Inspiratory flow resistive loading improves respiratory muscle function and endurance capacity in recreational runners.

The purpose of this study was to assess the efficacy of inspiratory flow resistive loading (IFRL) on respiratory muscle function, exercise performance and cardiopulmonary and metabolic responses to exercise. Twenty-four recreational road runners (12 male) were randomly assigned from each gender into an IFRL group (n=8) and sham-IFRL group (n=8), which performed IFRL for 6 weeks, or a control group (n=8). Strength (+43.9%Delta), endurance (+26.6%Delta), maximum power output (+41.9%Delta) and work capacity (+38.5%Delta) of the inspiratory muscles were significantly increased (P<0.05) at rest following the study period in IFRL group only. In addition, ventilation (-25.7%Delta), oxygen consumption (-13.3%Delta), breathing frequency (-11.9%Delta), tidal volume (-16.0%Delta), heart rate (HR) (-13.1%Delta), blood lactate concentration (-38.9%Delta) and the perceptual response (-33.5%Delta) to constant workload exercise were significantly attenuated (P<0.05), concomitant with a significant improvement (P<0.05) in endurance exercise capacity (+16.4%Delta) during a treadmill run set at 80% VO2max in IFRL group only. These data suggest that IFRL can alter breathing mechanics, attenuate the oxygen cost, ventilation, HR, blood lactate and the perceptual response during constant workload exercise and improve endurance exercise performance in recreational runners.

What community measurements can be used to predict bone disease in patients with COPD?

BACKGROUND: Osteoporosis is common in patients with COPD. Previously we have reported that loss of fat-free mass (FFM), measured by dual X-ray absorptiometry (DXA) is associated with loss of bone mineral density (BMD). In addition, in patients with a low body mass index (BMI) and a low FFM, all had evidence of bone thinning, 50% having osteopenia and 50% osteoporosis. We explored the utility of different anthropometric measures in detecting osteoporosis in a community-based COPD population. METHODS: Patients with confirmed COPD and not on long-term oral corticosteroids (n=58) performed spirometry. They underwent nutritional assessment by skinfold anthropometry, midarm circumference, calculation of both % ideal body weight (IBW) and BMI. All had DXA assessment of BMD. RESULTS: A total of 58 COPD patients had anthropometric measurements taken, with a mean age of 66.8 (SD 8.7) years, 31 (58%) were male, with a forced expiratory volume in 1s (FEV(1)) of 54.17 (20.18)% predicted. Osteoporosis was present at either the hip or lumbar region in 14 patients (24%). The useful anthropometric measurements identifying those with osteoporosis were both % IBW and BMI. The adjusted odds ratio for %IBW was 0.93 (95% confidence interval (CI) 0.87, 0.99), p=0.016 and for BMI: 0.79 (0.64-0.98), p=0.03. The receiver operating characteristics (ROC) score for both was 0.88, indicating a good fit. CONCLUSION: Osteoporosis is common, even in patients with mild airways obstruction. Nutritional assessment, incorporating a calculation of their BMI or %IBW may confer an additional benefit in detecting those at risk of osteoporosis and guide referral for BMD measurement.

Attaining a correct diagnosis of COPD in general practice.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is common. Diagnosis should include objective evidence of airways obstruction and spirometry is recommended in guidelines and the general medical services contract in the UK. We assessed the impact of spirometry in general practice. METHOD: We determined by questionnaire the availability, staff training, use and the interpretation results of spirometry in 72% of general practices in Wales. We reviewed the diagnosis of COPD previously made in two general practices without spirometry. RESULTS: Most practices had a spirometer (82.4%) and used it (85.6%). Confidence in use and interpretation of results varied widely: 58.1% were confident in use and 33.8% confident in interpretation. Spirometry was performed more often if confident in use and interpretation (both P<0.001) and was related to greater training periods (P<0.001). Spirometric confirmation of COPD varied widely (0-100%, median 37%). Of the 125 patients previously diagnosed with COPD 61 had spirometric confirmation, while 25 had reversible obstruction (range 210-800 mls), 34 had normal and 5 had restrictive spirometry. CONCLUSION: Despite incentives to perform spirometry in general practice, lack of adequate training in use and interpretation suggests use is confounded and the diagnosis of COPD is likely to be made on imprecise clinical grounds.

The vegetation that was not a vegetation: excusable misinterpretation of transesophageal echocardiography findings in late infective endocarditis of a prosthetic mitral valve.

