Asthma may affect more than your ability to breathe, it may also make you more prone to developing psychological problems, new research suggests.

People with asthma are more than twice as likely to have depression or anxiety as people who don’t have the chronic airway disease, according to a report in the March issue of the journal Chest.

To make matters worse, the study authors found that when rates of serious psychological distress went up, health-related quality-of-life scores went down.

“The prevalence of serious psychological distress was 2.5 times higher among adults with asthma, and as serious psychological distress increased, health-related quality went down. So, asthma makes quality of life worse and serious psychological distress makes quality of life worse, and together they synergistically make quality of life even worse,” said study senior author Dr. David Callahan, a medical epidemiologist at the U.S. Centers for Disease Control and Prevention and the U.S. Public Health Service in Atlanta.

Study author Emeka Oraka said these findings may apply to other chronic diseases, such as diabetes, and that serious psychological distress may make it harder for people to manage these diseases properly.

“Any kind of mental distress impedes your ability to manage the disease well, whether it’s asthma, diabetes or something else,” said Oraka, who’s an Oak Ridge Institute for Science and Education fellow at the CDC.

Oraka noted that the findings should raise a red flag for clinicians. “Serious psychological distress is a powerful predictor of quality of life, and even more so in the presence of chronic illness,” he said. “Don’t disregard the importance of mental health in the quality of life of patients with chronic illness.”

For the study, the researchers reviewed data from 186,738 adults who had participated in the U.S. National Health Interview Survey between 2001 and 2007. From this database, they discovered that the rate of asthma was 7 percent.

Among all of the study participants, the average prevalence of serious psychological distress was 3 percent, but in people with asthma, the rate of serious psychological distress was 7.5 percent, the researchers found.

Adults with asthma who had other chronic conditions, a history of smoking or alcohol use, and those with a lower socioeconomic background had a greater risk of having serious psychological distress, according to the study.

Oraka said that the study wasn’t able to tease out whether asthma is a cause of serious psychological distress or whether asthma medications may make serious psychological distress more likely, or whether people with serious psychological distress may be more likely to have asthma or to report having asthma.

“This study found an association, but no causation,” Oraka said.

Dr. Jennifer Appleyard, chief of allergy and immunology at St. John Hospital and Medical Center in Detroit, said it was troubling to see that “the prevalence of anxiety or mental distress is higher in asthmatics than normal, and this is something we need to look for and try to prevent and address it.”

She said the subject definitely warrants further study, and that she would like to see a study that assesses asthma more objectively. In the current study, asthma was identified by the study participants, who were asked if a doctor had ever told them they had asthma, and if they still had asthma.

But, “even if you have mild asthma, it’s definitely an anxiety-provoking diagnosis,” Appleyard added.

“As with any chronic disease, asthma needs to be managed carefully by the patients, and serious psychological distress can get in the way of people managing their own asthma,” explained Callahan. “Clinicians need to ask about psychological symptoms in people with asthma, and they need to treat both psychological distress and asthma.”

Technorati Tags: Asthma, asthma and depression, mental distress, psychological distress

A new label warning will caution users of four widely used asthma drugs to avoid using these medicines as a sole or long-term means of symptom control, the U.S. Food and Drug Administration announced Thursday.

The medicines are GlaxoSmithKline’s Advair and Serevent, Novartis’s Foradil and AstraZeneca’s Symbicort. All are in the class of drugs known as long-acting beta agonists (LABAs). Serevent and Foradil are single-agent LABAs while Advair and Symbicort also contain an inhaled corticosteroid.

LABAs should no longer be used alone in treating adults and children, the FDA said. In making its decision, the agency cited studies that found that using the drugs alone can actually increase the severity of asthma, leading to hospitalizations and even death.

The drugs should only be used for the shortest time possible, until asthma symptoms are under control, and be “discontinued, if possible, once asthma control is achieved,” the agency said in a statement. People should then switch to another medication to maintain symptom control, the FDA said.

