Lung function parameters in omalizumab responder patients: An interesting tool?

BACKGROUND: Omalizumab, an anti-IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and nonresponder patients remain inconclusive. The objective of this real-life study was to compare the changes in forced expiratory volume in 1 second (FEV1) of omalizumab responders and nonresponders at 6 months. METHODS: A multicenter analysis was performed in 10 secondary and tertiary institutions. Lung function parameters (forced vital capacity (FVC), pre- and postbronchodilator FEV1, residual volume (RV), and total lung capacity (TLC) were determined at baseline and at 6 months. Omalizumab response was assessed at the 6-month visit. In the omalizumab responder patients, lung function parameters were also obtained at 12, 18, and 24 months. RESULTS: Mean prebronchodilator FEV1 showed improvement in responders at 6 months, while a decrease was observed in nonresponders (+0.2±0.4 L and -0.1±0.4 L, respectively, P<.01). After an improvement at 6 months, pre- and postbronchodilator FEV1 remained stable at 12, 18, and 24 months. The FEV1/FVC remained unchanged over time, but the proportion of patients with an FEV1/FVC ratio <0.7 decreased at 6, 12, 18, and 24 months (55.2%, 54.0%, 54.0%, and 44.8%, respectively, P<.05). Mean RV values decreased at 6 months but increased at 12 months and 24 months (P<.05). Residual volume/total lung capacity (RV/TLC) ratio decreased at 6 months and remained unchanged at 24 months. CONCLUSION: After omalizumab initiation, FEV1 improved at 6 months in responder patients and then remained stable for 2 years. RV and RV/TLC improved at 6 months.

[Management of non-small cell lung cancer patients harboring activating mutations and CNS progression]. / Caractéristiques et prise en charge de l'évolutivité cérébro-méningée des cancers bronchiques dans un contexte de mutation activatrice.

The central nervous system (CNS), through carcinomatous meningitis or solid brain metastases, is the most common site of recurrence in non-small cell lung cancers (NSCLC) with activating mutations. Our retrospective study describes the population of patients with CNS metastases of NSCLC harboring activating mutation with targeted therapy (EGFR, ALK, BRAF, HER2) in 4 French regional reference hospitals. 60 patients were analyzed. The proposed treatments were heterogeneous and included combinations of chemotherapy, targeted therapy and radiotherapy±associated with topical treatments. Median overall survival following CNS metastasis in these patients was 15.8 months for meningitis carcinoma and 26 months for brain metastases. In patients with brain metastases, the addition of targeted therapy treatment allows a significant improvement in median progression free survival from 5.9 months to 10.6 months (HR 0.48 CI95 [0.24 to 0.97] P=0.035). These patients seem therefore benefit from systemic therapy and particularly targeted therapy with better survival than usual.

[Cohort of patients initiated to home ventilation. Observational and prospective study]. / Cohorte de patients nouvellement traités par ventilation non invasive à domicile. Étude observationnelle, prospective et multicentrique.

Cohort of patients initiated to home ventilation. Observational and prospective study. The effectiveness of home noninvasive ventilation (NIV) for chronic respiratory failure (CRF) is well established. However, few data are available about home NIV prescription and utilization according to the different etiologies of respiratory failure. The ANTADIR Federation, in partnership with the Ventilatory Support Group of the French Speaking Pulmonary Society, has set up a national, observational and multicenter cohort study. The main goal of this study is to analyze the clinical data justifying home NIV prescription in patients with chronic respiratory insufficiency. The secondary objectives will be to assess: the evolution of comorbidities or their occurrence, hospitalizations, NIV compliance, dropout and survival. The population includes patients with chronic respiratory failure newly initiated onto NIV, both in a stable state and following an acute exacerbation who qualify for long-term NIV. Data collected include: diagnosis and comorbidities, age, sex, BMI, biomarkers (hematocrit, arterial blood gases, total CO2) and functional data (FEV1, VC, TLC), nocturnal results (SaO2, PtcCO2), type of ventilator used, ventilator parameters and mask type. Follow-up data will be collected at 4 months, 1 year and 2 years and will include: hospitalizations, changes in prescription, adherence, dropouts and deaths. This work will make it possible to obtain new scientific information on long-term NIV use in France.

[Social and housing conditions of patients with chronic respiratory failure treated in the ANTADIR Federation]. / La vie quotidienne et sociale des patients insuffisants respiratoires chroniques sévères pris en charge dans le réseau ANTADIR.

