Classical NF-κB activation impairs skeletal muscle oxidative phenotype by reducing IKK-α expression.

BACKGROUND: Loss of quadriceps muscle oxidative phenotype (OXPHEN) is an evident and debilitating feature of chronic obstructive pulmonary disease (COPD). We recently demonstrated involvement of the inflammatory classical NF-κB pathway in inflammation-induced impairments in muscle OXPHEN. The exact underlying mechanisms however are unclear. Interestingly, IκB kinase α (IKK-α: a key kinase in the alternative NF-κB pathway) was recently identified as a novel positive regulator of skeletal muscle OXPHEN. We hypothesised that inflammation-induced classical NF-κB activation contributes to loss of muscle OXPHEN in COPD by reducing IKK-α expression. METHODS: Classical NF-κB signalling was activated (molecularly or by tumour necrosis factor α: TNF-α) in cultured myotubes and the impact on muscle OXPHEN and IKK-α levels was investigated. Moreover, the alternative NF-κB pathway was modulated to investigate the impact on muscle OXPHEN in absence or presence of an inflammatory stimulus. As a proof of concept, quadriceps muscle biopsies of COPD patients and healthy controls were analysed for expression levels of IKK-α, OXPHEN markers and TNF-α. RESULTS: IKK-α knock-down in cultured myotubes decreased expression of OXPHEN markers and key OXPHEN regulators. Moreover, classical NF-κB activation (both by TNF-α and IKK-ß over-expression) reduced IKK-α levels and IKK-α over-expression prevented TNF-α-induced impairments in muscle OXPHEN. Importantly, muscle IKK-α protein abundance and OXPHEN was reduced in COPD patients compared to controls, which was more pronounced in patients with increased muscle TNF-α mRNA levels. CONCLUSION: Classical NF-κB activation impairs skeletal muscle OXPHEN by reducing IKK-α expression. TNF-α-induced reductions in muscle IKK-α may accelerate muscle OXPHEN deterioration in COPD.

TNF-alpha impairs regulation of muscle oxidative phenotype: implications for cachexia?

Chronic obstructive pulmonary disease (COPD) is characterized by weight loss, muscle wasting (in advanced disease ultimately resulting in cachexia), and loss of muscle oxidative phenotype (oxphen). This study investigates the effect of inflammation (as a determinant of muscle wasting) on muscle oxphen by using cell studies combined with analyses of muscle biopsies of patients with COPD and control participants. We analyzed markers (citrate synthase, ß-hydroxyacyl-CoA dehydrogenase, and cytochrome c oxidase IV) and regulators (PGC-1α, PPAR-α, and Tfam) of oxphen in vastus lateralis muscle biopsies of patients with advanced COPD and healthy smoking control participants. Here 17 of 73 patients exhibited elevated muscle TNF-α mRNA levels. In these patients, significantly lower mRNA levels of all oxidative markers/regulators were found. Interestingly, these patients also had a significantly lower body mass index and tended to have less muscle mass. In cultured muscle cells, mitochondrial protein content and myosin heavy chain isoform I (but not II) protein and mRNA levels were reduced on chronic TNF-α stimulation. TNF-α also reduced mitochondrial respiration in a nuclear factor kappaB (NF-κB) -dependent manner. Importantly, TNF-α-induced NF-κB activation decreased promoter transactivation and transcriptional activity of regulators of mitochondrial biogenesis and muscle oxphen. In conclusion, these results demonstrate that TNF-α impairs muscle oxphen in a NF-κB-dependent manner.

Safety and tolerability of NVA237, a once-daily long-acting muscarinic antagonist, in COPD patients.

NVA237 is a novel once-daily inhaled long-acting muscarinic antagonist administered via a dry powder inhaler. This randomized, double-blind, placebo-controlled study evaluated the safety, tolerability and bronchodilator efficacy of two doses of NVA237 (100 and 200 microg), versus placebo, in patients with moderate-to-severe COPD (forced expiratory volume in 1s [FEV(1)]>or=30% and <80% predicted and FEV(1)/forced vital capacity [FVC]<0.7, 30 min after inhalation of 80 microg ipratropium bromide). After appropriate washout periods, patients were randomized to treatment with NVA237 100 microg (n=92), NVA237 200 microg (n=98) or placebo (n=91) for 28 days. The primary objective was evaluation of safety, with efficacy measures included as secondary objectives. NVA237 was generally well tolerated and associated with a frequency and distribution of adverse events similar to placebo. Serious adverse events were uncommon and there was no evidence of adverse cardiovascular effects or unexpected events. Trough FEV(1) was significantly higher in those receiving NVA237 compared with placebo. For NVA237 100 microg the differences were 131 and 161 mL on Days 1 and 28, respectively (p<0.05), and for NVA237 200 microg the differences were 146 and 151 mL on Days 1 and 28, respectively (p<0.05). Peak FEV(1), FEV(1) at all timepoints up to 24h after dosing, and FEV(1) area under the curve during 5 min-5 h post-dosing were also significantly higher in both NVA237 groups, compared with placebo. Patients receiving NVA237 required fewer daily puffs of rescue medication and had a higher percentage of days on which rescue medication was not required. Overall, the present study provides further evidence of the safety, tolerability and bronchodilator efficacy of once-daily treatment with NVA237 100 and 200 microg in patients with moderate-to-severe COPD.

