The Prognostic Role of Early Postoperative Troponin I in Lung Transplantation-A Retrospective 7-Year Analysis.

OBJECTIVES: Postoperative cardiac troponin I concentration is predictive of worsened outcomes in cardiac surgery. Lung transplantation (LT) surgery shares common features with cardiac surgery, but postoperative troponin has yet to be investigated. The authors aimed to evaluate the association between early postoperative troponin concentration and the 1-year mortality after transplantation. DESIGN: A retrospective, observational, single-center study. SETTING: At a tertiary care, university hospital. PARTICIPANTS: Patients who underwent lung transplantation from January 2011 to December 2017 INTERVENTIONS: For each patient, preoperative, intraoperative, and postoperative data were collected, as well as the troponin I measurement at the moment of postoperative intensive care unit admission. MEASUREMENTS AND MAIN RESULTS: Two hundred twenty LT procedures were analyzed. Troponin I was elevated in all LT patients, with a median of 3.82 ng/mL-1 (2-6.42) ng/mL-1 significantly higher in non-survivors than in survivors with 5.39 (2.88-7.44) v 3.50 ng/mL (1.74-5.76), p = 0.005. In the multivariate analysis, the authors found that only the Simplified Acute Physiology Score II score (hazard ratio [HR] 1.03; 95% confidence interval [CI] [1.001; 1.05]; p = 0.007) and the need to maintain extracorporeal life support at the end of surgery (HR 2.54; 95% CI [1.36; 4.73]; p = 0.003) were independently associated with the 1-year mortality. The multiple linear regression model found that troponin levels were associated with the need for extracorporeal life support (ECLS) (p = 0.014), the amount of transfused packed red blood cells (p = 0.008), and bilateral LT (p < 0.001). CONCLUSION: Early postoperative troponin serum levels were not independently associated with 1-year mortality. Early postoperative troponin I levels were correlated to bilateral LT, the need for ECLS, and intraoperative blood transfusion.

Coping strategies, anxiety and depression related to the COVID-19 pandemic in lung transplant candidates and recipients. Results from a monocenter series.

BACKGROUND: The COVID-19 pandemic has been associated with an increase in anxiety and depression symptoms in people. We investigated the impact of the pandemic on coping strategies and anxiety and depression in lung transplantation (LT) recipients and patients with end-stage chronic lung disease awaiting LT. METHODS: We retrospectively investigated coping strategies by using the Coping Inventory for Stressful Situations questionnaire and anxiety and depression symptoms by the Hospital Anxiety and Depression scale in 115 LT candidates and recipients. RESULTS: Overall, 63 participants (20 women; median age 59 years [interquartile range 52•65]) answered one or both questionnaires (49 LT recipients and 14 LT candidates). The preferred coping strategy was task-focused for 51 (86.4%) participants, with no difference between LT recipients and candidates nor according to the main anamnestic and clinical data. Eleven patients had suspected or proven depression symptoms, and 18 had suspected or proven anxiety symptoms. Coping strategies related to COVID-19 did not differ by presence of anxiety or depression symptoms. CONCLUSION: In the current pandemic, healthcare professionals should consider these results to provide relevant psychological help to these fragile populations and promote a systematic and wide multidisciplinary assessment of LT recipients and candidates.

Burden and Characteristics of Severe Chronic Hypoxemia in a Real-World Cohort of Subjects with COPD.

