Asthma, Author Interviews / 26.07.2016
Loss of ADAM33 suppresses features of asthma, suggesting targeting ADAM33 as a potential new asthma therapy
MedicalResearch.com Interview with:
[caption id="attachment_26488" align="alignleft" width="167"]
Dr. Hans Michael Haitchi[/caption]
Hans Michael Haitchi, MD, MMed (INT)
PhD, PD, FHEA, PGcert
Associate Professor in Respiratory Medicine
Clinical and Experimental Sciences
Faculty of Medicine, University of Southampton
United Kingdom
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: It is estimated that 300 million people worldwide suffer from asthma with 1 in 10/11 (USA/UK) children and 1 in 12 (USA & UK) adults suffering from the disorder. In children asthma is the most common long-term medical condition.
ADAM33 is an asthma gene. Small changes in the gene have been associated with increased twitchiness of the airways (bronchial hyperresponsiveness), loss of lung function in children and decline in lung function in the general population.
ADAM33 makes an enzyme, which is attached to cells in the airway muscles. When the enzyme loses its anchor to the cell surface, it is prone to going rogue around the lung causing poorer lung function in people who have asthma.
Our research, published in The Journal of Clinical Investigation (JCI) Insight, analysed human tissue samples and mice. Our experiments suggest that the human rogue ADAM33 protein is increased and enzymatically active in asthma. Furthermore, ADAM33 protein initiates airway remodelling (more muscle and blood vessels around the airways) without causing any inflammation in early life. However, when we switch off ADAM33 or prevent it from going rouge, the features of asthma - airway remodelling (more muscle and blood vessels around the airways), twitchiness and inflammation - will be reversed or reduced.
These findings identify ADAM33 as a novel target for disease modifying therapy in asthma.
Dr. Hans Michael Haitchi[/caption]
Hans Michael Haitchi, MD, MMed (INT)
PhD, PD, FHEA, PGcert
Associate Professor in Respiratory Medicine
Clinical and Experimental Sciences
Faculty of Medicine, University of Southampton
United Kingdom
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: It is estimated that 300 million people worldwide suffer from asthma with 1 in 10/11 (USA/UK) children and 1 in 12 (USA & UK) adults suffering from the disorder. In children asthma is the most common long-term medical condition.
ADAM33 is an asthma gene. Small changes in the gene have been associated with increased twitchiness of the airways (bronchial hyperresponsiveness), loss of lung function in children and decline in lung function in the general population.
ADAM33 makes an enzyme, which is attached to cells in the airway muscles. When the enzyme loses its anchor to the cell surface, it is prone to going rogue around the lung causing poorer lung function in people who have asthma.
Our research, published in The Journal of Clinical Investigation (JCI) Insight, analysed human tissue samples and mice. Our experiments suggest that the human rogue ADAM33 protein is increased and enzymatically active in asthma. Furthermore, ADAM33 protein initiates airway remodelling (more muscle and blood vessels around the airways) without causing any inflammation in early life. However, when we switch off ADAM33 or prevent it from going rouge, the features of asthma - airway remodelling (more muscle and blood vessels around the airways), twitchiness and inflammation - will be reversed or reduced.
These findings identify ADAM33 as a novel target for disease modifying therapy in asthma.


Dr. James Kiley[/caption]
Dr. James P. Kiley Ph.D
National Institutes of Health Bethesda
Maryland
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Kiley: While a higher proportion of children have asthma compared to adults, the disease is limited to childhood for many individuals who appear to be unaffected as adults. Regardless of whether asthma continues into adulthood or reoccurs during adulthood, the impact of childhood asthma on lung function later in life is unclear. This study demonstrated that in children with chronic persistent asthma at the age of 5-12 years who continued to be followed through their early twenties, 75% of them had some abnormality in the pattern of their lung growth. The study examined the trajectory of lung growth, and the decline from maximum growth, in a large cohort of persons who had persistent, mild-to-moderate asthma in childhood and determined the demographic and clinical factors associated with abnormal patterns of lung growth and decline.
Dr. Michael McGeachie[/caption]
Michael McGeachie, PhD
Instructor in Medicine
Harvard Medical School
Channing Division of Network Medicine
Brigham and Women's Hospital
MedicalResearch.com: What is the background for this study?
Dr. McGeachie: In asthma, and in general but particularly in asthma, a person’s level of lung function has a big impact on his or her quality of life, level of respiratory symptoms and complications, and general morbidity. In asthma, low lung function leads to greater severity and frequency of asthma symptoms. Asthma is a common childhood illness, affecting 9-10% of children. Many children grow out of asthma as they become adults, but other asthmatics remain effected through adulthood, which can lead to a lifetime of respiratory symptoms and chronic airway obstruction, including chronic obstructive pulmonary disease (COPD).
