Proposal for a systematic analysis of polygraphy or polysomnography for identifying and scoring abnormal events occurring during non-invasive ventilation.

Non-invasive ventilation (NIV) is recognised as an effective treatment for chronic hypercapnic respiratory failure. Monitoring NIV during sleep may be preferable to daytime assessment. This paper reports the findings of an international consensus group which systematically analysed nocturnal polygraphic or polysomnographic tracings recorded with either volume-cycled or pressure-cycled ventilators. A systematic description of nocturnal respiratory events which occur during NIV is proposed: leaks, obstruction at different levels of the upper airway (glottis and/or pharynx), with or without decrease of respiratory drive and asynchrony.

[Systemic and oropharyngeal side effects of inhaled corticosteroids]. / Effets secondaires systémiques et oropharyngés des corticostéroïdes inhalés.

The use of inhaled corticosteroids (ICS) is an important component of asthma management. Although their main impact is on airway inflammation, ICS are not devoid of systemic side effects (adrenal insufficiency, osteoporosis, brittle skin, ocular effects, growth retardation). Oropharyngeal side effects are also reported. These effects appear dose and duration dependent. They also vary according to the type of ICS used, its method of administration and drug interactions. It is recommended to titrate ICS to the lowest effective dose, to regularly reconsider their indication and to be aware of drug interactions. In addition, a change in ICS may have a favorable impact on side effects.

[Chronic obstructive pulmonary disease: risk and benefit of testosterone therapy]. / Bronchopneumopathie chronique obstructive: risques et bénéfices d'un traitement de testostérone.

Muscular wasting is frequently encountered in COPD patients and is related to a decrease in exercise tolerance, a higher morbidity and mortality. One of the potential causes isa low serum testosterone, which is frequent in COPD. Various studies have explored the effect of testosterone administration alone or as part of combined pulmonary rehabilitation and nutrition protocols. Testosterone had a positive impact on muscle mass and force, and to a lesser extent on physical endurance and respiratory parameters. Future studies should better define appropriate dosage and treatment duration. In the meantime, testosterone should be administered to COPD patients with overt hypogonadism, or in multidisciplinary specialized programmes.

[Pneumology. Treatment of obstructive sleep apnea by continuous positive airway pressure: new options]. / Pneumologie. Traitement du syndrome d'apnées obstructives du sommeil par pression positive continue (PPC).

Continuous Positive Airway Pressure (CPAP) is accepted as first line therapy for Sleep Obstructive Apnea-Hypopnea Syndrome. Over the past few years, several new devices have been made available, aiming to improve patient comfort and compliance. In 25 years, major changes in technology have occurred, and CPAP has evolved from fixed pressure devices to auto-adjusting bi-level positive airway pressure. The algorithms and software of the newly commercialized devices are sometimes difficult to apprehend. In spite of impressive changes in technology, an obvious benefit in terms of compliance or comfort is yet to be demonstrated, and independent validations of these new devices are necessary.

Tuberculosis screening in patients with psoriasis before antitumour necrosis factor therapy: comparison of an interferon-gamma release assay vs. tuberculin skin test.

BACKGROUND: Antitumour necrosis factor (anti-TNF) treatments may reactivate latent tuberculosis infection (LTBI). For detecting LTBI, the tuberculin skin test (TST) has low sensitivity and specificity. Interferon-gamma release assays (IGRA) have been shown to be more sensitive and specific than TST. OBJECTIVE: To compare the TST and the T-SPOT.TB IGRA for identifying LTBI in patients with psoriasis before anti-TNF treatment. METHODS: A retrospective study was carried out over a 4-year period on patients with psoriasis requiring anti-TNF treatment. All were subjected to the TST, T-SPOT.TB and chest X-ray. Risk factors for LTBI and history of bacillus Calmette-Guérin (BCG) vaccination were recorded. The association of T-SPOT.TB and TST results with risk factors for LTBI was tested through univariate logistic regression models. Agreement between tests was quantified using kappa statistics. Treatment for LTBI was started 1 month before anti-TNF therapy when indicated. RESULTS: Fifty patients were included; 90% had prior BCG vaccination. A positive T-SPOT.TB was strongly associated with a presumptive diagnosis of LTBI (odds ratio 7.43; 95% confidence interval 1.38-39.9), which was not the case for the TST. Agreement between the T-SPOT.TB and TST was poor, kappa = 0.33 (SD 0.13). LTBI was detected and treated in 20% of the patients. In 20% of the cases, LTBI was not retained in spite of a positive TST but a negative T-SPOT.TB. All patients received an anti-TNF agent for a median of 56 weeks (range 20-188); among patients with a positive TST/negative T-SPOT.TB, no tuberculosis was detected with a median follow-up of 64 weeks (44-188). One case of disseminated tuberculosis occurred after 28 weeks of adalimumab treatment in a patient with LTBI in spite of treatment with rifampicin. CONCLUSION: This study is the first to underline the frequency of LTBI in patients with psoriasis (20%), and to support the use of IGRA instead of the TST for its detection. Nevertheless, there is still a risk of tuberculosis under anti-TNF therapy, even if LTBI is correctly diagnosed and treated.

