Pri-Med Southwest 2013

Dear All,

I will be speaking at Pri-Med Southwest 2013 Product Theater tomorrow about asthma therapy, sponsored by Teva Respiratory.  I look forward to sharing some cutting edge research on small airways disease and asthma as well as my personal clinical experiences.

See conference information here

Strange but true finding, animal airways have "taste buds" that allow them to react to exceedingly bitter substances -- causing the airways to relax, not unlike an asthma inhaler.  Dr. Susarla

Could a bitter compound give clues about asthma?

For a long time, scientists thought the taste receptors that signal sweet, bitter, or salty were found only in our taste buds. Then, things started to get weird.

Six years ago, researchers found taste receptors in the cells of the gut. Even more bizarre, scientists found them in cells that line the airway, and in the muscles that contract during an asthma attack. Basic scientific research began to suggest that bitter chemicals had potential as an asthma treatment. That is when Ronghua ZhuGe, a University of Massachusetts Medical School microbiologist, began to pay attention.

ZhuGe studies cell signaling involved in muscle function, a process that helps regulate blood pressure or airway constriction. He was intrigued when he read about experiments that showed that bitter compounds could cause those muscle cells to relax, pointing to a potential way to quell an asthma attack.

In that initial paper, the researchers called it a paradoxical result. They expected the bitter compounds would have the opposite effect, causing airway cells to contract. That would add to the problems patients experience in diseases caused by airway obstruction, such as asthma. But instead, bitter substances caused the cells to relax. ZhuGe decided to study how the compounds had that effect.

In a study published Tuesday in the journal PLOS Biology, ZhuGe and colleagues tease out the precise cellular mechanisms at work when bitter stuff, such as quinine and denatonium — ZhuGe says it is the most bitter compound that exists — are administered to those airway cells. The scientists took freshly procured muscle airway cells from mice and carefully figured out the complicated signaling that results in the relaxation of the cells. That is the goal with asthma medications, called bronchodilators.

“Definitely, we see a great potential to develop a new class of bronchodilators,” ZhuGe said. “When we compare how effective those compounds are to relax airways, we found we can relax them more completely compared” to existing treatments.

ZhuGe said the prospects are particularly exciting because there are so many bitter compounds that could be tried as potential new asthma treatments. The search will be guided, he hopes, by a more precise understanding of the mechanism at play when airway cells relax in response to a bitter stimulant.

But why did bitter taste receptors end up in our lungs in the first place? ZhuGe said his guess is it could be a protective mechanism; perhaps it is advantageous to have cells relax instead of contract when inhaling a bitter compound.

Read article here.

A New Way to Treat Severe Asthma?

Asthma is an extraordinarily complex, simple disease.  By that, I mean identifying its cause and proper treatment is often harder than diagnosing the disease itself.  Patients with the more severe spectrum of disease are even more challenging, and may require asthma specialists to re-examine our own dogma by using innovative ways to use common medications.  Using combination inhalers as rescue medication may be one way to do this as this study from Lancet suggests.  However, this therapy is not for everyone with asthma, and is not without risk.  Dr. Susarla

Single Combined Asthma Inhaler Better Than Recommended Treatment

Using two asthma medications combined in a single inhaler provides superior rescue and preventive treatment than guideline-based treatments among adults whose asthma symptoms are not well controlled, according to two large, randomized clinical trials that were published in The Lancet Respiratory Medicine.

This new therapy is known as SMART (Single Inhaler Maintenance and RelieverTherapy).

The findings in these two studies challenge national (USA) and international asthmaguidelines, especially in the United States, where this combined inhaler approach has not yet been approved.

The authors added that the two-medications-in-one inhaler is safe and well tolerated.

As background information, the researchers explained that most adults with asthma do not manage to achieve good control of symptoms, despite effective drug treatment options. A survey of 1,000 asthma patients found that controller drugs are not used by nearly half of all adults and children with persistent asthma.

Medical guidelines advise doctors to prescribe corticosteroids (ICS) plus rapid-onset long-acting β2 agonist (LABA) combination inhaler to achieve control, together with a second short-acting β2 agonist (SABA) inhaler for rescue usage, for the treatment of symptoms.

SMART, on the other hand, uses only a single ICS/LABA inhaler for both relief and preventive treatment.

First Study - Europe

The first study involved 1,714 adults patients with moderate, persistent asthma from 14 different European countries. The study found that the patients in the SMART beclometasone/formoterol combination had a considerably smaller risk of severe asthma attacks, being hospitalized, or requiring urgent care compared to those receiving current best practice.

