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International audience; Rationale: The relationship between the initial treatment strategy and survival in pulmonary arterial hypertension (PAH) remains uncertain. Objectives: To evaluate the long-term survival of patients with PAH categorized according to the initial treatment strategy. Methods: A retrospective analysis of incident patients with idiopathic, heritable, or anorexigen-induced PAH enrolled in the French Pulmonary Hypertension Registry (January 2006 to December 2018) was conducted. Survival was assessed according to the initial strategy: monotherapy, dual therapy, or triple-combination therapy (two oral medications and a parenteral prostacyclin). Measurements and Main Results: Among 1,611 enrolled patients, 984 were initiated on monotherapy, 551 were initiated on dual therapy, and 76 were initiated on triple therapy. The triple-combination group was younger and had fewer comorbidities but had a higher mortality risk. The survival rate was higher with the use of triple therapy (91% at 5 yr) as compared with dual therapy or monotherapy (both 61% at 5 yr) (P < 0.001). Propensity score matching of age, sex, and pulmonary vascular resistance also showed significant differences between triple therapy and dual therapy (10-yr survival, 85% vs. 65%). In high-risk patients (n = 243), the survival rate was higher with triple therapy than with monotherapy or dual therapy, whereas there was no difference between monotherapy and double therapy. In intermediate-risk patients (n = 1,134), survival improved with an increasing number of therapies. In multivariable Cox regression, triple therapy was independently associated with a lower risk of death (hazard ratio, 0.29; 95% confidence interval, 0.11-0.80; P = 0.017). Among the 148 patients initiated on a parenteral prostacyclin, those on triple therapy had a higher survival rate than those on monotherapy or dual therapy. Conclusions: Initial triple-combination therapy that includes parenteral prostacyclin seems to be associated with a higher survival rate in PAH, particularly in the youngest high-risk patients.

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.

International audience; Work-related asthma (WRA) is a very frequent condition in the occupational setting, and refers either to asthma induced (occupational asthma, OA) or worsened (work-exacerbated asthma, WEA) by exposure to allergens (or other sensitizing agents) or to irritant agents at work. Diagnosis of WRA is frequently missed and should take into account clinical features and objective evaluation of lung function. The aim of this overview on pulmonary function testing in the field of WRA is to summarize the different available tests that should be considered in order to accurately diagnose WRA. When WRA is suspected, initial assessment should be carried out with spirometry and bronchodilator responsiveness testing coupled with first-step bronchial provocation testing to assess non-specific bronchial hyper-responsiveness (NSBHR). Further investigations should then refer to specialists with specific functional respiratory tests aiming to consolidate WRA diagnosis and helping to differentiate OA from WEA. Serial peak expiratory flow (PEF) with calculation of the occupation asthma system (OASYS) score as well as serial NSBHR challenge during the working period compared to the off work period are highly informative in the management of WRA. Finally, specific inhalation challenge (SIC) is considered as the reference standard and represents the best way to confirm the specific cause of WRA. Overall, clinicians should be aware that all pulmonary function tests should be standardized in accordance with current guidelines.

Previous studies have suggested an association between uric acid (UA) and the severity of pulmonary arterial hypertension (PAH), but it is unknown whether UA contributes to disease pathogenesis.The aim of this study was to determine the prognostic value of circulating UA in the era of current management of PAH and to investigate the role of UA in pulmonary vascular remodelling.Serum UA levels were determined in idiopathic, heritable or anorexigen PAH at baseline and first re-evaluation in the French Pulmonary Hypertension Network. We studied protein levels of xanthine oxidase (XO) and the voltage-driven urate transporter 1 (URATv1) in lungs of control and PAH patients and of monocrotaline (MCT) and Sugen/hypoxia (SuHx) rats. Functional studies were performed using human pulmonary artery smooth muscle cells (PA-SMCs) and two animal models of pulmonary hypertension (PH).High serum UA levels at first follow-up, but not at baseline, were associated with a poor prognosis. Both the generating enzyme XO and URATv1 were upregulated in the wall of remodelled pulmonary arteries in idiopathic PAH patients and MCT and SuHx rats. High UA concentrations promoted a mild increase in cell growth in idiopathic PAH PA-SMCs, but not in control PA-SMCs. Consistent with these observations, oxonic acid-induced hyperuricaemia did not aggravate MCT-induced PH in rats. Finally, chronic treatment of MCT and SuHx rats with benzbromarone mildly attenuated pulmonary vascular remodelling.UA levels in idiopathic PAH patients were associated with an impaired clinical and haemodynamic profile and might be used as a non-invasive indicator of clinical prognosis during follow-up. Our findings also indicate that UA metabolism is disturbed in remodelled pulmonary vascular walls in both experimental and human PAH.