Tuberculosis cluster in an immigrant community: case identification issues and a transcultural perspective.

OBJECTIVES: In a low incidence area for tuberculosis (TB), a computerized database identified an unusually high proportion of patients coming from one single country between 2004 and 2006. To determine whether they constituted a cluster, whether clustering was due to recent transmission, and to understand what undermined the efficacy of the contact tracing procedure, we conducted a retrospective study of all patients with TB from this country. METHODS: Mycobacterium tuberculosis isolates of 15 TB cases originating from the same country over a 2(1/2) year period were analysed by restriction fragment length polymorphism (RFLP) and/or Rep-PCR. To identify links between patients, we revisited the social worker's files, cross-matched contacts' databases, and performed internet searches. A cultural evaluation was conducted by an anthropologist and an expert physician, through patient and community key informant interviews and a literature review. RESULTS: Genotyping confirmed that 11 of 15 patients had identical isolates. Additional data revealed an unsuspected complex network of social links between 9 of these 11 patients. The transcultural evaluation pointed out the major obstacles to efficient contact tracing, such as importance of social stigma related to TB, differences in communication style and health beliefs, and linguistic barriers. CONCLUSION: The combined finding of identical genotypes and important social links between patients confirmed the suspicion of a TB cluster due to recent transmission. The cultural evaluation helped to explain the difficulties encountered during the contact tracing procedure, and offered strategies to improve its efficacy despite the magnitude of the social stigma attached to TB in this community.

[How to perform and interpret spirometry in primary care]. / Pratique et interprétation de la spirométrie au cabinet du médecin de premier recours.

Spirometry is a simple test, which has a central role in the early diagnosis and management of diseases that are very prevalent and may become symptomatic late in their evolution. This manuscript explores all the necessary steps for an optimal use of spirometry (choice of equipment, quality control, technique, and interpretation). Spirometry is easy to perform in a primary care setting and its use should be encouraged among primary care physicians. We discuss the indications of this test in the follow up of patients and cover the situations that need referral to the specialist.

Accuracy of comprehensive PCR analysis of nasopharyngeal and oropharyngeal swabs for CT-scan-confirmed pneumonia in elderly patients: a prospective cohort study.

OBJECTIVES: We aimed to assess the accuracy of PCR detection of viruses and bacteria on nasopharyngeal and oropharyngeal swabs (NPS) for the diagnosis of pneumonia in elderly individuals. METHODS: We included consecutive hospitalized elderly individuals suspected of having pneumonia. At inclusion, NPS were collected from all participants and tested by PCR for the presence of viral and bacterial respiratory pathogens (index test, defined as comprehensive molecular testing). Routine diagnostic tests (blood and sputum culture, urine antigen detection) were also performed. The reference standard was the presence of pneumonia on a low-dose CT scan as assessed by two independent expert radiologists. RESULTS: The diagnosis of pneumonia was confirmed in 127 of 199 (64%) included patients (mean age 83 years, community-acquired pneumonia in 105 (83%)). A pathogen was identified by comprehensive molecular testing in 114 patients (57%) and by routine methods in 22 (11%). Comprehensive molecular testing was positive for viruses in 62 patients (31%) and for bacteria in 73 (37%). The sensitivity and specificity were 61% (95% CI 53%-69%) and 50% (95% CI 39%-61%) for comprehensive molecular testing, and 14% (95% CI 82%-21%) and 94% (95% CI 86%-98%) for routine testing, respectively. Positive likelihood ratio was 2.55 for routine methods and 1.23 for comprehensive molecular testing. CONCLUSION: Comprehensive molecular testing of NPS increases the number of pathogens detected compared with routine methods, but results are poorly predictive of the presence of pneumonia. Hence, comprehensive molecular testing is unlikely to impact clinical decision-making (NCT02467192). CLINICAL TRIALS REGISTRATION: NCT02467192.

