Reference values for dynamic and static pulmonary compliance in men

The aim of the present study was to determine new reference values and predictive variables for dynamic and static pulmonary compliance in men. The investigation was conducted as a prospective study in healthy, non-smoking men with normal pulmonary function parameters including spirometry, bodyplethysmography and CO diffusing capacity. The esophageal pressure method was used to measure dynamic compliance (Cdyn), specific dynamic compliance (Cdyn/ITGV), static compliance (Cstat) and specific static compliance (Cstat/ITGV). Lung recoil pressures were recorded at different levels of total lung capacity (TLC). A total of 208 men aged 20-69 years were included in the study. The mean values for the compliance parameters were: Cdyn: 2.91+/-1.08 L/kPa; Cdyn/ITGV: 0.71 +/- 0.30 kPa (-1); Cstat: 3.34 +/- 1.04 L/kPa; Cstat/ITGV: 0.82 +/- 0.31 kPa (-1). Cdyn, Cdyn/ITGV and Cstat/ITGV were significantly correlated with age and Cstat was related to height, but in multiple regression analyses the predictability for compliance parameters was very low. Lung recoil pressures at all TLC levels significantly decreased with ageing. In conclusion, we demonstrated that the contribution of anthropometric variables to the regression equations of pulmonary compliance was low. With ageing the static pressure-volume curve of the lung shifted to the left without substantial alteration of the slope.     

Long-term effects of depot long-acting somatostatin analog octreotide on hormone levels and tumor mass in acromegaly

The effects of a 12- to 24-month treatment with depot long-acting octreotide (OCT-LAR) on hormone profile, tumor mass, and clinical symptoms were reported in 36 patients with active acromegaly [GH, 34.2 +/- 5.6 microg/L; insulin-like growth factor I (IGF-I), 784.5 +/- 40.4 microg/L]. Fifteen patients were de novo whereas 21 had previously undergone unsuccessful surgery. Serum GH (P < 0.0001) and IGF-I levels (P < 0.0001) significantly decreased as early as after the first injection of OCT-LAR and progressively declined during the 12-24 months of treatment both in de novo and in operated patients. At the last follow-up, GH hypersecretion was controlled (< or =2.5 microg/L) in 69.4% whereas normal IGF-I levels were achieved in 61.1% of patients. GH and IGF-I suppression during OCT-LAR treatment was similar in de novo and operated patients as shown by nadir GH (2.3 +/- 0.6 vs. 2.2 +/- 0.6 microg/L) and IGF-I (323.1 +/- 34.9 vs. 275.5 +/- 33.0 microg/L), percent suppression of GH (92.7 +/- 2.0 vs. 85.9 +/- 3.3%) and IGF-I (57.4 +/- 4.9 vs. 61.5 +/- 4.6%), and prevalence of GH (73.3 vs. 76.2%) and IGF-I (53.3 vs. 71.4%) control. A decrease in tumor volume was observed in 12 of 15 de novo patients, whereas no shrinkage was detected in 4 of 9 operated patients. No patient had tumor reexpansion during OCT-LAR treatment. Significant clinical improvement was obtained in all patients; heart rate, systolic blood pressure, and diastolic blood pressure significantly decreased in the entire population. A mild but significant increase of blood glucose levels, followed by a decrease of serum insulin levels, was observed after 3 months of treatment: this effect subsided with treatment continuation. OCT-LAR treatment was well tolerated by most patients. In conclusion, long-term treatment with OCT-LAR was effective in controlling GH and IGF-I hypersecretion in most patients with acromegaly, when applied either as primary therapy or as adjunctive therapy after surgery. Tumor shrinkage was observed in de novo patients during OCT-LAR treatment, suggesting that it can be successfully applied as primary therapy in patients bearing invasive tumors, who are less likely to be cured after surgery.     

Bromocriptine treatment over 12 years in acromegaly: effect on growth hormone and prolactin secretion.

