Predictors of the response to phosphodiesterase-5 inhibitors in pulmonary arterial hypertension: an analysis of the Spanish registry.

BACKGROUND: Achieving and maintaining a low-risk profile is associated with favorable outcome in pulmonary arterial hypertension (PAH). The effects of treatment on risk profile are variable among patients. OBJECTIVE: To Identify variables that might predict the response to treatment with phosphodiesterase-5 inhibitors (PDE-5i) in PAH. METHODS: We carried out a cohort analysis of the Spanish PAH registry in 830 patients diagnosed with PAH that started PDE5i treatment and had > 1 year follow-up. 644 patients started PDE-5i either in mono- or add-on therapy and 186 started combined treatment with PDE-5i and endothelin receptor antagonist (ERA). Responders were considered when at 1 year they: (1) were alive; (2) did not present clinical worsening; and (3) improved European Society of Cardiology/European Respiratory Society (ESC/ERS) risk score or remained in low-risk. Univariate and multivariate logistic regression models were used to analyze variables associated with a favorable response. RESULTS: Two hundred and ten patients (33%) starting PDE-5i alone were classified as responders, irrespective of whether it was mono- or add-on therapy. In addition to known predictors of PAH outcome (low-risk at baseline, younger age), male sex and diagnosis of portopulmonary hypertension (PoPH) or HIV-PAH were independent predictors of favorable response to PDE-5i. Diffusing capacity for carbon monoxide (DLco) ≤ 40% of predicted was associated with an unfavorable response. When PDE-5i were used in upfront combination, 58% of patients were responders. In this group, diagnosis of idiopathic PAH (IPAH) was an independent predictor of favorable response, whereas connective tissue disease-PAH was associated with an unfavorable response. CONCLUSION: Male sex and diagnosis of PoPH or HIV-PAH are predictors of favorable effect of PDE-5i on risk profile when used as mono- or add-on therapy. Patients with IPAH respond more favorably to PDE-5i when used in upfront combination. These results identify patient profiles that may respond favorably to PDE-5i in monotherapy and those who might benefit from alternative treatment strategies.

Effects of Exercise Training on Circulating Biomarkers of Endothelial Function in Pulmonary Arterial Hypertension.

INTRODUCTION: In stable patients with pulmonary arterial hypertension (PAH), pulmonary rehabilitation (PR) is an effective, safe and cost-effective non-pharmacological treatment. However, the effects of PR on vascular function have been poorly explored. This study aimed to compare the amounts of circulating progenitor cells (PCs) and endothelial microvesicles (EMVs) in patients with PAH before and after 8 weeks of endurance exercise training as markers of vascular competence. METHODS: A prospective study of 10 consecutive patients with PAH that successfully finished a PR program (8 weeks) was carried out before and after this intervention. Levels of circulating PCs defined as CD34+CD45low progenitor cells and levels of EMVs (CD31+ CD42b-) were measured by flow cytometry. The ratio of PCs to EMVs was taken as a measure of the balance between endothelial damage and repair capacity. RESULTS: All patients showed training-induced increases in endurance time (mean change 287 s). After PR, the number of PCs (CD34+CD45low/total lymphocytes) was increased (p < 0.05). In contrast, after training, the level of EMVs (CD31+ CD42b-/total EMVs) was reduced. The ratio of PCs to EMVs was significantly higher after training (p < 0.05). CONCLUSION: Our study shows, for the first time, that endurance exercise training in patients with stable PAH has a positive effect, promoting potential mechanisms of damage/repair in favor of repair. This effect could contribute to a positive hemodynamic and clinical response.

Síndrome antisintetasa en paciente con COP como afección pulmonar / Antisynthetase Syndrome in Patient with COP as Pulmonary Disease

El síndrome antisintetasa es una miopatía inflamatoria autoinmune que puede presentar afectación pulmonar intersticial. La presencia de anticuerpos antisintetasa se relaciona con una mayor incidencia de enfermedad pulmonar intersticial. El patrón imagenológico y anatomopatológico de la EPID es variable, fundamentalmente inflamatorio. En el caso presentado se describe una paciente con miopatía inflamatoria y compromiso pulmonar presentando un patrón tomográfico de neumonía organizativa. Se destaca la importancia de elevar el índice de sospecha de síndrome antisintetasa ante un paciente con compromiso pulmonar y miopatía, siendo fundamental para arribar a un diagnóstico la evaluación multidisciplinaria. Se realiza una revisión de la evidencia al respecto en la discusión del caso

The antisynthetase syndrome is an autoimmune inflammatory miopathy that may show interstitial pulmonary involvement. The presence of antisynthetase antibodies is related to a higher incidence of interstitial pulmonary involvement. The imaging and anatomopathological pattern of diffuse interstitial pulmonary disease (DIPD) is variable, mainly inflammatory. This case describes a female patient with inflammatory miopathy and pulmonary involvement who shows a tomographic pattern of organizing pneumonia. It is important to increase suspicion for antisynthetase syndrome in a patient with pulmonary involvement and miopathy, where multidisciplinary evaluation is fundamental to reach a diagnosis. A review of the evidence is made in the discussion of the case.