Indeterminate test results of T-SPOT.TB performed under routine field conditions.

Interferon-gamma release assays for the diagnosis of tuberculosis (TB) can give indeterminate results. The prevalence of indeterminate test results (ITRs) among T-SPOT.TB tests was assessed. A retrospective analysis of samples processed in 2005 was performed. ITRs were assessed by age, sex, immunosuppression, distance to the laboratory and season. A subgroup of tests performed for specific indications (contact tracing, migrants with positive tuberculin skin test, TB suspects and immunosuppression) were analysed separately. Of a total of 1,429 tests, 49 (3.4%) were indeterminate. ITRs were significantly associated with old age (>75 versus 5-75 yrs; odds ratio (OR) 7.97, 95% confidence interval (CI) 3.968-15.438) and the season during which samples were transported (autumn and winter versus spring and summer; OR 3.47, 95% CI 1.753-7.514). The incidence of ITR was 302 (2.0%) among TB contacts, 75 (1.6%) among immigrants, 156 (3.0%) in TB suspects and 32 (3.0%) among immunosuppressed patients. Sex, young age and distance to the laboratory were not associated with the rate of ITR. Of the 13 tests with ITR that were repeated, 10 gave a clear positive or negative result. Indeterminate test results with T-SPOT.TB under routine conditions were infrequent and more common in individuals aged >75 yrs than in children and younger adults. The incidence of indeterminate test results was low and similar among healthy tuberculosis contacts, immigrants with a positive tuberculin skin test, tuberculosis suspects and the immunosuppressed. The conditions of transportation may influence the incidence of indeterminate test results.

[Limitations of active therapeutic and palliative care in chronic respiratory disease]. / Intensité des soins lors des exacerbations et des complications des pathologies respiratoires chroniques.

The issue of intensive and palliative care in patients with chronic disease frequently arises. This review aims to describe the prognostic factors of chronic respiratory diseases in stable and in acute situations in order to improve the management of these complex situations. The various laws on patients' rights provide a legal framework and define the concept of unreasonable obstinacy. For patients with chronic obstructive pulmonary disease, the most robust decision factors are good knowledge of the respiratory disease, the comorbidities, the history of previous exacerbations and patient preferences. In the case of idiopathic pulmonary fibrosis, it is necessary to know if there is a prospect of transplantation and to assess the reversibility of the respiratory distress. In the case of amyotrophic lateral sclerosis, treatment decisions depend on the presence of advance directives about the use of intubation and tracheostomy. For lung cancer patients, general condition, cancer history and the tumor treatment plan are important factors. A multidisciplinary discussion that takes into account the patient's medical history, wishes and the current state of knowledge permits the taking of a coherent decision.

Interaction of ionizing irradiation with steroid receptors in human breast cancer cells.

Human mammary tumor cells in continuous culture (MCF-7 cells) are hormone- and radiosensitive. The interaction of both factors is analyzed. Ionizing irradiation lowers the concentration of both the estradiol and progesterone receptors per cell. The reduction is dose dependent. However, the effects on the cytoplasmic and nuclear forms of the receptors are not similar. For the estradiol receptor, an accumulation in the nuclear fraction is observed 48 hr after irradiation when no appreciable amounts of estrogens are present. After administration of 10(-8) M estradiol, the cytoplasmic clearance is comparable to the unirradiated controls. However, nuclear accumulation is impaired. The processing of the nuclear estrogen receptor remains identical. Nuclear progesterone receptor is not significantly increased due to irradiation in the absence of progestins. Cytoplasmic decrease after incubation with progestins is unaffected. Again, nuclear accumulation is impaired in contrast to the unchanged processing of the nuclear form of the progesterone receptor. A decrease in "nuclear acceptor sites" for both receptors after irradiation may be an explanation for these observations. No significant effects of ionizing irradiation are observed in the initial steps of steroid hormone action.