It is not known whether bromocriptine treatment in acromegaly can be implemented for a life-long period. To elucidate this problem, the secretory GH and PRL states of 12 patients with acromegaly were determined, before bromocriptine treatment, under therapy (15.0 +/- 6.8 mg/day for 12 +/- 3 years; mean +/- SD) and during two-weeks long drug withdrawal after long-term treatment, respectively. Before therapy, all patients showed a non-sufficient GH suppression after oral glucose load (greater than 2 micrograms/l), whereas under dopaminergic treatment the post-glucose GH levels of three patients fell below 2 micrograms/l; normal IGF-I concentrations were found in five patients. However, under bromocriptine, only two patients showed GH suppressions below 2 micrograms/l following glucose, accompanied with normal IGF-I levels. During bromocriptine withdrawal, GH secretion at 60 min in the oral glucose tolerance test increased significantly (17.0 +/- 15.5 vs 5.7 +/- 5.2 micrograms/l; p less than 0.01); the mean IGF-I level rose from 2.1 +/- 0.8 to 4.9 +/- 2.2 kU/l (p less than 0.01). IGF-I was normal during bromocriptine cessation in only one patient; none of the 12 patients showed a GH suppression below 2 micrograms/l after oral glucose load. Under dopaminergic treatment hyperprolactinemia could not be detected. In conclusion, bromocriptine led to a stable suppression of both GH hypersecretion and--if present--concomitantly elevated PRL levels. Severe side effects or a further tumor growth could not be observed. Thus, the data of the longest follow-up investigation that has so far been published indicate that effective life-long bromocriptine therapy seems to be possible in selected patients with acromegaly.     

Long-term physiologic outcome after acute farmer's lung

We performed a follow-up study of 61 patients who had an acute episode of farmer's lung (54 men and seven women). Twenty-four subjects had ceased all contact with the barn, while 37 had continued farming. Pulmonary function tests for all subjects showed an initial improvement after the acute episode: 92.4 +/- 36.9 percent of predicted for carbon monoxide diffusing capacity (Dco) after one year, compared to 61.5 +/- 28.5 percent at diagnosis (p less than 0.01); and 6.01 +/- 1.50 L for total lung capacity (TLC) after three years, compared to 5.35 +/- 1.42 L (p less than 0.05). Subsequently, pulmonary function decreased over time. Five years or more after the acute episode, pulmonary function tests in subjects who had continued farm work were not worse than those of subjects who had ceased contact for Dco (68.1 +/- 21.4 percent of predicted vs 80.6 +/- 27.7 percent, respectively [p greater than 0.1]) and for TLC (5.55 +/- 1.31 L vs 5.90 +/- 0.84 L [p greater than 0.2]). This study shows that during a long-term follow-up, subjects with farmer's lung who stayed on the farm have subnormal values for pulmonary function but comparable values to those who left their farm.     

Cross-section study of pulmonary function in patients with insulin-dependent diabetes mellitus

In this study, we attempted to establish the prevalence and nature of pulmonary dysfunction in a cross section of a diabetic population and the relationship of pulmonary dysfunction to diabetic factors and complications. Forty insulin-dependent diabetic patients, 15 to 60 yr of age, and 40 healthy reference subjects, matched for age, sex, and race, were studied. All subjects were lifelong nonsmokers and had no clinical evidence of past or present respiratory disease. Lung function was assessed from the flow-volume curve, single-breath nitrogen washout, static lung elastic recoil, and pulmonary diffusing capacity (DLCO/VA) and its components: membrane diffusing capacity (Dm/VA) and pulmonary capillary blood volume (Qc/VA). The diabetic patients had an increased value for Kst(L) and in Kst(L), the exponential shape constant of the pressure-volume curve compared with that of the reference subjects (Kst(L), 0.184 +/- 0.011 versus 0.135 +/- 0.005; p less than 0.005, mean +/- SEM). The DL/VA was lower in the diabetic subjects (4.62 = 0.12 versus 5.31 +/- 0.10 ml/min/mm Hg/L; p less than 0.001), and this was due to a lower Qc/VA (9.45 +/- 0.43 versus 11.75 +/- 0.35 ml/min; p less than 0.001). The Kst(L) and Qc/VA were correlated with the duration of diabetes. The In Kst(L) was negatively correlated with both DL/VA (r = -0.32, p less than 0.05) and Qc/VA (r = -0.36, p less than 0.05). There was no association between abnormal pulmonary function and the presence of other diabetic complications. It is concluded that there are mild, duration-related abnormalities of lung elastic recoil and pulmonary diffusing capacity and a reduction in pulmonary capillary blood volume in insulin-dependent diabetes mellitus.     

