Noninvasive Ventilation: New Clinical Practice Guidelines

New clinical guidelines for use of noninvasive ventilation in critical care settings are published in CMAJ (Canadian Medical Association Journal).

The use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure by mask has increased significantly among acutely ill patients. A growing body of literature and variations in practice in recent years have necessitated the development of new clinical practical guidelines to help manage patients with acute respiratory distress or failure.

The guidelines were created by the Canadian Critical Care Trials Group/Canadian Critical Care Society Noninvasive Ventilation Guidelines Group. They address the use of noninvasive ventilation in the postoperative setting, in immunocompromised patients, in patients being weaned from conventional mechanical ventilation and in patients at high risk of respiratory failure after removal of breathing tube.

Noninvasive positive pressure ventilation should be the first choice in patients with chronic obstructive pulmonary disease (COPD) or cardiogenic pulmonary edema. It can be used postoperatively or in people with compromised immune systems.

“Implementation of these guidelines may require clinician education, additional health care personnel, organizational change or additional resources (equipment or beds with cardiopulmonary monitoring) to ensure safe and appropriate application of noninvasive positive-pressure ventilation and continuous positive airway pressure,” writes Dr. Sean Keenan, Royal Columbian Hospital, with coauthors.

“Strategies for the implementation of these guidelines should be developed for each relevant clinician group (physicians in different clinical areas and with different levels of training and expertise, respiratory therapists and nurses),” they conclude.

In a related commentary, Dr. Andrew Bersten from Flinders Medical Centre in Adelaide, Australia, writes “many factors appear to influence the effective implementation of noninvasive ventilation. These factors include an experienced team of health care staff able to provide 24-hour service and detailed attention to mask interface and leaks, choice of equipment, ventilator settings, inspired oxygen levels, glottic function and clearance of secretions.”

“For these guidelines to change clinical practice, they have to be supported by appropriate education, implementation and review. Helping clinicians know when and when not to use noninvasive ventilation is perhaps the most important role for these guidelines,” he concludes.

Source:
Kim Barnhardt

Canadian Medical Association Journal

New Publication Supports Asthma Management Strategy Of Achieving And Maintaining Control With The Regular Use Of Seretide

New data from the Gaining Optimal Asthma controL (GOAL) study published in the June edition of thePrimary Care Respiratory Journal (link here) entitled ‘Improvement in asthma endpoints when aiming for Total Control: a comparison of salmeterol/fluticasone propionate versus fluticasone propionate alone’ demonstrates that aiming for guideline-derived control in people with asthma results in sustained, clinically relevant improvements across a range of individual asthma outcomes, with superior improvements seen with Seretide (salmeterol/fluticasone propionate) compared with fluticasone propionate alone1.

According to Professor Ashley Woodcock, University of Manchester, UK, “These greater improvements in specific endpoints with the regular use of Seretide compared with fluticasone propionate are very relevant to patients. In particular, these data demonstrate that, compared with fluticasone propionate, treatment with Seretide results in 85 more symptom-free days per year-equivalent to nearly three additional symptom-free months a year for patients previously experiencing symptoms despite treatment with inhaled corticosteroids1.”

Professor Woodcock continued, “This new publication confirms the recent recommendation in international guidelines from the Global Initiative for Asthma (GINA) that asthma patients should be assessed according to the level of control and then treated with regular dosing to achieve and maintain asthma control, and that superior, clinically meaningful outcomes and sustained symptom prevention are achieved with an inhaled corticosteroid/ long acting ??2-agonist combination, such as Seretide, compared with inhaled corticosteroids alone2.”

International asthma guidelines, updated in November 2006, state that the goal of asthma treatment is to achieve and maintain prolonged control2, and the GOAL study confirmed for the first time that this guideline-defined control can be a reality for a wide range of patients with asthma, with 41% achieving Total Control of symptoms with the regular use of Seretide3. GOAL was a one-year, stratified, randomised, double-blind, parallel-group study comparing the efficacy and safety of individualised, predefined, stepwise increases with Seretide versus fluticasone propionate alone in achieving two composite measures of asthma control: Well Controlled (the primary endpoint) and the even more stringent definition of Total Control.

