[Inhaled marijuana and the lung, a toxic cocktail?] / Cannabis inhalé et poumon, une liaison dangereuse ?

Unlike the well-documented effects of tobacco smoke on the lung, the effects of cannabis smoke remain controversial, the main bias consisting in co-consumption of tobacco. That said, the composition of joint smoke is close to that of cigarettes, containing many compounds that are carcinogenic and/or alter the respiratory epithelium. Confirmed respiratory effects in chronic cannabis smokers include aggravated chronic bronchitis symptoms, a cumulative effect with tobacco on COPD and emphysema occurrence, an increased risk of bullous emphysema, and pneumothorax with heightened risk of recurrence after pleural symphysis. Recent prospective studies have shown a negative impact on lung function, with not only damage to the airways, but also DLCO alteration and an accelerated drop in FEV1. Finally, cannabis smoking is very common among young patients with lung cancer. Its consumption could lead to a different lung cancer profile, potentially more undifferentiated and less accessible to targeted therapy. Questioning about cannabis consumption must be systematic and targeted medical care should be offered.

[Therapeutic adherence among asthma patients: Variations according to age groups. How can it be improved? The potential contributions of new technologies]. / Observance thérapeutique dans l'asthme : variation selon les classes d'âge. Comment l'améliorer ? Apport des nouvelles technologies.

While asthma patients' treatment adherence (TA) generally leaves to be desired, few data exist on TA evolution from age group to another. During the meeting of a working group of pneumo-pediatricians and adult pulmonologists, we reviewed the literature on adherence according to age group, examined explanations for poor adherence, and explored ways of improving adherence via new technologies. Asthma is a chronic disease for which TA is particularly low, especially during adolescence, but also among adults. Inhaled medications are the least effectively taken. Several explanations have been put forward: cost and complexity of treatments, difficulties using inhalation devices, poor understanding of their benefits, erroneous beliefs and underestimation of the severity of a fluctuating disease, fear of side effects, neglect, and denial (especially among teenagers). Poor TA is associated with risks of needless treatment escalation, aggravated asthma with frequent exacerbations, increased school absenteeism, degraded quality of life, and excessive mortality. Better compliance is based on satisfactory relationships between caregivers and asthmatics, improved caregiver training, and more efficient transmission to patients of relevant information. The recent evolution of innovative digital technologies opens the way for enhanced communication, via networks and dedicated applications, and thanks to connected inhalation devices, forgetfulness can be limited. Clinical research will also help to ameliorate TA. Lastly, it bears mentioning that analysis of the existing literature is hampered by differences in terms of working definitions and means of TA measurement.

[Rapid outpatient diagnostic pathways for lung cancer: Evaluation after one year]. / Parcours de diagnostic rapide du cancer du poumon : évaluation à un an.

INTRODUCTION: The introduction of coordinated care pathways for lung cancer diagnosis and treatment is a complex process. The purpose of the French Cancer Plan 2014-2019 was to improve referral to treatment waiting times in people with suspected malignancy. The aim of this study was to assess a rapid outpatient diagnostic program for lung cancer established in 2016. METHOD: This retrospective study was carried out in the Pulmonology Department at Tenon Hospital, Paris, France between May 2016 and May 2017. RESULTS: During this period, 118 patients (60%) of patients in the pathway were diagnosed with lung cancer. The median waiting time to first consultation (D1) was 4 (2-7) days. The median waiting time between diagnosis and treatment decision (D4) was 4 (0-8) days. The median waiting time to the first treatment (D5) was 10 (4-15) days for chemotherapy and 27 (16-34) days for surgery. The median waiting time between the first abnormal chest X-ray and the first treatment (D6) was 49 days (34-70). CONCLUSION: Referral to treatment waiting times was consistent with international recommendations. Coordinating nurses improved care pathways in lung cancer patients.

[Combinations of pharmacological treatments in smoking cessation. A systematic review]. / Combinaisons des traitements pharmacologiques au cours du sevrage tabagique. Revue systématique.