血红素氧合酶在慢性阻塞性肺疾病患者中的表达

目的 观察血红素氧合酶（HO）在慢性阻塞性肺疾病（COPD）患者中的表达及其变化。方法 设COPD组、COPD合并肺癌组、单纯肺癌组及正常健康组。4组均进行血气分析和肺功能测定。应用紫外分光光度计间接测定动脉血一氧化碳血红蛋白（COHb)含量和肺脏HO－1的活性。用逆转录－聚合酶链反应检测肺脏和肺动脉组织HO mRNA表达水平。用免疫组化法测定肺脏组织HO蛋白的表达。结果 COPD组和COPD合并肺癌组患者动脉血氧分压低于60mm Hg(1mm Hg=0.133kPa),提示这两组患者均为Ⅰ型呼吸衰竭患者。与正常健康组比较,这两组患者的肺一氧化碳弥散量、肺一氧化碳弥散量／肺泡通气量及1秒钟用力呼气容积占预计值的百分比均显著降低,残气容积／肺总量显著升高,提示这两组患者均患有中度COPD（Ⅱ级）。这两组患者的COHb明显高于单纯肺癌组和正常健康组（P＜0.01),单纯肺癌组和正常健康组比较差异无显著性。COPD合并肺癌组患者胆红素生成量、肺脏及肺动脉组织HO－1mRNA吸光度值明显高于单纯肺癌组和正常健康组。HO－1免疫组化染色显示,COPD合并肺癌组非癌变肺组织肺泡壁细胞、肺内小血管和支气管壁细胞胞质HO－1的表达显著增强。结论 COPD患者HO－1表达增多。     

Lack of improvement of lung diffusing capacity following fluid withdrawal by ultrafiltration in chronic heart failure

OBJECTIVES: We sought to investigate the possibility that lung diffusing capacity reduction observed in chronic heart failure is reversible in the short term. BACKGROUND: Mechanical properties of the lung usually ameliorate with antifailure treatment including drugs, ultrafiltration and heart transplantation, whereas lung diffusion rarely improves. METHODS: We studied the mechanical properties of the lung (pulmonary function tests with determination of alveolar volume, extravascular lung fluids and lung tissue), lung diffusion for carbon monoxide (DLco), including membrane diffusing capacity (Dm), pulmonary capillary blood volume (Vc) and pulmonary hemodynamics, in 28 patients with stable chronic heart failure, before a single session of extracorporeal ultrafiltration (3,973 +/- 2200 ml) and four days thereafter. Lung mechanics and diffusion were also evaluated in 18 normal subjects. RESULTS: Vital capacity, forced expiratory volume (1 s) and maximal voluntary ventilation were lower in patients when compared with normal subjects, and increased after ultrafiltration from 2.1 +/- 0.7 to 2.5 +/- 0.7(1)*, 1.7 +/- 0.5 to 2.0 +/- 0.6(1)* and 67 +/- 25 to 79 +/- 26 (1/min)*, respectively (* p < 0.02 vs. pre-ultrafiltration). Post-ultrafiltration alveolar volume was augmented, while lung tissue, body weight (approximately 6 kg), chest X-ray extravascular lung water score and pulmonary vascular pressure were reduced. Heart dimensions (echocardiography) remained unchanged. DLco, Dm and Vc were 29.0 +/- 5.0 ml/min/mm Hg, 47.0 +/- 11.0 ml/min/mm Hg, 102 +/- 20 ml in normal subjects and 17.1 +/- 4.0#, 24.1 +/- 6.5#, 113 +/- 38 and 17.0 +/- 5.0#, 24.8 +/- 7.9#, 100 +/- 39 in patients before and after ultrafiltration, respectively (# = p < 0.01 vs. controls). CONCLUSIONS: In chronic heart failure, ultrafiltration improves volumes and mechanical properties of the lung by reducing lung fluids. Diffusion is unaffected by ultrafiltration, suggesting that, in chronic heart failure, the alveolar-capillary membrane abnormalities are fluid-independent.     

Lung membrane diffusing capacity, heart failure, and heart transplantation

The pulmonary diffusing capacity for carbon monoxide (DLCO) is reduced in chronic heart failure and remains decreased after heart transplantation. This decrease in DLCO may depend on a permanent alteration after transplantation of one or the other of its components: diffusion of the alveolar capillary membrane or the pulmonary capillary blood volume (Vc). Therefore, we measured DLCO, the membrane conductance, and Vc before and after heart transplantation. At the time of hemodynamic measurements, the Roughton and Forster method of measuring DLCO at varying alveolar oxygen concentrations was used to determine the membrane conductance, Vc, DLCO/alveolar volume (VA), the membrane conductance/VA and thetaVc/VA (theta = carbon monoxide conductance of blood, VA = alveolar volume) in 21 patients with class III to IV heart failure before and after transplantation, and in 21 healthy controls. Transplantation normalized pulmonary capillary pressure and increased cardiac index. DLCO was decreased before transplantation (7.11 vs 10.0 mmol/min/kPa in controls), but DLCO/VA was normal (1.67+/-0.44 vs 1.71+/-0.26 mmol/min/kPa/L in controls). DLCO/VA remained unchanged after transplantation, because the decrease in Vc (82+/-30 vs 65+/-18 ml before and after transplantation) and thetaVc/VA was not compensated by the changes in membrane conductance (11+/-4 vs 12+/-5 mmol/min/kPa before and after transplantation, respectively) and membrane conductance/VA. We conclude that the decrease in DLCO in patients with chronic heart failure is due to a restrictive ventilatory pattern because their DLCO/VA remains normal; the decrease in the membrane conductance is compensated by the increase in Vc. After transplantation, the decrease in Vc due to normalization of pulmonary hemodynamics is not completely compensated for by an increase in membrane conductance. Because the membrane conductances, measured before and after transplantation, are negatively correlated with duration of heart failure, its abnormal pulmonary hemodynamics may have irreversibly altered the alveolar capillary membrane.     