Effects of ionizing irradiation on the estradiol and progesterone receptors in rat mammary tumors.

The determination of estradiol and progesterone receptor concentrations in mammary tumors is useful in predicting the hormone responsiveness. As this assay is carried out on tumor tissue which may have been subjected to radiotherapy, the possibility of an ionizing irradiation affecting the steroid receptor levels in neoplastic tissue should be taken into account. The steroid receptor concentrations are examined in dimethylbenz(a)anthracene-induced tumors of Sprague-Dawley rats. The estradiol and the progesterone receptor titers become reduced significantly after treatment with 20 Gray while an application with 7 Gray does not affect the titer values. After treatment of the tumor with 20 Gray, the steroid receptor concentrations decrease progressively, reaching a maximal reduction 20 to 30 days after exposure. This measured reduction in binding sites seems to be the result of a specific irradiation effect and not due to a possible increase in lytic enzyme levels in the regressing tumors. As radiation treatment affects the receptor concentrations, this should be kept in mind when interpreting the steroid receptor concentrations.

[Leukotriene-modifiers in asthma treatment]. / Les antileucotriènes dans le traitement de l'asthme.

This review aims to evaluate the efficacy of the leukotriene modifiers in the different stages and subgroups of asthma. In mild asthma, they bring some improvement as monotherapy, but less than inhaled steroids. In moderate asthma, leukotriene modifiers associated with inhaled steroids seem to offer a slight advantage over placebo. No evidence of additional effect has been published in severe asthma. Exercice- and aspirin-induced asthma are particulary responsive to leukotriene modifiers. This treatment may also play a role in acute asthma. In practice, it is possible to select patients who benefit from those molecules. If only these "responders" are treated, leukotriene modifiers are an adequate treatment, easy to use and well tolerated.

[Lake Geneva Region guidelines on management of adult asthma]. / Recommandations suisses romandes sur la prise en charge de l'asthme de l'adulte.

Asthma is a major cause of chronic morbidity throughout the world. In Switzerland, 6.9% of the adult population is suffering from asthma. The standards of treatment are unfortunately not met in most western countries, as well as in Switzerland. We put forward a complete guideline on management of adult asthma, inspired from GINA and BTS guidelines, and adapted to the specific needs of general practitioners working in french part of Switzerland. This guideline reflects a consensus between allergy, lung and emergency specialists, working in the 2 university hospitals of the Lake Geneva Region (HUG and CHUV).

[Noninvasive ventilation. The 2015 guidelines from the Groupe Assistance Ventilatoire (GAV) of the Société de Pneumologie de Langue Française (SPLF)]. / Ventilation non invasive. Les conseils 2015 du Groupe assistance ventilatoire (GAV) de la Société de pneumologie de langue française (SPLF).

A task force issued from the Groupe Assistance Ventilatoire (GAV) of the Société de Pneumologie de Langue Française (SPLF) was committed to develop a series of expert advice concerning various practical topics related to long-term non invasive ventilation by applying the Choosing Wisely® methodology. Three topics were selected: monitoring of noninvasive ventilation, the interpretation of data obtained from built-in devices coupled to home ventilators and the role of hybrid modes (target volume with variable pressure support. For each topic, the experts have developed practical tips based on a comprehensive analysis of recent insights and evidence from the literature and from clinical experience.

Asthma outpatient education by multiple implementation strategy. Outcome of a programme using a personal notebook.

More than 10 years after publication, international guidelines remain poorly implemented. To better implement them, we need to develop new strategies adapted to the expectations of patients and health professionals outside hospital settings and to ensure better outpatient follow up in the community. We developed a bilingual education programme including a brochure designed to support an interdisciplinary health care network and measured hospitalisations (H), work absenteeism (WA), emergency visits (EV), asthma medication (AM) and quality of life (QL Juniper) before and 12 months after the intervention. All QL scores improved significantly in comparison with pre-intervention values. Health service use decreased dramatically when comparing the 12 months prior to and after the intervention(H: 35-8%, WA: 39-14%, EV: 88-53%). The final cost/benefit ratio of the programme was 1.96. Interdisciplinary implementation strategy of patient education is cost-effective, improves quality of life for asthmatics, and reduces strain on health services. Such a health care network does not require an expensive infrastructure and is better adapted to the reality and competences of clinical practice.