Atmospheric dispersion of methane emissions from sugarcane burning in Mexico.

Methane is a potent greenhouse gas whose atmospheric dispersion may have different implications at distinct scales. One significant contributor to methane emissions is sugarcane farming in tropical areas like in Mexico, which has the sixth highest production level in the world. A consequence of the industrial use of this resource is that sugarcane preharvest burning emits large quantities of methane and other pollutants. The objective of this research is to estimate the methane emissions by sugarcane burning and to analyze their atmospheric dispersion under the influence of meteorological parameters, according to different concentration scenarios generated during a period. The methane emissions were investigated using the methodology of Seiler and Crutzen, based on the stage production during the harvest periods of 2011/2012, 2012/2013 and 2013/2014. Average of total emissions (1.4 × 103 Mg) at the national level was comparable in magnitude to those of other relevant sugarcane-producing countries such as India and Brazil. Satellite images and statistical methods were used to validate the spatial distribution of methane, which was obtained with the WRF model. The results show a dominant wind circulation pattern toward the east in the San Luis Potosi area, to the west in Jalisco, and the north in Tabasco. In the first two areas, wind convergence at a certain height causes a downward flow, preventing methane dispersion. The concentrations in these areas varied from 9.22 × 10-5 to 1.22 × 102 ppmv and 32 × 10-5 to 2.36 × 102 ppmv, respectively. Wind conditions in Tabasco contributed to high dispersion and low concentrations of methane, varying from 8.74 × 105 to 0.33 × 102 ppmv. Methane is a potent greenhouse gas for which it is essential to study and understand their dispersion at different geographic locations and atmospheric conditions.

Impact of using the new GOLD classification on the distribution of COPD severity in clinical practice.

Objective: The objective of this study was to examine how COPD patients were classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometry-based severity system and the distribution of COPD severity using the new GOLD 2011 assessment framework. Materials and methods: This was an observational, retrospective cohort study conducted in a single tertiary center on a prospective database, which aimed to evaluate the prevalence, incidence, severity, and comorbidities of COPD. Inclusion criteria were age ≥40 years and COPD diagnosis according to GOLD 2007 classification. Clinical factors were compared between the categories in GOLD 2007 and 2011 groups by using the χ2 test for categorical data and the analysis of variance for continuous data. Results: In total, 420 COPD patients were included in the analysis. The distribution of patients into GOLD 2007 categories was as follows: 6.4% (n=27) of them were classified into subgroup I, 42.1% (n=177) into subgroup II, 37.9% (n=159) into subgroup III, and 13.6% (n=57) into subgroup IV. The distribution of patients into GOLD 2011 categories was as follows: 16.4% (n=69) of them were classified into subgroup A (low risk and fewer symptoms), 32.1% (n=135) into subgroup B (low risk and more symptoms), 21.6% (n=91) into subgroup C (high risk and fewer symptoms), and 29.7% (n=125) into subgroup D (high risk and more symptoms). After the application of the new GOLD 2011 (modified Medical Research Council [mMRC] system), 22% (n=94) of patients were upgraded to a higher level than their spirometry level, and 16.2% (n=68) of them were downgraded in their severity category, meaning that almost 40% of patients changed their severity assessment category. In total, 22% of patients in stage I were allocated to group B, and 35% of patients in stage IV were allocated to group C. Patients in stage III were the most frequently upgraded to a higher risk group (D), taking into account mMRC and exacerbation history. Conclusion: Classifying patients using the new GOLD 2011 criteria reallocated a relevant proportion of patients to a different risk category and identified larger proportions of patients in the mildest and more severe groups compared with GOLD 2007 classification.

An air pollution modeling study using three surface coverings near the New International Airport of Mexico City.

The dry lakebed of what once was the lake of Texcoco is the location selected for the New International Airport of Mexico City. This project will generate an important urban development near the airport with regional implications on air quality. Using a prognostic air quality model, the consequences of photochemical air pollution in the metropolitan area of Mexico City resulting from three possible coverings for the areas of the lakebed that are not occupied by the runway and terminal building are investigated. These coverings are desert, grassland, and water and occupy an area of 63 km2. This study is based on a representative high pollution episode. In addition to reducing the emission of primary natural particles, the water covering generates a land-water breeze capable of maintaining enough ventilation to reduce pollutant concentrations over a localized region of the metropolitan area and may enhance the wind speed on the coasts of the proposed lake.

An air quality modeling study comparing two possible sites for the new international airport for Mexico City.

Using an air quality model, two future urban scenarios induced by the construction of the new international airport for Mexico City are compared at a regional level. The air quality model couples the meteorology model MM5 and state-of-the-art photochemistry. The air quality comparison is made using metrics for the criterion gases selected for the study. From the two urban scenarios compared, the option for Tizayuca is moderately better than the option for Texcoco, because relative reductions in O3 and other photochemical pollutants are achieved over highly populated areas. Regardless of the site, the air quality for the central region of Mexico in the future will deteriorate. In the region of central Mexico, SO2 and NO2 will become important pollutants.