肺移植对5例慢性阻塞性肺疾病患者肺功能的影响

目的研究单肺移植手术治疗慢性阻塞性肺疾病(COPD)对呼吸生理及肺功能的影响。方法5例患者均为Ⅳ级COPD男性患者,年龄51～63岁。术前2周测定患者用力肺活量(FVC)、第一秒用力呼气容积(FEV1)、FEV1/FVC、最大通气量(MVV)、残气容积(RV)、肺总量(TLC)、残总比(RV/TLC)、深吸气量(IC)、胸腔气体容积(TGV)、呼气峰流量(PEF)、总气道阻力(Rawtotal)、肺一氧化碳弥散量(DLCO)、每升肺泡容积肺一氧化碳弥散量(DLCO/V·A)、6分钟行走距离(6MWD)、动脉血氧分压(PaO2)、肺泡气动脉血氧分压差[P(Aa)O2]、动脉血氧饱和度(SaO2)、动脉血二氧化碳分压(PaCO2)及平均肺动脉压(mPAP)等参数。术后2个月再行上述测定。结果5例患者术前2周、术后2个月检测的参数为MVV(23.6±5.8)、(71.6±21.8)L,FEV1(0.68±0.21)、(1.85±0.46)L,FEV1/FVC(37.4±8.3)、(75.6±13.9)%,PaO2(60.0±9.1)、(86.2±2.9)mmHg(1mmHg=0.133kPa),SaO2(90.0±4.6)%、(96.8±0.5)%及mPAP(31.2±5.5)、(16.6±1.8)mmHg,均有显著改善(P均<0.05);3例患者IC[(1.16±0.26)、(1.83±0.35)L]、TGV[(6.52±0.27)、(4.52±0.29)L]、RV[(5.12±0.39)、(3.20±0.32)L]、RV/TLC[(71.0±5.6)、(51.3±2.5)%]及Rawtotal[(6.62±0.99)、(2.48±0.87)cmH2O·L-1·s-1]改善显著(P均<0.05);4例患者PEF[(1.65±0.40)、(3.92±1.63)L/s]、DLCO[(8.5±3.0)、(21.0±6.2)ml·min-1·mmHg-1]及6MWD[(46.8±14.7)、(246.8±51.9)m]也显著增加(P均<0.05);FVC[(1.85±0.40)、(2.45±0.49)L]、TLC[(7.19±0.15)、(6.26±0.73)L]、DLCO/V·A[(2.90±1.50)、(5.41±0.87)L·min-1·mmHg-1]、P(Aa)O2[(37.6±16.3)、(17.8±6.3)mmHg]及PaCO2[(44.6±7.7)、(37.4±3.4)mmHg]有所改善,但差异无统计学意义(P均>0.05)。结论COPD患者肺移植术后肺通气、气道阻力、残气、弥散、运动耐力及气体交换功能均明显改善。     

Reduced vascular compliance is associated with impaired endothelium-dependent dilatation in the brachial artery of patients with congestive heart failure

