Torres, J.P. (Juan P.) de
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- Somatotypes trajectories during adulthood and their association with COPD phenotypes(European Respiratory Society, 2020) Bastarrika, G. (Gorka); Hersh, C.P. (Craig P.); Celli, B.R. (Bartolomé R.); Casanova, C. (Ciro); Divo, M. (Miguel); Silverman, E. (Edwin); Marín-Oto, M. (Marta); DeMeo, D. (Dawn); Polverino, F. (Francesca); Torres, J.P. (Juan P.) de; Maguire, C. (Cherie); Ezponda, A. (Ana); Cabrera-Lopez, C. (Carlos); Pinto-Plata, V. (Víctor); Marin-Trigo, J.M. (Jose Maria); Ross, J.C. (James C.)Rationale: Chronic obstructive pulmonary disease (COPD) comprises distinct phenotypes, all characterised by airflow limitation. Objectives: We hypothesised that somatotype changes – as a surrogate of adiposity – from early adulthood follow different trajectories to reach distinct phenotypes. Methods: Using the validated Stunkard’s Pictogram, 356 COPD patients chose the somatotype that best reflects their current body build and those at ages 18, 30, 40 and 50 years. An unbiased group-based trajectory modelling was used to determine somatotype trajectories. We then compared the current COPD-related clinical and phenotypic characteristics of subjects belonging to each trajectory. Measurements and main results: At 18 years of age, 88% of the participants described having a lean or medium somatotype (estimated body mass index (BMI) between 19 and 23 kg·m−2 ) while the other 12% a heavier somatotype (estimated BMI between 25 and 27 kg·m−2 ). From age 18 onwards, five distinct trajectories were observed. Four of them demonstrating a continuous increase in adiposity throughout adulthood with the exception of one, where the initial increase was followed by loss of adiposity after age 40. Patients with this trajectory were primarily females with low BMI and DLCO (diffusing capacity of the lung for carbon monoxide). A persistently lean trajectory was seen in 14% of the cohort. This group had significantly lower forced expiratory volume in 1 s (FEV1), DLCO, more emphysema and a worse BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) score thus resembling the multiple organ loss of tissue (MOLT) phenotype. Conclusions: COPD patients have distinct somatotype trajectories throughout adulthood. Those with the MOLT phenotype maintain a lean trajectory throughout life. Smoking subjects with this lean phenotype in early adulthood deserve particular attention as they seem to develop more severe COPD.
- Gender differences in plasma biomarker levels in a cohort of COPD patients: a pilot study(Public Library of Science, 2011) Celli, B.R. (Bartolomé R.); Casanova, C. (Ciro); Baz-Dávila, R. (Rebeca); Cordoba-Lanus, E. (Elizabeth); Torres, J.P. (Juan P.) de; Aguirre-Jaime, A. (Armando); Pinto-Plata, V. (Víctor); Restituto, P. (Patricia); Varo-Cenarruzabeitia, M.N. (Miren Nerea)Little is known about gender differences in plasma biomarker levels in patients with chronic obstructive pulmonary disease (COPD). HYPOTHESIS: There are differences in serum biomarker levels between women and men with COPD. OBJECTIVE: Explore gender differences in plasma biomarker levels in patients with COPD and smokers without COPD. METHODS: We measured plasma levels of IL-6, IL-8, IL-16, MCP-1, MMP-9, PARC and VEGF in 80 smokers without COPD (40 males, 40 females) and 152 stable COPD patients (76 males, 76 females) with similar airflow obstruction. We determined anthropometrics, smoking history, lung function, exercise tolerance, body composition, BODE index, co-morbidities and quality of life. We then explored associations between plasma biomarkers levels and the clinical characteristics of the patients and also with the clinical and physiological variables known to predict outcome in COPD. RESULTS: The plasma biomarkers level explored were similar in men and women without COPD. In contrast, in patients with COPD the median value in pg/mL of IL-6 (6.26 vs 8.0, p = 0.03), IL-16 (390 vs 321, p = 0.009) and VEGF (50 vs 87, p = 0.02) differed between women and men. Adjusted for smoking history, gender was independently associated with IL-16, PARC and VEGF levels. There were also gender differences in the associations between IL-6, IL-16 and VEGF and physiologic variables that predict outcomes. CONCLUSIONS: In stable COPD patients with similar airflow obstruction, there are gender differences in plasma biomarker levels and in the association between biomarker levels and important clinical or physiological variables. Further studies should confirm our findings.
