Is the 2009 H1N1 vaccine safe for people with asthma? If so, what is the optimal dose for this population? Is it true that the flu vaccine is less effective in asthmatics? If so, what mechanism reduces its efficacy?

Investigators hope to answer these questions - and quickly.

The stakes are high: People with asthma have a four-fold increased risk of landing in the hospital from H1N1, according to a CDC review of hospital records early in the 2009 H1N1 flu outbreak.

"Asthmatics are a high-risk population with pre-existing inflammatory airway disease that makes them susceptible to the pulmonary complications of influenza," said Eugene R. Bleecker, MD, professor of internal medicine - pulmonary at Wake Forest University School of Medicine, Winston-Salem, NC. "Asthmatics accounted for about 35 percent of hospitalizations for flu in the southern hemisphere this year, with a comparable rate so far in the U.S."

A randomized clinical trial under the auspices of the National Institute of Allergy and Infectious Diseases  is now under way at seven sites across the U.S. to determine the safety of the 2009 H1N1 influenza vaccine in people with asthma and the dose needed to induce a protective immune response in these patients, especially those with severe asthma.

'Abysmal' Vaccination Rates

Wake Forest's Center for Genomics and Personalized Medicine Research, which Bleecker directs, is one of those sites.

"We want to make sure the vaccine is safe in asthmatics," said co-investigator Wendy C. Moore, MD, associate professor of internal medicine - pulmonary at Wake Forest. "We have no expectation that it is any less safe. Nonetheless, there is a plethora of misinformation out there on the Internet."

In flu seasons past, the flu vaccination rate of asthmatics has been "abysmal," according to Moore, mainly because of concerns about the safety of flu vaccines in this population.

"About 30 percent of asthmatics get the seasonal flu vaccine even though they are on the list of those who should get it and the evidence shows seasonal vaccine is safe for asthmatics," she said.

The second question to be answered is: What is the right dose? "Some old data suggests the response of the blood in asthmatics to vaccines may not be as robust as the response in members of the general population," Moore said. "We don't really know the right dose in asthmatics."

Inhaled corticosteroids, the most common therapy for severe asthma, are safe "but do they affect the immunogenicity of the flu vaccine?" Bleecker asked.

Nurse Participation

The randomized study will gauge the effectiveness of two different doses of vaccine containing inactivated H1N1 influenza virus in two groups: those with mild-moderate asthma and those with severe asthma.

Half of the participants in each group will receive a 15 mg dose of the vaccine, manufactured by Novartis, and the other half a 30 mg dose. Three weeks later, each participant will receive a second dose of the same amount. Investigators will determine the strength of the immune response induced by the vaccine by measuring the level of antibodies against 2009 H1N1 flu virus in blood samples.

Enrollment began on Oct. 19 and will continue for 4 weeks, by which time investigators hope to enroll about 400 participants. "We started giving vaccine last week," Moore said. "We have vaccinated close to 80 people so far and we have people waiting in the wings."

Initially, a physician does a physical exam and takes a history of each participant. Then the trial becomes the domain of two research nurses who administer the vaccine, take vital signs and otherwise evaluate all participants day-to-day for any side effects as well as any asthma attacks occurring during the trial.

"We hope interim results will be available by the end of the year, and official results ready by next spring," Moore said. "If the interim analysis indicates that one shot is efficacious, that might change dosing parameters this flu season."

But the results will be relevant next year and beyond "because H1N1 is unlikely to die away," Bleecker stressed. "No one knows how prevalent it will be in the future, whether it will become the dominant flu strain or if another strain will emerge. 

"The other issue we hope to answer is: If I get H1N1 vaccine this year do I still need a vaccine for it next year? If you are infected next year with the same strain of H1N1, we think you don't but if H1N1 mutates, you may."

Michael Gibbons is senior associate editor at ADVANCE.