BACKGROUND: Alterations in elastic properties and vascular structure of conduit vessels are important detrimental factors contributing to increased cardiac load and reduced tissue perfusion in patients with congestive heart failure (CHF). It has been demonstrated that endothelial function in the peripheral vasculature is impaired in this disorder, which may induce abnormal vascular elastic properties and remodeling. However, it remains unknown whether changes in vascular structure or mechanical properties are related to endothelial dysfunction in conduit arteries of patients with CHF. METHODS AND RESULTS: Twenty-five CHF patients with nonischemic heart disease and 20 sex/age-matched controls were enrolled. Brachial artery diameter, intima-media thickness (IMT), and vascular stiffness as represented by distensibility and compliance were determined using a high-frequency linear transducer attached to a high-quality ultrasound system. In addition, flow-mediated dilatation (FMD) after 5-minute forearm occlusion and sublingual nitroglycerin-induced dilatation (NTG) were measured in the brachial artery. Brachial arterial diameter was similar between CHF and controls; however, IMT and wall/lumen ratio were significantly greater in CHF patients than in controls (IMT, 0.37+/-0.01 versus 0.31+/-0.01 mm; wall/lumen, 18.7+/-0.8 versus 15.1+/-0.8%: both P<.01). In addition, vascular stiffness parameters were lower in CHF than in controls (distensibility; 1.09+/-0.14 versus 1.60+/-0.15%/kPa, P<.01: compliance; 0.17+/-0.02 versus 0.26+/-0.02 mm(2) kPa, P<.05). FMD and TNG were significantly reduced in CHF (both P<.001). Although stiffness parameters in CHF were not significantly correlated with vascular structure (ie, IMT, wall/lumen) or clinical parameters (ie, age, lipids, glucose, blood pressure), elastic parameters were significantly correlated with FMD (distensibility; r=0.579, P<.005: compliance; r=0.433, P<.05), but not with NTG. CONCLUSION: The present study found that, in limb muscle conduit artery in patients with CHF, there are hypertrophic remodeling and endothelial dysfunction-associated alterations in vascular wall elastic properties.     

Long-term durable benefit after whole lung lavage in pulmonary alveolar proteinosis.

Whole lung lavage (WLL) is still the gold-standard therapy for pulmonary alveolar proteinosis (PAP). The few studies on the duration of the effect of WLL, belonging to a rather remote period, show significant but transient benefits. In 21 patients with idiopathic PAP, the duration of any benefit and, in 16 of them, the time course of lung function improvement (at baseline, 1 week, 6 months, 1 yr and then every 2 yrs after WLL) were evaluated. The present WLL technique takes longer, is invasively monitored and partially modified with respect to past techniques. More than 70% of patients remained free from recurrent PAP at 7 yrs. The bulk of the improvement in spirometric results was almost completely gained in the immediate post-WLL period due to the efficient clearance of the alveoli. At a median of 5 yrs, recovery of diffusing capacity of the lung for carbon monoxide was incomplete (75 +/- 19% of the predicted value) and there were residual gas exchange abnormalities (alveolar to arterial oxygen tension difference 3.6 +/- 1.5 kPa (27 +/- 11 mmHg)) and exercise limitation, probably explained by engorgement of lymphatic vessels. In conclusion, whole lung lavage for idiopathic pulmonary alveolar proteinosis is currently a safe procedure in an experienced setting, and provides long-lasting benefits in the majority of patients.     

Partitioning of alveolar and conducting airway nitric oxide in scleroderma lung disease

We partitioned exhaled nitric oxide (NO) into alveolar concentration (CA) and conducting airway flux (JNO(air,max)) in scleroderma (SSc) lung disease and hypothesized that CA would be elevated. Twenty patients with SSc, 15 with interstitial lung disease (SSc-ILD) alone, and 5 with pulmonary hypertension (SSc-PH) were compared with 20 control subjects. CA and JNO(air,max) were derived from the slope and y intercept, respectively, of the NO output versus expiratory flow rate ((V).exh) relationship obtained by measuring exhaled NO (FE(NO)) at multiple (V).exh values of 50-200 ml/second. There were no significant differences in FE(NO) at any (V).exh between the SSc group and control subjects. JNO(air,max) was reduced (0.6 +/- 0.1 versus 1.2 +/- 0.2 nl of NO per second; p = 0.01), whereas CA was increased (4.7 +/- 0.5 versus 1.8 +/- 0.2 ppb; p < 0.001) in the SSc group compared with control subjects. No differences were noted between SSc-ILD and SSc-PH. There was a negative correlation between CA and DL(CO) among the patients with SSc (R = -0.66, p = 0.002). We conclude that CA is increased whereas JNO(air,max) is decreased in SSc-ILD and SSc-PH. A reduced diffusing capacity of NO from the alveolar space into the blood could explain the observed increase in CA.     

