Parasitic helminth infections and the control of human allergic and autoimmune disorders

The profile of global health today presents a striking reciprocal distribution between parasitic diseases in many of the world’s lower-income countries, and ever-increasing levels of inflammatory disorders such as allergy, autoimmunity and inflammatory bowel diseases in the more affluent societies. Attention is particularly focused on helminth worm parasites, which are associated with protection from allergy and inflammation in both epidemiological and laboratory settings. One mechanistic explanation of this is that helminths drive the regulatory arm of the immune system, abrogating the ability of the host to expel the parasites, while also dampening reactivity to many “bystander” specificities. Interest has therefore heightened into whether helminth parasites, or their products, hold therapeutic potential for immunological disorders of the developed world. In this narrative review, progress across a range of trials is discussed, together with prospects for isolating individual molecular mediators from helminths that may offer defined new therapies for inflammatory conditions

Development of allergy in children. I. Association with virus infections.

Children born into allergic families, with two allergic parents, are at high risk of developing allergy within the first 5 years of life. In order to observe possible external factors in the sensitization process, a prospective study of 13 such children was done, in which serial clinical and immunologic observations were made at 3- to 6-month intervals over a period of 1 to 4 yr. Eleven of these children are now clinically allergic; 5 have asthma. Immunologic evidence for allergic sensitization was observed in these 11 children by RAST, antigen-induced leukocyte histamine release, lymphoblastogenesis, and rise in serum IgE. Upper respiratory infections (URI) occurred in these 11 allergic children 1 to 2 months prior to the onset of allergic sensitization. In 10 of these 11 URI children, complement-fixing antibodies to viruses (parainfluenza, RSV, CMV) increased in the same blood samples in which immunologic allergic sensitization was first evidenced. This coincidence suggests that certain viruses may contribute to the allergic sensitization process

Allergic Disorders in Africa and Africans: Is it Primarily a Priority?

In Africa, the burden of some diseases has been a problem for centuries. The spectrum of African diseases includes allergies, infections, nutritional deficiencies, and natural disasters. Efforts made by scientists to search for possible means of disease control have been outstanding; however, in some infections, solutions are still out of reach. In disease control programs, it might be worthwhile to pay attention to the most striking diseases than merely follow a holistic approach. This short review tackles the problems of allergy and allergens in Africa as compared with other disease burdens that may suggest the need for a more balanced approach based on priority

Regulation of the host immune system by helminth parasites

Helminth parasite infections are associated with a battery of immunomodulatory mechanisms, which impact all facets of the host immune response to ensure their persistence within the host. This broad-spectrum modulation of host immunity has intended and unintended consequences, both advantageous and disadvantageous. Thus the host may benefit from suppression of collateral damage during parasite infection, and from reduced allergic, autoimmune and inflammatory reactions. However, helminth infection can also be detrimental in reducing vaccine responses, increasing susceptibility to co-infection, and potentially reducing tumor immunosurveillance. In this review we will summarize the panoply of immunomodulatory mechanisms used by helminths, their potential utility in human disease, and prospective areas of future research

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

Chronic rhinosinusitis with nasal polyps in older adults : clinical presentation, pathophysiology, and comorbidity

Purpose of Review Chronic rhinosinusitis and nasal polyps (CRSwNP) is a common condition that significantly affects patients' life. This work aims to provide an up-to-date overview of CRSwNP in older adults, focusing on its aging-related clinical presentations, pathophysiology, and comorbidity associations including asthma. Recent Findings Recent large population-based studies using nasal endoscopy have shown that CRSwNP is a mostly late-onset disease. Age-related changes in physiologic functions, including nasal epithelial barrier dysfunction, may underlie the incidence and different clinical presentations of CRSwNP in older adults. However, there is still a paucity of evidence on the effect of aging on phenotypes and endotypes of CRSwNP. Meanwhile, late-onset asthma is a major comorbid condition in patients with CRSwNP; they frequently present with type 2 inflammatory signatures that are refractory to conventional treatments when they are comorbid. However, as they are more commonly non-atopic, causative factors other than classical atopic sensitization, such as Staphylococcus aureus specific IgE sensitization, are suggested to drive the type 2 inflammation. There are additional comorbidity associations in older patients with CRSwNP, including those with chronic otitis media and head and neck malignancy. Age is a major determinant for the incidence and clinical presentations of CRSwNP. Given the heterogeneity in phenotypes and endotypes, longitudinal investigations are warranted to elucidate the effects of aging on CRSwNP

