Asthma and smoking: A review.

Asthma occurrence is often associated with cigarette smoking. Surprisingly, active smokers are excluded from most clinical studies. Prevalence of asthma associated with smoking appears to be similar to asthma in the general population. However, in active smokers, asthma tends to be more difficult to manage and more severe. Several studies have demonstrated a poor response to inhaled corticosteroids (ICS) and an accelerated decline of lung function. Smoking decreases exhaled NO rate and down-regulates ICS receptors, which is associated with increased oxidative stress. Data on biologic therapies are scarce. Finally, nicotine dependence seems higher in asthmatic patients and smoking cessation is thus more difficult.

Risk stratification for predicting recurrent venous thromboembolism after discontinuation of anticoagulation: a post hoc analysis of a French prospective multicentre study.

BACKGROUND: We aimed to validate and to refine current recurrent venous thromboembolism (VTE) risk classification. METHODS: We performed a post hoc analysis of a multicentre cohort including 1881 patients with a first symptomatic VTE prospectively followed after anticoagulation discontinuation. The primary objective was to validate the International Society of Thrombosis and Haemostasis (ISTH) risk classification in predicting recurrence risk. The secondary objective was to evaluate a refined ISTH classification based on the recurrence risk estimate for each individual risk factor. RESULTS: During a 4.8-year median follow-up after anticoagulation discontinuation, symptomatic recurrent VTE occurred in 230 patients (12.2%). Based on the ISTH classification, patients with unprovoked VTE or VTE with minor or major persistent risk factors had a 2-fold increased recurrence risk compared with those with VTE and major transient risk factors. Recurrence risk was not increased in patients with minor transient factors (hazard ratio (HR) 1.31, 95% CI 0.84-2.06). Individual risk factors analysis identified hormone-related VTE (pregnancy: HR 0.26, 95% CI 0.08-0.82; oestrogens: HR 0.25, 95% CI 0.14-0.47) and amyotrophic lateral sclerosis (HR 5.84, 95% CI 1.82-18.70). After reclassification of these factors as major transient for the former and major persistent for the latter, the modified ISTH classification allowed us to accurately discriminate between patients at low risk of recurrence (i.e. with major transient risk factors) and those at high risk of recurrence (i.e. without major transient risk factors). CONCLUSIONS: Among patients who stopped anticoagulation after a first VTE, a refined ISTH classification based on recurrence risk intensity of individual factors allowed discrimination between patients at low recurrence risk, including hormonal exposure in women, and patients at high recurrence risk.

Screening for COPD in primary care, involving dentists, pharmacists, physiotherapists, nurses and general practitioners (the UNANIME pilot study).

BACKGROUND: COPD is underdiagnosed and is projected to be the third cause of death in 2030. However, recent reviews do not recommend screening for COPD in the general population. METHODS: We conducted a prospective study to assess the feasibility of implementing COPD screening in a high-risk COPD population, with the help of various healthcare professionals (General practitioners, pharmacists, dentists, physiotherapists, and nurses). Participants filled out a questionnaire, performed a spirometry (COPD6™) and counselling was performed, including smoking cessation and chest physician referral. Participants were contacted at two months to evaluate the effect of the intervention. RESULTS: Between April 7th, 2017 and July 30th, 2018, 157 participants filled out the questionnaires, performed spirometry and were contacted at two months. Thirty-five out of 157 (22% [95% CI, 15.8-28.8]) participants were detected with an airflow obstruction (FEV1/FEV6 < 0.7), using COPD6™ device. At the two-month-contact, 68 participants (43%, [95%CI 35.5-51.1]) were engaged in a smoking cessation program and 22 (14% [95 % CI, 8.6-19.4]) reported having quit smoking. CONCLUSION: This pilot study suggested that a predefined screening of COPD by different healthcare professionals could be implemented in primary care and might be part of counselling for smoking cessation (NCT03104348 on ClinicalTrials.gov).

Effect of Early Initiation of Varenicline on Smoking Cessation in COPD Patients Admitted for Exacerbation: The Save Randomized Clinical Trial.

