Use of FeNO to predict anti-IL-5 and IL-5R biologics efficacy in a real-world cohort of adults with severe eosinophilic asthma.

INTRODUCTION: Severe eosinophilic asthma (SEA) is associated with multiple exacerbations. Fractional exhaled nitric oxide (FeNO), a biomarker of airway T2 inflammation, is known to be correlated with the risk of exacerbations. While the use of FeNO is well established to predict the therapeutic response to dupilumab (anti-IL-4/IL-13), it remains uncertain for biologics targeting the IL-5 pathway. METHODS: We conducted an observational, retrospective, monocentric analysis of adults with SEA who started mepolizumab (anti-IL-5) or benralizumab (anti-IL-5R) between January 1, 2016 and December 31, 2020. RESULTS: Data were collected for 109 patients. All participants reported uncontrolled asthma with a median of 3 annual exacerbations and a median Asthma Control Test score of 12. They all had an initial blood eosinophilia >300/mm3, with a median at 610/mm3 (IQR 420-856). Patients with a baseline FeNO ≥50 ppb reported more exacerbations in the previous year than those with a FeNO <50 ppb (p = 0.02). After initiation of treatment, change in FeNO was not associated with therapeutic response. However, decrease in the annual number of exacerbations was significantly greater in patients with a baseline FeNO ≥50 ppb than in those with a baseline FeNO <50 ppb (-3.3 ± 2.7 vs -0.9 ± 2.4, respectively; p = 0.01). There was no association between baseline FeNO values and subsequent lung function, asthma control or reduction of oral corticosteroids use. CONCLUSION: In this real-world cohort, adults with SEA who had a baseline FeNO ≥50 ppb experienced a greater decrease in exacerbations after 12 months of anti-IL-5 or IL-5R biologics than those with a FeNO <50 ppb.

[A new pathophysiological element in severe asthma: GTPase Rac]. / Un nouvel acteur physiopathologique dans l'asthme sévère : la GTPase Rac.

Asthma is a chronic airway condition defined by hyperresponsiveness, bronchial remodeling and chronic inflammation. A significant proportion of severe asthmatic patients remain uncontrolled despite recent therapeutic breakthroughs (biotherapies). Better understanding of the signaling pathways involved in the pathophysiological mechanisms underlying severe asthma could successfully address this unmet need. Rac GTPase acts as a molecular switch and has already been convincingly associated with airway hyperresponsiveness and bronchial remodeling in asthma. Having been elucidated by acquired knowledge regarding other pathologies. Its role in the inflammation mechanisms characterizing asthma is currently under specific evaluation.

[Update in severe asthma physiopathology and treatments]. / Actualités physiopathologiques et thérapeutiques dans l'asthme sévère.

Asthma is an inflammatory airway disease which presentation is highly heterogeneous. Last two decades provided new clinical and basic data concerning asthma physiopathology that make global understanding much complex. Phenotypes based on clinical settings and paraclinical investigations from large cohorts confirm old paradigm (eosinophilic vs. non-eosinophilic asthma) but also introduce new concepts (obesity-related asthma, late onset asthma, etc.). Conversely, improvement of big data analytics allows to initiate new cohorts aiming at better understanding the pathophysiology underlying those phenotypes and unraveling new ones. However, clinical and therapeutic impacts of those big data need to be further detailed. In parallel, biotherapies and innovative techniques as bronchial thermoplasty become available for severe asthmatic patients who did not respond to specific treatment in the past. Development of a personalized medicine in severe asthma becomes an important challenge for tomorrow. This review will focus on new pathophysiological concepts arisen from large cohorts and new therapeutic strategies available and in progress for severe asthma.

[Contraception: CNGOF Guidelines for Clinical Practice (Short Version)]. / Contraception : Recommandations pour la Pratique Clinique du CNGOF (texte court).