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension. Heritable and sporadic forms have been distinguished. Hypoxemia, profound reduction in the diffusion of carbon monoxide and haemodynamic confirmation of pre-capillary pulmonary hypertension are the major diagnostic criteria. Thoracic CT scanning and a response to pharmaceutical therapy provide additional information to confirm the diagnosis. A 52-year-old patient, three of whose siblings had pulmonary hypertension, was admitted with dyspnoea, malaise and palpitations. Right heart catheterisation confirmed pre-capillary pulmonary hypertension. A search for an EIF2AK4 mutation was carried out, and this showed a composite biallelic heterozygous mutation compatible with the diagnosis of familial PVOD, identical to that showed in one of his brothers. Given the signs of severity of the disease and the diagnosis of PVOD, whose response to pharmaceutical therapy is often poor, the patient was placed on a waiting list for lung transplantation. Despite a similar diagnosis in 3 brothers and follow-up proposed 11 years before the diagnosis, pulmonary hypertension appeared within a few weeks and led immediately to a severe clinical situation. Annual clinical and echocardiographic monitoring had been strongly advised to the patient, but had not allowed diagnosis at a mild or moderate stage of the disease. This clinical case shows that the identification of factors predicting the development of heritable PVOD at a pre-symptomatic stage is an important issue for clinical research.

International audience

Resume Introduction Les pneumopathies a eosinophiles sont caracterisees par une alveolite a polynucleaires eosinophiles. Elles peuvent etre idiopathiques ou relever de differentes causes. L’origine medicamenteuse doit etre toujours evoquee. Observation Nous rapportons le cas d’une femme de 57 ans, fumeuse, atteinte d’un trouble bipolaire, traitee par divalproate de sodium depuis plus de 2 ans, qui presentait une dyspnee non febrile depuis 5 mois. Les explorations realisees montraient une hypoxemie severe, un trouble ventilatoire obstructif severe, de multiples images en verre depoli avec un aspect de crazy paving au scanner thoracique, une hypereosinophilie sanguine et une alveolite a eosinophiles au lavage broncho-alveolaire. Le diagnostic de pneumopathie a eosinophiles au divalproate de sodium etait retenu apres un bilan etiologique exhaustif, et l’amelioration radio-clinique etait rapide apres l’arret du medicament, sans recours a la corticotherapie systemique. Conclusion Le divalproate de sodium peut induire une pneumopathie a eosinophiles plusieurs annees apres son introduction. Un diagnostic rapide et un arret du traitement ont permis une guerison complete dans le cas rapporte.

IntroductionTBX4 mutation causes small patella syndrome (SPS) and/or pulmonary arterial hypertension (PAH). The characteristics and outcomes of PAH associated with TBX4 mutations are largely unknown.MethodsWe report the clinical, functional, radiologic, histologic and haemodynamic characteristics and outcomes of heritable PAH patients carrying a TBX4 mutation from the French pulmonary hypertension (PH) network.Results20 patients were identified in 17 families. They were characterised by a median age at diagnosis of 29 years (0–76 years) and a female to male ratio of three. Most of the patients (70%) were in New York Heart Association (NYHA) functional class III or IV with a severe haemodynamic impairment (median pulmonary vascular resistance (PVR) of 13.6 (6.2–41.8) Wood units). Skeletal signs of SPS were present in 80% of cases. Half of the patients had mild restrictive or obstructive limitation and diffusing capacity of the lung for carbon monoxide (DLCO) was decreased in all patients. High-resolution computed tomography (HRCT) showed bronchial abnormalities, peri-bronchial cysts, mosaic distribution and mediastinal lymphadenopathies. PAH therapy was associated with significant clinical improvement. At follow-up (median 76 months), two patients had died and two had undergone lung transplantation. One-year, three-year and five-year event-free survival rates were 100%, 94% and 83%, respectively. Histologic examination of explanted lungs revealed alveolar growth abnormalities, major pulmonary vascular remodelling similar to that observed in idiopathic pulmonary arterial hypertension (IPAH) and accumulation of cholesterol crystals within the lung parenchyma.ConclusionPAH due to TBX4 mutations may occur with or without skeletal abnormalities across a broad age range from birth to late adulthood. PAH is usually severe and associated with bronchial and parenchymal abnormalities.