“We think the overall public health benefit is to reduce the use of LABAs,” Dr. John Jenkins, director of FDA’s Office of New Drugs in the Center for Drug Evaluation and Research, said during an early afternoon press conference Thursday.

“As we weighed the risks against the benefit of the drug, we recognized that there is still benefit for these products in patients who aren’t adequately controlled on asthma controller medications,” Jenkins said. “We wanted to maintain availability of these products, while also encouraging the safe use of the product.”

According to Jenkins, most people should only require an inhaled corticosteroid to control their symptoms.

LABAs work to improve breathing and reduce asthma symptoms by relaxing the lung’s airway muscles.

One expert said the announcements don’t signal a radical departure for asthma care, although the recommendation to stop LABA use as soon as possible could bring problems for some.

“This could complicate care in certain settings,” said Dr. Norman Edelman, chief medical officer for the American Lung Association. “This will require careful tailoring of treatment to individuals’ disease and circumstance. Physicians should be aware of new guidelines and do so.”

The makers of the four drugs will have to add this information to their product labels:

* These drugs must be used along with other asthma medications such as an inhaled corticosteroid.
* The drugs should only be used in people whose asthma is not controlled by other drugs.
* They should be used for the shortest time possible to bring asthma under control, and then other asthma drugs should replace them.
* Children and adolescents who need these drugs should use only combination drugs that contain both a LABA and a corticosteroid.

Although the drugs are also approved for use in chronic obstructive pulmonary disease (COPD), this warning only applies to their use by asthma patients, the agency said.

In addition, the FDA is requiring that manufacturers of these drugs do more studies to determine the safety of the medications when combined with inhaled corticosteroids.

One industry representative said her company supported the FDA move.

“AstraZeneca supports the efforts of the FDA to share additional benefit/risk information within the product label and will work closely with the FDA to make the appropriate changes,” said company spokeswoman Dana Settembrino. “AstraZeneca is confident in the positive benefit-risk profile of Symbicort, which has been demonstrated by extensive clinical trial data and through use by millions of patients worldwide.”

Thursday’s announcement follows an FDA advisory panel decision in December 2008. The panel found that the risks linked to single-agent Serevent and Foradil outweighed their benefits for children and adults. At the time, Advair and Symbicort were excluded from that decision.

Technorati Tags: advair, Asthma Drugs, Asthma Drugs Warning, Serevent

THURSDAY, Nov. 19 (HealthDay News) — People’s genetic makeup has been shown to affect how they respond to asthma medications, but a new study finds that many people respond well to a particular combination treatment regardless of their genes.

However, the study did find a difference in response among blacks.

The drug combo in question combines the long-acting beta-agonist salmeterol (Serevent) and moderate doses of an inhaled corticosteroid. The genes in question relate to a receptor in the body that is crucial to the effectiveness of asthma bronchodilators.

Some research has suggested that a variation in these genes can affect how people respond to the drugs. The researchers tested that theory in 87 people who had two types of the genetic variation — B16 Arg/Arg or B16 Gly/Gly.

They found that lung function did not differ overall in the groups, although there was some difference in blacks. The results are reported online Nov. 19 in The Lancet.

“These findings provide reassurance that, in the general population, patients should continue to be treated with long-acting beta-agonists plus moderate-dose inhaled corticosteroids irrespective of B16 genotype,” the researchers wrote.

However, there are still questions to be answered, particularly involving blacks’ response to salmeterol, they said.

Technorati Tags: asthma bronchodilators, asthma combo, salmeterol, Serevent

Women with asthma may notice that their asthma symptoms get worse at certain times of the month. Now, a new study confirms that fluctuating female hormone levels appear to affect airway inflammation, but oral contraceptives might help ease those changes.

In women who were not using birth control pills, the study found that increased levels of estrogen were associated with decreased levels of exhaled nitric oxide — indicating decreased airway inflammation. In these same women, increased levels of progesterone were associated with increased levels of exhaled nitric oxide, indicating increased airway inflammation.