The French College of Obstetrics and Gynecology (CNGOF) releases its first global recommendations for clinical practice in contraception, to provide physicians with an updated synthesis of available data as a basis for their practice. The French Health Authority (HAS) methodology was used. Twelve practical issues were selected by the organizing committee and the task force members. The available literature was screened until December 2017, and allowed the release of evidence-based, graded recommendations. This synthesis is issued from 12 developed texts, previously reviewed by experts and physicians from public and private practices, with an experience in the contraceptive field. Male and female sterilization, as well as the use of hormonal treatments without contraceptive label were excluded from the field of this analysis. Specific practical recommendations on the management of contraception prescription, patient information including efficacy, risks, and benefits of the different contraception methods, follow up, intrauterine contraception, emergency contraception, local and natural methods, contraception in teenagers and after 40, contraception in vascular high-risk situations, and in case of cancer risk are provided. The short/mid-term future of contraception mostly relies on improving the use of currently available methods. This includes reinforced information for users and increased access to contraception for women, whatever the social and clinical context. That is the goal of these recommendations.

[Natural Family Planning methods and Barrier: CNGOF Contraception Guidelines]. / Méthodes de contraception naturelle et méthodes barrières. RPC contraception CNGOF.

OBJECTIVE: To develop clinical practice recommendations for the use of natural contraception and female and male barrier methods. MATERIALS AND METHODS: A systematic review of English and French literatures related to the safety and effectiveness of natural contraceptive methods based on PubMed, Cochrane Library, practice recommendations issued by international scientific societies and guidelines provided by the World Health Organization (WHO) as well as updates from the Center for Disease Control and Prevention (CDC). RESULTS: Natural contraceptives methods include fertility awareness-based methods, lactational amenorrhea method (LAM) and withdrawal method. The prevalence is low (4.6% of users) and remains stable over the years. Identification of the fertile period can be symptom-based cervical mucus (Billings), two-day method, basal body temperature, symptom-thermal method or based on calendar calculation (Ogino-Knauss, standard day method). Pregnancy rate after one-year utilization varies from 0.4% to 5% in perfect use but 8% in common practice. Effectiveness increases with absence of vaginal sex and decreases when combined to barriers method inadequately implemented. Data is scarce on reliability and effectiveness of ovulation predictor kits readily available on internet. Lactational amenorrhea method (LAM) can be very effective (98%) provided three conditions are fulfilled: within 6 months after birth, amenorrhea is effective, and breastfeeding is exclusive or quasi exclusive (day/night). Withdrawal method is constraining and of limited effectiveness. Male and female condom, diaphragm, cervical cap and spermicides are mechanical and chemical barrier methods, preventing spermatozoids from passing through the cervix into the uterus and therefore preventing fecundation. Female and male condoms offer a double protection to avoid pregnancy and prevent STD's. They are effective provided strict conditions of use are fulfilled. Male condom is favored by teenagers (45.6% among 15 to 19 years old), sometimes in combination with contraceptive pill (16% of cases). Women on the pill decreases according to their age. Pregnancy rates within the first year of consistent and correct use of these methods vary between 5 to 26% and reach 20 to 32% in practical use. Diaphragm and cervical cap need to be used in combination with spermicides. Spermicides have limited effectiveness when used alone. CONCLUSION: In common practice, natural and barrier contraceptive methods are more constraining and less effective than modern contraceptive method. They can be an alternative at given time and/or in situations where the women or the couple accept the possibility of an unexpected pregnancy which might be terminated or not. Women/couples need to be properly informed on how to use such methods, on their disadvantages and possible failures in common practice. Reminders are to be given on emergency contraceptive methods (IUD, hormonal) after unprotected sex.

