Severe hepatotoxicity due to anti-tuberculosis drugs in Spain.

OBJECTIVES: To determine the frequency of severe hepatotoxicity due to anti-tuberculosis (TB) drugs, and predictors of development of acute liver failure or of death. METHODS: A retrospective study conducted by members of the Spanish Society of Pneumology from 18 hospitals during 1997-2001. A case of severe hepatotoxicity was defined as any asymptomatic patient with a ten-fold increase in transaminases or three-fold increase in colostasis parameters, or, among patients with hepatitis symptoms, any raised hepatic parameters or development of hepatic failure. Predictive factors were studied using logistic regression, calculating odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: One hundred and six patients developed severe hepatotoxicity. Of a total of 3510 patients, 90 were treated for active TB (2.56%). Eleven cases (10.3%) presented with acute liver failure, three of whom underwent liver transplant. The global case fatality rate was 4.7% (five cases, three associated with alcohol use or hepatotoxic drugs). The predictors of poor prognosis were total bilirubin > 2 mg/dl (OR 9.4, 95% CI 1.0-85.5) and serum creatinine > 1.5 mg/dl (OR 32.1, 95% CI 2.4-424.6). CONCLUSIONS: Severe hepatotoxicity due to anti-tuberculosis drugs is associated with a high fatality rate. Prevention should be based on informing patients and frequent clinical and laboratory controls.

[Lung cancer at a university hospital: epidemiological and histological characteristics of a recent and a historical series]. / Características del cáncer de pulmón en un hospital universitario. Cambios epidemiológicos e histológicos en relación con una serie histórica.

OBJECTIVE: To describe the clinical, histological, and epidemiological characteristics of patients diagnosed with lung cancer in our hospital over a period of 5 years and compare them with those of historical cases treated at the same hospital. PATIENTS AND METHODS: The cases of patients diagnosed with lung cancer from January 1998 through December 2002 were studied retrospectively and compared with data published for the period from 1978 through March 1981. RESULTS: A total of 678 patients (89% men, mean age 67 years) were studied. Fifty-six percent of the men and 38% of the women were smokers (P<.001). The most common histological types were squamous cell carcinoma (33%) and adenocarcinoma (30%): squamous carcinoma in men (36%) and adenocarcinoma in women (56%). Metastasis was present in 42% of the patients with non-small cell lung cancer and in 55% of those with small cell lung cancer. In patients with a history of neoplastic disease, laryngeal tumors were most common in patients with squamous carcinoma whereas bladder tumors were the most frequent in patients with adenocarcinoma. The ratio of men to women was lower in the recent series than in the historical one. The percentage of squamous carcinoma was lower and that of adenocarcinoma higher (P<.001). The percentage of patients diagnosed with regional involvement was greater in the recent series (P<.001). CONCLUSIONS: Squamous cell carcinoma continues to be the most frequent histological type. Male sex and smoking are associated with squamous carcinoma and female sex is associated with adenocarcinoma. Epidemiological and histological patterns have changed, possibly in relation to changes in smoking habits.

Adaptation of the Asthma Quality of Life Questionnaire to a second language preserves its critical properties: the Spanish version.

To test the metric proprieties of the Spanish version of the Juniper Asthma Quality of Life Questionnaire (AQLQ), we studied 116 adult asthmatic patients with a wide range of disease severity (53 patients were recruited from the respiratory outpatient department, 38 from a primary health care centre and 25 were patients admitted into hospital due to acute asthma). The patients were assessed twice, at recruitment and after 2 months. The AQLQ showed a high internal consistency (Cronbach's alpha = 0.78 to 0.96) and a high 2-week reproducibility (ICC = 0.82 to 0.92). Expected significant differences in AQLQ scores were observed according to disease severity as measured by symptoms, medication, use of services and recruitment setting. The cross-sectional and longitudinal correlations between AQLQ and the overall St. George's Respiratory Questionnaire were strong, moderate to strong between AQLQ and dyspnea and weak to moderate between AQLQ and FEV(1). The changes in AQLQ scores were significantly different in patients who either improved or deteriorated from those patients who remained stable (P <.0001 and P <.01, respectively, for the overall AQLQ). We conclude that the Spanish version of the AQLQ is reliable, valid and sensitive to changes.

Testing the measurement properties of the Spanish version of the SF-36 Health Survey among male patients with chronic obstructive pulmonary disease. Quality of Life in COPD Study Group.

