Characterization of patients with dermatomyositis in a university hospital in Colombia

Introduction: Dermatomyositis is an idiopathic inflammatory myopathy characterized by the presence of skin lesions; it is considered a heterogeneous disease, due to its clinical presentation, course, and prognosis. In Colombia there are few records that describe the clinical characteristics of these patients. Methods: Cross-sectional study. Medical records of patients who consulted a university hospital in Colombia between January 2004 and December 2019 were reviewed. The records were obtained using databases from the dermatology, rheumatology, dermatopathology, and electrophysiology units, and CIE10 diagnostic codes. Results: Seventy patients with a dermatomyositis diagnosis were found, 63 (90%) fulfilled the Bohan and Peter diagnostic criteria and 7 (10%) had amyopathic dermatomyositis, with an average age of 43 years (SD ± 15.3). Forty-eight were women (68.5%). The most frequent clinical signs were Gottron's papules 80%, periorbital violaceous (heliotrope) erythema with edema 78.5% (n = 55) and poikiloderma 75.7% (n = 53). The most frequently found systemic manifestations were dysphagia (21.4%, n = 15), interstitial lung disease (11.4%, n = 8), and pulmonary hypertension (8.5%, n = 6). Cancer was documented in 8.5% (n = 6) of patients. Conclusion: We showed clinical information of patients with dermatomyositis in a referral hospital in Colombia. The data obtained is consistent with information from other case series worldwide.

Introducción: La dermatomiositis es una miopatía inflamatoria idiopática que se caracteriza por presentar lesiones en la piel; por su presentación clínica, su curso y su pronóstico, se la considera una enfermedad heterogénea. En Colombia existen pocos registros que describan las características clínicas de los pacientes afectados por esta enfermedad. Métodos: Estudio descriptivo de corte transversal, se revisaron las historias clínicas de pacientes que consultaron a un hospital universitario en Colombia entre enero del 2004 y diciembre del 2019. Los registros se obtuvieron utilizando bases de datos de las unidades de dermatología, reumatología, dermatopatología, electrofisiología y códigos diagnósticos CIE10 asociados con dermatomiositis. Resultados: Se obtuvieron 70 pacientes con diagnóstico de dermatomiositis, 63 (90%) de los cuales cumplían criterios de clasificación de Bohan y Peter, en tanto que 7 (10%) presentaban dermatomiositis amiopática. El promedio de edad fue de 43 arios (DS ± 15,3); 48 fueron mujeres (68,5%); los signos clínicos más frecuentes fueron: pápulas de Gottron (80%, n = 56), eritema heliotropo (78,5%, n = 55) y poiquilodermia (75,7%, n = 53). Las manifestaciones sistêmicas más comúnmente encontradas fueron: disfagia (21,4%, n = 15), enfermedad pulmonar intersticial (11,4%, n = 8) e hipertensión pulmonar (8,5%, n = 6). Se documentó cáncer en el 8,5% (n = 6) de los pacientes. Conclusión: Se presenta información clínica de pacientes con dermatomiositis en un centro hospitalario de referencia en Colombia; los datos obtenidos concuerdan con la información de otros estudios de series de casos a escala mundial.

Epidemiologic characteristics and burden of psoriasis: A multicenter, cross-sectional study.

Background: Although psoriasis burden and treatment have been well characterized in developed countries, there are scarce in-depth epidemiological studies in Latin American countries. Objectives: To describe the sociodemographic and clinical features and the economic burden of psoriasis among children and adult patients from Colombia. Methods: This cross-sectional study included patients from dermatology private practice offices, health provider institutions and hospitals in seven Colombian cities. We collected data on disease distribution, weight, height, body mass index, waist-hip ratio, disease severity, therapy, personal history of comorbidities, and direct costs. Multiple logistic regression analyses were conducted to assess the associations between severity scales and sociodemographic and clinical variables. Results: Two-hundred-three patients (43.8% women, 56.2% men) with an age range between 7 to 89 years old were included. The main subtype was psoriasis vulgaris and mean age of diagnosis was 37.1 years. The most common comorbidities were obesity, hypertension, psoriatic arthritis, dyslipidemia and diabetes. Women had a significant increased odds of presenting with psoriatic arthritis. Body-mass-index and hypertension were significantly associated with a higher psoriasis severity, whereas being female and non-obese was associated with a lower risk. A third of the patients had a family history of psoriasis and sleeping disorders. Forty-one percent of participants either had no income or had an income below 224 US dollars per month and >20% of their income was spent on their disease. Conclusions: This study is supported by robust scientific data and contributes to understanding the burden of psoriasis in Latin America. This study adds well-supported data through an in-depth clinical and economical characterization of Colombian children and adult patients with psoriasis and shows the high impact and burden of the disease on patients and their families.