BACKGROUND: Chronic respiratory failure may occur as a consequence of chronic obstructive pulmonary disease (COPD) and is associated with significant morbidity and mortality. Hypoxemia is determined by underlying disease characteristics and comorbidities. Severe hypoxemia is typically only found in subjects with severe airflow obstruction (FEV1<50% predicted). However, how hypoxemia relates to disease characteristics is not fully understood. METHODS: In the French Initiatives BPCO real-life cohort, arterial blood gases were routinely collected in most patients. Relationships between severe hypoxemia, defined by a Pa02<60 mmHg (8 kPa) and clinical/lung function features, comorbidities and mortality were assessed. In subjects with severe hypoxemia, clinical characteristics and comorbidities were compared between those with non-severe versus severe airflow limitation. Classification and regression trees (CART) were used to define clinically relevant subgroups (phenotypes). RESULTS: Arterial blood gases were available from 887 subjects, of which 146 (16%) exhibited severe hypoxemia. Compared to subjects with a PaO2≥60 mmHg, the severe hypoxemia group exhibited higher mMRC dyspnea score, lower FEV1, higher RV and RV/TLC, more impaired quality of life, lower 6-minute walking distance, less frequent history of asthma, more frequent diabetes and higher 3-year mortality rate (14% versus 8%, p=0.026). Compared to subjects with Pa02<60 mmHg and FEV1<50% (n=115, 13%), those with severe hypoxemia but FEV1≥50% predicted (n=31) were older, had higher BMI, less hyperinflation, better quality of life and a higher rate of diabetes (29% versus 13%, p=0.02). Severe hypoxemia was better related to CART-defined phenotypes than to GOLD ABCD classification. CONCLUSION: In this cohort of stable COPD subjects, severe hypoxemia was associated with worse prognosis and more severe symptoms, airflow limitation and hyperinflation. Compared to subjects with severe hypoxemia and severe airflow limitation, subjects with severe hypoxemia despite non-severe airflow limitation were older, had higher BMI and more diagnosed diabetes. TRIAL REGISTRATION: 04-479.

Outcome of Lung Transplantation Using Grafts From Donors Over 65 Years of Age.

BACKGROUND: The outcome of lung transplantation (LT) is correlated with donor selection. A donor age of 65 years is classically considered a contraindication to lung procurement, and the results of LT from elderly donors remain to be established. METHODS: This was a retrospective study of a prospectively maintained database including all LTs performed in a single institution (Bichat Hospital, University of Paris, Paris, France) from January 2014 to March 2019. Donors65 years of age or older were included in the elderly group, whereas donors younger than 65 years of age were included in the control group. RESULTS: The study group included 241 LTs, including 44 (18%) in the elderly group and 197 (82%) in the control group. As compared with the control group, the elderly group was characterized by the following: donors of shorter stature (166 cm vs 172 cm; P = .04) and with less smoking history (14% vs 40%; P = .001), less bronchoscopic abnormality (20% vs 36%; P = .042), and less chest opacity (16% vs 30%; P = .048); and recipients of shorter stature (166 cm vs 170 cm; P = .04) but with similar diagnoses and gravity. There was no significant difference between the groups in any of the outcomes studied, including primary graft dysfunction, 30-day mortality, 1-year survival, chronic lung allograft dysfunction-free survival, and overall survival. In univariate analysis, the Oto lung donor score was the only factor associated with 1-year survival (score of 6 in alive patients vs score of 7 in dead patients; P = .04); donor age 65 years old or older was not. CONCLUSIONS: Carefully selected lung grafts from donors 65 years of age or older are associated with outcomes similar to those reported with grafts from younger donors Grafts from older donors thus provide an interesting option to expand the donor pool during a shortage.

Use of CT-SCAN score and volume measures to early identify restrictive allograft syndrome in single lung transplant recipients.

BACKGROUND: Restrictive allograft syndrome (RAS) after lung transplantation (LTx) is associated with the poorer graft survival in patients with chronic lung allograft dysfunction (CLAD). Nevertheless, its diagnostic criteria have not been clearly defined after single-LTx (SLTx). Hence, we studied an SLTx cohort with CLAD to investigate the utility of both computed tomography (CT)-score/volume measures and functional spirometric criteria for the early identification of RAS in this population. METHODS: We included 51 patients with SLTx (17 RAS, 17 bronchiolitis obliterans syndrome [BOS], and 17 stable condition). The criteria for RAS diagnosis in SLTx included forced vital capacity (FVC) <80% baseline (BL) or forced expiratory volume in 1 second (FEV1) <80% BL with an FEV1/FVC ratiounchanged or >0.7 and persistent CT-scan-lung opacities. We defined 4 time points (T): T-baseline, T-onset (first CT-scan-opacities), T-follow-up, and T-last. RESULTS: In patients with RAS, the spirometric criteria for RAS at T-onset were reached in only 47% (FVC decline <80% BL [(29%] or FEV1 <80% BL/ratiounchanged or >0.7 [41%]), whereas at the same T-onset date, the graft CT-score increased to 5 (4-6) vs 1 (0-2) at baseline (p < 0.001) (CT - score ≥2 at T-onset in 100% and ΔCT - score ≥2 in 74% of patients with RAS), and the median CT-scan graft volume decreased to 1,722 ml (vs 1,796 ml at T-baseline, p = 0.003) (decreased CT-graft - volume <90% BL in 50% of patients). In contrast, in patients with BOS, CT-score/volume were unchanged at T-onset vs T-baseline (p = 0.8, p = 0.68, respectively). CONCLUSION: Our results suggest that the use of a simple CT-score and to a lesser extent, CT-volume measures, might allow for the early identification and/or prediction of RAS in SLTx rather than functional criteria.