The aim of this article is to evaluate the measurement properties of the Spanish version of the SF-36 Health Survey (SF-36). In total, 321 male chronic obstructive pulmonary disease (COPD) patients attending hospital outpatient or primary health clinics were cross-sectionally administered the SF-36, the St. George's Respiratory Questionnaire (SGRQ), and a dyspnea scale. A clinical measure of respiratory function, the proportion of the predicted Forced Expiratory Volume in 1 second (%FEV1) was also obtained. Internal consistency, central tendency, and dispersion statistics of scores were calculated, as well as the percentage of respondents with the highest and lowest scores for each scale and correlations between health status and clinical measures. All patients completed the SF-36 questionnaire, and less than 1% of items were missing. The proportion of patients with the worst possible score (floor effect) ranged from 0.9-20.1% among the different scales. The proportion of patients achieving the best possible score (ceiling effect) ranged from 0-61%. Cronbach's alpha coefficients were above 0.75 except for one scale (Social Functioning, alpha = 0.55). SF-36 scores were moderate to highly correlated with SGRQ scores (coefficients ranged from -.41 to -.79). Correlations were moderate to high with dyspnea and lower but statistically significant with %FEV1. A clear gradient of SF-36 scores was found according to dyspnea levels and disease staging based on %FEV1 impairment, the gradient being more marked for the Physical Functioning, Role-Physical, and General Health scales. Data presented suggest that the Spanish version of the SF-36 is acceptable, valid, and reliable in COPD patients. Although more studies are needed, this version is adequate in international comparisons of health outcomes.

Diaphragmatic activity induced by cortical stimulation: surface versus esophageal electrodes.

Evoked responses of the diaphragm can be induced by magnetic cortical stimulation and recorded by either surface or esophageal electrodes. The former recording system is tolerated better by the patient but has potential problems with the specificity of the diaphragmatic signal. This study compares the responses of the diaphragm to cortical stimulation that were recorded simultaneously with surface and esophageal electrodes on seven patients (61 +/- 4 yr) with chronic obstructive pulmonary diseases. Stimuli were delivered in three ventilatory conditions: at baseline, during deep breathing, and during voluntary panting. No differences were observed between results recorded by surface and esophageal electrodes [amplitude of the compound motor of the action potential (CMAP), 0.8 +/- 0.1 vs. 0.8 +/- 0.1 mV, NS; latency, 13.1 +/- 0.4 vs. 12.6 +/- 0.5 ms, NS]. In addition, significant correlations were found (CMAP, r = 0.77, P < 0.001; latency, r = 0.71, P = 0.002). The concordance analysis, however, indicated some dissimilarity between the recordings of the electrodes (CMAP, R1 = 0.31; latency, R1 = 0.26). These differences may be due to the area of the muscle mainly recorded by each electrode and/or to the additional activity from other muscles recorded by surface electrodes. On the other hand, the diaphragmatic responses observed in these patients with chronic obstructive pulmonary diseases were similar to those previously reported in healthy subjects.

Structure of the latissimus dorsi muscle and respiratory function.

The aim of this study was to evaluate whether respiratory function influences the structure of the latissimus dorsi muscle (LD). Twelve patients (58 +/- 10 yr) undergoing thoracotomy were studied. Lung and respiratory muscle function were evaluated before surgery. Patients showed a forced expired volume in 1 s (FEV1) of 67 +/- 16% of the reference value, an FEV1-forced vital capacity ratio of 69 +/- 9%, a maximal inspiratory pressure of 101 +/- 21% of the reference value, and a tension-time index of the diaphragm (TTdi) of 0.04 +/- 0.02. When patients were exposed to 8% CO2 breathing, TTdi increased to 0.06 +/- 0.03 (P < 0.05). The structural analysis of LD showed that 51 +/- 5% of the fibers were type I. The diameter was 56 +/- 9 microns for type I fibers and 61 +/- 9 microns for type II fibers, whereas the hypertrophy factor was 87 +/- 94 and 172 +/- 208 for type I and II fibers, respectively. Interestingly, the histogram distribution of the LD fibers was unimodal in two of the three individuals with normal lung function and bimodal (additional mode of hypertrophic fibers) in seven of the nine patients with chronic obstructive pulmonary disease. An inverse relationship was found between the %FEV1-forced vital capacity ratio and both the diameter of the fibers (type I: r = -0.773, P < 0.005; type II: r = -0.590, P < 0.05) and the hypertrophy factors (type I: r = -0.647, P < 0.05; type II: r = -0.575, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Mechanical and metabolic reproducibility of resistance test of expiratory muscles with incremental threshold loading]. / Reproducibilidad mecánica y metabólica de la prueba de resistencia de los músculos espiratorios con cargas umbrales incrementales.

