Allergic vs nonallergic asthma: what makes the difference?

BACKGROUND: The aim of this work was to describe clinical similarities and differences between allergic and nonallergic asthmatics, notably concerning the nasosinusal involvement. METHODS: A total of 165 asthmatics (122 allergics and 43 nonallergics) and 193 controls (40 allergics and 153 nonallergics), recruited in the frame of EGEA study (Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy), were included. Asthmatics were included on the basis of positive answer to four standardized items. To establish differences and similarities between allergic and nonallergic asthmatics, general characteristics (age, sex, smoking habits, history of hay fever and allergic dermatitis), history of asthma, severity and nasosinusal involvement were examined. Clinical assessment was based on the answers to a detailed questionnaire, and spirometry. RESULTS: Greater age, female sex, sinusal polyposis, and FEV1 below 80% of the predicted value increased the risk of displaying a nonallergic type of asthma, whereas history of hay fever, seasonal exacerbation of asthma, and asthma duration lowered this risk. Unexpectedly, we found no difference in terms of rhinitic symptoms between both groups, probably resulting from distinct causes. CONCLUSION: These results give new insights into the contrasts between clinical features of allergic and nonallergic asthma. The terminology of extrinsic asthma was first introduced by Rackeman in 1947 (1) and referred to the triggering role of allergens in asthma. By symmetry, he described intrinsic asthma as a disease characterized by later onset in life, female predominance, higher degree of severity, and more frequent association to nasosinusal polyposis. As these asthmatics were not improved by conventional treatment, this author considered their disease as caused by a nonallergic, unknown phenomenon. It is now widely admitted that nonallergic asthma can be objectively distinguished from allergic asthma based on negative skin tests to usual aeroallergens. On the other hand, positive skin test shows a tendency to produce IgE antibodies in response to low doses of allergens. "Atopy" and "atopic" are the terms used to describe this clinical trait and predisposition (2). Allergic clinical manifestations of atopy are of various types, for example rhinitis and asthma. Nowadays the terminology of "extrinsic" and "intrinsic" asthma should no longer be used, and should be replaced by the terminology of "allergic" or "nonallergic" asthma (2).     

Clinical prescribing of allergic rhinitis medication in the preschool and young school-age child: what are the options?

Allergic rhinitis (AR) is the most common chronic condition in children and is estimated to affect up to 40% of all children. It is usually diagnosed by the age of 6 years. The major impact in children is due to co-morbidity of sinusitis, otitis media with effusion, and bronchial asthma. AR also has profound effects on school absenteeism, performance and quality of life. Pharmacotherapy for AR should be based on the severity and duration of signs and symptoms. For mild, intermittent symptoms lasting a few hours to a few days, an oral second-generation antihistamine should be used on an as-needed basis. This is preferable to a less expensive first-generation antihistamine because of the effect of the latter on sedation and cognition. Four second-generation antihis-tamines are currently available for children under 12 years of age: cetirizine, loratadine, fexofenadine and azelastine nasal spray; each has been found to be well tolerated and effective. There are no clearcut advantages to distinguish these antihistamines, although for children under 5 years of age, only cetirizine and loratadine are approved. Other agents include pseudoephedrine, an oral vasoconstrictor, for nasal congestion, and the anticholinergic nasal spray ipratropium bromide for rhinorrhoea. Sodium cromoglycate, a mast cell stabiliser nasal spray, may also be useful in this population. For patients with more persistent, severe symptoms, intranasal corticosteroids are indicated, although one might consider azelastine nasal spray, which has anti-inflammatory activity in addition to its antihistamine effect. With the exception of fluticasone propionate for children aged 4 years and older, and mometasone furoate for those aged 3 years and older, the other intranasal corticosteroids including beclomethasone dipropionate, triamcinolone, flunisolide and budesonide are approved for children aged 6 years and older. All are effective, so a major consideration would be cost and safety. For short term therapy of 1 to 2 months, the first-generation intranasal corticosteroids (beclomethasone dipropionate, triamcinolone, budesonide and flunisolide) could be used, and mometasone furoate and fluticasone propionate could be considered for longer-term treatment. Although somewhat more costly, these second-generation drugs have lower bio-availability and thus would have a better safety profile. In patients not responding to the above programme or who require continuous medication, identification of specific triggers by an allergist can allow for specific avoidance measures and/or immunotherapy to decrease the allergic component and increase the effectiveness of the pharmacological regimen.     

Clinical management of genital herpes: what can be done in pregnancy?

Neonatal herpes infection is the major complication of genital herpes even if it occurs in less than 1/10,000 births. A great number of recent studies illustrates the natural history of genital herpes. The importance of viral transmission by asymptomatic shedding is now well established. The widespread use of viral diagnosis strategies is the prerequisite to efficient genital herpes prevention in order to eradicate viral mother-to-child transmission. This starts with the detection of at-risk situations such as primary infection in late pregnancy. Once the at-risk situation is known there should be concern about the adaptation of treatment strategies including antiviral therapy. The following work proposes different strategies facing each at-risk situation in order to discuss the efficiency of new diagnostic and treatment tools.     