- Genome expression profiling-based identification and administration efficacy of host-directed antimicrobial drugs against respiratory infection by nontypeable Haemophilus influenzae(American Society for Microbiology, 2015) Garmendia, J. (Junkal); Bengoechea, J.A. (José A.); Leiva, J. (José); Viadas, C. (Cristina); Euba, B. (Begoña); Torres, J.P. (Juan P.) de; Moleres, J. (Javier); Moranta, D. (David); Morey, P. (Pau); Segura, V. (Víctor)Therapies that are safe, effective, and not vulnerable to developing resistance are highly desirable to counteract bacterial infections. Host-directed therapeutics is an antimicrobial approach alternative to conventional antibiotics based on perturbing host pathways subverted by pathogens during their life cycle by using host-directed drugs. In this study, we identified and evaluated the efficacy of a panel of host-directed drugs against respiratory infection by nontypeable Haemophilus influenzae (NTHi). NTHi is an opportunistic pathogen that is an important cause of exacerbation of chronic obstructive pulmonary disease (COPD). We screened for host genes differentially expressed upon infection by the clinical isolate NTHi375 by analyzing cell whole-genome expression profiling and identified a repertoire of host target candidates that were pharmacologically modulated. Based on the proposed relationship between NTHi intracellular location and persistence, we hypothesized that drugs perturbing host pathways used by NTHi to enter epithelial cells could have antimicrobial potential against NTHi infection. Interfering drugs were tested for their effects on bacterial and cellular viability, on NTHi-epithelial cell interplay, and on mouse pulmonary infection. Glucocorticoids and statins lacked in vitro and/or in vivo efficacy. Conversely, the sirtuin-1 activator resveratrol showed a bactericidal effect against NTHi, and the PDE4 inhibitor rolipram showed therapeutic efficacy by lowering NTHi375 counts intracellularly and in the lungs of infected mice. PDE4 inhibition is currently prescribed in COPD, and resveratrol is an attractive geroprotector for COPD treatment. Together, these results expand our knowledge of NTHi-triggered host subversion and frame the antimicrobial potential of rolipram and resveratrol against NTHi respiratory infection.
- Sex differences in mortality in patients with COPD(European Respiratory Society, 2009) Oca, M.M. (M.M.) de; Nekach, V. (V.); Celli, B.R. (Bartolomé R.); Casanova, C. (Ciro); Cote, C.G. (C.G.); Marin, J.M. (José M.); Torres, J.P. (Juan P.) de; Aguirre-Jaime, A. (Armando); Lopez, M.V. (M.V.); Diaz, O. (O.); Pinto-Plata, V. (Víctor); Dordelly, L.J. (L. J.)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.
- Assessment of indeterminate pulmonary nodules detected in lung cancer screening: Diagnostic accuracy of FDG PET/CT(Elsevier BV, 2016) Torre, W. (Wenceslao); Campo, A. (Arantza); Lozano, M.D. (María Dolores); Bastarrika, G. (Gorka); Sancho, L. (Lidia); Richter, J.A. (José Ángel); Sanchez-Salcedo, P. (Pablo); Torres, J.P. (Juan P.) de; Garcia-Velloso, M. J. (María José); Alcaide, A.B. (Ana Belén); Nuñez-Cordoba, J.M. (Jorge M.); Zulueta, J. (Javier)Background: A major drawback of lung cancer screening programs is the high frequency of false-positive findings on computed tomography (CT). We investigated the accuracy of selective 2-[fluorine-18]- fluoro-2-deoxy-d-glucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) scan in assessing radiologically indeterminate lung nodules detected in lung cancer screening. Methods: FDG PET/CT was performed to characterize 64 baseline lung nodules >10 mm and 36 incidence nodules detected on low-dose CT screening in asymptomatic current or former smokers (83 men, age range 40–83 years) at high risk for lung cancer. CT images were acquired without intravenous contrast. Nodules were analyzed by size, density, and metabolic activity and visual scored on a 5-point scale for FDG uptake. Nodules were classified as negative for malignancy when no FDG uptake was observed, or positive when focal uptake was observed in the visual analysis, and the maximum standardized uptake value (SUVmax) was measured. Final diagnosis was based on histopathological evaluation or at least 24 months of follow-up. Results: A total of 100 nodules were included. The prevalence of lung cancer was 1%. The sensitivity, specificity, NPV and PPV of visual analysis to detect malignancy were 84%, 95%, 91%, and 91%, respectively, with an accuracy of 91% (AUC 0.893). FDG PET/CT accurately detected 31 malignant tumors (diameters 9–42 mm, SUVmax range 0.6–14.2) and was falsely negative in 6 patients. With SUVmax thresholds for malignancy of 1.5, 2, and 2.5, specificity was 97% but sensitivity decreased to 65%, 49%, and 46% respectively, and accuracy decreased to 85%, 79%, and 78% respectively (AUC 0.872). Conclusions: The visual analysis of FDG PET/CT scan is highly accurate in characterizing indeterminate pulmonary nodules detected in lung cancer screening with low-dose CT. Semi-quantitative analysis does not improve the accuracy of FDG PET/CT over that obtained with a qualitative method for lung nodule characterization.