Epidemiologic characteristics and burden of psoriasis: A multicenter, cross-sectional study

Antecedentes La carga de enfermedad y el tratamiento de la psoriasis han sido bien caracterizados en los países desarrollados, pero los estudios epidemiológicos realizados en America Latina son escasos. Objetivos Describir las características sociodemográficas, clínicas y económicas de la psoriasis en pacientes pediátricos y adultos de Colombia. Métodos Este fue un estudio observacional transversal que incluyó pacientes recolectados en consultorios privados de dermatología, instituciones prestadoras de salud y hospitales de siete ciudades de Colombia. Se incluyeron datos relacionados con la distribución de la enfermedad, peso, altura, índice de masa corporal, medición de la cintura/cadera, severidad de la enfermedad, tratamiento, antecedentes de comorbilidades y costos directos para el paciente o la familia. Se realizó un análisis de regresión logística múltiple para evaluar las asociaciones entre la severidad de la psoriasis y las variables sociodemográficas y clínicas. Resultados Se incluyeron 203 pacientes (43.8% mujeres y 56.2% hombres) con un rango de edad entre 7 a 89 años. El subtipo principal fue la psoriasis vulgar y la edad media de diagnóstico fue de 37,1 años. Las comorbilidades más frecuentes fueron la obesidad, la hipertensión arterial, la artritis psoriásica, la dislipidemia y la diabetes. Las mujeres tuvieron un mayor riesgo de presentar artritis psoriásica. El índice de masa corporal y la hipertensión se asociaron significativamente con la severidad de la psoriasis, mientras que ser mujer y no obeso se relacionó con un menor riesgo, respectivamente. Un tercio de los pacientes tenía antecedentes familiares de psoriasis y trastornos del sueño. Cuarenta y uno por ciento de los participantes no tenían ingresos o tenían ingresos inferiores a 224 dólares estadounidenses por mes y >20% de sus ingresos los gastaron en la enfermedad. Conclusiones Este estudio muestra un gran impacto de la psoriasis en los pacientes afectados y contribuye a comprender la carga de la psoriasis en América Latina aportando datos científicos sólidos a la comunidad dermatológica y a las autoridades sanitarias colombianas con respecto a los estándares de atención médica. También crea conciencia sobre la carga económica de la enfermedad y también enfatiza la necesidad de un seguimiento estrecho de los pacientes con psoriasis para prevenir, identificar y manejar sus comorbilidades.

Background Although psoriasis burden and treatment have been well characterized in developed countries, there are scarce in-depth epidemiological studies in Latin American countries. Objectives To describe the sociodemographic and clinical features and the economic burden of psoriasis among children and adult patients from Colombia. Methods This cross-sectional study included patients from dermatology private practice offices, health provider institutions and hospitals in seven Colombian cities. We collected data on disease distribution, weight, height, body mass index, waist-hip ratio, disease severity, therapy, personal history of comorbidities, and direct costs. Multiple logistic regression analyses were conducted to assess the associations between severity scales and sociodemographic and clinical variables. Results Two-hundred-three patients (43.8% women, 56.2% men) with an age range between 7 to 89 years old were included. The main subtype was psoriasis vulgaris and mean age of diagnosis was 37.1 years. The most common comorbidities were obesity, hypertension, psoriatic arthritis, dyslipidemia and diabetes. Women had a significant increased odds of presenting with psoriatic arthritis. Body-mass-index and hypertension were significantly associated with a higher psoriasis severity, whereas being female and non-obese was associated with a lower risk. A third of the patients had a family history of psoriasis and sleeping disorders. Forty-one percent of participants either had no income or had an income below 224 US dollars per month and >20% of their income was spent on their disease. Conclusions This study is supported by robust scientific data and contributes to understanding the burden of psoriasis in Latin America. This study adds well-supported data through an in-depth clinical and economical characterization of Colombian children and adult patients with psoriasis and shows the high impact and burden of the disease on patients and their families.