BACKGROUND: The study of respiratory muscle endurance has mainly focused on inspiratory muscles. A new method to measure expiratory muscle endurance, through incremental threshold loading using a weighted plunger valve, has recently been described. OBJECTIVES: To evaluate the mechanical features of the plunger valve and the reproducibility of the method from the standpoint of both mechanics and metabolism. METHODS: Four untrained healthy subjects performed an incremental test with expiratory threshold loading (50 g every 2 min) on each of three non-consecutive days; each test continued until the subject could no longer open the valve. Mouth pressure was recorded continuously during each test; on the first two test days, oxygen consumption (VO2) was also measured. RESULTS: Opening and closing pressures were the same and were independent of expiratory flow, with a linear load-pressure relationship (4 cmH2O) for every 10 g of weight). The maximal tolerated load (MTL) in the three tests was stable for two of the subjects, whereas the maximal load was reached by the other two subjects in the second and third tests, respectively. When MTL was reached in the third test, mean and peak mouth pressures (the latter expressed as percent of maximal expiratory pressure [MEP]) were 49 +/- 4% and 71 +/- 4%, respectively; the expiratory tension-time index measured at the mouth ([PMEANmouth/MEP] x [TE/Ttot]) was 0.25 +/- 0.02 (TE: expiratory time; Ttot: total time). In the first and second tests, we also measured oxygen consumption of the recruited muscles, which were mainly the expiratory muscles (VO2respmax); consumption in the last test was 213 +/- 65 ml O2/min (2.9 +/- 1.1 ml O2/kg/min). The intraindividual coefficient of variation ranged from 6.3% to 19.5% for the mechanical parameters and from 14% to 21% for the metabolic ones. CONCLUSIONS: The expiratory endurance test using a threshold valve allows quantification of muscle and metabolic reserve under incremental expiratory loads. The valve has appropriate mechanical characteristics for this purpose and reproducibility is acceptable, through the precise determination of the may require up to three tests.

[Neutrophilia in the bronchoalveolar lavage of patients with AIDS and Pneumocystis carinii pneumonia. Reflections on its prognostic value in the Spanish setting]. / Neutrofilia en el lavado broncoalveolar de pacientes con SIDA y neumonía por Pneumocystis carinii. Consideraciones sobre su valor pronóstico en nuestro medio.

The prognostic value of neutrophilia (> 5%) in bronchoalveolar lavage (BAL) in our context is studied in 21 patients with AIDS and Pneumocystis carinii pneumonia. Neutrophilia does not seem to be a good prognostic indicator in our context. We have found this condition, with a mean of 6 +/- 4%, in only 33% of our sample. The sensitivity of this parameter with respect to risk of death was very low (25%), while specificity was moderate (65%). In contrast with what has been reported in studies done with Anglo-Saxon populations, neutrophilia in BAL is probably of little prognostic use in our context. This may be due to various factors, among them the type of population (most being intravenous drug users) and the therapeutic protocol (early empirical treatment).

[Muscle relaxants in the morphometric study of the respiratory muscles in human beings]. / Relajantes musculares en el estudio morfométrico de los músculos respiratorios en seres humanos.

The morphological examination of respiratory muscle can be affected by muscular contraction following biopsy. Most morphometric studies of respiratory muscles, however, have been carried out without taking into account this factor, the effect of which can be reduced by using relaxants when taking samples. Objective. To examine the effect of using a relaxant in the morphometric analysis of muscle fibers. We examined 31 muscle samples from 7 patients. Immediately after removal, each pipe was divided in half. One was placed in an isotonic physiological solution and the other in a solution of curare 0.02%. Later, both samples were processed for morphometric study with ATP-ase, NADTH and PAS tincture. Morphological data recorded for the different types of fibers included measurement of minimum diameter (Dmin), atrophy and hypertrophy indices (AI and HI) and heterogeneity of distribution (SDDmin). The Dmin was smaller in fibers transported in a curare solution than in those transported in physiological solution (67 +/- 2 microns vs. 71 +/- microns, p < 0.05). The same was true of SDDmin (13 +/- 3 vs. 12 +/- 3, p < 0.05), HI (300 +/- 88 vs. 457 +/- 107, p < 0.05). Likewise, we found a similar direct correlation between size of fibers processed with physiological solution and those processed in curare (Dmin, r = 0.731, p < 0.001; HI, r = 0.827, p < 0.001; SDDmin, r = 0.636, p < 0.0001). The use of relaxants in processing muscle samples prevents contraction and should be used systematically in the morphological analysis of muscle fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

[The characteristics of the mechanical activity of the respiratory muscles during the diaphragmatic respiration technic]. / Características de la actividad mecánica de los músculos respiratorios durante la técnica de "respiración diafragmática".

