Search

Short telomere syndrome (STS) is a group of rare, often underrecognized, diseases caused by defects in telomere-maintenance genes, leading to abnormal telomere shortening and associated with diverse multi-organ manifestations. In pediatric patients, STS typically presents with mucocutaneous or gastrointestinal lesions, bone marrow failure and neoplasia. In adulthood, aplastic bone marrow disease, liver disease and pulmonary fibrosis are classic clinical manifestations. At present, medical treatment options for STS remain limited. Danazol, a synthetic androgenic hormone, can slow down telomere shortening and thus limit the progression of the disease. Finally, hematopoietic, hepatic and pulmonary transplantation, sometimes combined, may be discussed in a multidisciplinary setting in certain situations.

Interstitial lung disease is a frequent complication of systemic sclerosis and has now become the leading cause of death in this disorder. It mainly occurs during the first five years after the diagnosis of systemic sclerosis. Various risk factors are associated with the occurrence of interstitial lung disease, including the presence of anti-topoisomerase I antibodies (Scl-70) and the diffuse cutaneous form of systemic sclerosis. The most common radio-pathological presentation is nonspecific interstitial pneumonia, followed by usual interstitial pneumonia. The classical immunosuppressive treatment of systemic sclerosis-associated interstitial lung disease is evolving, as recent studies suggest a beneficial effect of biological agents such as rituximab and tocilizumab, and antifibrotic drugs such as nintedanib.

Diffuse interstitial lung disease (ILD) is one of the most frequent extra-articular manifestation of rheumatoid arthritis (RA) and is an important factor of morbidity and mortality. However, the physiopathological mechanisms underlying RA-associated ILD remain poorly understood, and disease management is difficult in the absence of effective treatments and international guidelines. The recent identification of genetic variants and mutations similar to those observed in idiopathic pulmonary fibrosis (IPF), a disease affecting exclusively the lung, provides new insights into the understanding of RA-associated ILD. Furthermore, new antifibrotic drugs approved for the treatment of IPF, including pirfenidone and nintedanib, could also prove to be effective for RA-associated ILD. Studies are ongoing to confirm this hypothesis.

International audience; Objective To guide nosology and classification of patients with eosinophilic granulomatosis with polyangiitis (EGPA) based on phenotype and presence or absence of ANCA. Methods Organ manifestations and ANCA status were retrospectively analyzed based on the presence or not of predefined definite vasculitis features or surrogates of vasculitis in patients asthma, eosinophilia, and at least one systemic organ manifestation attributable to systemic disease. Results The study population included 157 patients (mean age 49.4 ± 14.1), with a follow-up of 7.4 ± 6.4 years. Patients with ANCA (31%) more frequently had weight loss, myalgias, arthralgias, biopsy-proven vasculitis, glomerulonephritis on biopsy, hematuria, leukocytoclastic capillaritis and/or eosinophilic infiltration of arterial wall on biopsy, and other renal disease. A total of 41% of patients had definite vasculitis manifestations (37%) or strong surrogates of vasculitis (4%), of whom only 53% had ANCA. Mononeuritis multiplex was associated with systemic vasculitis (p = 0.005) and with the presence of ANCA (p

Die zystischen Lungenerkrankungen sind eine distinkte Gruppe seltener Lungenkrankheiten. Zwei von ihnen sind die Folge monogener Defekte von Tumorsuppressorgenen: Die Lymphangioleiomyomatose - entweder sporadisch oder im Rahmen des Tuberöse-Sklerose-Komplexes - und das Birt-Hogg-Dubé-Syndrom. Diese Krankheiten weisen Gemeinsamkeiten im klinischen Erscheinungsbild auf, vom Auftreten im jungen Erwachsenenalter über multiple pulmonale Zysten, rezidivierenden Pneumothorax und Hamartome der Haut bis hin zu Nierentumoren. Sie unterscheiden sich jedoch deutlich im Hinblick auf die Verteilung auf die Geschlechter, die Pathogenese, den Krankheitsverlauf und die Prognose. In der Erforschung beider seltenen Krankheiten werden derzeit rapide Fortschritte gemacht. Beim Management der Lymphangioleiomyomatose sind in den letzten zehn Jahren wesentliche Verbesserungen erzielt worden, nachdem die pathogenen Mechanismen erforscht, eine wirksame Therapie entdeckt und große Kohortenstudien sowie internationale Leitlinien erstellt wurden. Das Birt-Hogg-Dubé-Syndrom wurde erst vor kürzerer Zeit erstmals beschrieben; die Klärung der pathophysiologischen Hintergründe steht noch aus.