- Smokers with CT detected emphysema and no airway obstruction have decreased plasma levels of EGF, IL-15, IL-8 and IL-1ra(Public Library of Science, 2013) Seijo, L. (Luis); Campo, A. (Arantza); Pajares, M.J. (María José); Pio, R. (Rubén); Bastarrika, G. (Gorka); Ortiz-de-Solorzano, C. (Carlos); Blanco, D. (Daniel); Montes, U. (Usúa); Torres, J.P. (Juan P.) de; Montuenga-Badia, L.M. (Luis M.); Alcaide, A.B. (Ana Belén); Muñoz-Barrutia, A. (Arrate); Segura, V. (Víctor); Zulueta, J. (Javier); Pueyo, J. (Jesús)Current or former smokers expressing a well-defined disease characteristic such as emphysema, has a specific plasma cytokine profile. This includes a decrease of cytokines mainly implicated in activation of apoptosis or decrease of immunosurveillance. This information should be taken into account when evaluated patients with tobacco respiratory diseases.
- Assessing the relationship between lung cancer risk and emphysema detected on low-dose CT of the chest.(American College of Chest Physicians, 2007) Seijo, L. (Luis); Campo, A. (Arantza); Lozano, M.D. (María Dolores); Bastarrika, G. (Gorka); Montes, U. (Usúa); Torres, J.P. (Juan P.) de; Montuenga-Badia, L.M. (Luis M.); Alcaide, A.B. (Ana Belén); Wisnivesky, J.P. (Juan P.); Villanueva, A. (Alberto); Zulueta, J. (Javier); Pueyo, J. (Jesús)Identification of risk factors for lung cancer can help in selecting patients who may benefit the most from smoking cessation interventions, early detection, or chemoprevention. OBJECTIVE: To evaluate whether the presence of emphysema on low-radiation-dose CT (LDCT) of the chest is an independent risk factor for lung cancer. METHODS: The study used data from a prospective cohort of 1,166 former and current smokers participating in a lung cancer screening study. All individuals underwent a baseline LDCT and spirometry followed by yearly repeat LDCT studies. The incidence density of lung cancer among patients with and without emphysema on LDCT was estimated. Stratified and multiple regression analyses were used to assess whether emphysema is an independent risk factor for lung cancer after adjusting for age, gender, smoking history, and the presence of airway obstruction on spirometry. RESULTS: On univariate analysis, the incidence density of lung cancer among individuals with and without emphysema on LDCT was 25.0 per 1,000 person-years and 7.5 per 1,000 person-years, respectively (risk ratio [RR], 3.33; 95% confidence interval [CI], 1.41 to 7.85). Emphysema was also associated with increased risk of lung cancer when the analysis was limited to individuals without airway obstruction on spirometry (RR, 4.33; 95% CI, 1.04 to 18.16). Multivariate analysis showed that the presence of emphysema (RR, 2.51; 95% CI, 1.01 to 6.23) on LDCT but not airway obstruction (RR, 2.10; 95% CI, 0.79 to 5.58) was associated with increased risk of lung cancer after adjusting for potential cofounders. CONCLUSIONS: Results suggest that the presence of emphysema on LDCT is an independent risk factor for lung cancer.