UNLABELLED: Noteworthy among breathing training techniques is so-called diaphragmatic breathing. In spite of the technique's name, however, little is known of the functional characteristics of this ventilatory method. OBJECTIVE: To asses the mechanics of respiratory muscles, particularly diaphragm muscles, during diaphragmatic breathing in patients with severe chronic obstructive pulmonary disease (COPD). METHODS: Ventilatory pattern and respiratory pressures (abdominal [Pga], intrathoracic [Pes] and transdiaphragmatic [Pdi]) were studied in 10 patients with severe COPD in stable phase (age 69 +/- 6 years, FEV1 33 +/- 12% ref) at baseline and during deep breathing with spontaneous muscle recruitment (SMR) and during breathing training. Measurements were taken with the patient seated and in supine decubitus position. RESULTS: In seated position ventilatory pattern was similar with SMR and during breathing training. Mean Pdi during airflow, however, was greater during breathing training than with SMR (34.8 +/- 8.0 and 29.3 +/- 9.3 cmH2O, respectively, p < 0.05) for similar levels of Pes. Mechanical effectiveness of the diaphragm expressed as Vt/Pdi) was less during breathing training, however (36.1 +/- 10.4 and 49.5 +/- 15.8 cc/cmH2O, p < 0.05), with no changes in overall efficacy of respiratory muscles (Vt/Pes). In supine decubitus position, ventilatory patterns of SMR and breathing training were similar, although Vt and T1 were slightly higher in the latter (1,065 +/- 305 vs. 1,211 +/- 314 cc, p < 0.01; and 2.76 +/- 1.32 vs. 3.07 +/- 1.23 sec, p < 0.05). Pdi was also higher during breathing training (29.7 +/- 10.2 and 38.0 +/- 10.5 cmH2O, p < 0.05), although accompanied in this case by a higher Pes (21.2 +/- 7.5 to 26.4 +/- 8.4 cmH2O, p < 0.005). In supine decubitus position, the effectiveness of both diaphragm muscles and respiratory muscles overall was similar for both ventilatory modes. CONCLUSIONS: Breathing training truly involves greater use of the diaphragm, both in seated and supine decubitus positions. Breathing training does not provide greater ventilatory efficacy than SMR, however, in COPD patients.

[Obtaining samples of the human diaphragm during upper laparotomy. A structural analysis]. / Obtención de muestras del diafragma humano en el curso de laparotomía alta. Análisis estructural.

UNLABELLED: The diaphragm seems to undergo adaptive structural change in chronic obstructive pulmonary disease. The possibility of obtaining muscle specimens is limited, however, particularly when respiratory function is severely affected. OBJECTIVE: To assess the viability of a new technique for obtaining diaphragm muscle samples appropriate for structural assessment even from patients with severe functional change, and to study the size of fibers in relation to severity of disease. METHODS: Fifteen muscle specimens were obtained from patients (aged 57 +/- 15 years) by abdominal laparotomy. All had undergone full lung function testing. Muscle samples were taken during surgery using a new technique involving formation of a tobacco pouch with dome biopsy. The method had been previously validated in animal models. Later, the biopsies were processed to evaluate fiber proportions and sizes (ATPase dyes at different levels of pH). RESULTS: The 15 patients had a wide range of lung function results (FEV1 22-120% ref); 4 were severely affected (FEV1 < or = 50% ref). Nutritional status was normal in all cases; FEV1/FVC was 67 +/- 13%, RV was 134 +/- 55% ref, maximal mouth pressure (PImmax) was -75 +/- 27 cmH2O, transdiaphragmatic pressure (PIdimax) was 96 +/- 26 cmH2O, DLCO was 87 +/- 26% ref and PaO2 was 89 +/- 14 mmHg. We were able to obtain specimens valid for structural analysis from all patients with no complications. Light type I fibers predominated (54 +/- 9%) and size was normal overall (57 +/- 9 microns minimum diameter [Dm] atrophy index 195 +/- 243, and hypertrophy index 66 +/- 78), with no differences between the two fiber subtypes (Dm 58 +/- 8 microns for type I and 61 +/- 8 microns for type II). Overall size correlated inversely with static volumes (e.g. Dm with RV, r = -0.729, p < 0.01). CONCLUSIONS: The laparoscopic technique described is simple and safe for use in humans to obtain diaphragm muscle specimens that are valid for morphometric analysis, allowing us to enlarge the range of subjects that can be enrolled for this type of study. The fiber muscles studied are smaller when functional involvement is greater in chronic obstructive pulmonary disease.

[Diaphragmatic function during exercise in patients with severe COPD]. / Función diafragmática durante el ejercicio en pacientes con EPOC severa.

