Medical Journal Review
Posted: August 2009
Reviewed by Juan Carlos Ivancevich, MD, in collaboration with Richard Lockey, MD, WAO Web Editor-in-Chief.
1. Monitoring sputum eosinophils by mucosal inflammation and remodelling.
The authors compared bronchial inflammation and collagen deposition after 2-years of treatment guided by either sputum eosinophils (SS) or by clinical criteria (CS). This pilot study involved 20 mild to moderate asthmatics randomly assigned to either strategy and treated with inhaled corticosteroids adjusted to identify the minimum dose needed to maintain asthma control by SS or CS. Bronchial biopsies immunostained for inflammatory cells, MUC5A and collagen were obtained when minimum treatment to maintain control by either method was identified and continued for 2 years. The mean dose of ICS at the start and end of the study was similar in both the SS and CS groups. The FEV1 increased in both groups. In SS, mucosal lymphocyte and eosinophils counts, but not neutrophils were reduced. In CS, only activated eosinophils and neutrophils counts decreased. MUC5A staining decreased in the SS but not the CS group. No change in collagen deposition beneath the basement membrane was observed in either strategy.
Editor's comment: Treatment strategies that reduce mucosal inflammatory cells and MUC5A expression do not change sub-epithelial collagen deposition.
Chakir J et al., European Respiratory Journal 2009 Jul 16. Epub ahead of print.
2. The combination of LABA and inhaled steroids did not lead to a significant reduction in the rate of moderate exacerbations or hospital admissions in children.
The purpose of this review was to identify the benefits and safety profile of adding long-acting β2-agonists to inhaled corticosteroids in asthmatic children. A total of 25 trials representing 31 control-intervention comparisons randomizing 5572 children were included in the review. The addition of long-acting β2-agonists did not significantly reduce the risk of asthma exacerbations requiring rescue systemic steroids but improved lung function compared to ongoing treatment with a similar dose of inhaled corticosteroids. There was no evidence of increased serious side effects or withdrawals with the addition of long-acting β2-agonists. Compared to doubling the dose of inhaled corticosteroids, the combination of LABA and inhaled steroids improved lung function and resulted in a greater growth.
Editor's comment: This review indicates that combination therapy improves lung function in children.
Ni Chroinin M et al., Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD007949. DOI: 10.1002/14651858.CD007949
3. Basophil activation test in IgE mediated allergic reactions to dipyrone.
51 patients with selective immediate allergic reactions to pyrazolones and 56 controls were defined by skin testing or a drug provocation test and basophil activation test (BAT) with pyrazolones. Patients who were BAT positive were followed-up for 30 months to establish the rate of decline in positive tests. BAT was positive in 28 (54.9%) cases. BAT sensitivity was higher in those who were skin-test positive (85.7%) compared with those who were skin-test negative (33.3%). The time between the initial reaction and this study was significantly shorter in those who were skin-test positive (P=0.005) and those who were BAT positive (P=0.017). Follow-up of the BAT-positive patients showed a decrease over time, with 60% becoming negative after 6 months. The combination of skin testing and BAT can be used as a diagnostic tool. BAT could be the first choice, especially in cases at risk to develop symptoms after skin testing.
Editor's comment: BAT is a useful complement to skin testing to evaluate immediate allergic reactions to pyrazolones.
Gómez E et al., Clinical & Experimental Allergy 39, 8:1217-1224 (2009) August
4. Probiotics for the treatment of eczema: a systematic review.
This is a systematic review of randomized-controlled trials (RCTs) to evaluate the efficacy of probiotics for eczema treatment. Twelve trials (781 participants) were identified with live orally ingested microorganisms for the treatment of eczema. Meta-analysis of data from five of these trials showed that there was no significant reduction in eczema symptoms with probiotic treatment compared with placebo (mean difference -0.90 points on a 20-point visual analogue scale; 95% confidence interval -2.84, 1.04). Meta-analysis of data from seven trials showed no significant difference in investigator rated eczema severity between probiotic and placebo treatments. Subgroup analysis by eczema severity or presence of atopy did not identify a specific population in which probiotic treatment was effective. There was significant heterogeneity among studies; however, the results of three studies that used the same probiotic strain were concordant showing increased eczema severity after treatment. The adverse events search identified case reports of sepsis and bowel ischemia attributed to probiotics.
