Benefit of continuous positive airway pressure on work quality in patients with severe obstructive sleep apnea.

BACKGROUND: The objective of this prospective study was to assess the effect of CPAP therapy on job productivity and work quality for patients with severe obstructive sleep apnea (OSA). METHODS: A convenience sample of patients diagnosed with severe OSA using polysomnography or polygraphy and with a therapeutic indication for CPAP was enrolled in our study. Patients completed two self-administered questionnaires: the first before CPAP therapy and the second during the first 6 months after CPAP treatment. OSA symptoms were evaluated through self-administered questionnaires assessing potential effects on occupational activity: excessive daytime sleepiness was rated by the Epworth Sleepiness Scale (ESS), emotional status was rated by the Hospital Anxiety and Depression (HAD) scale, work quality was rated by the Work Role Functioning Questionnaire (WRFQ). RESULTS: Forty patients (30 men, mean age 47.3 ± 8.3, mean BMI 31.6 ± 7.4, mean apnea-hypopnea index 51.8 ± 16.3) showed a beneficial effect of CPAP therapy on ESS score (mean 11.6 to 8.2, p < 0.0001), the anxiety dimension (mean 57.5% to 20%, p = 0.0002), and the overall anxiety-depressive score (mean 50% to 22.5%, p = 0.0006). Mean WRFQ scores were significantly improved in the second questionnaire for the dimensions of timetable requirements (69.3% to 83.5%, p < 0.0001), productivity requirements (71.4% to 82.2%, p < 0.0001), mental requirements (72.0% to 84.3%, p < 0.0001), and social requirements (82.6% to 91.4%, p < 0.003). CONCLUSIONS: We observed that adherence to CPAP therapy for patients with severe OSA mitigates the impact of symptoms on work including excessive daytime sleepiness, impairment of work ability, and anxiety and depressive disorders.

[Mandibular advancement device and multidisciplinary consultation of sleep-disorders]. / Orthèse d'avancée mandibulaire et consultation pluridisciplinaire sur les pathologies du sommeil.

BACKGROUND: Multidisciplinary consultation of sleep-disorders can include recommendation of a mandibular advancement device (MAD) for some patients with obstructive sleep apnea syndrome (OSAS). AIM: To assess the outcomes of patients for whom an oral MAD was prescribed following multidisciplinary consultation for OSAS in a University Hospital Center. METHODS: All patients referred by hospital or community specialist who had visited this specialized service from December 2015 to December 2017 and to whom an MAD was prescribed were included in this study. The objective was to analyze their clinical course after this consultation and to assess the effectiveness of these devices in this population. RESULTS: In all, 184 patients were seen by the multidisciplinary consultation between December 2015 and December 2017. An MAD was offered to 148 patients and 70 of these went on to have one. Of these 52 of them received follow-up polygraphy (PG) with it in place. This confirmed effectiveness in 18 cases (decrease of at least 50% of the AHI. The average AHI went from 34.8/hr to 22.5/hr. Sixty-five of the 148 patients were lost to follow-up. CONCLUSION: After specialized consultation on sleep-disorders, only one-third of the patients to whom an OA was prescribed had polygraphic exam. OA was less effective than in equivalent series. Correctives measures (such as a multidisciplinary standard sheet) have been set up to ensure a close follow-up of patients.

17q21 variants modify the association between early respiratory infections and asthma.

Single nucleotide polymorphisms (SNPs) at chromosome 17q21 confer an increased risk of early-onset asthma. The objective was to study whether 17q21 SNPs modify associations between early respiratory infections and asthma. Association analysis was conducted in 499 children (268 with asthma, median age 11 yrs) from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA). The 12-yr follow-up data were used to assess persistent or remittent asthma in young adulthood. Respiratory infection before 2 yrs of age was assessed retrospectively. For the 12 17q21 SNPs studied, the odds ratios (OR) for association between infection and early-onset asthma (age at onset

[The relevance of diagnostic criteria for latent tuberculosis before initiation of TNF-alpha inhibitors in psoriasis patients]. / Pertinence des critères diagnostiques de tuberculose latente avant traitement du psoriasis par anti-TNF-alpha.

