In clinic today, a co-worker told me that a patient said, “Call it anything, but asthma.”  The patient’s mother was fine with the child having a diagnosis of “reactive airway disease” or “wheezing,” and she was happy to treat him with albuterol, but she didn’t want him to be labeled with asthma.

Every so often, I’ll look at a patient’s chart and ask, “Does she have a history of asthma?” and the parent will respond, “No! She doesn’t have asthma.” When I ask if the patient is still using albuterol, the parent will reply “yes.”

Many parents prefer not to label their children with asthma.  Part of me doesn’t understand why parents would be reluctant to give a name to their children’s symptoms because asthma is the most common chronic disease in children, and almost one in every 10 children in the U.S. has asthma.

Perhaps Hollywood plays a role.

A recent study examined how asthma is portrayed in Hollywood feature films.  The authors conducted an analysis of 66 movies (examples: Goonies, Sidekicks, Signs, Jimmy Neutron, etc) that contain scenes showing asthma.  The investigators analyzed movies from the 1980s to 2007.  They noted that the characters who were depicted with asthma could be either male or female, young or old, any ethnicity.

Four sorts of recurrent scenes for asthma were noted:

• Wimp or social outcast.  Story events used asthma to suggest the character is weak.  For example, a child might be bullied or made fun of by others because of asthma symptoms of the use of an inhaler.  This occurred in 17% of episodes.
• Asthma as a stress response.  This was the most common scenario (41.5%) depicting asthma in these 66 movies.  Characters are depicted as having an asthma attack in response to a stressful or dangerous situation.
• Will power.  In this scenario that occurs rarely in 3.3% of episodes, the character with asthma cures himself or herself by having the right mental attitude.
• Asthma as power.   In these story events, the character uses asthma or an asthma inhaler as a weapon. For example, in Jimmy Neutron, the aliens retreat after being sprayed with an inhaler. This occurred in 6.9% of films. 

In addition, the investigators conducted interviews with twelve children ages 9-12 years old about these scenes. They found that the children with asthma became more concerned that their asthma might create stigmatization after seeing the movie clips.

When the children were asked what advice they would give the movie establishment, the kids made these suggestions.

• Please dramatize positive social behavior without bullying or teasing when asthma is shown.
• Treat respiratory illness seriously rather than make fun of somebody who can’t breathe.
• Don’t use inhalers as comical props.
• Don’t forget asthma can be deadly and treatment is serious.

I’ll end with an excerpt from Nancy Sander, head of the organization Allergy and Asthma Network Mothers of Asthmatics, who wrote a letter to Nickelodeon about the movie Jimmy Neutron.  She wrote…

“Why asthma? Why did you select any life-threatening condition or the character, Carl Wheezer? Is asthma funnier than heart disease, diabetes, epilepsy, or AIDS?

There is nothing funny about growing up with asthma, a condition that robs children of oxygen, limits physical activity, and requires responsible use of inhaled medications and avoidance of allergens and irritants. 

Was the character intended to educate children and the public about asthma?

If so, your efforts backfired.

Jimmy Neutron perpetuates the painful myth that children with asthma are emotional wimps that tend to overuse inhaled medications when faced with excitement.”

Recently, I’ve seen a lot of kids with asthma symptoms that are triggered by seasonal allergies.  I decided to ask parents and patients, “If the sky is the limit, what would you want somebody to invent for asthma?”

These were some of the responses:
“Nothing needs to be invented.  Flovent is the best invention. As long as Johnny has Flovent, he’s fine.” –Mother of an 8 year old boy

“An inhaler that is attached to the spacer.  I can always find my inhaler but I can never find the spacer. –10 year old boy

“A propellant that gets deeper in the lungs.  The CFC-free albuterol just doesn’t work as well as the old inhalers.”  -Parent and patient with asthma

“A medicine that only needs to be given once a month.” –Parent to a 5 year old girl with asthma 

“I don’t know.” This was the most common response of the children with asthma.