Clinical aspects of mucosal healing in inflammatory bowel diseases: what is it and what is the real value for the everyday practice?

The course of inflammatory bowel diseases is heterogeneous and varies over time. Therefore, the search for predictive factors has increasingly become the focus of research. Mucosal healing has emerged as an important objective, as evidence indicates that it is associated with improved disease outcome. Nevertheless, many unsolved questions remain, including the definition of complete or partial healing as well as the best assessment method using endoscopic or imaging techniques, most of which are relatively invasive and expensive procedures, which therefore are not ideal for frequent monitoring and it is not clear. This review summarizes the available evidence in order to assist clinicians when assessing the mucosal status in the everyday practice.     

Regional specialization in the mucosal immune system: what happens in the microcompartments?

Mucosal immunity is an important arm of the immune system because it operates in tissues involved in everyday infectious defence as well as in tolerance against innocuous environmental and dietary antigens. Here, Per Brandtzaeg and colleagues discuss compartmentalized regulation of mucosal B cells and mechanisms that might explain the strikingly regionalized effector disparity of the human mucosal immune system.     

Amyloid β and neuromelanin—Toxic or protective molecules?: The cellular context makes the difference

Alzheimer's disease (AD) and Parkinson's disease (PD) share several pathological mechanisms. The parallels between amyloid beta (Aβ) in AD and -synuclein in PD have been discussed in several reports. However, studies of the last few years show that Aβ also shares several important characteristics with neuromelanin (NM), whose role in PD is emerging. First, both molecules accumulate with aging, the greatest risk factor for AD and PD. Second, in spite of their different structures, Aβ and NM have similar characteristics that could also lead to neuroprotection. Metals are required to catalyze their formation and they can bind large amounts of these metals, generating stable complexes and thus playing a protective role against metal toxicity. Moreover, they may be able to remove toxic species such as oligopeptides and excess cytosolic dopamine. Third, both Aβ and NM have been implicated in parallel aspects of the neuronal death that underlies AD and PD, respectively. For example, both molecules can activate microglia, inducing release of toxic factors such as tumor necrosis factor- (TNF-), interleukin-6 (IL-6), and nitric oxide (NO). A careful analysis of these parallel effects of Aβ and NM, including their seemingly paradoxical ability to participate in both cell death and protection, may lead to an improved understanding of the roles of these molecules in neurodegeneration and also provide insights into possible parallels in the pathological mechanisms underlying AD and PD.     

Severe asthma in adults: what are the important questions?

The term severe refractory asthma (SRA) in adults applies to patients who remain difficult to control despite extensive re-evaluation of diagnosis and management following an observational period of at least 6 months by a specialist. Factors that influence asthma control should be recognized and adequately addressed prior to confirming the diagnosis of SRA. This report presents statements according to the literature defining SRA in order address the important questions. Phenotyping SRA will improve our understanding of mechanisms, natural history, and prognosis. Female gender, obesity, and smoking are associated with SRA. Atopy is less frequent in SRA, but occupational sensitizers are common inducers of new-onset SRA. Viruses contribute to severe exacerbations and can persist in the airways for long periods. Inflammatory cells are in the airways of the majority of patients with SRA and persist despite steroid therapy. The T(H)2 immune process alone is inadequate to explain SRA. Reduced responsiveness to corticosteroids is common, and epithelial cell and smooth muscle abnormalities are found, contributing to airway narrowing. Large and small airway wall thickening is observed, but parenchymal abnormalities may influence airway limitation. Inhaled corticosteroids and bronchodilators are the mainstay of treatment, but patients with SRA remain uncontrolled, indicating a need for new therapies.     

Anthropometric variability in the USA: 1971–2002

Aim: The study analysed variability in physical stature, weight, and body mass index (BMI) in the USA during 1971–2002. Subjects: Subjects were non-Hispanic Blacks and Whites, 2–74 years of age from the National Health and Nutrition Examination Surveys (NHANES I–III and 1999–2002). Methods: The coefficient of variation and the standard deviation of the logarithm of stature, weight, and BMI were used to assess anthropometric variability for groups defined by age, race, sex, income, and survey year. Weighted ordinary least squares regressions were used to estimate the effect of socio-economic variables on anthropometric variability. Results: (a) The relation between age and variability in weight or BMI resembles an inverted U, (b) men have lower variability in BMI than women, (c) Blacks and the poor have greater variability in weight and BMI than Whites or than the non-poor, and (d) variability in anthropometric indices increased during 1971–2002. Results were robust to the measure of variability used and to the use of the mean and mean square of the anthropometric indicators as explanatory variables. Conclusion: Since anthropometric indices correlate reliably with canonical indicators of well-being (e.g. income), growing variability in anthropometric indices, particularly among the Blacks and the poor, signals growing inequality in quality of life—a worrisome trend.     

