Adaptation to Living at High Altitude in Patients with COPD. Comparative Study of Exercise Capacity and Ventilatory Variables between Patients Residing at High and Low Altitudes in the Andes.

González-García, Mauricio and Luis Ernesto Téllez. Adaptation to living at high altitude in patients with COPD. Comparative study of exercise capacity and ventilatory variables between patients residing at high and low altitudes in the Andes. High Alt Med Biol. 00:000-000, 2024. Introduction: Although some variables related to oxygen transport and utilization such as ventilation, pulmonary vascular responses to hypoxia, heart rate (HR), cardiac output, hemoglobin (Hb), and oxygen saturation (SpO2) are used to compare adaptation to altitude between populations, peak oxygen consumption (VO2) constitutes an integrative measure of total oxygen transport that may reflect successful adaptation to altitude. We designed this study to make a direct comparison of VO2 in a cardiopulmonary exercise test (CPET) between chronic obstructive pulmonary disease (COPD) patients residing at high altitude (Bogotá, Colombia: 2,640 m) (COPD-HA) and those living at low altitude (Bucaramanga, Colombia: 959 m) (COPD-LA). Methods: All patients performed a CPET with measurements of VO2, minute ventilation (VE), HR, oxygen pulse (VO2/HR), ventilatory equivalents (VE/VCO2), and SpO2. Unpaired T-test or Mann-Whitney U test were used for comparisons between COPD-HA and COPD-LA. Results: We included 71 patients with COPD, 53 COPD-HA, and 18 COPD-LA. There were no differences between groups in age, sex, or forced expiratory volume in 1 second. The means ± SD of Hb, g/dl was slightly higher in COPD-HA (15.9 ± 1.9 vs. 14.7 ± 1.8, p = 0.048), without differences in VO2, % pred (71.6 ± 17.9 vs. 69.0 ± 17.0, p = 0.584), VO2/HR, % pred (92.1 ± 22.0 vs. 89.7 ± 19.8, p = 0.733) or VE/MVV, % (75.5 ± 14.1 vs. 76.5 ± 14.3, p = 0.790) at peak exercise between groups. Median (IQR) of VE/VCO2 nadir [38.0 (37.0-42.0) vs. 32.5 (31.0-39.0), p = 0.005] was significantly higher, and SpO2, % at rest [88.0 (86.0-91.0) vs. 95.0 (94.0-96.0), p < 0.001] and at peak exercise [84.0 (77.0-90.0) vs. 93.0 (92.0-95.0), p < 0.001] were significantly lower in COPD-HA. Conclusions: Despite higher desaturation at rest and during exercise in COPD-HA, there were no differences in VO2 peak between COPD-HA and COPD-LA, suggesting a potential altitude adaptation in those patients chronically exposed to hypoxia.

Sputum Biomarkers in Wood and Tobacco Smoke Etiotypes of Chronic Obstructive Pulmonary Disease.

Introduction: There is a need to better understand the etiotypes of chronic obstructive pulmonary disease (COPD) beyond the tobacco-smoke (TS-COPD). Wood smoke COPD (WS-COPD) is characterized by greater airway compromise, milder emphysema, and slower rate of lung function decline than TS-COPD. However, it is unclear if these two etiotypes of COPD have differences in sputum biomarker concentrations. Objective was to compare sputum levels of selected sputum biomarkers between WS-COPD and TS-COPD, and healthy controls. Methods: Eighty-eight women (69±12 years) were recruited and classified into: WS-COPD (n=31), TS-COPD (n=29) and controls (n=28). Using ELISA, we determined induced sputum levels of metalloproteinase 9 (MMP-9), chemokine ligand 5 (CCL5), interleukin-8 (IL-8), chemokine ligand 16 (CCL16/HCC-4) and vascular endothelial growth factor (VEGF-1). Differences were analyzed by Kruskal-Wallis and Mann-Whitney-U tests and correlation between airflow limitation and biomarkers by Spearman's test. Results: At similar degree of airflow obstruction, anthropometrics and medications use, the level of sputum CCL5 was higher in TS-COPD than WS-COPD (p=0.03) without differences in MMP-9, IL-8, CCL16/HCC-4, and VEGF-1. Women with WS-COPD and TS-COPD showed significantly higher sputum levels of MMP-9, IL-8 and CCL5 compared with controls (p<0.001). FEV1% predicted correlated negatively with levels of MMP-9 (rho:-0.26; P=0.016), CCL5 (rho:-0.37; P=0.001), IL-8 (rho:-0.42; P<0.001) and VEGF (rho:-0.22; P=0.04). Conclusion: While sputum concentrations of MMP-9, IL-8, and CCL5 were higher in COPD women compared with controls, women with TS-COPD had higher levels of CCL5 compared with those with WS-COPD. Whether this finding relates to differences in pathobiological pathways remains to be determined.