The original publication of the GOAL study reported composite measures of asthma control3; but in this paper3 the relative magnitude of changes in specific endpoints-morning peak expiratory flow (PEF), asthma symptoms, symptom-free days, night-time awakenings, rescue ??2-agonist use, and severe exacerbations- were not included. This information would increase understanding of the benefits of a preventive therapeutic strategy that aims to control asthma completely1. The new publication of the GOAL data1 found that:

1. Aiming for Total Control of asthma by both stepping up and sustaining regular, stable treatment resulted in patients in both treatment arms achieving substantial benefits in individual outcomes1

2. However, Seretide was superior to fluticasone propionate alone in improving mean morning peak expiratory flow (PEF) (p

WFP Increases Mali Appeal to Help 175,000 Children Under Five

The United Nations World Food Programme today increased its emergency appeal for Mali in order to feed an additional 175,000 children in the hardest-hit parts of the country and avoid it slipping into a humanitarian crisis similar to neighbouring Niger.

WFP revised its appeal for Mali to US$13.6 million from US$7.4 million to feed the children under the age of five until the end of the year in the areas of Gao on the Niger river, Timbouctou, Kidal in the northeast and Kayes and Koulikoro near the border with Mauritania.

WFP was already targeting a total of 450,000 people in the most critical areas of Mali, which like Niger has a recurring problem with food shortages and associated malnutrition, especially at the height of the three-month annual lean season before the first harvests in October.

“The international community must respond now to avoid a humanitarian crisis,” said Pablo Recalde, WFP’s Mali Country Director. “This cyclical food shortage in an already burdened country like this will only further weaken the livelihoods of rural families unless we act immediately.”

“Mali is doing its best under dire conditions to help its people”, Recalde said. But across the Sahel, where drought and locusts in 2004 have made an always difficult lean season even more arduous, even the best efforts will fall short if they do not receive international support.”

Recent assessments show that the 175,000 children are at risk of malnutrition. WFP is already targeting 450,000 people to improve the ability of farmers to cope with poor production cycles. The most vulnerable receive food through Food-For-Work projects and the creation of cereal banks.

Ranked among the four least-developed countries in the world, Mali is subject to structural food insecurity stemming from poverty, lack of rain, rudimentary farming techniques, desertification and precarious health and sanitation conditions. Last year’s locust invasions, which were the worst in 15 years, further weakened Mali’s ability to grow enough food.

In March, the Malian government forecast 1.2 million people would face food shortages. In close collaboration with humanitarian partners, the government has released some 30,000 metric tons of food from its National Emergency Reserves to help stave off a crisis.

WFP has already released 3,700 tons of food to be distributed to those most in need.

WFP’s main aims are to help people who have exhausted their normal survival strategies and have begun to sell their productive stocks and migrate in search of work and to contribute to maintaining productive potential for next year’s harvest. WFP also supports the government’s capacity to respond to future emergencies by rebuilding the National Emergency Reserves.

To date, WFP has received contributions of US$2.7 million to its emergency operation in Mali, leaving a shortfall of US$10.9 million. It is vital that the remaining funds are provided as soon as possible so that food can be purchased within the region to provide an immediate response.

WFP’s has received confirmed contributions from the European Commission (US$808,000), Luxembourg (US$625,000), Belgium (US$484,000) and Turkey (US$300,000) and multilateral funds US$500,000).

To date, WFP’s emergency operation IN NIGER – seeking US$57.6 million – has received US$24.8 million – a current shortfall of 57 percent.

WFP is the world’s largest humanitarian agency: each year, we give food to an average of 90 million poor people to meet their nutritional needs, including 56 million hungry children, in at least 80 of the world’s poorest countries. WFP — We Feed People.