Reference values of respiratory and peripheral muscle function in rats.

Skeletal muscle dysfunction is a common systemic manifestation in several prevalent diseases. Predictive values are useful tools for the diagnosis and prognosis of diseases. In experimental animals, no reference values of muscle function evaluation have been so far reported. The objective was to obtain predictive values of maximal inspiratory pressure (MIP) and grip strength measurements in healthy rats. In 70 healthy rats, MIP and grip strength were measured in vivo weekly for five consecutive weeks using non-invasive methodologies. Three ranges of rat body weights (250-299, 300-349 and 350-399 g) and lengths (37.0-41.0, 41.1-42.0 and 42.1-44.0 cm) were established. MIP and grip strength measurements falling within the ranges of weight 350-399 and 300-349 g and length 42.1-44.0 cm were significantly greater than values falling within 250-299 g and 37.0-41.0 cm ranges respectively. Specific weight- and length-percentile distributions for MIP and grip strength measurements were calculated. As significant direct correlations were observed between rat weights and lengths and either MIP or grip strength measurements, regression equations relating all these variables were also determined. Skeletal muscle dysfunction is frequently associated with highly prevalent conditions. The significant predictive equations described for both MIP and grip strength measurements will enable scientists to better estimate the respiratory and peripheral muscle dysfunctions of laboratory animals, especially when conducting follow-up and/or intervention investigations.

Cytokine profile in quadriceps muscles of patients with severe COPD.

BACKGROUND: Systemic proinflammatory cytokines and oxidative stress have been described in association with peripheral muscle wasting and weakness of patients with severe chronic obstructive pulmonary disease (COPD), but their expression in skeletal muscle is unknown. The objectives of the present study were to determine muscle protein levels of selected cytokines in patients with COPD and to study their relationships with protein carbonylation as a marker of oxidative stress, quadriceps function and exercise capacity. METHODS: We conducted a cross sectional study in which 36 cytokines were detected using a human antibody array in quadriceps specimens obtained from 19 patients with severe COPD and seven healthy controls. Subsequently, selected cytokines (tumour necrosis factor (TNF)alpha, TNFalpha receptors I and II, interleukin (IL) 6, interferon gamma, transforming growth factor (TGF) beta and vascular endothelial growth factor (VEGF)), as well as protein carbonylation (oxidative stress index) were determined using an enzyme linked immunosorbent assay (ELISA) in all muscles. RESULTS: Compared with controls, the vastus lateralis of patients with COPD showed significantly lower protein ELISA levels of TNFalpha, which positively correlated with their quadriceps function, TNFalpha receptor II and VEGF. Protein ELISA levels of IL6, interferon gamma and TGFbeta did not differ between patients and controls. Quadriceps protein carbonylation was greater in patients and inversely correlated with quadriceps strength among them. CONCLUSIONS: These findings do not support the presence of a proinflammatory environment within the quadriceps muscles of clinically and weight stable patients with severe COPD, despite evidence for increased oxidative stress and the presence of muscle weakness.

Assessment of dyspnea and dynamic hyperinflation in male patients with chronic obstructive pulmonary disease during a six minute walk test and an incremental treadmill cardiorespiratory exercise test.

