Veno-venous extracorporeal membrane oxygenation (vv-ECMO) for severe respiratory failure in adult cancer patients: a retrospective multicenter analysis.

PURPOSE: The question of whether cancer patients with severe respiratory failure benefit from veno-venous extracorporeal membrane oxygenation (vv-ECMO) remains unanswered. We, therefore, analyzed clinical characteristics and outcomes of a large cohort of cancer patients treated with vv-ECMO with the aim to identify prognostic factors. METHODS: 297 cancer patients from 19 German and Austrian hospitals who underwent vv-ECMO between 2009 and 2019 were retrospectively analyzed. A multivariable cox proportional hazards analysis for overall survival was performed. In addition, a propensity score-matched analysis and a latent class analysis were conducted. RESULTS: Patients had a median age of 56 (IQR 44-65) years and 214 (72%) were males. 159 (54%) had a solid tumor and 138 (47%) a hematologic malignancy. The 60-day overall survival rate was 26.8% (95% CI 22.1-32.4%). Low platelet count (HR 0.997, 95% CI 0.996-0.999; p = 0.0001 per 1000 platelets/µl), elevated lactate levels (HR 1.048, 95% CI 1.012-1.084; p = 0.0077), and disease status (progressive disease [HR 1.871, 95% CI 1.081-3.238; p = 0.0253], newly diagnosed [HR 1.571, 95% CI 1.044-2.364; p = 0.0304]) were independent adverse prognostic factors for overall survival. A propensity score-matched analysis with patients who did not receive ECMO treatment showed no significant survival advantage for treatment with ECMO. CONCLUSION: The overall survival of cancer patients who require vv-ECMO is poor. This study shows that the value of vv-ECMO in cancer patients with respiratory failure is still unclear and further research is needed. The risk factors identified in the present analysis may help to better select patients who may benefit from vv-ECMO.

Pulmonary pulse transit time: a novel echocardiographic indicator of hemodynamic and vascular alterations in pulmonary hypertension and pulmonary fibrosis.

INTRODUCTION: Pulse transit time (PTT) is generally assumed to be a surrogate marker for blood pressure changes and arterial stiffness. The aim was to evaluate whether pulmonary PTT (pPTT) may be noninvasively measured by Doppler echocardiography and whether it might be valuable for detecting pulmonary hemodynamic and vascular alterations. METHODS: We defined pPTT as the interval between R-wave in the ECG and the corresponding peak late systolic pulmonary vein flow velocity measured by pw-Doppler in the pulmonary vein. Twelve consecutive patients with pulmonary hypertension (PH) and 12 subjects without any cardiovascular or respiratory disease were included in the study. All patients underwent a standard echocardiography including pPTT measurement. RESULTS: In the PH group, 5 patients had idiopathic pulmonary arterial hypertension (WHO 1), 1 patient PH associated with connective tissue disease (CTD, WHO 1) without pulmonary fibrosis (PF), and 6 patients PH associated with PF either due to CTD (WHO 1) or other etiology (WHO 3). Mean pPTT was significantly shorter in the PH group (138.0 ± 16.78 msec; P < 0.0001) than in the control group (383.5 ± 23.84 msec). Within the PH group, the subgroup of patients with PF showed significantly shorter mean pPTT (93.50 ± 15.47 msec; P = 0.004) than the subgroup of patients with PH without PF (182.6 ± 14.35 msec). CONCLUSIONS: The results of this study suggest that pPTT might be an interesting surrogate marker of pulmonary hemodynamic and vascular alterations in PH and PF. Further studies are warranted to evaluate the possible influence of other variables on pPTT.

Relation of exercise capacity with lung volumes before and after 6-minute walk test in subjects with COPD.