Association of Sputum Neutrophil Extracellular Trap Subsets With IgA Anti-Citrullinated Protein Antibodies in Subjects at Risk for Rheumatoid Arthritis.

OBJECTIVE: Mechanisms leading to anti-citrullinated protein antibody (ACPA) generation in rheumatoid arthritis (RA) are hypothesized to originate in the lung. We undertook this study to understand associations between neutrophil extracellular trap (NET) formation in the lung and local ACPA generation in subjects at risk of developing RA. METHODS: Induced sputum was collected from 49 subjects at risk of developing RA, 12 patients with RA, and 18 controls. Sputum neutrophils were tested for ex vivo NET formation, and sputum-induced NET formation of control neutrophils was measured using immunofluorescence imaging. Sputum macrophages were tested for ex vivo endocytosis of apoptotic and opsonized cells. Levels of ACPA, NET remnants, and inflammatory proteins were quantified in sputum supernatant. RESULTS: Spontaneous citrullinated histone H3 (Cit-H3)-expressing NET formation was higher in sputum neutrophils from at-risk subjects and RA patients compared to controls (median 12%, 22%, and 0%, respectively; P < 0.01). In at-risk subjects, sputum IgA ACPA correlated with the percentage of neutrophils that underwent Cit-H3+ NET formation (r = 0.49, P = 0.002) and levels of Cit-H3+ NET remnants (r = 0.70, P < 0.001). Reduced endocytic capacity of sputum macrophages was found in at-risk subjects and RA patients compared to controls. Using a mediation model, we found that sputum inflammatory proteins were associated with sputum IgA ACPA through a pathway mediated by Cit-H3+ NET remnants. Sputum-induced Cit-H3+ NET formation also correlated with sputum levels of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor in at-risk subjects, suggesting a causal relationship. CONCLUSION: These data support a potential mechanism for mucosal ACPA generation in subjects at risk of developing RA, whereby inflammation leads to increased citrullinated protein-expressing NETs that promote local ACPA generation.

Palmar and Plantar Pits, More than Just Viral Warts.

A 40-year-old woman with a family history of gastric, pulmonary, and endometrial cancers (parents and grandparents) was referred to our institution with a 3-year history of progressive pruritus with palmar and plantar papules. On physical examination, there were keratotic yellowish pinpoint papules on the hands (Figure 1) and yellowish keratotic plaques and papules on the plantar pressure points (Figure 2). The diagnosis of punctate palmoplantar keratoderma was confirmed histopathologically (Figure 3), and treatment was initiated with 30% urea cream, which proved helpful. Molecular studies were requested, which documented a variant in the AAGAB gene. After treatment, the patient slightly improved and clinical symptoms were better tolerated.

Subjects at-risk for future development of rheumatoid arthritis demonstrate a PAD4-and TLR-dependent enhanced histone H3 citrullination and proinflammatory cytokine production in CD14hi monocytes.

The presence of anti-citrullinated protein/peptide antibodies (ACPA) and epitope spreading across the target autoantigens is a unique feature of rheumatoid arthritis (RA). ACPA are present in the peripheral blood for several years prior to the onset of arthritis and clinical classification of RA. ACPA recognize multiple citrullinated proteins, including histone H3 (H3). Intracellular citrullination of H3 in neutrophils and T cells is known to regulate immune cell function by promoting neutrophil extracellular trap formation and citrullinated autoantigen release as well as regulating the Th2/Th17 T cell phenotypic balance. However, the roles of H3 citrullination in other immune cells are not fully elucidated. We aimed to explore H3 citrullination and cytokine/metabolomic signatures in peripheral blood immune cells from subjects prior to and after the onset of RA, at baseline and in response to ex vivo toll-like receptor (TLR) stimulation. Here, we analyzed 13 ACPA (+) subjects without arthritis but at-risk for future development of RA, 14 early RA patients, and 13 healthy controls. We found significantly elevated H3 citrullination in CD14hi monocytes, as well as CD1c+ dendritic cells and CD66+ granulocytes. Unsupervised analysis identified two distinct subsets in CD14hi monocytes characterized by H3 modification and unique cytokine/metabolomic signatures. CD14hi monocytes with elevated TLR-stimulated H3 citrullination were significantly increased in ACPA (+) at-risk subjects. These cells were skewed to produce TNFα, MIP1ß, IFNα, and partially IL-12. Additionally, they demonstrate peptidyl arginine deiminase 4 (PAD4) mediated upregulation of the glycolytic enzyme PFKFB3. These CD14hi monocytes with elevated H3 citrullination morphologically formed monocyte extracellular traps (METs). Taken together, dysregulated PAD4-driven cytokine production as well as MET formation in CD14hi monocytes in ACPA (+) at-risk subjects likely plays an important role in the development of RA via promoting and perpetuating inflammation and generation of citrullinated autoantigens.