Resume Introduction Les evenements osseux (EO) sont frequents chez les patients atteints de cancer bronchique (CB) metastatique au niveau osseux et ont un impact negatif sur la qualite de vie et la survie. L’objectif de cette etude est d’identifier les facteurs predictifs de survenue d’EO dans cette population. Methodes Une analyse retrospective sur 3 ans a ete realisee incluant 100 patients avec un CB metastatique au niveau osseux. Resultats Quatre-vingt-deux patients presentaient au moins un EO (69,5 % au diagnostic). La mediane de survenue d’un EO etait de 4,5 mois et les douleurs osseuses severes etaient l’EO le plus frequent (56 %). Les facteurs predictifs identifies pour la survenue d’EO etaient un taux serique de phosphatases alcalines (PAL) > 120 UI/L (risque relatif [RRs] = 2,8 ; intervalle de confiance (IC) 95 % [1,5–5,4] ; p = 0,002) et une calcemie > 2,6 mmol/L ([RRs] = 9,7 ; IC 95 % [5,1–18,4] ; p Conclusion Le taux eleve de PAL seriques et l’hypercalcemie sont des facteurs predictifs d’EO chez les patients ayant un CB metastatique au niveau osseux et devraient etre utilises dans la pratique courante comme biomarqueurs pour adapter la prise en charge de ces patients.

The analysis of right ventriculo-arterial coupling (RVAC) from pressure-volume loops is not routinely performed. RVAC may be approached by the combination of right heart catheterization (RHC) pressure data and cardiac magnetic resonance (CMR)-derived right ventricular (RV) volumetric data. RV pressure and volume measurements by Doppler and three-dimensional echocardiography (3DE) allows another way to approach RVAC.Ninety patients suspected of having pulmonary hypertension underwent RHC, 3DE, and CMR (RHC mean pulmonary artery pressure [mPAP] 37.9 ± 11.3 mm Hg; range, 15-66 mm Hg). Three-dimensional (3D) echocardiography was performed in 30 normal patients (echocardiographic mPAP 18.4 ± 3.1 mm Hg). Pulmonary artery (PA) effective elastance (Ea), RV maximal end-systolic elastance (Emax), and RVAC (PA Ea/RV Emax) were calculated from RHC combined with CMR and from 3DE using simplified formulas including mPAP, stroke volume, and end-systolic volume.Three-dimensional echocardiographic and RHC-CMR measures for PA Ea (3DE, 1.27 ± 0.94; RHC-CMR, 0.71 ± 0.52; r = 0.806, P .001), RV Emax (3DE, 0.72 ± 0.37; RHC-CMR, 0.38 ± 0.19; r = 0.798, P .001), and RVAC (3DE, 2.01 ± 1.28; RHC-CMR, 2.32 ± 1.77; r = 0.826, P .001) were well correlated despite a systematic overestimation of 3DE elastance parameters. Among the whole population, 3D echocardiographic PA Ea and 3D echocardiographic RVAC but not 3D echocardiographic RV Emax were significantly lower in patients with mPAP25 mm Hg (n = 41) than in others (n = 79). Among the 90 patients who underwent RHC, 3D echocardiographic PA Ea and 3D echocardiographic RVAC but not 3D echocardiographic RV Emax increased significantly with increasing levels of pulmonary vascular resistance.Three-dimensional echocardiography-derived PA Ea, RV Emax, and RVAC correlated well with the reference RHC-CMR measurements. Ea and RVAC but not Emax were significantly different between patients with different levels of afterload, suggesting failure of the right ventricle to maintain coupling in severe pulmonary hypertension.