Alveolar-capillary membrane conductance is the best pulmonary function correlate of exercise ventilation efficiency in heart failure patients

BACKGROUND: In heart failure (HF), changes in lung mechanics and gas diffusion are limiting factors to exercise. Their contribution to an increased exercise ventilation to CO2 production (VE/VCO2) slope is undefined. METHODS: A total of 67 stable HF patients underwent cardiopulmonary exercise and pulmonary function tests, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal voluntary ventilation (MVV), total lung capacity (TLC) and alveolar diffusing capacity with its subcomponents (alveolar-capillary membrane conductance (D(m)) and capillary blood volume (V(c))). RESULTS: Patients showed a mild restrictive pattern (FEV1=85+/-15% and FVC=75+/-13% of normal predicted) and a moderate D(m) reduction (32+/-12 ml min(-1) mm Hg(-1)). Average peak VO(2) was 15.6+/-4.0 ml min(-1) kg(-1) and the VE/VCO2 slope was 39.6+/-11.0. At simple Spearman correlation analysis, all variables, but V(c), correlated with peak VO2; only D(m) correlated with VE/VCO2 slope. At partial Spearman correlation, all variables lost the peak VO2 correlation, and D(m) still inversely correlated with VE/VCO2 slope (r=-0.35; p=0.005). In patients with a high VE/VCO2 slope (cutoff value 34), despite comparable lung volumes, D(m) was significantly more depressed (30+/-13 vs. 35+/-10 ml min(-1) mm Hg(-1); p<0.01). CONCLUSIONS: Pulmonary function tests and alveolar gas diffusing capacity poorly correlate with peak VO2. D(m) impairment rather than lung volumes correlates with exercise ventilation efficiency. This finding further adds to the pathophysiological relevance of an abnormal gas exchange in HF patients.     

During exercise non-invasive ventilation in chronic restrictive respiratory failure

BACKGROUND: Exercise intolerance limits chronic restrictive respiratory failure (CRF) patients from participating in daily activities. The specific modalities that could improve exercise tolerance in these patients remain to be established. OBJECTIVE: To investigate exercise endurance and associated physiological responses with non-invasive ventilation (NIV) during exercise in restrictive CRF patients. METHODS: Eighteen patients (63+/-11 years, total lung capacity (TLC)=59+/-16% of predicted value) performed maximal exercise in spontaneous breathing conditions (MWLE) and during two constant workload exercise (CWLE) tests at 75% Pmax, with or without NIV in random order. "NIV Responders" were defined by an increase in CWLE duration of more than 50% when using NIV. RESULTS: For the whole group, CWLE duration when using NIV increased from 5.6+/-4.6 to 9.6+/-8.1 min. Increase in CWLE duration correlated with reduction in heart rate and oxygen desaturation, and dyspnea relief during exercise. NIV responders (n=9) showed more severe lung restriction (TLC: 2.6+/-0.7 versus 3.5+/-1.1L; forced vital capacity: 1.0+/-0.16 versus 1.46+/-0.38 L). At the end of MWLE, responders had a lower Vt (0.60+/-0.09 versus 0.89+/-0.34 L), a higher dead-space ratio (0.51+/-0.06 versus 0.38+/-0.12) and lower oxygen pulse (4.5+/-1.2 versus 7.4+/-3.9 ml/beat). CONCLUSION: In severely restrictive patients, NIV during exercise significantly improved exercise duration and tolerance and increased alveolar ventilation. TRIAL REGISTRATION: The enrollment of the patients started before July 1, 2005.     

The role of IGF binding protein-3 as a parameter of activity in acromegalic patients.

OBJECTIVE: The production of insulin-like growth factor binding protein-3 (IGFBP-3), the main IGF-I binding protein, is regulated by GH, and its serum levels are increased in acromegaly. We investigated its potential value as a parameter of acromegaly activity or remission in comparison with IGF-I, taking GH suppression below 2 microg/l after glucose load as the normal standard. METHODS: Data from 40 acromegalic patients (12 males and 28 females, aged 28 to 79 years) were obtained retrospectively from stored samples. From these, 145 pairs of IGF-I/IGFBP-3 values were collected; in 67 of them, simultaneous measurement of GH after glucose loading allowed their classification as active or inactive acromegaly. Relationships between IGF-I, IGFBP-3 and GH after glucose load were assessed, as well as differences between IGF-I and IGFBP-3 levels in active and inactive acromegaly. RESULTS: Significant positive correlation between IGF-I and IGFBP-3 in 145 samples was observed (r=0.49, P<0. 0001). As for the 67 samples in which activity or remission could be defined in terms of GH after glucose load, 50 were active and 17 inactive. Both IGF-I and IGFBP-3 significantly correlated with minimum GH (r=0.53, P<0.0001 and r=0.41, P<0.001 respectively). For both parameters, significant differences of means between active and inactive cases were observed (623+/-296 vs 300+/-108 ng/ml, P<0.0001 for IGF-I, and 4.1+/-1.3 vs 3.2+/-0.9 microg/ml, P<0.006 for IGFBP-3). Yet, when comparing in individual cases their classification as active or inactive with the finding of normal or increased IGF-I and IGFBP-3, among active cases 16% appeared as normal according to IGF-I, and 50% appeared as normal in terms of IGFBP-3. Among inactive cases, 23.5% appeared as active according to IGF-I, while 17.5% appeared as active in terms of IGFBP-3. CONCLUSION: Even though IGFBP-3 reflects GH secretion, it offers no advantage over IGF-I in the assessment of acromegaly, and it may underestimate disease activity in acromegalic patients.     

