Expression and function of beta1 integrins on human eosinophils

Eosinophils preferentially accumulate at sites of chronic allergic diseases such as bronchial asthma. The mechanisms by which selective eosinophil migration occurs are not fully understood. However, interactions of cell-surface adhesion molecules on the eosinophil with molecular counterligands on endothelial and epithelial cells, and on extracellular matrix proteins, are likely to be critical during the recruitment process. One possible mechanism for selective eosinophil recruitment involves the alpha4beta 1 (VLA-4) integrin which is not expressed on neutrophils. Correlations have been found between infiltration of eosinophils and endothelial expression of VCAM-1, the ligand for VLA-4, in the lungs of asthmatic individuals as well as in late phase reactions in the lungs, nose and skin. Epithelial and endothelial cells respond to the Th2-type cytokines IL-4 and IL-13 with selective de novo expression of VCAM-1, consistent with the possible role of VCAM-1/VLA-4 interactions in eosinophil influx during allergic inflammation. Both beta 1 and beta 2 integrins on eosinophils exist in a state of partial activation. For example, eosinophils can be maximally activated for adhesion to VCAM-1 or fibronectin after exposure to beta 1 integrin-activating antibodies or divalent cations, conditions that do not necessarily affect the total cell surface expression of beta 1 integrins. In contrast, cytokines like IL-5 prevent beta 1 integrin activation while promoting beta 2 integrin function. Furthermore, ligation of integrins can regulate the effector functions of the cell. For example, eosinophil adhesion via beta 1 and/or beta 2 integrins has been shown to alter a variety of functional responses including degranulation and apoptosis. Thus, integrins appear to be important in mediating eosinophil migration and activation in allergic inflammation. Strategies that interfere with these processes may prove to be useful for treatment of allergic diseases.

A new murine model of persistent lung eosinophilic inflammation

We summarize here the main characteristics of a novel model of pulmonary hypersensitivity. Mice were immunized with a subcutaneous implant of a fragment of heat solidified chicken egg white and 14 days later challenged with ovalbumin given either by aerosol or by intratracheal instillation. This procedure induces a persistent eosinophilic lung inflammation, a marked bone marrow eosinophilia, and Th2-type isotypic profile with histopathological findings that resemble human asthma. Further, this model is simple to perform, reproducible in different strains of mice, does not require adjuvants nor multiple boosters. Based on these characteristics we propose it as a suitable murine model of allergic eosinophilic lung inflammation.

Acute hypersensitivity pneumonitis in a paint quality controller : a case report

Introduction: Isocyanates are sensitizing chemicals used in various industries such as polyurethane foam production or paint-related purposes. Acting as haptens recognized by T-lymphocytes, they can cause allergic asthma and rarely hypersensitivity pneumonitis (HP). We aim to present a case report of acute HP due to hexamethylene diisocyanate (HDI) in a paint quality controller, a profession not generally considered at a high risk for work-related Isocyanates exposure. Case report: A 30-yr-old otherwise healthy female, light smoker working as a paint quality controller developed shortness of breath, malaise, sweating and chills at workplace six hours after handling a HDI-based hardener. Upon admission to emergency department, symptoms had progressed to severe respiratory failure. HR computer tomography (HRCT) showed bilateral ground-glass attenuation without pleural effusion. Rapid clinical and radiological improvement occurred under facial oxygen supply and systemic steroid therapy. Occupational medicine investigations revealed regular handling of HDI using latex gloves without respiratory protection. Assessment at workplace showed insufficient air renewal (1.5 times per hour), inadequate local aspiration and HDI exposure at levels of 1-4.25 ppb/m3 (Swiss Occupation Exposure Limit 5 ppb/m3). Biological monitoring after identical work procedure executed by a co-worker showed HDI exposure (5.1 micrograms hexamethylene diamine/g creatinine). Resumption of work was disadvised because of the life-threatening event. Discussion: The diagnosis of occupational HP is highly supported by classical findings on imagery and typical symptoms occurring within approved latency interval, associated with rapid clinical improvement. Although neither broncho-alveolar lavage nor specific IgG diagnosis (en route) were performed during the acute episode, various blood tests managed to rule out evidence of an infection or autoimmune disease. Other causes of HP seem unlikely as the patient did not have any recurrence of symptoms since absence from work. Workplace evaluation provided significant information on HDI exposure and allowed substantial recommendations to diminish Isocyanate exposure for the 20 still healthy laboratory co-workers. Although the entryways (air or skin) and precise mechanism of toxicity remain unclear, the present case clearly shows that Isocyanates may trigger acute HP in susceptible workers in a profession not generally considered at a high risk.