“I want to know when the asthma is going to start. It comes out of nowhere.” —Parent to a 6 year old boy with asthma

“A rule that two kids in the family can’t have asthma at the same time.  I didn’t sleep at all last night.”  -Mom to a 9 month old girl and 4 year old boy. Both have asthma.

“A medicine that he’ll actually want to use.” -Mom to a 11 year old boy

I had lunch with a colleague in 2005 who confided in me that despite the medical guidelines that warned against LABA-containing agents, her LABA was the only thing that made her better.  She was going to take the risks of increased exacerbations or even death.

Two kinds of beta agonists are used for asthma: short acting and long acting. Short acting beta agonists include albuterol, which is the most commonly used inhaler that asthmatics typically use when they have symptoms.  Short acting beta agonists last around 4-6 hours.

Long acting beta agonists such as salmeterol were introduced relatively recently—in the 1990’s—because their effects lasted for over 12 hours.  I am part of the Mini-Sentinel Assessment of FDA Regulatory Policies for LABAs.

The FDA is requiring the manufacturers of LABA to conduct five randomized, double-blind, controlled trials to compare the addition of LABA to inhaled steroids versus inhaled steroids alone. The trials started in 2011 and should produce results in 2017.

 LABA-containing medicines include:

• Advair (salmeterol and fluticasone)
• Symbicort (formoterol and budesonide)
• Serevent (salmeterol)
• Foradil (formoterol)

Brief regulatory history for LABAs:

1. Salmeterol Nationwide Surveillance study in the UK in the 1990s suggested that there was an increase in death in patients taking salmeterol compared to albuterol, but the results were not statistically significant.

2. The Salmeterol Multicenter Asthma Research Trial (SMART) that was initiated in 1996 and ended early in 2003 because they found that patients treated with salmeterol had increased risk of asthma exacerbations and deaths.

3. In 2003, label changes included a boxed warning incorporating labeling changes based on results of SMART.

4. Public health advisory was issued in 2006. Manufacturers of Advair Diskus, Foradil Aerolizer, and Serevent Diskus to update their existing product labels with new warnings and a Medication Guide for patients to alert healthcare professionals and patients that these medicines may increase the chance of severe asthma episodes, and death when those episodes occur

5. In 2007 Pediatric Advisory Committee reviewed pediatric data from the existing safety data was presented, and did not show any new or unique safety signal for pediatric patients.  Committee members discussed the possibility of removal of salmeterol from the market, but it was concluded that an extensive discussion of the benefits in the context of risk was warranted

6. In 2010, Drug Safety Communication released for consumers and healthcare professionals. New safety requirements for LABAs included the following:

• Single-ingredient LABAs should only be used in combination with an asthma controller medication; they should not be used alone.
•  LABAs should only be used long-term in patients whose asthma cannot be adequately controlled on asthma controller medications.
• LABAs should be used for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved. Patients should then be maintained on an asthma controller medication.
• Pediatric and adolescent patients who require the addition of a LABA to an inhaled corticosteroid should use a combination product containing both an inhaled corticosteroid and a LABA, to ensure compliance with both medications.

Additional Information for Patients

• Long-Acting Beta Agonists (LABAs) do not relieve sudden-onset asthma symptoms. You should always have a rescue inhaler, such as an albuterol inhaler, to treat sudden onset asthma symptoms.
• LABAs must never be taken alone for the treatment of asthma.
• If you need a LABA plus a long-term asthma control medication that is not available as a combination product, you should work with your healthcare professional to ensure that each medication is taken correctly.
• You should read the Medication Guide for LABAs and talk to your healthcare professional about any questions you may have about the use of LABAs.

7. We can look forward to the 2017 clinical trial results.

Today’s guest post is from Susan Jick, DSc, a Professor of Epidemiology and Director of the Boston Collaborative Drug Surveillance Program at the Boston University School of Public Health.  She writes….

Three theories have been hypothesized to explain the increased rates of poor pregnancy outcomes among asthmatic women: hypoxia and other physiologic consequences of poor asthma control, adverse effects of medicines for treatment of asthma symptoms, and other unknown factors associated with asthma but not due to the disease or its treatment.

