Effect of uremia and its treatment on pulmonary function

Alterations in respiratory drive, mechanics, muscle function, and gas exchange are frequent if not invariable consequences of uremia. Pulmonary dysfunction may be the direct result of circulating uremic toxins or may result indirectly from volume overload, anemia, immune suppression, extraosseous calcification, malnutrition, electrolyte disorders, and/or acidbase imbalances. The pulmonary system is unique because it is affected by the disease and its treatment. Acetate hemodialysis reduces alveolar ventilation and PaO2 due to extrapulmonic CO2 unloading. Peritoneal dialysis increases alveolar ventilation and intraperitoneal pressure. The latter leads to an elevated and lengthened diaphragm, a reduced functional residual capacity, basilar atelectasis, possible hypoxemia, and altered respiratory muscle function. In patients on chronic peritoneal dialysis, adaptations may occur that limit the reductions in lung volumes, PaO2, and respiratory muscle strength that are often observed during acute peritoneal dialysis. This review details how uremia and dialysis interact to alter pulmonary function.     

Work of breathing and respiratory drive in obesity

Obesity, particularly severe central obesity, affects respiratory physiology both at rest and during exercise. Reductions in expiratory reserve volume, functional residual capacity, respiratory system compliance and impaired respiratory system mechanics produce a restrictive ventilatory defect. Low functional residual capacity and reductions in expiratory reserve volume increase the risk of expiratory flow limitation and airway closure during quiet breathing. Consequently, obesity may cause expiratory flow limitation and the development of intrinsic positive end expiratory pressure, especially in the supine position. This increases the work of breathing by imposing a threshold load on the respiratory muscles leading to dyspnoea. Marked reductions in expiratory reserve volume may lead to ventilation distribution abnormalities, with closure of airways in the dependent zones of the lungs, inducing ventilation perfusion mismatch and gas exchange abnormalities. Obesity may also impair upper airway mechanical function and neuromuscular strength, and increase oxygen consumption, which in turn, increase the work of breathing and impair ventilatory drive. The combination of ventilatory impairment, excess CO(2) production and reduced ventilatory drive predisposes obese individuals to obesity hypoventilation syndrome.     

Relation between pulmonary ventilation parameters,exercise tolerance and quality of life in patients with chronic obstructive lung disease

Patients with chronic obstructive pulmonary disease (COPD) do usually have decreased tolerance of exercise capacity and impaired quality of life. Several studies have shown that exercise capacity is related relatively weakly to lung functions in this group of patients. The aim of the present study was to find parameter which could better reflect or predict maximal exercise capacity. 19 patients with the diagnosis COPD with mean value of forced expiratory volume in one second (FEV1) 46% predicted (range 21-79%) entering pulmonary rehabilitation program were included into the study. Enrolled patients were chosen to cover the whole range of airway obstruction severity. Post-bronchodilator static and dynamic ventilation parameters were used for evaluation and calculation. Quality of live was measured using St. George's respiratory questionnaire (SGRQ), evaluating symptoms, activity and impact of the disease with range from 0 (the best level) to 100 (the worst level). Values of FEV1 (p < 0.001) and ratio of FEV1 to vital capacity (FEV1/VC, p < 0.001) were significantly positively correlated with 6 minute walking distance (6MWD). FEV1/VC were closely related to 6MWD then FEV1. The degree of hyperinflation expressed by residual volume (RV, p < 0.005) and by ratio of residual volume to total lung capacity (RV/TLC, p < 0.001) significantly negatively correlated with 6MWD. Maximal occlusion mouth pressures (PImax, p < 0.05) were positively related to 6MWD. Total score of SGRQ correlated significantly to maximal exercise capacity. Pulmonary function tests and respiratory muscle function have important impact on exercise tolerance in patients with COPD. Tolerance of exercise capacity is significantly reflected by total score of quality of life in this group of patients.     

Effect of salmeterol on the ventilatory response to exercise in chronic obstructive pulmonary disease.

