David Brill
Individualizing therapy on the basis of sputum cell counts could help to improve the treatment of severe asthma, new research suggests.
A recent small-scale randomized study found that patients treated in this way had significantly fewer exacerbations and were able to safely reduce their prednisone doses.
The trial involved a rare subset of patients with high levels of eosinophils in the sputum, but the same principles could be extended to other types of asthma, the researchers say.
“Our philosophy ... has been to measure bronchitis by a simple processing of sputum. Identify the type of bronchitis and treat it accordingly based on the type of cell. It’s a very simple message,” said lead author Dr. Parameswaran Nair, an associate professor of medicine at McMaster University, Ontario, Canada.
“Most patients with eosinophilia are easy to treat and can be controlled with small or moderate doses of inhaled corticosteroids. But in the severe patients people [should] take a step back if the patient is not getting better with prednisone and think ‘what is the type of bronchitis? Should we not understand what’s going on here before we increase or add new treatments?’”
The study, which lasted 26 weeks in total, included only patients whose sputum eosinophilia had persisted despite prior prednisone treatment. Nine received five monthly infusions of mepolizumab (750 mg) – a monoclonal antibody which disrupts the activation of eosinophils by targeting interleukin-5 – and 11 received placebo. [N Engl J Med 2009 Mar 5;360(10):985-93]
There was only one asthma exacerbation in the mepolizumab group and this was associated with sputum neutrophilia rather than eosinophilia. Placebo patients, in contrast, experienced a total of 12 exacerbations – nine associated with eosinophilia and three with neutrophilia (P=0.002).
Patients taking mepolizumab reduced their prednisone dosage by a mean of 83.4 percent of the maximum possible reduction, compared to 47.7 percent for patients on placebo (P=0.04).
The accumulation of eosinophils in the airway is thought to be an important event in the pathogenesis of asthma but the exact role of the cells remains unclear. Previous studies have failed to show any benefit of anti-interleukin-5 antibodies as a therapy for asthma, but these trials did not tailor the therapy to specific patients.
“We argued that if we give it to every patient with asthma it’s not going to work – it’s only going to work if you’ve got eosinophilia to begin with,” said Nair.
The McMaster respiratory group, led by Professor Freddy Hargreave, has already demonstrated the benefits of individualizing therapy in an earlier randomized trial of 117 asthma patients. The number and severity of eosinophilic exacerbations were both reduced using the sputum-based approach, as compared to standard treatment according to Canadian guidelines. [Eur Respir J 2006 Mar;27(3):483-94]
Nair hopes that latest new study will raise awareness of the benefits of sputum testing for asthma, admitting that he is “very frustrated” that such a simple procedure has not caught on more widely.
“A rheumatologist would aspirate fluid from a joint to look at inflammation before giving anti-inflammatories, and a gastrointestinal surgeon would take a rectal biopsy for colitis before giving corticosteroids.
“But we in respiratory medicine are giving bucketloads of corticosteroids and anti-inflammatory drugs without measuring inflammation. Most physicians all over the world only measure forced expiratory volume in 1 second (FEV1), which is just a measure of airway caliber and not of bronchitis,” he said.
The results of another study, published in the same edition of the journal, lend further support to the theories of Nair et al. In a randomized double-blind trial of 61 patients, UK researchers showed that mepolizumab, compared to placebo, reduced severe exacerbations and improved quality of life in patients with refractory eosinophilic asthma. [N Engl J Med 2009 Mar 5;360(10):973-84]
A separate study, meanwhile, is already underway at McMaster to assess the effects of blocking neutrophils, which are typically found in asthma patients who have bronchitis caused by an infection.
Individualizing therapy on the basis of sputum cell counts could help to improve the treatment of severe asthma, new research suggests.
A recent small-scale randomized study found that patients treated in this way had significantly fewer exacerbations and were able to safely reduce their prednisone doses.
The trial involved a rare subset of patients with high levels of eosinophils in the sputum, but the same principles could be extended to other types of asthma, the researchers say.
“Our philosophy ... has been to measure bronchitis by a simple processing of sputum. Identify the type of bronchitis and treat it accordingly based on the type of cell. It’s a very simple message,” said lead author Dr. Parameswaran Nair, an associate professor of medicine at McMaster University, Ontario, Canada.
“Most patients with eosinophilia are easy to treat and can be controlled with small or moderate doses of inhaled corticosteroids. But in the severe patients people [should] take a step back if the patient is not getting better with prednisone and think ‘what is the type of bronchitis? Should we not understand what’s going on here before we increase or add new treatments?’”
The study, which lasted 26 weeks in total, included only patients whose sputum eosinophilia had persisted despite prior prednisone treatment. Nine received five monthly infusions of mepolizumab (750 mg) – a monoclonal antibody which disrupts the activation of eosinophils by targeting interleukin-5 – and 11 received placebo. [N Engl J Med 2009 Mar 5;360(10):985-93]
There was only one asthma exacerbation in the mepolizumab group and this was associated with sputum neutrophilia rather than eosinophilia. Placebo patients, in contrast, experienced a total of 12 exacerbations – nine associated with eosinophilia and three with neutrophilia (P=0.002).
Patients taking mepolizumab reduced their prednisone dosage by a mean of 83.4 percent of the maximum possible reduction, compared to 47.7 percent for patients on placebo (P=0.04).
The accumulation of eosinophils in the airway is thought to be an important event in the pathogenesis of asthma but the exact role of the cells remains unclear. Previous studies have failed to show any benefit of anti-interleukin-5 antibodies as a therapy for asthma, but these trials did not tailor the therapy to specific patients.
“We argued that if we give it to every patient with asthma it’s not going to work – it’s only going to work if you’ve got eosinophilia to begin with,” said Nair.
The McMaster respiratory group, led by Professor Freddy Hargreave, has already demonstrated the benefits of individualizing therapy in an earlier randomized trial of 117 asthma patients. The number and severity of eosinophilic exacerbations were both reduced using the sputum-based approach, as compared to standard treatment according to Canadian guidelines. [Eur Respir J 2006 Mar;27(3):483-94]
Nair hopes that latest new study will raise awareness of the benefits of sputum testing for asthma, admitting that he is “very frustrated” that such a simple procedure has not caught on more widely.
“A rheumatologist would aspirate fluid from a joint to look at inflammation before giving anti-inflammatories, and a gastrointestinal surgeon would take a rectal biopsy for colitis before giving corticosteroids.
“But we in respiratory medicine are giving bucketloads of corticosteroids and anti-inflammatory drugs without measuring inflammation. Most physicians all over the world only measure forced expiratory volume in 1 second (FEV1), which is just a measure of airway caliber and not of bronchitis,” he said.
The results of another study, published in the same edition of the journal, lend further support to the theories of Nair et al. In a randomized double-blind trial of 61 patients, UK researchers showed that mepolizumab, compared to placebo, reduced severe exacerbations and improved quality of life in patients with refractory eosinophilic asthma. [N Engl J Med 2009 Mar 5;360(10):973-84]
A separate study, meanwhile, is already underway at McMaster to assess the effects of blocking neutrophils, which are typically found in asthma patients who have bronchitis caused by an infection.
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