Background: Some data suggest that anti-inflammatory macrolides may be effective to treat organizing pneumonia (OP) and prevent relapses, but no formal comparison with prednisone alone is available. To explore this issue, we retrospectively compared the efficacy of a 12-week combined regimen of clarithromycin and prednisone with a 24-week prednisone alone regimen in OP. Methods: A standard 12-week regimen of combined clarithromycin and prednisone was designed for the treatment of cryptogenic or radiation-induced OP, aiming at reducing the cumulated prednisone dose and the relapse rate. Its use was left to the discretion of the treating physicians, members of the Groupe d’Etudes et de Recherche sur les Maladies Orphelines Pulmonaires. Data were compared to a historical control group treated with a standard 24-week prednisone alone regimen. Results: 16 patients were treated with combined therapy and 21 with prednisone alone. Complete radiological remission was achieved in 63% of the combined therapy group and 81% of the prednisone alone group (p=0.38). Symptomatic relapses occurred in 81% of the combined therapy group, and 52% of the prednisone alone group (p=0.14). No side effect of clarithromycin was reported. Conclusions: In patients with cryptogenic or radiation-induced OP, a 12-week regimen of clarithromycin and prednisone showed no benefit on remission rate and relapse rate as compared to a 24-week prednisone only regimen. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 230-238)

The structure stability of double perovskite ceramics Ba2-xSrxCaTeO6 (0≤x≤2) has been studied using X-ray powder diffraction (XRD) and Raman spectroscopy. According to the Rietveld refinement three phases transition induced by composition were reported. The transition from the cubic symmetry to tetragonal (Fmm → I4/m) is observed between x= 0.4 and 0.6. The second transition from tetragonal symmetry to monoclinic symmetry with I2/m as space group takes place between x = 0.6 and 0.8. The third phase transition monoclinic to monoclinic (I2/m → P21/n) is located between x = 1.4 and 1.6. Furthermore, considerable changes of the composition dependence of the Raman modes recorded at ambient conditions confirm the phase transitions reported by X-ray studies., Journal of Applied Surfaces and Interfaces, Vol 1, No 1-3 (2017)

INTRODUCTION: Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease affecting mainly young women. BACKGROUND: The respiratory manifestations are characterized by a progressive cystic destruction of the lung parenchyma. Extrapulmonary involvement includes benign renal tumours called angiomyolipomas and abdominal lymphatic masses called lymphangioleiomyomas. At the pathological level, the cellular proliferation found in LAM is in part due to the presence of mutations in the tumour suppressor genes TSC1 and TSC2 (Tuberous Sclerosis Complex). These mutations lead to the activation of the mTOR pathway, which is currently the main therapeutic target. mTOR inhibitors such as sirolimus or everolimus have shown a beneficial effect on the decline in pulmonary function and a reduction of angiomyolipoma size, but are necessary in only some patients. PERSPECTIVES: LAM cells have migratory properties mediated by the formation of new lymphatic vessels. They are also able to secrete metalloproteases, which enhance their invasiveness. Moreover, the expression of estrogen and progesterone receptors by LAM cells suggests a possible role for sex hormones in the pathogenesis of the disease. CONCLUSION: A better understanding of mTOR-independent mechanisms would allow the development of novel therapeutic approaches.

