Management of dyspnea in severe chronic obstructive pulmonary disease.

Progression of chronic obstructive pulmonary disease (COPD) is frequently associated with increasing dyspnea; indeed, patients with severe COPD constitute the largest group of patients with chronic respiratory insufficiency. The sensation of dyspnea in these patients is mostly related to increased work of breathing, a consequence of an increased resistive load, of hyperinflation, and of the deleterious effect of intrinsic positive end-expiratory pressure (PEEP(i)). Once optimal medical treatment has been provided, pharmacological treatments of dyspnea exist (beta2-agonists, methylxanthines, opiates) but seldom suffice. Nonpharmacological complementary treatments must be envisioned. Patients with severe hyperinflation should be screened as possible candidates for lung reduction surgery. Pulmonary rehabilitation-including chest therapy, patient education, exercise training-has been established as effective on quality of life (QoL) and dyspnea. Noninvasive positive pressure devices may be effective for symptomatic treatment of severe dyspnea: continuous positive airway pressure (CPAP) counteracts the deleterious effect of PEEP(i) in patients with severe hyperinflation; intermittent positive pressure breathing (IPPB) may decrease dyspnea and discomfort during nebulized therapy; finally noninvasive positive pressure ventilation (NIPPV) has been shown to be effective on the sensation of dyspnea and QoL in COPD with severe hypercapnia.

Reactivity of antiglioma monoclonal antibodies for a large panel of cultured gliomas and other neuroectoderm derived tumors.

We produced three monoclonal antibodies, BF7, GE2 and CG12, against cultured human glioma cells. Their specificity was tested by an indirect antibody-binding radioimmunoassay on a panel of glial and non-glial tumor cell lines. BF7 and GE2 react preferentially with glioma cells and, except for one colon carcinoma line, they do not bind to the control non-neuroectodermal cells; they appear to be directed against common malignant glioma associated antigens. CG12, the third monoclonal antibody, binds to the great majority of tumor cell lines of neuroectodermal origin and does not bind to any other cell lines tested.

Is continuous transcutaneous monitoring of PCO2 (TcPCO2) over 8 h reliable in adults?

Monitoring of non-invasive ventilation (NIV) in a non-intensive care unit (non-ICU) setting requires a method of evaluating nocturnal PaCO2, such as transcutaneous CO2 monitoring (TcPCO2). However, changing the probe site after 4 h and recalibrating (as recommended) is time-consuming and impractical. Continuous (8-h) TcPCO2 monitoring at a lower electrode temperature (43 degrees C) in this setting has never been formally studied. Patients under intermittent NIV were studied (n = 28, aged 69 +/- 9 years, PaO2: 71 +/- 13 mmHg, PaCO2: 49 +/- 9 mmHg). After calibration and stabilization of TcPCO2 (Radiometer Tina TCM3 capnograph), arterial blood gases (ABG) were measured and compared with transcutaneous readings. In 10 patients who underwent continuous 8-h TcPCO2 recording, ABGs were also measured after 4 and 8 h. The correlation between TcPCO2 and PaCO2 was highly significant (r2 = 0.92, P<0.0001). Mean (TcPCO2 PaCO2) gradient (bias) was: -2.8 +/- 3.8 mmHg; limits of agreement were: (-10.4; +4.8 mmHg). TcPCO2-PaCO2 gradient was lowest (i.e. within-bias +/- 2 mmHg) between 40 and 54 mmHg, increasing below and above these values. Over 8 h, no significant drift of the TcPCO2 signal occurred (ANOVA). No discomfort or skin lesion was noted. In conclusion, with an electrode temperature of 43 degrees C, 8-h continuous monitoring of TcPCO2 was well tolerated, without any local side-effects or significant drift of TcPCO2 signal; when compared to previous reports, lowering the electrode temperature did not decrease performance for CO2 monitoring.

[Respiratory rehabilitation]. / Réadaptation respiratoire.

Pulmonary rehabilitation is directed at all patients with severe chronic respiratory insufficiency of any origin. Patients with chronic obstructive pulmonary disease clearly represent the majority. In a pulmonary rehabilitation programme, the patient must gain a better understanding of his disease and of the goals of the treatment. He benefits from permanent teaching on methods of independent self-treatment and follows a regular programme of exercise training and nutritional support aimed at increasing effort capacity. The ultimate goal of the programme is to send the patient home with improved quality of life and a higher degree of independence.

Peripheral neuropathy associated with high-dose Ara-C therapy.

Central nervous system toxicity associated with high-dose cytosine arabinoside (Ara-C) therapy (HD Ara-C) is well known. The authors report the case of a severe isolated peripheral polyneuropathy due to HD Ara-C. Electrophysiologic changes and histologic observations were consistent with axonal degeneration and scattered destruction of myelin sheaths. This observation emphasizes the need for careful complete neurologic evaluation for patients receiving HD Ara-C treatment.