BACKGROUND: Initiation of anti-TNF-alpha therapy requires prior screening for and treatment of tuberculosis. Diagnosis of relating to tuberculosis is based primarily on measurement of the papule induced by intradermal reaction to tuberculin (IDR). In this article, we discuss the validity of this criterion and the potential consequences of its use in relation to 15 patients. PATIENTS AND METHODS: This was a retrospective case study of patients presenting psoriasis and eligible for antibiotic therapy in whom latent tuberculosis was diagnosed and who received combined prophylactic antitubercular treatment for three months. All patients underwent thorough questioning and clinical examination, chest x-ray and QuantiFERON (QTF) testing, and all except one were tested for IDR. RESULTS: Thirteen patients were considered carriers of latent tuberculosis based on IDR greater than 5 mm, and on positive QTF for two others, one of whom had a documented history of primary tubercular infection. Six of these 15 patients (40%) developed hepatic cytolysis ascribable to their antitubercular treatment. DISCUSSION: Analysis of the respective characteristics of the IDR and QTF tests showed that only five of the 15 patients in our study were in fact presenting authentic latent tuberculosis, thereby suggesting that the diagnostic criteria for latent tuberculosis recommended by the French Medicines Agency (AFSSAPS), which are based solely on the size of the papule arising from IDR, are unsuitable for patients with psoriasis pending anti-TNF therapy. In our view, screening for latent tuberculosis in this patient population should involve both IDR for its sensitivity and QTF for its specificity, thereby avoiding overdiagnosis of tuberculosis leading to pointless exposure of patients to the risk of hepatic toxicity associated with antitubercular medication. CONCLUSION: We strongly recommend a change in the recommendations for prevention of tuberculosis by antibiotic therapy in patients with psoriasis, and that the review panels should include at least one dermatologist.

Sex-specific effect of IL9 polymorphisms on lung function and polysensitization.

Sex differences in asthma-associated phenotypes are well known but the genetic factors that may account for these differences have received little attention. This study aimed to characterize sex-specific and pleiotropic genetic factors underlying four quantitative phenotypes involved in the main asthma physiopathological pathways: immunoglobulin E levels, a measure of polysensitization (SPTQ), eosinophil counts and a measure of lung function FEV(1)/H(2) (forced expiratory volume in one second divided by height square). Sex-stratified univariate and bivariate linkage analyses were conducted in 295 families from the Epidemiological study on the Genetics and Environment of Asthma study. We found genome-wide significant evidence for a male-specific pleiotropic QTL (quantitative trait loci) on 5q31 (P=7 x 10(-9)) influencing both FEV(1)/H(2) and SPTQ and for a female-specific pleiotropic QTL on 11q23 underlying SPTQ and immunoglobulin E (P=2 x 10(-5)). Three other sex-specific regions of linkage were detected for eosinophil: 4q24 and 22q13 in females, and 3p25 in males. Further, bivariate association analysis of FEV(1)/H(2) and SPTQ with 5q31 candidate genes in males showed a significant association with two single-nucleotide polymorphisms within IL9 gene, rs2069885 and rs2069882 (P=0.02 and P=0.002, respectively, after Bonferroni's correction). This study underlies the importance of taking into account complex mechanisms, such as heterogeneity according to sex and pleiotropy to unravel the genes involved in asthma phenotypes.

[Sweet's syndrome associated with squamous cell bronchial carcinoma. Neutrophilic dermatosis and non-small cell lung cancer]. / Syndrome de Sweet révélant un carcinome bronchique épidermoïde. Cancer bronchique et dermatose neutrophilique.

INTRODUCTION: Sweet's syndrome, one of the neutrophilic dermatoses, is idiopathic in most cases. In 10-20% of cases it is paraneoplastic, associated with a solid tumour or haematological malignancy. An association with carcinoma of the bronchus has been only rarely described. CASE REPORT: We report the case of a 56 year old man who presented with Sweet's syndrome two months before the diagnosis of a squamous cell carcinoma of the bronchus. The dermatosis responded well to corticosteroids. The progress of the tumour was favourable, with stabilisation following 3 courses of chemotherapy and local radiotherapy. DISCUSSION: This case report updates this rare association and underlines the importance of undertaking appropriate thoracic investigations in the presence of this dermatosis. A paraneoplastic secretion of interleukin-8, GM-CSF and/or G-CSF by the bronchial tumour cells facilitating the recruitment of neutrophils, particularly in the skin, may account for the pathophysiology of this condition.

[Environmental factors for asthma severity and allergy: results from the EGEA study]. / Facteurs environnementaux de l'asthme sévère et de l'allergie: résultats de l'étude EGEA.