Radiological pleuroparenchymal fibroelastosis associated to limited cutaneous systemic sclerosis: a case report.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) is a very rare interstitial lung disease (ILD) characterized by progressive fibrotic lesions of the visceral pleura and the sub-pleural parenchyma, affecting predominantly the upper lobes. PPFE may occur in different contextes like bone marrow or lung transplantations, but also in the context of telomeropathy with mutations of telomerase reverse transcriptase (TERT), telomerase RNA component (TERC) or regulator of telomere elongation helicase 1 (RTEL1) genes. PPFE-like lesions have recently been described in patients with connective tissue disease (CTD)-related ILD. We report here the first detailed case of PPFE associated to systemic sclerosis (SSc) in a woman free of telomeropathy mutations. CASE PRESENTATION: A caucasian 46 year old woman was followed for SSc in a limited form with anti-centromere Ab since 1998, and seen in 2008 for a routine visit. Her SSc was stable, and she had no respiratory signs. Pulmonary function tests showed an isolated decreased cTLCO at 55.9% (of predicted value). Cardiac ultrasonography was normal. Thoracic CT-scan showed upper lobes predominant mild and focal pleural and subpleural thickenings, suggestive of PPFE, with a slight worsening at 8 years of follow-up. She remained clinically stable. Biology only found a moderate and stable peripheral thrombocytopenia, and sequencing analysis did not find any mutations in TERT and TERC genes. CONCLUSIONS: ILD is frequent in SSc but isolated PPFE has never been described so far. In our case, PPFE is not related to telomeropathy, has indolent outcome and seems to have good prognosis. PPFE might be an extremely rare form of SSc-related ILD, although a fortuitous association remains possible.

[Induced abortion: Guidelines for clinical practice - Text of the Guidelines (short text)]. / L'interruption volontaire de grossesse : recommandations pour la pratique clinique ­ Texte des recommandations (texte court).

OBJECTIVE: Develop recommendations for the practice of induced abortion. MATERIALS AND METHODS: The Pubmed database, the Cochrane Library and the recommendations from the French and foreign Gyn-Obs societies or colleges have been consulted. RESULTS: The number of induced abortions (IA) has been stable for several decades. There are a lot of factors explaining the choice of abortion when there is an unplanned pregnancy (UPP). Early initiation and choice of contraception in connection to the woman's life are associated with lower NSP. Reversible contraceptives of long duration of action should be positioned fist in line for the teenager because of its efficiency (grade C). Ultrasound before induced abortion must be encouraged but should not be obligatory before performing IA (Professional consensus). As soon as the sonographic apparition of the embryo, the estimated date of pregnancy is done by measuring the crown-rump length (CRL) or by measuring the biparietal diameter (BIP) from 11 weeks on (grade B). Reliability of these parameters being±5 days, IA could be done if measurements are respectively less than 90mm for CRL and less than 30mm for BIP (Professional consensus). A medical IA performed with a dose of 200mg mifepristone combined with misoprostol is effective at any gestational age (EL1). Before 7 weeks, mifepristone followed between 24 and 48hours by taking misoprostol orally, buccally sublingually or eventually vaginally at a dose of 400 ug possibly renewed after 3hours (EL1, grade A). Beyond 7 weeks, misoprostol given vaginally, sublingually or buccally are better tolerated with fewer side effects than oral route (EL1). It is recommended to always use a cervical preparation during an instrumental abortion (Professional consensus). Misoprostol is a first-line agent for cervical preparation at a dose of 400 mcg (grade A). Aspiration evacuation is preferable to curettage (grade B). A perforated uterus during an instrumental suction should not be considered as a scarred uterus (Professional consensus). IA is not associated with increased subsequent risk of infertility or ectopic pregnancy (EL2). The pre-abortion medical consultations does not affect, most of the time, the decision to request an IA. Indeed, a majority of women is quite sure of her choice during these consultations. Acceptability of the method of IA and satisfaction appears to be larger when they are able to choose the abortion method (grade B). There is no relationship between an increase in psychiatric disorders and IA (EL2). Women with psychiatric histories are at increased risk of mental disorders after the occurrence of an UPP (EL2). In case of instrumental abortion, oral estrogen-progestogen contraceptives and the patch should be started from the day of the abortion, the vaginal ring inserted within 5 days of IA (grade B). In case of medical abortion, the vaginal ring should be inserted within a week of taking mifepristone, oral estrogen-progestogen contraceptives and the patch should be initiated on the same day or the day after taking prostaglandins (grade C). In case of instrumental abortion, the contraceptive implant may be inserted on the day of the abortion (grade B). In case of medical abortion, the implant can be inserted on the day of mifepristone (grade C). The copper Intrauterine Device (IUD) and levonorgestrel should be inserted preferably on the day of instrumental abortion (grade A). In case of medical abortion, an IUD can be inserted within 10 days following mifepristone after ensuring by ultrasound of the absence of intrauterine pregnancy (grade C). CONCLUSION: The implementation of these guidelines may promote a better and more homogenous care for women requesting IA in our country.