Our main objective was to demonstrate that, in smoker patients hospitalised for Chronic Obstructive Pulmonary Disease (COPD) exacerbation, early initiation of varenicline during 12 weeks, combined with an intensive counselling, is associated with a higher continuous abstainers rate (CAR) at one year as compared to intensive counselling alone. In this multicenter, prospective, double-blind, randomised study, 81 smoking COPD patients hospitalised for an acute exacerbation for at least 24 h were allocated to receive either varenicline (n = 42) or placebo (n = 39) for 12 weeks, in association with an intensive counselling in the 2 groups, and followed up for 40 weeks. The primary outcome was CAR at week 52. Secondary outcomes included CAR at week 12 and 26, partial abstinence rate (PAR) at week 12, 26 and 52, nicotinic substitute consumption and adverse events. At week 52, CAR was not different in placebo and varenicline groups (25.6%). At week 12, CAR was significantly higher in the varenicline group (50%) as compared to placebo group (27%) (p = 0.041). Nicotine consumption was significantly higher at week 52 in the placebo group (55.3%) as compared to the varenicline group (24.4%) (p = 0.005). There was no significant difference in PAR at week 12, 26 and 52; the frequency of adverse events was similar between the two groups. Among active smoker COPD patients with exacerbation, 12-week varenicline associated with intensive counselling for smoking cessation increased the rate of continuous abstainers as compared to placebo. However, benefit was not maintained after varenicline discontinuation.Clinical Trials Registration: URL: http://www.controlled-trials.com. Unique identifier: NCT01694732.

Women and COPD: do we need more evidence?

The increasingly female face of chronic obstructive pulmonary disease (COPD) prevalence among women has equalled that of men since 2008, due in part to increased tobacco use among women worldwide and exposure to biomass fuels. This finding is supported by a number of characteristics. There is evidence of susceptibility to smoking and other airborne contaminants, along with epidemiological and phenotypic manifestations. COPD has thus become the leading cause of death in women in the USA. The clinical presentation is characterised by increasingly pronounced dyspnoea with a marked tendency towards anxiety and depression, undernutrition, nonsmall cell lung cancer (especially adenocarcinoma) and osteoporosis. Quality of life is also more significantly impacted. The theories advanced to explain these differences involve the role played by oestrogens, impaired gas exchange in the lungs and smoking habits. While these differences require appropriate therapeutic responses (smoking cessation, pulmonary rehabilitation, long-term oxygen therapy), barriers to the treatment of women with COPD include greater under-diagnosis than in men, fewer spirometry tests and medical consultations. Faced with this serious public health problem, we need to update and adapt our knowledge to the epidemiological changes.

Risk of venous thromboembolism in association with factor V leiden in cancer patients - The EDITH case-control study.

BACKGROUND: Cancer and factor V Leiden mutation are both risk factors for venous thromboembolism (VTE). Cancer critically increases the thrombotic risk whereas Factor V Leiden is the most common pro-thrombotic mutation. The impact of the factor V Leiden on the risk of VTE in cancer patients remains uncertain. OBJECTIVE: To assess the impact of factor V Leiden mutation in cancer-associated thrombosis. METHODS: The EDITH hospital-based case-control study enrolled 182 patients with cancer and VTE as well as 182 control patients with cancer, matched for gender, age and cancer location, between 2000 and 2012, in the University Hospital of Brest. All cases and controls were genotyped for the factor V Leiden mutation and interviewed with a standardized questionnaire. RESULTS: Twenty one of 182 (11.5%) patients with cancer-associated thrombosis carried the factor V Leiden mutation and 4 of 182 (2.2%) controls with cancer but no venous thrombosis. In multivariate analysis including cancer stage and family history of VTE, cancer patients with factor V Leiden mutation had a seven-fold increased risk of venous thromboembolism (adjusted odds ratio [OR], 7.04; 95% CI, 2.01-24.63). CONCLUSION: The pro-thrombotic Factor V Leiden mutation was found to be an independent additional risk factor for venous thromboembolism in cancer patients and might therefore be considered in the individual thrombotic risk assessment.

Lymphocyte Disturbances in Primary Antiphospholipid Syndrome and Application to Venous Thromboembolism Follow-Up.