UNLABELLED: Ventilatory requirements increase during exercise. The respiratory muscles of patients with chronic obstructive pulmonary disease (COPD) are at a particular disadvantage when dealing with such increased demand. The objective of this study was to evaluate the changes in respiratory muscles brought on by exercise in such patients. METHODS: Twelve patients with severe CFOPD (FEV1 < 50% ref., 63 +/- 7 years) were enrolled. Breathing patterns and esophageal (Pes and transdiaphragmatic (Pdi) pressures and SaO2 were measured during submaximal exercise/Ecsbmax, 60% of the maximum tolerated load). A sniff maneuver was performed with the patients breathing ambient air with added oxygen to achieve 99% SaO2. We also measured level of FRC by inductive plethysmograph in a subgroup of five patients. RESULTS: During EXsbmáx, SaO2 decreased (from 95.0 +/- 2.1 to 92.3 +/- 4.0%; p < 0.01); Vt increased (717 +/- 199 to 990 +/- 297 cc, p < 0.01), as did respiratory rate (RR, 17 +/- 6 a 28 +/- 9; p < 0.01). Pes and Pdi were greater at Vt, changing from -12.4 +/- 4.8 to -27.0 +/- 10.1 and 16.6 +/- 6.1 to 30.4 +/- 12.4 cmH2O, respectively (p < 0.01 in both cases), whereas no significant changes were observed for maximal effort (Pesmax, -61.4 +/- 16.5 cersus -65.9 +/- 15.2 cmH2O; Pdimac 89.7 +/- 26.1 versus 81.7 +/- 35.7 cmH2O). Used as a global measure, Pdi/Pdimáx worsened (0.21 +/- 0.12 a 0.42 +/- 0.20; p < 0.01), as dud the diaphragm tension-time (TTdi; 0.07 +/- 0.04 to 0.15 +/- 0.06, p < 0.01). Intrinsic positive end-expiratory pressure (PEEPi) increased an estimated 2.7 +/- 2.1 to 9.4 +/- 5.8 cmH2O (p < 0.001), while FRC (delta 357 +/- 274 ml). Durante el EXsbmáx with oxygen supplementation, SaO2 did not decrease. However supplementation, though Ti/TTOT and maximal pressures remained unchanged. CONCLUSIONS: Respiratory muscle function changes induced by Exsbmáx seem to relate mainly to a worsening of system mechanics.

[Fiber morphometry of the external intercostal muscle. Comparison of dominant and nondominant sides in patients with severe COPD]. / Morfometría fibrilar del músculo intercostal externo. Comparación entre los lados dominante y no dominante en pacientes con EPOC severa.

The general morphometric characteristics of the external intercostal muscle (EIM) of patients with chronic respiratory disease have been well described. Because this muscle is highly accessible, it can provide an ideal model for longitudinal studies using consecutive biopsies of both sides. Whether or not the EIM fiber phenotype is homogeneous on dominant (D) and non dominant (ND) sides is unknown, however. To evaluate possible structural differences in right and left EIM in patients with COPD, eight patients (63 +/- 7 years of age) were enrolled. Lung function, respiratory muscle power, general muscle power and nutritional state were evaluated. Biopsies of the fifth EIM were taken from both sides. Specimens were processed in parallel manner to determine conventional morphometry (hematoxylin-eosin staining), including minimum diameter (Dm) and fiber area (Ar) in cross sections. Fibers were typed by ATPase (at pH 4.2, 4.6 and 9.4) and NADH-TR staining. Nutrition was normal in all patients. All patients had severe COPD (FEV1 27 +/- 7% of reference, limits 13 to 38% of reference) with air entrapment (RV 163 +/- 36% of reference, limits 181 to 276% of reference). None of the patients showed respiratory insufficiency at rest (PaO2 72 +/- 7 mmHg). Peripheral musculoskeletal power measured by manual dynamometer showed no significant right-left differences: D 29 +/- 2 and ND 28 +/- 3 dynes. Morphometric study of 16 muscle specimens showed no significant differences between fiber size on D and ND sides. DmD was 47 +/- 10 microns and ArD, was 2,595 +/- 1,249 microns2. DmD was 49 +/- 9 microns and ArD was 2,636 +/- 953 microns2. Likewise, no significant differences were found between D and ND fiber types: type ID 51 +/- 4% and type IID 49 +/- 5% versus type IND 52 +/- 4% and type IIND 48 +/- 4%. EIM on N and ND sides is homogeneous at the fifth intercostal space. This finding, along with the scarcely invasive nature of the technique for collecting specimens leads us to suggest that longitudinal studies might be performed on the structural effects of various pharmacological or physical treatments followed by COPD patients

[Cellular homogeneity in diverse portions of the diaphragm]. / Homogeneidad celular en las diversas porciones del diafragma.