Most research suggests that there is no increased risk of congenital anomalies associated with use of short-acting beta agonists in pregnancy. There has been no information available on the newer long-acting beta agonists in humans, and a recent study reported an increased risk of heart defects associated with asthma and with use of bronchodilators. Additionally, the same author recently reported an increased risk of gastroschisis among the offspring of users of bronchodilators in early pregnancy.

Inhaled steroids have not been associated with abnormalities except for a possible association with cleft palate.Little information is available regarding the risk of theophylline use during pregnancy and leukotriene inhibitors are a new class of drugs for which there is currently no information in the literature on effects in human pregnancy.

To estimate the prevalence of congenital anomalies among the offspring of women exposed and unexposed to asthma drugs during early pregnancy we conducted a matched cohort study using data from the United Kingdom’s General Practice Research Database.

We followed women exposed to asthma drugs during early pregnancy and a sample of unexposed pregnant women and identified their babies and determine what congenital anomalies were present. We then compared the rates in the asthma drug exposed women to the rates in the unexposed women.

The prevalences of any anomaly among unexposed and exposed women were 27.8 (95% CI 25.4-30.6) per 1,000 pregnancies and 31.3 (95% CI 27.7-35.5) per 1,000 pregnancies respectively (RR 1.1 95% CI 1.0-1.3). These findings suggest that asthma drugs overall do not increase the risk of congenital anomalies in the offspring when taken during the first trimester of pregnancy.

However, while we found no overall increased risk of congenital anomalies we did find some increased risks of specific anomalies associated with specific asthma drugs including: increased risk of cleft lip or palate associated with exposure to long-acting beta agonists, short-acting beta agonists, and oral steroids; increased risk of musculoskeletal anomalies associated with exposure to long-acting beta agonists, and; increased risk of multiple anomalies among the offspring of women exposed to long-acting beta agonists and inhaled steroids. It is important to keep in mind that these findings are based on small numbers and are not statistically significant.

We plan to update this study as more data become available and hope to have more data on this topic soon, but these data add to the current sparse knowledge about this topic and do provide some reassurance that use of asthma drugs in pregnancy does not lead to strong risks of congenital anomalies.

I can’t get the results of one poster that I saw at the American Thoracic Society conference last week out of my mind.  I’m intrigued by the question the investigators asked and the preliminary answers they have. Apparently not everyone takes albuterol when they have asthma symptoms.

The investigator who presented the poster was just as perplexed by the preliminary answers as I was.

The investigators studied use of short-acting beta agonists, such as albuterol, in response to asthma symptoms.  They conducted an analysis using data from a clinical trial of asthma patient education led by the American Lung Association. Subjects in the trial were given instructions to use albuterol when they experienced asthma symptoms. 

When patients experience symptoms, they were considered adherent if they used albuterol.  Because albuterol is a rescue medication and provides quick relief of symptoms, I would expect most patients to be adherent to albuterol.  In my own home and in clinic, I’ve found that my daughter and patients often prefer albuterol over their inhaled corticosteroids because they can feel a change. They feel better immediately.

So, the idea that patients could be non-adherent to albuterol hadn’t entered my mind.

The investigators found that in the patients who reported at least one symptom day, 59% were always adherent with albuterol use, 38% were sometimes adherent, and 3% were never adherent.  So, when these asthma patients experience symptoms, 38% may or may not take albuterol and 3% never take it.

When looking at patients who had at least one day of no symptoms, 39% never used albuterol on symptom-free days, 51% sometimes used albuterol, and 10% always used albuterol.  This is shocking to me too but maybe less shocking. Even without symptoms, many patients still take albuterol.

The investigators concluded that patients are frequently non-adherent to recommendations for short-acting beta agonist use.  Patients who used more albuterol than needed were more likely to report poorer asthma control.