Common variable immunodeficiency (CVID) is the most frequent primary immune deficiency. Recurrent infections are classical consequences of CVID, but their impact has been largely reduced by immunoglobulin replacement. CVID is also associated with various inflammatory and autoimmune manifestations resulting from abnormal cellular immunity. The lungs are especially affected by a recently described entity called granulomatous lymphocytic interstitial lung disease (GLILD). GLILD currently constitutes an important cause of morbidity and mortality in these patients. It is distinct from bronchiectasis secondary to recurrent infections, and presents similarities but also striking differences with sarcoidosis.

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is characterized by formation and proliferation of fibroblast foci. Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A (ETA) receptor. OBJECTIVE To determine whether ambrisentan, an ETA receptor-selective antagonist, reduces the rate of IPF progression. DESIGN Randomized, double-blind, placebo-controlled, event-driven trial. (ClinicalTrials.gov: NCT00768300). SETTING Academic and private hospitals. PARTICIPANTS Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans. INTERVENTION Ambrisentan, 10 mg/d, or placebo. MEASUREMENTS Time to disease progression, defined as death, respiratory hospitalization, or a categorical decrease in lung function. RESULTS The study was terminated after enrollment of 492 patients (75% of intended enrollment; mean duration of exposure to study medication, 34.7 weeks) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study. Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression (90 [27.4%] vs. 28 [17.2%] patients; P = 0.010; hazard ratio, 1.74 [95% CI, 1.14 to 2.66]). Lung function decline was seen in 55 (16.7%) ambrisentan-treated patients and 19 (11.7%) placebo-treated patients (P = 0.109). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) patients in the ambrisentan and placebo groups, respectively (P = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (P = 0.100). Thirty-two (10%) ambrisentan-treated patients and 16 (10%) placebo-treated patients had pulmonary hypertension at baseline, and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point. LIMITATION The study was terminated early. CONCLUSION Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations. PRIMARY FUNDING SOURCE Gilead Sciences.

Lung cancer screening has been the focus of intense interest since the publication in 2011 of the NLST trial (National Lung Screening Trial) showing a mortality reduction in smokers undergoing 3-year screening by chest computed tomography. Although these data appear promising, many issues remain to be resolved, such as high rate of false positive cases, risk of overdiagnosis, optimal intervals between screens, duration of the screening process, feasibility, and cost. Structured screening programs appear crucial to guarantee patient information, technical quality, and multidisciplinary management. Despite these uncertainties, several guidelines already state that screening should be performed in patients at risk, whereas investigators stress that more data are needed. How should the primary care physician deal with individual patients requests? This review provides some clues on this complex issue.

Primary ciliary dyskinesia (PCD) is an autosomal recessive disease with an incidence estimated between 1:2,000 and 1:40,000. Ciliated epithelia line the airways, nasal and sinus cavities, Eustachian tube and fallopian tubes. Congenital abnormalities of ciliary structure and function impair mucociliary clearance. As a consequence, patients present with chronic sinopulmonary infections, recurrent glue ear and female subfertility. Similarities in the ultrastructure of respiratory cilia, nodal cilia and sperm result in patients with PCD also presenting with male infertility, abnormalities of left-right asymmetry (most commonly situs inversus totalis) and congenital heart disease. Early diagnosis is essential to ensure specialist management of the respiratory and otological complications of PCD. Diagnostic tests focus on analysis of ciliary function and electron microscopy structure. Analysis is technically difficult and labour intensive. It requires expertise for interpretation, restricting diagnosis to specialist centres. Management is currently based on the consensus of experts, and there is a pressing need for randomised clinical trials to inform treatment.

