Decreased Exercise Tolerance Research Articles

The Influence of Treatment with Formoterol, Formoterol with Tiotropium, Formoterol with Inhaled Glucocorticosteroid and Tiotropium on Lung Functions, Tolerance of Exercise and Simple, Morning Everyday Activities in Patients with Chronic Obstructive Pulmonary Disease (COPD)

Bronchodilators - long-acting b2-adrenergic agonists (formoterol and salmeterol) and a long-acting antimuscarinic drug (tiotropium), are the main drugs applied in symptomatic treatment of COPD. In patients with COPD, dyspnea is frequently associated with simple everyday activities. Two questionnaires have been published recently as a means of assessing the patients' ability to perform morning activities and symptoms. Dynamic hyperinflation is the pathophysiological disorder responsible for dyspnea and decreased exercise tolerance in COPD. Formoterol is faster than salmeterol in diminishing air-trapping. It has been shown that treatment with formoterol and tiotropium in COPD patients improves FEV(1), FVC, IC, symptoms score and quality of life in comparison with tiotropium applied alone. Among LABA and inhaled glucocorticosteroids combinations, those containing formoterol have a more beneficial effect on the ability to perform simple morning activities (budesonide/formoterol was better than fluticasone/salmeterol). Beclomethasone/formoterol - 400/24 mcg/die, in comparison with fluticasone/salmeterol - 500/100 mcg/die significantly reduced air-trapping and dyspnea in COPD patients. The comparison of budesonide/formoterol - 400/12 mcg 2 x die with beclomethasone/ /formoterol - 200/12 mcg 2 x die has shown similar influence of both combinations on FEV(1), dyspnea, 6-minute walk test, symptoms score and quality of life. The addition of budesonide and formoterol combination to tiotropium gives further benefits: reduces number of exacerbations, improves FEV1, symptoms score and performance of simple morning routines. Doctors should pay more attention to symptoms and limitations in simple activities in the morning and adequately adjust the treatment.

Right ventricular long-axis response to different chronic loading conditions: Its relevance to clinical symptoms

BackgroundThe intervention timing in atrial septal defect (ASD) or pulmonary valvular stenosis (PVS) is more dependent on symptoms than right ventricular (RV) damage in clinical practice. RV long-axis function is sensitive in revealing RV myocardial dysfunction. We evaluate the impact of different chronic loading conditions on RV long-axis function and its relationship to patients' symptoms in ASD or PVS. MethodsTransthoracic echocardiography was performed in normals (n=39) and patients with isolated secundum ASD (n=45) or PVS (n=38). RV volume- and pressure-overloading were defined as the ratio of RV/left ventricular end-diastolic dimension ≥0.5 and RV systolic pressure ≥40mmHg, respectively. RV long-axis dysfunction was defined as M-mode tricuspid annular plane systolic excursion (TAPSE) <1.6cm. New York Heart Association (NYHA) functional class and other symptoms (decreased exercise tolerance, palpitation and chest pain) were recorded. ResultsThirty-nine (32.0%) had normal loading (Group 1; 39 normals); 24 (19.6%) had isolated volume-overloading (Group 2; all ASDs); 21 (17.2%) had isolated pressure-overloading (Group 3; 21 PVSs) and 38 (31.1%) had both overloading conditions (Group 4; 21 ASDs and 17 PVSs). RV long-axis dysfunction in abnormal loading groups were zero (0%, Group 2), 21 (100%, Group 3) and 22 (57.8%, Group 4) (χ2=45.9, p<0.001). Group 3 were more symptomatic (NYHA functional class 2.5±0.6 versus 1.6±0.5, p<0.05) and had lower TAPSE (1.6±0.4 versus 3.0±0.7cm, p<0.05) than Group 2. RV long-axis dysfunction was the strongest predictor of the presence of symptoms (odds ratio=9.298, p<0.001). ConclusionChronic volume-overloading accentuates while pressure-overloading attenuates RV long-axis excursion and its impairment was associated with the presence of symptoms.