However, birth control pills lessen dramatic hormone fluctuations, and researchers didn’t find differences in asthma symptoms throughout the month for women who took them.

“This study is a first step in looking at the relationship between hormones and asthma,” said the study’s lead author, Dr. Piush Mandhane, an assistant professor of pediatric pulmonology at the University of Alberta in Canada. The findings might be of use in managing asthma among premenopausal women, the researchers said.

“Among women not on oral contraceptives, we did have changes in exhaled nitric oxide that were related to estrogen and progesterone levels. We didn’t have an association with estrogen and progesterone in women on oral contraceptives,” said Mandhane.

Results of the study are published in the November issue of the journal Chest.

Mandhane said that because many women report a change in asthma symptoms related to menstrual cycles, it’s often assumed that there is an association. But, he said, the relationship between hormonal fluctuations and asthma symptoms hasn’t been well-studied.

The current study included 17 women. Eight were on birth control pills that contained estrogen and progesterone. The average age of the women using oral contraceptives was 25.5, while the average age of the women not taking birth control pills was 37.5.

Three of the women in the group not on birth control reported experiencing menstrual-cycle related asthma prior to the study, while just one woman in the birth control group did.

The researchers gathered daily information about symptoms and conducted blood tests to measure estrogen and progesterone levels, performed spirometry (a lung function test) and took measurements of exhaled nitric oxide. They also conducted allergy tests, via skin pricks every other day.

They found that women who didn’t take birth control pills had an average exhaled nitric oxide level of 48.2 parts per billion (ppb), while those on oral contraceptives had an average level of 27 ppb. In women who weren’t taking oral contraceptives, each increase in estrogen levels was associated with a decrease in exhaled nitric oxide, while each increase in progesterone was associated with an increase in exhaled nitric oxide. That means when progesterone levels are elevated (before menstruation), asthma symptoms are likely to be worse.

Progesterone increases also aggravated allergy symptoms, with more severe allergic reactions evident on skin prick tests when progesterone levels were elevated.

The researchers didn’t find any statistically significant differences in allergic reactions during the month for women on birth control pills.

Mandhane said that “birth control works by flattening out the fluctuations in hormone levels,” and that’s likely why there weren’t many differences in asthma symptoms for women taking birth control pills.

“Hormones do play a role,” said Mandhane, “and women need to be aware that there’s a potential relationship between their asthma symptoms and their menstrual cycles.”

Dr. Jennifer Appleyard, chief of allergy and immunology at St. John Hospital and Medical Center in Detroit, said that this study “lends credence to the fact that asthma is affected by hormones. This is definitely not something women should just write off. It’s not just all in their minds.”

But she also pointed out that this was a small study, and that the women in each group were very different from each other. “There were a lot of older women in one group who took more asthma medication. It’s not really comparing apples to apples,” she said.

Because birth control pills can have some serious side effects, Appleyard said she would not advise someone to go on oral contraceptives just to help their asthma. However, if a woman notices a difference in her symptoms throughout her menstrual cycle, she may want to talk to her doctor about increasing her asthma medications during that particular time in her cycle, she said.

Technorati Tags: airway inflammation, asthma symptoms, birth control pills, menstrual cycles, oral contraceptives

CHICAGO (Reuters) – An experimental asthma treatment that uses heat to reduce airway constriction provided some relief from severe asthma that is poorly controlled with medications, U.S. researchers said on Monday.

They said the Alair device, made by privately held Asthmatx Inc of Sunnyvale, California, cut the rates of extreme asthma attacks by 32 percent and reduced trips to the emergency room by 84 percent in patients with severe asthma.

Patients missed fewer days of work or school because of asthma symptoms and had more symptom-free days compared with people who received a placebo, according to results of the late-stage clinical trial, which was presented at a meeting of the American Thoracic Society in San Diego.

The Alair device uses a thin tube to gently heat the walls of the lung’s air passages, killing off some of the muscle tissue to reduce narrowing of the airways.