WFP Global School Feeding Campaign – For just 19 US cents a day, you can help WFP give children in poor countries a healthy meal at school – a gift of hope for a brighter future.
For more information please contact (email address: firstname.lastnamewfp):

Ramin Rafirasme
WFP/Mali
Tel. 223 222 2045
Italian Mob. +39 340 581 6350

Peter Smerdon
WFP/Nairobi
Tel. 254 20 622 179
Mob. +254 733 528 911

Christiane Berthiaume
WFP/Geneva
Tel. +41-22-9178564
Mob. +41-797743821

Caroline Hurford
WFP/Rome
Tel. +39-06-65132430
Mob +39-348 1325018

Gregory Barrow
WFP/London,
Tel. +44-20-72409001
Mob +44-7968-008474

WORLD FOOD PROGRAM

3 Million Central Africans Targeted For Massive Polio Vaccination Campaign

On November 12th the first wave of a 3-million-people polio immunization campaign starts in Ponte Noire, as well as in the Department of Kouilou, Republic of Congo, and 16 districts in the Democratic Republic of Congo, and Angola, the World Health Organization (WHO), Africa announced today. WHO says individuals of all ages are being targeted in this campaign.

A polio outbreak was confirmed in the Republic of Congo on November 4th. Of the 226 reported cases of AFP (acute flaccid paralysis) 97 have died; what WHO describes as “an unusually high mortality”. Four AFP cases have been confirmed as polio so far. Patients with flaccid paralysis typically experience weakness, possibly paralysis and reduced muscle tone – without an obvious cause. When the signs and symptoms come on suddenly, it is called acute flaccid paralysis (AFP). AFP is the most common sign of acute polio.

The majority of people becoming ill are aged from 15 to 29 years, an example that populations that have not been exposed to full immunization are particularly vulnerable. Vaccinating everyone, regardless of age, is aimed at stemming the spread of the disease by raising general immunity levels.

Dr Luis Sambo, WHO Regional Director for Africa, said:
“Every man, every woman, every child will be immunized irrespective of their past immunization status. This way we can be assured that everybody is reached, including young adults, whose immunity may be low.”
A hospital in Pointe Noire reported the first case of AFP on October 1st. The majority of cases were reported between 11th and 31st October, WHO informs. Between the 18th and 24th October the number of cases being reported peaked.

Prof. Georges Moyen, Minister of Health and Population of the Republic of Congo, said:
“The Government has a good assessment of the situation; it is worrying. Partners and resources are being mobilized to implement an appropriate response and to ensure a good take-up by the population.”
Dr Gianfranco Rotigliano, Regional Director for West and Central Africa, UNICEF, explained:
“We have to stem this fast-moving outbreak. The overriding priority is to vaccinate all people to prevent more cases and deaths as quickly as possible. We are at a critical juncture and stopping polio in Africa requires our absolute commitment”.
So far, $48 million, 1.7 million oral polio vaccine doses, and several team of experts have been deployed to assist in the campaign – these came from a joint venture involving Rotary International, CDC (USA), and UNICEF. Denmark has sent another 5 million doses of oral polio vaccines, which should arrive at their destination on November 12th.

Ambroise Tshimbalanga Kasongo, Chairman, Rotary’s Africa PolioPlus Committee, said:
“Rotary has mobilized emergency funding to respond to this outbreak. With a quick response, we can stop the disease from further spread.”
WHO says the rest of Congo’s population will be covered from 18th to 22nd November, and then again during two spells in December, which will also include some parts of neighboring countries.

Polio, caused by the poliovirus, is an extremely contagious virus specific to humans. The virus typically enters the environment in the feces of an infected individual. In areas where sanitation is poor, the virus easily and rapidly spreads via the fecal-oral route, through contaminated water or food. Humans in direct contact with an infected person can also become ill.

Signs and symptoms, such as neck and back stiffness, abnormal reflexes and breathing and swallowing difficulties will usually alert a doctor to the possibility of polio. A doctor who suspects polio will need to test samples from either the patient’s throat, stool or cerebrospinal fluid to confirm a diagnosis.

