Factors predicting survival following noninvasive ventilation in amyotrophic lateral sclerosis.

BACKGROUND/AIMS: The involvement of respiratory muscles is a major predicting factor for survival in amyotrophic lateral sclerosis (ALS). Recent studies show that noninvasive ventilation (NIV) can relieve symptoms of alveolar hypoventilation. However, factors predicting survival in ALS patients when treated with NIV need to be clarified. METHODS: We conducted a retrospective study of 33 consecutive ALS patients receiving NIV. Ten patients had bulbar onset. We determined the median survivals from onset, diagnosis and initiation of NIV and factors predicting survival. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models. RESULTS: The median initial and maximal total uses of NIV were 10 and 14 h/24h. The overall median survival from ALS onset was 34.2 months and worsened with increasing age and bulbar onset of the disease. The median survival from initiation of NIV was 8.4 months and was significantly poorer in patients with advanced age or with airway mucus accumulation. Survival from initiation of NIV was not influenced by respiratory parameters or bulbar symptoms. CONCLUSION: Advanced age at diagnosis and airway mucus accumulation represent poorer prognostic factors of ALS patients treated with NIV. NIV is a helpful treatment of sleep-disordered breathing, including patients with bulbar involvement.

High-efficiency gene transfer to primary monkey airway epithelial cells with retrovirus vectors using the gibbon ape leukemia virus receptor.

The efficiency of retrovirus-mediated gene transfer to primary airway epithelial cells from rhesus monkeys was evaluated. We compared the use of murine amphotropic retrovirus vectors to the use of murine retrovirus vectors containing the envelope (Env) glycoproteins from gibbon ape leukemia virus (GALV). These vectors use distinct receptors to gain entry into host cells. We found that vectors with the GALV Env glycoproteins are up to 10-fold more efficient at transducing genes into primary monkey airway epithelial cells than vectors with the amphotropic Env glycoproteins. Under optimal conditions, up to about 80% of primary monkey airway epithelial cells could be transduced with the vector containing the GALV Env glycoproteins. In addition, we found that delivery of retrovirus vectors to the apical side of polarized airway epithelial cultures was significantly more efficient than delivery to the basal side. These results suggest the feasibility of luminal delivery of retrovirus vectors to the lung.

[Prospects of gene therapy in mucoviscidosis using viral infection of the airway epithelium]. / Perspectives de thérapie génique de la mucoviscidose par infection virale de l'épithélium des voies aériennes.

Mucoviscidosis is the most common severe inherited autosomal recessive disease. Since the gene has been recognised (cystic fibrosis transmembrane conductance regulator gene) (CFTR) the technique of genetic transfer has been applied to the airway epithelium. The prospect for gene therapy to treat the consequences of bronchopulmonary mucoviscidosis is now evident. The in vitro introduction of the normal CFTR human gene in epithelial cells has been obtained using recombinant retrovirus, adenovirus and parvovirus rendered defective for replication. The abnormal bioelectric phenotype of the cells from patients with mucoviscidosis has been corrected. Of these, only adenovirus and parvovirus have been capable of assuring effective genetic transfer by direct introduction into the airways. This data has been considered sufficient to justify starting clinical trials in man with adenovirus; the preliminary results confirm the possibility of correcting the chloride transport. Nevertheless the observation of an immune response and secondary inflammation raises ethical questions relative to the safety of such trials. This observation justifies research into an alternative non-viral technique such as employing liposomes. The authors have made a review of the data which may be established as a basis for genetic therapy for mucoviscidosis.

[Pulmonary metastases from a hormone-induced clear cell adenocarcinoma of the vagina]. / Métastases pulmonaires d'un adénocarcinome vaginal à cellules claires hormon-induit.

The authors report the case of a patient aged 27 suffering from a clear cell adenocarcinoma of the vagina which was related to her mother taking Diethylstilboestrol or Distilbene (DES) during her pregnancy. This young woman presented with pulmonary metastases for which several trials of chemotherapy ended in failure. The case raises several problems amongst which are epidemiologies of cancers induced by Diethylstilboestrol (DES), their prognosis as well as the therapeutic strategies at the time of diagnosis and the recurrences which occur as metastases.

[Proximal bronchial cancer with hypoxemia due to right to left intrapulmonary shunt. Correction of hypoxemia after pneumonectomy]. / Cancer bronchique proximal avec hypoxémie par shunt droit-gauche intrapulmonaire. Correction de l'hypoxémie après pneumonectomie.

