Airway responses to antigen challenge in allergic rhinitis and allergic asthma

The density dependence of the maximum expiratory flow-volume curve, functional residual capacity (FRC), and specific airway conductance (SGaw) were determined before and during bronchial provocation with ragweed extract in 27 subjects with ragweed hypersensitivity and a history of either bronchial asthma (16 subjects) or allergic rhinitis (11 subjects). Mean baseline SGaw was significantly lower while mean volume of isoflow (Visov) and FrC were significantly higher in subjects with bronchial asthma. During antigen challenge, 10 of 16 subjects with bronchial asthma (63%) and five of 11 subjects with allergic rhinitis (45%) showed a greater than 35% decrease in SGaw ("reactors"): mean relative decreases in SGaw from baseline were 46% and 53%, respectively. The remaining subjects showed a less than 35% decrease in SGaw ("nonreactors") with mean relative decreases of 9% (allergic asthma) and 6% (allergic rhinitis). Mean Visov increased in all subjects with bronchial asthma and in eight of 11 subjects with allergic rhinitis. A significant increase in FRC (6%) was seen only in the "reactors" with bronchial asthma. Following antigen challenge, the beta adrenergic agonist, isoetharine, increased SGaw and decreased Visov. We conclude that in asymptomatic subjects with ragweed hypersensitivity, (1) central and peripheral airway function is more abnormal in subjects with bronchial asthma than in subjects with allergic rhinitis, (2) subjects of both groups show quantitatively and qualitatively comparable airway responses during antigen challenge with a decrease in SGaw or an increase in Visov, possibly representing increase in central and/or peripheral airflow resistance, respectively, (3) Visov may be a more sensitive indicator of airway response to antigen challenge than SGaw, and (4) the bronchodilator effects of a beta adrenergic agonist on antigen-induced bronchospasm are similar in both groups.     

A very frequent mutation and remarkable association of R761H with M694V mutations in Turkish familial Mediterranean fever patients

Familial Mediterranean fever (FMF) is an autosomal-recessive disease. It is characterized by recurring fever, abdominal pain, and serositis. The Mediterranean fever (MEFV) gene is localized on 16p13.3 and more than 35 mutations have been described to date. There are some differences in the gene mutations of FMF in the various ethnic groups. The aim of this study is to determine the frequency of the mutations which has been reported comparatively rare, to define the most effective mutation set, and to select the most suitable DNA analysis system for Turkish FMF patients. Mutations in 330 Turkish FMF patients with typical phenotypes from various regions of Turkey were evaluated for the research purposes. These patients were analyzed for six MEFV gene mutations by the NanoChip® Molecular Genetics Workstation. The most frequent mutation was M694V, identified in 50.00% of the alleles examined; M680I followed with 14.10% and V726A—9.70%. Consequently, we determined that R761H (n?=?23; 3.48%) was the most frequent rare mutations in Turkish FMF patients. Frequency of the rare mutations were R761H (3.48%), E148Q (1.36%), and M694I (1.21%). All of these mutations were in the compound heterozygote state. Our study showed that R761H mutations were higher than it has been reported in literature until now and were mainly associated with M694V. We suggest that mutation R761H should be included in the mutation scanning analysis researches or considered if the patient has M694V/? mutation especially in Turkish FMF patients. Larger serial studies need to be done to investigate the rate and coexistence of these mutations.     

Differential mutational profiles of familial Mediterranean fever in North Africa

Familial Mediterranean fever (FMF) is a recessive autoinflammatory disease, mainly occurring in the eastern Mediterranean. In these populations, the five FMF founder mutations are differently distributed. In Algeria, the FMF-causing variants remain poorly explored. This retrospective study aims to report the mutational profile of Algerian FMF patients and to compare it with North African FMF patients. One hundred eighty-three unrelated patients clinically suspected of FMF were recruited from various Algerian hospitals (2007–2015) and tested for mutations in exon 10 of MEFV gene. Molecular analysis identified 144 mutant alleles among 87 of 183 patients (47.5%). p.M694I was the most prevalent pathogenic allele, accounting for 63.2% of mutant alleles, followed by p.M694V and p.M680I occurring with a same frequency (14.5%). Others, p.A744S (6.2%) and p.I692del (1.3%), are less frequent. Interestingly, p.M694I was the most recurrent in patients with renal AA-amyloidosis. Our results provide the first genetic data on FMF in Algeria, demonstrating the predominance of p.M694I and the absence of p.V726A, compared to other North African countries (Morocco, Tunisia, and Egypt). In conclusion, North African FMF patients display differential mutational profiles that may result from the difference in ethnic origin and the genetic heterogeneity among these populations.     

Are systemic lupus erythematosus patients carrying MEFV gene less prone to renal involvement? Report of three cases and review of the literature

Abstract

Familial Mediterranean fever (FMF) is an autosomal recessive auto inflammatory disease, characterized by acute attacks of serositis, arthritis or skin rash. Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease characterized by multisystem inflammatory lesions affecting any organ systems in the body. Coexistence of FMF and SLE is rare in literature. In this report, we present three patients with FMF associated with SLE.     

MEFV mutations in multiplex families with familial Mediterranean fever: is a particular genotype necessary for amyloidosis?