Sniff nasal inspiratory pressure in patients with chronic obstructive pulmonary disease.

In subjects with normal lung mechanics, inspiratory muscle strength can be reliably and easily assessed by the sniff nasal inspiratory pressure (SNIP), which is the pressure measured in an occluded nostril during a maximal sniff performed through the contralateral nostril. The aim of this study was to assess the validity of the SNIP in patients with chronic obstructive pulmonary disease (COPD), where pressure transmission from alveoli to upper airways is likely to be dampened. Twenty eight patients with COPD were studied (mean forced expiratory volume in one second (FEV1) = 36% of predicted). The SNIP and the sniff oesophageal pressure (sniff Poes) were measured simultaneously during maximal sniffs, and were compared to the maximal inspiratory pressure obtained against an occlusion (MIP). All measurements were performed from functional residual capacity in the sitting position. The ratio SNIP/sniff Poes was 0.80, and did not correlate with the degree of airflow limitation. The ratio MIP/sniff Poes was 0.87, and the ratio SNIP/MIP was 0.97. Inspiratory muscle weakness, as defined by a low sniff Poes, was present in 17 of the 28 patients. A false diagnosis of weakness was made in eight patients when MIP was considered alone, in four when SNIP was considered alone, and in only three patients when MIP and SNIP were combined. We conclude that both the sniff nasal inspiratory pressure and the maximal inspiratory pressure moderately underestimate sniff oesophageal pressure in chronic obstructive pulmonary disease. Although suboptimal in this condition, the sniff nasal inspiratory pressure appears useful to complement the maximal inspiratory pressure for assessing inspiratory muscle strength in patients with chronic obstructive pulmonary disease.

Administration of growth hormone to underweight patients with chronic obstructive pulmonary disease. A prospective, randomized, controlled study.

Patients with chronic obstructive pulmonary disease (COPD) often develop weight loss, which is associated with increased mortality. Recombinant human growth hormone (rhGH) treatment has been proposed to improve nitrogen balance and to increase muscle strength in these patients. The aim of this study was to assess the effects of rhGH administration on the nutritional status, resting metabolism, muscle strength, exercise tolerance, dyspnea, and subjective well-being of underweight patients with stable COPD. Sixteen patients attending a pulmonary rehabilitation program (age: 66 +/- 9 yr; weight: 77 +/- 7% of ideal body weight; FEV1: 39 +/- 13% of predicted) were randomly treated daily with either 0.15 IU/kg rhGH or placebo during 3 wk in a double-blind fashion. Measurements were made at the beginning (DO) and at the end (D21) of treatment and 2 mo later (D81). Body weight was similar in the two groups during the study, but lean body mass was significantly higher in the rhGH group at D21 (p < 0.01) and D81 (p < 0.05). The increase in lean body mass was 2.3 +/- 1.6 kg in the rhGH group and 1.1 +/- 0.9 kg in the control group at D21 and 1.9 +/- 1.6 kg in the rhGH group and 0.7 +/- 2.1 kg in the control group at D81. At D21, the resting energy expenditure was increased in the rhGH group (107.8% of DO, p < 0.001 compared with the control group). At D21 and D81, the changes in maximal respiratory pressures, handgrip strength, maximal exercise capacity, and subjective well-being were similar in the two groups. At D21, the 6-min walking distance decreased in the rhGH group (-13 +/- 31%) and increased in the control group (+10 +/- 14%; p < 0.01). We conclude that the daily administration of 0.15 IU/kg rhGH during 3 wk increases lean body mass but does not improve muscle strength or exercise tolerance in underweight patients with COPD.

Oxygen saturation during daily activities in chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) frequently develop nocturnal oxygen desturation because of alveolar hypoventilation, worsening of ventilation-perfusion mismatch, and sometimes obstructive sleep apnoeas. In contrast, little is known about their oxygen status during the various activities of daily life. The aim of this study was to compare the oxygen saturation profile during day and night, and to assess the influence of different daily activities in COPD. During a rehabilitation programme, we studied 30 patients with moderate-to-severe COPD (median forced expiratory volume in one second (FEV1) 37% of predicted), without marked hypoxaemia (median arterial oxygen tension (Pa,O2) 9.1 kPa). Arterial oxygen saturation (Sa,O2) was assessed by pulse oximetry during night (8 h) and day (10.5 h). The mean and minimal Sa,O2 were calculated, and desaturations were defined as Sa,O2 falls > 4%.h-1. Daily activities were identified by the patients as resting, eating, washing, nebulization therapy and walking. Mean Sa,O2 was lower during the night (88%) than during the day (89%). In contrast, minimal Sa,O2 was lower during the day (69%) than during the night (72%), and the number of desaturations was higher during the day (8.6 desaturations.h-1) than during the night (6.8 desaturations.h-1). Mean Sa,O2 was 88% during walking, which was lower than during resting (90%), nebulization (90%), and meals (89%). The number of desaturations was higher during walking (13.1 desaturations.h-1), washing (12.6 desaturations.h-1), and eating (9.2 desaturations.h-1) than during resting (5.3 desaturations.h-1). We conclude that daily activities, such as walking, washing and eating, are associated with transient oxygen desaturation in patients with moderate-to-severe chronic obstructive pulmonary disease, even without marked resting hypoxaemia.

