Effect of Triple Combination CFTR Modulator Therapy on Sleep in Adult Patients with Cystic Fibrosis.

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.

Investigation of respiratory rate in patients with cystic fibrosis using a minimal-impact biomotion system.

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.

Obstructive sleep apnea and nocturnal hypoxemia in adult patients with cystic fibrosis.

BACKGROUND: Obstructive sleep apnea (OSA), nocturnal hypoxemia and excessive daytime sleepiness (EDS) are common comorbidities in people with cystic fibrosis (pwCF). Most of the data showing this originates from children and adolescents. The aim of this study was to collect data on sleep parameters, EDS and pulmonary function from a large cohort of adult pwCF. METHODS: Full overnight polysomnography (PSG) was performed. EDS was determined using the Epworth Sleepiness Scale (ESS). Demographic and clinical data (body mass index [BMI], pulmonary function, capillary blood gases) were collected. RESULTS: A total of 52 adult pwCF were included (mean age 30.7 ± 8.0 years, mean percent predicted forced expiratory volume in 1 s [ppFEV1] of 52.1 ± 14.8). Overall AHI was in the normal range (4.5 ± 4.0/h); 21/52 pwCF (40%) had an apnea-hypopnea index > 5/h. Nocturnal hypoxemia was found in 25% of participants and this was associated with ppFEV1 (p = 0.014), awake oxygen saturation (SpO2; p = 0.021) and awake partial pressure of oxygen (pO2; p = 0.003); there were no significant differences in age, lung function and BMI were found for pwCF with versus without OSA (all p > 0.05). Eight pwCF (15%) had an ESS score > 10 (indicating EDS). OSA was best predicted by awake pO2 (area under the curve [AUC] 0.66, p = 0.048), while nocturnal hypoxemia was best predicted by ppFEV1 (AUC 0.74, p = 0.009), awake pO2 (AUC 0.76, p = 0.006) and awake SpO2 (AUC 0.71; p = 0.025). CONCLUSION: OSA, nocturnal hypoxemia and EDS were common in adult pwCF, but no strong predictors were identified. Therefore, we suggest regular PSG and ESS scoring in adult pwCF, regardless of disease severity.

A novel minimal-contact biomotion method for long-term respiratory rate monitoring.

PURPOSE: In this study, we assessed the diagnostic accuracy of the device VitaLog (SWG Sportwerk GmbH & Co. KG, Dortmund, Germany) for estimation of respiratory rate (RR) variability. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Proof of principle study: diagnostic accuracy of a novel algorithm for the estimation of sleep stages and disease severity in patients with sleep-disordered breathing based on actigraphy and respiratory inductance plethysmography.

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.

Cognitive Function After Lung Transplantation.

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.

Influence of Sleep-Disordered Breathing on Quality of Life and Exercise Capacity in Lung Transplant Recipients.

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.

Independent Predictors for Higher Postoperative Pain Intensity During Recovery After Open Thoracic Surgery: A Retrospective Analysis in 621 Patients.

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 < 0.001). Stepwise backward elimination in multivariate logistic regression identified preexisting pain disease (P = 0.034), no epidural analgesia (P < 0.001), opioids in preoperative pain therapy (P < 0.001), and antidepressant medication (P = 0.003) as independent risk factors for higher pain intensity at rest on PODs 1-4. Same on PODs 5-8 with regard to opioids in preoperative pain therapy (P < 0.001) and antidepressant medication (P = 0.018). Moreover, on PODs 5-8, male gender had a lower risk (P < 0.003) for pain, and preexisting musculosceletal disease had a lower risk for more postoperative pain (P = 0.009). On coughing, male gender and younger age proved to have a lower risk for postoperative pain on PODs 1-8 and on PODs 1-4, respectively. Opioids in preexisting pain therapy and antidepressant medication were identified as risk factors for pain on PODs 1-8 on coughing, and pain disease was identified as a risk factor for more pain on PODs 1-4 (P = 0.041). Moreover, preexisting cardiac disease indicated more pain on PODs 1-4 (P = 0.05), and musculoskeletal disease and neurological disease indicated more pain on PODs 5-8 (P = 0.041, and P = 0.023). Conclusions: We present data on independent risk factors for higher pain intensity during recovery after thoracotomy. The lack of postoperative epidural analgesia, female gender, preexisting opioid pain therapy, and chronic pain are the strongest risk factors for higher pain intensity. Antidepressant medication was identified as an independent risk factor at rest and on coughing on all PODs. Study limitations: The study design is retrospective.

Validation of a non-contact screening device for the combination of sleep-disordered breathing and periodic limb movements in sleep.

PURPOSE: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

An association of particulate air pollution and traffic exposure with mortality after lung transplantation in Europe.

Air pollution from road traffic is a serious health risk, especially for susceptible individuals. Single-centre studies showed an association with chronic lung allograft dysfunction (CLAD) and survival after lung transplantation, but there are no large studies.13 lung transplant centres in 10 European countries created a cohort of 5707 patients. For each patient, we quantified residential particulate matter with aerodynamic diameter ≤10 µm (PM10) by land use regression models, and the traffic exposure by quantifying total road length within buffer zones around the home addresses of patients and distance to a major road or freeway.After correction for macrolide use, we found associations between air pollution variables and CLAD/mortality. Given the important interaction with macrolides, we stratified according to macrolide use. No associations were observed in 2151 patients taking macrolides. However, in 3556 patients not taking macrolides, mortality was associated with PM10 (hazard ratio 1.081, 95% CI 1.000-1.167); similarly, CLAD and mortality were associated with road lengths in buffers of 200-1000 and 100-500 m, respectively (hazard ratio 1.085- 1.130). Sensitivity analyses for various possible confounders confirmed the robustness of these associations.Long-term residential air pollution and traffic exposure were associated with CLAD and survival after lung transplantation, but only in patients not taking macrolides.