INTRODUCTION: EGEA (Epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), a case control and family study including 2048 individuals, was initiated to look for environmental and genetic risk factors for asthma. A synthesis of the results obtained since 2002 on phenotypic and environmental aspects of asthma severity and allergy are presented in this article. METHODS AND RESULTS: The results support a role for hormonal factors in asthma severity and in various allergic markers of asthma. A greater body mass index was related to a more severe asthma in women with early menarche. Associations between markers of allergy (eosinophils, IgE and atopy) and hormonal dependent events in women (premenstrual asthma, menopause and oral contraceptive use) have been found. In asthmatics, exposure to agents known to be associated with occupational asthma, active and passive smoking were associated with an increased clinical asthma severity score. The study underlines the protective role of country living and exposure to pets in early life on allergy markers in adulthood, supporting the hygiene hypothesis. CONCLUSIONS: New hypothesis will be tested in the near future from the second stage of this survey.

[Genetic and environmental factors of asthma and allergy: Results of the EGEA study]. / Facteurs génétiques et environnementaux de l'asthme et de l'allergie: synthèse des résultats de l'étude EGEA.

INTRODUCTION AND METHODS: The EGEA study (epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), which combines a case-control and a family-based study of asthma case (n=2120 subjects) with three surveys over 20 years, aims to identify environmental and genetic factors associated with asthma and asthma-related phenotypes. We summarize the results of the phenotypic characterization and the investigation of environmental and genetic factors of asthma and asthma-related phenotypes obtained since 2007 in the EGEA study (42 articles). RESULTS: Both epidemiological and genetic results confirm the heterogeneity of asthma. These results strengthen the role of the age of disease onset, the allergic status and the level of disease activity in the identification of the different phenotypes of asthma. The deleterious role of active smoking, exposure to air pollution, occupational asthmogenic agents and cleaning products on the prevalence and/or activity of asthma has been confirmed. Accounting for gene-environment interactions allowed the identification of new genetic factors underlying asthma and asthma-related traits and better understanding of their mode of action. CONCLUSION: The EGEA study is contributing to the advances in respiratory research at the international level. The new phenotypic, environmental and biological data available in EGEA study will help characterizing the long-term evolution of asthma and the factors associated to this evolution.

Pretreatment staging evaluation in small cell lung carcinoma. A new approach to medical decision making.

The real need for extensive staging at the time of diagnosis is discussed in regard to small cell lung carcinoma. We performed a decisional retrospective analysis on a series of 182 patients, based on three staging steps: the first step included physical examination and routine biologic tests. The second step consisted of liver ultrasonography and needle aspiration of any clinically detectable tumor mass, and the third step included bone marrow examination, radionuclide bone scan, thoracic, abdominal, and brain CT scan. A stepwise multivariate logistic regression performed on 11 variables considered in the first step shows that a four-parameter model can predict the spread of the disease (limited or extensive): weight loss, performance status, and elevated LDH or alkaline phosphatase levels. Limited disease can be predicted in two ways: (1) elevated LDH with normal alkaline phosphatases, no weight loss, and good performance status, or (2) normal LDH and alkaline phosphatases. In this series, 28 percent of patients can be predicted as having extensive disease and can be treated with chemotherapy alone without chest irradiation. After the second step, the probability of disease being extensive is only 25 percent, and only 84 (46.15 percent) patients would need to undergo the third step of staging procedures (brain CT scan, bone marrow aspiration and biopsy, radionuclide bone scan) with this method. We conclude that a multistep approach represents a simple staging method and offers the advantage of harmlessness and lower costs for patients not to be evaluated in prospective clinical trials.

Long-term results of surgical treatment for gastroesophageal reflux in asthmatic patients.

We report the long-term results of surgical repair of gastroesophageal reflux in 44 asthmatic patients who underwent surgery more than five years earlier (mean = 7.9 +/- 1.5 years). The severe asthma was associated with clinically evident reflux, and repair was attempted by surgical technique Nissen transabdominal gastropexy, with the following results: total cure, 11 cases (25 percent); marked improvement, 7 (16 percent); moderate improvement, 11 (25 percent); no improvement, 15 (34 percent). Cure was attained in intrinsic asthma with a predominance of nocturnal crises, associated with nocturnal tracheitis and with significant reflux, objective signs of which had appeared before the beginning of the asthma. Other results concerned asthmas complicated secondarily by GER in which it was impossible to determine whether the reflux was only a complication, without effect on the respiratory illness, or exacerbating the asthma. The question of surgery in these patients should be considered with care, being reserved for cases of severe asthma, poorly controlled by antiasthmatic drugs, and complicated by a severe reflux that encompasses ulcerative esophagitis.

Alteration of membrane phospholipid methylation by adenosine analogs does not affect T lymphocyte activation.

