Clinical validation of a prognostic tool in a population of outpatients treated for incurable cancer undergoing anticancer therapy: PRONOPALL study.

BACKGROUND: In 2008, a study of the characteristics of hospitalised patients led to the development of a prognostic tool that distinguished three populations with significantly different 2-month survival rates. The goal of our study aimed at validating prospectively this prognostic tool in outpatients treated for cancer in terminal stage, based on four factors: performance status (ECOG) (PS), number of metastatic sites, serum albumin and lactate dehydrogenase. PATIENTS AND METHODS: PRONOPALL is a multicentre study of current care. About 302 adult patients who met one or more of the following criteria: life expectancy under 6 months, performance status ≥ 2 and disease progression during the previous chemotherapy regimen were included across 16 institutions between October 2009 and October 2010. Afterwards, in order to validate the prognostic tool, the score was ciphered and correlated to patient survival. RESULTS: Totally 262 patients (87%) were evaluable (27 patients excluded and 13 unknown score). Median age was 66 years [37-88], and women accounted for 59%. ECOG PS 0-1 (46%), PS 2 (37%) and PS 3-4 (17%). The primary tumours were: breast (29%), colorectal (28%), lung (13%), pancreas (12%), ovary (11%) and other (8%). About 32% of patients presented one metastatic site, 35% had two and 31% had more than two. The median lactate dehydrogenase level was 398 IU/l [118-4314]; median serum albumin was 35 g/l [13-54]. According to the PRONOPALL prognostic tool, the 2-month survival rate was 92% and the median survival rate was 301 days [209-348] for the 130 patients in population C, 66% and 79 days [71-114] for the 111 patients in population B, and 24% and 35 days for [14-56] the 21 patients in population A. These three populations survival were statistically different (P <0.0001). CONCLUSION: PRONOPALL study confirms the three prognostic profiles defined by the combination of four factors. This PRONOPALL score is a useful decision-making tool in daily practice.

[Intra-alveolar pulmonary haemorrhage, an unusual manifestation of the primary antiphospholipid syndrome]. / L'hémorragie intra-alvéolaire, une complication rare du syndrome primaire des antiphospholipides.

Pulmonary embolism is the main pulmonary manifestation of primary antiphospholipid syndrome. Other pulmonary manifestations including intra-alveolar haemorrhage are less common. We report a 36-year-old man with a primary antiphospholipid syndrome who presented with an acute respiratory failure due to the association of pulmonary embolism and intra-alveolar haemorrhage. This diagnosis should be systematically considered as it is life threatening and requires a specific therapy.

[Malignant pleural effusion as the presenting site of cancer: comparison with metastatic pleural effusions from known cancers]. / Pleurésies malignes révélatrices d'un cancer: comparaison des étiologies avec les pleurésies métastatiques d'un cancer connu.

INTRODUCTION: Few studies have focused on malignant pleural effusions as the presenting site of cancer. The aim of our study is to evaluate their proportion in the total number of malignant pleural effusions, to identify their causes and determine their prognosis. PATIENTS AND METHODS: Patients were selected retrospectively from the database of the Pathology Department of the University Hospital of Nantes (France), which contained only the patients in whom a diagnosis of malignant effusion was made as the result of cytology of pleural fluid or pleural biopsy, between January 1999 and December 2001. Pleural effusions as the presenting site of cancer (R group) and those metastatic from known cancer (C group) were identified by study of the clinical data. RESULTS: Of 209 cases, the malignant effusion was presenting site of cancer in 85 patients. In this group (R), a male predominance was identified (sex-ratio 1.36 vs. 0.42 in group C, p<0.01). In order of frequency the causes were: lung cancer (31 cases), mesothelioma (18 cases), primary cancer unknown (15 cases), ovarian carcinoma (10 cases), lymphoma (5 cases) and other carcinoma (2 cases). In men lung cancer was the leading cause (42.8%); and in women its frequency was the same as ovarian carcinoma (27.7%). The median survival of these patients was 6.5 months. CONCLUSION: Pleural effusions as the presenting site of cancer account for 41% of all malignant pleural effusions. Their causes are mainly lung cancer in men and lung and ovarian cancers in women.