Resume Le syndrome de Doege-Potter associe une hypoglycemie paraneoplasique a une tumeur fibreuse solitaire. Les tumeurs fibreuses solitaires sont rares et le plus souvent asymptomatiques. L’apparition de signes cliniques ou de syndromes paraneoplasiques est le fait de tumeurs volumineuses avec un index mitotique eleve. Le diagnostic est evoque par l’imagerie mais la confirmation diagnostique est apportee par la chirurgie qui reste le traitement de choix. L’hypoglycemie resulte de la secretion par la tumeur de formes incompletes d’un facteur de croissance apparente a l’insuline appele « big »-IGF-2 ( insulin-like growth factor ). Plusieurs tests biologiques permettent de demontrer l’augmentation du taux plasmatique du « big »-IGF-2 confirmant le diagnostic de « non islet cell tumour induced hypoglyceamia ». L’exerese tumorale conduit a la resolution de l’hypoglycemie. Ces tumeurs ont un potentiel de malignite intermediaire. Malgre l’analyse histologique et immunohistochimique, leur pronostic et leur agressivite restent difficiles a etablir. Des recidives et des transformations malignes sont possibles tardivement, ce qui impose un suivi radiologique au long terme. Nous rapportons un cas de syndrome de Doege-Potter concernant une tumeur fibreuse solitaire pleurale a recidive maligne tardive dont l’interet est de documenter la physiopathologie de l’hypoglycemie paraneoplasique.

Background: New therapies have emerged in the treatment of pulmonary alveolar proteinosis (PAP) and, therefore, there is a real need to evaluate the efficacy of whole-lung lavage (WLL) in this rare disease. Objectives: The aim of this study was to assess the efficacy of WLL in patients with PAP. Methods: We included 33 patients from 12 centers, which are members of the French-Speaking Thoracic Endoscopy Group, for analysis. Data collection concerned patients and disease characteristics, pulmonary function tests (PFTs) and technical information on the procedure. Results: The median age of the patients was 44 years (range 13-77). There were 23 (71.9%) patients with respiratory insufficiency at presentation. All patients underwent WLL by general anesthesia and selective lung ventilation, except 1 who underwent awake flexible bronchoscopy. We noted differences in the technique, as 12 (36.36%) patients had percussion during the procedure and only 4 (12.1%) patients underwent 2-lung lavage during 1 anesthesia. A median of 12 L was used to perform WLL (1.0-40 L). Complications occurred in 11 (33.3%) patients, and 18 (56.25%) of them relapsed in a median period of 16.9 months. No significant changes were found in any PFT parameters studied, except for PaO2, which was significantly improved by 6.375 mm Hg (p = 0.0213) after the procedure compared to before. Conclusions: Although the application of the WLL technique was variable, overall, it significantly improved patients' short-term respiratory condition by improving PaO2. However, a long-term effect needs to be confirmed, as many of our patients relapsed.

Resume Introduction L’histoire naturelle des maladies pulmonaires orphelines est rarement connue. Nous presentons l’evolution a long terme d’une forme bronchectasiante de la maladie a depots de chaines legeres (MDCL) d’immunoglobulines non amyloides. Observation Il s’agit d’une femme fumeuse chez qui le diagnostic de dilatation des bronches d’etiologie indeterminee est porte a l’âge de 50 ans. Dix ans apres, l’hypothese d’une MDCL pulmonaire est evoquee devant l’aspect caracteristique des bronchectasies, l’apparition de kyste pulmonaires, l’augmentation du taux serique des chaines legeres Kappa. La confirmation diagnostique est obtenue par biopsie pulmonaire chirurgicale. Aucune hemopathie maligne n’est retrouvee. Durant les 12 ans de suivi, l’aggravation de la dyspnee d’effort est lente et concomitante a l’extension des bronchectasies et des kystes realisant un aspect de pneumopathie multikystique. Les EFR montrent une preservation des volumes pulmonaires et une diminution moderee de la capacite de diffusion du monoxyde de carbone (DLCO). Conclusion Nous decrivons l’evolution d’une presentation rare de la MDCL pulmonaire isolee sous la forme de bronchectasies kystiques diffuses, a parois fines, non secretantes, s’associant a une destruction kystique du parenchyme pulmonaire. L’hypothese d’une MDCL pulmonaire doit etre evoquee devant des bronchectasies atypiques d’etiologie indeterminee.