I had a multiple questions for the presenting author.  For the patients who didn’t take their albuterol even when they were experiencing symptoms, did the symptoms self-resolve?  Were they mistakenly reporting symptoms when they really didn’t have them? Or did the symptoms develop into exacerbations that required a visit to the doctor, emergency room, or hospital?

For the patients who used albuterol but didn’t have symptoms, were they experiencing poor asthma control even though they didn’t report symptoms?

Why would patients not take a medication that will help relieve their symptoms immediately?

Are patients misunderstanding the recommendation to take albuterol when experiencing symptoms? Or are patients misunderstanding that their symptoms are really symptoms?

Did patients avoid albuterol because they were worried about side effects?

He agreed my questions need to be answered, but he didn’t have any answers.  Yet.

Today’s guest post is from Brandon Vosika, an artist who has asthma.  He writes…

My name is Brandon Vosika, I’m 24 years old and I’ve had asthma for 22 years of my life. I’m also a watercolor painter and artist of many mediums. This project, Shake Well Before Use is something I’ve been thinking about and wanting to make for a long time now. What I want to create is a softcover book of my paintings, drawings, and words on asthma. I want this project to be as DIY and personal as possible so each book will be handmade by me.

Everyone who pledges to my Kickstarter project should know that what they’re getting is coming straight from the hands of the original artist. The book will consist of 12-16 full color pages of paintings as well many others with drawings, illustrations and writings I’ve done about asthma. Because I know children have the highest incidence of asthma, the book will be completely appropriate for everyone, of any age. I want to make something that not only appeals to adults who enjoy art but something that would have helped me feel better about myself when I was a kid, embarrassed to use my inhaler at school.

There were so many things that I didn’t really understand when I was younger. I wish I would have had something like this to relate or feel connected to. One thing I’m sure about is that people of all ages should realize that maybe something good, like art, can be made from something as terrible as asthma.

If you feel like this may be important to anyone you know, please share it with them! Spreading the word, re-posting and doing a little guerrilla marketing is extremely important with small independent projects like this. The goal here is to get the art out to as many people as possible and with all of your help and generosity I really think we can do it!

To read more about how you can make a pledge to help make Brandon’s project a reality, click [here]. Read more about Brandon’s work at: www.BrandonVosika.com. 

I’ve already made my pledge, and I hope you support Brandon too.  -Ann  

More artwork from Brandon…

Today’s guest post is from Elizabeth Townsend, a post-doctoral research fellow in the Department of Anesthesiology at Columbia University.  She presented her results at the American Thoracic Society Conference this past week.  

Some titles in the press this week are “Adding ginger to asthma medications can help make them more effective,” “Ginger may relieve asthma symptoms,” and “Good news for 13 million Indian asthmatics-Ginger abundantly found, shown to ease asthma attack.”   Dr. Townsend writes…

Many asthmatics report using complementary and alternative medicines to treat their asthma symptoms including the use of herbal supplements. Also, there are anecdotal reports from several populations and ethnicities that ginger alleviates respiratory symptoms, dyspepsia, and gastrointestinal motility disorders; however there is little to no mechanistic evidence to explain these effects.

There are similarities between gut smooth muscle and airway smooth muscle, so we wanted to investigate the signaling mechanisms by which purified components of ginger exerted effects on airway smooth muscle. Our goal was to provide insight into how these compounds worked independently, but also in combination with existing asthma therapies in the hopes of better alleviating asthma symptoms.

We first investigated 4 individual components of ginger, 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol, and their effects on airway smooth muscle relaxation. We used human tracheal tissue and contracted it with the bronchoconstrictor acetylcholine in in vitro experiments. We then added increasing concentrations of the individual purified components and found that 10-gingerol had no effect on the airway tissue while the other 3 compounds relaxed airway tissues.

Using a mouse model of airway hyperreactivity, we nebulized 8-gingerol 15 minutes prior to exposing mice to methacholine in vivo. Methacholine produces a dose-dependent increase in airway resistance by contracting the airways; this is similar to what happens during an asthma exacerbation. The mice that were treated with 8-gingerol were protected from this bronchoconstriction.