The authors said:

"We believe that the additional cost of inhaled corticosteroid and rapid-onset, long-acting β2 agonist combination (29 Eurocents per patient per day) is justifiable because of the significant reduction in severe exacerbations, and specifically hospital admissions, known to have a huge effect on health-care costs in asthma."

Read article here.

Poor Sleep and Chronic Disease

Researchers are just beginning to understand how both sleep deprivation and poor sleep quality can not only contribute to poor daytime functioning, but also contribute to chronic disease. Dr. Susarla

Lack of sleep 'switches off' genes

One week of bad sleep can "switch off" hundreds of genes and raise the risk of a host of illnesses including obesity and heart disease, scientists claim.

Getting fewer than six hours' sleep per night deactivates genes which play a key role in the body's constant process of self-repair and replenishment, according to a new study.

Our bodies depend on genes to produce a constant supply of proteins which are used to replace or repair damaged tissue, but after a week of sleep deprivation some of these stopped working.

The findings suggest that chronic lack of sleep could prevent the body from fully replenishing itself and raise the risk of a host of diseases, researchers said.

Scientists from Surrey University divided 26 volunteers into two groups, one of which slept for less than six hours per night for an entire week, and one which slept for ten hours per night.

At the end of the week each group was kept awake for 40 hours and donated blood samples, which were studied to examine the effects of their sleep regimes.

The week of sleep deprivation was found to have altered the function of 711 genes, including some involved in metabolism, inflammation, immunity and stress.

Inadequate sleep also interfered with genes which are designed to become more or less active at certain points in the day, by throwing off the body's 24-hour internal clock.

Although a week's normal sleep was enough to restore the affected genes to their normal pattern, researchers said that prolonged periods of sleeplessness could lead to serious health problems including obesity and heart disease.

Studies have also shown a lack of sleep can lead to cognitive impairment, for example limiting our ability to drive a car safely.

Prof Colin Smith, one of the authors of the new paper, which was published in the Proceedings of the National Academy of Sciencesjournal, said: "This is only a week of sleep restriction and it is only five and a half or six hours a night. Many people have that amount of sleep for weeks, months and maybe even years so we have no idea how much worse it might be.

"If these processes continue to be disrupted, you could see how you are going to get impairment of organs, tissues, heart disease, obesity, diabetes. If you are not able to replenish cells and tissues that are damaged then you are going to suffer permanent ill health."

Read article here

Asthma or Pneumonia?

Perhaps an association between both, according to a recent study investigating the role of a bacteria commonly associated with "walking pneumonia" in children. Dr. Susarla

M. pneumoniae IgM higher in children with asthma

Mycoplasma pneumoniae may play a key role in pediatric asthma, according to study data published online.

 Tamar A. Smith-Norowitz, PhD, of the department of pediatrics and the Center for Allergy and Asthma Research at SUNY Downstate Medical Center, Brooklyn, N.Y., and colleagues published data on specific anti-M. pneumoniae immunoglobulin M, IgG and IgE antibody responses in 23 patients with asthma and 13 control patients.

All patients were aged younger than 20 years, had a physician’s diagnosis of asthma or current clinically defined persistent asthma symptoms, or both, along with allergic rhinoconjunctivitis with elevated serum IgE levels (>100 IU/mL). Patients were recruited from the Pediatric Asthma Clinic at Kings County Hospital Center, and outpatient pediatric offices in Brooklyn.

The researchers said, “Asthmatic subjects had higher levels of specific IgM [anti-M. pneumoniae antibodies] levels compared with non-asthmatics. In addition, IgM positivity was significantly higher in asthmatic compared with non-asthmatic subjects.”

M. pneumoniae may be more common or persistent in children with asthma than other populations, they said. However, further data are needed because the sample size of this study was small.

“Atypical respiratory infection such as M. pneumoniae continues to be a significant concern in children with asthma. More research is needed to identify high risk groups and develop intervention strategies directed at children with asthma,” Smith-Norowitz told Infectious Diseases in Children.

Although the researchers assessed respiratory tract infection incidence, they said it was only assessed by patient recall, which could have limited the results.

Read article here.

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Health Tip: Does Asthma Affect Your Sleep?

Take medications as your doctor prescribes

By Diana Kohnle

Friday, January 25, 2013

(HealthDay News) -- Asthma can affect your sleep, as symptoms often worsen at night.