Thermogenic effect of bronchodilators in patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are frequently malnourished and have increased resting energy expenditure (REE). An increase in the work of breathing is generally considered to be the main cause of this hypermetabolism, but other factors may also be implicated. Bronchodilators may decrease the work of breathing by reducing airway obstruction, but beta 2 adrenergic agents have a thermogenic effect. The aim of this study was to determine the effect of salbutamol and ipratropium bromide administration on REE in patients with COPD. METHODS: Thirteen patients (10 men) of mean (SD) age 68.3 (7.3) years and forced expiratory volume in one second (FEV1) 39.0 (17.0)% predicted were studied on three consecutive days. The REE was measured by indirect calorimetry at 30, 60, 120, and 180 minutes after double blind nebulisation of either salbutamol, ipratropium bromide, or placebo in random order. RESULTS: FEV1 increased both after salbutamol and after ipratropium. The difference in the mean response between salbutamol and placebo over 180 minutes was +199 ml (95% CI +104 to +295). The difference in mean response between ipratropium and placebo was +78 ml (95% CI +2 to +160). REE increased after salbutamol but was not changed after ipratropium. The difference in mean response between salbutamol and placebo was +4.8% of baseline REE (95% CI +2.2 to +7.4). Heart rate increased after salbutamol but not after ipratropium. The difference in the mean response between salbutamol and placebo was +5.5 beats/ min (95% CI +2.6 to +8.4). CONCLUSION: Salbutamol, but not ipratropium bromide, induces a sustained increase in the REE of patients with COPD despite a reduction in airway obstruction.

[Candida fungemia]. / Fongémies à Candida.

From 1980 to 1986, 52 patients presented with an episode of fungemia due to Candida species at the Centre Hospitalier Universitaire Vaudois (representing 2% of the patients with positive blood cultures). In 51 of the 52 patients (98%) the infection was nosocomial, occurring after a median hospital stay of 24 days (range 4-250 days). Only 36 patients (69%) presented with an underlying condition (neoplasms in 18 patients, alcoholism in 7, diabetes in 6, immunosuppressive therapy in 5). In 19 patients (37%) an episode of bacteremia occurred prior to fungemia (median time 14 days, range 1-70 days). Candida albicans was the most commonly isolated species (71%). In 50 patients (96%) the episode of fungemia was associated with a significant, although nonspecific, clinical impairment. The digestive tract (38%) and N intravascular catheter (31%) were the two most common portals of entry for the fungemia. 32 patients (62%) received specific antifungal therapy consisting of amphotericin B in 29 patients (median total dose 450 mg, administered either alone or in association) or of ketoconazole in 3 patients. The global mortality was 46% and the fungemia-related mortality was 21%. Global and fungemia-related mortalities were significantly higher in patients not treated with antifungals than in those treated with them (87% versus 30%, p less than 0.001, and 47% versus 11%, p = 0.01 respectively).

Phenotyping of 60 cultured human gliomas and 34 other neuroectodermal tumors by means of monoclonal antibodies against glioma, melanoma and HLA-DR antigens.

The reactivity spectrum of three monoclonal antibodies (Mabs) to human malignant glioma, five Mabs to melanomas and one Mab anti-HLA-DR was investigated by an indirect antibody binding radioimmunoassay on a panel of cells derived from 60 glioma lines, including 47 malignant astrocytomas, 11 low-grade astrocytomas and two malignant ependymomas as well on cells from 12 melanoma, three neuroblastoma, three medulloblastoma, two schwannoma, two retinoblastoma, two choroïd plexus papilloma, ten meningioma and 12 unrelated tumor lines. The anti-glioma Mabs BF7 and GE2 reacted preferentially with gliomas, while the anti-glioma Mab CG12 reacted with gliomas, melanomas, neuroblastomas and medulloblastomas. The five anti-melanoma Mabs reacted with gliomas, neuroblastomas and medulloblastomas. The anti-HLA-DR Mab D1-12 reacted with gliomas, melanomas and some meningiomas. On the basis of the data presented, we describe three different antigenic systems; the first one is glioma-associated, the second one is related to differentiation antigens expressed on cells derived from the neuroectoderm and the third is represented by HLA-DR antigens which are expressed not only on B-lymphoblastoid cells but also on melanomas and gliomas.