Tropical high altitude and severe asthma in adults: house dust mite sensitization and phenotypic distribution.

BACKGROUND: There is a lack of information on house dust mite (HDM) sensitization and phenotype distribution in patients with severe asthma (SA) living permanently at high-altitude (HA) in tropical regions, which may be different. OBJECTIVE: The aim of this study was to characterize adults with SA in a tropical high altitude city (2,640 m): Bogotá, Colombia. MATERIAL AND METHODS: This observational cross-sectional study included severe asthmatic outpatients (n = 129) referred to the ASMAIRE program of the Fundación Neumológica Colombiana in Bogotá (2,640 m). Clinical history, spirometry, total IgE, blood eosinophils, and skin prick test (SPT), including HDM allergens, were performed. Phenotype definitions: Allergic/atopic (AA): IgE ≥100 IU/mL and/or at least one positive SPT; eosinophilic (EOS): blood eosinophils ≥300 cells/µL; type 2-high: AA and/or EOS phenotype; type 2-low: non-AA/non-EOS phenotype (IgE <100 IU/mL, negative SPT, and blood eosinophils <300 cells/µL). RESULTS: A total of 129 adults with SA were included, 79.8% female. Phenotype distribution: AA: 61.2%; EOS: 37.2%; type 2-high: 72.1%; type 2-low: 27.9%. Among AA patients, HDM sensitization was present in 87% and 34.9% were non-eosinophilic. There was a significant overlap between the phenotypes. CONCLUSIONS: In contrast to non-tropical high-altitude regions, we found a high frequency of HDM sensitization in patients with AA phenotype living in a tropical high-altitude city. We also found a discrete lower frequency of EOS phenotype with no other significant differences in the phenotypic distribution compared to that described at low altitudes. We propose that tropical location may modify the effect of high altitude on HDM concentrations and allergenicity.

Knowledge of Vaccination Against Influenza and Pneumococcus in Patients with Chronic Obstructive Pulmonary Disease in an Integrated Care Program.

Purpose: To compare the level of knowledge in vaccination against influenza and pneumococcus of patients with chronic obstructive pulmonary disease (COPD) who are managed in an Integrated Care Program (ICP) with those who receive usual care (UC). Methods: A telephone survey of patients diagnosed with COPD registered in public care networks or private institutions was done. A descriptive and comparative analysis of the characteristics of the ICP and UC groups was carried out. The relationship between belonging to an ICP and the level of knowledge about vaccination was evaluated using Propensity Score Matching (PSM) and multivariate logistic and ordinal regression models. Results: Of 674 study participants, 27.2% were from the ICP group. ICP patients were older, more frequently men, from a higher socioeconomic stratum and a higher educational level (p<0.05). 75.5% of the patients in the ICP group had a high level of vaccination knowledge compared to 42.7% in the UC group (p<0.001). In the multivariate analysis, adjusting for sociodemographic variables, years of COPD diagnosis, and comorbidities, belonging to the ICP was associated with a higher probability of answering questions about vaccination correctly and having a high level of knowledge (OR 3.397, IC 95% 2.058-5.608, p<0.001). Conclusion: Patients with COPD managed in an ICP have a higher level of knowledge in vaccination against influenza and pneumococcus, compared to patients in usual care.

Prevalence of genetic mutations in alpha-1 antitrypsin deficiency (aatd) in patients with chronic obstructive pulmonary disease in Colombia.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is an underrecognized genetic disorder associated mainly with pulmonary emphysema and Chronic Obstructive Pulmonary Disease (COPD). All individuals with COPD regardless of age or ethnicity should be tested for AATD, but in Colombia its prevalence in unknown. MAIN OBJECTIVE: To determine the prevalence of the genetic mutations, present in AATD in adult patients with COPD in Colombia, using a genotyping test on cells from the oral mucosa. METHODS: This was a multicentre, observational, cross-sectional study which included adult patients attending seven COPD care centres in Colombia. Demographic data, medical history, including history of exposure to smoking and biomass smoke, most recent spirometry, pharmacological and non-pharmacological treatment received, serum AAT levels, and mutations detected by the genotyping test were recorded for all the recruited patients. For the comparison of variables between the groups with and without mutation, we used the X2 test for the qualitative variables and the Student's t-test or Mann-Whitney U test according to their distribution. MAIN FINDINGS: We collected a sample of 1,107 patients, the median age was 73.8 years (87.6-79.9). Mutations were documented in 144 patients (13.01%), the majority had the M/S mutation (78.50%), followed by M/Z (9.72%). One patient had a ZZ mutation and two patients had null alleles. In total, 23 patients had mutations associated with serum AAT deficiency (levels below 60 mg/dl). CONCLUSIONS: Genetic mutations were documented in 13.01% of patients with COPD in Colombia and 2.07% were AATD-related, showing that there is a significant number of underdiagnosed patients.