The diaphragm is the main inspiratory muscle. It is composed of two parts, the costal and crural, with both anatomical and functional differences. The general morphometric characteristics of the diaphragm have been described in various species but homogeneity throughout the muscle has not been adequately studied. The aim of this study was to evaluate the fiber phenotype of various parts of the diaphragm. The entire diaphragm muscles of five New Zealand rabbits were removed and each was divided into quarters. The specimens were processed for morphometry (hematoxyllineosin stains, NADH-TR and ATPase at pH levels of 4.2, 4.6 and 9.4). For each portion we measured percent and size of fibers, expressing the latter as minimum diameter (Dm), measured area (Ar) and calculated area (Ac). Left and right diaphragm hemispheres (20 portions examined) were similar for fiber percentages and sizes. For left and right halves, respectively 50 +/- 2 and 51 +/- 4% of fibers were type I; type I Dm measurements were 38 +/- 5 and 41 +/- 4 microns; type I Ar values were 1798 +/- 481 and 2030 +/- 390 micron 2; type I Ac values were 1181 +/- 360 and 1321 +/- 382 micron 2; type II Dm values were 46 +/- 4 and 46 +/- 5 microns; type II Ar values were 2466 +/- 388 micron 2 and 2539 +/- 456 micron 2; type II Ac data were 1642 +/- 255 and 1655 +/- 382 micron 2. We likewise found no differences between costal and crural portions of the muscle (n = 20). For costal and crural portions, respectively, 50 +/- 3 and 50 +/- 2% of fibers were type I; type I Dm sizes were 39 +/- 5 and 40 +/- 4 microns; type I Ar measurements were 1859 +/- 521 and 1964 +/- 365 micron 2; type I Ac figures were 1231 +/- 317 and 1266 +/- 288 micron 2; type II Dm were 47 +/- 4 and 44 +/- 3 microns; type II Ar were 2563 +/- 481 and 2430 +/- 331 micron 2; type II Ac were 1729 +/- 373 and 1557 +/- 212 micron 2. Type II fibers, however, were somewhat larger than type I fibers in all portions (p = 0.001). New Zealand rabbit diaphragm muscle has similar percentages of slow and rapid contraction fibers. The size is not different from that observed in other species of mammals of similar size. Fiber type proportions are similar throughout the muscle, with more type II fibers present in all areas. The morphometric characters, therefore, suggest an homogeneous throughout the diaphragm, suggesting homogeneous response of the muscle to usual loads, and also suggesting the possibility of proposing longitudinal morphometric studies using this species as a model.

[Respiratory muscle force and resistance in patients with SAHS. The effect of using nighttime CPAP]. / Fuerza y resistencia de los músculos respiratorios en pacientes con SAHS. Efecto de la aplicación nocturna de CPAP.

UNLABELLED: During nighttime episodes of obstructive apnea in patients with sleep apnea-hypopnea syndrome (SAHS), repeated and progressive inspiratory efforts are made. Such intense nighttime activity can have a deleterious effect on daytime function of respiratory muscles. OBJECTIVE: The objective of this study was to evaluate daytime respiratory muscle function in a group of SAHS patients before and after two months of treatment with nighttime continuous positive airway pressure (CPAP). METHODS: We enrolled 12 patients with SAHS and 10 normal subjects (control group). To evaluate respiratory muscle strength we measured maximum esophageal pressure (Pesmax), transdiaphragmatic pressure (Pdimax) and inspiratory pressure in the mouth (PM). Respiratory muscle resistance was assessed using peak pressure in the mouth (PMPeak), time of tolerance (Tlim) and maximum inspiratory pressure-time index (PTimax). We also analyzed the nighttime function of respiratory muscles during apneic episodes in 10 of the 12 SAHS patients. We propose and define an index of nighttime respiratory muscle activity (RMian) as the product of the tension-time index for the diaphragm observed at the end of nighttime apneic episodes (TTdiapnea) and the apnea-hypopnea index (AHI). RESULTS: Respiratory muscle strength was similar in the two groups and no changes were observed in SAHS patients after treatment with nighttime CPAP. However, tolerance was lower in SAHS patients (PMpeak--30%, Tlim--31% and PTimax--49%). Two months of nighttime CPAP normalized all three variables in these patients. MRian was related to percent improvement in PMpeak after treatment with nighttime CPAP in SAHS patients (r = 0.66, p < 0.04). CONCLUSION: SAHS has an adverse effect on the daytime endurance of respiratory muscles that is proportional to the increase of nighttime mechanical muscle activity. The application of nighttime CPAP is restorative, probably because it allows respiratory muscles to rest.

[Fiber-optic bronchoscopic biopsy of bronchial smooth muscle. Efficacy of the technique in individuals with normal lung function and patients with COPD]. / Biopsia de músculo liso bronquial mediante fibrobroncoscopia. Eficacia de la técnica en individuos con función pulmonar normal y en pacientes con EPOC.