The reliance on short and long-acting b-agonists to manage asthma symptoms and exacerbations can increase the risk for asthma-related death and necessitates the development of novel therapeutics that can a) decrease the reliance on b-agonists by potentiating their bronchodilating effects at lower effective concentrations and b) work to relax airway smooth muscle by complementary yet alternative signaling pathways.

After our initial discovery that these components of ginger could relax airways and prevent hyperresponsiveness on their own, we wanted to investigate how they interacted with existing asthma therapies, namely b-agonists. We found that each of the 3 components of ginger, 6-gingerol, 8-gingerol, and 6-shogaol potentiate the effects of b-agonist isoproterenol in in vitro studies using human airway smooth muscle.

These effects are attributed to inhibition of the enzyme phosphodiesterase 4D, which breaks down the pro-relaxant molecule cAMP produced when b-agonists are used. By inhibiting this enzyme, 6-gingerol, 8-gingerol, and 6-shogaol may promote relaxation and decrease the amount of b-agonist that is necessary to relieve bronchoconstriction during an asthma attack.

It is important to note that we have not performed any clinical trials in asthmatic patients to date, but hope to move in this direction in the future. Additionally, we are investigating the effects of these constituents on airway tissues directly and via inhalation.

It is difficult to know how much ginger would need to be ingested to achieve the same effects we are observing since many compounds are metabolized during digestion and subsequently in the liver, further complicating bioavailability of these active constituents.

By better understanding the mechanisms through which purified components of ginger exert their effects on the airway, we can explore the use of these naturally derived phytotherapeutics in alleviating asthma symptoms. We also hope that our research may lead to the development of safer and more efficacious herbal therapies that gain clinical acceptance and increase adherence to herbal and classic therapies in patients choosing to self-treat their asthma symptoms with complementary and alternative medicine. No new classes of drugs have been approved for acute relief of asthma symptoms in many years.

We hope that our research will contribute to the availability of new asthma therapies in the future. Ongoing studies in our laboratory are focusing on the effects of these individual components of ginger on the airway epithelium as well as investigating the anti-inflammatory properties of these constituents. In addition to 6-gingerol, 8-gingerol, and 6-shogaol, we are also investigating the effects of quercetin, a naturally derived anti-inflammatory/anti-oxidant found in tea, fruits and vegetables on airway reactivity as it relates to asthma. 

Dr. Townsend’s Principle Investigator/Mentor is Charles W. Emala, MS, MD.

From Candace Lavin, Field Organizer for Massachusetts Healthy Air Campaign…

One in 10 people in Massachusetts have asthma.  The Breath of Life Dorchester (BOLD) Teens know this fact all too well, which is why they have joined the American Lung Association in working to protect those with asthma by making the air we breathe cleaner and healthier.  

The BOLD Teens is a youth-led organization which focuses on environmental and social justice by addressing the health and safety concerns of their community. As members of the American Lung Association’s Massachusetts Healthy Air Campaign, they work on issues such as supporting the reduction of pollutants emitted from coal-burning power plants to vehicle exhaust. Air pollution has been scientifically linked to increased asthma attacks, heart attacks, strokes, and even premature death.

To help make a point about the link between asthma and air pollution, the BOLD Teens created this YouTube video, which was produced by Elena Guy, a communications major at Northeastern University.

May is Asthma Awareness Month. To learn more about how to protect yourself from asthma, please see this tip sheet.

One of the most fun (and intimidating) parts of international conferences is meeting other investigators.  At one of the poster sessions, I met Dr. Silvia Pascual, a pulmonologist from Spain who has a passion for improving quality of life in asthma patients.   She carefully described her poster and politely answered my questions while her collaborator smiled.

Anxiety and depression frequently coexist with asthma, and symptoms from anxiety and depression can worsen asthma control and quality of life.   They conducted a cross-sectional study of asthma patients who were recruited from two hospitals in Spain. 

They collected data through a survey of 354 patients.  They found that 31% had anxiety, 2% had depression, and 10% had both anxiety and depression. 