- Pulmonary arterial enlargement predicts long-term survival in COPD patients(Public Library of Science, 2018) Campo, A. (Arantza); Bastarrika, G. (Gorka); Celli, B.R. (Bartolomé R.); Casanova, C. (Ciro); Bertó, J. (Juan); Torres, J.P. (Juan P.) de; Alcaide, A.B. (Ana Belén); Ezponda, A. (Ana); Rodriguez-Delgado, L.E. (Luisa Elena); González, J. (Jessica); Zulueta, J. (Javier)Rationale Pulmonary artery enlargement (PAE) is associated with exacerbations in Chronic Obstructive Pulmonary Disease (COPD) and with survival in moderate to severe patients. The potential role of PAE in survival prediction has not been compared with other clinical and physiological prognostic markers. Methods In 188 patients with COPD, PA diameter was measured on a chest CT and the following clinical and physiological parameters registered: age, gender, smoking status, pack-years history, dyspnea, lung function, exercise capacity, Body Mass Index, BODE index and history of exacerbations in year prior to enrolment. Proportional Cox regression analysis determined the best predictor of all cause survival. Results During 83 months (±42), 43 patients died. Age, pack-years history, smoking status, BMI, FEV1%, six minute walking distance, Modified Medical Research Council dyspnea scale, BODE index, exacerbation rate prior to enrollment, PA diameter and PAE (diameter≥30mm) were associated with survival. In the multivariable analysis, age (HR: 1.08; 95%CI: 1.03–1.12, p<0.001) and PAE (HR: 2.78; 95%CI: 1.35–5.75, p = 0.006) were the most powerful parameters associated with all-cause mortality. Conclusions In this prospective observational study of COPD patients with mild to moderate airflow limitation, PAE was the best predictor of long-term survival along with age.
- Longitudinal study of a mouse model of chronic pulmonary inflammation using breath hold gated micro-CT.(Springer, 2010-05-24) Bastarrika, G. (Gorka); Ortiz-de-Solorzano, C. (Carlos); Blanco, D. (Daniel); Torres, J.P. (Juan P.) de; Montuenga-Badia, L.M. (Luis M.); Biurrun, G. (Gabriel) de; Artaechevarria-Artieda, X. (Xabier); Muñoz-Barrutia, A. (Arrate); Perez-Martin, D. (Daniel); Zulueta, J. (Javier)Abstract Objectives To evaluate the feasibility of using automatic quantitative analysis of breath hold gated micro-CT images to detect and monitor disease in a mouse model of chronic pulmonary inflammation, and to compare image-based measurements with pulmonary function tests and histomorphometry. Material and methods Forty-nine A/J mice were used, divided into control and inflammation groups. Chronic inflammation was induced by silica aspiration. Fourteen animals were imaged at baseline, and 4, 14, and 34 weeks after silica aspiration, using micro-CT synchronized with ventilator-induced breath holds. Lung input impedance was measured as well using forced oscillation techniques. Five additional animals from each group were killed after micro-CT for comparison with histomorphometry. Results At all time points, micro-CT measurements show statistically significant differences between the two groups, while first differences in functional test parameters appear at 14 weeks. Micro-CT measurements correlate well with histomorphometry and discriminate diseased and healthy groups better than functional tests. Conclusion Longitudinal studies using breath hold gated micro-CT are feasible on the silica-induced model of chronic pulmonary inflammation, and automatic measurements from micro-CT images correlate well with histomorphometry, being more sensitive than functional tests to detect lung damage in this model.
- The global burden of pulmonary diseases: most prevalent problems and opportunities for improvement(Ubiquity Press, Ltd., 2019) Torres, J.P. (Juan P.) de; Wisnivesky, J.P. (Juan P.)Diseases of the respiratory system are a leading cause of morbidity, mortality and disability worldwide. The lungs are constantly exposed to a myriad of noxious agents present in ambient air, such as particles, chemicals and infectious organisms. At least 2 billion people are exposed globally to the toxic smoke produced by combustion of biomass fuel, inefficiently burned in poorly ventilated indoor stoves or fireplaces used for cooking or warming. One billion people inhale polluted outdoor air, and another billion are exposed primarily or secondarily to tobacco smoke. As a consequence, respiratory disease is a major cause of morbidity, disability and death worldwide primarily affecting individuals of low socioeconomic status, who are exposed to crowding, environmental exposures and poor living conditions.