The echocardiographic detection of a valvar mobile mass with independent mobility is one of the major Duke criteria for diagnosing infective endocarditis.(1) We report a case in which a mobile mass seen by transesophageal echocardiography on a prosthetic mitral valve with proven endocarditis was not a vegetation but pannus. This is an important clinical message for the interpretation of mobile masses on artificial valves.

Periaortic fat pad mimicking an intramural hematoma of the thoracic aorta: lessons for transesophageal echocardiography.

We report a patient whose clinical and echocardiographic findings were compatible with a diagnosis of aortic intramural hematoma, but magnetic resonance imaging demonstrated a prominent and localized periaortic deposit of fat as the cause of the transesophageal echocardiographic appearance. This is a significant caveat that must be borne in mind when interpreting echocardiographic images obtained in patients with suspected intramural aortic hematomas.

Prospective study of routine perioperative transesophageal echocardiography for elective valve replacement: clinical impact and cost-saving implications.

Transesophageal echocardiography (TEE) is widely used during heart valve replacement operations, but its clinical impact and cost-saving profile have not been studied prospectively for this indication. We investigated the clinical benefits and cost-savings of routine TEE for elective valve replacement at a regional tertiary center. We prospectively studied 300 patients (140 men; mean age [+/-SD], 66 +/- 9 years) undergoing aortic valve, mitral valve, or double-valve replacements. Transesophageal echocardiography with a biplane (in 161 patients) or a multiplane probe was performed before and after surgery. We assessed whether the TEE findings changed the operation or the postoperative treatment and the cost of TEE either as an extension of a preexisting service or as a new development. In 2 patients undergoing aortic valve replacement, significant mitral regurgitation on TEE led to additional mitral valve replacement, and in 1 patient undergoing mitral valve replacement, aortic regurgitation also required aortic valve replacement. Immediate reoperation (dehisced mitral valve prosthesis) and delayed extubation (suspected obstruction of an aortic valve prosthesis) were prompted by postoperative TEE. Extending an existing TEE service to routine intraoperative use saved up to $109 (US) per patient per year. Routine intraoperative TEE can provide major clinical benefit to a small proportion of patients undergoing elective valve replacement, and this can lead to cost savings, but only if the service can be provided without major capital investment.

Morphologic analysis of a strand recovered from a prosthetic mitral valve: No evidence of fibrin.

We report the first morphologic analysis of a linear mobile structure (strand) detected by transesophageal echocardiography on a bioprosthetic mitral valve and then recovered at surgery. Electron microscopy showed it to consist of a sparsely cellular component, with extracellular amorphous or fibrillary areas. Collagen was largely responsible for the fibrillary appearance.

Insulin resistance and inflammation - A further systemic complication of COPD.

Chronic obstructive pulmonary disease (COPD) is associated with a continuous systemic inflammatory response. Furthermore, COPD is associated with an excess risk for cardiovascular disease and type II diabetes. Systemic inflammation in other populations is a factor in atherogenesis and has been associated with insulin resistance. We assessed the association between systemic inflammation and insulin resistance in non-hypoxaemic patients with COPD. Fasting plasma glucose, insulin and inflammatory mediators were measured in 56 patients and 29 healthy subjects. Body mass index (BMI) and height squared fat- and fat-free-mass index were similar between subject groups. Using homeostatic modelling techniques, mean (SD) insulin resistance was greater in the patients, 1.68 (2.58) and 1.13 (2.02) in healthy subjects, p=0.032. Fasting plasma insulin was increased in patients while glucose was similar to that in healthy subjects. Patients had increased circulating inflammatory mediators. Insulin resistance was related to interleukin-6 (IL-6), r=0.276, p=0.039, and tumour necrosis factor alpha soluble receptor I, r=0.351, p=0.008. Both IL-6 and BMI were predictive variables of insulin resistance r(2)=0.288, p<0.05. We demonstrated greater insulin resistance in non-hypoxaemic patients with COPD compared with healthy subjects, which was related to systemic inflammation. This relationship may indicate a contributory factor in the excess risk of cardiovascular disease and type II diabetes in COPD.

Osteoporosis in chronic obstructive pulmonary disease.

