|
 Asthma
Could be Several Diseases Masquerading as One
Age at onset and inflammatory cells define patient subsets,
guide treatment.
from the National Jewish Medical & Research Center,
January 8, 2004
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People who
develop asthma as children may have a different disease than
those who develop it as an adult. A study in the January issue
of The Journal of Allergy and Clinical Immunology adds to the
growing body of evidence that asthma is not a single disease,
but a group of syndromes with different origins and biological
characteristics. The research team, led by Sally Wenzel, M.D., a
pulmonologist at National Jewish Medical and Research Center,
also found that the absence or presence of inflammatory cells,
called eosinophils, helped distinguish differences among asthma
patients.
"We found that patients whose asthma began in childhood were
more frequently allergic than those whose asthma began as
adults, while adult-onset asthma was associated with more rapid
loss of lung function," said Wenzel. "We were surprised to find
that many patients showed no signs of inflammation, generally
considered a hallmark of the asthma, yet they still had severe
airflow limitation and many asthma symptoms."
The study represents the first time that a research team has
combined information from a detailed questionnaire with
extensive biological data to define subsets of asthma patients.
This data should help physicians better diagnose and treat their
asthma patients and make better predictions about the course of
their disease. The data may also help guide the search for
genetic causes of the disease.
The researchers studied 80 patients with severe asthma who had
been referred to National Jewish Medical and Research Center
because high doses of inhaled or oral steroids had failed to
control their symptoms. Patients were divided into those whose
asthma developed before 12 years of age and those whose asthma
developed later. The early-onset group developed asthma at the
mean age of 2.6 years, while the late-onset group developed
asthma at the mean age of 27. They were evaluated for
differences in allergic responses, symptoms, lung function and
pathology.
More than 75% of patients who developed asthma before the age of
12 reported that they wheezed "most or all of the time" when
exposed to dust or pollens, while less than 40% of patients
whose asthma developed after 12 did so. Patients with
early-onset asthma were also more likely to respond positively
to allergens in a skin test and to have had eczema, an allergic
skin disease.
Although early-onset patients had had the disease, on average,
almost twice as long as the late-onset patients, lung function
was slightly worse in the late-onset group. That suggests that
patients with late-onset disease suffer a more rapid loss of
lung function.
The pattern of inflammation also differed depending upon the age
of onset. Late-onset patients were more likely than early-onset
patients to have inflammatory cells known as eosinophils in
their airways, in spite of treatment with powerful oral
steroids. Early-onset patients also showed a pattern of
inflammation more frequently associated with allergies than did
late-onset patients.
"Asthma has traditionally been very broadly defined in terms of
symptoms rather than underlying biological processes," said
Wenzel. "Our research helped us divide these severe asthma
patients into four subsets, based on age of onset and presence
or absence of eosinophils. We believe these subsets represent
different biological processes and mechanisms of steroid
resistance."
The definition of these subsets could help guide diagnosis,
treatment and future research. For example, since early onset
patients were more often allergic than late-onset patients,
treatments would be more likely to include an anti-allergy
component. Late-onset patients without eosinophils, may well
have a completely different disease associated with infection or
gastroesophageal reflux.
These subsets might also help guide a search for genes
associated with asthma, which has, so far, proven difficult.
Different phenotypes could be influenced by different genes,
said Wenzel. If so, then searches focusing on specific patient
subsets might uncover stronger genetic influences in asthma.
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