Electroanatomical mapping improves procedural outcomes of cryoballoon pulmonary vein isolation (the Achieve Plus study).

BACKGROUND: Validation of pulmonary vein (PV) isolation (PVI) using only the Achieve catheter following cryoballoon ablation (CBA) is imperfect since pulmonary vein potentials (PVP) can be recorded in only 50-85% of the veins and residual PVP are found in up to 4.3-7.6% of the isolated veins in remapping studies. OBJECTIVE: To study if addition of electroanatomical mapping to Achieve catheter-guided CBA is superior for PVI. METHODS: One hundred patients were randomized between Achieve catheter-guided CBA (control group; N = 50) and Achieve catheter-guided CBA with additional EnSite voltage maps performed pre- and post-CBA (Achieve Plus group; N = 50). Confirmation of PVI was done by circular mapping catheter (CMC) and EnSite mapping by a second blinded operator. RESULTS: Despite apparent PVI in all PVs after CBA, incomplete PVI was present in 0 out of 50 patients (0%) and 0 out of 204 PVs in the Achieve Plus group versus 6 patients out of 50 (12%; P = 0.012) and 6 out of 203 PVs (3%; P = 0.013) in the control group. All 6 non-isolated PVs could be successfully isolated by additional cryoapplications. Procedure time was longer in the Achieve Plus group (75.76 ± 21.65 vs 66.06 ± 16.83 min; P = 0.014) with equal fluoroscopy times (14.85 ± 6.41 vs 14.33 ± 8.55; P = 0.732). CONCLUSION: The addition of electroanatomical EnSite mapping to the Achieve catheter improves the PVI rate of CBA and could be considered for future use. Design and Results of the Achieve Plus study. The Achieve Plus study shows that the addition of electro-anatomical EnSite mapping to the Achieve catheter improves PVI rate of CBA and could be considered for future use. See text for further explanation. ABBREVIATIONS: CBA: cryoballoon ablation; PVI: pulmonary vein isolation.

Similar programmed death ligand 1 (PD-L1) expression profile in patients with mild COPD and lung cancer.

Programmed Death Ligand 1 (PD-L1) is crucial in regulating the immunological tolerance in non-small cell lung cancer (NSCLC). Alveolar macrophage (AM)-derived PD-L1 binds to its receptor, PD-1, on surveilling lymphocytes, leading to lymphocyte exhaustion. Increased PD-L1 expression is associated with cigarette smoke (CS)-exposure. However, the PD-L1 role in CS-associated lung diseases associated with NSCLC, such as chronic obstructive pulmonary disease (COPD), is still unclear. In two different cohorts of ever smokers with COPD or NSCLC, and ever and never smoker controls, we evaluated PD-L1 expression: (1) via cutting-edge digital spatial proteomic and transcriptomic profiling (Geomx) of formalin-fixed paraffin-embedded (FFPE) lung tissue sections (n = 19); and (2) via triple immunofluorescence staining of bronchoalveolar lavage (BAL) AMs (n = 83). PD-L1 mRNA expression was also quantified in BAL AMs exposed to CS extract. PD-L1 expression was increased in the bronchiolar wall, parenchyma, and vascular wall from mild-moderate (GOLD 1-2) COPD patients compared to severe-very severe (GOLD 3-4) COPD patients and controls. Within all the COPD patients, PD-L1 protein expression was associated with upregulation of genes involved in tumor progression and downregulation of oncosuppressive genes, and strongly directly correlated with the FEV1% predicted, indicating higher PD-L1 expression in the milder vs. more severe COPD stages. In bronchioles, PD-L1 levels were strongly directly correlated with the number of functionally active AMs. In BAL, we confirmed that AMs from patients with both GOLD 1-2 COPD and NSCLC had the highest and similar, PD-L1 expression levels versus all the other groups, independently from active cigarette smoking. Intriguingly, AMs from patients with more severe COPD had reduced AM PD-L1 expression compared to patients with mild COPD. Acute CS extract stimulation increased PD-L1 mRNA expression only in never-and not in ever-smoker AMs. Lungs from patients with mild COPD and NSCLC are characterized by a similar strong PD-L1 expression signature in bronchioles and functionally active AMs compared to patients with severe COPD and controls. Active smoking does not affect PD-L1 levels. These observations represent a new resource in understanding the innate immune mechanisms underlying the link between COPD and lung cancer onset and progression and pave the way to future studies focused on the mechanisms by which CS promotes tumorigenesis and COPD.