Membrane phospholipid methylation has been described during activation of various immune cells. Moreover recent data indicated modulation of immune cells functions by adenosine. As S-Adenosyl-methionine and S-Adenosyl-homocysteine are adenosine analogs and modulators of transmethylation reactions, the effects of SAH and SAM were investigated on membrane phospholipid methylation and lymphocyte activation. SAM (10(-5) M) was shown to induce the membrane phospholipid methylation as assessed by the 3H-methyl-incorporation in membrane extract. This effect was inhibited by SAH. In contrast SAM and SAH did not affect the phytohemagglutinin-induced proliferative response of peripheral blood mononuclear cells. SAH neither modified the early internalization of membrane CD3 antigens nor did it prevent the late expression of HLA-DR antigens on lymphocytes activated by phytohemagglutinin. These results indicate that in vitro alteration of phospholipid methylation does not affect subsequent steps of human T lymphocyte activation and proliferation.

[Epidemiological study of genetic and environmental factors in asthma, bronchial hyperresponsiveness and atopy. Protocol and potential selection bias]. / Etude épidémiologique des facteurs génétiques et environnementaux de l'asthme, l'hyperréactivité bronchique et l'atopie (EGEA). Protocole et biais de sélection potentiels.

BACKGROUND: The EGEA study combines a case-control study and a family study to assess genetic and environmental risk factors and their interactions for asthma, bronchial hyperresponsiveness and atopy. Information is scanty regarding potential selection biases, in particular regarding familial ressemblance in epidemiological surveys of this kind. METHODS: Asthmatic probands (adult and paediatric) were recruited in chest clinics of six clinical centres. Controls were mostly population-based (electoral rolls) for adults and recruited in surgery departments for children. RESULTS: The population examined includes 348 nuclear families ascertained by one asthmatic and 416 controls, totalling 1847 subjects (EGEA I) and an additional sample of 40 families ascertained by two asthmatic siblings (EGEA II). Potential biases for the various types of analyses have been studied. Quantification of the consequences of the greater participation of probands with a parental history of asthma shows it does not introduce a major bias in the estimates of familial resemblance. Cases and controls showed a good comparability regarding sex, age, area of residence and familial geographical origin, allowing proper associations studies for environmental and candidate genetic factors. CONCLUSIONS: The case-control component of the study will allow to perform studies on environmental factors and association studies for various genetic polymorphisms. Using the family base collected, segregation and genetic linkage/association analyses with DNA markers may be performed.

[Sleep apnea syndrome in obese patients: are there any predictive factors ?]. / Syndrome d'apnées du sommeil chez les obèses: existe-t-il des facteurs prédictifs?

The aim of this study was to determine whether clinical, spirometric, or arterial blood gas data could predict sleep apnea syndrome (SAS) among obese patients with at least one functional complaint. Eighty three obese patients, 46 males and 37 females, aged 53.2 +/- 13.7 years, with a body mass index (BMI) above 30 kg/m2 were investigated with: clinical questionnaire; pulmonary function tests; arterial blood gas measurements; nocturnal monitoring of oronasal airflow, thoracic and abdominal movements, and arterial oxygen saturation. Thirty five patients (42.2%) had a SAS, 18 (26.7%) had nocturnal oxygen desaturations, and 30 (36.1%) had a normal nocturnal monitoring. There were 63% males in the SAS group and 32% in the group without SAS (P < 0.01). Age, weight, frequency of systemic hypertension, frequency of each clinical symptom, spirometric and arterial blood gas data were identical in the two groups. In conclusion, rate of SAS is very high in obese patients presenting a BMI above 30 and at least one functional complaint. No predictive test is identified.

[Asthma and infection: interrelations]. / Asthme et infection: interrelations.

The frequent interaction of infection in asthma is a result of a complex interrelationship. Infectious agents are capable both of inducing asthmatic crises and, at least for viruses, of initiating the asthmatic process. They also favour a specific IgE response to allergens. Similar immunity is involved in defence against these infectious agents but this immunity can be disturbed in asthmatic subjects; as seen with defects in immunoglobulin subclasses, disturbance in T lymphocyte function, monocytes and blood neutrophils. The determination of the genetic or acquired character of these disturbances is pre-condition for the development of a therapeutic substitute.

[Metachronous primary pulmonary cancers. Apropos of a new case report]. / Cancers pulmonaires primitifs métachrones. A propos d'une nouvelle observation.

The appearance of a second primary lung cancer more than four months after the initial cancer is called a metachronous cancer (as opposed to a synchronous cancer). We provide a case report of an epidermoid carcinoma coming more than three years after the initial diagnosis of an anaplastic small cell cancer of the lung. This second cancer developed in a different territory from the initial lesion. Amongst the hypotheses proposed chemotherapy may through an oncogenic action favour the appearance of a new type of cancer.