Risk factors for persistent tomographic abnormalities at 6 months of follow-up in a cohort of hospitalized patients with moderate and severe COVID-19 living at high altitude.

Introduction: After COVID-19, functional and tomographic lung alterations may occur, but there are no studies at high altitude where, due to lower barometric pressure, there are lower levels of arterial oxygen pressure and saturation in both normal subjects and patients with respiratory disease. In this study, we evaluated the computed tomographic (CT), clinical, and functional involvement at 3 and 6 months post-hospitalization in survivors with moderate-severe COVID-19, as well the risk factors associated with abnormal lung computed tomography (ALCT) at 6 months of follow-up. Materials and methods: Prospective cohort, after hospitalization for COVID-19, of patients older than 18 years residing at high altitude. Follow-up at 3 and 6 months with lung CT, spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), six-minute walk test (6MWT), and oxygen saturation (SpO2). Comparisons between ALCT and normal lung computed tomography (NLCT) groups with X2 and Mann-Whitney U test, and paired test for changes between 3 and 6 months. A multivariate analysis was performed to evaluate the variables associated with ALCT at 6-month follow-up. Results: We included 158 patients, 22.2% hospitalized in intensive care unit (ICU), 92.4% with typical COVID CT scan (peripheral, bilateral, or multifocal ground glass, with or without consolidation or findings of organizing pneumonia), and median hospitalization of 7 days. At 6 months, 53 patients (33.5%) had ALCT. There were no differences between ALCT and NLCT groups in symptoms or comorbidities on admission. ALCT patients were older and more frequently men, smokers and hospitalized in ICU. At 3 months, ALCT patients had more frequently a reduced forced vital capacity (< 80%), and lower meters walked (6MWT) and SpO2. At 6 months, all patients improved lung function with no differences between groups, but there were more dyspnea and lower exercise SpO2 in ALCT group. The variables associated with ALCT at 6 months were age, sex, ICU stay, and typical CT scan. Conclusion: At 6-month follow-up, 33.5% of patients with moderate and severe COVID had ALCT. These patients had more dyspnea and lower SpO2 in exercise. Regardless of the persistence of tomographic abnormalities, lung function and 6MWT improved. We identified the variables associated with ALCT.

Sex differences regarding the impact of a standardized adaptation session in Colombian patients with obstructive sleep apnea and poor adherence to positive airway pressure devices / Diferencias por sexo respecto al impacto de una sesión de adaptación en pacientes colombianos con apnea obstructiva del sueño y mala adherencia a dispositivos de presión positiva

Abstract Introduction: Positive airway pressure (PAP) is the most effective treatment for obstructive sleep apnea (OSA) but adherence to this device is poor. The Sleep and Breathing Disorders Clinic of Fundación Neumológica Colombiana (FNC) has a standardized adaptation session (SAS) aimed at patients with difficulties in using PAP devices. Objective: To evaluate the impact of a SAS in short-term adherence to PAP therapy in patients with OSA, and to determine differences by sex. Materials and methods: Before-and-after single cohort study conducted in 40 people aged >18 years with an apnea-hypopnea index >15/hour and treated at the FNC, Bogotá D.C. (Colombia) between 2015 and 2017, who attended a SAS due to poor adherence to PAP therapy (defined as <4 hours use in 70% of nights). Data on the hours of use of the PAP device and the percentage of days in which it was used >4 hours were recorded before and after the intervention to evaluate changes in patients' adherence. Descriptive statistics were used for data analysis. The paired samples t-test was used for the comparison of variables before and after the intervention. Results: A significant increase was observed in PAP device use (1.8 hours, 95%CI: 1.3-2.3; p<0.001) and in the percentage of days it was used >4 hours (35.6%, 95%CI: 26.0-45.3; p<0.001). Among men, the increase was higher in both cases (2.3 hours, 95%CI: 1.7-2.9; p=0.029 and 47.8%, 95%CI: 32.9-62.8; p=0.029). Conclusion: The SAS offered by the FNC, which includes education strategies and the identification and solving of barriers hindering the use of PAP devices, significantly increased the hours of PAP device use and the percentage of days in which it was used >4 hours in the study population, particularly in men.