BACKGROUND AND OBJECTIVES: The epithelium and airway smooth muscles of patients with chronic obstructive pulmonary disease (COPD) or bronchial asthma undergo certain structural changes that are probably related to increased expression of inflammatory molecules and cell growth factors. Studying the relation between disease and changes in bronchial smooth muscle is difficult if investigation is restricted to samples from autopsies or thoracotomies. This study was designed to evaluate the probability of obtaining bronchial smooth muscle by endoscopic bronchial biopsy in patients with COPD and from individuals with normal lung function, the relation of disease to bronchial epithelial histology, and the potential usefulness of studying airway muscle remodeling events. METHODS: Forty-two patients undergoing diagnostic fiberoptic bronchoscopy were enrolled. Bronchial biopsies were taken systematically from the lobar and segmental dividing ridges. The epithelial structure was analyzed by conventional histology. The smooth muscle was identified by immunohistochemistry (anti-desmin antibody assay) and Western-blot analysis (anti-desmin, actin and myosin antibodies). RESULTS: Sixty-nine percent of the biopsies contained bronchial smooth muscle. The probability of obtaining smooth muscle was higher in segmental than in lobar biopsies (72 vs 30%, p < 0.05). This probability was unrelated to the presence of COPD or to signs of epithelial inflammation. The fragments allowed us to use electrophoresis to identify protein structures (myosin, actin, desmin) involved in muscle remodeling processes. CONCLUSIONS: Endoscopic biopsy of the bronchi allows us to obtain bronchial smooth muscle samples in a large percentage of patients, particularly when performed on segmental bronchi. The technique may be useful for future studies examining the processes of airway smooth muscle remodeling.

[Low-weight syndrome associated with COPD in our setting]. / Síndrome de bajo peso asociado a la EPOC en nuestro medio.

UNLABELLED: The high prevalence of chronic obstructive pulmonary disease (COPD) has considerable economic and health-related impact. The consequences arise largely from limitations on a patient's activity and shortened life expectancy. Low body weight has recently been implicated as a factor affecting limitations. Although the reason is not clear, weight loss appears to affect many patients (from 25 to 35% in different series), at least in Europe and North America. However, the situation is thought to be different in the Mediterranean area. OBJECTIVE: To estimate the prevalence of the low weight syndrome in patients with COPD in our area. METHODS: COPD patient characteristics monitored by our laboratory over the last two years (2000 and 2001) were reviewed. RESULTS: The prevalence of a body mass index (BMI) less than 20 kg/m2 was only 6.6% among the 3,126 patients studied. That percentage fell to 3.1% with a cutoff of 18 kg/m2. The figure was even more striking if we consider that half the patients had severe disease (FEV1 < 50% of reference). BMI was directly related to FEV1/FC and CO transfer. CONCLUSIONS: These results suggest that COPD patients in our geographic area have characteristics that distinguish them from those previously described in other countries. Specifically, the prevalence of low weight syndrome in our area appears to be lower. However, larger studies should be performed to confirm this finding.

[Metabolic activity of the external intercostal muscle of patients with COPD]. / Actividad metabólica del músculo intercostal externo en pacientes con EPOC.

INTRODUCTION: The external intercostal muscle is a relevant contributor to ventilatory work in situations of overloading. Like other respiratory muscles, the external intercostal muscle seems to undergo a process of structural remodeling to adapt to a situation of functional disadvantage. However, findings from published studies of morphology have differed to a certain degree. On the one hand, the proportion of fibers involved in anaerobic metabolism increases; on the other hand, the number of capillaries also increases, an occurrence that would facilitate aerobic metabolism. OBJECTIVE: This study was designed to analyze the activity of several key enzymes involved in the principal metabolic pathways in the external intercostal muscles of patients with COPD. METHODOLOGY: We studied 6 patients with COPD (65 +/- 8 years, BMI 23 +/- 3 kg/m2, FEV1 51 +/- 9% ref, RV 184 +/- 38% ref, PaO2 81 +/- 10 mmHg) and 6 control subjects matched for age and anthropometric variables but with normal lung function. External intercostal muscle samples were taken from each patient (fifth intercostal space, non-dominant side). The samples were treated by conventional spectrophotometry to determine enzyme activity as follows: citrate synthase (CS, Krebs cycle), phosphofructokinase (PFK, by common glycolysis), lactate dehydrogenase (LDH, anaerobic glycolysis) and creatine phosphokinase (CPK, use of energy reserves). RESULTS: Patients with COPD showed greater PFK enzyme activity (93 +/- 25 versus 44 +/- 9 micromol/min/g of fresh weight; p = 0.001) and LDH (308 +/- 42 versus 231 +/- 29 micromol/min/g; p < 0.01) than did control subjects. However, CS and CPK activity was similar in both groups (82 +/- 31 versus 90 +/- 20 micromol/min/g and 4017 +/- 1734 versus 3048 +/- 464 micromol/min/g, respectively), although the latter displayed noteworthy dispersion of values among COPD patients, with levels in some patients being three-fold greater than in controls. RV was directly related to glycolytic enzyme activity (with PFK, r = 0.716, p < 0.01; with LDH r = 0.697, p < 0.05) and PFK and LDH also correlated with each other (r = 0.737, p < 0.01). CONCLUSIONS: Based on the enzyme activity studied, oxidative activity seems to be conserved in the external intercostal muscle of patients with COPD. Activity in the glycolytic pathway seems to increase and the increase is proportional to the severity of COPD. These findings are probably the expression of a combination of adaptive structural factors.