Relationship between gender and survival in a real-life cohort of patients with COPD.

BACKGROUND: Although COPD affects both men and women, its prevalence is increasing more rapidly in women. Disease outcomes appear different among women with more frequent dyspnea and anxiety or depression but whether this translates into a different prognosis remains to be determined. Our aim was to assess whether the greater clinical impact of COPD in women was associated with differences in 3-year mortality rates. METHODS: In the French Initiatives BPCO real-world cohort, 177 women were matched up to 458 menon age (within 5-year intervals) and FEV1 (within 5% predicted intervals). 3-year mortality rate and survival were analyzed. Univariate and multivariate logistic regression analyses were performed. RESULTS: For a given age and level of airflow obstruction, women with COPD had more severe dyspnea, lower BMI, and were more likely to exhibit anxiety. Nevertheless, three-year mortality rate was comparable among men and women, respectively 11.2 and 10.8%. In a multivariate model, the only factors significantly associated with mortality were dyspnea and malnutrition but not gender. CONCLUSION: Although women with COPD experience higher levels of dyspnea and anxiety than men at comparable levels of age and FEV1, these differences do not translate into variations in 3-year mortality rates. TRIAL REGISTRATION: 04-479.

Predictors in routine practice of 6-min walking distance and oxygen desaturation in patients with COPD: impact of comorbidities.

Background: The 6-min walk test (6MWT) allows exercise tolerance to be assessed, and it has a significant prognostic value in COPD. The goal of this study was to analyse the determinants (obtained in routine practice) of a low 6-min walking distance (6MWD) and exercise-induced desaturation (EID) in COPD, including comorbidities. Methods: Patients were recruited from the real-life French COPD cohort "Initiatives BPCO". A low 6MWD was defined as <350 m. EID was defined by a minimum pulse oxygen saturation (SpO2)<90% and delta SpO2≥4% from baseline. Multivariate logistic regression analyses assessed the influence on 6MWD and EID of age, sex, obesity (body mass index, BMI >30 kg/m2), low BMI (BMI <18.5 kg/m2), modified Medical Research Council (mMRC) dyspnea scale, FEV1% pred, FVC % pred, hyperinflation and comorbidities including cardiovascular diseases. Results: Among 440 patients with available 6MWT data, a 6MWD <350 m was found in 146 patients (33%), which was positively associated in multivariate analyses with age and mMRC and negatively with resting SpO2 and FVC % pred (rescaled r2=0.34), whereas no comorbidity was associated with a low 6WMD. EID was found in 155 patients (35%). This was positively associated with hypertension and negatively with age, obesity, FEV1% pred and resting SpO2 (rescaled r2=0.37). Conclusion: 6MWD and EID exhibit different determinants in COPD with a minor impact of comorbidities limited to hypertension in EID and to obesity, which was unexpectedly associated with less EID. Other variables including age, routine resting lung function and SpO2 were weakly associated with 6MWD and EID. Altogether, these results suggest that 6MWT performance remains difficult to predict with routine clinical/functional parameters.

Role of C1q-binding anti-HLA antibodies as a predictor of lung allograft outcome.

Presence of anti-human leukocyte antigen donor-specific antibodies (DSAs) is associated with poor outcome after lung transplantation. Currently, DSAs are detected using the Luminex technique, which may be overly sensitive. The new C1q assay allows for the exclusive detection of complement (C1q)-binding antibodies, involved in antibody-mediated rejection. We investigated whether early detection of complement-binding DSAs is associated with chronic lung allograft dysfunction (CLAD) and survival.From 2009 to 2012, lung transplant recipients from three transplantation centres were screened for the presence of DSA and their complement-binding capacity during the 6-12 months post-transplantation in a stable condition.The analysis included 168 patients. The 3-year rates of freedom from CLAD and graft survival were lower for patients with complement-binding DSAs (33.6% and 53.7%, respectively), as compared with patients with non-complement-binding DSAs (61.9% and 77.4%, respectively) and patients without DSA (70% and 84.9%, respectively) (p<0.001 and p=0.001, respectively). Detection of complement-binding DSA was associated with a risk of graft loss that was nearly tripled after adjustment for clinical, functional, histological and immunological factors (hazard ratio 2.98, 95% CI 1.33-6.66; p=0.008).Assessment of the C1q-binding capacity of DSA appears to be useful in identifying stable lung transplant recipients at high risk of lung allograft loss.

