- Email: [email protected]
Can bacteria fight asthma?
Cost of asthma control with omalizumab Asthma continues to impose a significant clinical and economic burden on society. Omalizumab can reduce hospitalizations and emergency department visits and improve quality of life in patients with moderate-to-severe, suboptimally controlled allergic asthma. However, it is not clear that omalizumab, with an estimated annual cost of $10,000 to $12,000, will prove to be cost-effective if given to a broad population with asthma. In this issue of the Journal, Drs Oba and Salzman (p 265) report on a retrospective economic analysis of the cost-effectiveness of omalizumab using 52-week data from 2 randomized-controlled clinical trials in adults and adolescents with moderate to severe allergic asthma. The rates of hospitalization were 0.39 per 100 patient-years for omalizumab treatment and 2.77 per 100 patient-years for placebo; the incidence rates of
CTACK/CCL27 chemokine involvement in drug-induced exanthemas Chemokines and their receptors have gained considerable interest as new targets for inflammatory diseases. In this context, cutaneous T cell–attracting chemokine (CTACK/CCL27) is the only chemokine with a keratinocyte-restricted pattern of expression. The skin is the main target organ in several drug-induced adverse reactions with an immunologic basis, such as maculopapular exanthemas and severe diseases such as StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN), in which cytotoxic T lymphocytes seem to be the effector cells. In this issue of the Journal, Tapia et al (p 335) explore the involvement of CTACK in T-lymphocyte migration to skin in drug-induced reactions, finding increased CTACK expression at the mRNA and protein levels extended to suprabasal layers of keratinocytes in skin biopsy specimens from patients with drug-induced exanthemas (see Figure). Moreover, the authors find increased levels of expression of CCR10, which
Can bacteria fight asthma? The prevalence and severity of allergic asthma is increasing worldwide. Historically, clinical treatment of asthma has focused on relieving the symptoms of the disease rather than addressing the cause. As our understanding of the cellular and molecular mechanisms involved in asthma pathogenesis improves, emerging therapeutic strategies now look to target the underlying disease mechanisms. Some epidemiologic studies associate the increase in disease prevalence with a decrease in the occurrence of early childhood infections in developed and developing nations. Included in this group of infectious agents are mycobacteria. The immune response to whole
Page 212 August 2004
emergency room visits for asthma exacerbations were 1.16 per 100 patient-years and 2.98 per 100 patient-years, respectively. The outcome measures examined by the authors were an increase in the Juniper Asthma Quality of Life Questionnaire (AQLQ) score and an increase in the number of successfully controlled days (which allowed mild daytime asthma symptoms and use of up to 2 puffs of rescue b-agonist). The authors calculated that in 2003 dollars the incremental cost to achieve an additional successfully controlled day on omalizumab was $523 and the daily cost to achieve an increase of at least 0.5 points in the AQLQ score was $378. They conclude that omalizumab would be better used in allergic asthmatic individuals whose disease is poorly controlled despite maximal therapy. It could be cost-saving if given to nonsmoking patients who are hospitalized 5 times or more or 20 days or longer per year despite maximal asthma therapy. is the receptor specific for CTACK, in peripheral blood lymphocytes, with the higher chemokine and receptor expression levels during the acute phase of severe bullous reactions (SJS and TEN) that return to basal levels on resolution of the disease. The investigators conclude that CTACK-CCR10 interactions might play an important role in attracting cytotoxic T cells to skin in these reactions and might be putative therapeutic targets in the treatment of these diseases.
CTACK expression in suprabasal keratinocytes in the acute phase of TEN (left panel) and restricted to the basal layer keratinocytes on resolution of the disease (right panel)
mycobacteria is complex, lending itself to side effects if used as a therapy for the treatment of allergy. Isolation of individual components from mycobacteria will simplify the immune response and hence lower the likelihood of undesirable side effects. In this issue of the Journal, Sayers et al (p 302) describe the successful use of mycobacterial cell wall components to suppress allergic airway inflammation in the context of allergic asthma. In contrast to existing medications, mycobacteria-based immunotherapeutics provide exciting possibilities for vaccine development, ultimately preventing the underlying pathologic changes that culminate in chronic, established asthma.
J ALLERGY CLIN IMMUNOL
CTACK/CCL27 chemokine involvement in drug-induced exanthemas Chemokines and their receptors have gained considerable interest as new targets for inflammatory diseases. In this context, cutaneous T cell–attracting chemokine (CTACK/CCL27) is the only chemokine with a keratinocyte-restricted pattern of expression. The skin is the main target organ in several drug-induced adverse reactions with an immunologic basis, such as maculopapular exanthemas and severe diseases such as StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN), in which cytotoxic T lymphocytes seem to be the effector cells. In this issue of the Journal, Tapia et al (p 335) explore the involvement of CTACK in T-lymphocyte migration to skin in drug-induced reactions, finding increased CTACK expression at the mRNA and protein levels extended to suprabasal layers of keratinocytes in skin biopsy specimens from patients with drug-induced exanthemas (see Figure). Moreover, the authors find increased levels of expression of CCR10, which
Can bacteria fight asthma? The prevalence and severity of allergic asthma is increasing worldwide. Historically, clinical treatment of asthma has focused on relieving the symptoms of the disease rather than addressing the cause. As our understanding of the cellular and molecular mechanisms involved in asthma pathogenesis improves, emerging therapeutic strategies now look to target the underlying disease mechanisms. Some epidemiologic studies associate the increase in disease prevalence with a decrease in the occurrence of early childhood infections in developed and developing nations. Included in this group of infectious agents are mycobacteria. The immune response to whole
Page 212 August 2004
emergency room visits for asthma exacerbations were 1.16 per 100 patient-years and 2.98 per 100 patient-years, respectively. The outcome measures examined by the authors were an increase in the Juniper Asthma Quality of Life Questionnaire (AQLQ) score and an increase in the number of successfully controlled days (which allowed mild daytime asthma symptoms and use of up to 2 puffs of rescue b-agonist). The authors calculated that in 2003 dollars the incremental cost to achieve an additional successfully controlled day on omalizumab was $523 and the daily cost to achieve an increase of at least 0.5 points in the AQLQ score was $378. They conclude that omalizumab would be better used in allergic asthmatic individuals whose disease is poorly controlled despite maximal therapy. It could be cost-saving if given to nonsmoking patients who are hospitalized 5 times or more or 20 days or longer per year despite maximal asthma therapy. is the receptor specific for CTACK, in peripheral blood lymphocytes, with the higher chemokine and receptor expression levels during the acute phase of severe bullous reactions (SJS and TEN) that return to basal levels on resolution of the disease. The investigators conclude that CTACK-CCR10 interactions might play an important role in attracting cytotoxic T cells to skin in these reactions and might be putative therapeutic targets in the treatment of these diseases.
CTACK expression in suprabasal keratinocytes in the acute phase of TEN (left panel) and restricted to the basal layer keratinocytes on resolution of the disease (right panel)
mycobacteria is complex, lending itself to side effects if used as a therapy for the treatment of allergy. Isolation of individual components from mycobacteria will simplify the immune response and hence lower the likelihood of undesirable side effects. In this issue of the Journal, Sayers et al (p 302) describe the successful use of mycobacterial cell wall components to suppress allergic airway inflammation in the context of allergic asthma. In contrast to existing medications, mycobacteria-based immunotherapeutics provide exciting possibilities for vaccine development, ultimately preventing the underlying pathologic changes that culminate in chronic, established asthma.
J ALLERGY CLIN IMMUNOL