INTRODUCTION: The effectiveness of the three validated smoking cessation medications, nicotine replacement therapy, varenicline and bupropion, may be insufficient, in hard-core smokers. OBJECTIVES: This systematic review investigates the efficacy of combinations of different medications in smoking abstinence and their tolerability. RESULTS: Three randomized controlled trials (RCTs) compared the combined medications with varenicline and nicotine patches vs. varenicline; two found an increase in abstinence rates with the combined medications. In one study, the beneficial effect was only observed in heavy smokers. The four RCTs comparing the combined medications with varenicline and bupropion (vs. varenicline) demonstrated an increase in abstinence rates with the combined medications, most often in heavy smokers who are very dependent on tobacco. The results of the three RCTs comparing the combined medications with bupropion and nicotine replacement therapy vs. varenicline were discordant. Three studies included other molecules (mecamylamine, selegiline, sertraline, buspirone). Combined medications were well tolerated. CONCLUSION: Combination treatments can achieve higher smoking abstinence rates than monotherapies, especially in smokers who have failed to quit (Hard-core smokers). Treatment with a combination of varenicline and nicotine replacement therapy is a therapeutic option in smoking cessation.

[Smoking cessation and lung cancer screening]. / Sevrage tabagique et dépistage du cancer du poumon.

Several studies have shown that lung cancer screening, using annual low-dose computed tomography (CT) scan in a targeted population of smokers and ex-smokers reduces overall and lung cancer specific mortality rates. This form of screening strategy is not currently established for use in France by the French High Authority for Health. Quitting smoking is the most important measure in reducing mortality from lung cancer. The maximum benefit in reducing mortality from lung cancer should be seen through an effective combination of smoking cessation intervention and chest CT screening to identify early, curable disease. However, current data to guide clinicians in the choice of smoking cessation interventions in this specific context are limited due to the small number of randomized studies that have been carried out. The optimal approach to smoking cessation during lung cancer screening needs to be clarified by new studies comparing different motivation strategies, establishing the ideal moment to propose stopping smoking and the most effective therapies to use.

[How to reduce lung cancer mortality among people living with HIV?] / Comment réduire la mortalité par cancer du poumon chez les personnes vivant avec le VIH ? Du sevrage tabagique au dépistage radiologique.

Lung cancer is the leading cause of cancer related death among people living with HIV (PLHIV). Tobacco exposure is higher among PLHIV (38.5%) and mainly explains the increased risk of lung cancer. To reduce lung cancer mortality, two approaches need to be implemented: lung cancer screening with low-dose thoracic CT scan and smoking cessation. Low dose CT scan is feasible in PLHIV. The false positive rate is not higher than in the general population, except for cases with CD4 <200/mm3. The impact on survival remains to be assessed. Despite the high prevalence, smoking cessation research among PLHIV is scarce. Very low quality data from 11 studies showed that more intensive smoking cessation interventions were effective in achieving short-term abstinence. A single randomized phase 3 trial showed the superiority of varenicline compared to placebo in long-term smoking cessation. The maximum benefit of reducing lung cancer mortality should be obtained by combining smoking cessation and lung cancer screening.

Detection of secondary causes of spontaneous pneumothorax: Comparison between computed tomography and chest X-ray.

PURPOSE: The aim of this study was to compare the effectiveness of chest X-ray to that of thoracic computed tomography (CT) for the detection of the causes of secondary spontaneous pneumothorax (SP). METHODS: A prospective cohort of patients with SP was studied. All chest X-ray and CT examinations of the patients were reviewed retrospectively by an expert radiologist blinded to clinical data. The concordance between the CT examination and chest X-ray was assessed using the Cohen Kappa coefficient (κ), based on a bootstrap resampling method. RESULTS: A total of 105 patients with SP were included. There were 78 men and 27 women, with a mean age of 34.5 years±14.2 (SD) (range: 16-87 years). Of these, 44/105 (41%) patients had primary SP and 61/105 (59%) had secondary SP due to emphysema (47/61; 77%), tuberculosis (3/61, 5%), lymphangioleiomyomatosis (3/61; 5%), lung cancer (2/61, 3%) or other causes (6/61; 10%). Apart from pneumothorax, CT showed abnormal findings in 85/105 (81%) patients and chest X-ray in 29/105 (28%). Clinically relevant abnormalities were detected on 62/105 (59%) CT examinations. The concordance between chest X-ray and CT was fair for detecting emphysema (κ=0.39; 95% CI: 0.2420-0.55), moderate for a mass or nodule (κ=0.60; 95% CI: 0.28-0.90), fair for alveolar opacities (κ=0.39; 95% CI: -0.02-1.00), and slight for interstitial syndrome (κ=0.20; 95% CI: -0.02-0.85). CONCLUSION: Chest X-ray is not sufficient for detecting the cause of secondary SP. As the detection of the cause of secondary SP may alter the therapeutic approach and long-term follow-up in patients with SP, the usefulness of a systematic CT examination should be assessed in a prospective trial.