Smoking-Related Interstitial Fibrosis: Evidence of Radiologic Regression with Advancing Age and Smoking Cessation.

More data are needed regarding the radiology, co-morbidities and natural history of smoking-related interstitial fibrosis (SRIF), a common pathological finding, mainly described heretofore in association with lung cancer, where respiratory bronchiolitis (RB) usually co-exists. We prospectively acquired high resolution CT scan data (edge-enhancing lung reconstructions) to detect any radiologic interstitial lung abnormality (ILA) in individuals who ultimately underwent surgical lobectomy for lung cancer (n = 20), for radiologic/pathologic correlation. We also re-examined other smoking-related benign histologic cases: chronic obstructive pulmonary disease (COPD lung explants, n = 20), alpha 1-antitrypsin deficiency (A1AT, explanted lungs n = 20), combined pulmonary fibrosis and emphysema (CPFE, n = 8) and idiopathic pulmonary fibrosis (IPF, n = 10). Finally, we pooled our data with all peer-reviewed published data describing histologic SRIF of known ILA status. SRIF was observed in 40% of cancer lobectomies, mean (±SD) age 65.8 ± 8.7 years, none of whom had ILA. SRIF was observed in other smoking-related benign diseases (COPD 35%, A1AT 20%, CPFE 25%, and IPF 10%). 71.4% of benign SRIF cases had no RB (nearly all ex-smokers) versus 0% of cancer-associated SRIF cases (P = 1.7 × 10-3). Pooled data showed that those SRIF subjects without ILA were 15.05 years older than those with ILA (95% confidence interval 8.99 to 21.11, P = 2.5 × 10-5) and more likely to be former smokers (P = 7.2 × 10-3). SRIF is frequently found without lung cancer, and mostly without RB in former smokers. SRIF is less likely to have ILA in older subjects and with smoking cessation, which could represent RB+/-SRIF regression.

Relationship between blood eosinophils, clinical characteristics, and mortality in patients with COPD.

In patients with COPD, there is controversy regarding the association of blood eosinophil (Eos) levels with 1) exacerbation frequency and 2) the effect of inhaled corticosteroids for prevention of exacerbations. To determine whether Eos define subgroups of patients exhibiting attributes of COPD clinical phenotypes, we compared clinical features and mortality rates in COPD patients from the Initiatives BPCO French cohort categorized using different thresholds of blood Eos levels. The following data were collected at inclusion: medical and smoking history, occupational exposures, dyspnea, cough and sputum production, exacerbations in the previous year, history of allergy and asthma, nasal symptoms, body mass index, St George Respiratory Questionnaire (SGRQ) total score, post-bronchodilator spirometry, comorbidities, and medications. Three-year survival between groups was compared using Kaplan-Meier analysis. Three sets of analyses were performed to compare patients with ≥2% versus <2%, ≥3% versus <3%, and ≥4% versus <4% Eos. Eos was available in 458 patients (mean age: 62 years, 72% male, mean forced expiratory volume in 1 second: 51% pred), including 235 patients with Eos ≥2% (49%), 149 with Eos ≥3% (33%), and 90 with Eos ≥4% (20%). For all cutoffs, there was no difference between Eos+ and Eos- groups in univariate analyses except for diabetes and SGRQ score (more frequent and more impaired, respectively, in lower Eos categories). In particular, there was no difference in exacerbation rate, history of asthma, or three-year survival. In conclusion, regardless of the cutoff, Eos+ COPD patients exhibited no specific characteristic in terms of symptoms, lung function, exacerbation rate, and prognosis. These findings suggest that the association of higher Eos with exacerbations reported in previous studies could be population specific, which does not support generalizing the use of Eos as a biomarker for COPD phenotyping.