Among patients with venous thromboembolism (VTE), the persistent detection of antiphospholipid (aPL) antibodies (Ab) represents an independent high risk factor for recurrence. However, oral anticoagulation vitamin K antagonist therapy, frequently used in these patients, is problematic in assessing and/or confirming a diagnosis of primary aPL syndrome (pAPS), suggesting use of alternative strategies. For this reason, and by analogy with other autoimmune diseases, a flow cytometer approach testing peripheral T cell subsets (CD3, CD4, and CD8), B cell subsets (B1, transitional, naive, and memory), and NK cells can be proposed. As an example and to validate the concept, pAPS patients selected from the monocentric VTE case-control EDITH's cohort were selected during their follow-up. As suspected and in contrast to non-APS VTE patients, other autoimmune diseases, and controls, pAPS VTE patients displayed specific lymphocyte disturbances. Quantitative and qualitative modifications were related to total CD4+ T cell reduction, a lower CD4/CD8 ratio, and disturbance in B cell homeostasis with increased proportions of B1 cells, transitional B cells (CD24++CD38++), and naive B cells (IgD+CD27-), while memory B cells (IgD+CD27+ and IgD-CD27+) were reduced. Interestingly, the absolute number of CD4+ T cells positively correlated with IgG anti-cardiolipin Ab levels. Altogether, disturbances of T and B cell homeostasis characterized pAPS VTE patients during their follow-up. This suggests a means of profiling that could be used in addition to existing criteria to characterize them.

Tinzaparin and VKA use in patients with cancer associated venous thromboembolism: a retrospective cohort study.

INTRODUCTION: After 6months, little is known about the optimal anticoagulant strategy for an acute episode of VTE in cancer patients. AIMS, OBJECTIVES AND METHODS: The objective was to determine the risk of recurrent VTE and anticoagulant-related bleeding at 6months of follow-up and after 6months, in cancer patients who received tinzaparin during at least 3months for an acute episode of VTE. We conducted a multicenter retrospective cohort study from January 2004 to March 2011. RESULTS: Two hundred fifty patients were included. Stopping anticoagulation before 6months in patients considered at low risk by physicians (i.e.; patients who had prior cancer surgery) and for another reason than bleeding or death was the only factor associated with a significant increased risk of recurrent VTE (OR 7.2 95%CI, 2.0-25.7; p=0.002). The type of anticoagulation did not influence the risk of recurrent VTE. We found a trend towards an increased risk of recurrent VTE when anticoagulation was stopped because of major bleeding while on anticoagulant therapy and patients with metastatic cancer (OR 2.3, 95%CI, 0.9-5.4; p=0.07; and OR 1.8 95%CI, 1.0-3.3; p=0.07; respectively). No factors were found to increase the risk of major bleeding at 6months and after. The overall mortality was 42.8%. CONCLUSIONS: The risk of recurrent VTE was mainly related to early discontinuation of anticoagulation in patients considered at low risk of recurrence (after surgery). When the anticoagulation was stopped before the sixth month, the risk was eight fold higher. After 6month, the risks of recurrent VTE, major bleeding and death were similar in patients with either VKA or tinzaparin when patients were treated according to the guidelines.

Comorbidities of COPD.

By 2020, chronic obstructive pulmonary disease (COPD) will be the third cause of mortality. Extrapulmonary comorbidities influence the prognosis of patients with COPD. Tobacco smoking is a common risk factor for many comorbidities, including coronary heart disease, heart failure and lung cancer. Comorbidities such as pulmonary artery disease and malnutrition are directly caused by COPD, whereas others, such as systemic venous thromboembolism, anxiety, depression, osteoporosis, obesity, metabolic syndrome, diabetes, sleep disturbance and anaemia, have no evident physiopathological relationship with COPD. The common ground between most of these extrapulmonary manifestations is chronic systemic inflammation. All of these diseases potentiate the morbidity of COPD, leading to increased hospitalisations and healthcare costs. They can frequently cause death, independently of respiratory failure. Comorbidities make the management of COPD difficult and need to be evaluated and treated adequately.

Delayed noninvasive reduction of large bullae following thoracic irradiation.