Resumen Introducción. La terapia de presión positiva en la vía aérea (PAP) es el tratamiento más efectivo de la apnea obstructiva del sueño (AOS); sin embargo, la adherencia no es óptima. La clínica de trastornos respiratorios del sueño de la Fundación Neumológica Colombiana (FNC) tiene una sesión de adaptación estandarizada (SAE) dirigida a pacientes con dificultades en el uso de equipo PAP. Objetivo. Evaluar el impacto de una SAE en la adherencia a corto plazo a la terapia de PAP en pacientes con AOS y determinar diferencias por sexo. Materiales y métodos. Estudio de cohorte única de antes y después realizado en 40 pacientes >18 años con un índice de apnea-hipopnea >15/hora atendidos en la FNC, en Bogotá D.C., Colombia, entre 2015 y 2017 y que asistieron a una SAE debido a una pobre adherencia a la terapia de PAP (<4 horas de uso el 70% de las noches). Se registraron los datos de uso en horas del equipo de PAP y el porcentaje de días en que se usó más de 4 horas antes y después de la intervención. Los datos se analizaron mediante estadística descriptiva y se empleó la prueba T de muestras emparejadas para comparar las variables antes y después de la intervención. Resultados. Se observó un aumento significativo después de la SAE en las horas de uso del equipo de PAP (1.8 horas, IC95%: 1.3-2.3; p<0.001) y del porcentaje de días en que su uso fue >4 horas (35.6%, IC95%: 26.0-45.3; p<0.001); el incremento fue mayor en los hombres en ambos casos (2.3 horas, IC95%: 1.7-2.9; p=0.029, y 47.8%, IC95%: 32.9-62.8; p=0.029). Conclusión. La SAE que brinda la FNC, la cual incluye estrategias educativas y la identificación y solución de barreras que dificultan el uso del equipo de PAP, aumentó de forma significativa las horas de uso de los dispositivos de PAP y el porcentaje de días con uso >4 horas en la población de estudio, en particular en los hombres.

Effect of pulmonary hypertension on exercise capacity and gas exchange in patients with chronic obstructive pulmonary disease living at high altitude.

BACKGROUND: Pulmonary hypertension (PH) is associated with decreased exercise tolerance in chronic obstructive pulmonary disease (COPD) patients, but in the altitude the response to exercise in those patients is unknown. Our objective was to compare exercise capacity, gas exchange and ventilatory alterations between COPD patients with PH (COPD-PH) and without PH (COPD-nonPH) residents at high altitude (2640 m). METHODS: One hundred thirty-two COPD-nonPH, 82 COPD-PH, and 47 controls were included. Dyspnea by Borg scale, oxygen consumption (VO2), work rate (WR), ventilatory equivalents (VE/VCO2), dead space to tidal volume ratio (VD/VT), alveolar-arterial oxygen tension gradient (AaPO2), and arterial-end-tidal carbon dioxide pressure gradient (Pa-ETCO2) were measurement during a cardiopulmonary exercise test. For comparison of variables between groups, Kruskal-Wallis or one-way ANOVA tests were used, and stepwise regression analysis to test the association between PH and exercise capacity. RESULTS: All COPD patients had a lower exercise capacity and higher PaCO2, A-aPO2 and VD/VT than controls. The VO2 % predicted (61.3 ± 20.6 vs 75.3 ± 17.9; p < 0.001) and WR % predicted (65.3 ± 17.9 vs 75.3 ± 17.9; p < 0.001) were lower in COPD-PH than in COPD-nonPH. At peak exercise, dyspnea was higher in COPD-PH (p = 0.011). During exercise, in COPD-PH, the PaO2 was lower (p < 0.001), and AaPO2 (p < 0.001), Pa-ETCO2 (p = 0.033), VE/VCO2 (p = 0.019), and VD/VT (p = 0.007) were higher than in COPD-nonPH. In the multivariate analysis, PH was significantly associated with lower peak VO2 and WR (p < 0.001). CONCLUSION: In COPD patients residing at high altitude, the presence of PH was an independent factor related to the exercise capacity. Also, in COPD-PH patients there were more dyspnea and alterations in gas exchange during the exercise than in those without PH.

Impacto clínico de un grupo de discusión multidisciplinaria en el diagnóstico de fibrosis pulmonar idiopática en Colombia / Clinical impact of a multidisciplinary discussion group on the diagnosis of idiopathic pulmonary fibrosis in Colombia

