Proposición de nuevas ecuaciones para calcular valores espirométricos de referencia en población chilena adulta: Sociedad Chilena de Enfermedades Respiratorias (SER) / New spirometric reference equations for healthy Chilean adults

Background: To correctly interpret spirometric results, reference values should come from the same population. Current spirometric reference equations have been under scrutiny due to deficiencies to fit adequately for Chilean population, specially, for those aged over 65 years old. Aim: To develop new spirometric reference values for Chilean adults, based on national studies in which spirometries were performed in healthy non-smoker adults. Material and Methods: A standardized database of spirometric values was developed combining spirometric data collected from five population-based studies, in which healthy nonsmoker adults participated. Spirometries from 448 males aged 19 to 84 years and from 726 females aged 19 to 94 years, obtained according to guidelines from the American Thoracic and European Respiratory Societies, were analyzed. Using multiple regression models, which included height, gender, and age, the theoretical value and inferior limits of normality were calculated for 1st second (FEV1), forced vital capacity (FVC), FEV1/FVC, and forced mid-expiratory flow rate (FEF25-75). Results: Reference values and lower limits of normality (LLN) were constructed for Chilean adults of both genders. The new proposed set of equations had a better fit, when compared with the current reference values used in Chile. Conclusions: The new spirometric references values derived from this study, fit better than currently used ones. Therefore, they should be used as new references values for Chilean adults.

Etiología y biomarcadores de inflamación sistémica en las exacerbaciones leves a moderadas de la enfermedad pulmonar obstructiva crónica / Etiology and biomarkers of systemic inflammation in mild to moderate COPD exacerbations

Background: The etiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) is heterogeneous and still under discussion. Inflammation increases during exacerbation of COPD. The identification of inflammatory changes will increase our knowledge and potentially guide therapy. Aim: To identify which inflammatory parameters increase during COPD exacerbations compared to stable disease, and to compare bacterial and viral exacerbations. Material and Methods: In 85 COPD patients (45 males, mean age 68 ± 8 years, FEV1 46 ± 17% of predicted) sputum, nasopharyngeal swabs and blood samples were collected to identify the causative organism, during a mild to moderate exacerbation. Serum ultrasensitive C reactive protein (CRP), fibrinogen and interleukin 6 (IL 6), neutrophil and leukocyte counts were measured in stable conditions, during a COPD exacerbation, 15 and 30 days post exacerbation. Results: A total of 120 mild to moderate COPD exacerbations were included. In 74 (61.7%), a microbial etiology could be identified, most commonly Mycoplasma pneumoniae (15.8%), Rhinovirus (15%), Haemophilus influenzae (14.2%), Chlamydia pneumoniae (11.7%), Streptococcus pneumoniae (5.8%) and Gram negative bacilli (5.8%). Serum CRP, fibrinogen and IL 6, and neutrophil and leukocyte counts significantly increased during exacerbation and recovered at 30 days post exacerbation. Compared to viral exacerbations, bacterial aggravations were associated with a systemic inflammation of higher magnitude. Conclusions: Biomarkers of systemic inflammation increase during mild to moderate COPD exacerbations. The increase in systemic inflammation seems to be limited to exacerbations caused by bacterial infections.

Prueba de caminata en seis minutos en sujetos chilenos sanos de 20 a 80 años / Reference values for the 6-minutes walking test in healthy subjects 20-80 years old

Background: The six minute walking distance test (6MWD) is widely used to evaluate exercise capacity in several diseases due to its simplicity and low cost. Aim: To establish reference values for 6MWD in healthy Chilean individuals. Material and methods: We studied 175 healthy volunteers aged 20-80 years (98 women) with normal spirometry and without history of respiratory, cardiovascular or other diseases that could impair walking capacity. The test was performed twice with an interval of 30 min. Heart rate, arterial oxygen saturation (with a pulse oxymeter) and dyspnea were measured before and after the test. Results: Walking distance was 576 ± 87 m in women and 644 ± 84 m in men (p < 0.0001). For each sex, a model including age, height and weight produced 6MWD prediction equations with a coefficient of determination (R²) of 0.63 for women and 0.55 for men. Conclusions: Our results provide reference equations for 6MWD that are valid for healthy subjects between 20 and 80 years old.