The authors report a case of a patient who was in hospital for a bronchial cancer completely occluding the left superior and inferior lobar bronchi. Respiratory function tests showed: an FEV1 of 1.7 litres, FEV1 (vital capacity ratio of 60%), a TLC of 76% of the predicted value and a PaO2 of 52 mm of mercury with an elevated alveolar arterial oxygen gradient. The ventilation perfusion lung scan showed that the left lung was not ventilated but was perfused. A left pneumonectomy was judged to have removed the cancer and enabled a correction of the hypoxaemia. The authors recall the functional repercussions of absent ventilation of one lung by a proximal bronchial obstruction and the therapeutic implications in the realm of neoplastic pathophysiology.

[A predominant manifestation of pleural cryptococcosis in acquired immunodeficiency syndrome]. / Cryptococcose d'expression pleurale dominante au cours du syndrome d'immunodéficience acquise.

Systemic cryptococcosis occurs in at least 6% patients with human immunodeficiency virus infection (HIV). The lung infection by cryptococcus neoformans, less frequently observed than meningeal involvement, consists usually in focal parenchymal mycosis. Authors report an apparently isolated pleural cryptococcosis in a 41 years old mal with HIV infection. Diagnosis was performed initially by pleural and bronchial alveolar lavage (BAL) fluid culture. Characteristic cryptococcosis pathological and histologic findings from thoracoscopy and open pleural biopsy are described. Cryptococcus capsular polysaccharides stainings and thoracoscopy interests are emphasized.

[Mediastinal-pulmonary sarcoidosis with unilateral pseudotumorous presentation. Apropos of a case]. / Sarcoïdose médiastino-pulmonaire à forme pseudo-tumorale unilatérale. A propos d'un cas.

We report a case of a patient of forty two years who was admitted with a chronic cough and had a left hilar "tumour". Scanning showed a hilar opacity with an air bronchogram. Fibreoptic bronchoscopy did not succeed in achieving a precise diagnosis, the biopsies showed no sign of malignancy. An open lung biopsy was necessary to establish the diagnosis of pulmonary mediastinal sarcoidosis with a pseudo-tumoral presentation and localised unilateral disease involving a segmental bronchus and the left upper lobe. There was a rapidly favourable outcome after treatment with steroids.

[Indolent mastocytosis and bronchial hyperreactivity. A case report]. / Mastocytose indolente et hyperréactivité bronchique. A propos d'une observation.

Mastocytosis (MS) may be exclusively cutaneous or, more rarely, systemic. MS may be indolent (benign), aggressive, leukaemic or associated with a myeloproliferative disorder. The clinical expression of MS may be secondary to the direct consequences of the development of mastocytes in tissue or correspond to the paroxysmal features related to the liberation of vasoactive and spasmogenic mediators by activated mastocytes. Dyspnoeic episodes are classical but the physiopathological mechanism is poorly documented. True asthma or bronchopulmonary mastocytosis seems rare. The authors report evidence of non-specific bronchial hyper-reactivity (HRB) to Carbachol in a patient effected with benign cutaneous mastocytosis with secondary elevation of the total serum IGE. Factors determining the HIB are discussed and appear primarily linked to the mastocytosis.

[Diagnostic difficulties in angiosarcoma of the pulmonary artery with hemoptysis]. / Difficultés diagnostiques d'une forme hémoptoïque d'angiosarcome de l'artère pulmonaire.

Intimal sarcomas growing from the pulmonary trunk or branches of the pulmonary artery, are rare tumours in which the diagnosis is most often made at autopsy or during a thoracotomy. Usually the clinical pictures is non specific resembling a severe pulmonary embolus which is resistant of all treatment. With the help of new imaging techniques, a pre-operative diagnosis is made in more than half the cases. When there is a tumour which is relatively localised and without endoluminal invasion, as in the observation reported here, the diagnosis rests on the histology from the operative specimen.

[Hypoxemia secondary to inferior vena cava return into left atrium]. / Hypoxémie secondaire à un abouchement de la veine cave inférieure dans l'oreillette gauche.