International audience; With healthcare objectives and budget constraint, remote monitoring of chronic obstructive pulmonary disease (COPD) patients is an important challenge in most European countries. Recent works have shown that it is possible to predict COPD exacerbation based on monitoring of simple parameters, such as the respiratory rate (RR) of the patient in spontaneous ventilation or under non-invasive ventilation. Until now, these devices do not allow a daily automatic data remote transmission,[4] or it is restricted to patients under mechanical ventilation. TeleOx® (SRETT, Boulogne-Billancourt, France), the first oxygen flow rate remote monitoring device, also allows a RR measurement by associating a pressure sensor and a fluidic oscillator flow sensor. A median RR is output every 5 minutes based on time interval between two consecutive respiratory cycles.In this study, we compared the corresponding RR measurements between TeleOx® and the reference polygraph (Nox-T3®, Nox Medical Inc. Reykjavik, Iceland) from COPD patients under nasal oxygen therapy with flow rates between 0.5 and 5.0 litres per minute. Patients without mechanical ventilation and without any other respiratory pathology were eligible to the study if they would undergo a ventilatory polygraph record for other reasons

International audience; Inflammatory bowel disease (IBD) is a chronic systemic inflammatory condition. Previously, the focus has been on extraintestinal manifestations of IBD, including arthritis, psoriasis, and uveitis. Although comorbidities have long been the subject of intensive research in other chronic inflammatory diseases such as rheumatoid arthritis, the concept of comorbidities is only beginning to emerge in IBD. Several comorbid conditions have been proposed to be related to IBD, including cardiovascular disease, neuropsychological disorders, and metabolic syndrome. Recognition of these conditions and their treatment could lead to better management of IBD. This Review aims to explore current knowledge regarding classic and emerging comorbidities related to IBD.Copyright © 2019 Elsevier Ltd. All rights reserved.

International audience; BACKGROUND:Paraneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with a PNS. Our objective was to describe the outcome for patients with a pre-existing or newly diagnosed PNS following the initiation of anti-PD-1 or anti-PD-L1 immunotherapy.METHODS:We included all adult patients (aged ≥18) treated with anti-PD-1 or anti-PD-L1 immunotherapy for a solid tumor, diagnosed with a PNS, and registered in French pharmacovigilance databases. Patients were allocated to cohorts 1 and 2 if the PNS had been diagnosed before vs. after the initiation of immunotherapy, respectively.FINDINGS:Of the 1304 adult patients screened between June 27th, 2014, and January 2nd, 2019, 32 (2.45%) had a PNS and were allocated to either cohort 1 (n = 16) or cohort 2 (n = 16). The median (range) age was 64 (45-88). The tumor types were non-small-cell lung cancer (n = 15, 47%), melanoma (n = 6, 19%), renal carcinoma (n = 3, 9%), and other malignancies (n = 8, 25%). Eleven (34%) patients presented with a neurologic PNS, nine (28%) had a rheumatologic PNS, eight (25%) had a connective tissue PNS, and four (13%) had other types of PNS. The highest severity grade for the PNS was 1-2 in 10 patients (31%) and ≥ 3 in 22 patients (69%). Four patients (13%) died as a result of the progression of a neurologic PNS (encephalitis in three cases, and Lambert-Eaton syndrome in one case). Following the initiation of immunotherapy, the PNS symptoms worsened in eight (50%) of the 16 patients in cohort 1.INTERPRETATION:Our results show that PNSs tend to be worsened or revealed by anti-PD-1 or anti-PD-L1 immunotherapy. Cases of paraneoplastic encephalitis are of notable concern, in view of their severity. When initiating immunotherapy, physicians should carefully monitor patients with a pre-existing PNS.

International audience; To study vertebral fracture (VF) prevalence and the scanographic bone attenuation coefficient of the first lumbar vertebra (SBAC-L1) on computed tomography scans (CT-scans) in systemic sclerosis patients. This monocentric retrospective study included patients followed from 2000 to 2014 and fulfilling ACR/EULAR 2013 criteria for systemic sclerosis and who underwent a thoracic or thoraco-abdomino-pelvic CT-scan during their follow-up. Clinical characteristics for sclerosis and osteoporosis risk factors were collected. For CT-scan, the VFs were determined according to Genant’s classification, the SBAC-L1 was measured in Hounsfield Units (HU), and a SBAC-L1 ≤ 145 HU (fracture threshold) defined patients at VF risk. Predictive factors for SBAC-L1 ≤ 145 HU were studied. A total of 70 patients were included [mean age, 62.3 (± 15.6) years, women 88.5%, diffuse sclerosis 22.9% (n = 16)]. On CT-scans, three VFs were detected in three patients (4.3%). The mean SBAC-L1 was 157.26 HU (± 52.1), and 35 patients (50%) presented a SBAC-L1 ≤ 145 HU. In multivariate analysis, only age (especially patients older than 63 years, OR = 1.08, CI 95% 1.04–1.13, p = 0.001) and calcinosis (OR = 6.04, CI 95% 1.27–28.70, p = 0.02) were independently associated with a SBAC-L1 ≤ 145 HU. On a large sample of patients with systemic sclerosis, the VF prevalence on CT-scan was low (4.3%) while 50% of the patients presented a SBAC-L1 ≤ 145 HU. Interestingly, the presence of calcinosis, periarticular calcifications or acro-osteolysis was linked with low SBAC-L1 and should lead to an osteoporosis screening, especially for patients under 63 years old.