An adolescent girl with signs and symptoms of anaphylaxis and negative immunologic workup: a case report.

BackgroundThe increasing incidence of allergies and allergic reactions among children and adults has become a major public health concern. The etiology of allergic reactions can often be confirmed based on a detailed history and supportive testing. However, there are cases where the underlying factors are more complex and difficult to identify.Case presentationHere we present the case report of a 14-year-old Caucasian  girl with weight loss and a 3-year history of reported angioedema culminating in five intensive care unit admissions over the course of 2.5 months. Her initial clinical presentation included hypotension, dyspnea, and reported facial edema, but allergy and immunological workup were negative. A psychiatric workup identified an eating disorder with food restriction, comorbid major depression, obsessive compulsive disorder, and posttraumatic stress disorder. A close collaboration between Adolescent Medicine, Allergy and Immunology, and Psychiatry helped disentangle medical from psychiatric problems, including fluoxetine medication effects, as well as develop a treatment plan that was acceptable to the family. The angioedema was ultimately diagnosed as factitious disorder.ConclusionsThis patient's treatment highlights the importance of a multidisciplinary team approach, a multifactorial etiology that needed to be addressed by multiple specialists, and the importance of long-term treatment and support

Contact-allergy time

The most commonly used techniques for the in vivo evaluation of the cellular immune response include intracutaneous testing with microbial recall antigens or sensitization with neoantigens. The reliability of these tests for the individual patient usually is low due to the lack of standardization and quantification. Moreover only the efferent branch of the immune response can be judged. The dinitrochlorobenzene-contact allergy time (DNCB-CAT) is a quantitative approach for the assessment of the cellular immune response. 2% DNCBointment is applied on the upper arm in a 1 cm2 area. On the following days patch-testing with 0.05% DNCB-ointment is done on the homolateral forearm in alternating localizations till an allergic contact dermatitis reaction appears. As assessed in patients with malignant melanoma (MM, n=\\5) and with lymphoproliferative disorders (LD, η = 25), the DNCB-CAT correlates with the age of the patients and can be expressed by a formula given by the age (years) χ factor (MM = 0.16; LD = 0.17) + constant figure (MM = 5.5; LD = 4.3). There was no significant difference between the two groups or subgroups investigated. By DNCB-CAT quantitative analysis of the cellular immune response in vivo is possible. It is an appropriate model for further investigations of the cellular immunity under different clinical, histological, prognostic, and therapeutic aspects

Occupational asthma: a review.

Occupational asthma is the most common form of occupational lung disease in the developed world at the present time. In this review, the epidemiology, pathogenesis/mechanisms, clinical presentations, management, and prevention of occupational asthma are discussed. The population attributable risk of asthma due to occupational exposures is considerable. Current understanding of the mechanisms by which many agents cause occupational asthma is limited, especially for low-molecular-weight sensitizers and irritants. The diagnosis of occupational asthma is generally established on the basis of a suggestive history of a temporal association between exposure and the onset of symptoms and objective evidence that these symptoms are related to airflow limitation. Early diagnosis, elimination of exposure to the responsible agent, and early use of inhaled steroids may play important roles in the prevention of long-term persistence of asthma. Persistent occupational asthma is often associated with substantial disability and consequent impacts on income and quality of life. Prevention of new cases is the best approach to reducing the burden of asthma attributable to occupational exposures. Future research needs are identified