[Peri-operative management of smoking]. / Prise en charge du tabagisme en périoperatoire.

Smoking is a public health issue, especially during the perioperative period. Tobacco increases the risk of hospital mortality by 20% and major postoperative complications by 40%. Active smoking is associated with respiratory complications particularly bronchospasm and pneumonia, but also all surgical complications as scar infections, local thrombosis, suture release and delayed bone healing. The perioperative period is an opportunity to stop smoking. Smoking cessation should always be recommended, regardless of the surgery and the date of intervention. All health professionals, doctors, surgeons, anesthetists, but also nurses and physiotherapists, must inform smokers of the benefits of stopping smoking, offer them a dedicated support and a personalized follow-up. Tobacco consultation and the prescription of nicotine replacement increase the rate of smoking cessation. Stopping smoking reduces perioperative complications and is associated with health benefits that increase with time.

Effect of cannabis and tobacco on emphysema in patients with spontaneous pneumothorax.

PURPOSE: To compare imaging findings on thoracic computed tomography (CT) examination in patients with primary spontaneous pneumothorax (SP), depending on their tobacco and/or cannabis consumption. MATERIALS AND METHODS: A total of 83 patients who had thoracic CT for primary SP were prospectively included. There were 65 men and 18 women with a median age of 33 years (IQR: 27; 44 years). The patients were further categorized into three groups according to their smoking habits. Thirteen patients were non-smokers, 38 were tobacco only smokers and 32 were tobacco and cannabis smokers. CT examinations were retrospectively reviewed for the presence of blebs, centrilobular and paraseptal emphysema and lung nodules in each group for comparison. RESULTS: Emphysema was detected in 43/85 patients (51.8%), including 1/13 patients (7.7%) in the non-smoking group, 19/38 patients (50%) in the tobacco only group and 23/32 patients (71.9%) in the tobacco and cannabis smokers, with no difference between tobacco only and tobacco and cannabis smokers. No differences in type and location of emphysema was found between tobacco only and tobacco and cannabis smokers. Tobacco and cannabis smokers with emphysema were significantly younger than tobacco only smokers with emphysema (35 vs. 46 years, respectively) (P=0.009). CONCLUSION: The prevalence of emphysema visible on CT is not different between tobacco and tobacco/cannabis smokers, however, it occurs at a younger age in tobacco and cannabis smokers. This result suggests that cannabis, when added to tobacco, may lead to emphysema at a younger age.

[Role of the Sonic Hedgehog pathway in thoracic cancers]. / Rôle de la voie Sonic Hedgehog dans les cancers thoraciques.

INTRODUCTION: Sonic Hedgehog (Shh) pathway is physiologically activated during embryogenesis and development. It plays a role in idiopathic lung fibrosis and is also activated in several solid cancers. STATE OF THE ART: Shh pathway is reactivated in thoracic cancers, as small cell lung carcinoma, non-small cell lung carcinoma and malignant pleural mesothelioma. Shh pathway is associated with cancer stem cells and seems to have a crucial role in tumor proliferation, aggressiveness and chemoresistance in these cancers. This review describes the activation mode of Shh pathway in thoracic cancers and its role in small cell lung carcinoma, non-small cell lung carcinoma and malignant pleural mesothelioma, using in vitro and in vivo models. Notably, data from literature show that inhibition of Shh pathway has an antitumor action and sensitizes to chemotherapy. PERSPECTIVES: These results incite to develop targeted therapies against Shh pathway in the treatment of thoracic cancers.

Titania-Supported Catalysts for Levulinic Acid Hydrogenation: Influence of Support and its Impact on γ-Valerolactone Yield.

A series of titania-supported ruthenium and platinum catalysts was investigated in the levulinic acid hydrogenation towards γ-valerolactone, a key reaction for the catalytic transformation of biomass. It was shown that various morphologies and phases of titania strongly influence the physicochemical and catalytic properties of supported Ru and Pt catalysts in different ways. In the case of the catalyst supported on mixed TiO2 phases, Ru particles are exclusively located on the minority rutile crystallites, whereas such an effect was not observed for platinum. The platinum catalyst activity could be increased when the metal was dispersed on the large surface-area anatase, which was not the case for ruthenium as a result of its agglomeration on this support. The activity of ruthenium on anatase could be increased in two ways: a) when RuO2 formation during catalyst preparation was avoided; b) when pure anatase support material was modified so that it exhibited no microporosity. The obtained results allow a better understanding of the role of the support for Ru and Pt catalysts.

