PubMed | French Institute of Health and Medical Research, Service de pneumologie et oncologie thoracique, Lille 2 University of Health and Law and University Paris Est Creteil
Type: Journal Article | Journal: Revue des maladies respiratoires | Year: 2014
Alpha-1 antitrypsin (1-AT) deficiency is an autosomal recessive genetic disorder, which predisposes affected patients to development of pulmonary emphysema or liver cirrhosis. Despite the guidelines from the American Thoracic Society and the European Respiratory Society about 1-AT deficiency screening, it remains significantly under recognized. So, it seems necessary to propose an efficient and suitable biological approach to improve diagnosis and management of 1-AT deficiency. 1-AT is a 52 kDa glycoprotein predominantly produced in the liver and its physiological serum concentration for adults ranges from 0.9 to 2.0g/L (17-39 mol/L). It is encoded by the SERPINA1 gene, which is highly pleomorphic, and to date, more than 100 alleles have been identified. 1-AT testing would initially involve quantification of serum 1-AT concentration with possible complementary measurement of the elastase inhibitory capacity of serum. If the serum 1-AT concentration is reduced below the reference value, two strategies for laboratory testing can be used: (i) serum 1-AT phenotyping by isoelectric focusing which allows identification of the most common variant designated as the PI M variant but also of various deficient variants besides the predominant PI S and PI Z ones; (ii) genotyping by allele-specific PCR methods which allows only identification of the deficient PI S and PI Z alleles. Identification of the null alleles or of other rare deficient alleles can be performed by direct sequencing of the whole SERPINA1 gene as a reflex test.
Impact of Continuing First-Line EGFR Tyrosine Kinase Inhibitor Therapy Beyond RECIST Disease Progression in Patients with Advanced EGFR-Mutated Non-Small-Cell Lung Cancer (NSCLC): Retrospective GFPC 04-13 Study
PubMed | Service de Pneumologie et oncologie thoracique, Hoffmann-La Roche and Prigny
Type: Journal Article | Journal: Targeted oncology | Year: 2016
Retrospective studies suggested a benefit of first-line tyrosine kinase inhibitor (TKI) treatment continuation after response evaluation in solid tumors (RECIST) progression in epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. The aim of this multicenter observational retrospective study was to assess the frequency of this practice and its impact on overall survival (OS). The analysis included advanced EGFR-mutated NSCLC patients treated with first-line TKI who experienced RECIST progression between June 2010 and July 2012. Among the 123 patients included (6712.7years, women: 69%, non smokers: 68%, PS 0-1: 87%), 40.6% continued TKI therapy after RECIST progression. There was no difference between the patients who did and did not continue TKI therapy with respect to progression-free survival (PFS1: 10.5 versus 9.5months, p=0.4). Overall survival (OS) showed a non-significant trend in favor of continuing TKI therapy (33.0 vs. 21.2months, p=0.054). Progressions were significantly less symptomatic in the TKI continuation group than in the discontinuation group (18% vs. 37%, p<0.01). Univariate analysis showed a higher risk of death among patients with PS >1 (HR 4.33, 95 %CI: 2.21-8.47, p=0.001), >1 one metastatic site (HR 1.96, 95 %CI: 1.06-3.61, p=0.02), brain metastasis (HR 1.75, 95 %CI: 1.08-2.84, p=0.02) at diagnosis, and a trend towards a higher risk of death in cases of TKI discontinuation after progression (HR 1.62, 95 %CI: 0.98-2.67, p=0.056 ). In multivariate analysis only PS >1 (HR 6.27, 95 %CI: 2.97-13.25, p=0.00001) and >1 metastatic site (HR 2.54, 95 %CI: 1.24-5.21, p=0.02) at diagnosis remained significant. This study suggests that under certain circumstances, first-line TKI treatment continuation after RECIST progression is an acceptable option in EGFR-mutated NSCLC patients.NCT02293733.
PubMed | Service danatomo pathologie, Service de pneumologie et oncologie thoracique, Service de cardiologie, Service de medecine nucleaire and 2 more.
Type: | Journal: Revue des maladies respiratoires | Year: 2016
A 60-year-old patient was under follow-up for pulmonary hypertension consistent with pulmonary veno-occlusive disease. During his follow-up, a parenchymal opacity was discovered. We describe the management of the suspicion of lung cancer, highlighting the modification of the conventional diagnostic and therapeutic strategy on account of the pulmonary hypertension. Chest physicians should be able to adapt their diagnostic and therapeutic management in the case of neoplasia in patients with severe pulmonary hypertension.