Source: WHO

WHO Sending Medicines For 60 000 Affected By Congo Crisis

The World Health Organization and Italy will be sending 10 tonnes of medical supplies to help the tens of thousands of people affected by the ongoing insecurity in eastern Democratic Republic of Congo. Intensive efforts are needed to prevent the spread of communicable diseases among the fleeing population and to treat the physical trauma caused by the violence.

The World Health Organization is coordinating the health response to the emergency, and today convened an urgent meeting of partners including UN agencies, international and national nongovernmental organization and government health providers. The meeting was held to identify the urgent health needs confronting those in the affected areas.

The Government of Italy and WHO are sending a shipment of essential medicines that can assist 60 000 people for one month, along with drugs and supplies to treat diarrhoeal diseases, malaria and trauma injuries. WHO has already provided emergency medical supplies from its stocks to NGOs operating in Goma, the main city in eastern DRC.

WHO has also helped re-establish activities of the blood bank at Goma’s main hospital, where staffing shortages and insecurity had hampered its operations. Staffing and financial support have been provided by WHO to ensure the bank’s operations.

Major health concerns in the region include:

– The widespread threat of violence that translates into deadly wounds, sexual violence, and mental and psychosocial traumas;
– Limited or no access to food that can result in acute malnutrition;
– Limited access to water and appropriate sanitation, which can cause outbreaks of diarrhoeal diseases;
– A lack of shelter and consequent acute respiratory infections;
– Low vaccine-coverage, combined with mass displacement, will contribute to the spread of measles, a highly fatal illness in such emergency situations;
– Loss of access to reproductive health services contributes to high numbers of maternal and neonatal deaths;
– Limited essential drugs contributes and restricted access the health facilities contributes to increased illness and death;
– The breakdown of the disease surveillance system in the face of the growing risk of outbreaks.

World Health Organization
who.int

Bone’s Proactive Arthritis Drug Attacks The Cause Of Arthritic Pain

Bone Medical Limited’s (ASX-BNE) revolutionary rheumatoid arthritis drug, which attacks the cause of sufferers’ pain rather than dealing with the resultant pain, is to undergo advanced testing in the state-of-the-art facility at London’s world-renowned Kennedy Institute of Rheumatology.

The new research follows on from positive results in animal studies.

The most effective treatment to date, pioneered by Kennedy Institute Director, Professor Marc Feldmann, and Sir Ravinder Maini, is an antibody that mops up the cause of the painful inflammation, TNF, which is produced by the cells after they have been stimulated.

However, Bone Medical has adopted a more proactive approach of developing the drug, TNF down-regulator candidate BN006, which reduces pain by blocking the response to the stimulus that leads to the production of the unwanted TNF.

“The Kennedy Institute’s “cognate assay” in vitro testing system mimics immunological processes in the joints of rheumatoid arthritis (RA) sufferers and is the closest that researchers have ever come to reproducing the conditions found in arthritic joints”, the assay’s lead developer, Professor Fionula Brennan, said.

“The test uses human cells taken from patients suffering from the disease and mirrors closely the way in which the production of TNF is stimulated”, she said.

“Bone’s TNF down-regulator is a second-generation approach to the treatment of rheumatoid arthritis and has tremendous promise because of its potential to be administered orally and at a low cost. More research is important to make sure this project progresses rapidly to the clinic.” Professor Feldmann said.

About Bone Medical Limited

Bone Medical Limited is an international biopharmaceutical development company positioned to exploit the growing market in the treatment of bone disease particularly in osteoporosis and arthritis. Bone has a portfolio of biopharmaceutical development projects for the treatment of bone disease including,

Osteoporosis

– Capsitonin™ oral calcitonin

– oral parathyroid hormone

– bone cell regulators BN005 & BN008

Arthritis

– TNF re/gulators BN006

– joint protection & collagen tolerance BN007

bonemedical

New Research Raises Hope That Autism Effects May Be Reversible

A new study by researchers at The George Washington University School of Medicine and Health Sciences’ Department of Biochemistry and Molecular Biology raises hope that autism may be more easily diagnosed and that its effects may be more reversible than previously thought. Researchers have identified potentially removable chemical tags (called “methyl groups”) on specific genes of autistic individuals that led to gene silencing. They also observed these changes in cells derived from blood, opening the way to molecular screening for autism using a blood test.