2014 update on non-small cell lung cancer (excluding diagnosis).

Lung cancer (LC) is a major public health issue because of its frequency, but especially because of the severity of this disease. The epidemiology has changed with an increased incidence in non-smokers and women. The ATS/ERS/IASLC classification of adenocarcinomas was modified in 2011, and they are now the most frequent histological subtype. More than half the cases of LC are diagnosed at the metastatic stage. Biopsies must provide tissue samples that are quantitatively large enough and of a good enough quality for diagnosis and to search for biomarkers. When the cancer seems to be localized, precise staging must be obtained. Treatment is based on the TNM classification. In localized stages, lobectomy associated with lymph node dissection is the standard therapy. Intraoperative chemotherapy improves survival in case of lymph node infiltration. Stereotactic radiation therapy and radiofrequency can be considered as specific cases. In cases with local progression, treatment is more controversial. In the presence of metastases, the goal is not a cure, but improving survival and quality of life. Numerous advances have been made with personalized treatment, (in particular in relation to the histological type and oncogenic addiction in tumors, access to new drugs, and improved management). Clinical research in thoracic cancer is very active. The fight against tobacco should remain a priority.

[Lung cancer and HIV infection]. / Cancer du poumon et infection par le Virus de l'Immunodéficience Humaine.

AIDS was the cause of the majority of deaths from HIV infection before 1996 but since the introduction of antiretroviral therapies the causes of mortality have changed considerably. In 2010, 75 % of deaths were due to diseases other than AIDS, the majority being cancers. Lung cancer is the most common in terms of both incidence and mortality. It shows specific features when compared to the general population: there is an excess risk due to heavy smoking but also probably due to immunosuppression. The age of onset is younger and the prognosis worse than in the general population. Management is difficult, partly due to the aggressive nature of the tumor and partly to co-morbidities and potential interactions between anticancer and antiretroviral therapies. A phase II therapeutic trial (IFCT-CHIVA 1001) is under way nationally.

Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC-IFCT network.

BACKGROUND: There is scarce data available about epidermal growth factor receptor (EGFR) mutations other than common exon 19 deletions and exon 21 (L858R) mutations. PATIENTS AND METHODS: EGFR exon 18 and/or exon 20 mutations were collected from 10 117 non-small-cell lung cancer (NSCLC) samples analysed at 15 French National Cancer Institute (INCa)-platforms of the ERMETIC-IFCT network. RESULTS: Between 2008 and 2011, 1047 (10%) samples were EGFR-mutated, 102 (10%) with rare mutations: 41 (4%) in exon 18, 49 (5%) in exon 20, and 12 (1%) with other EGFR mutations. Exon 20 mutations were related to never-smoker status, when compared with exon 18 mutations (P < 0.001). Median overall survival (OS) of metastatic disease was 21 months [95% confidence interval (CI) 12-24], worse in smokers than in non-smoker patients with exon 20 mutations (12 versus 21 months; hazard ratio [HR] for death 0.27, 95% CI 0.08-0.87, P = 0.03). Under EGFR-tyrosine kinase inhibitors (TKIs), median OS was 14 months (95% CI 6-21); disease control rate was better for complex mutations (6 of 7, 86%) than for single mutations (16 of 40, 40%) (P = 0.03). CONCLUSIONS: Rare EGFR-mutated NSCLCs are heterogeneous, with resistance of distal exon 20 insertions and better sensitivity of exon 18 or complex mutations to EGFR-TKIs, probably requiring individual assessment.

[Smoking cessation therapy in thoracic oncology]. / Le sevrage tabagique en oncologie thoracique.

In France, the number of tobacco-related deaths is estimated at 73,000 per year, including 44,000 from cancer and more than 20,000 from lung cancer (LC). Smoking cessation is the most effective measure to reduce the epidemic of LC, but it is also important in the management of patients with LC regardless on stage. In localized cancers, continuing to smoke is associated with decreased survival by increasing the risk of recurrence and of developing a second cancer. During the perioperative period, smoking cessation reduces infectious complications and length of hospitalization. At all stages of the cancer, smoking cessation improves dyspnoea and appetite, and reduces fatigue, leading to improved quality of life. Tobacco addiction causes a strong physical, psychological and behavioral dependence, explaining the high rate of recurrence at 1year of approximately 80%. Nicotine replacement therapy is indicated in cases of physical addiction to nicotine. Cognitive behavioral therapy helps the smoker to get rid of the smoking habit and is important in preventing relapse.