Anxiety and depression were associated with poor asthma control.  Anxiety was associated with reduced quality of life. Anxiety and depression together had even worse effect on quality of life.

They concluded that treating anxiety and depression could improve asthma control and quality of life.

I’ve known that asthma is associated with anxiety and depression and that people with asthma are more likely to have anxiety disorders compared to the general population.  But I didn’t know of any studies that demonstrated that people with anxiety and depression had poorer asthma control.

Read more about this study here.

This week I’m featuring presentations that I’ve seen at the American Thoracic Society Annual Meeting in Philadelphia.  Today’s guest post is from Joanne Sordillo, ScD, Instructor of Medicine at Brigham and Women’s Hospital.   She writes about a study that she presented….

Analgesics like ibuprofen and acetaminophen are routinely given to treat fever in infants, and several studies have shown a link between the use of analgesics during infancy and the subsequent development of asthma and asthma symptoms including wheeze. However, although respiratory infections are a common cause of fever in infants, these earlier studies did not consider whether the underlying respiratory infection played a role in the eventual development of asthma and asthma symptoms in these children.

Many children are given over-the-counter analgesics to treat the fever that accompanies respiratory infections, so it seemed unclear to us whether asthma and wheeze were really linked to the use of these drugs or perhaps to the respiratory infection itself.

In our study, we wanted to try to determine if accounting for early life respiratory infections mitigated the relationship between analgesic use and development of wheeze and asthma in children.

We used data from 1,139 mother-child pairs who participated in Project Viva, a research study of pregnant women and their children that examined lifestyle factors during pregnancy and after birth and evaluated their effects on the development of asthma and other childhood conditions. Mothers completed questionnaires during early pregnancy, at mid-pregnancy and at one year following birth to determine acetaminophen and ibuprofen use. Also, during the first three years of each child’s life, every mother provided an annual report of any doctor’s diagnosis of asthma or wheezing symptoms.

To quantify prenatal exposure in early and mid-pregnancy, we divided subjects’ acetaminophen exposure into three categories: those who never used the drug; those who used it less than 10 times; and those who used acetaminophen more than 10 times. Ibuprofen use was much less frequent during early pregnancy and mothers were grouped into two categories: those who took the drug and those who did not. Ibuprofen use beyond the first trimester was rare and was not included in the analysis.

For childhood exposure during the first year of life, we divided infants into four groups for each drug: those who were never given the drug; those who were given the drug one to five times; those who were given the drug six to 10 times; and those who received more than 10 doses of the drug during the first year of life.

Reviewing the study data, we found a higher exposure to acetaminophen both prenatally and during the first 12 months of life compared to ibuprofen: 70 percent of mothers reported acetaminophen use during pregnancy while only 16 percent of mothers said they had used ibuprofen while pregnant; 95 percent of children were given at least one dose of acetaminophen during infancy versus 70 percent of children who had been given at least one dose of ibuprofen. About 43 percent of children were given more than 10 doses of acetaminophen before they were a year old compared to 25 percent of children who received more than 10 doses of ibuprofen.

Next, we looked at drug use and the occurrence of asthma and asthma-like symptoms overall, and then adjusted the analysis to account for respiratory infections the children experienced by the age of three. These infections included bronchiolitis, pneumonia, bronchitis, croup or any other respiratory infection.

At the conclusion of their study, we found that while use of the drugs was associated with wheeze and asthma in unadjusted models, after adjusting the results to account for respiratory infections, the association between medication use in early childhood and asthma symptoms was substantially reduced.

These results suggest that respiratory infections in infancy, and not analgesic use, are the actual underlying risk factor for asthma and wheeze in children.

We also found that prenatal exposure to analgesics was associated with wheeze and asthma in the children. However, because we did not have information regarding why the women took analgesics while pregnant, we were unable to adjust for those potential factors; for now, this link must be interpreted with caution.

Future studies will need to carefully collect information regarding the reasons for taking such over-the-counter drugs as analgesics during pregnancy.