INTRODUCTION: Chronic respiratory failure (CRF) has an impact on quality of life because of respiratory handicap. METHODS: The purpose of this study was to analyse the daily life and social activities of patients with CRF. A questionnaire was addressed to over 9000 patients being cared for in the ANTADIR homecare network, with over a 60% response rate. RESULTS: The data showed that patients were old, and frequently had comorbidity. The predominant diagnosis was chronic obstructive airways disease (COPD) and the number of women in this population continues to increase. Respiratory handicap led to a loss of autonomy, a reduction in social activity and mobility of patients, but the impact differed markedly according to the cause of the respiratory failure, as well as age and social class. A typological study of behavioural characteristics revealed three groups of patients with contrasting profiles. CONCLUSION: These results lead to recommendation for better management of social aspects of patient care in the ANTADIR network.

[Diagnosis of lung cancer. Role of PET/CT fusion scan in lung cancer]. / Diagnostic des CBP. L'apport de la fusion TEP-TDM dans le diagnostic des cancers bronchiques.

Whole-body positron emission tomography (PET) with radiolabeled [18F]-fluoro-2-deoxy-D-glucose (18FDG) plays an important role in the diagnosis, staging, and management of lung cancer. The preferential accumulation of FDG in malignant cells assists in the differentiation of benign and malignant tissue. However, PET alone does not allow an accurate anatomic localisation of FDG uptake. The combination of PET with CT images improves the spatial resolution, sensitivity and specificity of the test. PET/CT, as with PET alone, is indicated for the diagnosis of pulmonary nodules as well as the locoregional and extrathoracic staging of non-small-cell lung cancer (NSCLC). In many published studies, PET/CT has been shown to be superior to CT alone, to PET alone, or to both imaging techniques used separately to evaluate pulmonary nodules or for staging NSCLC. Now, PET/CT imaging is being investigated in the staging and management of small-cell lung cancer, in radiation treatment planning, in response prediction following treatment and in the detection of lung cancer recurrence in NSCLC. PET/CT is likely to have an important role in the management of lung cancer. New machines are in development and new radiopharmaceutical agents must be assessed.

[Investigation of allergic reactions to platinum salts]. / Exploration d'une allergie aux sels de platine.

INTRODUCTION: We report two cases occurring in 2004 of patients being treated for pleural mesothelioma with a combination of cisplatin or carboplatin and pemetrexed. Investigation by skin tests and flow cytometry confirmed the clinical diagnosis in both cases. CASE REPORTS: Case 1: a man of 62 developed, after 12 courses of cisplatin-pemetrexed, an anaphylactic reaction 5 minutes after the infusion of cisplatin. Treatment was withdrawn permanently. Case 2: a man of 66 developed, after 7 courses of cisplatin-pemetrexed, an anaphylactic reaction within the first minute of the infusion of cisplatin. Subsequently, in March 2004, he received pemetrexed alone without any problems. In August 2004 he was prescribed carboplatin-pemetrexed. Within 5 minutes he developed urticaria, pruritus and abdominal pain. He was treated later with pemetrexed alone with no problems. CONCLUSION: Hypersensitivity to platinum salts usually occurs after several courses of treatment. Skin tests and flow cytometry are a simple, concordant, and reliable way of confirming the diagnosis.

[Economic analysis of home based versus hospital outpatient chemotherapy in stage IV non small cell lung cancer]. / Analyse économique de l'administration d'une chimiothérapie en hospitalisation à domicile (HAD) comparée à l'hospitalisation de jour dans les cancers bronchopulmonaires non à petites cellules de stade IV.

BACKGROUND: French law and government decisions have induced new development for home base treatments. The objective was to compare cost of home base chemotherapy (HBC) versus outpatient infusions, for non small cell lung cancer (NSCLC). METHODS: 10 patients were selected in each category. D8 of their cycles was performed at home compared to outpatient infusion. Costs were based on national fees with cytostatic drugs as supplement. The real cost was also assessed through a specific questionnaire. RESULTS: 30 D8 infusions were carried out at hospital and 24 D8 infusions at home. Average cost by cycle was 2,829.51 euros [2 560.74-3 147.02] for hospital infusion, 2,372.50 euros [1 962.75-2 792.88] for HBC (-16.15%). Difference was -457.01 euros by cycle [-919.74; 26.82]. Real costs by injection for BHC was 484.42 euros [424.18; 540.32] versus a fee of 699.89 euros [643.64; 750.23]. There were no difference in terms of adverse events. CONCLUSION: HBC for NSCLC is feasible. Average costs by cycle is lower of 16% versus hospital infusion. The results of this non randomized study had to be confirm by further clinical trials.