Marcadores de inflamación sistémica en pacientes ex fumadores con enfermedad pulmonar obstructiva crónica en etapa estable / Systemic inflammation among stable ex smokers with chronic obstructive pulmonary disease

Background: Low grade systemic inflammation is commonly observed in chronic obstructive pulmonary disease (COPD). Aim: To evaluate the extent of systemic inflammation in a group of ex-smokers with COPD in stable condition and its relation with pulmonary function and clinical manifestations. Patients and Methods: We studied 104 ex-smokers aged 69 ± 8 years (62 males) with mild to very severe COPD and 52 healthy non-smoker subjects aged 66 ± 11 years (13 males) as control group. High sensitivity serum C reactive protein (CRP), interleukin 6 (IL6), fibrinogen (F) and neutrophil count (Nc) were measured. Forced expiratory volume in the first minute (FEV1), inspiratory capacity (IC), arterial blood gases, six minutes walking test, dyspnea and body mass index (BMI) were measured, calculating the BODE index. Health status was assessed using the Saint George Respiratory Questionnaire (SGRQ), the chronic respiratory questionnaire (CRQ), registering the number of acute exacerbations (AE) during the previous year and inhaled steroids’s use. Systemic inflammation was considered present when levels of CRP or IL6 were above the percentile 95 of controls (7.98 mg/L and 3.42 pg/ml, respectively). Results: COPD patients had significantly higher CRP and IL6 levels than controls. Their F and Nc levels were within normal limits. Systemic inflammation was present in 56 patients, which had similar disease severity and frequency of inhaled steroid use, compared with patients without inflammation. Patients with systemic inflammation had more AE in the previous year; lower inspiratory capacity, greater dyspnea during the six minutes walk test and worse SGRQ and CRQ scores. Conclusions: Low-grade systemic inflammation was found in 56 of 104 ex-smokers with COPD. This group showed a greater degree of lung hyperinflation, dyspnea on exercise and poor quality of life.

Nomogramas de ecuaciones de referencia espirométrica SER 2009 / Spirometric nomograms for Chilean normal adults

As a result of the availability of programmes to detect and treat respiratory disease in Chile there has been a greater use of spirometry in diagnosis. To be able to correctly interpret spirometry results there must be reference patterns which, ideally come from the same population in which they will be used. In order to facilitate the use and application of new spirometric reference equations recently calculated for the adult population, there follows a series of nomograms. These nomograms have been designed for each of the following parameters: gender, age, and size of subjects between 19 and 50 years old and also for subjects over 51 years old. These equations are taken from 5 national studies. These studies included a population which complied with universal criteria to determine reference values ( 1.174 subjects, between 19 and 94 years old), spirometries were carried out on this population following international recommendations (ATS).

La actual disponibilidad de programas de detección y tratamiento de enfermedades respiratorias en Chile ha determinado una mayor utilización de la espirometría en el diagnóstico de dichas enfermedades. La adecuada interpretación de los resultados de la espirometría requiere disponer de patrones de referencia idealmente originados en la misma población en la cual se utilizarón. Para facilitar el uso y aplicación de nuevas ecuaciones de referencia espirométricas recientemente modeladas en población adulta chilena, se presentan nomogramas diseñados para cada uno de los parámetros en base al género, edad y talla para sujetos entre 19 y 50 años y en mayores de 51 años. Estas ecuaciones derivan de 5 estudios nacionales que incluyeron población que cumplió criterios universales para determinar valores de referencia, (1.174 sujetos, 19 a 94 años), que efectuaron espirometrías siguiendo recomendaciones internacionales (ATS).

Sarcoidosis pulmonar y gástrica: caso clínico / Pulmonary and gastric sarcoidosis: report of one case

We report a 66 year-old woman with a history of pulmonary sarcoidosis, diagnosed with a lung biopsy in 1993 and treated with prednisone for 2 years. She presented at our institution in 1999 with a stage IV disease and important functional and clinical impairment. A bronchial biopsy disclosed non caseating granulomas. Tuberculosis was intensively studied and persistently negative. Due to frequent nausea and vomiting an endoscopic gastric biopsy was performed which revealed non caseating granulomas involving the gastric mucosa. There was no evidence of Helicobacter pylori and stains for fungi and acid-fast bacilli were negative. Treatment with prednisone relieved digestive symptoms, although a control biopsy of the gastric mucosa revealed persistence of non caseating granulomas. Both lung stage IV and gastric sarcoidosis are uncommon forms of the disease.