Rapidly fatal poisoning with an insecticide containing rotenone.

Introduction: Rotenone is a botanical pesticide derived from extracts of Derris roots, which is traditionally used as piscicide, but also as an industrial insecticide for home gardens. Its mechanism of action is potent inhibition of mitochondrial respiratory chain by uncoupling oxidative phosphorylation by blocking electron transport at complex-I. Despite its classification as mild to moderately toxic to humans (estimated LD50, 300-500 mg/kg), there is a striking variety of acute toxicity of rotenone depending on the formulation (solvents). Human fatalities with rotenone-containing insecticides have been rarely reported, and a rapid deterioration within a few hours of the ingestion has been described previously in one case. Case report: A 49-year-old Tamil man with a history of asthma, ingested 250 mL of an insecticide containing 1.24% of rotenone (3.125 g, 52.1-62.5 mg/kg) in a suicide attempt at home. The product was not labeled as toxic. One hour later, he vomited repeatedly and emergency services were alerted. He was found unconscious with irregular respiration and was intubated. On arrival at the emergency department, he was comatose (GCS 3) with fixed and dilated pupils, and absent corneal reflexes. Physical examination revealed hemodynamic instability with hypotension (55/30 mmHg) and bradycardia (52 bpm). Significant laboratory findings were lactic acidosis (pH 6.97, lactate 17 mmol/L) and hypokalemia (2 mmol/L). Cranial computed tomography (CT) showed early cerebral edema. A single dose of activated charcoal was given. Intravenous hydration, ephedrine, repeated boli of dobutamine, and a perfusor with 90 micrograms/h norepinephine stabilized blood pressure temporarily. Atropine had a minimal effect on heart rate (58 bpm). Intravenous lipid emulsion was considered (log Pow 4.1), but there was a rapid deterioration with refractory hypotension and acute circulatory failure. The patient died 5h after ingestion of the insecticide. No autopsy was performed. Quantitative analysis of serum performed by high-resolution/accurate mass-mass spectrometry and liquid chromatography (LC-HR/AM-MS): 560 ng/mL rotenone. Other substances were excluded by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS/MS). Conclusion: The clinical course was characterized by early severe symptoms and a rapidly fatal evolution, compatible with inhibition of mitochondrial energy supply. Although rotenone is classified as mild to moderately toxic, physicians must be aware that suicidal ingestion of emulsified concentrates may be rapidly fatal. (n=3): stridor, cyanosis, cough (one each). Local swelling after chewing or swallowing soap developed at the earliest after 20 minutes and persisted beyond 24 hours in some cases. Treatment with antihistamines and/or steroids relieved the symptoms in 9 cases. Conclusion: Bar soap ingestion by seniors carries a risk of severe local reactions. Half the patients developed symptoms, predominantly swellings of tongue and/or lips (38%). Cognitive impairment, particularly in the cases of dementia (37%), may increase the risk of unintentional ingestion. Chewing and intraoral retention of soap leads to prolonged contact with the mucosal membranes. Age-associated physiological changes of oral mucosa probably promote the irritant effects of the surfactants. Medical treatment with antihistamines and corticosteroids usually leads to rapid decline of symptoms. Without treatment, there may be a risk of airway obstruction.