The case of a right-to-left shunt-induced hypoxemia with an abnormal return of the inferior vena cava (AIVCR) into the left atrium (LA) is reported in a 30-year-old male with cyanosis and polycythemia. The chest X ray and the lung CT scan was normal. Spirometry was normal but the transfert-CO coefficient (KCO) was lowered. Hypoxemia was observed at rest and worsening during exercise. The alveolo-arterial oxygen tension difference under hyperoxia was increased (56 kPa). Contrast echocardiography (CEch) suggested the presence of an AIVCR with a right-to-left shunt only observed by the inferior route. The inferior vena cava (IVC) angiography and the magnetic resonance imaging demonstrated an AIVCR characterized by a direct drainage of IVC in the left atrium. The good tolerance can be explained by the association of AIVCR with an inter-auricular septal defect resulting in a left-to-right shunt which partially corrected the right-to-left shunt. After surgical treatment, arterial blood gases normalized, KCO remained low and CEch became negative.

[Thoracoscopy in pulmonary histiocytosis X]. / Apport de la thoracoscopie dans l'histiocytose X pulmonaire.

We report 4 cases of recurrent multiple pneumothorax in patients with diffuse interstitial lung disease diagnosed as histiocytosis X. These cases demonstrate the dual value of thoracoscopy in that disease: (1) it facilitates the diagnosis by showing the characteristic macroscopic aspect of the lung with multiple blebs and by enabling pulmonary biopsies to be performed; (2) it contributes to the treatment and prevention of pneumothorax by diffuse pleural poudrage. Immediate thoracoscopy should therefore be contemplated in special conditions, such as pulmonary interstitial lung disease with pneumothorax as first presentation.

[Bronchial tuberculosis. Report of 4 cases]. / La tuberculose bronchique. A propos de 4 cas.

Four cases of bronchial tuberculosis are reported. The first case was revealed by signs of bronchitis; in the second patient M. tuberculosis was found at light microscopy but x-ray films of the chest were normal; the third patient presented with signs of bronchitis and upper lobe infiltration on fibrous sequelae; the fourth patient showed a pseudo-tumoral bronchial image. These cases and those of the literature show that clinical signs are usually those of bronchitis sometimes with the systemic symptoms of tuberculosis. Chest radiography may be normal or may display disorders of ventilation of lung opacities suggestive of recent tuberculosis. Endoscopy reveals granular inflammation with whitish secretion and progressive stenosis. Diagnosis rests on bacteriological and pathological examinations. Medical treatment does not differ from the standard one. Sequelae consisting of bronchial stenosis or bronchiestasis are extremely frequent. Bronchial tuberculosis is now seldom encountered and usually affects elderly women. However, it may now become more frequent due to the greater number of cases of tuberculosis with a slightly atypical course, as found in AIDS patients.

[Isolated pleuropulmonary metastases of uterine sarcoma]. / Métastases pleuro-pulmonaires isolées d'un sarcome utérin.

We report the case of a 52-year old post-menopausal woman in whom the finding of a right paravertebral mediastinal and pulmonary mass and a homolateral pleural effusion revealed the presence of a large uterine tumour. Pleural fluid cytology was in favour of an undifferentiated tumour, and biopsy of the endometrium pointed to a connective tissue tumour. Following immunohistochemical staining, hysterectomy combined with adnexectomy confirmed the diagnosis of uterine sarcoma. Later on, the patient underwent thoracoscopy which showed multiple pleural metastases. In view of concordant histological results and of the appearance of multiple spherical images at radiology, chemotherapy with adriamycin, ifosfamide and vincristine was instituted but proved to be ineffective: the patient died after two cycles of this therapeutic regimen.

["Spontaneous" resolution of two severe methotrexate-induced pneumonias]. / Résolution spontanée de deux pneumopathies sévères au méthotrexate.

The beneficial role of corticosteroid therapy for the treatment of methotrexate-induced pneumonia remains controversial. We report two cases of acute severe interstitial pneumonia induced by methotrexate in patients with non-Hodgkin lymphoma given a polychemotherapy protocol (M'BACOD). The first signs appeared on the eleventh day of the first cycle in patient one and on the tenth day of the third cycle in patient two. The causal implication of methotrexate was based on the history, the clinical and radiological presentation, and the negative tests in both patients: lymphocyte alveolitis with granulomatous lesions on the transbronchial biopsy in patient one and positive leukocyte migration test in the presence of methotrexate in patient two. Early acute respiratory failure required high flow rate oxygen therapy with positive expiratory pressure ventilatory assistance. The course was rapidly favorable both for blood gases and radiographic presentation without corticosteroids. These two cases illustrate that pulmonary disease can be cured without corticosteroids despite severe respiratory failure at onset. This provides a further argument on reservations about using corticosteroids for suspected methotrexate-induced pneumonia.