Prevalence of renal dysfunction and its influence on functional capacity in elderly patients with stable chronic heart failure

Chronic heart failure (CHF) is highly prevalent and constitutes an important public health problem around the world. In spite of a large number of pharmacological agents that successfully decrease mortality in CHF, the effects on exercise tolerance and quality of life are modest. Renal dysfunction is extremely common in patients with CHF and it is strongly related not only to increased mortality and morbidity but to a significant decrease in exercise tolerance, as well. The aim of our study was to investigate the prevalence and influence of the renal dysfunction on functional capacity in the elderly CHF patients. We included 127 patients aged over 65 years in a stable phase of CHF. The diagnosis of heart failure was based on the latest diagnostic principles of the European Society of Cardiology. The estimated glomerular filtration rate (eGRF) was determined by the abbreviated modification of diet in renal disease (MDRD2) formula, and patients were categorized using the kidney disease outcomes quality initiative (K/DOQI) classification system. Functional capacity was determined by the 6 minute walking test (6MWT). Among 127 patients, 90 were men. The average age was 72.5 +/- 4.99 years and left ventricular ejection fraction (LVEF) was 40.22 +/- 9.89%. The average duration of CHF was 3.79 +/- 4.84 years. Ninty three (73.2%) patients were in New York Heart Association (NYHA) class II and 34 (26.8%) in NYHA class III. Normal renal function (eGFR > or = 90 mL/min) had 8.9% of participants, 57.8% had eGFR between 60-89 mL/min (stage 2 or mild reduction in GFR according to K/DOQI classification), 32.2% had eGFR between 30-59 mL/min (stage 3 or moderate reduction in GFR) and 1.1% had eGFR between 15-29 mL/min (stage 4 or severe reduction in GFR). We found statistically significant correlation between eGFR and 6 minute walking distance (6MWD) (r = 0.390, p < 0.001), LVEF (r = 0.268, p < 0.05), NYHA class (p = -0.269, p < 0.05) and age (r = 0.214, p < 0.05). In multiple regression analysis only patients' age was a predictor of decreased 6MWD < 300 m (OR = 0.8736, CI = 0.7804 - 0.9781, p < 0.05). Renal dysfunction is highly prevalent in the elderly CHF patients. It is associated with decreased functional capacity and therefore with poor prognosis. This study corroborates the use of eGFR not only as a powerful predictor of mortality in CHF, but also as an indicator of the functional capacity of cardiopulmonary system. However, clinicians underestimate a serial measurement of eGFR while it should be the part of a routine evaluation performed in every patient with CHF, particularly in the elderly population.

Carbamazepine-induced interstitial pneumonitis associated with pan-hypogammaglobulinemia

Carbamazepine remains a first-line drug for treatment of epilepsy in children. A wide variety of side effects have been attributed to its use, including a mild involvement of the immune system, usually a transient decline in IgA. Pulmonary complications, including interstitial pneumonitis, were mainly described in adults, and are considered rare side effects. In this report we describe the first pediatric patient who developed a severe interstitial pneumonitis and a pan-hypogammaglobulinemia 2 months after starting carbamazepine. A gradual resolution of symptoms and complete immune recovery was observed after the drug withdrawal, but 6 months later our patient still has a marked reduction in lung volumes and decreased exercise tolerance. We suggest that immunoglobulins should be carefully examined after carbamazepine initiation, particularly if the patient develops any sign of immunosuppression.

Adolescent with Unfeasible Body Mass Index: A Risk Factor for Iron Deficiency Anemia

Iron deficiency anemia (IDA) is the most common disease in developing countries. It is a major health problem in the general population particularly in infants, pregnant women, pre-adolescents and adolescents. Overweight and underweight are common nutrition disorders of adolescents in southwest Iran. IDA has been associated with behavioural disturbances, growth and puberty delay, impaired cognitive functions and decreased exercise tolerance. The Study of IDA and weight parameters among adolescents in southwest Iran may appear to be of significance. Thus, this study aims to assess the prevalence of IDA among adolescents and also intends to evaluate the impact of body mass index (BMI) on iron deficient groups. A total of five hundred adolescents (240 boys and 260 girls) were enrolled in the study. Three millilitres of blood was obtained from each participant. Cell Blood Count (CBC) and ferritin were measured for everyone. A reliable scale and a standing height measuring device were selected for determining of BMI. Out of them 23 (4.6%) cases had IDA. The prevalence of IDA was not significant by gender and age (P: 0.194 and P: 0.225); however, the peak incidence of IDA was thirteen years old. Out of the five hundred subjects 91 individuals (18.2%) had abnormal BMI. Subjects with abnormal BMI envisage more IDA than individuals with normal BMI (p: 0.001).Conclusively, the prevalence of IDA among adolescents is 4.6% in southwest Iran. Unfeasible BMI is a risk factor for IDA developing in adolescents’ period.