Exacerbaciones en pacientes ex-fumadores con enfermedad pulmonar obstructiva crónica: efectos clínicos y funcionales a corto plazo / Short term effects of acute exacerbations in COPD patients

Acute exacerbations of COPD (AECOPD) are associated with decline of FEV1 and health related quality of life. Our aim was to evaluate the short-term effects of AECOPD on several functional and clinical indices in a cohort of 60 ex-smokers patients with COPD. During a 6-month follow up, 40 patients experienced one exacerbation (Group 1), mainly moderate, evaluated 30 days after by measuring BMI, dyspnea, FVC, FEV1, inspiratory capacity (IC), Sp02, six-min walking distance (6MWD), BODE index and quality of life (SGRQ). Values were compared with those measured at recruitment in stable conditions and with those obtained in the 20 patients without AECOPD during a similar period (Group 2). Baseline values were similar in both groups. Group 1 showed a significant worsening in FVC, FEV1, Sp02, BMI, 6MWD, and BODE index. Improvement in SGRQ and BODE was found in group 2. Significant differences in changes between groups were found for all variables, except IC and Sp02. The most noteworthy differences were found for BODE index (p = 0.001) and SGRQ (p = 0.004). Results demonstrate that moderate AECOPD produces significant short term functional and clinical impairment in ex-smokers COPD.

Las exacerbaciones de la EPOC deterioran el FEV1y la calidad de vida. Nuestro objetivo fue evaluar el efecto a corto plazo de las exacerbaciones sobre otros índices funcionales y clínicos. Sesenta pacientes ex fumadores con EPOC fueron seguidos durante 6 meses. Cuarenta presentaron una exacerbación (Grupo 1), generalmente moderada, estudiada 30 días después. los 20 pacientes no exacerbados constituyeron el grupo control (Grupo 2). Se midió IMC, disnea, CVF, FEV1h capacidad inspiratoria (CI), SpO2, caminata en 6 min (C6M), índice BODE y calidad de vida (SGRQ). En condiciones basales no hubo diferencias entre grupos. El grupo 1 empeoró CVF, VEF1, SpO2, IMC, C6M e índice BODE, sin cambios de CI ni SGRQ. El grupo 2 no presentó deterioro, mejorando SGRQ y BODE. Al comparar ambos grupos, hubo diferencias significativas en los cambios de todas las variables, excepto Cly SpO2, siendo estas diferencias más notorias en el índice BODE (p = 0,001) y SGRQ (p = 0,004). En suma, las exacerbaciones de la EPOC producen deterioro clínico y funcional significativo en el corto plazo.

La prueba de caminata en seis minutos en la evaluación de la capacidad de ejercicio en pacientes con enfermedad pulmonar obstructiva crónica / Six minutes walk for the assessment of patients with chronic obstructive pulmonary disease

Exercise capacity can be evaluated in patients with chronic obstructive pulmonary disease (COPD), measuring the distance that patients are able to walk in 6 minutes (six-minute walk distance test; 6WDT). This test is simple to perform, inexpensive, reproducible and safe. It has been frequently employed for the assessment of COPD patients due to its high prognostic valué of mortality and its usefulness to evalúate long-term of therapeutic interventions. In severe stages of the disease, the declining results of the best are useful to detect worsening. This review describes the method, standardization and reference valúes for the 6WDY and the results obtained with different therapeutic interventions, based on data from the literature and from the authors experíence. We also review its predictive valué for mortality and its valué in the assessment of patients with more severe COPD.

Características clínicas y funcionales según género de pacientes con enfermedad pulmonar obstructiva crónica / Clinical and functional characteristics of COPD according to gender

Chronic obstructive pulmonary disease (COPD) prevalence is continuously rising in females. In addition, mortality due to COPD is higher in females, suggesting that women may develop a more severe disease than males. Our aim was to study possible differences in disease severity according to gender in 95 COPD patients (38 females) consecutively recruited to participate in a follow up protocol. Severity of COPD was assessed by FEV1, BODE index and the impairment of quality of life was measured with the Saint George's respiratory questionnaire (SGRQ) and the chronic respiratory questionnaire (CRQ). We found no differences according to gender in any of the severity indices studied. However, female smoked significantly less than males (35.5 +/- 19.4 versus 45.7 +/- 21 pack-year; p = 0.02). Our results suggest that women are more susceptible to develop COPD than men, without differences in disease severity.