Valerie Hu, Ph.D., professor of Biochemistry and Molecular Biology, with a GW graduate student and collaborators from the City of Hope, have identified chemical changes in DNA taken from cells of identical twins and sibling pairs, in which only one of the twins or siblings was diagnosed with autism. The researchers compared the genes that showed changes in DNA tagging (called “methylation”) with a list of genes that showed different levels of expression (or gene “activity”) from these same individuals. The amount of protein produced by two genes that appear on both lists in the cerebellum and frontal cortex of autistic and control subjects was studied, and the researchers found that both proteins, as predicted by the observed increase in DNA tagging, were reduced in the autistic brain.

These outcomes suggest that blocking the chemical tagging of these genes with drugs that prevent the methylation process may reverse symptoms of autism if the specific genes can be targeted, and demonstrate the feasibility of using more easily accessible cells from blood (or other non-brain tissues) for diagnostic screening.

“As the mother of a now 22-year-old son with an autism spectrum disorder, I hope that our studies, as well as those of others, will lead to therapies that are designed to address specific deficiencies that are caused by autism, thus improving the lives of affected individuals,” said Dr. Hu. “Since autism is very diverse in the array of symptoms present in any given individual, it is first necessary to be able to identify specific deficits in each individual in order to design and then prescribe the best treatment.”

The research is highlighted in the study, titled “Global Methylation Profiling of Lymphoblastoid Cell Lines Reveals Epigenetic Contributions to Autism Spectrum Disorders and a Novel Autism Candidate Gene, RORA, Whose Protein Product is Reduced in Autistic Brains,” was recently published in the Federation of American Societies for Experimental Biology (FASEB) Journal.

“For far too long, autism research has been side-tracked by the cranky notion that it’s caused by the MMR vaccine,” said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. “Studies like this, which define genetic and epigenetic changes in discrete subgroups of the autism spectrum, offer real hope that effective treatments and accurate diagnosis are closer at hand.”

Source: George Washington University

WFP Pre-Positions Food Stocks to Assist Needy Afghans

Ahead of the winter freeze, the United Nations World Food Programme (WFP) has started pre-positioning food supplies for nearly half a million impoverished Afghans who will be cut off from markets once the cold weather sets in.

About 23,000 metric tonnes of food – including wheat, pulses, oil and salt – will be distributed to nearly half a million people throughout Afghanistan in the coming weeks.

“Winter is a brutal time for poor and needy Afghans. There are literally tens of thousands of people trapped by heavy snowfalls and freezing winds, and they have absolutely no way of getting food. These are the people that WFP is determined to assist,” said Charles Vincent, WFP Representative in Afghanistan.

“Winterization is WFP’s largest annual operation in Afghanistan and requires enormous planning. Food must be trucked to some of the remotest and desolate parts of the country, and then distributed to the needy before the cold weather hits,” said Vincent.

WFP uses creative food aid schemes to support development, including food for the construction of roads, wells and other community assets, food for people attending training and food for school children. Poor people who are unable to join these projects receive special food rations.

Deliveries have already commenced in Badakhshan in northeastern Afghanistan where winter normally begins as early as September. Around 5,900 tonnes of various food commodities have been allocated to remote and mountainous districts.

Some WFP operations in Badakshan have been hampered by the poor state of roads and bridges, which were destroyed by heavy snowfalls and devastating floods in recent months. To alleviate blockages, WFP will provide food to workers fixing the road between Hawzi Shah and Koofab districts. The new road will provide immense benefits to surrounding communities and enable WFP to truck food aid to the needy. Winter food stocks will be stored in Ragh and Ishakashim districts while the road is repaired.

Similarly, WFP food convoys to communities in the Pamir Mountains have been affected by the loss of a bridge in Baharak, which was washed away by floods last week. Efforts by the local government and NGOs are ongoing to divert the road so that WFP can dispatch food to remote and high altitude areas before the weather turns cold.

