Role of multidrug-resistant bacteria in weaning from invasive mechanical ventilation.

BACKGROUND: Although multidrug-resistant bacteria (MDR) are common in patients undergoing prolonged weaning, there is little data on their impact on weaning and patient outcomes. METHODS: This is a retrospective analysis of consecutive patients who underwent prolonged weaning and were at a university weaning centre from January 2018 to December 2020. The influence of MDR colonisation and infection on weaning success (category 3a and 3b), successful prolonged weaning from invasive mechanical ventilation (IMV) with or without the need for non-invasive ventilation (NIV) compared with category 3c (weaning failure 3cI or death 3cII) was investigated. The pathogen groups considered were: multidrug-resistant gram-negative bacteria (MDRGN), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE). RESULTS: A total of 206 patients were studied, of whom 91 (44.2%) showed evidence of MDR bacteria (32% VRE, 1.5% MRSA and 16% MDRGN), with 25 patients also meeting the criteria for MDR infection. 70.9% of the 206 patients were successfully weaned from IMV, 8.7% died. In 72.2% of cases, nosocomial pneumonia and other infections were the main cause of death. Patients with evidence of MDR (infection and colonisation) had a higher incidence of weaning failure than those without evidence of MDR (48% vs. 34.8% vs. 21.7%). In multivariate analyses, MDR infection (OR 4.9, p = 0.004) was an independent risk factor for weaning failure, along with male sex (OR 2.3, p = 0.025), Charlson Comorbidity Index (OR 1.2, p = 0.027), pH (OR 2.7, p < 0.001) and duration of IMV before admission (OR 1.01, p < 0.001). In addition, MDR infection was the only independent risk factor for death (category 3cII), (OR 6.66, p = 0.007). CONCLUSION: Patients with MDR infection are significantly more likely to die during the weaning process. There is an urgent need to develop non-antibiotic approaches for the prevention and treatment of MDR infections as well as clinical research on antibiotic stewardship in prolonged weaning as well as in ICUs.

Clinical analysis on diagnostic accuracy of Bosch Vivalytic SARS-CoV-2 point-of-care test and evaluation of cycle threshold at admission for COVID-19 risk assessment.

BACKGROUND: Point-of-care (POC) polymerase chain reaction (PCR) tests have the ability to improve testing efficiency in the Coronavirus disease 2019 (COVID-19) pandemic. However, real-world data on POC tests is scarce. OBJECTIVE: To evaluate the efficiency of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) POC test in a clinical setting and examine the prognostic value of cycle threshold (CT) on admission on the length of hospital stay (LOS) in COVID-19 patients. METHODS: Patients hospitalised between January and May 2021 were included in this prospective cohort study. Patients' nasopharyngeal swabs were tested for SARS-CoV-2 with Allplex™2019-nCoV (Seegene Inc.) real-time (RT) PCR assay as gold standard as well as a novel POC test (Bosch Vivalytic SARS-CoV-2 [Bosch]) and the SARS-CoV-2 Rapid Antigen Test (Roche) accordingly. Clinical sensitivity and specificity as well as inter- and intra-assay variability were analyzed. RESULTS: 120 patients met the inclusion criteria with 46 (38%) having a definite COVID-19 diagnosis by RT-PCR. Bosch Vivalytic SARS-CoV-2 POC had a sensitivity of 88% and specificity of 96%. The inter- and intra- assay variability was below 15%. The CT value at baseline was lower in patients with LOS ≥ 10 days when compared to patients with LOS < 10 days (27.82 (± 4.648) vs. 36.2 (25.9-39.18); p = 0.0191). There was a negative correlation of CT at admission and LOS (r[44]s = - 0.31; p = 0.038) but only age was associated with the probability of an increased LOS in a multiple logistic regression analysis (OR 1.105 [95% CI, 1.03-1.19]; p = 0.006). CONCLUSION: Our data indicate that POC testing with Bosch Vivalytic SARS-CoV-2 is a valid strategy to identify COVID-19 patients and decrease turnaround time to definite COVID-19 diagnosis. Also, our data suggest that age at admission possibly with CT value as a combined parameter could be a promising tool for risk assessment of increased length of hospital stay and severity of disease in COVID-19 patients.