Osteoporosis is one of the systemic effects associated with chronic obstructive pulmonary disease (COPD). Potential risk factors of osteoporosis may be due to the lifestyle, genetics, treatment with corticosteroids, endocrine abnormalities or the impairment of the body composition and peripheral skeletal muscles. Evidence for the possible contribution of such factors is reviewed. The occurrence of fractures, as a consequence of osteoporosis, can contribute to the disability and mortality of patients with COPD and add to the economic burden of the disease. The treatment with corticosteroids for the lung disease is associated with increased prevalence of fractures, but other factors may contribute. There is a remarkable paucity of interventional studies targeting the osteoporosis in patients with COPD. The results of studies on the treatment of osteoporosis in chronic lung diseases, some including small numbers of patients with COPD, are reviewed in the paper. Prospective longitudinal studies on the incidence of osteoporosis in chronic obstructive pulmonary disease need to assess patients with various degrees of disease severity and investigate the possible contribution of etiological factors. Randomised placebo-controlled trials are required to assess the effect of intervention, such as bisphosphonates, hormone replacement, calcium supplementation, on the prevention and treatment of osteoporosis and fractures in chronic obstructive pulmonary disease.

Assessment of left ventricular long axis contraction can detect early myocardial dysfunction in asymptomatic patients with severe aortic regurgitation.

OBJECTIVE: To identify variables that could be applied at rest to diagnose subclinical ventricular dysfunction in asymptomatic patients with severe aortic regurgitation. DESIGN: Cross sectional study. PATIENTS: Left ventricular long axis contraction was studied using tissue Doppler and M mode echocardiography in 21 patients with no symptoms (New York Heart Association (NYHA) functional class 40%). MAIN OUTCOME MEASURES: Left ventricular ejection fraction (LVEF) at baseline and peak exercise (Weber protocol), cardiopulmonary function, and left ventricular long axis function at rest (peak systolic velocity and excursion of the mitral annulus). RESULTS: In 11 patients, ejection fraction increased or did not change (from mean (SD) 55 (5)% to 58 (4)%, p < 0.05) (group I); in 10 patients it decreased by > 5% (from 54 (4)% to 42 (5)%, p < 0.001) (group II). Exercise ejection fraction was < 50% in all patients in group II. At rest, there were no differences between the groups in ejection fraction, left ventricular diameter indices, wall stress, and short axis contraction. However, patients in group II had reduced long axis contraction compared with group I: peak systolic velocity 8.6 (0.6) v 11.9 (2.2) cm/s (p < 0.001); excursion 11 (2) v 14 (2) mm (p < 0.01). A resting velocity of < 9.5 cm/s was the best indicator of poor exercise tolerance (sensitivity 90%, specificity 100%). CONCLUSIONS: Markers of reduced long axis contraction may provide simple and reliable indices of subclinical left ventricular dysfunction in asymptomatic patients with severe aortic regurgitation.

[The clenbuterol treatment of patients with the chronic obstructive syndrome]. / Tratamentul cu Clenbuterol al bolnavilor cu sindrom obstructiv cronic.

We have studied the effect of a new long acting bronchodilator: CLENBUTEROL, in 10 patients suffering from chronic obstructive diseases. All patients received 1 tablet of Clenbuterol, then we measured the following parameters in each patient, 2 and 6 hours after the drug administration: VC (vital capacity), FEV1 (forced expiratory volume in the first second of forced expiration), FEV1 x 100/VC, Raw (airways resistance), RV (residual volume). In all patients, excepting one of them, we registered a modification of all or some of the parameters 2 hours after drug administration. The bronchodilator effect was still present at 6 hours after drug administration. This data suggest that Clenbuterol induced a significant and long acting improvement of chronic obstruction; this drug might offer the advantage of sustained effect in patients suffering from chronic bronchospastic obstruction.

[Errors committed in using dosed aerosols in patients with obstructive lesions]. / Studiul erorilor comise în practica folosirii aerosolilor dozati la bolnavii cu afectiuni obstructive.

Errors committed in applying dosed aerosols in 100 patients were registered. Some criteria of correct technique being established, it was found out that more than 73% of the patients committed at least one error. The non-synchronization between inspiration and inhaler activation, considered as the most severe error, was met in 52% of cases, 14% of the patients being unable to do it even after repeated training. The importance of a refreshing instruction of patients, concerning the technique and advantages in using the expansion chambers and the conditioning as powders of inhaling drugs, are discussed.

Subclinical right ventricular dysfunction in cystic fibrosis. A study using tissue Doppler echocardiography.