Endoscopic gastroplasty to treat medically uncontrolled obesity needs more quality data: A systematic review.

Endoscopic gastroplasty (EG) has been used in clinical practice to treat obesity. This systematic review has the objective of assessing if there is an acceptable level of scientific evidence on the safety and effectiveness of EG. A thorough search strategy was used up to October 2018, including the 2 most common techniques: endoscopic suturing and the primary obesity surgery endolumenal procedure. The quality of the studies was evaluated through the Joanna Briggs Institute Critical Appraisal tools for use in Systematic Reviews-"Checklist for Case Series"-and summarized using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Only 1 randomized controlled trial (moderate GRADE evidence) was found, and the remaining were case reports or small case series (very low GRADE evidence). The literature has low scientific quality. All studies, with 1 exception, are small case series with short follow-up. One of the randomized controlled trials did not meet the primary endpoint for weight loss in both groups (EG × sham) after 1-year follow-up. The case series reported from 16% to 19% total weight loss, but few had more than 6 months of follow-up. Serious adverse events ranged from 2% to 10%. Based on current literature, there is not enough quality scientific evidence regarding long-term weight loss and the procedure's safety to recommend the use of EG in current clinical practice.

Cotinine reduces depressive-like behavior and hippocampal vascular endothelial growth factor downregulation after forced swim stress in mice.

Cotinine, the predominant metabolite of nicotine, appears to act as an antidepressant. We have previously shown that cotinine reduced immobile postures in Porsolt's forced swim (FS) and tail suspension tests while preserving the synaptic density in the hippocampus as well as prefrontal and entorhinal cortices of mice subjected to chronic restraint stress. In this study, we investigated the effect of daily oral cotinine (5 mg/kg) on depressive-like behavior induced by repeated, FS stress for 6 consecutive days in adult, male C57BL/6J mice. The results support our previous report that cotinine administration reduces depressive-like behavior in mice subjected or not to high salience stress. In addition, cotinine enhanced the expression of the vascular endothelial growth factor (VEGF) in the hippocampus of mice subjected to repetitive FS stress. Altogether, the results suggest that cotinine may be an effective antidepressant positively influencing mood through a mechanism involving the preservation of brain homeostasis and the expression of critical growth factors such as VEGF. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Cotinine halts the advance of Alzheimer's disease-like pathology and associated depressive-like behavior in Tg6799 mice.

Alzheimer's disease (AD) is associated with cognitive and non-cognitive symptoms for which there are currently no effective therapies. We have previously reported that cotinine, a natural product obtained from tobacco leaves, prevented memory loss and diminished amyloid-ß (Aß) plaque pathology in transgenic 6799 mice (Tg6799 mice) when treated prior to the development of the pathology. We have also shown that cotinine reduces depressive-like behavior in normal and chronically stressed C57BL/6 mice. Here, we extend our previous studies by investigating the effects of cotinine on the progression of AD-like pathology, depressive-like behavior, and the mechanisms underlying its beneficial effects in Tg6799 mice when left untreated until after a more advanced stage of the disease's development. The results show that vehicle-treated Tg6799 mice displayed an accentuated loss of working memory and an abundant Aß plaque pathology that were accompanied by higher levels of depressive-like behavior as compared to control littermates. By contrast, prolonged daily cotinine treatment to Tg6799 mice, withheld until after a mid-level progression of AD-like pathology, reduced Aß levels/plaques and depressive-like behavior. Moreover, this treatment paradigm dramatically improved working memory as compared to control littermates. The beneficial effects of cotinine were accompanied by an increase in the expression of the active form of protein kinase B and the postsynaptic density protein 95 in the hippocampi and frontal cortices of Tg6799 mice. This suggests that cotinine halts the progression of AD-like pathology while reducing depressive-like behavior by stimulating signaling pathways supporting synaptic plasticity in Tg6799 mice. The potential use of cotinine to treat cognitive and non-cognitive symptoms of AD is discussed.