Resumen Introducción: la fibrosis pulmonar idiopática (FPI) es una enfermedad pulmonar intersticial (EPID) de mal pronóstico, considerada huérfana en Colombia. Un diagnóstico correcto tiene implicaciones para el paciente y los costos de atención. Los grupos de discusión multidisciplinaria (GDM) se consideran el estándar de oro en el diagnóstico. No hay estudios previos en Colombia de la experiencia de un GDM. Objetivos: evaluar el impacto de un GDM en una institución de cuarto nivel en Bogotá en cambio de diagnóstico de pacientes con EPID y la concordancia entre el diagnóstico inicial y final de FPI. Material y métodos: pacientes con EPID evaluados entre 2015-2018 por el GDM conformado por neumólogos, radiólogo, patólogo y reumatólogos. Criterios ATS/ERS/JRS/ALAT de diagnóstico de FPI. Descripción del cambio en el diagnóstico y concordancia entre el diagnóstico inicial y del GDM en FPI. Resultados: de 165 pacientes con EPID se cambió el diagnóstico en 35.2%. En 77.3% pacientes con diagnóstico inicial de FPI y en 6.7% con diagnóstico inicial diferente a FPI el GDM confirmó FPI. Al descartar FPI, los principales diagnósticos fueron neumonitis de hipersensibilidad en fase crónica (29.4%) y neumonía intersticial no específica (23.5%). El índice kappa entre el diagnóstico inicial y final de FPI fue 0.71 (0.60-0.82). Conclusiones: el GDM en EPID tuvo un importante impacto clínico demostrado por un alto porcentaje de cambió del diagnóstico de remisión. Se descartó el diagnóstico inicial de FPI en un porcentaje significativo de pacientes y se ratificó en un grupo menor sin esta sospecha clínica inicial. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2017).

Abstract Introduction: idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease (ILD) with a poor prognosis, considered an orphan disease in Colombia. An accurate diagnosis has implications for the patient and healthcare costs. Multidisciplinary discussion groups (MDGs) are considered the gold standard for diagnosis. There are no prior studies in Colombia on the experience of an MDG. Objectives: to evaluate the impact of an MDG in a quaternary care institution in Bogotá on the change in the diagnosis of patients with ILD and the concordance between the initial and final diagnosis of IPF. Materials and methods: patents with ILD evaluated from 2015-2018 by the MDG made up of pulmonologists, a radiologist, a pathologist and rheumatologists. The ATS/ERS/JRS/ALAT diagnostic criteria for IPF. A description of changes in the diagnosis and the agreement between the initial diagnosis and the MDG diagnosis of IPF. Results: out of 165 patients with ILD, the diagnosis was changed in 32.5%. The MDG confirmed IPF in 77.3% of patients with an initial diagnosis of ILD and 6.7% of those with a different initial diagnosis. When IPF was ruled out, the main diagnoses were chronic hypersensitivity pneumonitis (24.8%) and nonspecific interstitial pneumonia (23.5%). The Kappa index between the initial and final IPF diagnoses was 0.71 (0.60-0.82). Conclusions: the MDG on ILD had a significant clinical impact evidenced by a high percentage of change in the referral diagnosis. The initial diagnosis of IPF was ruled out in a significant percentage of patients and confirmed in a smaller group which did not have this initial clinical suspicion. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2017).

Intermittent hypoxia and respiratory patterns during sleep of preterm infants aged 3 to 18 months residing at high altitude.

STUDY OBJECTIVES: The aim of this study was to determine the impact of apneas on oxygen saturation and the presence of intermittent hypoxia, during sleep of preterm infants (PTIs) born at high altitudes and compare with full-term infants (FTIs) at the same altitude. METHODS: PTIs and FTIs from 3 to 18 months were included. They were divided into three age groups: 3-4 months (Group 1); 6-7 months (Group 2), and 10-18 months (Group 3). Polysomnography parameters and oxygenation indices were evaluated. Intermittent hypoxia was defined as brief, repetitive cycles of decreased oxygen saturation. Kruskal-Wallis test for multiple comparisons, t-test or Mann-Whitney U-test were used. RESULTS: 127 PTI and 175 FTI were included. Total apnea-hypopnea index (AHI) was higher in PTI that FTI in all age groups (Group 1: 33.5/h vs. 12.8/h, p = 0.042; Group 2: 27.0/h vs. 7.4/h, p < 0.001; and Group 3: 11.6/h vs. 3.1/h, p < 0.001). In Group 3, central-AHI (8.0/h vs. 2.3/h, p < 0.001) and obstructive-AHI (1.8/h vs. 0.6/h, p < 0.008) were higher in PTI than FTI. T90 (7.0% vs. 0.5, p < 0.001), oxygen desaturation index (39.8/h vs. 11.3, p < 0.001) were higher in PTI than FTI, nadir SpO2 (70.0% vs. 80.0, p<0.001) was lower in PTI. CONCLUSION: At high altitude, compared to FTI, PTI have a higher rate of respiratory events, greater desaturation, and a delayed resolution of these conditions, suggesting the persistence of intermittent hypoxia during the first 18 months of life. This indicates the need for follow-up of these infants for timely diagnosis and treatment of respiratory disturbances during sleep.

Comorbidities of Patients With Idiopathic Pulmonary Fibrosis in Four Latin American Countries. Are There Differences by Country and Altitude?