INTRODUCTION: There is growing evidence that exercise-induced variation in lung volumes is an important source of ventilatory limitation and is linked to exercise intolerance in COPD. The aim of this study was to compare the correlations of walk distance and lung volumes measured before and after a 6-min walk test (6MWT) in subjects with COPD. METHODS: Forty-five subjects with stable COPD (mean pre-bronchodilator FEV1: 47 ± 18% predicted) underwent a 6MWT. Body plethysmography was performed immediately pre- and post-6MWT. RESULTS: Correlations were generally stronger between 6-min walk distance and post-6MWT lung volumes than between 6-min walk distance and pre-6MWT lung volumes, except for FEV1. These differences in Pearson correlation coefficients were significant for residual volume expressed as percent of total lung capacity (-0.67 vs -0.58, P = .043), percent of predicted residual volume expressed as percent of total lung capacity (-0.68 vs -0.59, P = .026), inspiratory vital capacity (0.65 vs 0.54, P = .019), percent of predicted inspiratory vital capacity (0.49 vs 0.38, P = .037), and percent of predicted functional residual capacity (-0.62 vs -0.47, P = .023). CONCLUSIONS: In subjects with stable COPD, lung volumes measured immediately after 6MWT are more closely related to exercise limitation than baseline lung volumes measured before 6MWT, except for FEV1. Therefore, pulmonary function testing immediately after exercise should be included in future studies on COPD for the assessment of exercise-induced ventilatory constraints to physical performance that cannot be adequately assessed from baseline pulmonary function testing at rest.

Effects of nasal positive expiratory pressure on dynamic hyperinflation and 6-minute walk test in patients with COPD.

INTRODUCTION: Dynamic hyperinflation is an important target in the treatment of COPD. There is increasing evidence that positive expiratory pressure (PEP) could reduce dynamic hyperinflation during exercise. PEP application through a nasal mask and a flow resistance device might have the potential to be used during daily physical activities as an auxiliary strategy of ventilatory assistance. The aim of this study was to determine the effects of nasal PEP on lung volumes during physical exercise in patients with COPD. METHODS: Twenty subjects (mean ± SD age 69.4 ± 6.4 years) with stable mild-to-severe COPD were randomized to undergo physical exercise with nasal PEP breathing, followed by physical exercise with habitual breathing, or vice versa. Physical exercise was induced by a standard 6-min walk test (6 MWT) protocol. PEP was applied by means of a silicone nasal mask loaded with a fixed-orifice flow resistor. Body plethysmography was performed immediately pre-exercise and post-exercise. RESULTS: Differences in mean pre- to post-exercise changes in total lung capacity (-0.63 ± 0.80 L, P = .002), functional residual capacity (-0.48 ± 0.86 L, P = .021), residual volume (-0.56 ± 0.75 L, P = .004), S(pO2) (-1.7 ± 3.4%, P = .041), and 6 MWT distance (-30.8 ± 30.0 m, P = .001) were statistically significant between the experimental and the control interventions. CONCLUSIONS: The use of flow-dependent expiratory pressure, applied with a nasal mask and a PEP device, might promote significant reduction of dynamic hyperinflation during walking exercise. Further studies are warranted addressing improvements in endurance performance under regular application of nasal PEP during physical activities.

Histology as a potential clinical predictor of outcome in advanced non-small-cell lung cancer treated with vinorelbine and mitomycin combination chemotherapy.

BACKGROUND: The importance of clinical predictors in the treatment of non-small-cell lung cancer (NSCLC) has increased during the last decade. This retrospective study analyzed the combined patient-level data from two phase II trials that investigated the efficacy and safety of combination chemotherapy with vinorelbine and mitomycin in patients with locally advanced or metastatic NSCLC. The aim of this analysis was to determine if patients' baseline and disease characteristics, including histology, gender, smoking history, and expression of TTF-1, might be potential predictors of outcome. METHODS: Response rates, unadjusted survival times, and Cox covariate-adjusted hazard ratios (HRs) were calculated. Results were reported separately for each subgroup in each individual trial and in the pooled data set. RESULTS: A total of 175 patients were included in this analysis. Adjusted HRs for both overall survival (OS) and progression free survival (PFS) favored the nonadenocarcinoma histology subgroup, achieving a statistical significance for OS in the pooled data (n = 175; HR 0.68; 95 % CI 0.49-0.94; p = 0.019). TTF-1-negative immunohistochemistry was associated with a significantly higher response rate (25 vs. 0 %; p = 0.04) and with a nonsignificant advantage in OS (n = 33; HR 1.23; 95 % CI 0.56-2.73; p = 0.608). Gender and smoking history were not strongly related to outcome. CONCLUSIONS: The results of this analysis indicate that patients with nonadenocarcinoma histology might get superior benefit from combination chemotherapy with vinorelbine and mitomycin. These results should be confirmed in a prospective study.