Familial Mediterranean fever (FMF) is an autosomal recessive disease. It is characterized by recurrent febrile episodes in association with peritonitis, pleuritis, and arthritis. Progressive systemic amyloidosis is the most important complication of FMF that inevitably leads to chronic renal failure. Recently, the gene for FMF, MEFV, has been cloned and four missense mutations have been described: M694V, M680I, V726A, and M694I. Initial studies have suggested that the presence of the M694V mutation carries a significant risk for the development of amyloidosis. In this study, we present seven families, in which at least two individuals have been diagnosed with FMF and at least one with amyloidosis. Among 18 individuals, in whom molecular testing was performed for the four aforementioned mutations, ten had amyloidosis. None of these ten individuals was found to be homozygous for the M694V mutation. In three families, there were two sibs with amyloidosis. None of the sib-pairs with amyloidosis was found to have the same genotype. There were two or more sibs with the same genotype in four families. Only one sib from each family developed amyloidosis in these families. These results provide evidence that FMF patients without the M694V mutation are also at risk for the development of amyloidosis. Particular mutations themselves do not appear to be sufficient to explain the occurrence of amyloidosis in all cases with FMF.     

Infevers: an evolving mutation database for auto-inflammatory syndromes

The Infevers database (http://fmf.igh.cnrs.fr/infevers/) was established in 2002 to provide investigators with access to a central source of information about all sequence variants associated with periodic fevers: Familial Mediterranean fever (FMF), TNF Receptor Associated Periodic Syndrome (TRAPS), Hyper IgD Syndrome (HIDS), Familial Cold Autoinflammatory Syndrome/Muckle-Wells Syndrome/Chronic Infantile Neurological Cutaneous and Articular Syndrome (FCAS/MWS/CINCA). The prototype of this group of disorders is FMF, a recessive disease characterized by recurrent bouts of unexplained inflammation. FMF is the pivotal member of an expanding family of autoinflammatory disorders, a new term coined to describe illnesses resulting from a defect of the innate immune response. Therefore, we decided to extend the Infevers database to genes connected with autoinflammatory diseases. We present here the biological content of the Infevers database, including the introduction of two new entries: Crohn/Blau and Pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA syndrome). Infevers has a range of query capabilities, allowing for simple or complex interrogation of the database. Currently, the database contains 291 sequence variants in related genes (MEFV, TNFRSF1A, MVK, CARD15, PSTPIP1, and CIAS1), consisting of published data and personal communications, which has revealed or refined the preferential mutational sites for each gene. This database will continue to evolve in its content and to improve in its presentation.     

Model-Based Prediction of Expiratory Resistance Index in Patients with Asthma

Objectives. Develop a sensitive algorithm and index for detection of asthma patients using forced expiratory flow curves. Methods. A lumped-parameter model of forced expiration was developed. The model can predict the flow-volume curve during forced expiratory maneuver. The flow-volume curves generated by the model depend on values of resistance parameters (FER). Use of flow-volume curves recorded from normal subjects and from patients with asthma before and after ventolin inhalation as inputs for the inverse model, yielded the resistance parameters for each case. These parameters are based on the entire information presented in the flow-volume curve and on the reduction in flow at all lung volumes. Results. Forced Expiratory Resistance (FER _N ) indices were estimated at different percent of lung volumes using the inverse model. The index was significantly affected by inhalation of ventolin in asthmatic patients and was insensitive to ventolin inhalation in normal patients. In asthmatic patients, the FER index at five lung volumes (out of eight), was two–five times greater than in normal subjects with p ≪ 0.05 (three of them with p ≪ 0.01). Conclusions. The estimated parameters were sensitive indicators of the degree of lung function impairment and were able to accurately distinguish between healthy and asthmatic patients. Barnea O, Abboud S, Guber A. Model-based prediction of expiratory resistance index in patients with asthma     

质疑氦氧混合气最大呼气流量-容积曲线的理论与意义

目的：探讨氦氧混合气最大呼气流量－容积曲线（MEFVHe-O2)理论及意义的可靠性和实用性。方法：分别测定支气管哮喘（支喘组）和慢阻肺（COPD组）患者呼吸He-O2前后的MEFVHe-O2，并设对照组进行比较。结果：3组受检者空气最大呼气流量－容积曲线（MEFVair）比较除支喘组用力肺活量（FVC）与对照组比较差异无显著性外, 其余数据支喘组、COPD组与对照组比较均差异有显著性（P＜0．05）；MEFVHe-O2支喘组、COPD组与对照组比较全部数据均差异有显著性（P＜0．05）；呼吸He-O2后3组受检者的MEFV数据都有明显的增加，但增加的百分率支喘组、COPD组与对照组比较皆差异无显著性（P＞0．05）；支喘组呼吸He-O2前后MEFV自身相比虽然FVC、第1s用力呼气容积（FEV1）、最大呼气流量峰值（PEF）差异有显著性（P＜0．05），但主要反映大、小气道的75％肺活量最大呼气流（Vmax75)、50％肺活量最大呼气流（Vmax50）、25％肺活量最大呼气流量（Vmax25）以及等流量容积（Visov)却差异无显著性（P＞0．05）；COPD组呼吸He-O2前后MEFV自身比较全部数据差异无显著性。结论：MEFVHe-O2的理论存在缺陷，在一定浓度He存在的条件下，肺的弹性不是一成不变的，因而MEFVHe-O2的意义亦即其可以判断气道阻塞部位及小气道阻塞是否可逆的作用是不能成立的。呼吸He-O2后FVC大幅增高（即肺的弹性发生改变）的现象至今未见科技期刊报道，值得深入研究阐明。