This study examined the effects of bronchodilator-induced reductions in lung hyperinflation on breathing pattern, ventilation and dyspnoea during exercise in chronic obstructive pulmonary disease (COPD). Quantitative tidal flow/volume loop analysis was used to evaluate abnormalities in dynamic ventilatory mechanics and their manipulation by a bronchodilator. In a randomised double-blind crossover study, 23 patients with COPD (mean +/- SEM forced expiratory volume in one second 42 +/- 3% of the predicted value) inhaled salmeterol 50 microg or placebo twice daily for 2 weeks each. After each treatment period, 2 h after dose, patients performed pulmonary function tests and symptom-limited cycle exercise at 75% of their maximal work-rate. After salmeterol versus placebo at rest, volume-corrected maximal expiratory flow rates increased by 175 +/- 52%, inspiratory capacity (IC) increased by 11 +/- 2% pred and functional residual capacity decreased by 11 +/- 3% pred. At a standardised time during exercise, salmeterol increased IC, tidal volume (VT), mean inspiratory and expiratory flows, ventilation, oxygen uptake (VO2) and carbon dioxide output. Salmeterol increased peak exercise endurance, VO2 and ventilation by 58 +/- 19, 8 +/- 3 and 12 +/- 3%, respectively. Improvements in peak VO2 correlated best with increases in peak VT; increases in peak VT and resting IC were interrelated. The reduction in dyspnoea ratings at a standardised time correlated with the increased VT. Mechanical factors play an important role in shaping the ventilatory response to exercise in chronic obstructive pulmonary disease. Bronchodilator-induced lung deflation reduced mechanical restriction, increased ventilatory capacity and decreased respiratory discomfort, thereby increasing exercise endurance.     

Ventilatory control in patients with hypoxemia due to obstructive lung disease.

In 20 patients with chronic hypoxemia due to chronic obstructive pulmonary disease, we measured responses to CO2 and hypoxia in terms of ventilation and P0.1, the pressure generated by the respiratory muscles during the first 0.1 s of inspiratory effort against a closed airway at functional residual capacity. These responses were compared to those of a control group of 17 patients with similar ventilatory abnormality but without hypoxemia. Hypoxemic patients demonstrated significantly less response to hypoxia than did control subjects in terms of both ventilation and P0.1 The decreased hypoxic response might be analogous to that reported in high altitude dwellers and patients with cyanotic congenital heart disease. Ventilatory responses to CO2 were depressed in hypoxemic patients, but P0.1 responses were not significantly decreased. While breathing at rest with arterial O2 saturation of 95 per cent, hypoxemic patients demonstrated the same minute ventilation as control subjects, but tidal volume was smaller, inspiratory duration was shorter, and breathing frequency was slightly higher. This breathing pattern appeared to be independent of whether or not these patients retained CO2.     

Sleep in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death, affecting 14 million adults in the United States. Symptoms related to sleep disturbances are common in moderate to severe COPD, particularly in elderly patients, in the form of morning tiredness and early awakenings. One major cause of morbidity in this population is abnormalities in gas exchange and resultant hypoxemia. Sleep has profound adverse effects on respiration and gas exchange in patients with COPD. There are several mechanisms underlying nonapneic oxygen desaturation during sleep. They include decreased functional residual capacity, diminished ventilatory responses to hypoxia and hypercapnia, impaired respiratory mechanical effectiveness, diminished arousal responses, respiratory muscle fatigue, diminished nonchemical respiratory drive, increased upper airway resistance, and the position of baseline saturation values on the oxyhemoglobin dissociation curve. Smoking cessation, bronchodilation, and pulmonary rehabilitation are cornerstones of treatment of COPD. Improvement in lung mechanics and gas exchange should lead to better sleep quality and health status.     

Ventilatory markers during exercise for congestive heart failure

The exaggerated ventilatory response in patients with heart failure is clearly multifactorial and complex beyond a mere reduction in pulmonary blood flow. Pulmonary dysfunction, including ventilation-perfusion mismatching, decreased lung compliance, restriction, airway obstruction, decreased diffusion capacity, and decreases in respiratory muscle strength and endurance, contributes to an inefficient breathing pattern and increased work of breathing. This is further compounded by the limited ability of the failing heart to meet the metabolic demands of the respiratory muscles, leading to underperfusion and ischemia.Although VO2max has important implications with regard to functional capacity, exercise test personnel must be knowledgeable concerning the clinical physiology of ventilation during exercise in the patient with heart failure. Ventilatory markers, as Arena and coworkers have demonstrated, are most indicative of disease severity and enhance the prognostic value of the test results.     

