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Immunotherapy targeting the PD-L1/PD-1 axis has shown recently some promising results in metastatic lung cancer patients. This treatment seems to be more effective when a high expression of PD-L1 is detected by immunohistochemistry in bronchial biopsies. In this regard, this targeted therapy will be proposed soon in metastatic lung cancer patients. This immunotherapy could be dependent to the immunohistochemical (IHC) assessment of PD-L1 expression, thus considered as a companion diagnostic test. This near perspective poses challenges with regard to the positivity threshold value for PD-L1 expression before therapy administration, the positive cellular compartment (tumour cells and/or immune cells), the percentage of positive cells and the clone which is used. A couple of patients have a good response to treatment targeting the PD-1/PD-L1 axis despite the absence or a weak PD-L1 expression. However the assessment of PD-L1 expression by immunohistochemistry will be the only mandatory approach before therapeutic strategies targeting the PD1/PD-L1 axis for lung cancer patients. In this review, the main challenges of using PD-L1 immunohistochemistry as a potential companion diagnostic tool for metastatic lung cancer patient immunotherapy will be discussed., (Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The receptors responsible for taste perception distinguish the four basic tastes : salty, sweet, bitter and umami. Among them, the bitter taste receptors (TAS2R) are G protein coupled receptors, including 25 subtypes identified in humans to date. Although the existence of endogenous agonists remains uncertain, the TAS2R receptors have the ability to recognize natural or synthetic molecules, as various molecules produced by bacteria, or caffeine, chloroquine, or erythromycin. The expression of these receptors, initially thought to be confined to the oral cavity, has recently been described in extra-oral tissues such as the gastrointestinal tract and the lungs. The effects in the lung tissue are essentially at three levels : TAS2R receptors expressed on the cilia of epithelial cells increase the cilia vibration frequency; the stimulation of TAS2R receptors expressed in bronchial smooth muscle cells leads to bronchial relaxation; while TAS2R receptors expressed on immune cells in the lung tissue, including macrophages, are involved in the modulation of the production of pro-inflammatory cytokines. In conclusion, in view of these complementary mechanisms, TAS2R receptors may become a pharmacological target of interest for the treatment of obstructive lung diseases., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The respiratory system undergoes progressive involution with age, resulting in anatomical and functional changes that are exerted on all levels. The rib cage stiffens and respiratory muscles weaken. Distal bronchioles have reduced diameter and tend to be collapsed. Mobilized lung volumes decrease with age while residual volume increases. Gas exchanges are modified with a linear decrease of PaO(2) up to the age of 70 years and a decreased diffusing capacity of carbon monoxide. Ventilatory responses to hypercapnia, hypoxia and exercise decrease in the elderly. Knowledge of changes in the respiratory system related to advancing age is a medical issue of great importance in order to distinguish the effects of aging from those of diseases., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

To identify the active element of automotive exhaust gas responsible for masculine infertility, previously proved by our laboratory, we undertook these experiments. Four hundred young male and female rats were exposed during two months (30 min/d) to three types of automotive exhaust gases. The first type emanated from an engine running on gasoline with lead, the second from an unleaded gasoline engine, the third from a diesel engine. These three engines had the same power (5 horsepower vehicles < 3.5 tons). For the first type of emissions, some lead deposits were found in the lungs by histologic techniques. This gas also induced in male rats the atrophy of the testicle, seminal vesicle and epididym, certain pathological changes in spermatogenesis shown by the histologic study, and a decrease of the serum's testosterone level. In female rats, the relative weights of the ovary and uterus, as well as the percentage of the arrival of oestrus, were not affected by the gaseous treatment. Both the second and third types of gases seemed less active on the masculine sex as far as these parameters are concerned. Our study suggests that, for light vehicles, leaded gasoline pollutes more than unleaded gasoline or diesel fuels, and that the lead present only in the first type would be the active element responsible for the masculine infertility and body weight gain reduction in rats.

