Pulmonary hypertension associated with interstitial lung disease (PH-ILD) represents a major clinical challenge due to its impact on prognosis and the complexity of diagnosis and management. The objective of this work was to develop practical, region-specific guidelines primarily aimed at supporting healthcare professionals in Latin America. A multidisciplinary working group of Latin American experts in PH-ILD developed an expert opinion paper, from which a diagnostic and therapeutic algorithm was derived. The resulting algorithm provides a stepwise approach to identifying suspected PH in patients with interstitial lung disease, confirming the diagnosis, and guiding management and treatment. Clinical, functional, biological, and imaging findings, including transthoracic Doppler echocardiography, are integrated to estimate the probability of PH, with tricuspid regurgitation velocity used to stratify risk. Right heart catheterization is proposed to confirm the diagnosis and to inform treatment decisions according to current recommendations. This algorithm offers a structured and practical tool that may facilitate earlier diagnosis and support appropriate management of patients with PH-ILD in routine clinical practice.
Objective To examine whether obstructive sleep apnea (OSA) is associated with pro-B-type natriuretic peptide and its N-terminal fragment (proBNP/NT-proBNP), a blood marker of myocardial wall stress, and with echocardiographic measures of cardiac size and function in children living at high altitude. Methods 274 children aged 5–16 years living in Bogotá, Colombia (2,660 m) underwent overnight polysomnography, from which OSA and hypoxic-burden measures (oxygen desaturation index, percentage of sleep time with oxygen saturation below 90%) were derived. Serum proBNP/NT-proBNP and interleukin-10 (IL-10, an anti-inflammatory cytokine) were measured by enzyme-linked immunosorbent assay, and pediatric cardiologists performed echocardiography. Statistical analysis: proBNP/NT-proBNP was analysed with median regression adjusted for sex and body mass index z-score; six echocardiographic outcomes were tested with Holm correction; hypoxic-burden and IL-10 analyses were exploratory. Results 187 (68%) children had OSA. Median proBNP/NT-proBNP was higher with OSA (adjusted ratio of medians 1.56, 95% confidence interval 1.02–2.39). No echocardiographic outcome differed after correction (all Holm-adjusted p ≥ 0.14). In exploratory analyses, a higher oxygen desaturation index was associated with higher proBNP/NT-proBNP (p = 0.014), but this did not remain after false-discovery-rate correction (q = 0.22). IL-10 analyses were exploratory. Conclusions In children living at 2,660 m, OSA was associated with higher proBNP/NT-proBNP but not with echocardiographic differences. Longitudinal, multi-altitude studies are needed.
BACKGROUND:In Latin America, the evidence regarding the use of prostanoids at high altitude in patients with Group 1 pulmonary hypertension (PH-1) is limited. Therefore, it is essential to describe the clinical characteristics and outcomes associated with prostanoid treatment in this population. METHODS:This retrospective study involved patients with PH-1. Hemodynamic and clinical variables were compared before the initiation of prostanoids and during clinical follow-up. Overall survival was analyzed using Kaplan-Meier estimation, with survival rates calculated at 3 and 5 years. The strength of the association for each variable concerning the proposed outcomes was estimated by calculating the odds ratio (OR). RESULTS:The study included 55 patients (mean age 34.6 ± 10.3 years), 83.6% women, all receiving triple combination therapy with endothelin receptor antagonists (ERAs), phosphodiesterase Type 5 inhibitors, and parenteral prostacyclin analogues. Idiopathic pulmonary arterial hypertension was present in 62%, and 60% were classified as intermediate risk at baseline. Median time from PH-1 diagnosis to prostacyclin initiation was 8.96 months (IQR 1.88-41.42). At 1 year, complete follow-up data were available for 49 patients. St. George's Respiratory Questionnaire scores improved significantly from 49.0 to 36.5 at 1 year and 31.5 at the last follow-up (p < 0.001). Cardiac index increased from 2.24 to 2.96 L/min/m2 at 1 year (p < 0.001), whereas mixed venous oxygen saturation improved significantly. In survivors, the 6-min walk test distance increased by 53.5 m, and pulmonary vascular resistance decreased by 3.8 WU. Diffusing capacity for carbon monoxide (DLCO) < 25% was associated with an OR of 7.35 (95% CI: 1.28-41.92; p = 0.015), and tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio (TAPSE/PASP) < 0.10 mm/mmHg had an OR of 5.78 (95% CI: 0.64-52.03; p = 0.088). Female sex had an OR of 0.13 (95% CI: 0.02-0.78; p = 0.016). Three- and five-year survival rates were 87.2% and 78.1%, respectively. CONCLUSION:Parenteral prostanoids in patients with PH-1 demonstrate improvements in hemodynamic variables during clinical follow-up. A DLCO < 25% and a TAPSE/PASP < 0.10 mm/mmHg were associated with an increased risk of mortality, whereas female sex was identified as a protective factor.
BACKGROUND:The way in which risk predictors combine and contribute to severe asthma exacerbations may differ between clinical trials and real-world settings. RESEARCH QUESTION:How do the interactive pathways of risk predictors leading to severe asthma exacerbations compare under clinical trials vs real-world settings? STUDY DESIGN AND METHODS:The analysis involved 345 patients with severe asthma from the placebo arms of 2 international randomized controlled trials (RCTs), compared with 6,814 biologic-naïve patients from the International Severe Asthma Registry (ISAR). Sixteen key risk predictors, including demographics, biomarkers, lung function, health care use, exacerbation history, long-term oral corticosteroid use, asthma control, and nasal polyps, were covered. The outcome was the occurrence of severe asthma exacerbations over the 365 days after study enrollment. Bayesian networks (BNs), obtained from machine learning combined with expert knowledge, elucidated significant interplay processes of risk predictors that led to severe asthma exacerbations. External validation was performed in each cohort. RESULTS:The RCTs revealed 44 significant arcs (ie, probabilistic interdependency) between 16 risk factors, whereas the ISAR showed 170. Despite this difference, the main downstream prediction pathways were consistent across both settings, with 2 key pathways: total serum IgE level influenced blood eosinophils to predict future severe exacerbations, and severe exacerbation history directly predicted future severe exacerbations. In external validation, RCT-BN generalized well to ISAR patients (area under the receiver operating characteristic curve, 0.68), whereas ISAR-BN underperformed in RCT patients (area under the receiver operating characteristic curve, 0.50), and ISAR-BN demonstrated better calibration. INTERPRETATION:Our results show that the core pathways predicting severe asthma exacerbations were similar in both RCTs and real-world settings, with comparable predictive performance.
Objective: To identify changes in cytokine concentration in the plasma of patients with IPF and healthy controls residing in Bogotá. Methods: Peripheral blood samples were taken from 13 patients over 60 years old with a diagnosis of IPF and 13 healthy counterparts. Plasma separation was performed and stored at -20°C. Cytokines were measured using the Human TH1/TH2 Cytometric Bead Array (CBA). This work was approved by the ethics and research committee of the Fundación Neumológica Colombiana. Results: Patients with Idiopathic Pulmonary Fibrosis (IPF) showed increased levels of cytokines such us IL-4, INF-γ and IL-6 compared to healthy older adults. Conclusions: Inflammaging has been associated with the development and coexistence of multiple non-communicable chronic diseases that have a higher incidence after the age of 65. The involvement of adaptive immunity in the pathogenesis of IPF has been described as an imbalance in the Th1/Th2 lymphocyte response. IL-4 stimulation favors the phenotypic shift to M2 macrophages and Th2 cells, along with the promotion of pro-fibrotic environments by Innate lymphoid cells type 2 (ILC-2).