[T-lymphocytes disorders in pulmonary sarcoidosis]. / Perturbations lymphocytaires T au cours de la sarcoïdose pulmonaire.

Sarcoidosis is a granulomatous disorder of unknown aetiology accompanied by variable immunological changes which concern both the monocyte and lymphocyte cell line. During the course of this disease anomalies of distribution (with accumulation in the disease tissue contrasting with a peripheral lymphopenia) and also of T cell functions (a predominance of CD4 T lymphocytes within the lesions and spontaneous expression of activation criteria) have been described. Recent works show some disturbances of T cell function and evoke the possibility of the initial pathology being related to this cell. Some current hypotheses place the T cell receptor for the antigen and the interleukin 2 receptor whose dysfunction will lead to an anomaly of the transduction of the activating signal of the T lymphocyte. The intrinsic origin (genetically determined) or extrinsically (retroviral) of these disturbances remains however to be determined.

[Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA) - First results of a multi-disciplinary study]. / Etude Epidémiologique sur les facteurs Génétiques et Environnementaux de l'Asthme, l'hyperréactivité bronchique et l'atopie (EGEA). Premiers résultats d'une étude multidisciplinaire.

The French co-operative epidemiological study EGEA realised in 1991/95 combines a case control study and a study of the families of asthmatic cases. A synthesis of the results already obtained is presented. Smoking was related to IgE, even in asthmatics and was clearly related to the clinical severity of asthma, an aspect insufficiently taken into account. The relationships of occupational exposures to asthma have been assessed using a job exposure matrix. Segregation analyses on IgE have shown, after correction for the mode of ascertainment, the existence of a dominant major gene and familial residual correlation. A systematic genome screen realised in families with 2 asthmatic siblings showed linkage of various regions in the genome implicated to asthma or related phenotypes (1p, 11p, 11q, 12q, 13q, 17q, 19q), coherent with genome screens realised in other studies. Regarding candidate genes, no association was evidenced between asthma and the AF508 mutation of the cystic fibrosis gene. The analysis is still in progress by studies on the heterogeneity of asthma with refined genetic studies and by searching to integrate results regarding environmental and genetic factors and studying their interactions.

[Asthma and gastroesophageal reflux]. / Asthme et reflux gastro-oesophagien.

The authors review the now well-established data that concerns the relationship between asthma and gastro-oesophageal reflux (GER). These include the high frequency of the association in severe asthma, the diagnostic procedure of GER in asthmatics and the significance of reflux in these patients (reflux that causes asthma or reflux that is secondary to asthma). Then the mechanism of the action of GER on asthma are discussed. In the second part the authors summarise the following issues, that are only partly resolved. Evaluation of the possible worsening effect of GER on the symptoms of asthma. They insist in particular on the valuable contribution of clinical data and the results of the Bernstein acid infusion test. Therapeutic indications, particularly those for surgical correction. Recent results from a long term study of surgical treatment of 46 patients are presented.

[Corticoid resistance in asthma]. / La corticorésistance dans l'asthme.

Incorrect application of corticosteroid treatment, whether due to non-compliance, misinterpretation of etiological factors, or inadapted treatment, can lead to the difficult problem of corticoresistance. The expression of the phenomenon are varied and may concern all or part of the effector cells responsible for the inflammatory reaction. The underlying mechanism is still poorly understood but appears to involve a generally acquired, though sometimes inborn or genetically induced, desensitization of the receptor cells. Several substitute treatments have been proposed including methotrexate, gold salts, cyclosporin A, but the results have not been very promising.

[Neoadjuvant chemoradiotherapy and peroperative radiotherapy for non-small-cell lung cancer of the apex. A study of 5 cases]. / Chimio-radiothérapie néoadjuvante et radiothérapie per-opératoire dans les carcinomes non à petites cellules (CBNPC) de l'apex. Etude dur 5 cas.

The management of superior sulcus tumors with Pancoast 's syndrome is not well defined, especially in view of their low frequency. Even if surgery performed by "en bloc" resection of the tumor and the chest wall is recommended, neoadjuvant treatment could have a potential benefit on the resecability and pain control. We report five cases of Pancoast tumors (NSCLC), treated by radiotherapy and chemotherapy before surgery. Four tumors was on stage IIIb. A regimen with radiotherapy (50 Gy) and chemotherapy (cisplatinum + etoposide) was initially performed. Four tumors were resected, with 2 complete pathologic responses and good control on pain. Three patients received radiotherapy during surgery. No toxic reaction was observed. This regimen may be discussed with locally advanced tumors and poor prognosis.