IPH response to NICE consultation on new indicators for Quality and Outcomes Framework (QOF)

IPH responded to the consultation on potential new indicators for the 2013/14 Quality and Outcomes Framework (QOF) in the UK. The 20 potential new indicators relate to chronic obstructive pulmonary disease (COPD), heart failure, coronary heart disease, diabetes, depression, hypertension, rheumatoid arthritis, asthma and cancer. The consultation asked people to consider whether there were any barriers to the implementation of the care described by any of the indicators; whether there were potential unintended consequences to the implementation of any of the indicators; whether there was potential for differential impact (in respect of age, disability, gender reassignment, pregnancy and maternity, race, religion or belief, sex and sexual orientation); and whether the indicators may have an adverse impact in different groups in the community.”

Longstanding health conditions among three-year-old children in the Republic of Ireland in 2011

Access audio, video and slides from the launch of the report The Institute of Public health in Ireland (IPH) produces population prevalence estimates and forecasts for a number of chronic conditions among adults. IPH has now applied the methodology to longstanding health conditions among young children across the island of Ireland. This report, based on a systematic analysis of data from the Growing Up in Ireland National Longitudinal Study of Children in the Republic of Ireland, is the first comprehensive look at longstanding health conditions among young children in Ireland. Estimated prevalence (per cent and number of cases) of longstanding health conditions among three-year-olds in the Republic of Ireland in 2011 by administrative counties/cities. The conditions are carer-reported: - "Longstanding illness, condition or disability” (where longstanding was defined as “anything that has troubled him/her over a period of time or that is likely to affect him/her over a period of time”) - Diagnosed asthma or asthma symptoms - Diagnosed eczema/any kind of skin allergy - Sight problem that required correction - Hearing problem that required correction - The estimates are based on data from the Growing Up in Ireland National Longitudinal Study of Children (www.growingup.ie) and population data. See the Chronic Conditions Hub for more details.  

Longstanding health conditions among three-year-old children in the Republic of Ireland in 2011: Executive Summary

Access audio, video and slides from the launch of the report The Institute of Public health in Ireland (IPH) produces population prevalence estimates and forecasts for a number of chronic conditions among adults. IPH has now applied the methodology to longstanding health conditions among young children across the island of Ireland. This report, based on a systematic analysis of data from the Growing Up in Ireland National Longitudinal Study of Children in the Republic of Ireland, is the first comprehensive look at longstanding health conditions among young children in Ireland. Estimated prevalence (per cent and number of cases) of longstanding health conditions among three-year-olds in the Republic of Ireland in 2011 by administrative counties/cities. The conditions are carer-reported: - "Longstanding illness, condition or disability” (where longstanding was defined as “anything that has troubled him/her over a period of time or that is likely to affect him/her over a period of time”) - Diagnosed asthma or asthma symptoms - Diagnosed eczema/any kind of skin allergy - Sight problem that required correction - Hearing problem that required correction - The estimates are based on data from the Growing Up in Ireland National Longitudinal Study of Children (www.growingup.ie) and population data. See the Chronic Conditions Hub for more details.    

Longstanding health conditions among three-year-old children in the Republic of Ireland in 2011: Factsheet

Access audio, video and slides from the launch of the report The Institute of Public health in Ireland (IPH) produces population prevalence estimates and forecasts for a number of chronic conditions among adults. IPH has now applied the methodology to longstanding health conditions among young children across the island of Ireland. This report, based on a systematic analysis of data from the Growing Up in Ireland National Longitudinal Study of Children in the Republic of Ireland, is the first comprehensive look at longstanding health conditions among young children in Ireland. Estimated prevalence (per cent and number of cases) of longstanding health conditions among three-year-olds in the Republic of Ireland in 2011 by administrative counties/cities. The conditions are carer-reported: - "Longstanding illness, condition or disability” (where longstanding was defined as “anything that has troubled him/her over a period of time or that is likely to affect him/her over a period of time”) - Diagnosed asthma or asthma symptoms - Diagnosed eczema/any kind of skin allergy - Sight problem that required correction - Hearing problem that required correction - The estimates are based on data from the Growing Up in Ireland National Longitudinal Study of Children (www.growingup.ie) and population data. See the Chronic Conditions Hub for more details.    