Several tools are available for the evaluation of the exposure to asbestos, particularly occupational questionnaire and mineralogical analysis of biological samples. These analysis allow quantification of the level of retention of asbestos fibres in the respiratory tract. Two groups of analysis may be used: quantification of asbestos bodies in sputum, bronchoalveolar lavage fluid or lung tissue samples using light microscopy; quantification and identification of asbestos fibres in bronchoalveolar lavage fluid or lung tissue using analytical electron microscopy. Profiles of lung retention of asbestos bodies or asbestos fibres have been described in various asbestos-related disorders, and reference values are available in control populations mainly for asbestos bodies using light microscopy. Mineralogical analysis of biological samples is not required for compensation of occupational asbestos-related diseases. However, this type of analysis may prove to be useful to the chest physician when looking for the etiology of some nonspecific respiratory diseases (interstitial pulmonary fibrosis, lung cancer), particularly when the occupational questionnaire is not contributive. As they are quite easier and less expensive, analysis using light microscopy will be performed first.

This study was designed to assess the diffusion into lung tissue and systemic circulation of amikacin administered endotracheally. Eleven consecutive patients, suffering from lung carcinoma and scheduled for elective pneumonectomy or lobectomy, were included in the study. After induction of anaesthesia and before tracheal intubation, a single 500 mg amikacin dose was administered endotracheally through a catheter whose tip was located 5 cm below the vocal cords. Blood was then collected every 15 min for serum assays, until pulmonary resection had been carried out. Pulmonary concentrations were assessed in a healthy area. Measurements were carried out in duplicate using fluorescence polarizing immunoassay and microbiological methods. Serum peak concentrations were found 105 min after administration (7.97 +/- 5.62 micrograms.ml-1). Six and 12 h after administration, serum concentrations were 3.19 +/- 1.87 and 1.20 +/- 0.67 micrograms.ml-1 respectively. Mean lung concentrations were 1.85 +/- 2.12 micrograms.g-1, with a corresponding serum level of 7.22 +/- 4.36 micrograms.ml-1. However, endotracheal instillation of amikacin provided serum concentrations which, were not high enough for treatment of gram negative pneumonia. Lung concentrations are lower than both serum levels and MIC90 for gram negative bacilli. Moreover, there was a major heterogeneity in serum and lung levels, which seemed to be unpredictable. This was probably due to heterogenous tracheal, bronchial and alveolar absorption. The results obtained in this study with a single dose administration should be reassessed in the light of data obtained with long-term amikacin administration.

We have established a sensitive and specific radioimmunoassay for measurement of ET-1 in tissues and human plasma. Half maximal inhibition of binding of ET-1125 I was obtained at 6.6 pg/tube and the lowest concentration detectable was 0.785 pg/tube (p less than 0.001). Inter and intra-assay precisions were 14 and 9.6%, respectively. The antibody cross-reacted with ET-2 at 36.5%, ET-3 at 23.4% and Big ET at 9.9% but did not recognize non related vasoactive peptides. Immunoreactive ET-1 was extracted from human and rat tissues (lung, kidney) or human plasma using Sepak C18 columns. Human lung contains 2.3 ng/g ir-ET, corresponding mainly to synthetic ET-1 as revealed by reverse phase HPLC coupled to RIA. Rat lung and kidney ir-ET concentrations were 2.4 ng/g and 0.45 ng/g, respectively. Preliminary results indicated that the basal level of ir-ET in human plasma was 1.24 pg/ml. The RIA could be very useful to study the role of ET in various physiopathological states.

We measured transthoracic electrical impedance in 17 anesthetized and mechanically ventilated dogs with a four-electrode system. A current (5 KHZ, 50 mu A) is injected and detected at axillary levels. Transthoracic impedance was 67 +/- 14 ohms (S.D.) with insignificant shifts in control animals. Pulmonary edemas were induced by saline and dextrose overloads with large but opposite variations in impedance. Fifty to hundred per cent increases in total lung water content (determined at autopsy) were induced by intravenous injection of alloxan or instillation of endotracheal saline. Significant but small decreases in impedance followed. Validity of experimental pulmonary edemas with or without blood resistivity and pulmonary blood volume changes is discussed.

Measurement of pulmonary interstitial fluid may be useful in clinical medicine for early diagnosis or measurement of interstitial and/or alveolar pulmonary edema. A modification of the double dilution method of CHINARD and GORESKY is proposed. Compared to previous methods, this technique, using two isotopes gamma emitters, is rapid, simple, reproductible and may be repeated. The values obtained in normal subjects at rest 3.5 +/- 0.5 ml/kg, are comparable with those of other authors. They increase considerably in cases of fluid load.