If you consider lung function longitudinally, throughout development, plateau, and decline, different people and different asthmatics tend to exhibit different patterns of lung function. Healthy, non-asthmatic people tend to have a period of rapid lung function increase in adolescence, a plateau of lung function level in their late teens and early 20s, and starting around 25 or so a slow, gradual decline of lung function that continues throughout old age. We call this Normal Growth of lung function. However, some people exhibit Reduced Growth, where they don’t reach their expected maximum lung function for a person of the same age, sex, height, and race. Others can show Early Decline, who might reach a normal maximum but then begin to decline immediately without a plateau or with a truncated plateau. We hypothesized that these patterns, Reduced Growth and Early Decline, might have different baseline indicators, precursors, outcomes, and risk of developing COPD.
Prof. Christian Virchow[/caption]
Prof Dr. med. J. Christian Virchow, FRCP, FCCP, FAAAA
University of Rostock, Germany
What is the background for this study? What are the main findings?
Dr. Virchow: House Dust mite related allergic asthma is a very frequent chronic disease. Allergen Immunotherapy (AIT) for this condition in asthma has not been well studied and subcutaneous treatment has been associated with (systemic, potentially serious) side effects. Aim of the study was to investigate, if sublingual AIT can improve a patient relevant endpoint, namely reduce the frequency of exacerbations (primary endpoint: time to first exacerbation compared to placebo) .





Prof. Bisgaard[/caption]
MedicalResearch.com Interview with:
Hans Bisgaard, MD, DMSc
Professor of Pediatrics
The Faculty of Health Sciences
University of Copenhagen
Head of the Copenhagen Prospective Studies on Asthma in Childhood
University of Copenhagen and Naestved Hospital
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Bisgaard: Vitamin D deficiency has become a common health problem in westernized societies, possibly caused by a more sedentary indoor lifestyle and decreased intake of vitamin D containing foods. Vitamin D possesses a range of immune regulatory properties, and it has been speculated that vitamin D deficiency during pregnancy may affect fetal immune programming and contribute to asthma pathogenesis. Asthma often begins in early childhood and is the most common chronic childhood disorder. Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring, but the preventive effect of
Dr. Augusto Litonjua[/caption]
MedicalResearch.com Interview with:
Augusto A. Litonjua, MD, MPH
Associate Professor
Channing Division of Network Medicine
and Division of Pulmonary and Critical Care Medicine
Department of Medicine
Brigham and Women's Hospital
Harvard Medical School
Boston, MA 02115 USA
Medical Research: What is the background for this study? What are the main findings?
Response: Vitamin D deficiency has been hypothesized to contribute to the asthma and allergy epidemic. Vitamin D has been shown to affect lung development in utero. However, observational studies have shown mixed results when studying asthma development in young children. Since most asthma cases start out as wheezing illnesses in very young children, we hypothesized that vitamin D supplementation in pregnant mothers might prevent the development of asthma and wheezing illnesses in their offspring. We randomly assigned 881 pregnant women at 10 to 18 weeks' gestation and at high risk of having children with asthma to receive daily 4,000 IU vitamin D plus a prenatal vitamin containing 400 IU vitamin D (n = 440), or a placebo plus a prenatal vitamin containing 400 IU vitamin D (n = 436). Eight hundred ten infants were born during the study period, and 806 were included in the analyses for the 3-year outcomes. The children born to mothers in the 4,400 IU group had a 20% reduction in the development of asthma or recurrent wheeze compared to the children born to mothers in the 400 IU group (24% vs 30%, respectively; an absolute reduction of 6%). However, this reduction did not reach statistical significance (p=0.051).
Dr. Mairead Black[/caption]
MedicalResearch.com Interview with:
Dr Mairead Black MBChB, MRCOG, MSc
Research Fellow, Wellcome Trust
Clinical Lecturer, Obstetrics and Gynaecology
School of Medicine and Dentistry, Division of Applied Health Sciences
University of Aberdeen
Aberdeen Maternity Hospital, Cornhill Road
Aberdeen AB25 2ZD
Medical Research: What is the background for this study?
Dr. Black: The current thinking is, if a baby is exposed to labour, then it is also exposed to ‘good bacteria’ that mothers pass on during the birth, and they are also exposed to a degree of natural stress at the time of birth that might make them more resistant to developing future illnesses.
The World Health Organisation formerly recommended that no more than 15 percent of deliveries should be C-sections. However rates in some countries have soared – China and Brazil have rates in excess of 50%, whilst in the UK the figure is 26% with almost half of these being planned in advance.
The main purpose of this study was to explore whether health outcomes in children up to very early adulthood differ according to how they are delivered and whether avoiding labour entirely, i.e. via a planned C-section, could put children at a disadvantage compared to those delivered vaginally or by emergency C-section, where most will have been exposed to labour. The study analysed data from over 300,000 births between 1993 and 2007 across Scotland, using routinely collected data from seven linked databases.