Patients with severe cystic fibrosis can develop cor pulmonale, but little is known about the function of the right ventricle (RV) early in the disease. We hypothesized that such patients might have subclinical RV dysfunction, detectable by tissue Doppler echocardiography, and related to the severity of lung disease. We studied 21 clinically stable patients (Group 1), five patients with severe lung disease (Group 2), and 23 age-matched healthy subjects. Patients had impaired RV systolic function. The mean (SD) systolic velocities of the RV free wall were 8.9 (1.7) cm/s in Group 1, 7.7 (1.0) in Group 2, and 10.8 (1.9) in healthy subjects (p < 0.001). The velocities of the tricuspid annulus were less in patients (p < 0.0001). Patients had a greater isovolumic relaxation time (p < 0.001), indicating RV diastolic dysfunction. RV wall thickness was greater in patients (0.4 [0.1] versus 0.3 [0.1] cm/m(2), p < 0.01). RV systolic function was related to C-reactive protein (r = - 0.66, p < 0.001) and FEV(1) (r = 0.62, p = 0.003) and diastolic function to interleukin-6 (r = 0.64, p < 0.005). Patients with cystic fibrosis have subclinical RV dysfunction, which correlates with the severity of lung disease. Tissue Doppler echocardiography provides a quantifiable indicator useful for detection and monitoring of disease progression.

A short-term comparison of two methods of sputum expectoration in cystic fibrosis.

The aim of this study was to determine whether repeated maximum inspiratory vital capacity manoeuvres against a fixed resistance increased effective short-term sputum clearance in adults with cystic fibrosis (CF). Twenty adults with CF were randomised to receive, on alternate days, either standardised physiotherapy (SP) for 30 min, comprising postural drainage and the active cycle of breathing technique, or a series of resistive inspiratory manoeuvres (RIM) at 80% of their maximum sustained inspiratory pressure developed between residual volume and total lung capacity during the first 4 days of the treatment of an exacerbation of respiratory symptoms. Expectorated sputum was collected during and for 30 min after each treatment and weighed. Total protein, immunoreactive interleukin (IL)-8 and human neutrophil elastase (HNE) concentrations, and the amount of each component expectorated, were determined. Compared with SP, RIM increased sputum weight two-fold, independent of treatment order or day. The concentrations of protein, IL-8 and HNE in sputum were similar for both treatments, while the quantity expectorated was greater with RIM treatment. In conclusion, short-term resistive inspiratory manoeuvres treatment was more effective at clearing sputum and inflammatory mediators than standardised physiotherapy.

[Effectiveness of salbutamol powder (Ventodisk Glaxo) compared to dosed aerosols (sultanol)]. / Studiu privind eficacitatea salbutamolului pulbere (Ventodisk Glaxo) comparativ cu aerosolii dozati (sultanol).

The study deals with the effect of salbutamol powder (Ventodisk) administered with Diskhaler device comparatively to salbutamol dosed aerosols. The analysis of PEF variations on morning and evening in a group of patients unable to use correctly the dosed aerosols leads to the conclusion that salbutamol powder succeeds in a higher effect since the administration by Diskhaler is far easier.

Inspiratory muscle function and body composition in cystic fibrosis.

Loss of body mass, which occurs in the later stages of cystic fibrosis (CF), probably affects all body compartments. We hypothesized that loss of skeletal muscle mass would include inspiratory muscles and impair their function. To test this, we determined the effect of body mass index (BMI) and lean body mass (LBM) depletion on handgrip (HG) force and inspiratory muscle function (IMF). The maximum inspiratory pressure (MIP) and the sustained maximum inspiratory pressure (SMIP) were measured with a computerized system. The relationship of IMF and reduced BMI to survival was studied in 49 patients, and a further 25 patients were studied to define the link between IMF and LBM. LBM was assessed by anthropometry. In the survival study a BMI < 20 kg/m2 was associated with a low SMIP (p < 0.001) and reduced survival, whereas MIP was relatively preserved. In the cross-sectional study SMIP (p < 0.001), MIP (p < 0.01), and HG (p < 0.01) were all reduced in the low LBM group, but not when related to total LBM. C-reactive protein and LBM were inversely related (r = -0.71, p < 0.01). Impaired IMF was chiefly a loss of sustained muscle contraction secondary to a reduced skeletal muscle mass, which may be related to pulmonary inflammation.

Luminometric measurement of subnanomole amounts of key metabolites in extracts from isolated heart muscle cells.