[Medical induced abortion]. / Interruption volontaire de grossesse par voie médicamenteuse.

OBJECTIVE: Updated clinical recommendations for medical induced abortion procedure. METHODS: A systematic review of French and English literature, reviewing the evidence relating to the provision of medical induced abortion was carried out on PubMed, Cochrane Library and international scientific societies recommendations. RESULTS: The effectiveness of medical abortion is higher than 95% when the protocols are adjusted to gestational age (EL1). Misoprostol alone is less effective than a combination of mifepristone and misoprostol (EL1). Gemeprost is less effective than misoprostol (EL2). The dose of 200mg of mifepristone should be preferred to 600mg (NP1, Rank A). Mifepristone can be taken at home (professional agreement). The optimum interval between mifepristone and misoprostol intake should be 24 to 48 hours (EL1, grade A). Before 7 weeks LMP, the dose of 400µg misoprostol should be given orally (EL1, grade A) eventually repeated after 3hours if no bleeding occurs. For optimal effectiveness between 7 and 14 LMP, the interval between mifepristone and misoprostol should not be shortened to less than 8hours (grade 1). An interval of 24 to 48hours will not affect the effectiveness of the method provided misoprostol dosage is 800µg (EL1). Vaginal, sublingual or buccal routes of administration are more effective and better tolerated than the oral route, which should be abandoned (EL1). An amount of 800µg sublingual or buccal misoprostol route has the same effectiveness than the vaginal route but more gastrointestinal side effects (EL1, grade A). Between 7 and 9 LMP, it does not seem necessary to repeat misoprostol dose whereas it should be repeated beyond 9 SA (grade B). Between 9 and 14 LMP, the dose of 400µg misoprostol given either vaginally, buccally or sublingually should be repeated every 3hours if needed (with a maximum of 5 doses) (EL2, grade B). There is no strong evidence supporting routine antibiotic prophylaxis for medical abortion (professional agreement). Rare contraindications should be respected (known hypersensitivity to misoprostol or mifepristone, inherited porphyria, severe anemia, hemorrhagic disorders or current anticoagulation therapy, suspected or confirmed ectopic pregnancy) as well as precautions of use (severe disease or on-going corticosteroid therapy). With no risk factors or symptoms, a pregnancy of unknown location (PUL) at the endovaginal ultrasound associated with a level of hCG usually chosen at less than 1500IU (or 2500IU with an abdominal probe) is not a contraindication of medical abortion as long as the woman is informed of the risk of undiagnosed ectopic pregnancy and knows how and when to seek emergency attention. An earlier than usual follow-up of the decrease of hCG levels is highly recommended. Breastfeeding, obesity, twin pregnancy and scared uterus are not contraindications for first trimester medical abortion. Side effects (gastro intestinal and thermoregulation disorders) during the procedure are generally of low intensity and short duration. A prophylactic treatment for nausea should be proposed (professional agreement). The pain increases with gestational age of the pregnancy (EL1). Ibuprofen is the first choice of painkiller (EL1). Ibuprofen will be systematically proposed or given on demand according to the practice of each facility (professional agreement). After a medical abortion, a follow-up assessment to confirm completion of the abortion is recommended (EL2, grade B). Clinical history combined with ultrasound and/or hCG blood level are both reliable methods and can be left with the choice of each facility (grade B). A fall of more than 80% of the initial blood level of hCG, fifteen days after the procedure is in favor of the success of the method (grade B). CONCLUSION: Medical abortion is a safe and efficient abortion method up to 14 weeks LMP. To be effective, the drug regimen should be adapted to gestational age. Women should be informed of advantages and disadvantages of the method according to the gestational age and side effects so she can choose the method that fits her best.