Chest radiotherapy is a mainstay of management of thoracic oncology patients. Radiotherapy also injures nontarget tissues such as the lungs, coronary arteries, and esophagus, and safe limits to the doses that can be delivered to tumors have been determined empirically. Patients afflicted with lung cancer due to smoking often have concomitant chronic obstructive pulmonary disease which, on occasion, manifests as bullous emphysema. We describe a case and course of treatment of lung cancer found incidentally in a patient followed for severe pulmonary emphysema. Treatment consisted of radiochemotherapy after induction chemotherapy. Three years after the end of antineoplastic treatment, a follow-up computed tomography scan revealed complete retraction of a large emphysematous bulla that had been present prior to treatment.

Benfluorex and unexplained valvular heart disease: a case-control study.

BACKGROUND: Recent case reports suggest that benfluorex, a fenfluramine derivative used in the management of overweight diabetic patients and dyslipidemia, is associated with cardiac valve regurgitation. METHODS: We conducted a case-control study. Eligible patients were those admitted in the cardiology or the cardiac surgery units of our hospital between January, 1(st) 2003 and June 30(th) 2009, with mitral insufficiency diagnostic codes (ICD-10 I340 and I051). Patients with either a primary cause (degenerative, known rheumatic heart disease, infectious endocarditis, congenital, radiation-induced valvular disease, associated connective and/or vasculitis disease, trauma, tumor) or a secondary (functional) cause were considered as having an "explained" mitral regurgitation. Other patients were considered as having an "unexplained" mitral regurgitation and were included as cases. For each case, two controls were matched for gender and for the closest date of birth, among a list of patients with an "explained" mitral regurgitation. Drug exposures were assessed blindly regarding the case or control status, through contacts with patients, their family and/or their physicians. RESULTS: Out of the 682 eligible patients, 27 cases and 54 matched controls were identified. The use of benfluorex was reported in 22 patients: 19 of the 27 cases, versus 3 of the 54 controls, odds-ratio 17.1 (3.5 to 83), adjusted for body mass index, diabetes and dexfenfluramine use. CONCLUSION: The use of benfluorex is associated with unexplained mitral regurgitation.

Family history as a risk factor for venous thromboembolism.

INTRODUCTION: There are very few data assessing a family history of venous thromboembolism (VTE) as a risk factor for VTE. This question is nonetheless of interest as inherited risk factors are involved but at least partly unknown. METHODS: The E.D.I.TH. study is a prospective hospital-based case-control study. The family history was assessed by using a standard questionnaire, considering the total number of the first-degree relatives and the number of these relatives who had suffered from VTE. We analysed 698 first VTE cases and their matched controls, 507 pairs without and 191 pairs with a major acquired risk factor (active malignancy, surgery or plaster cast in the past three months, pregnancy or delivery in the past three months). RESULTS: A family history of VTE was associated with VTE occurrence, irrespective of carrying or not factor V Leiden mutation or G20210A prothrombin gene mutation and irrespective of the presence or absence of major acquired risk factors; adjusted conditional odds ratio: 2.7 (95%CI, 1.8-3.8). CONCLUSION: A family history might well be considered when estimating type and duration of prophylaxis for VTE specifically in patients with active cancer or who experienced surgery. Family history of VTE could be added to a prior VTE history to define a concept of clinical thrombophilia which is not necessarily related to carrying a known inherited risk factor.

High frequency of factor V Leiden in surgical patients with symptomatic venous thromboembolism despite prophylaxis.

Among candidate risk factors associated with postoperative venous thromboembolism (VTE), the role of factorV Leiden (FVL) mutation remains unclear. We performed a case-control study to assess the potential significance of FVL mutation in postoperative VTE cases despite prophylaxis. We used data from the ongoing case-control "EDITH" study. We extracted 133VTE cases and 144 controls who had undergone either surgery or had plaster cast in the previous three months. Prophylaxis adequacy with regard to the recommendations published by the American College of Chest Physicians was retrospectively assessed. FVL mutation was present in 20VTE cases and four controls (OR 5.9, 95% CI 2-18). Prophylaxis was judged as adequate in 116 cases (88.5%) and in 129 controls (87.2%) (p=0.66). The frequency of FVL mutation was not different in VTE cases occurring while on adequate prophylaxis and in VTE cases occurring after the end of adequate prophylaxis (p=0.27). FVL mutation was closely associated with postoperative VTE in patients classified as having received an adequate prophylaxis (8.4; 95% CI, 2.4 to 29). This study shows a close association between the presence of factorV Leiden mutation in symptomatic VTE occurring after surgery despite prophylaxis.