Ergospirometry after repair of Fallot's tetralogy

Ergospirometry was performed in 19 children and adolescents operated for tetralogy of Fallot (TOF) to assess their exercise capacity compared to an active non sportive control group. The test was carried out on a treadmill with measurement of oxygen consumption cycle by cycle throughout exercise. In comparison with the control group, the patients had: a working capacity which was normal or reduced by 30 to 40 p. 100; a decrease d'oxygen consumption (-30 to 40 p. 100) throughout exercise and at maximal effort: this corresponds to a lower stroke volume secondary to the absence of physical activity during childhood and/or residual cardiac lesions; abnormal chronotropism: the test was stopped at a lower heart rate corresponding to a fall in oxygen uptake during exercise, or to an increase in the systolic ejection period probably due to right ventricular dysfunction or to the patient reaching maximal ventilation; decreased maximal ventilation capacity due to a lower tidal volume and a higher respiratory rate. This type of ventilation increases to role of the dead space and may be related to progressive "pulmonary dysfunction" or secondary to residual cardiac lesions. These different parameters cannot be assessed by simple ergospirometry: the test must be coupled with an evaluation of ventilatory function on effort in order to control and evaluate the long term functional results and the aptitude of these patients to regular physical activity.     

Effect of inhaled anticholinergic drug on pulmonary function and quality of life in elderly patients with chronic obstructive pulmonary disease

Effects of inhaled anticholinergic drug on the physiological function of the respiratory system and quality of life (QOL) in elderly patients with chronic obstructive pulmonary disease (COPD) have not been fully elucidated. We examined the pulmonary function, static respiratory pressures, and ventilation during exercise, before and after inhalation of oxitropium bromide (OTB) in 12 male patients with COPD (mean age 82.1 +/- 0.6 years). QOL was measured with a St George's Respiratory Questionnaire (SGRQ) in the patients. Forced expiratory volume in one second was increased by the inhalation of OTB in the patients, whereas the ratio of residual volume to total lung capacity was decreased by the inhalation. Maximum inspiratory pressure was significantly increased after the administration of OTB. Dyspnea sensation during exercise measured on the Borg scale was reduced by the inhalation of OTB. The scores of SGRQ were improved by one-month treatment with OTB. These results suggest that the treatment with OTB are effective for both physiological function and several aspects of QOL in elderly patients with COPD.     

Hypoxemia and hypercapnia during exercise and sleep in patients with cystic fibrosis.

BACKGROUND: In patients with cystic fibrosis (CF), it has been proposed that hypoxemia and hypercapnia occur during episodes of stress, such as exercise and sleep, and that respiratory muscle weakness because of malnutrition may be responsible. METHODS: Pulmonary function, respiratory muscle strength, and nutrition were assessed and correlated with the degree of hypoxemia and hypercapnia during exercise and sleep in 14 patients with CF and 8 control subjects. RESULTS: Despite no differences in maximum static inspiratory pressure (PImax) between the two groups, the CF group developed more severe hypoxemia (minimum oxyhemoglobin saturation [SpO2], 89 +/- 5% vs 96 +/- 2%; p < 0.001) and hypercapnia (maximum transcutaneous CO2 tension [PtcCO2], 43 +/- 6 vs 33 +/- 7 mm Hg; p < 0.01) during exercise. Similarly, during sleep, the CF group developed greater hypoxemia (minimum SpO2, 82 +/- 8% vs 91 +/- 2%; p < 0.005), although CO2 levels were not significantly different (maximum PtcCO2, 48 +/- 7 vs 50 +/- 2 mm Hg). Within the CF group, exercise-related hypoxemia and hypercapnia did not correlate with FEV1, residual volume/total lung capacity ratio (RV/TLC), PImax, or body mass index (BMI). Hypoxemia and hypercapnia during sleep correlated with markers of gas trapping (RV vs minimum arterial oxygen saturation [r = -0.654; p < 0.05]), RV vs maximum PtcCO2 (r = 0.878; p < 0.001), and RV/TLC vs maximum PtcCO2 (r = 0.790; p < 0.01) but not with PImax or BMI. CONCLUSION: Patients with moderately severe CF develop hypoxemia and hypercapnia during exercise and sleep to a greater extent than healthy subjects with similar respiratory muscle strength and nutritional status. Neither respiratory muscle weakness nor malnutrition are necessary to develop hypoxemia or hypercapnia during exercise or sleep.     