[Pleural metastases of sclerosing epithelioid fibrosarcoma]. / Métastases pleurales d'un fibrosarcome épithélioïde sclérosant.

Sclerosing epithelioid fibrosarcoma is a rare tumor recently described. The histological presentation can be confused with certain soft tissue benign tumors and certain sarcomas. Metastatic spread is usually late in the natural course of the disease. We report a case of recurrent sclerosing epithelioid fibrosarcoma with pleural metastases which developed ten years after surgical resection of the primary tumor. The tumor was formed by small uniform round epithelioid cells with a clear cytoplasm. The tumor cells were strongly positive for vimentin. This clinical case is discussed in light of other cases reported in the literature.

Silica-exposed macrophages release a growth-promoting activity for type II pneumocytes.

This study addresses the hypothesis that silica-activated alveolar macrophages could release soluble factors stimulating type II cell proliferation. Macrophages from control sheep were exposed or not in vitro to silica, aluminum-treated silica (Si-Al), or titanium dioxide (TiO2). In addition, macrophages from a model of chromic silica-exposed sheep were studied. Supernatants from unstimulated macrophages were found to double basal type II cell DNA synthesis. Alveolar macrophage-conditioned media (AMCM) collected from cells exposed in vitro to silica induced an additional growth-promoting activity for type II cells. Supernatants from Si-Al- or TiO2 dust-exposed alveolar macrophages had the same effects as unstimulated AMCM. In addition, AMCM from in vivo silicotic sheep cells also contained elevated levels of type II cell mitogenic activity. These results suggest that in vitro as in vivo, silica-activated macrophages produce a type II cell growth factor(s) for type II epithelial cells.

Partial characterization of the proliferative activity for fetal lung epithelial cells produced by silica-exposed alveolar macrophages.

The proliferation of lung epithelial cells is a prominent feature of lung tissue response following silica-induced lung injury and alveolar macrophages are recognized as a major contributing cell to the lung inflammatory processes. In previous studies, a growth-promoting activity for fetal rat lung epithelial cells was observed in silicotic alveolar fluids and in supernatants from in vitro and in vivo silica-exposed alveolar macrophages. In the present work, the biological and physicochemical properties of the macrophage-derived growth-promoting activity for fetal lung epithelial cells were explored. Four peaks of growth-promoting activity for lung epithelial cells ranging from 32 to 7 kDa were found in both in vitro and in vivo silica-exposed macrophage supernatants. The investigations were coupled with biochemical treatments of the mitogenic peaks and blocking antibodies or antisera were used to specify further the nature of the proliferative activities. Among the established growth factors, alveolar macrophage-derived growth fractions had characteristics consistent with platelet-derived growth factor-, insulin-like growth factor 1-, and fibroblast growth factor-like molecules. The cytokine production following in vitro exposure, which reflects very early events in the pathogenesis of silicosis, was more strongly related to the high-molecular-weight PDGF-like molecules, whereas the cytokine production following in vivo exposure, which reflects later events in the pathogenesis of silicosis, was more influenced by intermediate-molecular-weight FGF- and IGF-like molecules.

[Hypoglycaemic coma revealing a malignant recurrence during Doege-Potter syndrome]. / Coma hypoglycémique révélant une récidive maligne lors du syndrome de Doege-Potter.

INTRODUCTION: The Doege-Potter syndrome is a rare paraneoplastic syndrome, first described by Doege and Potter in 1930, that usually involves solid fibrous pleural tumours. Hypoglycaemia is a rare complication of these tumours, due to secretion of insulin-like growth factors, and it can be the presenting symptom. The incidence of malignancy is low, about 12-15 %. CASE REPORT: An 81-year-old Caucasian man, operated on 20 years previously for a benign pleural fibroma, presented with several episodes of loss of consciousness due to profound hypoglycaemia and a history of increasing dyspnea. The chest X-ray revealed an intrathoracic mass. Following excision histological examination confirmed recurrence with malignant transformation to a high-grade sarcoma. CONCLUSION: The Doege-Potter syndrome is a rare condition but it should be suspected in episodes of hypoglycaemia associated with a history of dyspnea. These patients should be followed up postoperatively because of the risk of tumour recurrence.