Exercise-induced microalbuminuria in patients with active acromegaly: acute effects of slow-release lanreotide, a long-acting somatostatin analog

Recent clinical studies have demonstrated an increase of urinary albumin excretion (UAE) at rest in acromegalic patients and, on the other hand, a reduced UAE in patients with growth hormone (GH) deficiency. Physical exercise is known to induce abnormal UAE in patients with diabetes, probably unmasking early glomerular alterations. The effect of exercise on UAE in acromegaly is not known. Moreover, the effect of acute but sustained GH inhibition in acromegaly on UAE at rest and after exercise has never been studied. The aim of our study was to evaluate the acute short-term effects of slow-release lanreotide (SR-L), a long-acting somatostatin analog, on UAE and alpha1-microglobulinuria (A-1-M), a marker of renal tubular damage, at rest and after exercise in 7 normotensive patients with active acromegaly and normal renal function (4 males and 3 females; mean age, 53 +/- 3.1 years; body mass index [BMI], 27.3 +/- 1.1 kg/m2) at baseline and 7 and 14 days after SR-L injection (30 mg). Two of the acromegalic patients were microalbuminuric at rest, and in other 3 cases, UAE was in the borderline range (10 to 20 microg/min). At baseline in the acromegalic subjects, we found a significant increase in UAE at rest with respect to 7 normal subjects considered as a control group. GH and insulin-like growth factor-1 (IGF-1) were also reduced compared with baseline 7 and 14 days after SR-L injection (GH, 13.4 +/- 7.3 and 13.61 +/- 7 v 18.5 +/- 9.3 microg/L, P < .05; IGF-1, 230 +/- 53 and 255 +/- 54 v 275 +/- 64 microg/L). Concomitantly, we observed a significant decrease of UAE at rest and after exercise and 7 and 14 days after SR-L injection as compared with baseline values (27.3 +/- 20.5 and 18.2 +/- 13.7 v 35.3 +/- 12.8 microg/min, P < .05; exercise, 48.5 +/- 24.1 and 18.6 +/- 6.8 v68.3 +/- 39.7 microg/min, P < .05). A-1-M always remained in the normal range (< 12 mg/L) both at rest and after exercise. We can thus conclude that in acromegaly, submaximal exercise induces abnormal increases in microalbuminuria. We hypothesize that this phenomenon may be due to the functional glomeruler involvement. SR-L can significantly reduce UAE at rest and after exercise in the short-term in acromegaly, probably via a decrease in circulating GH levels.     

Pulmonary alveolar proteinosis: step-by-step perioperative care of whole lung lavage procedure.

BACKGROUND: Pulmonary alveolar proteinosis is a rare disease characterized by the accumulation of surfactant-like material within the alveolar spaces that causes progressive respiratory failure. Improvement can be achieved with whole lung lavage. OBJECTIVE: Our objective was to conduct a study of the feasibility of treating pulmonary alveolar proteinosis in a community hospital. METHODS: Five patients were treated. We assessed procedure pulmonary functions. RESULTS: No major sequelae occurred. Each lung was lavaged with 12 to 20 L of normal saline in cycles of 970 +/- 150 mL each (mean +/- standard deviation), over 106 +/- 49 minutes. Extubation was performed when compliance of the lavaged lung was restored. All patients showed subjective improvement. Resting and exercise oxygen saturation improved within 1 week after the lavage. A significant improvement was also noted in forced expiratory volume in 1 second, forced vital capacity, and maximal oxygen uptake, whereas total lung capacity and carbon monoxide single-breath diffusion capacity remained unchanged. CONCLUSION: Although retrospective and based on a small sample size, our results suggest that whole lung lavage may be performed safely even in medical centers that have limited experience, if strict adherence to a protocol is maintained.     