The six minute walk test (6MWT) is a standardized test that provides information on exercise capacity in patients with COPD. It is considered a submaximal test in opposition to incremental cardiopulmonary exercise tests (CPET) that provide valuable information on all the systems involved in exercise. OBJECTIVES: 1. To compare the perceptive, physiological responses and degree of dynamic hyperinflation during two exercise tests: the 6MWT and the incremental CPET on a treadmill. 2. To evaluate how dyspnea is related to dynamic hyperinflation (DH) and other functional parameters in both tests. METHODS: 29 stable COPD male patients, age 68±5.8 years, mean post-bronchodilator FEV1 57±11%, were recruited. To evaluate dynamic hyperinflation, inspiratory capacity (IC) was measured at rest and upon completing each one of the tests. At the same time, perceived dyspnea and leg discomfort were rated on specific modified Borg scales. RESULTS: The mean walk distance in 6MWT was 494±88m. The Borg scale rating for shortness of breath upon completing the test was 4.7±2, whilst 2.9±2 for leg discomfort. IC changed from 2.53±0.63l before to 2.34±0.60l after completion of the test. In the treadmill CPET, maximal oxygen consumption (V˙O2max) was 21.8±5mL/kg/min with 6.6±2 dyspnea and 4.3±2 leg discomfort on Borg scales. IC changed from 2.17±0.53l to 1.20±0.43l. CONCLUSIONS: Dynamic hyperinflation occurs in male COPD patients during submaximal exercise such as the 6MWT. This phenomenon is more pronounced after incremental CPET on a treadmill. Despite being dyspnea the dominant limiting symptom for both tests, we observed different physiological responses.

Respiratory loading intensity and diaphragm oxidative stress: N-acetyl-cysteine effects.

We hypothesized that resistive breathing of moderate to high intensity might increase diaphragm oxidative stress, which could be partially attenuated by antioxidants. Our objective was to assess the levels of oxidative stress in the dog diaphragm after respiratory muscle training of a wide range of intensities and whether N-acetyl-cysteine (NAC) might act as an antioxidant. Twelve Beagle dogs were anesthetized with 1% propophol, tracheostomized, and subjected to continuous inspiratory resistive breathing (IRB) (2 h/day for 2 wk). They were further divided into two groups (n = 6): NAC group (oral NAC administration/24 h for 14 days) and control group (placebo). Diaphragm biopsies were obtained before (baseline biopsy) and after (contralateral hemidiaphragm) IRB and NAC vs. placebo treatment. Oxidative stress was evaluated in all diaphragm biopsies through determination of 3-nitrotyrosine immunoreactivity, protein carbonylation, hydroxynoneal protein adducts, Mn-SOD, and catalase, using immunoblotting and immunohistochemistry. Both protein tyrosine nitration and protein carbonylation were directly related to the amount of the respiratory loads, and NAC treatment abrogated this proportional rise in these two indexes of oxidative stress in response to increasing inspiratory loads. A post hoc analysis revealed that only the diaphragms of dogs subjected to high-intensity loads showed a significant increase in both protein tyrosine nitration and carbonylation, which were also significantly reduced by NAC treatment. These results suggest that high-intensity respiratory loading-induced oxidative stress may be neutralized by NAC treatment during IRB in the canine diaphragm.

[Comparison of mouth pressure, twitch, after anterior magnetic stimulation against posterior magnetic stimulation in healthy subjects]. / Comparación de la presión en boca, twitch, tras estimulación magnética anterior frente a estimulación magnética posterior en sujetos sanos.

BACKGROUND: If techniques for studying respiratory muscle function are easy to use and well tolerates by patients, they can be used routinely. Measuring mouth twitches (TwM) using either bilateral anterior or posterior magnetic stimulation meets both criteria. SUBJECTS AND METHODS: We studied 16 healthy subjects. TwM was measured using bilateral anterior (TwMA) and posterior (TwMP) stimulation. Ten stimuli were applied for each technique for each subject. Five subjects repeated the test was repeated on a different day. RESULTS: The mean TwMA in healthy subjects was 21.07 +/- 4.4 cmH2O (range 13.72-30.11); the mean TwMP was 21.12 +/- 5.9 cmH2O (range 12.7-35.7) (NS). The mean difference was 2.8 +/- 2.5 cmH2O, while the ratio TwMP/PImax was 0.15 (range 0.08-0.10) and TwMA/PImax was 0.14 (range 0.07-0.15). The correlation between the two technique was 0.8. The patients who underwent testing twice had a mean TwMA of 20 cmH2O on the first day and 10.18 cmH2O on the second (NS). The coefficient of variation (CoV%) was 5.9% for TwMA and 7.2% for TwMP. CONCLUSIONS: The two techniques for measuring TwM give similar results and coefficients of variation in healthy subjects; either technique can be used. Variation from one testing day to another is low.

[Asthma emergencies: can we lower the rate of readmission after discharge?]. / Asma en urgencias: podemos disminuir la tasa de reingresos tras el alta?