[Management of asthma attacks in primary care practice]. / Prise en charge d'une crise d'asthme au cabinet médical.

Most fatal asthma attacks are explained by an underestimation of the severity of the episode and by an underutilization of adequate treatments. The primary care physician should: 1) identify predictors of poor outcome requiring immediate hospital admission, 2) evaluate the severity of the attack, using clinical criteria and peak-flow measurements, and 3) initiate a treatment combining inhaled beta2-agonists and oral steroids. Life threatening asthma attacks warrant immediate hospitalisation as well as severe attacks persisting after initial treatment. Moderate attacks don't usually require referral. Other factors, such as social factors, compliance to treatment, or co-morbid conditions, may warrant hospitalisation.

Medium-term cost-effectiveness of an automated non-invasive ventilation outpatient set-up versus a standard fixed level non-invasive ventilation inpatient set-up in obese patients with chronic respiratory failure: a protocol description.

INTRODUCTION: Obesity is an escalating issue, with an accompanying increase in referrals of patients with obesity-related respiratory failure. Currently, these patients are electively admitted to hospital for initiation of non-invasive ventilation (NIV), but it is unknown whether outpatient initiation is as effective as inpatient set-up. We hypothesise that outpatient set-up using an autotitrating NIV device will be more cost-effective than a nurse-led inpatient titration and set-up. METHODS AND ANALYSIS: We will undertake a multinational, multicentre randomised controlled trial. Participants will be randomised to receive the usual inpatient set-up, which will include nurse-led initiation of NIV or outpatient set-up with an automated NIV device. They will be stratified according to the trial site, gender and previous use of NIV or continuous positive airway pressure. Assuming a 10% dropout rate, a total sample of 82 patients will be required. Cost-effectiveness will be evaluated using standard treatment costs and health service utilisation as well as health-related quality of life measures (severe respiratory insufficiency (SRI) and EuroQol-5 dimensions (EQ-5D)). A change in the SRI questionnaire will be based on the analysis of covariance adjusting for the baseline measurements between the two arms of patients. ETHICS AND DISSEMINATION: This study has been approved by the Westminster National Research Ethics Committee (11/LO/0414) and is the trial registered on the UKCRN portfolio. The trial is planned to start in January 2015 with publication of the trial results in 2017. TRIAL REGISTRATION NUMBER: ISRCTN 51420481.

Irritable esophagus.

An esophageal origin of noncardiac chest pain is generally accepted if prolonged pH and pressure recordings show that the pain episodes correlate in time with acid reflux, esophageal motor abnormalities, or a combination of both, or if provocative testing (acid perfusion, edrophonium, balloon distention) is positive. Many patients with noncardiac chest pain of esophageal origin are said to have an irritable esophagus. Irritable esophagus has been defined in two ways. Some researchers suggest it is actually a lowered esophageal pain threshold, based on the finding that such patients feel chest pain at lower balloon volumes than controls during intraesophageal balloon distention; they are said to be hypersensitive to balloon distention. Hypersensitivity to an esophageal stimulus is generally found in patients with noncardiac chest pain of esophageal origin, and hypersensitivity to a single stimulus is one criterion for a diagnosis. Our group defines irritable esophagus as a condition in which several different stimuli result in the same type of chest pain. Accordingly, we have grouped patients with esophageal chest pain into three categories: (a) patients with an acid-sensitive esophagus, in whom spontaneous pain episodes can be related to acid reflux (with or without accompanying motor disorders), and/or the acid perfusion test is positive; (b) patients with a mechano-sensitive esophagus, in whom the spontaneous pain episodes can be related to motility disturbances (without reflux), and/or the edrophonium test or balloon distention test is positive; (c) patients with an irritable esophagus, in whom some spontaneous pain episodes are related to reflux, while others are related to abnormal motility (without reflux). The last group includes patients whose spontaneous chest pain is related to reflux, with a positive motility tests; whose pain is related to abnormal motility, with a positive reflux test; and patients with positive tests for both reflux and abnormal motility. Seven studies examined a total of 281 noncardiac chest pain patients using prolonged pH and pressure recordings and provocative tests. An acid-sensitive, a mechano-sensitive, or an irritable esophagus was found in 20%, 14%, and 24% of patients, respectively.