Get Healthwise this new year!

The Public Health Agency is encouraging people with specific health conditions to join the Healthwise scheme – a free 12 week physical activity programme to get their new year off to a healthy start. The scheme is available at registered leisure centres and Healthy Living Centres (HLCs) within the Belfast and South Eastern Health and Social Care Trust areas and is for people with certain health conditions who have been referred by their GP, nurse or other health professionals. The scheme is suitable for those with: • high blood pressure; • a body mass index (BMI) of more than 25; • asthma or chronic obstructive pulmonary disease (COPD); • diabetes; • osteoporosis; • hypertension; • coronary heart disease and associated risk factors; • anxiety; • stress; • depression.

PHA supports World No Tobacco Day

The Public Health Agency is taking the opportunity to highlight this year's World No Tobacco Day which takes place on Tuesday 31 May.In Northern Ireland, around 340,000 people aged 16 and over smoke. Smoking contributes not only to many cancers, heart disease, bronchitis and asthma, but to other illnesses, including stroke. In fact, smoking causes around 2,700 deaths per year here, all of them avoidable.The PHA is committed to saving lives by reducing the percentage of people who smoke. The PHA:works with councils to ensure smoking-related laws are enforced; funds a range of support to smokers who want to quit; educates young people to not start smoking, through programmes like 'Teenage Kicks' and 'Smokebusters'. In January this year, the PHA also launched its smoking campaign 'Things to do before you die' to encourage smokers, particularly those aged 20-49, to stop smoking.Health Minister Edwin Poots said:"Smoking is the greatest cause of preventable illness and premature death in Northern Ireland. While good progress has been made in the last number of years to reduce the number of people who smoke, more needs to be done."I would appeal to all smokers to use the wide range of support services available to make every effort to stop smoking - it is the single best step you can take to improve your health and quality of life."Mark Mc Bride, Health Improvement Manager, PHA, said "Smoking is the single greatest preventable cause of death in the world today. Across Northern Ireland there are over 600 support services for people who wish to stop smoking. These are based in GP surgeries, community pharmacies, hospitals, community centres and workplaces."From April 2010 to end March 2011 more than 1 in 10 of all adult smokers sought help from the support services and approximately half had quit after four weeks. This is a substantial - roughly 50% increase - on previous years and shows the benefit of the PHA campaigns and the dedication of the many specialists who help smokers quit."I would encourage everyone who is either thinking about quitting or ready to log on to our Want 2 Stop website www.want2stop.info or to contacting the Smokers' Helpline on 0808 812 8008 a Quit Kit free of charge."