Estrogen receptor alpha polymorphism and venous thromboembolism in male and female: data from the EDITH study.

BACKGROUND: Association between estrogen receptor (ER) alpha polymorphism c.454-397 T>C and venous thromboembolism (VTE) has been reported in postmenopausal women. Comprehensive data are lacking. We herein evaluated the risk for VTE related to c.454-397 T>C ER alpha gene polymorphism in both men and women. PATIENTS/METHODS: The EDITH Study enrolled consecutive patients, aged over 18 years, hospitalized between May 2000 and December 2004 in Brest University Hospital with an objectively proven symptomatic VTE. For each case, one control who matched the case for age within a five-year age band, gender and major acquired risk factors, was selected. The present analysis was restricted to 677 cases with a VTE event not related to major acquired risk factors and their matched controls. RESULTS AND CONCLUSIONS: The relationship between VTE and c.454-397 T>C ER alpha polymorphism was consistent with a dominant model in women and a recessive model in men. Adjusted conditional odds ratios (95% CI) were 1.37 (1.05-1.78) and 1.29 (0.85-1.94) for CT/CC genotypes in women and CC genotype in men respectively compared to TT genotype. Among women hormone use did not substantially modify effect-measure estimate. Our results further extend results from previous studies. Other investigations are required to precise underlying mechanisms.

[Diagnosis of postoperative venous thromboembolism]. / Le diagnostic de la maladie veineuse thrombo-embolique en post-opératoire.

UNLABELLED: AN IMPORTANT SUBJECT: The thromboembolic disease still prevails in the context of surgery, despite the progression in prophylaxis. Particular attention must be paid to the possibility of delayed events, often occurring within the three months following a surgical procedure. Although many general studies, assessing supplementary examination or diagnostic strategies are available, the proportion of patients concerned by a post-operative context varies. IN PRACTICE: The Doppler is the diagnostic examination of choice in the case of suspected deep vein thrombosis, but it is not recommended in a strategy of screening for asymptomatic thrombosis in surgery. A suspected embolism can be confirmed or eliminated using noninvasive examinations, but it requires that invasive tests be performed more often than in a medical context. The indication for a helical computed tomography, presently more readily available than a pulmonary angiography, would appear legitimate, so long as a Doppler of the lower limbs is systematically associated. RESERVATIONS IN THE POST-OPERATIVE PERIOD: The results of this strategy, most satisfactory in the majority of patients, do not appear as interesting post-operatively. The studies targeting the management of suspected post-operative pulmonary embolism are rare and warrant further encouragement.

High prevalence of asymptomatic deep vein thrombosis on admission in a medical unit among elderly patients.

The prevention of venous thromboembolism in medical patients remains questioned. All consecutive outpatients admitted in our medical unit were considered for inclusion in this study which aimed to estimate the prevalence of asymptomatic venous thrombosis on admission and the incidence during hospital stay. Exclusion criteria were: age <18 years, suspicion of venous thromboembolism, stay <4 days, ongoing anticoagulant therapy. Venous compression ultrasonography of the lower limbs was performed within 48 h. 234 patients were included. The prevalence of asymptomatic deep vein thrombosis on admission and the incidence during hospital follow-up were respectively 5.5% (95% confidence interval, 3.1 to 9.5%) and 2.6 per 1,000 person-days (95% confidence interval, 0.0 to 5.2). The prevalence and the incidence reached respectively 17.8% (95% confidence interval, 8.5 to 32.6%) and 6.0 per 1,000 person-days (95% confidence interval, 0.0 to 12.7) among patients over 80 years. A high prevalence of asymptomatic deep vein thrombosis on admission was suggested particularly among elderly medical patients.