Perioperative Lung Protective Strategies

Perioperative Lung Protective Strategies

Inflammation in Overuse Tendon Injuries

Overuse tendon injuries present with pain and swelling of the affected tendon with associated decrease in exercise tolerance and function of the limb. After early inflammatory and degenerative hypotheses, the term "tendinopathy" is now deemed a more appropriate reflection of the mixed histopathological picture seen in operative biopsies from affected patients. The condition presents histopathological evidence of "failed healing response," but its etiology remains unclear. The incidence of tendinopathy is increased in individuals with obesity and decreased insulin sensitivity (as seen in type 1 and type 2 diabetes mellitus). These groups of patients also exhibit an increased risk of developing a state of chronic low-grade, systemic inflammation. This paper considers the theoretical bases to discuss whether these conditions may predispose to the development of tendinopathy and the implication that such a relationship may have on its management.

Cardiac Amyloidosis

Case presentation: A 55-year-old woman, who had previously been very physically active, noted a gradual decrease in exercise tolerance over a period of 3 to 4 months to the extent that she had to rest briefly after climbing a single flight of stairs. She had consulted a dermatologist 6 months earlier because of recurrent, small bruises of her eyelids, but no cause had been found. An ECG suggested an old myocardial infarction with an unusual axis (Figure 1), and a cardiology consultation described symmetrical left ventricular hypertrophy on the echocardiogram with normal left ventricular ejection fraction, normally functioning valves, and mild right ventricular hypertrophy. There was no family history of cardiovascular or neurological disease. Physical examination revealed mild elevation of the jugular venous pressure, normal heart sounds, no murmurs, and mild peripheral edema with clear lung fields and a mildly congested liver. Blood pressure was 110/65 mm Hg. There was 1+ proteinuria. Serum protein electrophoresis revealed no abnormal bands, but serum immunofixation revealed a monoclonal spike determined to be IgGλ. A bone marrow biopsy demonstrated 5% to 10% monotypical plasma cells staining for λ light chains. Serum-free light chains showed an elevation in free λ with an abnormal κ/λ ratio. Brain natriuretic peptide was 1019 pg/mL (normal <100), and troponin I was 0.07 ng/mL (normal <0.01). Endomyocardial biopsy (Figure 2) showed extracellular amorphous material that stained with Congo red and sulfated Alcian blue and that, on immunohistochemistry, reacted with antibodies to λ light chains but not to κ, AA, or transthyretin antibodies. A diagnosis of IgGλ light chain AL amyloidosis was made. Figure 1. ECG from the case described. There is borderline low limb-lead voltage with extreme right axis deviation. Atrial premature beats are present, and the chest leads, although typically showing preserved voltage, demonstrate very poor R-wave progression, …

Effects of dead space loading on neuro-muscular and neuro-ventilatory coupling of the respiratory system during exercise in healthy adults: Implications for dyspnea and exercise tolerance

We examined the effects of dead space loading (DSL) on ventilation (V˙E), neural respiratory drive (EMGdi%max, diaphragm EMG expressed as a % of maximal EMGdi), contractile respiratory muscle effort (Pes,tidal%P(Imax), tidal esophageal pressure swing expressed as a % of maximal inspiratory Pes) and exertional dyspnea intensity ratings in 11 healthy adults with normal spirometry. Subjects completed, in random order, symptom-limited incremental cycle exercise tests under control (CTRL) and DSL (500 ml) conditions. Compared with CTRL, DSL decreased exercise tolerance by 20-25%; increased exertional dyspnea intensity ratings in direct proportion to concurrent increases in EMGdi%max, Pes,tidal%P(Imax) and V˙E; and had little/no effect on the inter-relationships between EMGdi%max, Pes,tidal%P(Imax) and V˙E during exercise. In conclusion, DSL was associated with an earlier onset of intolerable dyspnea; however, neuro-muscular and neuro-ventilatory coupling of the respiratory system remained relatively preserved during exercise in the presence of an increased external dead space. Under these circumstances, DSL-induced increases in exertional dyspnea intensity ratings reflected, at least in part, the awareness of increased neural respiratory drive, contractile respiratory muscle effort and ventilatory output.