Impact of current cough on health-related quality of life in patients with COPD.

BACKGROUND: Cough and sputum production are frequent in chronic obstructive pulmonary disease (COPD). The objective of this study was to examine the relationship between cough and sputum production and health-related quality of life in COPD. METHODS: A cross-sectional study was conducted in the French Initiatives COPD cohort and assessed cough and sputum production within the past 7 days using the cough and sputum assessment questionnaire (CASA-Q), health-related quality of life, spirometry, smoking status, dyspnea, exacerbations, anxiety and depression, and comorbidities. RESULTS: One hundred and seventy-eight stable COPD patients were included (age, 62 [56-69] years, 128 male, forced expiratory volume in 1 second [FEV1]: 57 [37-72] % predicted) (median [Q1-Q3]). In univariate analyses, health-related quality of life (Saint George's respiratory questionnaire total score) was associated with each CASA-Q domain and with chronic bronchitis, exacerbations, dyspnea, FEV1, depression, and anxiety. All four domains introduced separately were independently associated with health-related quality of life. When introduced together in multivariate analyses, only the cough impact domain remained independently associated with health-related quality of life (R2=0.60). With chronic bronchitis (standard definition) instead of the CASA-Q, the R2 was lower (R2=0.54). CONCLUSION: This study provides evidence that current cough in the previous 7 days is an important determinant of health-related quality of life impairment in stable COPD patients.

Impact of gender on COPD expression in a real-life cohort.

Reports regarding gender-related differences in COPD expression have provided conflicting results. In the French Initiatives BPCO real-world cohort, which contained 688 patients (146 women) when data were extracted, women were matched with men (1:3 ratio: n = 107:275) on age (5-year intervals) and FEV1 (5% predicted intervals) and comparisons were performed using univariate logistic regressions. For a given age and level of airflow obstruction, women with COPD had higher BOD scores due to more pronounced dyspnea and lower BMI, suggesting worse prognosis, and were more likely to exhibit anxiety, suggesting the need for specific assessment and care.

Neural mechanisms underlying breathing complexity.

Breathing is maintained and controlled by a network of automatic neurons in the brainstem that generate respiratory rhythm and receive regulatory inputs. Breathing complexity therefore arises from respiratory central pattern generators modulated by peripheral and supra-spinal inputs. Very little is known on the brainstem neural substrates underlying breathing complexity in humans. We used both experimental and theoretical approaches to decipher these mechanisms in healthy humans and patients with chronic obstructive pulmonary disease (COPD). COPD is the most frequent chronic lung disease in the general population mainly due to tobacco smoke. In patients, airflow obstruction associated with hyperinflation and respiratory muscles weakness are key factors contributing to load-capacity imbalance and hence increased respiratory drive. Unexpectedly, we found that the patients breathed with a higher level of complexity during inspiration and expiration than controls. Using functional magnetic resonance imaging (fMRI), we scanned the brain of the participants to analyze the activity of two small regions involved in respiratory rhythmogenesis, the rostral ventro-lateral (VL) medulla (pre-Bötzinger complex) and the caudal VL pons (parafacial group). fMRI revealed in controls higher activity of the VL medulla suggesting active inspiration, while in patients higher activity of the VL pons suggesting active expiration. COPD patients reactivate the parafacial to sustain ventilation. These findings may be involved in the onset of respiratory failure when the neural network becomes overwhelmed by respiratory overload We show that central neural activity correlates with airflow complexity in healthy subjects and COPD patients, at rest and during inspiratory loading. We finally used a theoretical approach of respiratory rhythmogenesis that reproduces the kernel activity of neurons involved in the automatic breathing. The model reveals how a chaotic activity in neurons can contribute to chaos in airflow and reproduces key experimental fMRI findings.

Impact of comorbidities on COPD-specific health-related quality of life.