Haemodynamic follow up in pulmonary arterial hypertension (PAH) is currently based on right heart catheterisation (RHC). The primary objective of the EVITA study is to compare the use of cardiac magnetic resonance imaging (cMRI) with RHC in the identification of an unfavourable hemodynamic status. The secondary objectives are to determine the role of cMRI in the follow up process. Patients will undergo at diagnosis and at follow up visits both RHC and cMRI. Patients will be followed and treated according to the current guidelines. The primary endpoint will be an unfavourable haemodynamic status defined by cardiac index

Current European guidelines recommend periodic risk assessment for patients with pulmonary arterial hypertension (PAH). The aim of our study was to determine the association between the number of low-risk criteria achieved within 1 year of diagnosis and long-term prognosis. Incident patients with idiopathic, heritable and drug-induced PAH between 2006 and 2016 were analysed. The number of low-risk criteria present at diagnosis and at first re-evaluation were assessed: World Health Organization (WHO)/New York Heart Association (NYHA) functional class I or II, 6-min walking distance (6MWD) >440 m, right atrial pressure, Simplified risk assessment using the number of low-risk criteria predicts prognosis at baseline and follow-up in PAH http://ow.ly/KMsj30cPNbm

International audience; Background: The relationships between asbestos exposure and colorectal cancer remain controversial. Objectives: We examined the association between asbestos exposure and colorectal cancer incidence. Methods: Volunteer retired workers previously exposed to asbestos were invited to participate in the French ARDCo screening program between 2003 and 2005. Additional data on risk factors for colorectal cancer were collected from the ARDCo-Nut subsample of 3,769 participants in 2011. Cases of colon and rectal cancer were ascertained each year through 2014 based on eligibility for free medical care following a cancer diagnosis. Survival regression based on the Cox model was used to estimate the relative risk of colon and rectal cancer separately, in relation to the time since first exposure (TSFE) and cumulative exposure index (CEI) to asbestos, and with adjustment for smoking in the overall cohort and for smoking, and certain risk factors for these cancers in the ARDCo-Nut subsample. Results: Mean follow-up was 10.2 years among 14,515 men, including 181 colon cancer and 62 rectal cancer cases (41 and 17, respectively, in the ARDCo-Nut subsample). In the overall cohort, after adjusting for smoking, colon cancer was significantly associated with cumulative exposure (HR = 1.14; 95% CI: 1.04, 1.26 for a 1-unit increase in ln-CEI) and ≥ 20–40 years since first exposure (HR = 4.67; 95% CI: 1.92, 11.46 vs. 0–20 years TSFE), and inversely associated with 60 years TSFE (HR = 0.26; 95% CI: 0.10, 0.70). Although rectal cancer was also associated with TSFE 20–40 years (HR = 4.57; 95% CI: 1.14, 18.27), it was not associated with ln-CEI, but these findings must be interpreted cautiously due to the small number of cases. Conclusions: Our findings provide support for an association between occupational exposure to asbestos and colon cancer incidence in men. Citation: Paris C, Thaon I, Hérin F, Clin B, Lacourt A, Luc A, Coureau G, Brochard P, Chamming’s S, Gislard A, Galan P, Hercberg S, Wild P, Pairon JC, Andujar P. 2017. Occupational asbestos exposure and incidence of colon and rectal cancers in French men: the Asbestos-Related Diseases Cohort (ARDCo-Nut). Environ Health Perspect 125:409–415; http://dx.doi.org/10.1289/EHP153

Pulmonary veno-occlusive disease is characterized by remodeling of pulmonary arteries, capillaries and venules. We report a case of diffuse lung emphysema and pulmonary veno-occlusive disease with the characteristic of having no airflow limitation. A very low diffusing capacity for carbon monoxide and results of high-resolution computed tomography of the chest suggested pulmonary veno-occlusive disease. The diagnosis was confirmed on histological analysis after lung transplantation. The combination of results of the computed tomography of the chest and the histological analysis suggested a relationship between diffuse lung emphysema and remodeling of pulmonary vessels. A distinctive pattern of mild-to-moderate airflow limitation in patients with chronic obstructive pulmonary disease and severe pulmonary hypertension has been described. This observation of the combination of diffuse emphysema, pulmonary veno-occlusive disease and no airflow limitation supports further pathophysiological studies on severe pulmonary hypertension in chronic obstructive pulmonary disease.