Rehabilitation and acute exacerbations

Recent evidence indicates that acute exacerbations of chronic obstructive pulmonary disease aggravate the extrapulmonary consequences of the disease. Skeletal muscle dysfunction, a sustained decrease in exercise tolerance, enhanced symptoms of depression and fatigue are reported. Avoidance of physical activities is likely to be a key underlying mechanism and increases the risk of new exacerbations. Pulmonary rehabilitation is an intervention targeting these systemic consequences. Exercise strategies need to be adapted to the increased feelings of dyspnoea and fatigue. This review aims to describe the systemic consequences of acute exacerbations and compiles evidence for the feasibility and effectiveness of different rehabilitation strategies to counteract these consequences during and/or immediately after the acute phase of the exacerbation. Resistance training and neuromuscular electrical stimulation have been applied safely in frail, hospitalised patients and have the potential to prevent muscle atrophy. Comprehensive pulmonary rehabilitation, including general exercise training, can be implemented immediately after the exacerbation, leading to a reduction in hospital admissions and an increase in exercise tolerance and quality of life. Self-management strategies play a crucial role in changing disease-related health behaviour and preventing hospital admissions.

Relationship between leg muscle capillary density and peak hyperemic blood flow with endurance capacity in peripheral artery disease

The aim of this study was to determine if skeletal muscle capillary density is lower in patients with peripheral artery disease (PAD) and if capillary density relates to functional limitations. PAD patients with intermittent claudication (IC) have a decreased exercise tolerance due to exercise-induced muscle ischemia. Despite the apparent role diminished arterial flow has in this population, the degree of walking pain and functional limitation is not entirely explained by altered hemodynamics of the affected limbs. We hypothesized that skeletal muscle capillary density is lower in PAD and is related to the functional impairment observed in this population. Sixty-four patients with PAD and 56 controls underwent cardiopulmonary exercise testing and a gastrocnemius muscle biopsy. A subset of these patients (48 PAD and 47 controls) underwent peak hyperemic flow testing via plethysmography. Capillary density in PAD patients was lower compared with controls (P < 0.001). After adjustment for several baseline demographic imbalances the model relating capillary density to peak oxygen consumption (Vo(2)) remained significant (P < 0.001). In PAD subjects, capillary density correlated with peak Vo(2), peak walking time (PWT), and claudication onset time (COT). Peak hyperemic blood flow related to peak Vo(2) in both PAD and control subjects. PAD is associated with lower capillary density, and capillary density is related to the functional impairment as defined by a reduced peak Vo(2), PWT, and COT. These findings suggest that alterations in microcirculation may contribute to functional impairment capacity in PAD.

What provokes experienced COPD clinical practitioners in the UK to initiate or change medication? A consensus study

In the absence of clarity in national guidelines, this study aimed to reach a consensus among experts in chronic obstructive pulmonary disease (COPD) regarding when medication should be initiated or changed in patients demonstrating a gradual decline. An electronic three-stage Delphi exercise was undertaken with 37 leading UK experts in COPD. The panel submitted criteria which they scored in subsequent rounds. Consensus was defined as ≥ 80% of the panel scoring an item as important. Consensus was reached on seven criteria: decreased exercise tolerance (97%); increased breathlessness at rest or on exertion (97%); quality of life impairment (91%); low or reduced oxygen saturations based on pulse oximetry readings (86%); ability to perform activities of daily living independently (85%); increase in sputum (80%); and increase in wheeze (80%). These criteria could be used to guide clinical practice. Empirical research is now required to test their reliability and validity.

Fenestrated ASD Closure in a Child with Idiopathic Pulmonary Hypertension and Exercise Desaturation

Pulmonary arterial hypertension is a progressive disorder that may result in right heart failure and death. Atrial level shunts in the presence of pulmonary hypertension may allow right-to-left mixing with maintenance of cardiac output and improved survival. However, excessive mixing at the atrial level can cause undue systemic desaturation, increased fatigue and decreased exercise tolerance even in the presence of adequate cardiac output. A 5½-year-old was diagnosed with pulmonary hypertension, a large atrial septal defect and right-to-left shunting. Medical therapy over an 18-month period was successful in decreasing pulmonary artery pressure and pulmonary vascular resistance. However, because of the size and position of the intracardiac defect, symptoms of fatigue, and severe systemic desaturation with only minor activities persisted. Fenestrated surgical closure of the defect was thus undertaken to decrease the degree of atrial mixing, but still allow atrial decompression if necessary. Subsequent hemodynamic evaluation has demonstrated continued improvement, and all previous symptoms have resolved. Repeated echocardiography has confirmed patency of the atrial fenestration with left-to-right atrial flow.