[Difficulties in the management of localised pulmonary Goodpasture's syndrome]. / Difficultés de la prise en charge d'une forme pulmonaire isolée du syndrome de Goodpasture.

INTRODUCTION: The diagnosis of the pulmonary forms of Goodpasture's syndrome is not easy and requires a renal biopsy when no anti-glomerular basement membrane antibodies are detected, since the disease can lead to spontaneous massive intra-alveolar haemorrhage that can be fatal. Treatment for the pulmonary-renal form combining corticosteroids, cyclophosphamide and plasmapheresis should be applied to the pulmonary form to control haemorrhage and prevent relapse. CASE REPORT: We report the case of a patient suffering from the localised pulmonary form of Goodpasture's syndrome in whom the diagnosis was delayed due to a negative indirect immunofluorescent antibody bioassay. After a serious early relapse remission was achieved with comprehensive treatment and a tobacco withdrawal programme. CONCLUSION: If there is no delay in diagnosis and comprehensive treatment is given, the prognosis for these patients is good with a recovery rate of 80 to 90%.

[Carrington's disease without eosinophils in the bronchial lavage]. / Une maladie de Carrington sans éosinophilie au lavage broncho-alvéolaire.

INTRODUCTION: Idiopathic chronic eosinophilic pneumonia (ICEP) or Carrington's disease is an infiltration of the lung parenchyma by eosinophils without known cause. The diagnosis of ICEP is based on well defined clinical and radiological characteristics associated with blood and/or alveolar eosinophilia. Alveolar hypereosinophilia is marked and regarded as a constant feature. CASE REPORT: We report the case of a 57 year old man seen on account of a cough and deterioration of general health associated with radiographic peripheral pulmonary infiltrates, blood hypereosinophilia but no hypereosinophilia in the bronchial lavage (BL). The diagnosis of ICEP was made after histological examination of a surgical lung biopsy. CONCLUSION: Absence of alveolar hypereosinophilia in ICEP remains exceptional and in this case confirmation of the diagnosis may depend on examination of a lung biopsy.

[Complex respiratory aspergillosis: diagnostic and therapeuthic difficulties]. / Aspergilloses respiratoires complexes: difficultés diagnostiques et thérapeutiques.

INTRODUCTION: Respiratory aspergillosis with different physiopathologic mechanisms can be associated in one patient in rare occasions. CASE REPORT: We review three cases associating an allergic bronchopulmonary aspergillosis (ABPA) and an other form of aspergillosis: aspergilloma, chronic necrotizing pulmonary aspergillosis and we present a review of literature. CONCLUSION: Such associations result in diagnostic and therapeutic difficulties. Corticosteroid treatment used for ABPA can increase the risk of severe infections. Such cases are a good indication of systemic antifungal therapy.

Regional gas distributions and single-breath washout curves in head-down position.

Regional distributions of inspired 133Xe and single-breath washout curves were compared in six young healthy subjects for the upright and the head-down positions. The regional distributions of volumes (at 0, 25, 50, and 75% vital capacity, VC) and of 133Xe boluses inhaled at residual volume (RV) were inverted in the head-down position, thus behaving as if they were determined by gravity acting via the weight of the lung rather than by thoracicoabdominal shape adaptations. Nevertheless no mirror image was obtained. The vertical differences in regional distribution of the 133Xe RV bolus and of the volumes at 25% VC were increased in the head-down position, whereas the vertical difference in volumes at RV was decreased, indicating enhanced air trapping and sequential ventilation at low volumes. This was attributed to the effect of the increased pulmonary blood volume in the head-down posture. Accordingly the size of phase IV on the washout curves with the SF6-bolus as well as with the N2-resident gas method was increased in the head-down position.

[Cardiorespiratory function in young bronchitis patients, mostly mineworkers, before and after kinesitherapy and exertion training. Comparison with a control group (Preliminary results)]. / Cardiorespiratoire functie bij jonge bronchitislijders, voor het merendeel mijnwerkers, vóór en na kinesitherapie en inspanningstraining. Vergelijking met een controlegroep (Preliminaire resultaten).