Robotic thoracic surgery results in shorter hospital stay and lower postoperative pain compared to open thoracotomy: a matched pairs analysis.

BACKGROUND: To evaluate postoperative pain intensity and length of hospital stay after open or robotic thoracic surgery in a standardized postoperative pain therapy setting. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The Influence of Type of Anesthesia, Perioperative Pain, and Preoperative Health Status on Chronic Pain Six Months After Thoracotomy-A Prospective Cohort Study.

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.

Do patients with intake of drugs labelled as sleep disturbing really sleep worse? A population based assessment from the Heinz Nixdorf Recall Study.

AIM: The sleep disturbing effect of many drugs is derived from clinical trials with highly selected patient collectives. However, the generalizability of such findings to the general population is questionable. Our aim was to assess the association between intake of drugs labelled as sleep disturbing and self-reported nocturnal sleep disturbances in a population-based study. METHODS: We used data of 4221 participants (50.0% male) aged 45 to 75 years from the baseline examination of the Heinz Nixdorf Recall Study in Germany. The interview provided information on difficulties falling asleep, difficulties maintaining sleep and early morning arousal. We used the summary of product characteristics (SPC) for each drug taken and assigned the probability of sleep disturbances. Thereafter, we calculated cumulative probabilities of sleep disturbances per subject to account for polypharmacy. We estimated prevalence ratios (PR) using log Poisson regression models with robust variance. RESULTS: The adjusted PRs of any regular nocturnal sleep disorder per additional sleep disturbing drug were 1.01 (95% confidence interval (CI) 0.97, 1.06) and 1.03 (95% CI 1.00, 1.07) for men and women, respectively. Estimates for each regular nocturnal sleep disturbance were similarly close to 1. PRs for regular nocturnal sleep disturbances did not increase with rising cumulative probability for drug-related sleep disturbances. CONCLUSIONS: SPC-based probabilities of drug-related sleep disturbances showed barely any association with self-reported regular nocturnal sleep disturbances. We conclude that SPC-based probability information may lack generalizability to the general population or may be of limited data quality.

Decreased Hypercapnic Ventilatory Response in Long-Term Lung Transplant Recipients is Associated with Exercise Impairment.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: HCVR is reduced in long-term bilateral lung transplant recipients and this might explain the observed impairment of exercise capacity.

Short- and Mid-Term Changes in Lung Function after Bilateral Pulmonary Metastasectomy.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Association of short-term ozone and temperature with sleep disordered breathing.

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±sd AHI 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.

Controlled-Release Oxycodone as "Gold Standard" for Postoperative Pain Therapy in Patients Undergoing Video-Assisted Thoracic Surgery or Thoracoscopy: A Retrospective Evaluation of 788 Cases.

BACKGROUND: To assess the clinical efficacy of controlled-release oxycodone for postoperative analgesia after video-assisted thoracic surgery (VATS) or thoracoscopy. METHODS: 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. RESULTS: 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. CONCLUSION: 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. STUDY LIMITATIONS: The study design is retrospective in nature.

Thoracic pain in patients with chronic interstitial lung disease-an underestimated symptom.

Introduction: Prevalence and predisposing factors for the development of thoracic pain (TP) in patients with chronic interstitial lung disease (cILD) are largely unknown. Underestimation and insufficient therapy of pain can lead to worsened ventilatory function. Quantitative sensory testing is an established tool for characterization of chronic pain and its neuropathic components. We investigated frequency and intensity of TP in cILD patients and the potential association with lung function and quality of life. Materials and methods: We prospectively investigated patients with chronic interstitial lung disease to analyze risk factors for the development of thoracic pain and quantify thoracic pain through quantitative sensory testing. In addition, we studied the relationship between pain sensitivity and lung function impairment. Results: Seventy-eight patients with chronic interstitial lung disease and 36 healthy controls (HCs) were included. Thoracic pain occurred in 38 of 78 patients (49%), most frequently in 13 of 18 (72%, p = 0.02) patients with pulmonary sarcoidosis. The occurrence was mostly spontaneous and not related to thoracic surgical interventions (76%, p = 0.48). Patients with thoracic pain showed a significant impairment of mental well-being (p = 0.004). A higher sensitivity to pinprick stimulation during QST can be observed in patients with thoracic pain (p < 0.001). Steroid treatment was associated with lower sensitivity within thermal (p = 0.034 and p = 0.032) and pressure pain testing (p = 0.046). We observed a significant correlation between total lung capacity and thermal (p = 0.019 and p = 0.03) or pressure pain sensitivity (p = 0.006 and p = 0.024). Conclusion: This study was performed to investigate prevalence, risk factors and thoracic pain in patients with chronic interstitial lung disease. Thoracic pain mostly occurs spontaneous as a frequent symptom, and seems to be an underestimated symptom in patients with chronic interstitial lung disease, especially those with pulmonary sarcoidosis. Timely identification of thoracic pain may allow starting symptomatic treatment at early stage, before impairment in quality of life occurs. Clinical Trial Registration: https://www.drks.de/drks_web/, Deutsches Register Klinischer Studien (DRKS) DRKS00022978.

Significantly favourable outcome for patients with non-small-cell lung cancer stage IIIA/IIIB and single-station persistent N2 (skip or additionally N1) disease after multimodality treatment.

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.

Potential Prognostic Value of Preoperative Leukocyte Count, Lactate Dehydrogenase and C-Reactive Protein in Thymic Epithelial Tumors.

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.