A Silent Patent Ductus Arteriosus

A 4-mm patent ductus arteriosus (PDA) was serendipitously diagnosed during intraoperative transesophageal echocardiography for a noncardiac procedure in an obese adult patient with a history of decreased exercise tolerance and dyspnea, despite a negative preoperative transthoracic examination. This uncommon event poses questions regarding the relevance of this finding to the differential diagnosis of dyspnea in an obese adult with a negative transthoracic echocardiography study, given the unknown prevalence of this pathology and the absence of consensus regarding the clinical management.

Hepatocellular Carcinoma with IVC and Right Atrium Extension

Purpose: Hepatocellular carcinoma (HCC) is the fifth most common malignancy of the world. Most cases are diagnosed at an advanced stage, with metastasis to the lungs, peritoneum, adrenal glands and bones. Tumor extension to the heart via Inferior vena cava is most frequently implicated in primaries from renal cell, thyroid and testicular carcinomas and rarely in HCC. This report describes an unusual case of HCC with tumor thrombus extension to right atrium. Case Report: 64-year-old man with history of alcoholism, chronic hepatitis C presented with 2 week history of abdominal distention, leg swelling and decrease in exercise tolerance. Examination was significant for cachexia with bilateral leg, scrotal edema and ascites. Labs were significant for AST 279, ALT 62, ALP 146 and total bilirubin of 3.5 with Albumin of 1.6 and protein 8.9. Alpha feto protein was elevated to 19,282. Magnetic resonance imaging showed confluent tumor involving right hepatic lobe consistent with HCC with tumor thrombus extending into the right hepatic vein, inferior vena cava and right atrium. Discussion: Extra hepatic spread at the time of diagnosis of HCC is found in 10% cases. The most common sites being lung, intraabdominal lymph nodes, bone and adrenals. Few cases with tumor extension to the heart have been reported. These patients usually die because of pulmonary embolism, heart failure or cancer progression. Diagnosis of tumor thrombus extension should be considered in patients with HCC presenting with symptoms suggestive of CHF or pulmonary embolism. Different treatment modalities like surgical resection, transarterial chemo embolization or resection and external beam radiation therapy (EBRT) are being used with varied success and should be considered.Figure: MRI scan (contrast enhanced T1-weighted, coronal view).Figure: MRI scan (T2-weighted, axial view) IVC tumor thrombus.

Primary pleural epithelioid hemangioendothelioma (EHE) – two cases and review of the literature

We present two cases with symptoms of progressively worsening cough, dyspnea, decreased exercise tolerance and right-sided back pain in the first case and upper respiratory symptoms characterized by cough and a low grade fever in the second case. Report of two cases. The initial chest X-ray in both the cases showed pleural effusion. Further imaging with computed tomography of the chest confirmed the effusion in both cases. Thoracentesis was done in both of them revealed an exudative effusion that did not reveal any infection or malignancy. Both cases underwent surgical biopsy and the diagnosis of primary pleural epithelioid hemangioendothelioma was made. Both the cases had progressive clinical deterioration despite chemotherapy with Taxol and Bevacizumab in one case and carboplatin, etoposide, and bevacizumab, in the second case. Both developed metastatic disease to lungs and died.