La prevalencia, al igual que la mortalidad de la enfermedad pulmonar obstructiva crónica (EPOC), ha aumentado en las mujeres. Esto último sugiere que la enfermedad sería más grave en el sexo femenino. El propósito de este estudio fue evaluar si existen diferencias en la gravedad según género en 95 pacientes (38 mujeres) con EPOC ingresados consecutivamente a un protocolo de seguimiento. Evaluamos la magnitud del tabaquismo, características demográficas, gravedad según VEF1 e índice BODE y compromiso de la calidad de vida. Los resultados no demostraron diferencias entre hombres y mujeres en ninguno de los índices de gravedad. Sin embargo, la magnitud del tabaquismo fue inferior en las mujeres que en los hombres (35,5 +/- 19,4 vs 45,7 +/- 21 paquetes-año; p = 0,02). Nuestros resultados sugieren una mayor susceptibilidad de las mujeres para desarrollar EPOC, pero no demuestran que la gravedad de la enfermedad dependa del género.

Reversibilidad espirométrica en pacientes con enfermedad pulmonar obstructiva crónica: ¿debe emplearse 200 ó 400 µg de salbutamol? / Spirometric reversibility in COPD patients: 200 or 400 mg salbutamol should be used?

The optimal dose of salbutamol for testing spirometric reversibility in patients with chronic obstructive pulmonary disease (COPD) has not been determined and either 200 or 400 µg are commonly used. The purpose of the present study is to test both doses in a group of patients with mild to severe COPD. Forty stable COPD patients were included to receive in random order both doses of salbutamol, with spirometry being performed before and after 15 min of their administration. Absolute and percent predicted changes were evaluated. For the latter, an increase in forced expiratory volume in one second (FEV1), slow vital capacity (SVC), forced vital capacity (FVC) and inspiratory capacity (IC) equal or greater than 10 percent predicted was considered clinically significant. No differences were found in absolute post-bronchodilator values between the two doses. In addition, the proportion of responders to 200 and 400 µg of salbutamol according to the percent predicted changes was similar with both doses. This was particularly true when all variables related to volume changes (SVC, FVC, and IC) were included in the analysis. In conclusion, the present results indicate that for testing spirometric reversibility in COPD patients the 200 µg dose of salbutamol is as effective as the 400 µg dose.

La óptima dosis de salbutamol que se debe emplear para evaluar la reversibilidad espirométrica en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) no ha sido establecida, por lo que 200 ó 400 mg son corrientemente utilizados. El propósito del presente estudio fue evaluar el efecto de ambas dosis de salbutamol en un grupo de pacientes con enfermedad leve a grave. El estudio incluyó a 40 pacientes con EPOC estable a los cuales se les realizó una espirometría antes y 15 minutos después de recibir en orden aleatorio 200 ó 400 µg de salbutamol en dos días consecutivos. Los cambios se evaluaron en valores absolutos y en porcentaje del valor teórico. Se midió los cambios en VEF1, CVF, capacidad vital lenta (CVL) y capacidad inspiratoria (CI). Se consideró clínicamente significativo un aumento igual o mayor al 10 por ciento del valor teórico. No se observó diferencias en los valores absolutos post broncodilatador entre las dos dosis como tampoco expresados en porcentaje del valor teórico. Además, la proporción de pacientes que respondieron con 200 y 400 µg de salbutamol fue similar. Esto fue particularmente importante cuando se incluyó en el análisis todas las variables relacionadas con el cambio de volumen (CVL, CVF y CI). Concluimos que para evaluar la reversibilidad espirométrica en pacientes con EPOC, 200 µg de salbutamol son tan efectivos como 400 µg.

Beneficios clínicos y funcionales de agregar teofilina a la terapia inhalatoria con broncodilatadores de acción corta en pacientes con enfermedad pulmonar obstructiva crónica / Clinical and functional benefits of adding theophylline to a standard treatment with short acting bronchodilators in patients with COPD