Surgical Outcomes in a Lung Cancer-Screening Program Using Low Dose Computed Tomography.

OBJECTIVE: Lung cancer (LC) is the leading cause of death from cancer worldwide. More than 27,000 LCs are diagnosed annually in Spain, and most are unresectable. Early detection and treatment reduce LC mortality. This study describes surgical outcomes in a longstanding LC screening cohort in Spain. METHODS: We conducted a retrospective study of surgical outcomes in a LC screening (LCS) program using low dose computed tomography (LDCT) since the year 2000. A descriptive analysis of clinical and radiological parameters, presence or absence of a preoperative diagnosis, pathological staging, morbidity, mortality, and survival was performed. RESULTS: Ninety-seven (2.5%) LC were diagnosed in 3825 screened. Twenty individuals with LC had no surgery due to advanced stage or small cell histology. Eighty-seven surgical procedures were carried out for suspected or biopsy proven LC, detected by LDCT. Most operated patients were male (57[85%]) aged 64±9.1 years. Nine patients underwent a second operation for a metachronous primary lung cancer. Mean tumor size was 15.2±7.6mm. Eight nodules were benign (9.2%). Lobectomy was performed in 56 cases (83.6%). Adenocarcinoma (n=39; 58.2%) was the most frequent histological type followed by squamous cell carcinoma (n=17; 25.4%). Fifty-nine (88%) tumors were in Stage I. Thirteen patients (15.4%) had 16 complications. The estimated survival rates at 5 and 10 years for stage I were 93% (95% CI: 79%-98%) and 83% (95% CI: 65%-92%), respectively. CONCLUSION: Lung cancer screening was associated with excellent surgical outcomes with 5 and 10-year survival rates exceeding 90 and 80%, respectively.

Protein succination as a potential surrogate biomarker of airway obstruction. The ilervas project.

BACKGROUND: Airway obstruction (AO) is associated with hypoxemia, systemic inflammation and oxidative stress. These conditions can favor the formation of Advanced Glycation End-products (AGEs) and induce mitochondrial stress. The latter can alter metabolite intermediates in the Krebs cycle leading to the formation of the cysteine-fumarate adduct S-(2-succino) cysteine (2SC) in proteins (protein succination). Protein succination has not been described in airways diseases. RESEARCH QUESTION: To assess differences in levels of AGEs and 2SC between patients with AO and normal spirometry. STUDY DESIGN: and Methods: In this case-control study, we investigated 35 moderate to severe AO patients and 31 subjects with normal spirometry, matched for age, gender, body mass index (BMI), tobacco history, prediabetes and adherence to Mediterranean diet. Plasma 2SC and AGEs concentrations were measured by GS/MS, and AGEs in skin were determined measuring autofluorescence (SAF). Multivariate logistic regression models explored the association between AGEs in the skin, 2SC and the presence of AO. RESULTS: The population was predominantly middle-age (mean of 58.7 years-old), overweight (median of BMI 26.7 kg/m2) and male subjects (69.7%). Patients with AO showed higher values of SAF (p = 0.04) and 2SC (p = 0.047). No differences were observed for plasma AGEs. SAF and 2SC were significantly associated with the presence of AO after adjusting for age, gender, smoking history, BMI and Mediterranean diet score (p = 0.041 and p = 0.038, respectively). INTERPRETATION: Skin AGEs and 2SC are increased in patients with moderate to severe AO and independently associated with its presence. Further studies should confirm these findings and explore their potential role as a biomarker for the disease.

Gas exchange and breathing pattern in women with postmenopausal bone fragility.