Définies par une prévalence inférieure à 1⁄2000, lesmaladies rares toucheraient 5 à 6 % de la population,soit environ 500 000 personnes en Suisse. Une vasteenquête européenne a révélé pour la première foisavec précision les difficultés et les besoins despatients atteints, et montré que leur prise en chargen'est pas optimale. Des plans nationaux pour lesmaladies rares ont été développés ou vont l'être aucours de prochaines années dans la plupart des payseuropéens. La Suisse a un retard de plusieurs annéesdans ce domaine, mais des initiatives récentespourraient permettre de le combler si elles sontlargement soutenues. Les médicaments orphelins,destinés à un petit nombre de patients mais souventextrêmement coûteux, sont une source potentiellede tensions entre intérêt individuel et intérêt collectif.Entité éthique, sociale, économique, mais aussiscientifique et clinique, les maladies rares et leurstraitements confrontent aux limites des connaissanceset des ressources. Elles constituent un enjeu de santépublique et un défi que la Suisse est invitée à relever.

Von seltenen Erkrankungen, die definitionsgemässeine Prävalenz von unter 1/2000 aufweisen, sindschätzungsweise 5 bis 6 % der Bevölkerung betroffen,d. h. in der Schweiz rund 500 000 Menschen.Eine breit angelegte Umfrage hat erstmals dieSchwierigkeiten und Bedürfnisse der betroffenenPatientinnen und Patienten genau erfasst und aufgezeigt,dass diese Menschen nicht optimal versorgtwerden. In den meisten europäischen Ländernbestehen bereits nationale Pläne für seltene Erkrankungenoder werden in den nächsten Jahren entwickelt.Die Schweiz weist in diesem Bereich einenRückstand von mehreren Jahren auf, der jedoch aufgeholtwerden könnte, falls die kürzlich eingeleitetenInitiativen breite Unterstützung erhalten. BeiOrphan-Medikamenten, die für eine kleine Zahl vonPatientinnen und Patienten bestimmt, aber oft sehrteuer sind, kann das Einzelinteresse dem Allgemeininteresseentgegenstehen. Die seltenen Erkrankungenund ihre Behandlung werfen ethische, gesellschaftliche,ökonomische, aber auch wissenschaftlicheund klinische Fragen auf und zeigen die Grenzendes Wissens und der Mittel auf. Sie sind ein Problemfür das Gesundheitswesen, und eine Herausforderung,der sich die Schweiz stellen sollte.

Lymphangioleiomyomatosis (LAM) is a rare lung disease, which occurs sporadically or in association with the genetic disease tuberous sclerosis complex (TSC) 1, 2. Sporadic LAM affects ∼1 in 400,000 adult females; in TSC, LAM occurs in 30–40% of adult females 3, 4 and exceptionally in males and children 5, 6. Patients with LAM usually develop progressive dyspnoea and recurrent pneumothorax, chylous collections and occasional haemoptysis 1. Extra pulmonary lymphadenopathy and cystic masses of the axial lymphatics termed lymphangioleiomyomas can result in abdominal and pelvic lymphatic obstruction 7. LAM is often associated with angiomyolipoma in the kidneys 8, and an increased frequency of meningioma 9. LAM varies in clinical features and rate of progression: this together with an absence of clear prognostic factors results in patients being given conflicting information about prognosis. Diagnosis is made by tissue biopsy (generally from the lung but occasionally from lymph nodes or lymphangioleiomyomas) and/or a combination of history and high-resolution computed tomography scanning (HRCT). Pathological diagnosis relies on characteristic LAM cell morphology and positive immunoreactivity to smooth muscle actin and HMB-45 antibodies. Increasingly HRCT is used to diagnose LAM without resorting to lung biopsy; however a number of conditions with multiple pulmonary cysts can mimic LAM. As LAM is rare, there have been no controlled trials of its management. Supportive treatment includes management of airflow obstruction and hypoxaemia with bronchodilators and oxygen respectively, specific treatment for surgical or pleural complications including pneumo- and chylothorax, and interventional treatment of renal lesions 10, 11. As LAM is a disease of females and is thought to be accelerated by oestrogen, oophorectomy, tamoxifen, progesterone and gonadotropin-releasing hormone (GnRH) analogues have been used without evidence that they are effective. The recent finding of abnormalities in the TSC1/2 genes resulting …