2.1%; range, 0.1%–9.1%). Of the 2-point kinetics C2/C6 ( R 2 = 0.96; APE, 5.3% ± 3.7%; range, 0.1%–12.7%), C2/C4 ( R 2 =0.94, APE 6.7% ± 4.8%; range 0.1%–14.6%) and C0/C4 ( R 2 = 0.94; APE 4.1% ± 2.9%; range, 0.5%–11.4%) performed best. Single point strategies (best was C4: R 2 = 0.94; APE 7.1% ± 5.5%, range, 0.2%–24.1%) all had unacceptably high APE (range > 15%). Conclusion True TAC exposure shows high variability in stable lung transplant patients and is poorly predicted by C0. Abbreviated kinetics covering at least 2 concentration points between 0 and 4 hours post-drug intake are required for an accurate estimation of AUC.