[A rare cause of pleurisy from subdiaphragmatic origin: epidermoid cyst of the spleen]. / Une cause rare de pleurésie d'origine sous-diaphragmatique: le kyste épidermoïde de la rate.

Subdiaphragmatic diseases are a classical but uncommon cause of pleural effusion. We report here the case of a woman admitted for a left pleural effusion which led to the discovery of a splenic tumour. Pathological examination of the splenectomy specimen showed that the tumour was an epidermoid cyst of the spleen. Cysts of the spleen are exceptionally revealed by pleurisy. Epidermoid cysts account for 10% of all non-parasitic splenic cysts. They remain silent for a long time and are usually disclosed by such complications as compression of surrounding organs, rupture or superinfection.

[Bronchospasm disclosing pulmonary embolism]. / Bronchospasme révélateur d'une embolie pulmonaire.

We report the case of an 82-year old male patient without history of chronic obstructive lung disease in whom a sudden respiratory distress syndrome with sibilant rales in both lungs revealed a moderately severe pulmonary embolism, later confirmed by angiography. Bronchospasm occurring in the acute phase of pulmonary embolism may be expressed as acute asthma refractory to bronchodilators. This bronchoconstriction, seldom detectable clinically, seems to be related to regional alveolar hypocapnia in the territories embolized and to platelet-produced mediators, through a vagus nerve-mediated reflex. It must not hide pulmonary embolism, particularly in a suggestive context and when bronchodilators are ineffective.

Migratory organizing pneumonitis "primed" by radiation therapy.

We report on two women presenting with cough and fever, 4 and 7 months, respectively, after starting breast radiation therapy following surgery for breast carcinoma. Chest roentgenogram and computed tomographic (CT) scan demonstrated alveolar opacities, initially limited to the pulmonary area next to the irradiated breast, but later migrating within both lungs. Intra-alveolar granulation tissue was found in transbronchial lung biopsies. Corticosteroid treatment resulted in dramatic clinical improvement, together with complete clearing of the pulmonary opacities on chest imaging. However, clinical and imaging relapses occurred when corticosteroids were withdrawn too rapidly; with further improvement when they were reintroduced. The reported cases clearly differ from radiation pneumonitis. They were fairly typical of cryptogenic organizing pneumonitis, also called idiopathic bronchiolitis obliterans organizing pneumonia, with the exception of the radiation therapy, partially affecting the lung, which had been performed within the previous months. Since focal radiation therapy involving the lung may induce diffuse bilateral lymphocytic alveolitis, we hypothesize that this may "prime" the lung to further injury, leading to cryptogenic organizing pneumonitis.

Sodium- and chloride-conductive pathways in cultured mouse tracheal epithelium.

The utility of a transgenic murine model of cystic fibrosis (CF) lung disease will likely depend on whether the mouse's proximal airway epithelium is characterized by Na(+)- and Cl(-)-conductive pathways comparable to those found in human airways. Therefore, the electrophysiological properties of primary cultures of mouse tracheal epithelium (MTE) were investigated using double-barreled, Cl(-)-selective microelectrodes. Epithelial cells isolated from freshly excised mouse tracheae formed confluent polarized monolayers on permeable collagen supports and developed significant transepithelial potential differences (approximately -10 mV) within 5-6 days postseeding. Under basal conditions, the MTE monolayers had an equivalent short-circuit current (Ieq) of -21.1 +/- 2.1 microA/cm2 and a transepithelial resistance of 424 +/- 49 omega.cm2. Intracellular measurements indicated that the apical (Va) and basolateral (Vb) membrane potential differences were -16.9 +/- 1.5 and -25.4 +/- 1.5 mV, respectively; apical membrane fractional resistance was 0.36 +/- 0.03; and intracellular Cl- activity was 56.1 +/- 2.3 mM. The presence of an apical Na+ conductance was demonstrated by luminal amiloride application (10(-4)M), which decreased Ieq, hyperpolarized Va, and increased the fractional resistance of the apical membrane. The presence of an apical Cl- conductance was demonstrated by substitution of Cl- with gluconate in the luminal bath, which decreased intracellular Cl- activity and increased the fractional resistance of the apical membrane. Luminal application of ATP (10(-4) M was also found to increase the rate of Cl- secretion.(ABSTRACT TRUNCATED AT 250 WORDS)