[A simple view on lung cancer biology: the MET pathway]. / Un regard simple sur la biologie du cancer bronchique : MET.

MET is a cell membrane tyrosine kinase receptor for its ligand the hepatocyte growth factor (HGF), also called scatter factor (SF). MET conveys mitogenic, motogenic and proangiogenic signals, important during embryonic development and during the development of cancer. Activation of the HGF-MET pathway seems to be associated with a poor prognosis in lung cancer. Activation in lung cancer may be related to several molecular anomalies: ligand overexpression, receptor overexpression, genomic amplification or MET mutation. In MET amplified or mutated lung cancer, MET may be an important oncogene, as the tumor appears "MET addicted". In other lung cancers, MET may be implicated in tumour progression by tissue invasion and formation of metastases. MET amplification is also a mechanism known to be implicated in 20% of secondary resistance to EGFR inhibitors in patients presenting EGFR mutated lung cancer. Different strategies of MET inhibition in lung cancer are being studied, particularly in EGFR mutated lung cancer. In this review we discuss the structure of the MET receptor, the activated pathways, the main genomic anomalies in lung cancer and the development of MET inhibitors.

[A simple view on lung cancer biology: The EGFR pathway]. / Un regard simple sur la biologie du cancer bronchique : EGFR.

Epidermal growth factor receptor (EGFR) is a cell membrane tyrosine kinase receptor. Activating mutations at exon 19 and 21 of the EGFR gene are associated with the occurrence and development of lung adenocarcinoma. These gain of function mutations predict responsiveness to EGFR tyrosine kinase inhibitors (TKis), erlotinib or gefitinib and are also a favorable prognostic factor in lung cancer. Sequencing is the recommended technique to detect the mutations, but other more sensitive technics are under evaluation. Treatment as first line therapy by gefitinib is limited to lung cancer patients harboring an EGFR mutation. Erlotinib can be given regardless of the EGFR status as second or third line therapy, as well as maintenance therapy in patients with a stable disease after platinum based chemotherapy. In EGFR mutated tumors, most patients present a recurrence of the disease, despite an initial response on EGFR TKis. Two mechanisms of secondary resistance have been identified, the selection of the T790M mutation in EGFR exon 20 and the MET amplification. Other molecular anomalies as the ras mutations or the EMLA-ALK protein fusion are mutually exclusive with the EGFR mutations and are associated with primary resistance to EGFR TKis.

Coexisting pulmonary nodules in operable lung cancer: prevalence and probability of malignancy.

INTRODUCTION: Coexistence of pulmonary nodules in operable non small cell lung cancer (NSCLC) may influence the therapeutic indication. The aim of this study was to evaluate prospectively the prevalence and the probability of malignancy of pulmonary nodules in operable lung cancer. METHODS: From a prospective database, all surgically treated patients diagnosed with NSCLC from 1998 to 2003 were retrospectively reviewed. Patients presenting pulmonary nodule(s) were identified. RESULTS: Two hundred thirty nine patients had a complete resection for a NSCLC and 56 patients (24%) presented altogether 88 nodules on thoracic CT. Twenty-four of these nodules (27%) were malignant, 28 (32%) benign and 36 (41%) of undetermined nature. Five factors associated with nodule's malignancy were identified: tumour histology (non-squamous (non-SCC) 44% vs. SCC 7%, p=0.001), localization of the nodules in an upper lobe (vs. other lobe, p=0.004), co localization in the same lobe as the NSCLC (vs. another lobe, p=0.03), nodule size (p=0.05) and shape (speculated vs. non spiculated, p=0.02). From these factors, a probability score was assessed with a malignancy rate in SCC of 0% in nodules presenting ≤ 1 feature, 33% with 2 features and 100% with ≥ 3 features and in non-SCC of 40% with 1 feature, 82% with 2 features and 100% with 3 ≥ features. CONCLUSION: Diagnosis of satellite nodules associated with early stage NSCLC is common. We developed a predictive score to estimate the probability of malignancy which may be a precious aid in the management of pulmonary nodules associated to a NSCLC.