Background: Although theophylline is considered a third line bronchodilator drug for the treatment of chronic obstructive pulmonary disease (COPD), it is widely used in Chile, because it is administered orally and has a moderate cost. Aim: To evaluate if theophylline adds clinical and/or functional benefits when associated to standard recommended inhaled bronchodilator therapy. Subjects and methods: Thirty-eight stable COPD patients who accepted to participate in the study approved by the Ethics Committee of our institution were studied. Using a randomized double-blind placebo-controlled study, theophylline (250 mg) or placebo was administered twice a day for 15 days in addition to inhaled salbutamol and ipratropium bromide. Prior to and at the end of the study, patients underwent: a) a spirometry to evaluate changes in dynamic pulmonary hyperinflation using slow vital capacity (SVC) and inspiratory capacity (IC), b) the 6 min walking distance (6 MWD); and c) measurement of maximal inspiratory and expiratory pressures. Dyspnea and quality of life (QoL) were evaluated using appropriate questionnaires. Results: Compared to placebo, patients on theophylline showed significant increases in SVC (p=0.014), IC (p=0.002), and 6 MWD (p=0.005). They also experienced an improvement in dyspnea (p=0.042) and QoL (p=0.011). All patients improved at least one of these parameters with 53% of the patients showing an improvement in 3 or more. Conclusions: Our results indicate that adding theophylline to standard treatment with inhaled bronchodilators provides additional benefits in stable COPD patients by reducing dynamic pulmonary hyperinflation, improving exercise tolerance, dyspnea and QoL.

Calidad de las espirometrías en un estudio epidemiológico de terreno: Factores determinantes de la necesidad de repetir el examen en el estudio Platino-Chile / Spirometries in a population based study: factors determining the need of test repetition, in Chile's Platino study

Spirometry, the most used test to evaluate pulmonary function, is only occasionally measured in field epidemiological studies. Our aim was to determine which of the following factors in the Platino study can be associated low quality spirometries in the first session: sex, age, socioeconomic level, educational level, body mass index, cold chill, smoking, operating technician, date and subject's previous spirometric experience. 1.168 individuals were evaluated with spirometry. Fifteen nurses and 1 midwife were trained according to NIOSCH standards. Easy One NDD spirometers were used. 1.037 subjects (88.8 percent) performed a satisfactory spirometry in the first session, and 131 (11.2 percent) failed to do so. Only two significant predictors of this failure were identified: age and educational level. Causes for test repetition were 1) Non satisfactory acceptability (77.1 percent); 2) lack of reproducibility (67.9 percent); 3) decline of post bronchodilator CVF without concomitant change in VEF1 (36.6 percent). Eighty nine of the 131 subjects accepted to repeat the test. A satisfactory spirometry was obtained in 79 subjects. Hence, at the end of the study 95.5 percent of the subjects attained a satisfactory test. We conclude that personnel without experience, with appropriate training, can perform high quality field spirometries. Acceptability and repoducibility were the most sensitive factors associated with a bad performance of spirometry. Age and schooling were the main factors related with a low quality spirometry. No association was detected regarding technician as a predictor of low quality spirometries carried out in a population setting.

La espirometría es el examen más utilizado para evaluar la función pulmonar y ocasionalmente se usa en estudios epidemiológicos. Evaluamos si las variables: sexo, edad, nivel socioeconómico, escolaridad, IMC, cursar concomitantemente con resfrío, tabaquismo, fecha del examen, haberse efectuado espirometría anteriormente y técnico responsable, se asociaban con la probabilidad de espirometrías insatisfactorias en una primera sesión. Quince enfermeras y una matrona que recibieron capacitación realizaron las espirometrías en 1.168 sujetos empleando un espirómetro Easy One NDD. En la primera sesión 1.037 individuos (88,8 por ciento) efectuaron una espirometría satisfactoria fracasando 131 (11,2 por ciento). Se identificaron dos variables predictoras del fracaso: edad y años de instrucción. Las causas más frecuentes de espirometrías insatisfactorias fueron: 1) No cumplir con criterios de aceptabilidad (77,1 por ciento); 2) Falta de reproducibilidad (67,9 por ciento); 3) Caída de CVF post broncodilatador sin cambio en el VEF1 (36,6 por ciento). De los 131 sujetos cuya espirometría fue insatisfactoria en la primera sesión, ochenta y nueve aceptaron repetirla, lográndose al final del estudio una espirometría satisfactoria en el 95,5 por ciento de la muestra. Personal técnico sin experiencia previa y adecuadamente entrenado, es capaz de lograr espirometrías de buena calidad en un estudio epidemiológico de campo. Las causas más frecuentes de repetición de examen guardan relación con dificultad de alcanzar criterios de aceptabilidad y reproducibilidad de la prueba. Factores gravitantes en la repetición son la edad y el nivel de instrucción de los sujetos examinados. El desempeño de los técnicos no constituyó un factor limitante para obtener una adecuada calidad de la espirometría en terreno.