PHA urges parents to get 'at risk' children vaccinated against seasonal flu

The Public Health Agency is urging Northern Ireland parents to make sure children in 'at risk' groups get their flu vaccine early.The message has been issued to parents and carers of children as the PHA's seasonal flu vaccination programme gets underway for 2011/12.It is very important that children with any condition that puts them more at risk of the complications of flu get the vaccine.These 'at risk' conditions include:chronic lung conditions such as asthma;chest infections that have required hospital admission;chronic heart conditions;chronic liver disease;chronic kidney disease;diabetes;lowered immunity due to disease or treatment such as steroids or cancer therapy;chronic neurological conditions such as stroke, multiple sclerosis or a condition that affects the nervous system, such as cerebral palsy;hereditary and degenerative diseases of the central nervous system or muscles.Children who attend special schools for severe learning or physical disabilities are considered to be particularly at risk, as well as those with other complex health needs.The PHA has written to principals of local special schools, as well as parents of children at these schools, to raise awareness of the importance of getting vaccinated early.Dr Richard Smithson, PHA Flu Vaccination Lead, said: "For many people, flu is a short, unpleasant illness, but it does not usually cause any serious problems. However, for others, it can have very serious complications including, in rare cases, being fatal."We have been particularly reminded over the last two winters that children with chronic neurological problems and other complex health needs are very vulnerable to these complications. We have seen children become very seriously ill and, tragically, there have even been a few deaths in children who attend special schools."For this reason, we recommend that all children who attend special schools for severe learning disability, and special schools for physical disability, are offered the flu vaccine early in the autumn, before the flu viruses start circulating."The vaccine is now available from GP surgeries and the PHA recommends that parents check arrangements with their own GP's surgery so that their child can get the jab.The earlier you get vaccinated the better, as it takes the body about 10-14 days after the jab to develop antibodies. These will then protect you against the same or similar viruses if the body is exposed to them. The vaccine contains three strains of the flu virus, which are considered the most likely to be circulating this winter, including the H1N1 (swine flu) virus."Your child needs to get the flu jab every year - the protection it gives only lasts for one winter, so even if they got it last year, they still need to get it this year," added Dr Smithson."Also, if your child has been diagnosed with flu or swine flu in the past couple of years, they will still need the jab this year as there are different types of flu that the jab will protect against. Getting the flu jab is the best way to protect your child against flu and we would strongly recommend that you arrange for them to have it."Although the vaccine gives good protection, no vaccine gives total protection, so if your child develops flu-like symptoms (such as fever, cough, aches and pains, and sore throat) you should contact your GP for advice. If your child has any of these symptoms, they should be kept at home until they feel better."For more information on seasonal flu, go to www.fluawareni.info and follow us on Facebook and Twitter.

Consultation launched on Community Development Strategy - your views matter

Issued jointly by the Health and Social Care Board and Public Health AgencyThe Health and Social Care Board and the Public Health Agency have today launched, for public consultation, a new Community Development Strategy.The consultation period will run for 12 weeks from Friday 10 June until Friday 2 September 2011.The Board and Agency want to see strong, resilient communities where everyone has good health and wellbeing, places where people look out for each other and have community pride in where they live.Residents from deprived areas in Northern Ireland experience;lower life expectancy;higher rates of emergency admission to hospital;higher rates of lung cancer;higher rates of suicide; andhigher rates of smoking and alcohol related deaths.The kinds of health and social care issues which can be improved by community development approaches include depression; isolation; falls amongst elderly people; child protection; teenage pregnancy; childhood asthma; postnatal depression; drug and alcohol abuse; and ultimately also long term conditions such as obesity, diabetes and cancer.The Board and Agency seek a number of benefits from implementing this strategy such as; a reduction in health and wellbeing inequalities, which also means addressing the social factors that affect health; strengthening partnership working with service users, the community and voluntary sectors and other organisations; strengthening families and communities; supporting volunteering and making best use of our resources.John Compton, Chief Executive of the Health and Social Care Board said: "Community development is an important way to improving health and wellbeing - driving a message that 'prevention is better than cure' between different groups and communities, and helping to ensure the most effective use of the health and social care budget."Now more than ever we need to work in partnership with families and communities to achieve better health and wellbeing for those living in Northern Ireland.No one organisation can meet this challenge on its own and strong partnerships are needed. "Chief Executive of the Public Health Agency, Eddie Rooney added: "Every health and social care organisation should incorporate a community development approach into their programmes, and this strategy assists them to do so."The Board and Agency have jointly held pre-consultation workshops over the past few months across Northern Ireland on their Community Development Strategy and have engaged widely with the community and voluntary sectors. We are now keen to receive feedback from individuals, families and the wider community as your views are very important to us - they will help shape the future of community development across the province," he said.The draft Community Development Strategy, as well as information on how you can respond, can be found in the attachments below.