Alterations in the muscle-to-capillary interface in patients with different degrees of chronic obstructive pulmonary disease

BackgroundIt is hypothesized that decreased capillarization of limb skeletal muscle is implicated in the decreased exercise tolerance in COPD patients. We have recently demonstrated decreased number of capillaries per muscle fibre (CAF) but no changes in CAF in relation to fibre area (CAFA), which is based on the diffusion distance between the capillary and muscle fibre. The aim of the current study is to investigate the muscle-to-capillary interface which is an important factor involved in oxygen supply to the muscle that has previously been suggested to be a more sensitive marker for changes in the capillary bed compared to CAF and CAFA.Methods23 COPD patients and 12 age-matched healthy subjects participated in the study. Muscle-to-capillary interface was assessed in muscle biopsies from the tibialis anterior muscle using the following parameters:1) The capillary-to-fibre ratio (C:Fi) which is defined as the sum of the fractional contributions of all capillary contacts around the fibre2) The ratio between C:Fi and the fibre perimeter (CFPE-index)3) The ratio between length of capillary and fibre perimeter (LC/PF) which is also referred to as the index of tortuosity.Exercise capacity was determined using the 6-min walking test.ResultsA positive correlation was found between CFPE-index and ascending disease severity with CFPE-index for type I fibres being significantly lower in patients with moderate and severe COPD. Furthermore, a positive correlation was observed between exercise capacity and CFPE-index for both type I and type IIa fibres.ConclusionIt can be concluded that the muscle-to-capillary interface is disturbed in the tibialis anterior muscle in patients with COPD and that interface is strongly correlated to increased disease severity and to decreased exercise capacity in this patient group.

Lung Volume Reduction Surgery and Lung Volume Reduction in Advanced Emphysema: Who and Why?

Emphysema is a disabling and progressive disease that is hallmarked by decreased exercise tolerance and impaired quality of life. Hyperinflation is the sentinel physiological characteristic of emphysema that has been shown to be responsible for exercise intolerance, dyspnea, impaired quality of life, and mortality. Surgical interventions that reduce lung volume have been the focus of multiple proposed interventions over the past century; however, evidence documenting their effectiveness has been lacking. Recently, lung volume reduction surgery (LVRS) has undergone rigorous study in the National Emphysema Treatment Trial (NETT) that documented its short and long-term effectiveness, associated morbidity and mortality, and essential characteristics that predict success or failure. Additional recent investigation has examined the use of less invasive techniques, predominantly bronchoscopic techniques that reduce lung volume without open thoracotomy. This article summarizes the major results of the NETT and briefly reviews some preliminary results of studies examining new techniques of bronchoscopic lung volume reduction.

Training Effects on Skeletal Muscle Calcium Handling in Human Chronic Heart Failure

Patients with chronic heart failure (CHF) typically complain about skeletal muscle fatigue. In rat experiments, reduced intracellular calcium release seems to be related to fatigue development in normal skeletal muscle but not in muscle from rats with CHF. We therefore hypothesize that training may not improve intracellular calcium cycling to the same extent in muscles from patients with CHF compared with healthy controls (HC). Thirteen HC and 11 CHF patients performed 6 wk of unilateral knee extensor endurance training. Computed tomographic examinations of the thigh and biopsies of vastus lateralis were obtained bilaterally before and after the training period. Peak power of the trained leg was 10% and 14% greater than that in the untrained leg in HC and CHF, respectively. For the HC, training resulted in a higher Ca2+ release rate and a lower leak in the trained leg associated with a tendency of increased ryanodine receptor (RyR) content with reduced phosphorylation level. In the trained leg of CHF patients, RyR content was reduced without associated changes of either Ca2+ leak or release rate. Training in HC has an effect on Ca2+ leak and release of the sarcoplasmic reticulum, but in CHF patients, training is achieved without such changes. Thus, calcium handling seems not to be the site of decreased exercise tolerance in CHF.

Bioprosthetic mitral valve thrombosis less than one year after replacement and an ablative MAZE procedure: a case report

Occurrence of bioprosthetic valve thrombosis less than a year after replacement is very uncommon. Here, we describe a case of a 57 year old male, who presented 10 months after receiving a bioprosthetic mitral valve replacement with a two week history of dyspnea on exertion, worsening orthopnea and decreased exercise tolerance. Echocardiography revealed severe mitral regurgitation (MR), thrombosis of the posterior mitral leaflet, left atrial (LA) mural thrombus and a depressed left ventricular ejection fraction of twenty-five percent. Given severe clot burden and decompensated heart failure (New York Heart Association - NYHA class III) repeat sternotomy was done to replace the bioprosthetic mitral valve and remove LA mural thrombus. MR was resolved postoperatively. This brief report further reviews promoting factors, established guidelines and management strategies of bioprosthetic valve thrombosis.