Isolated IgG4-related interstitial lung disease: unusual histological and radiological features of a pathologically proven case.

IgG4-related lung disease is commonly associated with autoimmune pancreatitis. Recently, isolated IgG4-related interstitial lung disease (ILD) without other organ involvement has newly been reported in two cases with clinical features of nonspecific interstitial pneumonitis (NSIP).We report the first case of an isolated IgG4-related ILD in a 78-year-old man with dry cough and dyspnea, whose clinical findings proved to be different from NSIP. Serum IgG4 levels were increased. Chest CT scan revealed bilateral consolidations especially in the lower lobes, enlarged mediastinal and hilar lymph nodes and pleural effusions. Video-assisted thoracoscopic (VATS) lung biopsy revealed a pattern similar to usual interstitial pneumonia (UIP) and an abundant IgG4-positive plasma cell infiltration. He was effectively treated by steroid therapy.Increasing recognition of IgG4 related diseases has led to a growing number of new entities. The novel concept of isolated IgG4-related ILD as a pulmonary manifestation of a systemic IgG4-related disorder should be taken into account as a possible differential diagnosis of ILD and mass-forming lesions, even when no other organ manifestation is clinically apparent at the time of diagnosis. Lung specific diagnostic criteria and algorithms are required to enhance diagnostic accuracy in cases of possible IgG4-related ILD.

Omalizumab in patients with severe asthma: the XCLUSIVE study.

BACKGROUND AND AIMS: Although the efficacy and safety of omalizumab (OMA) in uncontrolled severe allergic asthma has been demonstrated in several randomised controlled trials (RCTs), information on the treatment in a practice-related setting is limited. Thus, the purpose of this prospective multi-centre study (XCLUSIVE) was to investigate the efficacy, compliance and utilisation of OMA therapy in real-life clinical practice in Germany. METHODS: One hundred ninety-five asthmatic patients initiated on anti-Immunoglobulin E (IgE) IgE treatment were followed-up for 6 months. Forced expiratory volume in 1 s (FEV(1) ), exacerbation rate, days of absence, asthma symptoms [Asthma Control Questionnaire (ACQ)], a Global Evaluation of Treatment Effectiveness (GETE) and medication use were assessed. RESULTS: Measured outcome variables improved after a 16-week treatment period with OMA (FEV(1) +13.7% predicted P < 0.05, exacerbation rate -74.9% P < 0.0001, days of absence -92.1% P < 0.001, ACQ -43.7% P < 0.0001). Investigators evaluated the effectiveness of OMA by GETE in 78.8% as excellent or good (responder), and in 12.6%/8.6% as moderate/poor or worse (non-responder). Responders demonstrated better improvement of FEV(1), exacerbation rate, days of absence, ACQ and reduction of oral corticosteroids compared with non-responders. CONCLUSION: Results of effectiveness strongly suggest that the efficacy demonstrated in RCTs can be transposed to a clinical practice-related setting.

Effectiveness of omalizumab in patients 50 years and older with severe persistent allergic asthma.