“In asthma, what happens is these patients develop enlarged smooth muscles surrounding their bronchial tubes. That contributes to asthma attacks. The idea is to decrease that,” Dr. Mario Castro of Washington University in St. Louis, who led the study, said in a telephone interview.

Castro and colleagues tested the device in 297 patients with severe asthma in six countries.

Researchers split the patients into two groups. Two-thirds got three treatments with the Alair device, and the rest received a placebo treatment, in which the heat was not applied.

The patients were followed closely for a year.

Overall, 79 percent of patients who got the experimental treatment improved.

Castro said the other group also improved, but the treatment group showed a statistically significant improvement.

“I think it’s a meaningful advance,” Castro said. “We have very limited options for these patients, who are very disabled.”

He said all of the patients were taking inhaled drugs combining a corticosteroid and a long-acting beta-agonist, such as in GlaxoSmithKline Plc’s best-selling drug Advair. But they were still not getting adequate relief.

The only other option for these patients is taking Xolair or omalizumab, Novartis AG’s drug for treating allergic asthma, but not everyone has asthma caused by allergies, Castro said.

Asthmatx Inc is seeking U.S. Food and Drug Administration approval for the device, Castro said, and a decision is expected this fall. The treatment has been approved in Europe.

(Editing by Maggie Fox)

Technorati Tags: advair, allergic asthma, asthma symptoms, asthma treatment, asthma treatment device, experimental asthma treatment, severe asthma

A number of products that block the histamine receptor (anti-histamines) have been developed to treat the allergies that trigger attacks in those suffering from atopic asthma attacks. These include hydroxyzine (Atarax, Vistaril) and its breakdown product cetirizine (Zyrtec). These medications cause sleepiness. Other side effects include dry mouth and urinary retention, and more rarely, confusion, nightmares, nervousness, and irritability. Chlorpheniramine (Chlor-trimeton), cyproheptadine (Periactin), and diphenhydramine (Benadryl) are other older antihistamines. They can be associated with anti-cholinergic side effects (dry mouth, confusion, urinary retention), in addition to the side effects of Atarax.

The so-called second-generation antihistamines supposedly cause less drowsiness than the older products, but this is more hype than hope. They claim to specifically block the H-1 antihistamine receptor, and include fexofenadine (Allegra), loratadine (Claratin), and azelastine (Astelin). Side effects are similar to the older antihistamines. Drowsiness with all of the antihistamines is dose dependent. It is best to start with a low dose and work up.

One of the best selling allergy medications on the market is desloratadine (Clarinex). Clarinex is a newer generation anti-histamine medication that is marketed as a magic bullet for allergies. However what most people don’t know is that Clarinex is merely an old drug, loratadine (Claritin), marketed by the drug company as new and improved. However Clarinex doesn’t add anything to Claritin (other than more money for the coffers of its manufacturer, since Clarinex is still on patent). Clarinex is merely a metabolite (breakdown product) of its precursor, Claritin. That means that 20 minutes after you take Claritin, you will be getting Clarinex, but you’ll be paying much less for it than if you took Clarinex. Folks have been getting Clarinex for years, even though they didn’t know it, every time they took Claritin. The company patented the metabolite of their original product, and then did a misleading study where they compared differing doses of the two medications, coming to the erroneous conclusion that Clarinex was less sedating than the old drug. This was misleading because if a drug causes sedation, then higher doses of the drug will cause more sedation, so if you are not comparing the same doses of the drug, you are not making a fair comparison. This allowed them to promote Clarinex, which costs much more than the old drug that went off patent, and which in 2004 was bringing in close to a billion dollars a year in sales. Claritin and Clarinex as far as you are concerned are the same drug; so take Claritin and save some money.

