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Novel Biologicals for the Treatment of Allergic Diseases and Asthma

Tan HT, Sugita K, Akdis CA

Curr Allergy Asthma Rep, 2016 10;16(10):70.
PMID: 27613653 DOI: 10.1007/s11882-016-0650-5

PURPOSE OF REVIEW: The development of biological therapies has rapidly progressed during the last few years, and major advances were reported for the treatment of allergic diseases, such as atopic dermatitis, allergic rhinitis, urticaria, food allergy, and asthma. Here, we review biologicals targeting the type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, natural killer T cells, mast cells, basophils, and epithelial cells, such as IL-4, IL-5, IL-13, IL-31, tumor necrosis factor alpha (TNF-α), and thymic stromal lymphopoietin (TSLP).
RECENT FINDINGS: The biologicals that have been currently approved for asthma are omalizumab targeting IgE and reslizumab and mepolizumab targeting interleukin (IL)-5. Many other monoclonal antibodies are currently in various phases of clinical development. The new biological therapies for allergic diseases will eventually be tailored to the endotypes of these diseases and the identification of novel biomarkers. Further development of novel biologicals for the treatment of allergic diseases and asthma will be possible upon improved understanding of mechanisms of allergic diseases. Accordingly, further refinement of endotypes of allergen-specific and non-specific type 2 immune response and related inflammatory mediators is needed for optimal treatment of allergic diseases.

Matched MeSH terms: Hypersensitivity/physiopathology
Fulltext Contribution of early nutrition on the development of malnutrition and allergic diseases in the first year of life: a study protocol for the Mother and Infant Cohort Study (MICOS)

Woon FC, Chin YS, Ismail IH, Chan YM, Batterham M, Abdul Latiff AH, et al.

BMC Pediatr, 2018 Jul 18;18(1):233.
PMID: 30021541 DOI: 10.1186/s12887-018-1219-3

BACKGROUND: Nutrition and environmental factors are essential for the education of the neonatal immune system. Epidemiological evidence has shown that malnutrition and allergic diseases that occur during early childhood share similar protective and risk factors. This paper describes the protocol of the Mother and Infant Cohort Study (MICOS), which aims to determine the contribution of early nutrition to the development of malnutrition and allergic diseases in infants' first year of life.
METHODS: MICOS is a prospective cohort study conducted at selected government health clinics in two states, namely Selangor and Wilayah Persekutuan Kuala Lumpur, Malaysia. Women in their third trimester of pregnancy are recruited into the study and their infants will be followed-up at 3, 6, and 12 months of age. Information on prenatal factors including socio-demographic characteristics, obstetric history, pre-pregnancy body mass index, gestational weight gain, smoking, family history of allergic diseases, maternal dietary intake and sunlight exposure during pregnancy are obtained through face-to-face interviews. Postnatal factors including dietary intake, sun exposure, and anthropometric measurements of the mothers, as well as feeding practices, dietary intake, anthropometric measurements, and development of allergic diseases of the infants are assessed at each follow-up. Blood samples are collected from the mothers in the third trimester to determine 25-hydroxyvitamin D levels as well as from the infants at age 12 months to determine atopic sensitisation.
DISCUSSION: The concept of developmental origins of health and disease (DOHaD) which emphasises on the role of early life environments in shaping future health and disease susceptibility in adulthood has gained a huge interest in recent years. The DOHaD paradigm has influenced many fields of research including malnutrition and allergic diseases. While findings from the developed countries remain controversial, such studies are scarce in developing countries including Malaysia. The present study will determine the cause and effect relationship between early nutrition and the development of malnutrition and allergic diseases in infants' first year of life.

Matched MeSH terms: Hypersensitivity/physiopathology*
Fulltext Effects of Air Pollution and the Introduction of the London Low Emission Zone on the Prevalence of Respiratory and Allergic Symptoms in Schoolchildren in East London: A Sequential Cross-Sectional Study

Wood HE, Marlin N, Mudway IS, Bremner SA, Cross L, Dundas I, et al.

PLoS One, 2015;10(8):e0109121.
PMID: 26295579 DOI: 10.1371/journal.pone.0109121

The adverse effects of traffic-related air pollution on children's respiratory health have been widely reported, but few studies have evaluated the impact of traffic-control policies designed to reduce urban air pollution. We assessed associations between traffic-related air pollutants and respiratory/allergic symptoms amongst 8-9 year-old schoolchildren living within the London Low Emission Zone (LEZ). Information on respiratory/allergic symptoms was obtained using a parent-completed questionnaire and linked to modelled annual air pollutant concentrations based on the residential address of each child, using a multivariable mixed effects logistic regression analysis. Exposure to traffic-related air pollutants was associated with current rhinitis: NOx (OR 1.01, 95% CI 1.00-1.02), NO2 (1.03, 1.00-1.06), PM10 (1.16, 1.04-1.28) and PM2.5 (1.38, 1.08-1.78), all per μg/m3 of pollutant, but not with other respiratory/allergic symptoms. The LEZ did not reduce ambient air pollution levels, or affect the prevalence of respiratory/allergic symptoms over the period studied. These data confirm the previous association between traffic-related air pollutant exposures and symptoms of current rhinitis. Importantly, the London LEZ has not significantly improved air quality within the city, or the respiratory health of the resident population in its first three years of operation. This highlights the need for more robust measures to reduce traffic emissions.

Matched MeSH terms: Respiratory Hypersensitivity/physiopathology
Fulltext Cholecystokinin hyperresponsiveness in functional dyspepsia

Chua AS, Keeling PW

World J Gastroenterol, 2006 May 07;12(17):2688-93.
PMID: 16718754 DOI: 10.3748/wjg.v12.i17.2688

Functional dyspepsia (FD) is a common disorder of yet uncertain etiology. Dyspeptic symptoms are usually meal related and suggest an association to gastrointestinal (GI) sensorimotor dysfunction. Cholecystokinin (CCK) is an established brain-gut peptide that plays an important regulatory role in gastrointestinal function. It inhibits gastric motility and emptying via a capsaicin sensitive vagal pathway. The effects on emptying are via its action on the proximal stomach and pylorus. CCK is also involved in the regulation of food intake. It is released in the gut in response to a meal and acts via vagal afferents to induce satiety. Furthermore CCK has also been shown to be involved in the pathogenesis of panic disorder, anxiety and pain. Other neurotransmitters such as serotonin and noradrenaline may be implicated with CCK in the coordination of GI activity. In addition, intravenous administration of CCK has been observed to reproduce the symptoms in FD and this effect can be blocked both by atropine and loxiglumide (CCK-A antagonist). It is possible that an altered response to CCK may be responsible for the commonly observed gastric sensorimotor dysfunction, which may then be associated with the genesis of dyspeptic symptoms.

Matched MeSH terms: Food Hypersensitivity/physiopathology