The National Sleep Foundation offers this advice to help control asthma and enjoy a better night's sleep:

• Take all medications as prescribed, at the same time each day.
• Use a peak flow meter regularly to monitor changes in lung function.
• Learn what your asthma triggers are, and take steps to avoid those triggers.
• Get plenty of sleep each night.
• Ask your doctor about the potential benefits of an anti-inflammatory medication.

HealthDay

Marfan Syndrome and Pulmonary Problems - Asthma, pneumothorax, apnea!

Sleep apnea is very common in marfan syndrome. See a sleep specialist for diagnosis and treatment. JR

Pulmonary Management

Pulmonary issues are not a major criteria for people with Marfan syndrome however many people with Marfan syndrome have serious pulmonary symptoms such pneumothorax, restrictive lung diseases, chest wall deformaties and sleep apnea.

Overview

Q & A

• Is it possible to confuse lung symptoms of Marfan syndrome with asthma and incorrectly make an asthma diagnosis?
• What are the pulmonary function tests needed to evaluate lung function In people with Marfan syndrome?
• What is the appropriate management of restrictive lung disease? Is it different for people with Marfan syndrome?
• Is there a recommendation regarding chemical versus mechanical scarring for the treatment of repeated collapsed lungs (spontaneous pneumothorax)?

   

OVERVIEW 

Because fibrillin is expressed in the lung and is associated with elastin there, it is thought to affect both lung development and homeostasis. One possible effect of fibrillin-1 deficiency is pneumothorax. The symptoms of this are shortness of breath, dry cough or an acute onset of pleuritic chest pain. People with Marfan syndrome are at-risk of pneumothorax although they might not smoke. For them, it can be recurrent, present in both lungs and frequently associated with emphysema.

"Small" pneumothorax is treated in the hospital with supplemental oxygen. “Moderate to large” pneumothorax is treated by chest tube evacuation and possibly pleurodesis if necessary.

Restrictive lung disease occurs in more than 70 percent of people with Marfan syndrome. Often, this is due to severe pectus abnormalities and/or scoliosis. In either case, the result is that the chest cannot expand fully. The primary symptom is shortness of breath during exertion.

Emphysema, which results from loss of alveolar walls and enlargement of the air spaces, causes airway obstruction and inflammation. Approximately 10-15 percent of people with Marfan syndrome have emphysema, but it is probably under-diagnosed. It is the structural predisposition of the lungs in people with Marfan syndrome that is probably to blame. Symptoms include shortness of breath during activity, frequent bronchitis (often as a result of common colds or viruses settling in the chest) and low blood oxygen. The diagnosis can be confirmed by a chest x-ray, CT scan, pulmonary function test or arterial blood test. The conventional treatment for emphysema is supplemental oxygen, bronchodilator and aggressive treatment of infections. Research is underway on other pharmaceutical agents that may be useful.

Asthma, which is very common in the general population, is also present in the Marfan community.  Respiratory specialists should coordinate care with the other Marfan specialists because the conventional treatments for asthma (beta-agonists) have the opposite effect of beta-blockers which are prescribed to many people with Marfan syndrome.

Pectus deformaties can influence pulmonary function.  While surgery can correct the pectus, there is no evidence that pulmonary function will improve. Scoliosis is typically corrected early, but it can be progressive and cause more problems with pulmonary restriction. Serial pulmonary function tests can determine the progress of the lung restriction. Lung dysfunction can be worse if another airway disease, such as asthma or emphysema, is present. Supplemental oxygen and pulmonary rehabilitation are recommended to improve the quality of life.

Some people with Marfan syndrome have sleep apnea, which can have a number of causes.  One seems to be laxity of the connective tissues of the airways, which then further relax during sleep and cause partial obstruction to air flow.  Often persons with sleep apnea are overweight, but thin persons with Marfan syndrome are also at risk. 

Q & A

Is it possible to confuse lung symptoms of Marfan syndrome with asthma and incorrectly makde an asthma diagnosis?This is often a problem because people who are first diagnosed with Marfan syndrome are frequently children or young adults, an age group in which asthma is a common cause of shortness of breath. Making the correct diagnosis of asthma or another lung problem is important because the beta blocker medication often prescribed to minimize aortic enlargement in people with Marfan syndrome may complicate asthma treatment or make the asthma worse. If the asthma diagnosis is questionable, other explanations for the shortness of breath should be explored.

What are the pulmonary function tests needed to evaluate lung function in people with Marfan syndrome?In order to rule out asthma, emphysema and restrictive lung disease, people should typically have tests including: routine spirometry with and without bronchodilators, lung volume measurements and a diffusing capacity study. If asthma is a strong possibility, provocative testing should be performed. If there is any evidence of restrictive lung disease, maximal inspiratory and expiratory flows should be tested. When sleep apnea is a concern, measurement of upper airway resistance during sleep is a required part of any study for a person with Marfan syndrome.