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.

Expression pattern of co-inhibitory molecules on CMV-specific T-cells in lung transplant patients.

OBJECTIVES: Cytomegalovirus infection (CMVi) occurs frequently in transplant patients. Co-inhibitory molecules on CMV-specific T-cells (TCMV) in patients after lung transplantation were investigated. METHODS: 59 lung transplant patients were stratified according to anti-CMV serostatus at time of transplantation. The co-inhibitors Programmed-Death-Receptor-1 (PD1) and B-and-T-Lymphocyte-Attenuator (BTLA) were detected on TCMV by flow cytometry (FACS). RESULTS: TCMV were detectable in CMV sero-positive patients (R+) and in CMV sero-negative patients with a lung graft of a CMV sero-positive donor (D+/R-); in both cases, the frequency of TCMV was higher than in healthy controls (HC). PD-1 on TCMV was increased in D+/R+ and D+/R- patients as compared to HC. BTLA was significantly enhanced on TCMV of D+/R- patients vs. HC. R+ patients with CMV reactivation in the past had an increased fraction of BTLA+ TCMV. CONCLUSION: In conclusion, the expression pattern of co-inhibitory molecules on TCMV is altered in patients after lung transplantation.

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.

Association between the time after transplantation and different immunosuppressive medications with dental and periodontal treatment need in patients after solid organ transplantation.

OBJECTIVE: The aim of this study was to investigate the association of time after transplantation and different immunosuppressive medications with dental and periodontal treatment needs in patients after solid organ transplantation (SOT). METHODS: After lung, liver, or kidney transplantation, patients were included and divided into subgroups based on the time after SOT (0-1, 1-3, 3-6, 6-10, and >10 years) and immunosuppression (tacrolimus, cyclosporine, mycophenolate, glucocorticoids, sirolimus, and monotherapy vs combination). Dental treatment need was determined by the presence of carious lesions, while periodontal treatment need was diagnosed based on a Periodontal Screening index score of 3-4. The overall treatment need included both the dental and/or periodontal treatment needs. Statistical analysis was performed using the Kruskal-Wallis test and chi-squared test (P < .05). RESULTS: A total of 169 patients were included after SOT. A dental treatment need of 44%, a periodontal treatment need of 71%, and an overall treatment need of 84% were detected in the total cohort. Only patients with >10 years after SOT had a lower dental treatment need compared to the other groups (P = .02). All other comparisons of dental, periodontal, and overall treatment needs were comparable between subgroups depending on time since SOT. Furthermore, no statistically significant differences were found in terms of the dental, periodontal, or overall treatment needs following the administration of different immunosuppressive medications. CONCLUSION: The high treatment need of patients after SOT, irrespective of the time since transplantation, suggests insufficient dental and periodontal treatment before and maintenance after organ transplantation. Furthermore, immunosuppressive medication was not associated with the treatment need.

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.

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.

Primary Ciliary Dyskinesia in Adult Bronchiectasis: Data from the German Bronchiectasis Registry PROGNOSIS.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by the malfunction of motile cilia and a specific etiology of adult bronchiectasis of unknown prevalence. A better understanding of the clinical phenotype of adults with PCD is needed to identify individuals for referral to diagnostic testing. RESEARCH QUESTION: What is the frequency of PCD among adults with bronchiectasis; how do people with PCD differ from those with other etiologies; and which clinical characteristics are independently associated with PCD? STUDY DESIGN AND METHODS: We investigated the proportion of PCD among the participants of the German Bronchiectasis Registry PROGNOSIS, applied multiple imputation to account for missing data in 64 (FEV1), 58 (breathlessness), 26 (pulmonary exacerbations), and two patients (BMI), respectively, and identified predictive variables from baseline data using multivariate logistic regression analysis. RESULTS: We consecutively recruited 1,000 patients from 38 centers across all levels of the German health care system. Overall, PCD was the fifth most common etiology of bronchiectasis in 87 patients (9%) after idiopathic, postinfective, COPD, and asthma. People with PCD showed a distinct clinical phenotype. In multivariate regression analysis, the chance of PCD being the etiology of bronchiectasis increased with the presence of upper airway disease (chronic rhinosinusitis and/or nasal polyps; adjusted OR [aOR], 6.3; 95% CI, 3.3-11.9; P < .001), age < 53 years (aOR, 5.3; 95% CI, 2.7-10.4; P < .001), radiologic involvement of any middle and lower lobe (aOR, 3.7; 95% CI, 1.3-10.8; P = .016), duration of bronchiectasis > 15 years (aOR, 3.6; 95% CI, 1.9-6.9; P < .001), and a history of Pseudomonas aeruginosa isolation from respiratory specimen (aOR, 2.4; 95% CI, 1.3-4.5; P = .007). INTERPRETATION: Within our nationally representative cohort, PCD was a common etiology of bronchiectasis. We identified few easy-to-assess phenotypic features, which may promote awareness for PCD among adults with bronchiectasis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02574143; URL: www. CLINICALTRIALS: gov.