Over the counter (OTC) epinephrine inhalers such as Primatene Mist are commonly used for the treatment of mild asthma. Over 115 million Primatene Mist inhalers have been sold over the past 20 years. These inhalers, however, are not as benign as they appear. About 20% of patients using OTC inhalers have severe asthma that needs medical care. Unfortunately, many asthma patients delay professional medical treatment while they use their OTC inhalers, often due to a lack of health insurance, to the point where it may be too late. OTC inhalers can also increase heart rate, and should not be used in patients with heart or thyroid disease. Thirteen deaths, mostly cardiovascular, have been reported to be associated with the use of OTC inhalers over the last 20 years. If you have a history of chronic asthma or a history of hospitalization for asthma you should not use OTC inhalers. If asthma symptoms do not resolve in 20 minutes after using an OTC inhaler, you should seek emergency treatment. Delaying medical treatment when you are using OTC inhalers may contribute to the overall severity and chronic nature of the disease over the lifetime.

Prescription short acting bronchodilators (²-2 agonists) are inhaled and promote dilation of airways. The most commonly prescribed inhalers are albuterol (Proventil) and levalbuterol (Xopenex). Side effects include tremors, jitters, and nervousness. There are no known long-term side effects. These medications are designed for temporary relief. If you find yourself using them often or with increasing frequency that means your asthma is getting worse and you need further evaluation by a doctor.

Asthma patients can also be treated with steroids in pill form for a short period of time. Corticosteroids can inhibit growth in children and decrease bone mineral density, although growth inhibition is reversible. Steroids suppress the immune response, increasing risk of infection, and decrease bone mineral density. Other side effects of steroids include low blood sugar, changes in consciousness, nauseas, seizures, or in rare cases death. You can also develop symptoms like Cushing’s Disease (an excess production of cortisol in the body). These include deposits of fat on the upper back and face, high blood pressure, diabetes, slow wound healing, osteoporosis, cataracts, acne, muscle weakness, ulcers, thinning of the skin, and mood changes. When patients are treated for a long period of time, deaths from adrenal insufficiency have occurred with transfer from oral to inhalation steroids, especially during stressors like surgery. You should not be on steroids for long periods of time.

Non-allergic asthma is a chronic problem, and needs to be treated somewhat differently than allergic asthma, which may come and go with avoidable triggers and seasonal changes. Chronic asthma sufferers are more at risk for fatalities if they are not treated.

Corticosteroids

Patients with chronic asthma should be treated with inhaled corticosteroids. These include fluticasone (Flonase, Flovent), beclomethasone (Qvar, Beconase, Vancenase), flunisolide (Aerobid), budesonide (Rhinocort, Pulmicort), and triamcinolone (Azmacort, Nasacort). Inhaled corticosteroids have the same side effects of systemic steroids, but to a much lesser degree. Corticosteroids can inhibit growth in children and decrease bone mineral density, although growth inhibition is reversible. Steroids suppress the immune response, increasing risk of infection, and decrease bone mineral density. Other side effects of steroids include low blood sugar, changes in consciousness, nauseas, seizures, or in rare cases death. You can also develop symptoms like Cushing’s Disease (an excess production of cortisol in the body). These include deposits of fat on the upper back and face, high blood pressure, diabetes, slow wound healing, osteoporosis, cataracts, acne, muscle weakness, ulcers, thinning of the skin, and mood changes. Studies have shown that inhaled corticosteroids (budesonide) can be used intermittently; there is no advantage to regular use of these medications.

Theophylline (theodur, slophyllin) and the related aminophylline drugs are xanthine derivatives related to caffeine that act to dilate the bronchi. Aminophylline can cause rash in some people. They can be given either orally or intravenously for asthma emergencies. Toxicity results in seizures, irregular heartbeats, and pounding heartbeat. It interacts with ciprofloxacine and the other fluoroquinolone antibiotics (i.e. those ending with -xacine) as well as caffeine. They are not used much any more due to safety concerns and side effects.

Long acting beta-2 agonists have been promoted as reducing the need for inhaled quick relief medication. Drugs on the market include salmeterol (Serevent) and formoterol (Foradil). Serevent, approved in 1994, dilates breathing passages by stimulating the beta-2 adrenergic receptor. At least 300,000 children take this drug.