On behalf of the CNR MyRMA and the Tuberculosis Consilium of the CNR MyRMA; International audience; Bedaquiline (BDQ) has demonstrated potent clinical activity against multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis complex strains [1–3]. It has now been used in >50 countries, and it is estimated that ∼2500 patients had been treated with BDQ by the end of 2015. In spite of its recent clinical use, there are few reports of BDQ-resistant strains [4, 5]. Mutations in the rv0678 gene encoding the MmpL5 efflux pump repressor generate low-level BDQ resistance and clofazimine (CFZ) cross-resistance [6]. To our knowledge, this is the sole mechanism of BDQ resistance described in clinical strains [4, 5]. Despite its introduction in France in 2011 for XDR- and MDR-tuberculosis (TB) treatment, we report herein four BDQ-resistant cases, and discuss strategies to avoid a surge of BDQ resistance.

Background The place of magnetic resonance imaging (MRI) in the assessment of pulmonary hypertension (PH) remains controversial. Several studies proposed to use MRI to assess pulmonary pressure but the level of proof is low. Purpose To evaluate the diagnostic power of cardiac MRI within a non-selected population of patients suspected of PH after an echocardiography. Material and Methods Fifty-six consecutive patients, suspected of PH after an echocardiography, were assessed with right heart catheterization and cardiac MRI (including a high temporal resolution pulmonary flow curve). We extracted from the MRI data the main parameters proposed by all precedent studies available in the literature. We looked for multivariate linear relations between those parameters and the mean pulmonary arterial pressure (mPAP), and eventually assessed with a logit regression the ability of those parameters to diagnose PH in our population. Results The multivariate model retained only two parameters: the right ventricle ejection fraction and the pulmonary trunk minimum area. The prediction of mPAP (r2 = 0.5) yielded limits of agreement of 15 mmHg. However, the prediction of PH within the population was feasible and the method yielded a specificity of 80% for a sensitivity of 100%. Conclusion The performance of MRI to assess mPAP is too low to be used as a replacement for right heart catheterization but MRI could be used as second line examination after echocardiography to avoid right heart catheterization for normal patients.

Introduction: Moringa oleifera is a small native tree of North West India. Many bioactive compounds of Moringa have recently been isolated, leading to industrial and medicinal uses worldwide. We report the first case of occupational asthma (OA) to Moringa. Patient, Methods and Results: A 32 year-old cosmetic factory technician (without allergy history) exposed into the workplace to a powder of Moringa seed progressively complained of rhinitis and respiratory symptoms. Initial investigations (patient still working) didn9t show baseline airway obstruction (FEV1=4.15L, 96% of predicted value; FEV1/FVC%=81%), exhaled nitric oxide fraction ( F eno) was increased to 91.21 ppb, methacholine challenge showed nonspecific bronchial hyperresponsiveness (22% decrease of FEV1), and the Oasys II score was 3.29. Specific inhalation challenge (SIC) to Moringa seed powder showed immediate positive reaction (21% decrease of FEV1). Sputum eosinophil counts and F eno evaluated at baseline and 24h after SIC showed an increase of eosinophils from 6% to 62%, and an increase of F eno from 32.37 to 94.34 ppb. The prick-tests to a 10% solution of Moringa seed powder was positive while we observed negative control prick tests in 4 volunteers never exposed. OA to Moringa seed was retained and the patient removed from further exposure to the implicated agent into the workplace. Conclusion: Moringa has shown numerous health benefits rapidly leading the cosmetic industry to incorporate Moringa as a compound of various products (moisturizers or skin ointment). New cases of allergy could therefore appear regarding to the increasing consumption of Moringa worldwide, as suggested by our description of the first case of OA to Moringa.