Is there a role of platelet-activating factor in human lung cancer?

Platelet-activating factor (PAF) is a lipid mediator that stimulates the in vitro growth of various human tumour cell lines and that enhances the effect of vascular endothelial growth factor that plays a key role during angiogenesis of human cancer. In this study, we assessed the levels of PAF and of the acetylhydrolase activity (AHA, the PAF degrading enzyme) in patients with lung cancer. Results indicated no significant differences between blood PAF amounts of lung cancer patients (91+/-33 pg/ml, n=31) and a control group of patients with chronic obstructive pulmonary disease (COPD) induced by habitual smoking (117+/-28 pg/ml, n=10). Similarly, their serum AHA levels were not different (67.9+/-3.0 nmol/min/ml as compared to 68.3+/-5.2 nmol/min/ml for lung cancer patients and controls, respectively). In contrast, PAF amounts were markedly (P=0.01, t-test for paired data) reduced in the lung tumour tissues (77+/-29 pg/g, n=10) as compared to the non-tumour tissues (208+/-67 pg/g, n=10). These low levels of PAF were not related to a lower amounts of the lyso-PAF precursor but to an elevated (P=0.01, t-test for paired data) AHA in the tumour tissues (37.0+/-4.9 nmol/min/g, n=10) as compared to the non-tumour tissues (24.6+/-2.6 nmol/min/ml, n=10). Reverse transcriptase polymerase chain reaction experiments showed the presence of the PAF receptor (PAF-R) transcript 1 but not transcript 2 in blood mononuclear cells of lung cancer patients and COPD patients. Flow cytometry experiments did not highlight differences in the number and the distribution of PAF-R on their circulating leukocytes. In conclusion, this clinical study highlights no evidence for a potential important role of PAF during human lung cancer.

Eyelid hyperlaxity and obstructive sleep apnea (O.S.A.) syndrome.

PURPOSE: An association between the floppy eyelid syndrome and the obstructive sleep apnea syndrome (O.S.A.) has been reported. We studied eyelid tissue elasticity and other ophthalmologic findings in a large number of patients with sleep disorders. MATERIAL AND METHODS: Sixty-nine patients with sleep disorders were evaluated. Two thirds were found to have O.S.A., and one third was treated at night by nasal continuous positive airway pressure (nasal C.P.A.P.). Slit lamp examination, eyelid measurements and Schirmer test were performed. RESULTS: Eyelid hyperlaxity was increased in patients with O.S.A. The floppy eyelid syndrome (associated papillary conjunctivitis), however, was rare. Associated corneal lesions were rare, and most patients were asymptomatic. In some cases, ocular irritation was due to air leaks from nasal C.P.A.P. A significant proportion of patients required treatment for primary open angle glaucoma. CONCLUSIONS: Our study of 69 patients found an association between O.S.A. and eyelid hyperlaxity.

[Review of nutritional and respiratory support in ALS]. / Prise en charge nutritionnelle et respiratoire des patients atteints de Sclérose Latérale Amyotrophique (SLA).

During the evolution of amyotrophic lateral sclerosis (ALS), quality of life and survival of patients are related to respiratory and nutritional status. After diagnosis, a multidisciplinary care has to be promptly organized and coordinated by the referring neurologist. The nutritional and respiratory support imply that neurologists know their specific means of evaluation with their sensitivity and sensibility and be able to recognize clinical risk situations. The informations of patients on assisted-ventilation and nutritional support by using gastrostomy may be done early, precisely and trustfully. Well informed patient's choices must be respected. Nutritional and respiratory supports may be based on recommendations established by the American Academy of Neurology. This review will present and discuss their main aspects in patients with ALS.

[Hodgkin's disease limited to intrathoracic sites. Case report]. / Maladie de Hodgkin de localisation intrathoracique pure. A propos d'un cas.

UNLABELLED: Hodgkin's disease without peripheral lymphadenopathy or hepatosplenomegaly is exceptional. CASE REPORT: Hodgkin's disease was revealed by lung nodules, one of them cavitating, with mediastinal enlargement. Diagnosis was confirmed on a video-assisted pleuroscopic biopsy. CONCLUSION: Hodgkin's disease should be considered in case of mediastinal enlargement with lung nodules.

[Pneumopathy caused by amiodarone. An often unrecognized iatrogenic entity]. / Pneumopathie à l'amiodarone. Une entité iatrogène sovent méconnue.