Secundarismo sifilítico en infección por VIH, con fenómeno de Prozona / Secondary syphilis in hiv infection, with Prozone phenomenon

Resumen La sífilis es una enfermedad infectocontagiosa, de transmisión sexual, con una expresión clínica muyvariada, que tiene clara relación la evolución clínica, tiempo de infección e inmunidad del huésped. En los pacientes con infección por VIH, las etapas de la sífilis pueden tener formas evolutivas diferentes, habitualmente más severas. En pacientes con sífilis e infección por VIH se puede presentar el fenómeno de Prozona, que consiste en serología VDRL no reactiva, falsamente negativa, que debemostener en cuenta en estos pacientes para hacer estudios adicionales que nos encaminen a diagnóstico y tratamiento acertado. (Acta Med Colomb 2014; 39: 69-71).

Abstract Syphilis is an infectious disease, sexually transmitted, with a varied clinical expression, which has clear relationship to clinical evolution, time of infection and host immunity. In patients with HIV infection, stages of syphilis may have different evolutionary forms usually more severe. In patients with syphilis and HIV infection can occur Prozone phenomenon, which consists of nonreactive VDRL serology falsely negative that we must take into account in these patients for additional studies that will lead us to succesful diagnosis and treatment. (Acta Med Colomb 2014; 39: 69-71).

Regional variation on rates of bronchopulmonary dysplasia and associated risk factors.

Background. An abnormally high incidence (44%) of bronchopulmonary dysplasia with variations in rates among cities was observed in Colombia among premature infants. Objective. To identify risk factors that could explain the observed high incidence and regional variations of bronchopulmonary dysplasia. Study Design. A case-control study was designed for testing the hypothesis that differences in the disease rates were not explained by differences in city-of-birth specific population characteristics or by differences in respiratory management practices in the first 7 days of life, among cities. Results. Multivariate analysis showed that premature rupture of membranes, exposure to mechanical ventilation after received nasal CPAP, no surfactant exposure, use of rescue surfactant (instead of early surfactant), PDA, sepsis and the median daily FIO(2), were associated with a higher risk of dysplasia. Significant differences between cases and controls were found among cities. Models exploring for associations between city of birth and dysplasia showed that being born in the highest altitude city (Bogotá) was associated with a higher risk of dysplasia (OR 1.82 95% CI 1.31-2.53). Conclusions. Bronchopulmonary dysplasia was manly explained by traditional risk factors. Findings suggest that altitude may play an important role in the development of this disease. Prenatal steroids did not appear to be protective at high altitude.

Inadequate glucose control in type 2 diabetes is associated with impaired lung function and systemic inflammation: a cross-sectional study.

BACKGROUND: Inadequate glucose control may be simultaneously associated with inflammation and decreased lung function in type 2 diabetes. We evaluated if lung function is worse in patients with inadequate glucose control, and if inflammatory markers are simultaneously increased in these subjects. METHODS: Subjects were selected at the Colombian Diabetes Association Center in Bogotá. Pulmonary function tests were performed and mean residual values were obtained for forced expiratory volume (FEV1), forced vital capacity (FVC) and FEV1/FVC, with predicted values based on those derived by Hankinson et al. for Mexican-Americans. Multiple least-squares regression was used to adjust for differences in known determinants of lung function. We measured blood levels of glycosylated hemoglobin (HBA1c), interleukin 6 (IL-6), tumor necrosis factor (TNF-alpha), fibrinogen, ferritin, and C-reactive protein (C-RP). RESULTS: 495 diabetic patients were studied, out of which 352 had inadequate control (HBA1c > 7%). After adjusting for known determinants of lung function, those with inadequate control had lower FEV1 (-75.4 mL, IC95%: -92, -59; P < 0.0001) and FVC (-121 mL, IC95%: -134, -108; P < 0,0001) mean residuals, and higher FEV1/FVC (0.013%, IC95%: 0.009, 0.018, P < 0.0001) residuals than those with adequate control, as well as increased levels of all inflammatory markers (P < 0.05), with the exception of IL-6. CONCLUSIONS: Subjects with type 2 diabetes and inadequate control had lower FVC and FEV1 than predicted and than those of subjects with adequate control. It is postulated that poorer pulmonary function may be associated with increased levels of inflammatory mediators.