The PHA message is clear for World COPD Day - smoking is bad for your lungs

In 2011, 31,574 people were registered as having Chronic Obstructive Pulmonary Disease (COPD) in Northern Ireland. The most common cause of COPD is smoking and to mark this year's World COPD day, which takes place on Wednesday 16 November, the Public Health Agency is encouraging all smokers to make a decision to stop smoking today and reduce their risk of developing the disease.COPD refers to a group of diseases which includes emphysema, chronic bronchitis, and in some cases asthma. With COPD, the airways in the lungs become damaged, causing them to become narrower, therefore restricting airflow and thus making it harder to breathe. The most common symptoms of COPD are breathlessness, wheezing, abnormal sputum (a mix of saliva and mucus in the airway), and a chronic cough often mistaken for a 'smokers' cough'. Symptoms can range from mild to severe, depending upon how advanced the disease is. In advanced cases, daily activities, such as walking up a short flight of stairs, can become very difficult.There is no cure for COPD. Stopping smoking is the single most effective wayto reduce your risk of developing COPD and avoid any further damage to the lungs. Gerry Bleakney, Head of Health and Social Wellbeing Improvement, PHA, said: "Smoking causes the lining of the airways to become inflamed and damaged and is the biggest cause of COPD. The risk of developing COPD increases the more an individual smokes and the longer they smoke. "The good news is that making changes to your lifestyle can reduce your risk of developing COPD. Stopping smoking reduces the risk of developing COPD and also slows down its progression. There is support available to help you quit and I would encourage everyone thinking about stopping smoking to log on to our Want 2 Stop website www.want2stop.info and order a 'Quit Kit' free of charge. Alternatively contact the Smokers' Helpline on 0808 812 8008 for help on planning to stop smoking or to find out where your nearest Stop Smoking Service is. "The Health Minister Edwin Poots said: "The impact of living with COPD can place a considerable strain on the lives of those suffering from the condition and their families. I understand that most smokers want to quit but it is not always easy to succeed and that several attempts are frequently necessary. I would therefore urge all smokers on world COPD day, to make that commitment to stop smoking. Professional help and support are readily available. There are almost 650 smoking cessation services provided all over Northern Ireland, mostly in community pharmacies, but also in GP surgeries, hospitals, community halls and schools."

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Pulmonary involvement in Fabry disease has received less attention than the effects of the disease on the kidneys, nervous system or heart. However, data from FOS -the Fabry Outcome Survey - are now helping to elucidate the pulmonary manifestations of Fabry disease. Twenty-three patients out of a cohort of 67 analysed in FOS have been identified with airway obstruction, as defined by a ratio of forced expiratory volume in 1 second to forced vital capacity of less than 0.7. This prevalence is much greater than would be expected in the general population, with the main risk factors appearing to be increasing age and male gender. Spirometric analysis has revealed that the airway obstruction is clinically much more similar to chronic obstructive pulmonary disease than to asthma. Although little is known about the anatomical changes responsible for airway obstruction in patients with Fabry disease, airway wall hyperplasia and/or fibrosis are potential causes. Treatment of patients with moderate or severe airway obstruction should include inhaled bronchodilators, and individuals who smoke should be encouraged to stop. Further studies and future analyses of FOS data should determine whether enzyme replacement therapy is able to help or prevent the pulmonary manifestations of Fabry disease.

Schistosoma mansoni infection modulates the immune response against allergic and auto-immune diseases

Chronic Schistosoma mansoni infection leads to a type 2-immune response with increased production of interleukin (IL-10). Evidence indicates chronic exposure to S. mansoni down regulates the type 1 immune response and prevents the onset of Th1-mediated diseases such as multiple sclerosis, diabetes mellitus and Cronh's disease. Furthermore, our own studies have revealed that chronic exposure to S. mansoni also down regulates atopic disease, Th2-mediated diseases. Our studies show an inverse association between the skin prick test reactivity and infection with S. mansoni and show the severity of asthma is reduced in subjects living in an endemic area of S. mansoni. Moreover, we hypothesize the mechanisms involved in the modulation of inflammatory response in atopic individuals, is likely dependent on IL-10 production, an anti-inflammatory cytokine elevated during helminth infections. Patients with asthma and helminth infections produced less IL-5 than patients with asthma without helminth infections, and this down regulation could, in part, be mediated by IL-10. In conclusion, helminthic infections, through induction of regulatory mechanisms, such as IL-10 production, are able to modulate the inflammatory immune response involved in the pathology of auto-immune and allergic disease.