Effect of sustained release of theophylline on pulmonary physiologic function in elderly patients with chronic obstructive pulmonary disease

We tested the effects of the sustained release of theophylline on the physiologic function of the respiratory system in elderly patients with chronic obstructive pulmonary disease (COPD). We measured the pulmonary function, static respiratory pressures, and ventilation during exercise, before and after the administration of sustained release of theophylline. Unifil, in 12 male COPD patients (mean age 82.1 +/- 0.6 years old). Forced expiratory volume in one second was increased by the administration of 400 mg of Unifil, but not by 200 mg of Unifil, whereas the ratio of residual volume to total lung capacity was decreased by the administration of 400 mg Unifil. Maximum inspiratory pressure was significantly increased after the administration of 400 mg of Unifil. Dyspnea sensation during exercise assessed by the Borg scale was reduced by the administration of 400 mg of Unifil. These results indicate that the treatment with the greater dosage administration of Unifil is effective to improve the physiological function of the respiratory system in elderly patients with COPD, and it may be the treatment of choice for elderly COPD patients.     

The effect of non-invasive mechanical ventilation in postoperative respiratory failure

Postoperative respiratory failure is related with the highest mortality and morbidity among all perioperative complications. The most common underlying mechanism of postoperative respiratory failure is the development of atelectasis. Anaesthesia, medications which cause respiratory depression, high FiO2 use, postoperative pain and disruption of muscle forces due to surgery leads to decrease in functional residual capacity and results in atelectasis formation. Atelectasis causes severe hypoxemia due to ventilation, perfusion mismatch, shunt and increased peripheral vascular resistance. Intrathoracic positive pressure is an effective therapeutic option in both prevention and treatment of atelectasis. Non-invasive mechanical ventilation is related with a lower mortality and morbidity rate due to lack of any potential complication risks of endotracheal intubation. Non-invasive mechanical ventilation can be applied as prophylactic or curative. Both of these techniques are related with lower reintubation rates, nosocomial infections, duration of hospitalization and mortality in patients with postoperative respiratory failure. The differences of this therapy from standard application and potential complications should be well known in order to improve prognosis in these group of patients. The primary aim of this review is to underline the pathogenesis of postoperative respiratory failure. The secondary aim is to clarify the optimum method, effect and complications of non-invasive mechanical ventilation therapy under the light of the studies which was performed in specific patient groups.     

Current concepts in the pathogenesis of the obesity-hypoventilation syndrome. Mechanical and circulatory factors

The pathogenesis of carbon dioxide retention associated with obesity, the obesity hypoventilation syndrome (OHS), remains obscure. In an attempt to Identify factors which might Initiate or contribute to this syndrome, we reviewed respiratory and circulatory function in two groups of obese subjects: those who were not hypercapnic (simple obesity) and those who were (OHS).Obese subjects in both groups display reduction of lung and chest wall compliance, normal airway resistance, closure of peripheral lung units and increased energy cost of breathing. These abnormalities are more severe in those who hypoventilate, especially the reduction In compliance. Respiratory muscle efficiency is reduced in both groups. Inspiratory muscle strength of patients with OHS is 60 to 70 per cent of normal. In OHS arterial carbon dioxide tension (PaCO₂), vital capacity and maximum voluntary ventilation improve significantly with weight toss, whereas in simple obesity there Is little change in these factors with weight loss.In both groups the major circulatory findings are increased total and pulmonary blood volume, with preservation of a normal ratio between the two; and good perfusion but marked underventilation of dependent regions of the lung. These changes are more pronounced In OHS. Left ventricular end diastolic pressure is elevated in some patients, but the rise is not confined to those with OHS. In OHS alveolar hypoxia and acidemia produce pulmonary arterial vasoconstriction and pulmonary arterial hypertension. As a consequence pulmonary artery pressure exceeds left ventricular pressure at the end of diastole.We suggest that excessive reduction of chest wall compliance and inspiratory muscle weakness interact with the circulatory abnormalities already present in simple obesity to generate carbon dioxide retention. The contribution of altered central nervous system function to this process remains controversial.     