INTRODUCTION: The rate of readmission among asthmatic emergency patients varies. In 1991 we observed a 9% rate of readmission following emergency room release. Studies of the number of readmissions or request for medical care are used as the basis for recommendations for releasing patients from hospital emergency care. No studies have assessed disease stability following release or factors related to stability. OBJECTIVES: To assess the course of disease and clinical stability of patients in the period immediately following release from emergency room care. To determine factors that might predict such stability. to determine the rate of readmission in the month following release after applying a treatment protocol and release criteria, with follow-up examination 72 h later. MATERIAL AND METHODS: Prospective, descriptive study with follow-up 72 h and one month after release. SETTING: Emergency and pneumology departments of a general hospital. PERIOD: six months. PATIENTS: 82 asthmatic patients released from the emergency room. RESULTS: Two patients (2.43% were readmitted. At the first follow-up visit (72 h) 81 patients (98.78%) were seen. At the second visit, 66 patients (80.5%) were examined. We observed stability in 70.3% of patients at 72 h and in 86.4% after on month. Stability was statistically related to whether peak expiratory flow greater or less than 70% (76.92% stable versus 46.66% unstable) (p < 0.05). No other clinical, epidemiological or treatment variables recorded upon release were found to influence stability. CONCLUSIONS: 1) A large proportion of patients are in stable condition 72 h after release. 2) When peak expiratory flow upon release is > 70%, stability is significantly increased 72 h later. 3) Our 2.43% rate of readmission one month after release is very low. 4) No differences in stability were seen to be related to oral corticoid prescription upon release.

[Usefulness of computerized tomography in the study of pleural effusion with no presumed diagnosis]. / Utilidad de la tomografía computarizada para el estudio del derrame pleural sin presunción diagnóstica.

To establish the diagnostic yield of computerized tomography (CT) in pleural effusions with no presumed diagnosis arising from standard clinical examination. A prospective protocol study enrolling all cases of effusion admitted to our hospital between January 1994 through July 1995 without a presumed diagnosis after initial testing that included thoracocentesis. Twenty-two patients were enrolled. All were given a CT scan as well as other complementary examinations considered appropriate and were referred to our outpatient clinic for follow-up. The CT images were read by an expert radiologist and their contribution was classified as "diagnostic", "suggestive" or "nil". A definitive etiologic diagnosis was achieved in 14 cases (8 neoplasms, 4 benign due to asbestos, 1 tuberculosis and 1 pulmonary embolism). The CT contribution was nil in 13 cases (59%), "diagnostic" in 6 (2 mesotheliomas, 1 hypernephroma, 1 lymphoma, 1 adenocarcinoma of the colon and another of the ovary) and "suggestive" in 3 (2 benign due to asbestos and 1 lymphoma). Positive information was obtained in 9 cases (41%). CT gives good yield in the investigation of pleural effusions with no presumed diagnosis and should be made available to this group of patients before other more invasive procedures are resorted to. It is especially useful for detecting neoplastic disease of the upper abdomen, mesothelioma and sings of unsuspected exposure to asbestos.

[Early discharge and home health care program for patients with exacerbated COPD and asthma]. / Programa de altas precoces y asistencia domiciliaria en pacientes con exacerbación de enfermedad pulmonar obstructiva crónica y asma.

OBJECTIVE: To shorten hospital stays of patients with exacerbated chronic obstructive pulmonary disease (COPD) or asthma by way of a home care program and to assess whether the program increased the number of readmissions. METHODS: Patients admitted due to COPD exacerbation or asthma who did not need critical care and were discharged before the fourth day. A registered nurse experienced with respiratory disease patients and in regular contact with the pneumologist who supervised the program made follow-up home care visits to give instructions and check compliance with treatment. RESULTS: Sixty-nine patients enrolled in the program, 53 with COPD and 16 with asthma. A mean 7.2 home care visits per patient were made. The mean hospital stay was 3.69 ( 0.5 days for patients receiving home care and 7.89 ( 5 days for those who received no home care (p < 0.005). Severity of COPD in terms of age, FEV1 and PaO2 was similar in both groups, as follows: FEV1 was 39.4 12% and PaO2 66.3 7,7% for patients receiving home care; FEV1 was 40.6 ( 12% and PaO2 was 64.3 ( 7% for those receiving no home care (ns). The mean hospital stay overall for both groups was 7.4 (4.9 days; the mean hospital stay for the same diseases in the same previous the year before the study was 8.3 ( 5.5 (p < 0.05). The rate of readmissions for new exacerbations within 30 days of discharge was 4.3% (3/69) in the group receiving home care and 7.2% (29/401) among patients receiving only hospital care (ns.). A questionnaire survey at the end of the program showed satisfaction to be very high. CONCLUSIONS: A program of home care provided by a registered nurse experienced with respiratory diseases allows mean hospital stay to be reduced without increasing the number of readmissions within 30 days, with high patient satisfaction.