In inaccessible areas of northern Baghlan province, where many roads are in bad condition or do not exist, WFP has managed to provide biscuits and food to the poor. A total of 2,400 tonnes of biscuits will be dispatched to an estimated 85,500 people in the province.

Parts of central Bamyan province are so remote they are only accessible for five months a year. To assist poor people living in these areas, WFP will preposition close to 7,000 tonnes of food commodities in September and October to tide them over the long harsh winter.

In the western region, WFP will deliver 1,668 tonnes of food in Ghor and Badghis provinces. In these two provinces, there are about 14 districts targeted for assistance.

Last year, WFP delivered aproximately 21,300 tonnes of food to 525,500 people throughout Afghanistan as part of its winterization operations.

WFP’s overall operational budget in Afghanistan is US$341 million from April 2003 to September 2005. To date WFP still faces a shortfall of 15 percent of total funds required.

Recent donations to WFP’s operations in Afghanistan include: the United States (US$ 31.6 million), India (US$ 19.4 million), European Commission (US$ 1.9 million), Saudi Arabia (US$ 1.2 million), the Netherlands (US$ 1.1 million), Switzerland (US$ 397,000), Poland (US$ 161,000), and private donors from Japan (US$ 150,000), and the United Kingdom and Canada (US$ 102,000).

WFP is the world’s largest humanitarian agency: in 2003 we gave food aid to a record 104 million people in 81 countries, including 56 million hungry children.

WFP Global School Feeding Campaign – For just 19 US cents a day, you can help WFP give children in poor countries a healthy meal at school –a gift of hope for a brighter future.

World Food Program

CHEST Journal Highlights, March 2006

MANY ASTHMATICS VIEW ASTHMA AS TEMPORARY, NOT CHRONIC, CONDITION

New research shows that many adults with asthma view their condition as temporary, believing they have asthma only when they have symptoms. Researchers from Mount Sinai School of Medicine, New York, NY, and Rutgers University, New Brunswick, NJ, surveyed 198 adult patients hospitalized with asthma regarding their asthma beliefs and behaviors and characteristics related to their beliefs. More than half of the patients indicated that they only had asthma when they were experiencing symptoms, a belief researchers labeled as, “no symptoms, no asthma.” In contrast, 40 percent believed they had chronic asthma, while 6 percent indicated they had asthma most or some of the time. When asked about the lifelong nature of asthma, 20 percent of patients believed they would not always have asthma, and 15 percent expected the doctor to cure them of asthma. Male patients, those over 65 years old, and patients with no usual place of care were more likely to hold the “no symptoms, no asthma” belief. The belief also was associated with one-third lower odds of adherence to asthma medications during asymptomatic times. Researchers suggest that asthma interventions tailored to an individual’s beliefs and behaviors may help with asthma management. The study appears in the March issue of CHEST, the peer-reviewed journal of the American College of Chest Physicians.

GLUCOSE CONTROL YIELDS SIGNIFICANT SAVINGS FOR HOSPITALS
Intensive management of glucose levels in hospitalized critically ill patients can lead to decreased utilization of hospital resources and substantial cost savings. Researchers from Stamford Hospital, Stamford, CT, analyzed the economic impact of an intensive glycemic management protocol by comparing the clinical outcomes of 800 patients admitted to the intensive care unit (ICU) prior to the established protocol, with 800 patients admitted to the ICU after the protocol. Clinical outcomes reported in a previous study indicated a 29.3 percent decrease in hospital mortality for treated patients, as well as decreased ICU length of stay and ventilator days. In addition, treated patients showed decreases in all major areas of resource utilization, including laboratory, pharmacy, and diagnostic imaging. The annualized adjusted total cost savings amounted to $1.3 million, and the mean adjusted cost saving per patient was $1,580. Researchers believe that extending their findings to large numbers of ICUs could have a major impact on national health-care expenditures. The study appears in the March issue of CHEST, the peer-reviewed journal of the American College of Chest Physicians.