Elevated gamma-glutamyltransferase is associated with mortality in lung transplantation for cystic fibrosis.

Cystic fibrosis (CF) is a life-threatening autosomal recessive hereditary disease, affecting multiple organs. In end stage disease, lung transplantation improves the quality of life and prolongs survival. CF liver disease (CFLD) as co-morbidity develops in 8-17% of CF patients. We aimed to investigate the impact of liver injury on prognosis following lung transplantation. Thirty-one patients with CF who underwent double lung transplantation (DLTx) from 1999 to 2009 were included. Post-transplant survival, liver serum parameters as well as INR, creatinine and the MELD-Score were determined preoperatively, 1 day and 4 weeks postoperatively. Prognostic impact of liver function on outcome was analysed. Mean patient age was 25 (15-38) and post-transplant 1 year-survival was 74%, 3 years 71% and 5 years 68%. Patients were grouped according to post-transplant survival, those deceased within the first year as group I (n = 8) and patients who survived longer as group II (n = 23). Group I exhibited significantly elevated gamma-glutamyltransferase (GGT), bilirubin and reduced platelets postoperatively. Low platelet count, increased bilirubin and GGT were associated with mortality after DLTx. Prospective studies are needed to determine a potential use and clinical implications for liver function tests in patients with CF before lung transplantation.

Cardiac autonomic function and cardiovascular response to exercise in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with impaired exercise tolerance, but it has not been established to what extent cardiac autonomic function impacts on exercise capacity. OBJECTIVE: To evaluate whether there is an association between airflow limitation and cardiac autonomic function and whether cardiac autonomic function plays a role in exercise intolerance and daily physical activity (PA) in patients with COPD. METHODS: Univariate and multivariate analyses were performed to evaluate the association between both 6-minute walking test (6MWT) and PA (steps per day) and pulmonary function, cardiac autonomic function (HR at rest, HRR and heart rate variability, HRV) in patients with COPD. RESULTS: In 154 COPD patients (87 females, mean [SD]: age 62.5 [10.7] years, FEV(1) %predicted (43.0 [19.2]%), mean HR at rest was elevated (86.4 [16.4] beats/min) and HRV was reduced (33.69 [28.96] ms) compared to published control data. There was a significant correlation between FEV(1) and HR at rest (r = -0.32, p < 0.001), between HR at rest and 6MWD (r = -0.26, p = 0.001) and between HR at rest and PA (r = -0.29, p = 0.010). No correlation was found between HRV and 6MWD (r = 0.089, p = 0.262) and PA (r = 0.075, p = 0.322). In multivariate analysis both HR and FEV(1) were independent predictors of exercise capacity in patients with COPD. CONCLUSIONS: In patients with COPD the degree of airflow limitation is associated with HR at rest. The degree of airflow limitation and cardiac autonomic function, as quantified by HR at rest, are independently associated with exercise capacity in patients with COPD.

Combination of everolimus with calcineurin inhibitor medication resulted in post-transplant haemolytic uraemic syndrome in lung transplant recipients--a case series.