Background: Comorbidities in idiopathic pulmonary fibrosis (IPF) affect quality of life, symptoms, disease progression and survival. It is unknown what are the comorbidities in patients with IPF in Latin America (LA) and if there are differences between countries. Our objective was to compare IPF comorbidities in four countries and analyze possible differences by altitude. Methods: Patients with IPF according 2012 ATS/ERS/JRS/ALAT guidelines, from two cities with an altitude of ≥2,250 m: Mexico City (Mexico) and Bogotá (Colombia) and from three at sea level: Buenos Aires (Argentina) and Lima and Trujillo (Peru). Comorbidities and pulmonary function tests were taken from clinical records. Possible pulmonary hypertension (PH) was defined by findings in the transthoracic echocardiogram of systolic pulmonary arterial pressure (sPAP) >36 mmHg or indirect signs of PH in the absence of other causes of PH. Emphysema as the concomitant finding of IPF criteria on chest tomography plus emphysema in the upper lobes. ANOVA or Kruskal Wallis and χ2-tests were used for comparison. Results: Two hundred and seventy-six patients were included, 50 from Argentina, 86 from Colombia, 91 from Mexico and 49 from Peru. There prevalence of PH was higher in Colombia and Mexico (p < 0.001), systemic arterial hypertension in Argentina (p < 0.015), gastro-esophageal reflux and dyslipidemia in Colombia and Argentina (p < 0.001) and diabetes mellitus in Mexico (p < 0.007). Other comorbidities were obesity (28.4%), coronary artery disease (15.2%) and emphysema (14.9%), with no differences between countries. There was more PH in the altitude cities than those at sea level (51.7 vs. 15.3%, p < 0.001). In patients from Bogotá and Mexico City, arterial oxygen pressure, saturation (p < 0.001) and carbon monoxide diffusing capacity (p = 0.004) were significantly lower than in cities at sea level. Conclusions: In this study with a significant number of patients, we were able to describe and compare the comorbidities of IPF in four LA countries, which contributes to the epidemiological data of this disease in the region. The main results were the differences in comorbidities between the countries and more PH in the subjects residing in the cities of higher altitude, a finding that should be validated in future studies.

Exercise Capacity, Ventilatory Response, and Gas Exchange in COPD Patients With Mild to Severe Obstruction Residing at High Altitude.

BACKGROUND: Exercise intolerance, desaturation, and dyspnea are common features in patients with chronic obstructive pulmonary disease (COPD). At altitude, the barometric pressure (BP) decreases, and therefore the inspired oxygen pressure and the partial pressure of arterial oxygen (PaO2) also decrease in healthy subjects and even more in patients with COPD. Most of the studies evaluating ventilation and arterial blood gas (ABG) during exercise in COPD patients have been conducted at sea level and in small populations of people ascending to high altitudes. Our objective was to compare exercise capacity, gas exchange, ventilatory alterations, and symptoms in COPD patients at the altitude of Bogotá (2,640 m), of all degrees of severity. METHODS: Measurement during a cardiopulmonary exercise test of oxygen consumption (VO2), minute ventilation (VE), tidal volume (VT), heart rate (HR), ventilatory equivalents of CO2 (VE/VCO2), inspiratory capacity (IC), end-tidal carbon dioxide tension (PETCO2), and ABG. For the comparison of the variables between the control subjects and the patients according to the GOLD stages, the non-parametric Kruskal-Wallis test or the one-way analysis of variance test was used. RESULTS: Eighty-one controls and 525 patients with COPD aged 67.5 ± 9.1 years were included. Compared with controls, COPD patients had lower VO2 and VE (p < 0.001) and higher VE/VCO2 (p = 0.001), A-aPO2, and V D /V T (p < 0.001). In COPD patients, PaO2 and saturation decreased, and delta IC (p = 0.004) and VT/IC increased (p = 0.002). These alterations were also seen in mild COPD and progressed with increasing severity of the obstruction. CONCLUSION: The main findings of this study in COPD patients residing at high altitude were a progressive decrease in exercise capacity, increased dyspnea, dynamic hyperinflation, restrictive mechanical constraints, and gas exchange abnormalities during exercise, across GOLD stages 1-4. In patients with mild COPD, there were also lower exercise capacity and gas exchange alterations, with significant differences from controls. Compared with studies at sea level, because of the lower inspired oxygen pressure and the compensatory increase in ventilation, hypoxemia at rest and during exercise was more severe; PaCO2 and PETCO2 were lower; and VE/VO2 was higher.

Arterial blood gases and ventilation at rest by age and sex in an adult Andean population resident at high altitude.