[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.

[Interleukin 10 and tumor necrosis factor alpha gene expression in respiratory and peripheral muscles. Relation to sarcolemmal damage]. / Expresión de los genes de la interleucina 10 (IL-10) y del factor de necrosis tumoral alfa (TNF-alpha) en músculos respiratorios y periféricos. Relación con el daño sarcolémico.

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) has been implicated in loss of muscle mass in chronic obstructive pulmonary disease and other consumptive processes. TNF-alpha production would be related to inflammation arising from pulmonary disease itself or, alternatively, from smoking, and would be carried to the muscle through the blood stream. However, it has also been suggested that TNF-alpha may be expressed directly in muscle tissue. Regardless the site of production of TNF-alpha, its relation to subsequent muscle damage is unclear. OBJECTIVE: We studied the expression of TNF-alpha and an interleukin inhibitor of its production (IL-10) in the main respiratory muscles and a peripheral muscle in the dog. METHOD: Nine young, male Beagle dogs were included. From all animals we obtained a biopsy of the diaphragm (Dph) and external intercostal (ExtI) muscles and a leg muscle (internal vastus of the quadriceps, IntV). TNF-alpha and IL-10 gene expressions were measured through the analysis of messenger RNA levels, using reverse transcription and polymerase chain reaction. We also assessed sarcolemmal damage using intracellular fibronectin detection (immunohistochemistry). RESULTS: The expression of both cytokines showed wide interindividual variability. On the one hand, TNF-alpha (was very low in Dph and ExtI (0.02 0.03 and 0.05 0.06 a.u., respectively), but relatively high in the IntV (0.14 0.08 a.u.). IL-10 expression, on the other hand was low in the Dph (0.06 0.05 a.u.) and slightly higher in the ExtI (2.7 1.9 a.u., p < 0.01) and IntV (1.6 1.7 a.u.). Sarcolemmal damage was minimal in all three muscles and was related to TNF-alpha expression in the peripheral muscle (r = 0.682, p < 0.05). CONCLUSIONS: 1) TNF-alpha and IL-10 appear to be constitutively expressed within the skeletal muscle in dogs. 2) Basal TNF-alpha expression is lower in respiratory muscles than in peripheral muscles. 3) The expression in the latter is related to membrane damage.

[Basic structure of respiratory and peripheral muscles in the beagle dog]. / Estructura básica de los músculos respiratorios y periféricos en el perro beagle.

BACKGROUND: The dog is one of the most widely used animals in studies of respiratory physiopathology, mainly because of its physiological characteristics. However, ethical and legal constraints are placed on the use of some species in our context. OBJECTIVE: We studied the underlying structural features of respiratory and peripheral muscles in the beagle dog in order to suggest reference values for future studies. METHOD: Fourteen young beagles were selected. Samples were taken from the costal diaphragm (DFG), external intercostal (EI) and vastus medialis (VM) muscles. We analyzed fiber percentages and sizes (immunohistochemistry, using myosin heavy chain [MyHC (monoclonal antibodies), percentages and absolute number of MyHC isoforms (electrophoresis and ELISA), and level of membrane damage (immunohistochemistry, using anti-fibronectin monoclonal antibodies). RESULTS: In the EI muscle, type I fibers were larger (by 20%) than type II fibers. Fibers resistant to fatigue (type I) predominated greatly over fast contraction fibers (type II) in all three muscles analyzed (DFG 57% 11% vs. 45% 12%; EI 58% 5% vs. 43% 5%; and VM 70% 8% vs. 34% 7 %). Few hybrid fibers (co-expression of fast and slow MyHC) were found and their percentages were similar in all three muscles. The absolute expression of MyHC was greater in the VM than in the respiratory muscles, with a relative predominance of the MyHC I isoform in the DFG and VM muscles and a similar tendency in the EI muscle. Membrane damage was very slight in all three muscles. CONCLUSIONS: The phenotype characteristics of respiratory and peripheral muscles in the beagle correspond to what we would expect functionally for a breed initially selected for hunting, with minimal lesions under normal circumstances, a predominance of fibers and proteins that are resistant to fatigue, and larger fibers in the EI, a muscle that plays a role in respiration in dogs.