We have studied the effects of respiratory physiotherapy and physical training on the cardiopulmonary function of patients with early chronic bronchitis and broncho-obstruction presumably at the beginning stages. The trained group was compared with a control group who was treated with infra-red rays on the thorax. Both groups were treated during four weeks. All patients were less than 50 years old and all were smokers. They complained of dyspnea on exertion (stage 2 ECCS), cough and expectoration for at least one year. Their spirometry and airway resistance values were normal or near normal but at least two of the following functional indices were altered in all: the He residual volume, the slope of N2 phase III and/or the He bolus phase IV. In the trained group, functional indices of central or peripheral airway obstruction did not change after the four weeks of treatment. On the contrary, the slow vital capacity (SVC) and the peak expiratory flow (PEF), which are presumably more influenced by the force of respiratory muscles, were significantly increased after respiratory rehabilitation. During steady-state exercise of moderate intensity 1.) a slight increase of pH (P less than 0.1 at a VO2 of 1.5 l/min and 1.75 l/min), perhaps due to a lessened lactacidemia, 2.) a decrease in ventilation (VE) (P less than 0.1 at a VO2 of 1.25 l/min) and 3.) a reduction in the alveolo-arterial gradient (AaDO2) (P less than 0.1 at a VO2 of 1.25 l/min) were observed. In the control group there was no change of respiratory functional indices at rest or during exercise after treatment. The reduction of AaDO2 observed in the trained group could be due to an improvement of pulmonary gas exchange. This was small, however, and probably without clinical significance. We believe that the improvement of dyspnea noted in the trained group could be due to the increase in ventilatory performance (SVC, PEF and VE) and to a better O2 extraction in the peripheral muscles.

[Treatment of bronchial obstruction with beta-2-mimetic and anticholinergic agents in aerosol. Advantages of the combination of both groups of pharmaceuticals]. / Behandeling van bronchusobstructie met bêta 2-mimetica en anticholinergica in aërosol. Voordelen van het associëren van beide groepen farmaca.

The authors remind the fundamental items of the bronchodilating treatments by means of pressurized aerosols using beta 2-agonists and parasympatholytics; a review of the literature on the toxicity of the different propellants used in the cartridges is presented. The problems proceeding from inequalities of deposition of the aerosols in the normal subjects and in lung diseases are stressed. Results regarding the prevalence of positive responses to aerosols of atropine methonitrate and to aerosols of a beta-agonist given to a group of patients with reversible broncho-obstruction are presented and discussed. The advantages of oxitropium bromide, a recently synthetized parasympatholitic drug which appears more interesting than ipratropium bromide, are discussed by means of the ventilatory results observed with both drugs in 19 patients with reversible broncho-obstruction. The interest of associating atropinics and beta 2-agonists in the same cartridges is discussed. The efficacy of a recently commercialized preparation associating fenoterol and ipratropium bromide is commented.

Oxitropium bromide (Ba 253), an advance in the field of anticholinergic bronchodilating treatments. Preliminary results.

The changes in FEV1 and in specific conductance induced by 200 micrograms oxitropium bromide given as pressurized aerosol were measured at 8 time intervals during 7 hours after inhalation in a group of 19 patients with reversible broncho-obstruction. The working of the drug was compared to the functional values observed at the same time intervals after placebo, 40 micrograms ipratropium bromide and 400 micrograms fenoterol. Both oxitropium and ipratropium were definitely and significantly superior to placebo at all time intervals. Oxitropium was superior to ipratropium at the 7th hour. At this time interval the difference was significant At the 7th hour oxitropium gave higher mean results than fenoterol, but this difference was not significant. The drug was also compared to its competitors regarding its subjective and cardiovascular tolerance. No unfavourable side-effects were observed.

[Effect of almitrine on arterial gases in patients with chronic respiratory insufficiency. Comparison with doxapram. Preliminary results]. / Invloed van almitrine op de arteriële gassen bij patiënten met chronische respiratoire insufficiëntie. Vergelijking met doxapram. Voorlopige resultaten.