BACKGROUND: Post-transplant haemolytic uraemic syndrome (HUS) is a rare but serious disease with a high mortality rate, when left untreated. Immunosuppressive drugs like calcineurin inhibitors as well as mammalian target of rapamycin inhibitors have been reported as causative agents for post-transplant HUS. METHODS: A retrospective observational study was performed in lung transplant recipients, who took part in an interventional study, in two centres. Haemoglobin, platelets, creatinine and lactate dehydrogenase levels were monitored during routine follow-up and patients with deteriorating kidney function were screened for post-transplant HUS. All cases of post-transplant HUS were identified by clinical and laboratory findings. Outcome was recorded until 6 months after diagnosis. RESULTS: A total of 2188 visits in 512 lung transplant recipients (outpatients) were analysed. Out of those, 126 patients took part in an interventional study. In this study, 67 were switched to everolimus in combination with calcineurin inhibitors 4 weeks after transplantation, 59 patients remained on standard immunosuppression (calcineurin inhibitors, mycophenolate mofetil and prednisolone). Five cases of post-transplant HUS were identified in the everolimus group. None of the patients had evidence of gastrointestinal infection or preexisting renal disease. Post-transplant HUS was treated with therapeutic plasma exchange and methylprednisolone pulse therapy. Everolimus was discontinued in all five patients. This treatment regimen led to normalization of haemoglobin, platelets and improved renal function. Two patients developed end-stage renal failure and were maintained on haemodialysis. One patient died due to multiorgan failure. Improvement of renal function was seen in two patients. No further cases were recorded in patients without everolimus during the study period. CONCLUSIONS: Our data should raise the awareness of post-transplant HUS in lung transplant recipients. Post-transplant HUS is a rare disease, but it is a serious cause of acute renal failure in lung transplant recipients treated with a combination of everolimus and calcineurin inhibitors.

Bronchoscopically obtained volatile biomarkers in lung cancer.

BACKGROUND: The exhaled breath of lung cancer patients contains volatile organic compounds (VOCs) that differ from those in healthy individuals. These VOCs can be detected with methods such as ion mobility spectrometry (IMS); their origin remains unknown. METHODS: In 19 patients with lung cancer, exhaled breath was aspirated via the working channel of a flexible bronchoscope from both the tumor-bearing and the opposite lung and analyzed with IMS. RESULTS: IMS measurement through the working channel of a bronchoscope was feasible and safe. In comparison to the opposite lung, we found two peaks that were significantly higher and three peaks that were significantly lower on the IMS of the tumor-bearing site. VOCs differ in concentration depending on the histologic subtype. CONCLUSION: Our results indicate that VOCs in lung cancer patients are produced locally in or around the tumor, and it is most likely that these VOCs represent underlying metabolic processes of the tumor.

Oral health related quality of life depending on oral health and specific factors in patients after lung transplantation.

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 < .05). RESULTS: A total of 60 patients after LuTx and 70 HC were included. The DMF-T, D-T, and M-T as well as periodontal disease severity was significantly higher in LuTx group (P < .01). The OHIP G14 differed neither clinically relevant, nor statistically significant (LuTx: 1.70 ± 2.70, HC: 1.54 ± 2.86, P = .15). While in HC the DMF-T, M-T, and periodontal condition had an influence on OHIP G14 values (P < .05), in LuTx no influence was detected for dental and periodontal condition as well as specific factors investigated. CONCLUSIONS: The oral health perception of LuTx patients does not reflect the apparent oral health deficiencies. Consequently, sensitization and motivation for an increased dental behavior is needed.

Deficits in oral health behavior and oral health status in patients 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 < .005). CONCLUSIONS: This single center study shows deficits in oral health and oral health behavior in patients after LTx. There is a strong need for interdisciplinary collaboration and clinical guidelines to foster better oral health education of the transplant recipient and better oral health.

Ease of use of tobramycin inhalation powder compared with nebulized tobramycin and colistimethate sodium: a crossover study in cystic fibrosis patients with pulmonary Pseudomonas aeruginosa infection.