What is the appropriate management of restrictive lung disease?  Is it difference for people with Marfan syndrome?Restrictive lung disease is an inability of the lung to expand adequately in order to take in a full breath. This can be caused by either structural abnormalities of the thoracic cage, such as pectus abnormalities or scoliosis, weak respiratory muscles or lung scarring. For people with Marfan syndrome, the most common causes are chest wall structure or function. Lung scarring is unusual in people with Marfan syndrome. Therefore, the first task for the physician is to determine whether it is a skeletal, muscle or lung problem. This can be accomplished with appropriate pulmonary function testing and a chest CT. Unfortunately, sometimes the degree of restriction does not correlate with the extent of breathlessness or functional impairment. Additionally, apart from early correction of scoliosis, which does improve respiratory function, other surgical measures to normalize the dimensions of the thoracic cage do not always help. Thus, choices about interventions should be individualized to address cosmetic and functional concerns.

Is there a recommendation regarding chemical versus mechanical scarring for the treatment of repeated spontaneous pneumothorax?Physicians who care for people with Marfan syndrome should assume that all patients will eventually require aortic replacement. Therefore, any thoracic procedure should respect the anatomic mandates of future aortic surgery. If supplemental oxygen or chest tube insertion does not successfully treat the pneumothorax, doctors may recommend pleurodesis, which involves "scarring" the lung surface to attach the lung to the chest wall. The best pleurodesis method for individuals with Marfan syndrome is mechanical rather than chemical pleurodesis, as the former makes cardiac surgery easier.

http://www.marfan.org/marfan/2366/Pulmonary-Management

Sleep deficit may underlie kids' ADHD, migraines

Sleep deficit may underlie
kids' ADHD, migraines

Congratulations on raising awareness  Dr Joseph!

The child displays hallmark behaviors – fidgety, impulsive, irritable, inattentive – and has been diagnosed with ADHD. Dr. Kevin Joseph isn’t stepping through a DSM-IV screening, though. His questions tack in another direction.
“How well does your child sleep?”
Joseph, a board-certified pediatric neurologist and sleep specialist at Valley Medical Center, regularly witnesses the revelations of an overnight polysomnography.

“I saw a boy, 9 years old, who couldn’t sit still in class, couldn’t remember to brush his teeth. Turns out he had severe sleep apnea, like 101 events per hour, and for a child, normal is 1.5 events,” Joseph said. “His oxygen saturations were down in the 70-80 percent level when they should’ve been 95-100 percent. We sent him for a tonsillectomy and at follow-up his parents reported he was sitting in class, not fighting, even losing some weight.

“He was like a new kid, and they were thrilled. And I never put him on medication.”

When sleep disturbances such as apnea are brought to light, cases of childhood migraines and attention deficit hyperactivity disorder – even epilepsy – often can be ameliorated or resolved.

Joseph studied at Walter Reed Army Medical Center and added training in pediatric neurology at Children’s National Medical Center. In the last four of his nine years of active duty, he treated soldiers for brain injuries in Iraq and was chief of child neurology at Madigan Army Medical Center in Tacoma.

There he saw how a parent’s deployment can subvert a child’s evening routines, spurring migraines and nightmares. More recently, he has witnessed how economic hardship deprives the whole household, not just the breadwinners, of sleep.

“The key difference between pediatrics and adult medicine is that, with pediatrics, you have to attend to the family, not just the child,” Joseph said. “I always ask about stressors at home. If parents are out of work or have financial issues, even if they only talk about those issues behind closed doors, it tends to seep through. It’s easy for me to give guidance about structure a child should have around bedtime. It’s harder for a family to implement, especially in single-parent households.”

The American Academy of Pediatrics in August revised its clinical-practice guideline, recommending that all children and adolescents who snore regularly be screened in a lab setting for obstructive sleep apnea. But snoring isn’t the only red flag: “Daytime learning problems,” the guideline notes, should compel attention, too.
Despite well-documented negatives associated with adult sleep disorders, parents are often surprised to learn about sleeplessness’ impact on a child, Joseph said. Sleep is when growth hormone is secreted, fueling body and brain development.

Joseph’s patients at the Pediatric Sleep Center include NICU preemies and 18-year-olds. They are restless or listless or developmentally delayed. They (or their parents) present with concerns about snoring, night terrors, sleepwalking, headaches and seizures, poor report cards and other events.