Three cases of interstitial pneumopathy secondary to amiodarone are reported, in addition to almost 200 cases previously published in the literature. The main clinical, radiological, biological and evolutive characteristics are reminded in emphasizing the advantages of bronchioalveolar irrigation. Some factors seem to be predisposing, without any definite proof however. They are: high daily dosage, long term treatment, high cumulative dose, concomitant ingestion of another anti-arrhythmic medication, especially in elderly patients, and in patients who, before any treatment, presented a decreased total pulmonary capacity and a CO transfer capacity lower than 80 p. cent of the theoretical values. Discontinuation of amiodarone and administration of steroids usually produce a rapid regression of the clinical and radiological symptoms.

[Bronchial inflammation during chronic bronchitis, importance of fenspiride]. / Inflammation bronchique au cours de la bronchite chronique, intérêt du fenspiride.

PATHOPHYSIOLOGY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD): Chronic inflammation of the upper airways, pulmonary parenchyma and pulmonary vasculature is the characteristic feature of COPD. Two mechanisms besides inflammation are also involved: oxidative stress and imbalance between proteinases and antiproteinases. Cellular infiltration of the upper airways involved neutrophils, macrophages, T lymphocytes and eosinophils. Inflammatory mediators appear to play a crucial role in the interaction between inflammation and obstruction. PROPERTIES OF FENSPIRIDE: A nonsteroidal drug, fenspiride, exhibits interesting properties documented in vitro: anti-bronchoconstriction activity, anti-secretory activity, and anti-inflammatory activity (reduction in the activity of phospholipase A2 and release of proinflammatory leukotriens). Two french clinical trials have studied the efficacy of fenspiride in patients with acute excerbation or stable COPD and have demonstrated an improvement in the group treated with fenspiride compared with the placebo group.

[The influence of a new beta agonist: formoterol on mucociliary function]. / Influence sur la fonction muco-ciliaire d'un nouveau bêta-agoniste: formoterol.

The muco-ciliary apparatus has an essential role in the cleansing of the tracheo-bronchial tree of particulate matter. Disturbances linked to muco-ciliary function are well known in respiratory pathology and in cases of chronic bronchitis and asthma and lead to a reduced capacity for cleansing. In addition there are numerous pharmacological agents including sympathomimetics which are capable of altering the ciliary activity and the rheological properties of mucous. The role of Formoterol, administered as an aerosol has been assessed in vivo in 10 bronchitic patients who were in a stable state. After 6 days of treatment using the Formoterol aerosol the muco-ciliary clearance had significantly increased to 46% and was a real gain when compared to the muco-ciliary clearance measured on placebo. This gain was linked to a better function of the muco-ciliary carpet and not due to the bronchodilatation which was induced by Formoterol, because the penetration index did not change. At the same time the airway resistance was slightly reduced in a none significant fashion.

[Radon and domestic exposure]. / Radon et exposition domestique.

Radon is a noble gas derived from the decay of radium, which itself is a decay product of uranium. The decay products of radon can collect electrostatically on dust particles in the air and, if these particles are inhaled and attach to bronchial epithelium, produce a high local radiation dose. Alpha particles can induce DNA double-strand breaks and the development of cancer. A causal relation between lung cancer and radon exposure and its progeny has been demonstrated in epidemiological studies of miners. Radon exposure became a public health issue almost 15 years ago. Most radon exposure occurs indoors, predominantly in the home. There is however, a wide range of radon concentration values in different countries. The highest level occurs in areas with granite and permeable soils. The risk for smoking, the leading cause of lung cancer, is far greater than for radon, the second leading cause. The estimates obtained from case-control studies of indoor radon are very contradictory. Scientific knowledge of effects of low levels of exposure to radon and the role of cigarette smoking, as a combined factor, must be studied. Smoking and radon probably interact in a multiplicative fashion.

[Tuberculosis and acute respiratory insufficiency. Apropos of 2 cases]. / Tuberculose et insuffisance respiratoire aiguë. A propos de 2 observations.

We report two cases of death from acute respiratory insufficiency of tuberculous origin. There were rare clinical presentations in which the clinical and radiological aspects were particularly atypical, suggesting a diagnosis of an acute respiratory distress syndrome. Bacteriological confirmation is necessary but it is worth considering this aetiology with each case of unexplained respiratory distress because the mortality is high and the prognosis is related to how early drug therapy is given.