术前肺功能对肺切除术术后并发症及术后肺功能的预测

目的观察肺切除手术患者术前、后肺功能演变特征,探讨术前肺功能指标对患者术后并发症和术后肺功能的预测能力。方法对115例肺切除手术患者进行术前常规肺功能及运动心肺功能检测,术后3个月行肺功能复查;追踪患者1个月内术后心肺并发症(PPC)的发生情况。结果28例手术患者出现PPC(24.35%);有、无PPC组间比较有差异的肺功能指标为:FVC%pred、FEV1%pred、VO2m ax%pred、WRm ax%pred、VO2/HR%pred;术后肺通气功能、运动心肺功能与术前比较有不同程度下降;术后肺功能实测值与公式法预计的术后肺功能值比较差异有显著性。结论术后肺功能损害主要是限制性肺通气功能障碍,运动心肺功能亦有下降。建立预测PPC及术后肺功能的回归方程,能更准确地评估患者的手术耐受力。     

Effect of an inhaled beta 2-adrenergic agent on pulmonary function and quality of life in elderly patients with chronic obstructive pulmonary disease

We tested the effects of inhaled beta 2-adrenergic drug on the physiologic function of the respiratory system and quality of life (QOL) in elderly patients with chronic obstructive pulmonary disease (COPD). We measured the pulmonary function, static respiratory pressures, and ventilation during exercise, before and after inhalation of the beta 2-adrenergic drug, fenoterol bromide (FB) in 12 male COPD patients (mean age 82.1 +/- 0.6 years old), QOL was measured with a St George's Respiratory Questionnaire (SGRQ) in the patients. Forced expiratory volume in one second was increased by the inhalation of FB in the patients, whereas the ratio of residual volume to total lung capacity was decreased by the inhalation. Maximum inspiratory pressure was significantly increased after the inhalation of FB. Dyspnea sensation during exercise assessed by the Borg scale was reduced by the inhalation of FB. The scores on SGRQ were improved by one-month treatment with FB. These results indicate that treatment with FB is effective for both physiological function of the respiratory system and several aspects of QOL in elderly patients with COPD.     

2型糖尿病患者运动试验时肺气体交换功能变化初探

目的　探讨糖尿病患者运动能力及其运动时肺的通气与气体交换功能的变化。方法无明显慢性并发症住院的 2型糖尿病患者 2 1名和健康非吸烟对照组 2 0名进行限时递增负荷运动试验 ,测其静息时和运动中肺的通气与气体交换量的变化。结果　糖尿病患者最大运动负荷量、运动末的最大每分耗氧量及每搏耗氧量均较对照组低 ,运动末的最大每分通气量、最大潮气量、最大呼吸频率、最大心率与对照组差异无显著性 ;而呼吸商在运动前后均显著高于对照组 (P <0 .0 1)。结论　无明显慢性并发症的糖尿病患者运动能力显著下降 (P <0 .0 1) ,但运动中肺的通气功能无异常改变 ,推测其运动能力的下降可能与肌肉组织氧的摄取与利用障碍有关     

Disorders of hemodynamics and pulmonary gas exchange in the acute period of myocardial infarct

In 40 patients with massive myocardial infarction, the central hemodynamics was examined by probing the right-sided chambers of the heart and the pulmonary artery. The cardiac output was measured by thermodilution. The gas exchange (respiratory minute volume, capnography, gas analysis of arterial and mixed venous blood) was explored. Arterial hypoxemia was found to be associated with increased intrapulmonary blood shunting in patients with acute myocardial infarction complicated by congestive heart failure. Deterioration of arterial hypoxemia was promoted by a combination of increased overall pulmonary shunting and decreased residual venous oxygenation. Abnormalities in the ventilation-perfusion relations are of great importance.     

Pulmonary physiologic changes of morbid obesity.