Reversibilidad espirométrica en la enfermedad pulmonar obstructiva crónica: efecto diferencial del salbutamol sobre el volumen espiratorio forzado del primer segundo y el volumen pulmonar / Spirometric reversibility to Salbutamol in chronic obstructive pulmonary disease (COPD): differential effects on FEV1 and on lung volumes

Background: In recent years it has been suggested that in COPD, lung volumes can be modified more than expiratory flows, with bronchodilators. Aim: To study the acute effects of salbutamol on FEV1 and lung volumes at rest. Subjects and Methods: Forty stable COPD patients were studied using a single dose of salbutamol (200 µg). Forced expiratory volumen in 1 second (FEV1), slow vital capacity (SVC), forced vital capacity (FVC), and inspiratory capacity (IC) were measured at baseline and after salbutamol administration. Results: After salbutamol, 39/40 patients exhibited a clinically significant increase in volumes (SVC, FVC or IC ×10 percent predicted). A significant increase in FEV1 (×10 percent predicted) was observed in only 13 patients. Conclusions: Our results demonstrate that changes in lung volumes, and consequently in dynamic lung hyperinflation, take place more frequently than changes in maximal expiratory flows during the spirometric test in patients with COPD. Assessment of spirometric reversibility based only on changes in FEV1 underestimates the effect of bronchodilator drugs in these patients.

Hiperinflación pulmonar en la enfermedad pulmonar obstructiva crónica: importancia funcional y clínica / Dynamic hyperinflation in chronic obstructive pulmonary diseases: functional and clinical implications

Si bien es un hecho conocido que distintas drogas broncodilatadoras son capaces de producir alivio de la disnea en ausencia de mejoría significativa del VEF1 en pacientes con EPOC avanzada, sólo en los últimos años se ha avanzado en el conocimiento de los mecanismos por los cuales esto ocurre. La hiperinflación pulmonar dinámica (HPD) que se produce como consecuencia de la limitación del flujo espiratorio (LFE) en reposo, altera gravemente la mecánica del aparato respiratorio y el funcionamiento de los músculos inspiratorios en pacientes con EPOC avanzada. Los broncodilatadores, al disminuir la HPD producen alivio de la disnea, aún sin mejoría del VEF1. Los cambios en el grado de HPD pueden evaluarse con la espirometría, a través de los cambios de la capacidad inspiratoria o de la capacidad vital, parámetros que aumentan en mayor grado y más frecuentemente que el VEF1. A diferencia de lo que ocurre con el VEF1, la magnitud de la HPD se relaciona con el grado de disnea y de intolerancia al ejercicio. Es así, como la disminución de la máxima capacidad de ejercicio se relaciona con la reducción de la capacidad inspiratoria en estos pacientes. Otras intervenciones capaces de disminuir la HPD y producir alivio de la disnea con mejoría de la tolerancia al ejercicio son: la cirugía de reducción de volumen pulmonar, la administración de oxígeno y la ventilación mecánica no invasiva. Se analizan los mecanismos por los cuales estas intervenciones actúan mejorando los síntomas de estos pacientes.

Enfermedad de altura aguda y función ventilatoria en sujetos expuestos intermitentemente a hipoxia hipobárica / Acute altitude disease and ventilatory function in subjects intermittently exposed to hypobaric hypoxia

Aiming to assess the magnitude of acute mountain sickness symptoms and ventilatory function in subjects intermittently exposed to hypobaric hypoxia, we studies 48 healthy men aged 32.6 ñ 8.2 years old who worked in a gold mine at a altitude of 4600 m. using a schedule of 8-12 days of work at the mine followed by 4 days of rest at the sea level. Studies were performed at the sea level (A), during the first 2 days of ascention (B) and after 3 or 4 days of stay at 4600 m (C). Mountain sickness symptoms were evaluated with a questionnaire devised in the 1991 International Hypoxia Sumposium and respiratory function was assessed with Collins Eagle II respirometer, following American Thoracic Society recommendations. Subjects reported mild to moderate symptoms during the first 24 hours of ascending (mean score of 6.4 ñ 3.1 for a maximun of 15). Forced vital capacity fell significantly in period B and returned to normal in period C and forced expiratory volume in 1s did not change in any period. However, maximal expiratory flow and maximal midexpiratory flow rate significantly increased and remained elevated during the 4 days stay at the mine. No correlation was found between acute mountain sickness symptoms and changes in ventilatory function