Locatelli-Sanchez M.,Service de Pneumologie et Oncologie Thoracique |
Locatelli-Sanchez M.,University of Lyon |
Couraud S.,Service de Pneumologie et Oncologie Thoracique |
Couraud S.,University of Lyon |
And 5 more authors.
Lung | Year: 2013
Background: Epidermal growth factor receptor (EGFR)-targeting therapies dramatically modified the prognosis of stage 4 non-small-cell lung cancer. Sensitizing EGFR mutations are the best efficacy factor of these treatments. In 2006, the French National Cancer Institute launched a network of 28 centers for EGFR molecular analysis in routine practice. The aim of this retrospective study was to describe the results of routine EGFR analysis in one of these centers (Lyon University Hospital) and to assess outcomes in patients with the mutation. Methods: EGFR mutations were analyzed for exons 18-21 by direct sequencing. The characteristics of each sample were retrospectively collected from the lab archives. Subsequent outcomes for patients harboring at least one mutation were retrospectively collected from each referring physician. Results: During 1 year, 792 samples were analyzed, corresponding to 753 patients. A total of 133 mutations were diagnosed in 124 samples (15.7 %), corresponding to 121 patients. Most of them (77.4 %) were sensitizing mutations and were located in exons 19 and 21. Others were resistance mutations (8.3 %) or rare mutations (14.3 %) for which effects on tyrosine kinase inhibitor (TKI) sensitivity are unknown. The rate of indeterminate results (i.e., no sequencing of the entire exon 19 or 21) was 6.3 % (n = 50 samples). The only factor statistically associated with a risk of failure was sample from bone tissue: 13.7 % gave incomplete results (i.e., no whole sequencing of exons 18-21). Conclusions: Eighty-five of the 121 patients with EGFR mutations were treated with TKI. There were no differences in progression free survival (PFS) according to the type of molecule (erlotinib or gefitinib) or to the line of prescription of TKI. By contrast, exon 18 sensitizing mutations showed a worse PFS than exon 19 or 21 mutations. Finally, dose reduction was significantly more frequent in the erlotinib group than in the gefitinib group. © 2013 Springer Science+Business Media New York.
PubMed | Center National Of Reference Des Maladies Respiratoires Rares Respirare, Service de Pneumologie et Oncologie Thoracique, University of Paris 13, Aix - Marseille University and 4 more.
Type: Journal Article | Journal: Human molecular genetics | Year: 2016
Idiopathic interstitial pneumonias (IIPs) comprise a heterogeneous group of rare lung parenchyma disorders with high morbidity and mortality, which can occur at all ages. In adults, the most common form of IIPs, idiopathic pulmonary fibrosis (IPF), has been associated with an increased frequency of lung cancer. The molecular basis of IIPs remains unknown in most cases. This study investigates IIP pathophysiology in 12 families affected by IPF and lung cancer. We identified, in a multigenerational family, nine members carrying a heterozygous missense mutation with evidence of pathogenicity in SFTPA1 that encodes the surfactant protein (SP)-A1. The mutation (p.Trp211Arg), which segregates with a disease phenotype characterized by either isolated IIP/IPF, or IPF associated with lung adenocarcinoma, is located in the carbohydrate recognition domain (CRD) of SP-A1 and involves a residue invariant throughout evolution, not only in SP-A1, but also in its close paralog SP-A2 and other CRD-containing proteins. As shown through functional studies, the p.Trp211Arg mutation impairs SP-A1 secretion. Immunohistochemistry studies on patient alveolar epithelium showed an altered SP-A expression pattern. Overall, this first report of a germline molecular defect in SFTPA1 unveils the key role of SP-A1 in the occurrence of several chronic respiratory diseases, ranging from severe respiratory insufficiency occurring early in life to the association of lung fibrosis and cancer in adult patients. These data also clearly show that, in spite of their structural and functional similarities, SP-A1 and SP-A2 are not redundant.
Couraud S.,Service de Pneumologie et dOncologie Thoracique |
Couraud S.,University of Lyon |
Fournel P.,Institute Of Cancerologie Of La Loire |
Moro-Sibilot D.,Grenoble University Hospital Center |
And 3 more authors.