BACKGROUND: Little is known about the relationship between bone fragility and respiratory function. We hypothesized that women with osteoporosis or osteopenia, without cardio-pulmonary disease, have perturbations in the pattern of breathing and gas exchange. METHODS: In 44 women with bone fragility (BF, T score: < -1), and 20 anthropomorphically-matched control women (T score > -1) we compared pulmonary function tests, central respiratory drive (mouth occlusion pressure or P 0.1), pattern of breathing using optoelectronic plethysmograph and arterial blood gases at rest. RESULTS: Static pulmonary function was similar in BF subjects and controls. However, the arterial blood gas measurements differed significantly. The arterial pH was significantly higher in BF subjects than in controls (P < 0.001). The partial pressure of carbon dioxide (PaCO2) and oxygen (PaO2) in arterial blood were significantly lower in BF subjects than controls (P < 0.001 and P = 0.009, respectively). The BF subjects had a shorter inspiratory fraction compared with controls (P = 0.036). Moreover, T-scores were significantly inversely correlated with the alveolar-arterial gradient of oxygen (r = -0.5; P = 0.0003) and the arterial pH (r = -0.4; P = 0.002), and positively correlated with arterial PaO2 (r = 0.3; P = 0.01) and PaCO2 (r = 0.4; P = 0.002) among all subjects. CONCLUSION: In the absence of known cardio-pulmonary disease, BF is associated with statistically significant perturbations in gas exchange and alterations in the pattern of breathing including shortening of the inspiratory time.

The 6-min walk distance in healthy subjects: reference standards from seven countries.

The 6-min walk distance (6MWD) predicted values have been derived from small cohorts mostly from single countries. The aim of the present study was to investigate differences between countries and identify new reference values to improve 6MWD interpretation. We studied 444 subjects (238 males) from seven countries (10 centres) ranging 40-80 yrs of age. We measured 6MWD, height, weight, spirometry, heart rate (HR), maximum HR (HR(max)) during the 6-min walk test/the predicted maximum HR (HR(max) % pred), Borg dyspnoea score and oxygen saturation. The mean ± sd 6MWD was 571 ± 90 m (range 380-782 m). Males walked 30 m more than females (p < 0.001). A multiple regression model for the 6MWD included age, sex, height, weight and HR(max) % pred (adjusted r² = 0.38; p < 0.001), but there was variability across centres (adjusted r² = 0.09-0.73) and its routine use is not recommended. Age had a great impact in 6MWD independent of the centres, declining significantly in the older population (p < 0.001). Age-specific reference standards of 6MWD were constructed for male and female adults. In healthy subjects, there were geographic variations in 6MWD and caution must be taken when using existing predictive equations. The present study provides new 6MWD standard curves that could be useful in the care of adult patients with chronic diseases.

Sex differences in mortality in patients with COPD.

Little is known about survival and clinical prognostic factors in females with chronic obstructive pulmonary disease (COPD). The aim of the present study was to determine the survival difference between males and females with COPD and to compare the value of the different prognostic factors for the disease. In total, 265 females and 272 males with COPD matched at baseline by BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) and American Thoracic Society/European Respiratory Society/Global Initiative of Chronic Obstructive Lung Disease criteria were prospectively followed. Demographics, lung function, St George's Respiratory Questionnaire, BODE index, the components of the BODE index and comorbidity were determined. Survival was documented and sex differences were determined using Kaplan-Meier analysis. The strength of the association of the studied variables with mortality was determined using multivariate and receiver operating curves analysis. All-cause (40 versus 18%) and respiratory mortality (24 versus 10%) were higher in males than females. Multivariate analysis identified the BODE index in females and the BODE index and Charlson comorbidity score in males as the best predictors of mortality. The area under the curve of the BODE index was a better predictor of mortality than the forced expiratory volume in one second for both sexes. At similar chronic obstructive pulmonary disease severity by BODE index and forced expiratory volume in one second, females have significantly better survival than males. For both sexes the BODE index is a better predictor of survival than the forced expiratory volume in one second.

The 6-min walking distance: long-term follow up in patients with COPD.