BACKGROUND: Omalizumab is approved for the treatment of severe allergic asthma. OBJECTIVES: To compare the efficacy of omalizumab therapy in patients 50 years or older with patients younger than 50 years. METHODS: Between November 2005 and November 2007 a total of 174 asthma patients 50 years or older (40.7% male, 51.1% taking oral corticosteroids, and mean [SD] serum IgE level of 315 [353] U/L) and 297 asthma patients younger than 50 years (40.0% male, 50.5% taking oral corticosteroids, and mean [SD] serum IgE level of 363 [431] U/L) who met the European Union criteria for add-on therapy with anti-IgE were treated prospectively with omalizumab for 4 months as part of 2 postmarketing surveillance trials. RESULTS: Compared with the pretrial period omalizumab treatment reduced the rate of severe exacerbations in patients 50 years or older by 68.9% (P < .001) and in patients younger than 50 years by 75.4% (P < .001). After 4 months there was a marked reduction of daily asthma symptoms and nocturnal awakenings by 67.8% and 72.6% in the older and by 79.3% and 82.5% in the younger patients, respectively (P < .001, all 4 comparisons). In 60% of patients 50 years or older lung function improved compared with 69% of patients younger than 50 years. Efficacy of omalizumab was rated as excellent or good by most physicians in patients 50 years or older (68.4%) and younger than 50 years (76.8%, P = .05 elderly vs younger). Adverse events were reported in 35.5% of patients 50 years or older and 32.1% of patients younger than 50 years. There was a higher rate of discontinuation of omalizumab therapy in older patients (20.9% vs 11.1%, P = .006). CONCLUSIONS: The present study confirms the clinical efficacy of omalizumab in patients with severe allergic asthma irrespective of age in a real-life setting outside the omalizumab trial program.

Benefit of erlotinib in patients with non-small-cell lung cancer is related to smoking status, gender, skin rash and radiological response but not to histology and treatment line.

BACKGROUND: Erlotinib is a standard of treatment for metastatic non-small-cell lung cancer after failure of initial therapy. Patient selection based on clinical factors is under discussion. METHODS: We analyzed the outcome in relation to clinical factors of 121 consecutive Caucasian patients treated with erlotinib in a routine clinical setting in a comprehensive cancer center and 2 regional oncology centers. RESULTS: For patients with erlotinib treatment at the 1st/2nd/3rd/> or = 4th line, progression-free survival (PFS) was 4.5/3.5/2.5/3.0 months, and overall survival (OS) was 8.0/8.5/7.8/6.5 months. Patients with adenocarcinoma had an improved PFS, but a similar OS. Never-smokers had longer PFS (7 months) and OS (13 months) than smokers and ex-smokers. Male patients had a slightly longer survival than female patients (PFS 3.0 vs. 2.5 months, OS 8.5 vs. 7.0 months). After adjustment for smoking and histology, the gender difference in OS was significant (adjusted hazard ratio 0.57). Patients with clinically relevant skin toxicity (grade 2, 3) had a significantly prolonged PFS and OS. Patients with partial response on 1st radiological evaluation had a significantly prolonged PFS and OS. CONCLUSION: Among clinical factors, never-smoking status and male gender predicted a prolonged survival. During treatment, skin toxicity and radiological response were related to better survival.

Circulating biomarkers of tissue remodelling in pulmonary hypertension.

OBJECTIVE: Besides persisting high pulmonary arterial pressure and increased pulmonary vascular resistance, remodelling of pulmonary tissues and subsequently the right heart are the key pathomechanisms of pulmonary hypertension (PH). Extracellular matrix maintenance in this context plays a central role. METHODS: We tested the hypothesis that plasma concentration of matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinases (TIMP)-4 and tenascin C (TNC) might be useful as biomarkers for assessing the severity of PH. Therefore, the concentrations of MMP-2, TIMP-4, TNC and N-terminal b-type natriuretic peptide (NT-proBNP) of 36 PH patients were compared with those of 44 age- and gender-matched healthy volunteers. Additionally, lung function, 6-min walk distance and right heart function were assessed. RESULTS: In PH patients, significantly elevated plasma levels of MMP-2, TIMP-4, TNC and NT-proBNP were detected. In particular, TIMP-4 was significantly increased in patients with higher NYHA classification, and in patients with severe right ventricular hypertrophy. CONCLUSION: Monitoring of plasma TIMP-4 and to a lesser extent of MMP-2 and TNC levels in PH patients might help to assess the beneficial effects of PH pharmacotherapy on tissue remodelling.