[The quality-of-life questionnaire with asthma patients: the Spanish version of the Asthma Quality of Life Questionnaire]. / Cuestinario de calidad de vida en pacientes con asma: la versión española del Asthma Quality of Life Questionnaire.

This paper describes the translation to Castilian and adaptation of a quality of life measurement instrument: the Asthma Quality of Life Questionnaire (AQLQ). The AQLQ, developed by Juniper et al, contains 32 items, 5 of which relate to habitual activities that the patient can choose from among a list of 26 possibilities. Answers are given on a scale of 7 points. To adapt this instrument for use in Spain, we subjected it to a process of translation/back translation by bilingual informants. The translated and original versions of each item, activity and answer option were evaluated as being totally equivalent (A), fairly equivalent but with some questionable wording (B), or of questionable equivalence (C). The naturalness and correctness of the Spanish version were also evaluated on a scale of 1 to 10. Three (9%) items and 1 (4%) activity were considered to be of questionable equivalence (C) and 12 (37%) items and 1 activity (4%) were considered to be of type B equivalence. The questionable aspects of types B and C equivalence were discussed in 2 meetings, along with expressions that were equivalent but unnatural or grammatically incorrect; the first meeting involved researchers and translators and the second was held with a group of 6 asthmatics. Consensus was finally obtained for each item and activity included in the second draft. That draft was then administered to another group of 7 patients in order to check comprehension and equivalence, after which a definitive version was produced by the researchers.(ABSTRACT TRUNCATED AT 250 WORDS)

[Analysis of respiratory muscle structure and tumor necrosis and insulin-like growth factor expression in chronic obstructive pulmonary disease: are samples valid if obtained during thoracotomy performed because of localized pulmonary neoplasia?]. / Análisis estructual y expresión de los factores de necrosis tumoral y crecimiento insulina-like en los músculos respiratorios de pacientes con EPOS. Son válidas las muestras obtenidas en el curso de una toracotomía por neoplasia pulmonar localizada?

OBJECTIVE: Various methods have been used to obtain samples to study the structure of human respiratory muscles and the expression of diverse substances in them. Samples are most often obtained from autopsies, from muscle biopsies during thoracotomy performed because of a localized pulmonary lesion (TLL), and from ambulatory thoracoscopic biopsy in patients free of comorbidity (AT). The disadvantage of the first 2 of these methods lies in the possibility of interference from factors related to the patient's death in the first case or from the disease that necessitated surgery in the second. Although AT is free from the disadvantages of the other 2 methods, it is impossible to obtain samples of the diaphragm the principal respiratory muscle with this procedure. The objective of this study was to analyze the fibrous structure of the external intercostal muscle of patients with chronic obstructive pulmonary disease and to quantify the expression of the principal inflammatory cytokine tumor necrosis factor alpha (TNF-alpha)- and of insulin-like growth factor (IGF-1) in the same muscle, comparing the results obtained with TLL and AT samples. METHODS: Prospective and consecutive samples were taken of the external intercostal muscle (fifth space, anterior axillary line) in 15 patients with chronic obstructive pulmonary disease (mean [SD] age 66 [6] years; forced expiratory volume in 1 second 49% [9%] of predicted; PaO2 75 [9] mm Hg). Samples were taken during TLL (8 patients, all with pulmonary neoplasms but carefully selected in order to rule out systemic effects) or TA (7 patients). Patients with serious comorbidity were excluded from the second group. Samples were processed for structural analysis of fibers (immunohistochemical and enzymatic histochemical) and genetic expression of TNF-alpha and IGF-1 (real-time polymerase chain reaction). RESULTS: No differences in the structure of fibers were found between the 2 groups. No differences were observed in the expression of TNF-alpha or IGF-1. CONCLUSIONS: Using rigorous criteria, the TLL method appears to be suitable for studying the structural characteristics and expression of inflammatory cytokines and growth factors in the external intercostal muscle. Moreover, it can also be inferred that TLL is probably also useful for obtaining samples of the diaphragm, a muscle which cannot currently be sampled by any alternative method.