OBJECTIVE: Our objective was to study the effects of extreme obesity on pulmonary function tests and the effects of smoking on these variables in a population group larger than has previously been reported. DESIGN: Retrospective data analysis. SETTING: Academic medical center. PATIENTS: Forty-three patients with extreme obesity [ratio of weight in kilograms to height in centimeters greater than 0.9 (W/H)] who underwent pulmonary function testing at Cedars-Sinai on an out-patient or in-patient basis during the period of 1979 to 1 997. MEASUREMENTS AND RESULTS: Patients underwent standard pulmonary function testing. The patients were divided into 2 groups based on the W/H ratio: group A (0.9-0.99) and group B (greater than 1.0). Chart review was performed to identify pertinent history/co-morbidities. The independent effects of smoking between each group's patients were assessed. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), expiratory reserve volume (ERV), functional residual capacity (FRC), maximum voluntary ventilation (MVV), and forced expiratory flow during midexpiratory phase (FEF25-75%,) were significantly reduced in both groups. Single-breath diffusing capacity for carbon monoxide (DLCO) and the volume of gas into which the single-breath of carbon monoxide and helium was diluted were not elevated. Smoking did not account for the results in group A but did seem to partially explain the decrease in FVC, FEV1, and FEF25-75% in group B. CONCLUSIONS: Extreme obesity is associated with a reduction in ERV, FVC, FEV1, FRC, FEF25-75%, and MVV. However, contrary to prior reports, D(LCO) is not elevated. These effects are only partially explained by smoking.     

Early occurrence of respiratory muscle deoxygenation assessed by near-infrared spectroscopy during leg exercise in patients with chronic heart failure

The mechanisms of respiratory muscle deoxygenation during incremental leg exercise with expired gas analysis were investigated in 29 patients with chronic heart failure and 21 normal subjects. The deoxygenation and blood volume of the respiratory muscle and exercising leg muscle were assessed by near-infrared spectroscopy (NIRS). To evaluate the influence of the leg exercise on the blood volume of the respiratory muscle, 10 normal subjects also underwent a hyperventilation test with NIRS. The respiratory muscle deoxygenation point (RDP), at which oxygenated hemoglobin starts to decrease, was observed in both groups during exercise. The oxygen consumption (VO2) and the minute ventilation at the RDP in the patients was lower (p<0.01). At the same VO2, the respiratory rate was higher in patients (p<0.01). During exercise, the blood volume of the leg muscle increased, while that of the respiratory muscle decreased. During a hyperventilation test, the minute ventilation was higher than that of the RDP during exercise, the blood volume of the respiratory muscle did not decrease, and the RDP was not detectable. In conclusion, a limited ability to increase perfusion of respiratory muscles during exercise combined with the greater work of breathing results in early respiratory muscle deoxygenation in patients with chronic heart failure.     

Abnormalities of the respiratory function and control of ventilation in patients with anorexia nervosa

BACKGROUND: Anorexia nervosa is a good model to study the effects of malnutrition on the respiratory system, since it excludes the consequences that some chronic diseases can have on the lung. OBJECTIVE: The objective of this study was to assess pulmonary function and alterations in the respiratory system in patients with anorexia nervosa. METHODS: Twenty-two women, 12 with anorexia nervosa and 10 healthy volunteers, were studied. Anthropometric data were gathered for all the participants. In every case, an arterial blood gas test and functional respiratory study, that included spirometry, plethysmography, measure of maximum muscular respiratory pressure and study of the ventilatory pattern at baseline and after hypercapnic stimulation, were performed. RESULTS: No significant differences were found in mean age and height in both groups of patients but there was a difference in body mass index (p < 0.05). In pulmonary function tests, an increase in residual volume (RV), RV/total lung capacity (TLC) ratio and functional residual capacity and a decrease in maximum respiratory pressure were found in patients with anorexia nervosa compared to the control group (p < 0.05). Differences were also found in the ventilatory pattern, with a reduction in minute ventilation and occlusion pressure as well as a decreased response of these parameters to hypercapnic stimulation (p < 0.05) in the patients with anorexia nervosa. CONCLUSION: In patients with anorexia nervosa, a significant elevation in RV, in the RV/TLC ratio and in functional residual capacity and a decrease in the maximum respiratory pressure were noted. In addition, they present an alteration in the central respiratory drive and a response of the respiratory system to hypercapnic stimulation. Although these alterations have no repercussion on the maintenance of gas exchange in baseline conditions, they may have in extreme situations.