[Ambulatory medical abortion performed in a family planning center]. / L'interruption volontaire de grossesse médicamenteuse dans un centre de planification familiale.

In France, since 2001, medical abortion can be performed in ambulatory conditions, provided an agreement is signed with a hospital serving as referral for complications or failures of the method. This study, reports on the experience of a family planning center (NGO MFPF, Mouvement français de planning familial) in partnership with Delafontaine Hospital in Saint-Denis. In 2004, the MFPF has managed 161 cases of ambulatory medical abortion using a protocol of 200mg of mifepristone on day 1 and 400 to 800 microg of misoprostol on day 3, with possibility for the women to stay at home or go to the hospital for the expulsion. The average age of the women was 24 years and the proportion of young and vulnerable women quite high. The rate of success, defined as the absence or surgical intervention, approached 94.5% and only one case of severe complication was reported, massive hemorrhage 40 days after the initial intake of misoprostol. 75% of women chose to stay home. Acceptance of the method was very good with minimal request for more consultations than the three visits proposed in the protocol. The quality of the follow-up was high with 82% of women attending the medical check, with no difference being observed with regard to age, obstetrical history or socio-economic groups. Ambulatory medical abortion was successful and safe even among vulnerable women. NGOs with multidisciplinary staff involving counsellors, nurses and doctors can offer high quality preparation and follow-up.

Home use of two doses of misoprostol after mifepristone for medical abortion: a pilot study in Sweden and France.

OBJECTIVE: To test the feasibility, safety, and efficacy of home use of two doses of misoprostol for medical abortion (MA) in European settings. METHODS: One hundred thirty women (100 in Sweden, 30 in France) presenting for first-trimester MA were administered oral mifepristone in the clinic and sent home with two 400 microg doses of misoprostol, along with instructions to take the misoprostol at 24 h intervals. Women were also asked to complete a daily symptom diary. Outcomes of interest included effectiveness, side-effects, and adherence to and acceptability of the home-use regimen. RESULTS: Three women (all in France) were lost to follow-up. Of the remaining 127 women, 124 (98%) had a successful MA. All women adhered successfully to the home-use regimen, and satisfaction with home use was high (98%). Most women experienced noticeable, if transitory, side effects after both the first and second doses of misoprostol (97% and 94%, respectively). CONCLUSIONS: Misoprostol may successfully and satisfactorily be used at home as part of a MA regimen in European settings as it has been for years in the US. Further research to determine if two doses of misoprostol are more effective than a single dose would be useful.

[Induced abortion in France: results of the COCON study]. / Prise en charge de l'IVG en France: résultats de l'enquête COCON.

OBJECTIVE: The aim of this article is to describe conditions of abortions practices in France. MATERIALS AND METHODS: The study was based on the COCON survey. This survey was carried out among a representative sample of 2863 women aged 18 to 44 living in metropolitan France. Women were interviewed by telephone. The analysis was performed among a sub-sample of 320 women who had had an abortion between 1996 and 2000. Results were compared with those of the national notification of induced abortions. RESULTS: Altogether, the way in which abortions were carried out was appropriate, but differences were observed according to the type of hospital: access to care was easier in the private sector; however a pre-abortion interview was less often carried out and a post-abortion interview less often proposed in the private sector. Besides, in both sectors, women were rarely allowed to choose the abortion technique, or the type of anesthesia in the case of a surgical abortion. CONCLUSION: The COCON study is the first population based survey describing the characteristics of care regarding voluntary abortion. It shows the persistence of differences in practices between the public and the private sectors.

Analysis of the underestimation of induced abortions in a survey of the general population in France.