The 6-min walking distance (6MWD) test is used in clinical practice and research into patients with chronic obstructive pulmonary disease (COPD). However, little is known about natural long-term change in this parameter. The 6MWD was measured at baseline and then annually for 5 yrs in 294 patients with COPD and its annual rate of decline was determined. Forced expiratory volume in one second (FEV1) was also measured and the relationship between changes in both markers was explored. At baseline, the median 6MWD was 380 m (range 160-600 m). It declined by 19% (16 m.yr(-1)) over the 5 yrs compared with baseline in patients with American Thoracic Society/European Respiratory Society stage III COPD (FEV1 30-50% predicted) and by 26% (15 m.yr(-1)) in patients with stage IV COPD (FEV1 <30% pred). Over the 5-yr follow-up, the proportion of patients with a minimal clinically significant decline of 54 m increased with the severity of the disease. It was 24% in stage II, 45% in stage III, and 63% in stage IV disease. In contrast, the rate of decline of FEV1 was greater in patients with milder airflow obstruction and lesser in patients with lower absolute FEV1 values. In conclusion, the 6-min walking distance test provides increasingly useful information as the severity of chronic obstructive pulmonary disease increases.

C-reactive protein levels and clinically important predictive outcomes in stable COPD patients.

The aim of this study was to determine the relationship between C-reactive protein (CRP) levels and factors known to predict outcome in stable chronic obstructive pulmonary disease (COPD) patients. The following were studied in 130 stable COPD patients: spirometry, lung volume, arterial oxygen tension (P(a,O2)), dyspnoea, 6-min walk distance (6MWD), body mass index, fat-free mass index, BODE (body mass index, obstruction, dyspnoea and exercise capacity), health-related quality of life, smoking status, the presence of cardiovascular risk factors or disease, corticosteroid use and number of exacerbations in the previous year. CRP levels were measured in these patients and in 65 controls. Using univariate and multivariate analyses, any possible association with the predictors of outcomes was evaluated. CRP levels were higher in COPD patients than in controls (4.1 versus 1.8 mg.L(-1), respectively). Correlation was found with the following variables: forced expiratory volume in one second (FEV1; -0.23), FEV1 % (-0.20), forced vital capacity (FVC; -0.24), FVC % (-0.24), Global Initiative for Chronic Obstructive Lung Disease stage (0.17), BODE (0.17), inspiratory capacity/total lung capacity (-0.20), P(a,O2) (-0.40) and 6MWD (-0.30). Using multivariate analysis, P(a,O2) and 6MWD manifested the strongest negative association with CRP levels. C-reactive protein levels in stable chronic obstructive pulmonary disease patients are best correlated with arterial oxygen tension and 6-min walk distance. This should be considered when C-reactive protein levels are measured in stable chronic obstructive pulmonary disease patients.

Increased gastro-oesophageal reflux disease in patients with severe COPD.

The prevalence and clinical consequences of gastro-oesophageal reflux disease (GERD) in chronic obstructive pulmonary disease (COPD) are not well characterised. The present study prospectively studied 42 males with COPD (forced expiratory volume in one second % predicted: 35%, range 20-49) and 16 healthy volunteers of similar age without respiratory or gastro-oesophageal symptoms. The diagnosis of GERD was confirmed using oesophageal 24 h pH monitoring. In the current study group, reflux symptoms were measured using the Vigneri score, cough and dyspnoea with the modified Medical Research Council questionnaire, and pulmonary function with bronchodilator response and health status using St George's Respiratory Questionnaire. Pathological reflux was documented in 26 out of 42 patients (62%) and in three volunteers (19%). In patients with GERD, 15 patients (58%) did not report any reflux symptoms. There were no differences in symptoms, health status, bronchodilator treatment and pulmonary function test between patients with and without GERD. Oxygen desaturation coincided with episodes of increased oesophageal acidity in 40% of patients with GERD. Patients with severe chronic obstructive pulmonary disease have a high prevalence of asymptomatic gastro-oesophageal reflux. The association between this reflux and oxygen desaturation deserves further attention.

[Primary T-cell pulmonary lymphoma. A case report and review of the literature]. / Linfoma pulmonar primario de células T. Presentación de un caso y revisión de la bibliografía.

Non-Hodgkin's lymphomas rarely involve the pulmonary parenchyma. Most cases described to date involve B-cells. We report the first case of T-cell pulmonary lymphoma in the Spanish literature. The course of disease was rapid and response to treatment was poor. Such cases demonstrate the importance of open biopsy and the study of cell markers for diagnosis. T-cells lymphomas should be included in the differential diagnosis of febrile patients with pulmonary nodules.