For people with epilepsy, disrupted sleep can re-awaken symptoms that medication had largely controlled. Joseph mentioned cases of college freshmen whose newfound freedom led them to join a late-night study session, and then seizures struck anew.

It’s important to get a formal diagnosis of obstructive apnea before a tonsillectomy is weighed, because a child with the condition is at greater risk of postoperative problems with the airway and with bleeding, Joseph said. The usefulness of a CPAP device should be considered, as well, because tonsillectomy doesn’t always bring relief.
“I saw a girl who had migraines that we couldn’t control with medication. She had obstructive apnea. She had a tonsillectomy, which didn’t affect the apnea, but then we put the CPAP on her and her headaches went away,” he said. “It was a huge success for the family. She wears this thing religiously.”

Junk food linked to asthma and eczema in children

Asthma is a complex chronic medical condition with many genetic and environmental contributors.  Although food exposure does not suggest cause, research like this is certainly relevant and deserves attention.  Dr. Susarla

The high saturated fat levels in food such as burgers lower children's immune systems, it is believed.

A research project involving more than 50 countries found that teenagers who ate junk food three times a week or more were 39 per cent more likely to get severe asthma. Younger children were 27 per cent more at risk.

Both were also more prone to the eye condition rhinoconjunctivitis, according to The Sun newspaper

But just three weekly portions of fruit and vegetables could cut that risk by 14 per cent in the younger group and 11 per cent among the teens, it is believed.

Researchers from New Zealand's Auckland University looked at the diets of 181,000 youngsters aged six to seven and 319,000 aged 13-14.

The scientists then asked if the children had allergy symptoms.

They wrote in the journal Thorax, where the study is published: "Fast food may be contributing to increasing asthma, rhinoconjunctivitis and eczema.

"Regular consumption of fruit and vegetables is likely to protect against these diseases."

In the UK alone 1.1 million children already suffer with asthma and one in five get eczema.

The team of researchers warn that their results do not prove cause and effect.

Read article here.

Study Supports Notion of Leaving Infants to Cry Themselves Back to Sleep

Here is a little fuel for you new parents suffering with insomnia.  Dr. Susarla

Let Crying Babes Lie: Study Supports Notion of Leaving Infants to Cry Themselves Back to Sleep

Today, mothers of newborns find themselves confronting a common dilemma: Should they let their babies "cry it out" when they wake up at night? Or should they rush to comfort their crying little one?

The study, published inDevelopmental Psychology, supports the idea that a majority of infants are best left to self-soothe and fall back to sleep on their own.In fact, waking up in the middle of the night is the most common concern that parents of infants report to pediatricians. Now, a new study from Temple psychology professor Marsha Weinraub gives parents some scientific facts to help with that decision.

"By six months of age, most babies sleep through the night, awakening their mothers only about once per week. However, not all children follow this pattern of development," said Weinraub, an expert on child development and parent-child relationships.

For the study, Weinraub and her colleagues measured patterns of nighttime sleep awakenings in infants ages six to 36 months. Her findings revealed two groups: sleepers and transitional sleepers.

"If you measure them while they are sleeping, all babies -- like all adults -- move through a sleep cycle every 1 1/2 to 2 hours where they wake up and then return to sleep," said Weinraub. "Some of them do cry and call out when they awaken, and that is called 'not sleeping through the night.'"

For the study, Weinraub's team asked parents of more than 1,200 infants to report on their child's awakenings at 6, 15, 24 and 36 months. They found that by six months of age, 66 percent of babies -- the sleepers -- did not awaken, or awoke just once per week, following a flat trajectory as they grew. But a full 33 percent woke up seven nights per week at six months, dropping to two nights by 15 months and to one night per week by 24 months.

Of the babies that awoke, the majority were boys. These transitional sleepers also tended to score higher on an assessment of difficult temperament which identified traits such as irritability and distractibility. And, these babies were more likely to be breastfed. Mothers of these babies were more likely to be depressed and have greater maternal sensitivity.

The findings suggest a couple of things, said Weinraub. One is that genetic or constitutional factors such as those that might be reflected in difficult temperaments appear implicated in early sleep problems. "Families who are seeing sleep problems persist past 18 months should seek advice," Weinraub said.

Another takeaway is that it is important for babies to learn how to fall asleep on their own. "When mothers tune in to these night time awakenings and/or if a baby is in the habit of falling asleep during breastfeeding, then he or she may not be learning to how to self-soothe, something that is critical for regular sleep," she said.

Read article here.