INTRODUCTION: A pilot study has been conducted in France to estimate the extent of underreporting of induced abortion and the factors linked to underreporting. METHODS: A representative random sample of 300 women aged between 18 and 44 years of age who had been pregnant during the previous 2 years and 100 women who had not was selected from the telephone directory. Interviews were conducted by telephone. RESULTS: The annual incidence of induced abortion for the 18-44-year-old age group was 6.9 per 1000 (95% confidence interval 2.2-11.6), while the rate derived from national statistics was 15 per 1000. Five women who reported a therapeutic abortion in their lifetime had confused induced abortion and therapeutic abortion. There was no significant difference in the proportion of women reporting induced abortion in their lifetime between those answering with another adult present and those who were alone when answering (13.1% versus 11.1%, p = 0.8). There was also no significant difference according to the sex of the interviewer (10.0% for men versus 12.2% for women, p = 0.6). CONCLUSION: The results suggest that the context in which the questions were asked does not affect the validity of the answers and that there is a problem in the comprehension of the terminology used. Extensive rewriting and reformulation of the questions is required to minimize the underreporting of induced abortion.

[Conditions of induced abortion in France]. / Les conditions de l'interruption de grossesse en France.

In France, each woman will have an average of one unintended pregnancy in her life and she'll decide to abort once out of two. 21 years after the vote of the law which authorized the abortion, according to certains conditions, the abortion rate decreases slightly. The socioeconomics characteristics of women requesting an abortion are very similar to those found in 1976. The medical and psychological complications are very low. The law is applied except that some difficulties persist: to recruit professionals becomes more difficult, inadequate solutions of public hospitals, inappropriate and not always comprehensive towards the clients, no possibility to choose the methods. The law is limited for the minors, the foreigners and the pregnancies up to 10 weeks which increases the social inegalities. It is a major public health concern to make abortion as safe as possible because it gives accessibility to choose freely motherhood which is the best way for safe pregnancy, birth and parent and child relationship.

[Contraception and abortion in the countries of eastern Europe]. / Contraception et avortement dans les pays d'Europe de l'Est.

For various reasons, including the population policies of the former Socialist countries, abortion is much more frequent than contraception in Central and Eastern Europe. The contrary occurs in Western countries. In the current context, countries in Central and Eastern Europe should improve abortion services and this should be a priority target in their health policy. The study does not detect a clear-cut advantage as concerns substituting contraception to abortion in these countries in terms for instance of reducing maternal mortality. In fact a health policy favouring contraception instead of abortion is firstly inspired by political or ethical reasons. If implemented in Central and Eastern Europe, it would require several decades to bear evident results.

PIP: Although most countries of Europe have total fertility rates of under 2, these low rates are achieved in western and northern Europe primarily through widespread contraceptive usage with abortion serving as a backup, while in eastern Europe abortion plays the primary role. In eastern European countries, access to abortion preceded diffusion of modern contraception. When modern contraceptive methods became available in the 1960s, they did not reach the eastern European countries because of the lack of communication between Communist societies and the West. Erroneous ideas about the dangers of modern methods have persisted, while abortion is viewed as an everyday occurrence. Public opinion concerning modern methods is generally unfavorable. The availability of safe legal abortions in western Europe has resulted in a very low rate of abortion mortality, around 0.5 deaths per 100,000 abortions. In eastern Europe, abortion mortality rates range from 1 to 10/100,000 abortions, and infertility resulting from abortion is common. Illegal abortions persist because of poor accessibility of quality services. The psychological cost to couples of disorders resulting from abortion is difficult to evaluate but surely considerable. A comparison of the public health results of improving conditions of abortion in eastern Europe while continuing to limit contraceptive use to the traditional methods, or of providing modern contraception, indicates that there is no decisive advantage in favor of modern contraception. The manpower and thus the financial requirements would be less for the policy of providing safe abortions without modern contraception. The major argument against abortion is ethical, not financial or health related. Hungary and the German Democratic Republic have demonstrated that a change from fertility control through abortion to fertility control through contraception is feasible. Such a change would require a very large investment in services and manpower, and would not be fully achieved for many years.