To the Editor: Pulmonary ossification is a rare disease characterised by the formation of diffuse small fragments of mature bone tissue in the lungs. It can be idiopathic or associated with underlying chronic lung, heart or systemic disorders. We present the case of an 83-year-old male, who had diffuse dendriform pulmonary ossification (DPO) and a spontaneous pneumothorax. An 83-year-old male nonsmoker with a history of hypertension and carotid and coronary angioplasties visited his medical practitioner for right chest pain after a flight from Spain to France. He had no history of lung disease or heart failure. He worked as a dentist with a dental prosthesis manufacturer. Our patient was frequently in the same workshop as the prostheses technician. The patient had no trauma, cough, sputum disorders or dyspnoea. A physical examination and the usual biological analyses were normal, particularly the phosphocalcic values. Chest radiography revealed a partial right pneumothorax with micronodular calcified opacities in both lungs. Computed tomography revealed the presence of bilateral disseminated micronodular opacities of calcified densities, predominantly located in the lower lung, which had lower densities than silicosis. There were no calcified lymph nodes in the mediastinum (figs 1 and 2). Figure 1. a) Computed tomography (CT) of the chest in a parenchymal window demonstrating a right pneumothorax and a nodular round shadow in the collapsed lung; b) CT of the chest in …

Background Bronchial Hyperresponsiveness (BHR) is considered a hallmark of asthma. Other methods are helpful in epidemiological respiratory health studies including Fractional Exhaled Nitric Oxide (FENO) and Eosinophils Percentage (EP) in nasal lavage fluid measuring markers for airway inflammation along with the Forced Oscillatory Technique measuring Airway resistance (AR). Can their outcomes discriminate profiles of respiratory health in healthy subjects starting apprenticeship in occupations with a risk of asthma? Methods Rhinoconjunctivitis, asthma-like symptoms, FEV1 and AR post-Methacholine Bronchial Challenge (MBC) test results, FENO measurements and EP were all investigated in apprentice bakers, pastry-makers and hairdressers not suffering from asthma. Multiple Correspondence Analysis (MCA) was simultaneously conducted in relation to these groups and this generated a synthetic partition (EI). Associations between groups of subjects based on BHR and EI respectively, as well as risk factors, symptoms and investigations were also assessed. Results Among the 441 apprentice subjects, 45 (10%) declared rhinoconjunctivitis-like symptoms, 18 (4%) declared asthma-like symptoms and 26 (6%) suffered from BHR. The mean increase in AR post-MBC test was 21% (sd = 20.8%). The median of FENO values was 12.6 ppb (2.6-132 range). Twenty-six subjects (6.7%) had EP exceeding 14%. BHR was associated with atopy (p < 0.01) and highest FENO values (p = 0.09). EI identified 39 subjects with eosinophilic inflammation (highest values of FENO and eosinophils), which was associated with BHR and atopy. Conclusions Are any of the identified markers predictive of increased inflammatory responsiveness or of development of symptoms caused by occupational exposures? Analysis of population follow-up will attempt to answer this question.

Background Airway inflammation and airway hyperresponsiveness (AHR) are two characteristic features of asthma. Fractional exhaled nitric oxide (FENO) has shown good correlation with AHR in asthmatics. Less information is available about FENO as a marker of inflammation from work exposures. We thus examined the relation between FENO and AHR in lifeguards undergoing exposure to chloramines in indoor pools. Methods 39 lifeguards at six indoor pools were given a respiratory health questionnaire, FENO measurements, spirometry, and a methacholine bronchial challenge (MBC) test. Subjects were labeled MBC+ if the forced expiratory volume (FEV1) fell by 20% or more. The normalized linear dose-response slope (NDRS) was calculated as the percentage fall in FEV1 at the last dose divided by the total dose given. The relation between MBC and FENO was assessed using logistic regression adjusting on confounding factors. The association between NDRS and log-transformed values of FENO was tested in a multiple linear regression model. Results The prevalence of lifeguards MBC+ was 37.5%. In reactors, the median FENO was 18.9 ppb (90% of the predicted value) vs. 12.5 ppb (73% predicted) in non-reactors. FENO values ≥ 60% of predicted values were 80% sensitive and 42% specific to identify subjects MBC+. In the logistic regression model no other factor had an effect on MBC after adjusting for FENO. In the linear regression model, NDRS was significantly predicted by log FENO. Conclusions In lifeguards working in indoor swimming pools, elevated FENO levels are associated with increased airway responsiveness.