BACKGROUND: This study assessed the ease of use of tobramycin inhalation powder (TIP) administered via T-326 inhaler versus tobramycin inhalation solution (TIS) and colistimethate sodium (COLI), both administered via nebulizers, for the treatment of chronic pulmonary Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF). METHODS: A real-world, open-label, crossover, interventional phase IV study was conducted in CF patients aged ⩾6 years with forced expiratory volume in 1 second (FEV1) ⩾25% to ⩽90% predicted. Patients were assigned to one of the three treatment arms in Cycle 1; all patients received TIP in Cycle 2. Each cycle consisted of 28 days on and 28 days off the treatment. RESULTS: A total of 60 patients [mean (standard deviation) age, 27.6 (8.4) years] were allocated to three treatment arms [TIS/TIP ( n = 14); COLI/TIP ( n = 28); TIP/TIP ( n = 18)] in Cycle 1. The mean total administration time, which included device setup and cleaning, in Cycle 1 versus Cycle 2 for TIS/TIP, COLI/TIP, and TIP/TIP arms were 37.0 versus 5.0 min, 16.4 versus 3.8 min, and 4.2 versus 3.4 min, respectively. The difference in mean total administration time was significantly shorter in Cycle 2 than in Cycle 1 for TIS/TIP ( p = 0.0112) and COLI/TIP ( p = 0.0016) arms. Overall, 12 patients were found to have contaminated devices across the two treatment cycles. In the TIP/TIP arm, no contamination of the T-326 inhaler was observed in either cycle. Treatment satisfaction, assessed by the Treatment Satisfaction Questionnaire for Medication and ACCEPT® questionnaire, was better overall for TIP compared with TIS and COLI. There were no unexpected adverse events and most were mild or moderate in intensity. CONCLUSION: The T-326 inhaler used to deliver TIP was easy to use, required shorter total administration time, and was much less frequently contaminated than the nebulizers. The safety findings observed for TIP were generally consistent with its established safety profile.

Long-term safety of tobramycin inhalation powder in patients with cystic fibrosis: phase IV (ETOILES) study.

OBJECTIVE: Long-term treatment with inhaled antibiotics is recommended for chronic Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) patients. The ETOILES study (Clinicaltrials.gov identifier: NCT01519661) evaluated the safety of tobramycin inhalation powder (TIP) for 1 year. RESEARCH DESIGN AND METHODS: This single-arm, open-label, multicenter, phase IV trial, enrolled CF patients aged ≥6 years, with baseline FEV1 ≥25%-≤75% predicted and Pa infection, and assessed the safety of TIP over six cycles in terms of the incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs). Secondary endpoints included presence of airway reactivity, relative change in FEV1% predicted, and change in sputum Pa density (log10 colony forming units/g sputum). RESULTS: A total of 157 patients were enrolled, and 96 patients (61.1%) completed the study. The most commonly reported AE was infective pulmonary exacerbation of CF (55.4%). Cough was reported as an AE in 23.6% of patients; a majority were mild or moderate and two were severe (1.3%). SAEs were reported by 31.2% of patients. No deaths were reported during the study. There were no clinically meaningful changes reported in airway reactivity. Most frequently reported post-inhalation event was cough at all time points; however, it was of short duration (<4 minutes) and decreased over the course of the study, possibly due to patients becoming more experienced with the administration of TIP. The post-inhalation events resolved without intervention in most cases. FEV1% predicted remained stable from Cycles 1 to 4 and tended to decrease thereafter, although it was not statistically significant (change from baseline to study end mean [SD] = -1.9% [14.55]; P = 0.199). CONCLUSIONS: This was one of the largest studies with long-term TIP exposure. The majority of patients enrolled were adults with more advanced CF lung disease than those in previous TIP studies. No new emerging safety signals were seen and efficacy was sustained during the year.

Predictors of obstructive sleep apnea in lung transplant recipients.