PURPOSE: Arterial blood gases (ABG) are influenced by the altitude above sea level, age and sex. Most studies have been conducted at sea level and in small populations ascending to or residents at very high altitudes. Our objective was to evaluate the ventilation and ABG by age and sex in an Andean population resident at high altitude (2640 m). METHODS: Analytical cross-sectional study was done in healthy volunteers. ABG and minute ventilation (VE) were measured. T test and ANOVA for differences by sex and age, and Pearson test for correlations between age, VE and ABG were performed. RESULTS: We included 374 adults, 55% women from 18 to 83 years and hemoglobin of 15.7 ± 1.6 g/dl. There was a significant decrease in PaO2 and SaO2 and an increase in P(A - a)O2 with age (p < 0.001). Unlike men, with age women had a significant increase in PaCO2 and a higher decrease in PaO2. The correlations between age, the decrease in PaO2 and the increase in PaCO2 were greater in women than in men. The VE adjusted to body surface area decreased with age, but this correlation was significantly higher in women. CONCLUSIONS: In this study, with a considerable number of healthy adults living at high altitude (2640 m), we established the physiological impact of altitude, aging and gender in ABG. The PaO2 and PaCO2 were significantly lower and the hemoglobin values slightly higher than described at sea level. In addition to PaO2 decline with age, there was an age-related increase in PaCO2 in women, associated with a greater reduction of VE.

Impulse oscillometry reference values and bronchodilator response in three- to five-year old children living at high altitude.

INTRODUCTION: Impulse oscillometry (IOS) is used to measure airway impedance. It is an effective tool for diagnosing and treating respiratory diseases, and it has the advantage that it does not require forced respiratory maneuvers. IOS reference values are required for each population group. OBJECTIVE: This study aimed to determine the IOS reference values and bronchodilator response in healthy preschool children living in Bogotá, Colombia. METHODS: We performed a cross-sectional study in preschool children who had no history of respiratory disease; 96 children fit the parameters for testing to determine normal values according to the American Thoracic Society and European Respiratory Society criteria. RESULTS: Values for respiratory resistance (Rrs) and reactance (Xrs) at 5, 10, and 20 Hz, respiratory impedance (Zrs, and resonance frequency (Fres) were established. Height was the most influential independent variable for IOS values; an increase in height led to a reduction in Rrs5 and Rrs20 and an increase in Xrs5. After the administration of 400 mcg of salbutamol the values for Rrs5(-17.48%), Rrs20(-8.63%), Fres (-10.68%), and area of reactance (-35.44%) were reduced, meanwhile Xrs5 (15.35%) was increased. CONCLUSIONS: Normal IOS values before and after the administration of 400 mcg of salbutamol were determined for a population of children aged 3-5 years at 2,640 m. Reference IOS equations for these children are presented. A relative change of up to -28% and 36% after the use of salbutamol for respiratory resistance and reactance, respectively, should be considered as an upper limit of the normal range, and possible appropriate cut-off values for defining significant response for evaluating therapeutic interventions.

SMALLa AIRWAY DISEASE IN COPD ASSOCIATED TO BIOMASS EXPOSURE.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous entity that may result from different causative agents and risk factors and may follow diverse clinical courses, including COPD secondary to biomass smoke exposure. At present, this phenotype is becoming more important for two reasons: first, because at least almost half of the world's population is exposed to biomass smoke, and second, because the possibility of it being diagnosed is increasing. Biomass smoke exposure COPD affects primarily women and is related with insults to the airways occurred during early life. Although constituents of biomass smoke and tobacco smoke are similar, the physiopathological changes they induce differ depending not only on the chemical composition (related with the type of fuel used) but also on the particle size and the inhalation pattern. Evidence has shown that biomass smoke exposure affects the airway, predominantly the small airways causing anthracofibrosis and peribronchiolar fibrosis changes that will clinically translate into chronic bronchitis symptoms, with a high impact on the quality of life. In this review, we focus especially on the main epidemiological and clinical differences between COPD secondary to biomass exposure and COPD caused by tobacco exposure.

Small airway disease in COPD associated to biomass exposure

Abstract Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous entity that may result from different causative agents and risk factors and may follow diverse clinical courses, including COPD secondary to biomass smoke exposure. At present, this phenotype is becoming more important for two reasons: first, because at least almost half of the world’s population is exposed to biomass smoke, and second, because the possibility of it being diagnosed is increasing. Biomass smoke exposure COPD affects primarily women and is related with insults to the airways occurred during early life. Although constituents of biomass smoke and tobacco smoke are similar, the physiopathological changes they induce differ depending not only on the chemical composition (related with the type of fuel used) but also on the particle size and the inhalation pattern. Evidence has shown that biomass smoke exposure affects the airway, predominantly the small airways causing anthracofibrosis and peribronchiolar fibrosis changes that will clinically translate into chronic bronchitis symptoms, with a high impact on the quality of life. In this review, we focus especially on the main epidemiological and clinical differences between COPD secondary to biomass exposure and COPD caused by tobacco exposure.

Chronic bronchitis: High prevalence in never smokers and underdiagnosis- A population-based study in Colombia.