PATIENTS ON MEDICAID FACE UNIQUE BARRIERS TO ASTHMA CARE
Medicaid-insured families face unique barriers to asthma management, including income level and insurance limitations. Researchers from the University of Michigan, Ann Arbor, MI, and the University of Utah, Salt Lake City, UT, evaluated focus group responses from 36 primary caregivers of children with asthma who were currently using or previously used Medicaid insurance. Of the participants, 23 (64 percent) were African-American, 32 (89 percent) were the biological mother, and 25 (69 percent) reported an annual income of less than $20,000. Overall, caregivers demonstrated a high level of asthma knowledge but also identified unique barriers to asthma management, including difficulty maintaining continuity of care due to physician participation in Medicaid programs; concerns about possible differences in asthma care from health-care providers due to their Medicaid insurance status; and the inability to afford asthma supplies. A specific gap also was seen in the caregiver’s level of self-efficacy to control exposure to asthma triggers, monitor the child’s symptoms, and modify medications based on asthma symptoms. To overcome these barriers, researchers suggest that physicians employ strategies that demonstrate to patients and caregivers that decisions for care are not based on the type of patient insurance. The study appears in the March issue of CHEST, the peer-reviewed journal of the American College of Chest Physicians.

Contact: Jennifer Stawarz
jstawarzchestnet
American College of Chest Physicians

Yale Study Shows Why Cigarette Smoke Makes Flu, Other Viral Infections Worse

A new study by researchers at Yale School of Medicine could explain why the cold and flu virus symptoms that are often mild and transient in non-smokers can seriously sicken smokers. Published in the Journal of Clinical Investigation, the study also identified the mechanism by which viruses and cigarette smoke interact to increase lung inflammation and damage.

Until recently, scientists haven’t been able to explain why smokers have more exaggerated responses to viral infections. Smokers have been more likely than non-smokers to die during previous influenza epidemics and are more prone to chronic obstructive pulmonary disease (COPD). Furthermore, children who are exposed to second-hand smoke have more severe responses when infected with respiratory synctial virus.

The prevailing view has been that cigarette smoke decreases anti-viral responses. But the Yale researchers-lead author Jack A. Elias, M.D., the Waldermar Von Zedtwitz Professor of Medicine and chair of internal medicine at Yale School of Medicine, and first author Min-Jong Kang, M.D., associate research scientist-found the opposite to be true.

Their experiments showed that the immune systems of mice exposed to cigarette smoke from as little as two cigarettes a day for two weeks overreacted when they were also exposed to a mimic of the flu virus. The mice’s immune systems cleared the virus normally but the exaggerated inflammation caused increased levels of tissue damage.

“The anti-viral responses in the cigarette smoke exposed mice were not only not defective, but were hyperactive,” said Elias. “These findings suggest that smokers do not get in trouble because they can’t clear or fight off the virus; they get in trouble because they overreact to it.”

“It’s like smokers are using the equivalent of a sledge hammer, rather than a fly swatter, to get rid of a fly,” said Elias.

The team found that mice with viral infections that had been exposed to cigarette smoke had accelerated emphysema and airway scarring. Elias and his team also defined the signaling pathway that mediates this exaggerated innate immune response.

“If the exaggerated responses are verified in human studies, it will be the first explanation for why viral infections are more serious in smokers,” said Elias. “Once verified, we can find ways to prevent the destruction of lung tissue and the higher illness and death among smokers.”

“These studies have identified molecular pathways that can explain how cigarette smoke exposure and viral infections interact to make breathing problems worse in diseases like COPD,” said James P. Kiley, director, Division of Lung Diseases of the National Heart, Lung, and Blood Institute. “With further research, these findings may even lead to more effective drug treatments for COPD.”

Other authors on the study included Chun Geun Lee, Jae-Young Lee, Charles S. Dela Cruz, Zhijian J. Chen and Richard Enelow.

Citation: The Journal of Clinical Investigation, Vol. 118, No. 8 (August 2008)

Yale School of Medicine
medicine.yale