BACKGROUND: The aim of our study was to determine the prevalence and clinical predictors of obstructive sleep apnea in lung transplantation recipients. METHODS: In a cross-sectional analysis we studied 77 clinically stable lung transplant recipients (45 men, time range after lung transplantation [LTX]: from one month to 15 years). Indications for LTX were 36 chronic obstructive lung disease (COPD), 27 idiopathic pulmonary fibrosis (IPF), eight cystic fibrosis, and six others. In-lab polysomnography (PSG) was performed to investigate sleep characteristics. Obstructive sleep apnea (OSA) and central sleep apnea were defined by an apnea-hypopnea index (AHI) ≥ 10/h. RESULTS: The prevalence of OSA and central sleep apnea (CSA) were 42.9% and 6.5%, respectively. OSA was present in 61% of patients with pre-transplant COPD and 52% of patients with pre-transplant IPF. Univariate analysis showed that OSA was significantly associated with neck circumference per 1-cm size increment (odds ratio [OR] = 1.21, 95% confidence interval [CI] = 1.04-1.42, p = 0.01) and pre-transplant COPD/IPF vs other lung diseases (cystic fibrosis, pulmonary arterial hypertension, α-1 antitrypsin deficiency, and lymphangioleiomyomatosis) (OR = 6.89, 95% CI = 1.41-33.56, p = 0.02), whereas age ≥57 years (OR = 1.76, 95% CI = 0.69-4.48, p = 0.24), male gender (OR = 2.33, 95% CI = 0.89-6.01, p = 0.08), and BMI ≥ 24.6 kg/m(2) (OR = 1.73, 95% CI = 0.68-4.40, p = 0.25) did not reach a level of statistical significance. In a multivariate analysis neck circumference per 1-cm size increment (OR = 1.20, 95% CI = 1.02-1.41, p = 0.025) and pre-transplant COPD/IPF (OR = 5.34, 95% CI = 1.01-28.13, p = 0.048) remained independently associated with OSA. CONCLUSIONS: The prevalence of OSA is high in stable lung transplant recipients. Pre-transplant COPD is an independent predictor of OSA.

Exhaled volatile organic compounds discriminate patients with chronic obstructive pulmonary disease from healthy subjects.

Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory disease characterized by incompletely reversible airway obstruction. This clinically heterogeneous group of patients is characterized by different phenotypes. Spirometry and clinical parameters, such as severity of dyspnea and exacerbation frequency, are used to diagnose and assess the severity of COPD. The purpose of this study was to investigate whether volatile organic compounds (VOCs) could be detected in the exhaled breath of patients with COPD and whether these VOCs could distinguish COPD patients from healthy subjects. Moreover, we aimed to investigate whether VOCs could be used as biomarkers for classifying patients into different subgroups of the disease. Ion mobility spectrometry was used to detect VOCs in the exhaled breath of COPD patients. One hundred and thirty-seven peaks were found to have a statistically significant difference between the COPD group and the combined healthy smokers and nonsmoker group. Six of these VOCs were found to correctly discriminate COPD patients from healthy controls with an accuracy of 70%. Only 15 peaks were found to be statistically different between healthy smokers and healthy nonsmokers. Furthermore, by determining the cutoff levels for each VOC peak, it was possible to classify the COPD patients into breathprint subgroups. Forced expiratory volume in 1 second, body mass index, and C-reactive protein seem to play a role in the discrepancies observed in the different breathprint subgroups.

Changes in lung function parameters after wedge resections: a prospective evaluation of patients undergoing metastasectomy.

BACKGROUND: Pulmonary metastasectomy with lung-sparing local excisions is a widely accepted method of treating stage IV malignancies in selected cases. The ability to predict postoperative lung function is an unresolved issue, especially when multiple wedge resections are planned. To help develop a method to predict postoperative lung function after wedge resections, we present this prospective observational study. METHODS: A total of 77 patients who underwent one or more wedge resections to remove lung metastases completed the study protocol. Spirometry results, diffusion capacity of lung for carbon monoxide (Dlco), and blood gases and potential confounding factors were measured prior to, immediately following, and 3 months after the procedure and were analyzed. RESULTS: Seventy-seven patients with a median age of 61.3 years underwent up to 22 wedge resections. The mean lung function losses were FVC (-7.5%), total lung capacity (TLC) (-7.9%), FEV(1) (-9.2%), and Dlco (-8.8%), and all were statistically significant (P < .001). The lung function losses also differed significantly between those having a single and those with more than eight wedge resections. Using regression analysis, we found that for every additional wedge resection, there was a reduction in FVC of 30 mL (0.7%), in TLC of 44 mL (0.65%), and in FEV(1) of 23 mL (0.58%). CONCLUSIONS: Metastasectomy by wedge resection significantly reduces lung function parameters. As a benchmark, we can predict a 0.6% decrease in spirometry values and Dlco for every additional wedge resection, and a decrease of approximately 5% that may be attributed to thoracotomy.