Very early surfactant without mandatory ventilation in premature infants treated with early continuous positive airway pressure: a randomized, controlled trial.

BACKGROUND: Chronic lung disease is one of the most frequent and serious complications of premature birth. Because mechanical ventilation is a major risk factor for chronic lung disease, the early application of nasal continuous positive airway pressure has been used as a strategy for avoiding mechanical ventilation in premature infants. Surfactant therapy improves the short-term respiratory status of premature infants, but its use is traditionally limited to infants being mechanically ventilated. Administration of very early surfactant during a brief period of intubation to infants treated with nasal continuous positive airway pressure may improve their outcome and further decrease the need for mechanical ventilation. OBJECTIVE: Our goal was to determine if very early surfactant therapy without mandatory ventilation improves outcome and decreases the need for mechanical ventilation when used in very premature infants treated with nasal continuous positive airway pressure soon after birth. DESIGN/METHODS: Eight centers in Colombia participated in this randomized, controlled trial. Infants born between 27 and 31 weeks' gestation with evidence of respiratory distress and treated with supplemental oxygen in the delivery room were randomly assigned within the first hour of life to intubation, very early surfactant, extubation, and nasal continuous positive airway pressure (treatment group) or nasal continuous airway pressure alone (control group). The primary outcome was the need for subsequent mechanical ventilation using predefined criteria. RESULTS: From January 1, 2004, to December 31, 2006, 279 infants were randomly assigned, 141 to the treatment group and 138 to the control group. The need for mechanical ventilation was lower in the treatment group (26%) compared with the control group (39%). Air-leak syndrome occurred less frequently in the treatment group (2%) compared with the control group (9%). The percentage of patients receiving surfactant after the first hour of life was also significantly less in the treatment group (12%) compared with the control group (26%). The incidence of chronic lung disease (oxygen treatment at 36 weeks' postmenstrual age) was 49% in the treatment group compared with 59% in the control group. All other outcomes, including mortality, intraventricular hemorrhage, and periventricular leukomalacia were similar between the groups. CONCLUSIONS: In premature infants treated with nasal continuous positive airway pressure early after birth, the addition of very early surfactant therapy without mandatory ventilation decreased the need for subsequent mechanical ventilation, decreased the incidence of air-leak syndrome, and seemed to be safe. Reduction in the need for mechanical ventilation is an important outcome when medical resources are limited and may result in less chronic lung disease in both developed and developing countries.

Diabetes mellitus tipo 2 y deterioro de la función pulmonar / Diabetes mellitus type 2 and deterioration of pulmonary function

Introducción: un aspecto poco estudiado de la diabetes mellitus tipo 2 (DM 2), es su posible asociación con alteraciones de la función pulmonar. Estudios recientes han mostrado niveles mayores de marcadores de inflamación sistémica de bajo nivel en pacientes con DM 2, lo que también podría afectar la función pulmonar. El objetivo de este estudio fue determinar si la función pulmonar de personas con DM 2 es diferente de la función pulmonar de un grupo control sin DM.Población y método: se realizó un estudio observacional transversal, comunitario, en diabéticos y en controles sanos, apareados por estratos de edad y sexo. Los controles fueron vecinos de cada diabético, del mismo sexo y grupo de edad, sin DM. La muestra de diabéticos se seleccionó de la población de pacientes que consultan a la Asociación Colombiana de Diabetes (ACD) en Bogotá. Se comprobó el estatus de diabético y de control sano mediante las pruebas de glucemia en ayunas y glucemia poscarga de glucosa. Se realizaron curvas de flujo volumen tanto para los diabéticos como para los controles, y de acuerdo con los valores de referencia obtenido por Hankinson para mexicoamericanos se obtuvieron valores residuales promedios (observado – esperado) para VEF1, CVF y relación VEF1/CVF. Mediante regresión lineal múltiple se ajustó por diferencias en determinantes conocidos de la función pulmonar (edad, sexo, talla, tabaquismo, exposición a humo de leña)...