We compared the effects of almitrine and doxapram on the arterial blood gases and ventilation of patients with chronic respiratory insufficiency and chronic hypercapnia and hypoxemia. Sixteen long-term in-patients were randomly allocated to one of the following treatment groups: the first group (8 patients) received IV almitrine 0.5 mg/kg and the second group (8 patients) IV doxapram 1 mg/kg by IV perfusion during 30 min. All gave their informed consent. Arterial blood gases and ventilation were measured 10 min and 5 min before treatment, at the 5th, 15th and 25th min of perfusion time, and 5, 10 and 15 min after infusion. There was a marked increase in paO2 in almitrine-treated patients, which was maximum at the 25th min of infusion (+ 14.6 mm Hg, p < 0.001), but only a slight improvement was observed in the doxapram group (+ 3.3 mm Hg, p < 0.05). After almitrine the maximum mean paCO2 decrease was at the 10th min after perfusion (-6.9 mm Hg, p < 0.001); after doxapram the maximum decrease, although highly significant, was much less (-2.8 mm Hg, p < 0.01). Thus, at the presently used and well-tolerated doses, almitrine is much more efficient than doxapram in improving gas exchange in patients with chronic hypoxemia and hypercapnia. However, complementary studies using higher dosage of doxapram are warranted.

Contribution to the standardization of pharmacodynamic tests in lung function.

By bringing the aerosols in a spirometrical bell from which a constant volume aerosol was thereafter inhaled by each subject through a bi-directional valve, we observed more consistent and reproducible ventilatory results than by giving the aerosols by means of a classical device via a face mask. Moreover the results were significantly higher with the first technique; this fact suggests that the quantity of inhaled broncho-active drug with suitable granulometry would have been on the average greater per minute with the first method.

Diurnal variations and reproducibility of the N2 closing volume test in healthy subjects.

To assess the diurnal variation of closing volume measurements, 11 non-smokers and 10 somkers, all healthy, were tested with the single-breath nitrogen test. In each subject, 3 satisfactory tracings were recorded at 9:a.m., 11:a.m., 1:p.m., 3:p.m. and 5:p.m. on each of two consecutive days. Duplicate copies of the tracings were read in radom order by two independent observers. The "best+ and the mean values of closing volume to vital capacity ratio (CV/VC or phase 4/VC) and of the slppe of phase 3 were calculated. The study shows that: (1) the time of the day may be a source of variation of the closing volume measurements. Meals and cigarette smoke did not appear to be responsible for this diurnal variation, (2) values obtained with the "best" tracing method can, at least in some readers, give systematic differences with the mean of several traces, (3) individual variations in CV/VC and in the slope of phase 3 are the highest with the "best" trace analysis, and (4) the vlaues obtained by two independent readers may significantly differ. The differences observed between hours, although significant, were nevertheless small in magnitude and did not explain most of the variation of the measurements. Variations in trace aspect were small in some subjects. The reproducibility of the test was remarkable in them, at least when the junction of phase 4 with phase 3 was well defined. In other subjects, the coefficient of variation was high mainly because of varying curve shape and/or poorly defined departure of phase 4. This explains for a great part the intra-and interreader variations observed in this study.

Carbuterol, fenoterol, orciprenaline, salbutamol and terbutaline per os in reversible obstructive chronic bronchitis.

The effects of tablets of carbuterol, orciprenaline, salbutemol, terbutaline and fenoterol at two dosages were studied using FEV1 and specific airway conductance as parameters. A placebo was used as a reference. Carbuterol and fenoterol proved to be more potent than the other sympathomimetic competitors. Fenoterol 5 mg was on the average somewhat less potent than 3 mg carbuterol. This differnce was not statistically significant for FEV1; it was significant three hours after intake for airway conductance. None of the drugs produced significant changes of the blood pressure. Carbuterol and 12 mg fenoterol caused a statistically significant increase in heart rate. ECG changes were observed in eight patients with the different beta-sympathomimetics, with the exception of 5 mg fenoterol.