In principle, luminometry allows very sensitive metabolite measurements as shown with standards in aqueous solutions (e.g., buffers). However, components of complex biological samples may largely interfere with luminometric reactions. We now describe a procedure by which subnanomole amounts of intermediary metabolites (malate, glucose 6-phosphate) can be measured by luminometry in extracts from isolated mammalian cells, namely rat heart muscle cells. Basically, measurements occur in two steps: (i) Enzymatically catalyzed reactions involving the metabolite to be measured lead to the stoichiometric production of NAD(P)H; (ii) the oxidation of this NAD(P)H in a luciferase/reductase system results in light production which is proportional to the original concentration of the metabolite. The reaction scheme is thus as follows: (1) Metabolite (malate, glucose 6-phosphate) + NAD(P)+ --> X + NAD(P)H + H+; (2) NAD(P)H + O2 + RCOH --> NAD(P)+ + RCOOH + H2O + hnu. The cardiomyocytes used are previously subjected to an ethanolic extraction in which the cellular NAD(P)H is destroyed by acidification. Subsequent evaporation of the extracts allows to neutralize and to concentrate the samples. This contributes, along with other experimental maneuvers, to increasing the sensitivity of the method. With this procedure, we were able to detect amounts of approximately 70 pmol of malate and approximately 90 pmol of glucose 6-phosphate in cardiomyocyte samples. In addition, the calculated cellular concentrations of malate and glucose 6-phosphate (101.1 +/- 4.5, and 202.8 +/- 26.1 microM, respectively, in the absence of exogenous substrate) correspond to values previously reported for heart tissue. In principle, the procedure described could be applied to the measurement of any ethanol-extractable metabolite that can be converted in reactions involving NAD(P)+.

Altered tissue distribution in adults with cystic fibrosis.

BACKGROUND: Regional body composition was determined in adults with cystic fibrosis (CF). Our hypothesis was that dual energy x ray absorptiometry (DXA) scanning could assess the fat free mass, bone mineral content, and fat mass and determine the distribution of the changes. METHOD: Height squared indices were derived for fat mass (FMI), fat free mass (FFMI), and bone mineral content (BMCI) of the arm, leg, and trunk by DXA in 51 patients and 18 age/sex matched healthy subjects. RESULTS: The arm and leg FFMI in patients were less than in healthy controls (p<0.05); the deficit was leg>arm>trunk (-18.19%, -14.86%, +0.09%, p<0.02) and was related to severity of lung disease. Patients with a normal BMI and low total FFM (hidden loss) had a lower arm, leg and trunk FFMI than those with a normal BMI and total FFM (p<0.05). The BMCI for all body segments was lower in patients than in controls (p<0.001). The BMCI was lower in the leg and trunk (p<0.01) in patients with severe disease than in those with mild lung disease. In those with hidden FFM loss the BMCI was lower (p<0.05 in leg and trunk). There was no difference in the BMCI deficit between body segments. Fat mass in patients was not reduced. CONCLUSION: Preferential loss of FFM is related to severity of lung disease and occurs in patients with a normal BMI. A similar loss of BMC occurs while FM is preserved. A hierarchical pattern of FFM loss of legs>arms>trunk was shown; BMC loss was evenly distributed.

Mobile echoes on prosthetic valves are not reproducible. Results and clinical implications of a multicentre study.

AIMS: To test the hypothesis that inter-observer variability accounts for the wide variation in reported prevalences of fibrin strands on prosthetic heart valves and to develop criteria for their identification and reporting. METHODS AND RESULTS: A videotape with 30 sequences of prosthetic heart valves imaged by transoesophageal echocardiography and showing abnormalities such as strands, microbubbles, and spontaneous echocardiographic contrast, was assessed in 13 European and three American centres. There were three duplicated examples, unbeknown to the observers. Definitions and reported prevalence rates of the abnormalities were analysed, and inter- and intra-observer agreement estimated with the kappa statistic. Mobile echoes were identified in 40 to 80% of the sequences on the tape. The reported prevalence of mobile echoes correlated with the time spent reporting the tape. There was moderate inter-observer agreement for the identification of any mobile echoes (kappa = 0.38), but no agreement for their labelling (kappa = 0.22), in spite of similar definitions. Intra-observer reproducibility was good (agreement in 76% of the reduplicated sequences). CONCLUSIONS: The true prevalence and potential significance of mobile echoes on prosthetic heart valves cannot be assessed unless inter-observer consensus on echocardiographic criteria for identifying such echoes is reached.

Bone density, body composition, and inflammatory status in cystic fibrosis.

Low body weight and loss of bone mass are major problems in adults with cystic fibrosis (CF) and chronic pulmonary infection. Although these complications probably have a multifactorial origin, we hypothesized that the continuous acute-phase inflammatory and catabolic state may contribute. We determined body composition, bone turnover, physical activity, and circulating interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and their soluble receptors in 22 adults with CF and 22 age- and sex-matched healthy subjects. Comparisons were also made within patients before and after treatment of an exacerbation of respiratory symptoms. The patients had a lower mean (95% confidence interval [CI]) fat-free mass (FFM) 39.9 (36.3, 43.6) kg than healthy subjects, 49.4 (45.1, 53.7) kg, p < 0.05. The patients were in negative nitrogen balance and 20 had bone mineral density (BMD) Z scores