Serevent was isolated as one of five dangerous drugs still on the market by Dr. David Graham of the FDA in testimony to congress in November of 2004. In that testimony he described Serevent users “dying while clutching their inhalers.”

In 1996, based on reports of paradoxical bronchospasm (a contraction of the breathing airway or bronchus that impairs breathing and can be fatal) with Serevent, the manufacturer undertook a large multi site randomized placebo controlled trial, the Salmeterol Multi-center Asthma Research Trial (SMART). This was a 28-week safety study comparing salmeterol (Serevent) and placebo in the treatment of asthma.115 In addition to their usual asthma therapy, patients received either Serevent or a placebo. The study was stopped in 2002 by the study’s Data Safety Monitoring Board because of an increase in asthma related deaths. Analysis of 26,355 patients showed statistically significantly higher rates of asthma related deaths (13 versus 3, relative risk greater than four fold) in patients on Serevent.

In African Americans, who made up 17% of the study population, the study showed a statistically significant greater number of respiratory related deaths and life threatening events. Many had to get intubated, or have a tube put down their throat to let them breath related to respiratory causes (20 versus 5 for placebo, a four fold increase). In addition, there was a more than four fold increase in asthma-related deaths and life threatening respiratory events in patients taking salmeterol compared to those taking placebo. Overall the risk of death from any cause or having a life-threatening event was doubled in African Americans, another finding that was statistically significant. The data suggested that the risks of Serevent were greater in African Americans than in whites. About half of the patients were also taking an inhaled corticosteroid. In those patients not taking an inhaled corticosteroid, there were significantly more asthma-related deaths in all patients taking salmeterol compared to those taking placebo.

The manufacturers of Serevent initially showed data to the FDA that included the results from the 28-week trial plus a 6 month follow up period. The results for this time period were better than the initial 28 weeks alone. However the initial study protocol was for a 28 week trial, and the FDA appropriately requested the 28 week outcomes, which they posted on their web site in 2005. However the potential risks of long-acting beta agonists have long been known.116 A long acting beta agonist drug marketed in New Zealand was associated with an increase in asthma related deaths and was pulled from the market there in 1976. A recent meta analysis (where data from all published studies were combined) looking at trials from the past 20 years involving a total of 33,826 asthma patients treated with long acting beta agonists showed that all drugs in this class are dangerous.116 Overall there was a statistically significant increase in a number of parameters, including an increase in asthma exacerbations requiring hospitalizations by 2.6 fold, increased life threatening exacerbations of asthma by 1.8, and increased risk of asthma related death by 3.5 fold.

Based on these findings, I do not recommend use of a long-acting beta-2-agonist.

Advair, which contains Serevent and a steroid, also carries the same black box warning about increased asthma related deaths. This hasn’t stopped it from running up 2 billion dollars in sales per year. Based on the SMART study we cannot conclude that long acting beta agonists when administered with steroids are safe; in studies where 75% of patients were taking a steroid there was still a 2-fold increased risk of asthma related death.

Montelukast (Singulair) and zafirlukast (Accolate) are part of a new generation of asthma medications that are leukotriene antagonists. These medications work by inhibiting the cysteinyl leukotriene CysLT-1 receptor, which is involved in the inflammatory response. In rare cases they may be associated with Churg-Strauss syndrome, which involves inflammation of the blood vessels. Zileuton (Zyflo) can cause lupus and liver toxicity and requires blood to be checked every six months. They are expensive and have not been shown to be more effective than steroids and antihistamines.

Other new drugs are the mast cell stabilizers like nedocromil (Tilade) and omalizumab (Xolair). Xolair is given by injection every 2-4 weeks. These meds have only recently been approved by the FDA, and so we have to adopt a wait and see attitude.

Technorati Tags: advair, asthma medications, asthma treatment, atarax, claritin, zyrtec