[Lung resection surgery in patients with functional limits]. / Cirugía resectiva pulmonar en pacientes en el límite funcional.

To determine whether there exists in our area concordance between forced expiratory volume in one second (FEV1) estimated before surgery by ventilation/perfusion scintigraphy and real values after surgery in patients undergoing pneumonectomy and lobectomy. Prospective descriptive study. We studied 15 patients undergoing pneumonectomy (M/F 14:1, age 62 +/- 7.5 years) and 11 undergoing lobectomy (M/F 11:0 age 66 +/- 3.5 years) in the thoracic surgery unit of Hospital de Cruces between 1 March 1990 and 1 March 1993. The FEV1 of all patients before surgery was under 2.1 liters. Tumors were malignant in 23 patients and benign in 3. Ventilation/perfusion gammagrams were obtained for all patients before surgery in order to predict the loss of function after resection of the parenchyma. Two months after surgery spirometric testing was done. The FEV1 calculated based on the results of scintigraphy was compared to the real FEV1 after resection by way of graphic concordance and by calculation of a within-group correlation coefficient. A correlation coefficient of 0.82 (p < 0.001) was obtained for FEV1 estimated by ventilation and real FEV1 in patients who underwent pneumonectomy, indicating good concordance. The correlation coefficient was 0.59 (p < 0.001) indicating moderate agreement between FEV1 estimated by perfusion and real FEV1 after resection. Correlation was statistically insignificant in lobectomy patients (0.28 by the method of Ali and 0.35 by Wernly's; p = 0.19 and 0.13, respectively). Ventilation scintigraphy offers an acceptably reliable prediction of FEV1 after lung resection. The reliability of measurements estimated by scintigraphy in lobectomized patients is not acceptable.

[Spirometry: quality in the respiratory medicine clinics of a public health care area]. / Calidad de la espirometría en las consultas neumológicas de un área jerarquizada.

BACKGROUND: Spirometry can be considered a routine way to evaluate patients with respiratory complaints, both inside and outside the hospital setting. OBJECTIVE: To assess the quality of spirometry in a public health care area with respect to two factors: the technicians' performance and the calibration of spirometers. MATERIAL AND METHOD: Four health care clinics were studied. Four technicians participated and the four spirometers were tested at different volumes (calibration syringes 1L and 3L) and different flows (explosive decompression). Eight patients with COPD participated in the study of inter-technician variability. RESULTS: Agreement among the technicians was very high: 0.98-0.99 for FEV1 and 0.91-0.98 for FVC. The mean results obtained by the technicians were: FEV1 = 2.15 0.03, range 2.20-2.14; FVC = 3.25 0.05, range 3.30-3.21 (ns). Volumetric readings from the spirometers were correct for the 1I calibration syringe, but 2 out of 4 spirometers lost linearity with the 3I calibration syringe. One spirometer gave readings out of range for all flow levels, and 2 out of 4 spirometers were out of range at low flows. CONCLUSIONS: 1. Results obtained by different technicians were not significantly different and there was high agreement among them, confirming that performance of spirometry was good. 2. The spirometers showed poor linearity at low flows.

Hyperleptinaemia, respiratory drive and hypercapnic response in obese patients.

Leptin is a powerful stimulant of ventilation in rodents. In humans, resistance to leptin has been consistently associated with obesity. Raised leptin levels have been reported in subjects with sleep apnoea or obesity-hypoventilation syndrome. The aim of the present study was to assess, by multivariate analysis, the possible association between respiratory centre impairment and levels of serum leptin. In total, 364 obese subjects (body mass index >or=30 kg.m(-2)) underwent the following tests: sleep studies, respiratory function tests, baseline and hypercapnic response (mouth occlusion pressure (P(0.1)), minute ventilation), fasting leptin levels, body composition and anthropometric measures. Subjects with airways obstruction on spirometry were excluded. Out of the 346 subjects undergoing testing, 245 were included in the current analysis. Lung volumes, age, log leptin levels, end-tidal carbon dioxide tension, percentage body fat and minimal nocturnal saturation were predictors for baseline P(0.1). The hypercapnic response test was performed by 186 subjects; log leptin levels were predictors for hypercapnic response in males, but not in females. Hyperleptinaemia is associated with a reduction in respiratory drive and hypercapnic response, irrespective of the amount of body fat. These data suggest the extension of leptin resistance to the respiratory centre.