The objective of the article was to establish the prevalence, underdiagnosis, and risk factors of chronic bronchitis (CB) in a general population in five Colombian cities. Cross-sectional study using a probabilistic sampling technique in five Colombian cities was adopted. The CB definition was "cough and expectoration for three or more months per year for at least two consecutive years." Underdiagnosis was considered in subjects with clinical definition without previous medical diagnosis. Univariate χ2 or Student's t-test and logistic regression analysis were used. The study included 5539 subjects. The prevalence was 5.5%, the underdiagnosis 50.3%, and 33.7% of the cases were in nonsmokers (53.6% in women vs. 16.9% in men, p < 0.001). The adjusted risk factors were living in Bogota, current smoking, male, age ≥ 64 years, low education, indoor wood smoke exposure, and occupational exposure to vapors, gases, dust, and fumes. CB is a common disease among adults in Colombia. The underdiagnosis was high and there were a large proportion of cases in nonsmokers, particularly in women. Our findings support the association of CB with indoor wood smoke and occupational exposures.

Severe sleep apnea, Cheyne-Stokes respiration and desaturation in patients with decompensated heart failure at high altitude.

OBJECTIVES: To determine the sleep-disordered breathing in patients with decompensated HF (DHF) at an altitude of 2640m. METHODS: Polysomnogram during the first 48 hours of admission in patients hospitalized for DHF. Sleep apnea (SA) was defined as an apnea hypopnea index (AHI) > 5/hour and central sleep apnea (CSA) as central apnea index (CAI) ≥ 50% of the AHI. RESULTS: Sixteen participants, LVEF 24.2±9.9%. All patients had SA, severe in 12 (75%), CSA in 8 (50%) and 7 (43.8%) presented Cheyne-Stokes respiration (CSR). Out of the eight patients with obstructive SA, five had a central component (CAI ≥ 5/h). The SpO2 decreased during sleep to 80.6±5.5% and in patients with CSR to 77.6±6.9%. CONCLUSIONS: At an altitude of 2640m all patients with DHF presented sleep apnea, most were severe, with CSA and a significant percentage of CSR that was associated with higher oxygen desaturation.

Altitude and COPD prevalence: analysis of the PREPOCOL-PLATINO-BOLD-EPI-SCAN study.

BACKGROUND: COPD prevalence is highly variable and geographical altitude has been linked to it, yet with conflicting results. We aimed to investigate this association, considering well known risk factors. METHODS: A pooled analysis of individual data from the PREPOCOL-PLATINO-BOLD-EPI-SCAN studies was used to disentangle the population effect of geographical altitude on COPD prevalence. Post-bronchodilator FEV1/FVC below the lower limit of normal defined airflow limitation consistent with COPD. High altitude was defined as >1500 m above sea level. Undiagnosed COPD was considered when participants had airflow limitation but did not report a prior diagnosis of COPD. RESULTS: Among 30,874 participants aged 56.1 ± 11.3 years from 44 sites worldwide, 55.8% were women, 49.6% never-smokers, and 12.9% (3978 subjects) were residing above 1500 m. COPD prevalence was significantly lower in participants living at high altitude with a prevalence of 8.5% compared to 9.9%, respectively (p < 0.005). However, known risk factors were significantly less frequent at high altitude. Hence, in the adjusted multivariate analysis, altitude itself had no significant influence on COPD prevalence. Living at high altitude, however, was associated with a significantly increased risk of undiagnosed COPD. Furthermore, subjects with airflow limitation living at high altitude reported significantly less respiratory symptoms compared to subjects residing at lower altitude. CONCLUSION: Living at high altitude is not associated with a difference in COPD prevalence after accounting for individual risk factors. However, high altitude itself was associated with an increased risk of undiagnosed COPD.

Estimation of personal exposure to asbestos of brake repair workers.

Exposure assessments are key tools to conduct epidemiological studies. Since 2010, 28 riveters from 18 brake repair shops with different characteristics and workloads were sampled for asbestos exposure in Bogotá, Colombia. Short-term personal samples collected during manipulation activities of brake products, and personal samples collected during non-manipulation activities were used to calculate 103 8-h TWA PCM-equivalent personal asbestos concentrations. The aims of this study are to identify exposure determinant variables associated with the 8-h TWA personal asbestos concentrations among brake mechanics, and propose different models to estimate potential asbestos exposure of brake mechanics in an 8-h work-shift. Longitudinal-based multivariate linear regression models were used to determine the association between personal asbestos concentrations in a work-shift with different variables related to work tasks and workload of the mechanics, and some characteristics of the shops. Monte Carlo simulations were used to estimate the 8-h TWA PCM-Eq personal asbestos concentration in work-shifts that had manipulations of brake products or cleaning activities of the manipulation area, using the results of the sampling campaigns. The simulations proposed could be applied for both current and retrospective studies to determine personal asbestos exposures of brake mechanics, without the need of sampling campaigns or historical data of air asbestos concentrations.