Hungry in the womb: what are the consequences? Lessons from the Dutch famine

An increasing body of evidence suggests that poor nutrition at the very beginning of life – even before birth – leads to large and long term negative consequences for both mental and physical health. This paper reviews the evidence from studies on the Dutch famine, which investigated the effects of prenatal undernutrition on later health. The effects of famine appeared to depend on its timing during gestation, and the organs and tissues undergoing critical periods of development at that time. Early gestation appeared to be the most vulnerable period. People who were conceived during the famine were at increased risk of schizophrenia and depression, they had a more atherogenic plasma lipid profile, were more responsive to stress and had a doubled rate of coronary heart disease. Also, they performed worse on cognitive tasks which may be a sign of accelerated ageing. People exposed during any period of gestation had more type 2 diabetes. Future investigation will expand on the finding that the effects of prenatal famine exposure may reach down across generations, possibly through epigenetic mechanisms. Recent evidence suggests that similar effects of prenatal undernutrition are found in Africa, where many are undernourished. Hunger is a major problem worldwide with one in seven inhabitants of this planet suffering from lack of food. Adequately feeding women before and during pregnancy may be a promising strategy in preventing chronic diseases worldwide.     

Clinical trials on platelets: recent studies and what next?

The ready availability of platelet concentrates has undoubtedly made a major contribution to the supportive management of thrombocytopenic bleeding in patients with haematological malignancies. The optimal use of prophylactic platelet transfusions for the prevention of haemorrhage in patients with bone marrow failure remains controversial. Two RCTs of prophylactic platelet transfusions have recently been completed in adults with thrombocytopenia due to haematological malignancies or their treatment. Both found a no-prophylaxis approach led to higher rates of World Health Organization (WHO) grade 2–4 bleeding overall. Other patient groups who are major users of platelet transfusions are cardiac and other types of major surgery, critical care, major obstetric haemorrhage, trauma and paediatrics/neonates.     

Monitoring reproductive health in Europe: what are the best indicators?

The Reprostat Steering Committee asks for the best monitors of reproductive health. In many European countries, some deleterious agents have caused declines over the past half-century in both dizygotic (DZ) twinning rates and sperm counts. No strong evidence suggests that these declines have reversed, though they may have ceased in some countries. Here attention is only directed at potential secular changes in the proximate biological determinants of fertility (ovulation, coitus, semen quality, fertilization, spontaneous fetal loss and 'dead time'). The most comprehensive biological monitor of reproductive health is the 'natural' DZ twinning rate (viz the rate of DZ twinning in the absence of any medical intervention around the time of conception). At present, natural DZ twins are augmented by twins produced by new techniques. So efforts should be made to estimate the annual numbers of these iatrogenic twins in each European country. Then it would be possible to follow the movements of each national natural DZ twinning rate, and thus to continue monitoring a useful measure of reproductive health that has been available in most European countries for many years. Efforts should be made to assess the sperm quality of volunteer donors in each European country.     

Who are physician-scientists' role models? Gender makes a difference.

PURPOSE: To determine for educational purposes whether differences exist in the role models physician-scientists-in-training or in their early years of career development envision when they self-assess their abilities to perform clinical research. METHOD: A 35-item clinical research self-efficacy questionnaire was administered to 251 health care professionals who attended programs at the University of Wisconsin-Madison from 2002-2004. Three questions were included to determine the sex, role, and qualities of the expert that are envisioned by participants. Frequency distributions were computed for each response and variables were compared by gender using chi-square analysis and Fisher exact test. RESULTS: Ninety-five physicians-in-training and junior faculty physicians responded to the questionnaire. Seventy-one percent of female and 95% of male respondents reported their envisioned experts to be male. The most frequently reported role of the envisioned expert was that of a mentor who was a faculty member in the respondent's own department (72% women, 60% men). The three most frequently reported qualities of the envisioned expert were "multiple publications," "scientific knowledge," and "supportiveness." However, women more frequently reported "communication skills" and "problem-solving abilities" than did men. This difference was statistically significant and largely due to the frequency of qualities selected by women whose envisioned expert was female. CONCLUSIONS: The results of this study emphasized the importance of a role model's gender in the career development of physician-scientists.     

Clinical research in India: great expectations?

India is considered as a preferred site for conducting global clinical trials. Existence of a large treatment-na?ve population, availability of English-speaking, skilled doctors, plenty of clinical material, and cost-savings are obvious advantages for carrying out clinical research in India. However, challenges exist at various levels. Lack of formal training in bioethics and research methodology, heavy burden of clinical duties and sub-optimal administrative support restrict investigators. Absence of oversight of functioning of ethics committees (ECs) and lack of mechanisms for ensuring quality of ethics review heighten societal concerns about safety of participants. Conducting research on issues not relevant to local needs and failure to ensure post-trial access further enhance society's cynicism. These issues need to be tackled through capacity building, training of investigators and EC members, strengthening of EC functioning and encouraging greater community participation.