Pulmonary function in young insulin-dependent diabetic subjects

To clarify the issue of pulmonary dysfunction in diabetes mellitus, lung mechanics and CO transfer were investigated in 22 young (mean age 19.5 +/- 5 years) non-smoking, insulin-dependent diabetic patients and an equal number of matched healthy subjects. Mean closing capacity/total lung capacity (CC/TLC) was significantly greater in the diabetic than in the control group (31.4 +/- 6.8 vs 27.2 +/- 2.9 percent, p less than 0.01), as was the mean value of the volume independent index of lung elasticity (exponent constant, Kst(L)) (0.148 +/- 0.045 vs 0.118 +/- 0.030, p less than 0.05). The transfer factor expressed per unit alveolar volume (TL/VA) was also significantly lower in the diabetic than in the control group (5.25 +/- 0.68 vs 5.61 +/- 0.57 ml/min/mm Hg/L, p less than 0.05) and this could be ascribed to a lower pulmonary capillary blood volume. There was evidence of mildly abnormal lung mechanics and/or a decreased pulmonary capillary blood volume in 16 (73 percent) of the diabetic group. Since pulmonary dysfunction was either an isolated non-endocrine finding or was associated with only early systemic complications in these young patients, our findings suggest that pulmonary dysfunction is an early measurable complication in insulin-dependent diabetes mellitus.     

Pulmonary membrane diffusing capacity and capillary blood volume measured during exercise from nitric oxide uptake.

STUDY OBJECTIVES: To validate lung diffusing capacity for nitric oxide (DLNO) as an index of conductance of the alveolar-capillary membrane during exercise, we compared DLNO to lung diffusing capacity for carbon monoxide (DLCO) and pulmonary membrane diffusing capacity for carbon monoxide (DMCO), and compared pulmonary capillary blood volume (Vc) calculated by two methods. SETTING AND PARTICIPANTS: The study was performed at a university medical center involving 12 nonsmoking healthy volunteers (age range, 23 to 79 years). DLCO, DLNO, cardiac output (c), and lung volume were measured simultaneously at rest and during graded ergometer exercise by a rebreathing technique. Pulmonary membrane diffusing capacity and Vc were compared by (1) the classic technique of Roughton and Forster from DLCO measured at two alveolar oxygen tension (PAO(2)) levels, and (2) from DLNO and DLCO assuming negligible erythrocyte resistance to nitric oxide (NO) uptake, ie, DLNO approximately equal to pulmonary membrane diffusing capacity for nitric oxide. RESULTS: In all subjects, DLNO increased linearly from rest to exercise; age, c, and lung volume were the major determinants of DLNO by stepwise regression analysis. The DLNO/DLCO ratio averaged 3.98 +/- 0.38 (+/- SD) and the DLNO/DMCO ratio averaged 2.49 +/- 0.28 irrespective of exercise intensity. Changing PAO(2) did not alter DLNO. Brief exposure to 40 ppm of inhaled NO during 16 s of rebreathing did not alter either DLCO or c. Estimates of pulmonary membrane diffusing capacity and Vc by the two methods showed a strong correlation. CONCLUSION: Results support DLNO as a direct measure of pulmonary membrane diffusing capacity, allowing the estimation of Vc in a single rebreathing maneuver during exercise. The DLNO-DLCO rebreathing technique can be applied clinically in the investigation of pulmonary microvascular regulation.     

Treatment of acromegaly with the long-acting somatostatin analog SMS 201-995

Current treatment of acromegaly (surgery, radiation, and bromocriptine) is often unsatisfactory, and a sizeable proportion of patients with this disease continue to have GH hypersecretion after all therapeutic modalities have been exhausted. Fifteen patients with active acromegaly (8 previously treated and 7 newly diagnosed) were treated with the long-acting somatostatin analog SMS 201-995 (Sandoz; 50-250 micrograms, sc, every 6-8 h for up to 21 months). The mean daily plasma GH concentration was significantly suppressed in 13 patients, and it became normal in 10. Two patients, however, did not have GH suppression by SMS 201-995 treatment alone; in 1, a significant decline in mean daily GH was achieved after the addition of bromocriptine. As expected, suppression of GH secretion was associated with normalization of plasma somatomedin-C values and significant clinical improvement. Plasma GH responses to synthetic GHRH-(1-44) and TRH were either abolished or blunted by SMS 201-995. Thyroid function remained normal, and glucose tolerance did not change. Significant shrinkage of pituitary tumors occurred in 7 previously untreated and 2 previously treated patients. Side-effects were minimal. SMS 201-995 is an effective agent for the treatment of acromegaly. Further studies are necessary to establish guidelines for identification of non-responders and to examine the effect of preoperative tumor shrinkage on subsequent surgical outcome.