Clinical Lung Cancer | Year: 2011
Background: In 2003 the French government initiated a large cancer plan. This program requested the latest edition of local guidelines in each of France's administrative regions. Since their creation, none of these guidelines has been assessed in the conditions of daily clinical practice. Method: A survey was performed to assess physicians' integrated knowledge of local guidelines in the Rhne-Alpes region in France. It included 4 patient cases with accompanying multiple-choice questions. Responses were judged as appropriate or inappropriate according to the 2007 edition of local guidelines. Results: Four hundred one physicians were contacted. The response rate was 56%. Among the responding physicians, 71 were eligible for analysis (those who were board certified in oncology and pulmonology and practiced thoracic oncology only). The rate of physicians who applied guidelines was 55%, 54%, 63%, and 25% for cases 1 to 4, respectively. There were no major differences in the responses between oncologists and pulmonologists. However significant differences were noted between physicians working in public health centers (cases 1 and 2) and those who practiced in private centers (cases 3 and 4) (appropriate response rate, 68% [case 3] vs. 36% [case 1] [P =.0494] for case 1; 28% [case 4] vs. 9% [case 2] (P =.0022)). Finally, no differences in physician responses were found in the administrative departments within the administrative region. Conclusion: The results of the survey illustrate that regional guidelines are not routinely applied in daily clinical practice. This nonapplication of regional guidelines by physicians may be due to either a lack of knowledge of updates to guidelines or a lack of agreement with them. © 2011 Elsevier Inc. All rights reserved.
Vincent M.,Service de pneumologie et oncologie thoracique |
Vergnon J.-M.,Service de pneumologie et oncologie thoracique
Revue des Maladies Respiratoires | Year: 2015
Introduction: Inhalation of foreign bodies is an unusual complication of dental care. When it occurs immediately during the intervention, it is generally a dental tool, such as the little screwdrivers used for dental implant procedures. Case report: A 59-year-old man was referred to our hospital for asymptomatic inhalation of a small drill during dental surgery. Because the drill had a barbed tip, prompt removal was indicated. The foreign body was localized in a sub-segmental division of the left lower lobe (B10b) and could be removed via a flexible bronchoscope under a short general anesthetic without intubation. There was no significant injury of the bronchial mucosa. Conclusion: Inhalation of foreign bodies during dental interventions is unusual and sometimes asymptomatic but their removal is always indicated. In some cases, the removal can be performed with a flexible bronchoscope. © 2015 SPLF.
PubMed | Service de pneumologie et oncologie thoracique
Type: Journal Article | Journal: Revue des maladies respiratoires | Year: 2016
Inhalation of foreign bodies is an unusual complication of dental care. When it occurs immediately during the intervention, it is generally a dental tool, such as the little screwdrivers used for dental implant procedures.A 59-year-old man was referred to our hospital for asymptomatic inhalation of a small drill during dental surgery. Because the drill had a barbed tip, prompt removal was indicated. The foreign body was localized in a sub-segmental division of the left lower lobe (B10b) and could be removed via a flexible bronchoscope under a short general anesthetic without intubation. There was no significant injury of the bronchial mucosa.Inhalation of foreign bodies during dental interventions is unusual and sometimes asymptomatic but their removal is always indicated. In some cases, the removal can be performed with a flexible bronchoscope.
Vincent M.,Service de Pneumologie et Oncologie Thoracique |
Vergnon J.-M.,Service de Pneumologie et Oncologie Thoracique
Revue des Maladies Respiratoires | Year: 2016
Introduction.-Inhalation of foreign bodies is an unusual complication of dental care. Whenit occurs immediately during the intervention, it is generally a dental tool, such as the littlescrewdrivers used for dental implant procedures.Case report.-A 59-year-old man was referred to our hospital for asymptomatic inhalation ofa small drill during dental surgery. Because the drill had a barbed tip, prompt removal wasindicated. The foreign body was localized in a sub-segmental division of the left lower lobe(B10b) and could be removed via a flexible bronchoscope under a short general anestheticwithout intubation. There was no significant injury of the bronchial mucosa.Conclusion.-Inhalation of foreign bodies during dental interventions is unusual and some-times asymptomatic but their removal is always indicated. In some cases, the removal can beperformed with a flexible bronchoscope. © 2015 SPLF.
PubMed | Unite Mixte Of Recherche Center National Of La Recherche Scientifique 5558, Service de Pneumologie et Allergologie Pediatriques, CNRS Immunology and Infectious Disease Center, Service de Pneumologie et Oncologie Thoracique. and 2 more.
Type: Journal Article | Journal: Open forum infectious diseases | Year: 2015
Linezolid (LNZ), a group 5 antituberculous drug (unclear efficacy), was used in the starter regimens of 23 adults with multidrug-resistant tuberculosis. The LNZ-containing regimens were effective in achieving culture conversions and relapse-free outcomes. The most frequent LNZ-related side effect was neuropathy. We propose that LNZ should be reclassified among bactericidal second-line drugs.