Biologic Eases Subset of Severe Asthma

For severe eosinophilic asthma, the novel monoclonal antibody mepolizumab cut exacerbations whether given as an injection or infusion and reduced steroid use in patients dependent on them, two trials showed.

The drug, which targets interleukin-5 (IL-5) to inhibit eosinophilic inflammation,cut exacerbations by 47% with intravenous dosing and by 53% with subcutaneous dosing when compared with placebo (0.93 and 0.81 versus 1.75 per year, both P<0.001), Hector G. Ortega, MD, ScD, of GlaxoSmithKline, found in the MENSA trial.

Mepolizumab injections more than doubled the likelihood of glucocorticoid dose strata reduction compared with placebo, with a median 50% dose reduction from baseline versus none with placebo (P=0.007), Elisabeth H. Bel, MD, PhD, of the University of Amsterdam, and colleagues found in a second study, dubbed SIRIUS. Investigators in both trials said that safety issues with the drug were no different from placebo.

Both trials were reported online in the New England Journal of Medicine in conjunction with presentation at the European Respiratory Society meeting in Munich.

Three prior trials had already shown that anti-IL-5 drugs helped in asthma cases targeted by sputum eosinophil levels, Parameswaran Nair, MD, PhD, of McMaster University in Hamilton, Ontario, noted in an accompanying editorial.

The two new trials provided some clinical observations with "important practical applications," though, he wrote.

"First, the subcutaneous administration of a lower dose of the drug (100 mg) than was previously reported was shown to be efficacious," he noted.

"Second, characterization of the eosinophilic phenotype on the basis of a blood eosinophil count of more than 300 cells per microliter despite concurrent treatment with high doses of glucocorticoids was sufficient to select patients who were likely to have a response to this therapy.

"Both these observations make it potentially simple and easy for practitioners to identify patients who are likely to benefit and administer the drug to them."

Some previous studies that had tried to identify candidates for treatment based on clinical characteristics alone had failed.

Sputum eosinophil counts have been used since, but their greater sensitivity to change than blood eosinophil levels comes at a cost in convenience.

"Although persistent blood eosinophilia may be sufficient to identify patients who are likely to have a response to this treatment, whether this biomarker is sufficient or is as effective as airway eosinophilia in monitoring the response to treatment remains to be seen," Nair pointed out.

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Singulair Doesn't Ease Wheeze in Most Kids

Intermittent montelukast (Singulair) didn't alleviate wheezing in children, except possibly for those with a specific genetic mutation, a trial showed.

Giving the leukotriene receptor blocker at the onset of wheezing didn't cut down on unscheduled medical visits for those episodes compared with placebo (mean 2.0 versus 2.3 over 12 months, incidence rate ratio 0.88, P=0.06), Jonathan Grigg, MD, of the Queen Mary University of London, and colleagues found.

However, the subgroup of children with the 5/5 ALOX5 promoter genotype associated with montelukast response in adults did have a 20% relative reduction in unscheduled wheeze-related medical visits with the drug (2.0 versus 2.4 over 12 months, P=0.01).

No effect was seen with other genotypes (P=0.79), the researchers reported at the European Respiratory Society meeting in Munich and simultaneously online in the Lancet Respiratory Medicine.

"These data do not support the routine use of intermittent montelukast for wheeze in children aged 10 months to 5 years," the group concluded. "Further data from stratified trials are needed before treatment is targeted to a responsive subgroup."

Their Wheeze And Intermittent Treatment (WAIT) trial included 1,358 children in the age range of 10 months to 5 years, who were seen at 21 primary care sites and 41 secondary care sites in England and Scotland. They had two or more wheeze episodes (at least one recent).

After stratification by genotype, the kids were randomized to montelukast or placebo given by parents at each wheeze episode over a 12-month period.

Overall, montelukast increased the time to first hospital admission (P=0.04) but without changing the rate of emergency department visits.

Also, montelukast-treated kids received fewer courses of rescue oral corticosteroids, but without reducing the proportion of children getting at least one course of those rescue meds.

And, "in the context of present U.K. prescribing practice, the clinical significance of a change in this indirect marker of wheeze severity is unclear," the researchers cautioned.

The number and duration of wheeze episodes didn't differ between treatment groups.

The only serious adverse event -- a skin reaction -- occurred in the placebo group.

Meta-analysis of the findings of those of three prior trials of montelukast in young children, yielded results similar to those of the trial by Grigg and colleagues, supporting no overall benefit from intermittent dosing.

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Enterovirus Triggering Respiratory Problems in Children

Enterovirus is one of many viruses capable of triggering airway problems in children similar to asthma.  As such, children with asthma are especially high risk for exacerbations.  A child with poorly controlled asthma would be especially high risk.  At this time, there does not appear to be an easy way to test for the virus. Dr Susarla

What is Enterovirus 68, the mysterious illness that may be sickening hundreds of children?

Health officials in at least 10 states have reported hundreds of cases of a respiratory illness that has sent scores of children to emergency rooms and, in some cases, even to intensive care units.

The culprit is believed to be Enterovirus 68 (also known as EVD-68 or Eentrovirus D68), a fairly rare viral infection that can cause symptoms such as coughing, wheezing and low blood oxygen levels (also known as hypoxemia). In some cases, however, the symptoms can be severe — particularly for children who already suffer from asthma or other respiratory problems.

Jennifer Cornejo of Colorado told Denver's ABC affiliate that her 13-year-old son, William, had cold symptoms that developed overnight into a life-threatening illness. "He was in really bad shape," she told the station. "He came really close to death. He was unconscious at our house and white as a ghost with blue lips — he just passed out."

Here is how William Cornejo described it: "My head started hurting. And after that my lungs started closing up. It felt different."

Until recently, Enterovirus 68 was only thought to cause sporadic infections, but there have been reports of more widespread outbreaks in Georgia, Pennsylvania and Arizona between 2008 and 2010.

Only Missouri and Illinois have confirmed cases of EV-D68, but cases with similar symptoms have been reported in Colorado, Georgia, Iowa, Kansas, Kentucky, North Carolina, Ohio and Oklahoma as well.

Because of how rare Enterovirus 68 is, scientists are still learning about it. But here is what you should know now:

Why is it called Enterovirus 68?

Enterovirus is the name used to describe a group of more than 100 of the most common viruses that affect humans and other mammals. Most people might interact with an enterovirus by way of the common cold, which can be caused by enteroviruses as well as rhinoviruses.

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