BACKGROUND: Comorbidities are frequent in subjects with COPD, but their contribution to health-related quality of life (HRQoL) impairment is not clearly established. METHODS: Cross-sectional analysis of data from the French COPD cohort Initiatives BPCO. Data were recorded in stable state and included spirometry, dyspnea (modified Medical Research Council - mMRC-scale), mood disorders (hospital anxiety-depression scale) and physician-diagnosed comorbidities including diabetes, hypertension, coronary artery disease, chronic heart failure, venous thromboembolism. HRQoL was assessed using the disease-specific St. George's Respiratory Questionnaire (SGRQ). Stepwise forward and backward multiple regression analyses were performed to examine the contribution of comorbidities to SGRQ scores. RESULTS: Data are median [IQR]. 326 COPD subjects were analyzed: male 77%, age 65.0 [57.0; 72.0] years, FEV(1) 48.9 [34.7; 65.9]% predicted. SGRQ total score was 44.2 [30.0; 61.2]. In univariate analysis, positive correlations were found between SGRQ total scores and dyspnea and exacerbations/patient/year, whereas negative correlations were found with FEV(1). SGRQ total scores were increased in women (P = 0.06), and in subjects with low BMI, anxiety or depression (each analysis, P < 0.001), but not in subjects with cardiovascular comorbidities or diabetes. In multivariate analyses, major independent determinants of SGRQ total score included dyspnea, exacerbations/patient/year and depression. Low BMI, coronary artery disease and FEV(1) were also independently associated with SGRQ total score, but their contribution was only modest. CONCLUSIONS: These data suggest that in the presence of dyspnea and exacerbation, depression is the most important contributor to HRQoL impairment measured by SGRQ in COPD subjects, whereas other comorbidities and FEV(1) have only limited impact.

Association between occupational exposure and the clinical characteristics of COPD.

BACKGROUND: The contribution of occupational exposures to COPD and their interaction with cigarette smoking on clinical pattern of COPD remain underappreciated. The aim of this study was to explore the contribution of occupational exposures on clinical pattern of COPD. METHODS: Cross-sectional data from a multicenter tertiary care cohort of 591 smokers or ex-smokers with COPD (median FEV1 49%) were analyzed. Self-reported exposure to vapor, dust, gas or fumes (VDGF) at any time during the entire career was recorded. RESULTS: VDGF exposure was reported in 209 (35%) subjects aged 31 to 88 years. Several features were significantly associated with VDGF exposure: age (median 68 versus 64 years, p < 0.001), male gender (90% vs 76%; p < 0.0001), reported work-related respiratory disability (86% vs 7%, p < 0.001), current wheezing (71% vs 61%, p = 0.03) and hay fever (15.5% vs 8.5%, p < 0.01). In contrast, current and cumulative smoking was less (p = 0.01) despite similar severity of airflow obstruction. CONCLUSION: In this patient series of COPD patients, subjects exposed to VDGF were older male patients who reported more work-related respiratory disability, more asthma-like symptoms and atopy, suggesting that, even in smokers or ex-smokers with COPD, occupational exposures are associated with distinct patients characteristics.

Impact of previous cardiovascular disease on the outcome of lung transplantation.

BACKGROUND: The impact of previous cardiovascular disease on the outcome of lung transplantation may be important but remains unstudied. METHODS: Cardiovascular risk factors, echocardiography, right heart catheterization, isotopic ventriculography and vascular ultrasonography data were obtained from 258 adults who underwent lung transplantation at our center between 1988 and 2007. The effect of these parameters on survival and cardiovascular disease after transplantation was determined using the Cox model. RESULTS: By multivariate analysis, diabetes (hazard ratio [HR]: 2.4), atrial fibrillation (HR: 3.51), elevated systolic pulmonary artery pressure (HR: 1.23 per 10 mm Hg) and low cardiac index (HR: 1.47 per-liters/min/m(2)) before transplantation were associated with a higher risk of death after transplantation. Heart failure (2.08 cases per 100 patient-years) and atherothrombosis (2.5 cases per 100 patient-years) were frequent after lung transplantation. A history of atherothrombosis (HR: 12.98) and diabetes (HR: 5.8) before transplantation were associated with a higher risk of atherothrombosis after transplantation. Major cardiovascular events led to death in 11 patients. Diabetes (HR: 62.5) and a low cardiac index (HR: 6.8 per-liters/min/m(2)) were associated with a higher risk of death from cardiovascular causes. CONCLUSIONS: Diabetes and a history of atrial fibrillation before lung transplantation were associated with excess mortality after transplantation. Diabetes was also associated with a major increase in the risk of atherothrombosis and death from cardiovascular causes. Lung transplant recipients may be considered at high risk for cardiovascular disease.