Editor's comment: This review indicates that probiotics should not be recommended for treating eczema, although novel probiotic strains may play a role in eczema management.
Boyle RJ et al., Clinical & Experimental Allergy 39, 8: 1117-1127 (2009) August
5. Internet-based self-management plus education compared with usual care in asthma.
To evaluate the effectiveness of Internet-based asthma self-management (IBSM), the authors designed a randomized, controlled trial. 200 adults with asthma who were treated with inhaled corticosteroids for 3 months or more during the previous year and had access to the Internet were included. Asthma-related quality of life at 12 months (minimal clinically significant difference of 0.5 on the 7-point scale), asthma control, symptom-free days, lung function, and exacerbations were recorded. Participants were randomly assigned by using a computer-generated permuted block scheme to IBSM (n = 101) or usual care (n = 99). The IBSM program included weekly asthma control monitoring and treatment advice, online and group education, and remote Web communications. IBSM improves asthma-related quality of life, asthma control, and lung function and increases the number of symptom-free days but does not reduce exacerbations. Improvement in asthma-related quality of life was not clinically significant.
Editor's comment: Although Internet-based self management can improve some asthma outcomes, the improvements are small and the program does not reduce the number of exacerbations.
van der Meer, V et al., Annals of Internal Medicine, 151, 2: 110-120 (2009) 21 July
6. The influence of parental educational level on the development of atopic sensitization.
The researchers evaluated the association between parental education, as a measure of socioeconomic status (SES), and the occurrence of atopic sensitization, recurrent wheezing and eczema among 609 children during the first year of life. Information on parental education, family history of atopic diseases and other factors was obtained from parental questionnaires completed at 5 months of pregnancy and 3 months after birth. Further parental questionnaires on early life illnesses experienced by the children were completed when they reached the age of 1 year. Blood samples were also taken from both parents and children and examined for total and specific IgE against common allergens. At the age of 1 year, 13.3% of the children were atopic, 9.1% had recurrent wheezing, and 25.1% had eczema. Eight out of 63 (12.7%) recurrent wheezers and 49 out of 173 (28.3%) children with eczema were atopic. Analysis revealed that a high parental educational vs. low parental education level was associated with a 2.1-fold increased risk for atopic sensitization and a 1.9-fold increased risk for eczema.
Editor's comment: Aspects associated with a high parental education level may play an important role in the development of atopic disorders.
Dom S et al., Pediatric Allergy and Immunology 20, 5: 438-447 (2009) August
7. Does higher body mass index contribute to worse asthma control in an urban population?
The researchers studied the relationship between BMI and asthma control among 292 people with asthma from an ethnically diverse urban community with a high prevalence of obesity. The average age of the participants was 47 years, 82% were women and 67% were African American. All the participants completed four validated asthma control questionnaires. Overall, 63% of the participants were obese (BMI ≥30 kg/m²), 22% were overweight (BMI 25-29.9 kg/m²), and 15% were of normal weight (18.5-24.9 kg/m²). Scores on the four questionnaires indicated that, on average, the participants had suboptimal asthma control with an average score of 8.3 out of 19 on the ACCI, 15.4 out of 25 on the ACT, 2.1 out of 6 on the ACQ, and 1.3 out of 4 on the ATAQ. 96% of the cohort met criteria for suboptimal control on at least one of the questionnaires. Regression analysis revealed no significant association between BMI and asthma control using any of the four control questionnaires.
Editor's comment: This study does not suggest that weight loss would result in improved asthma control.
Clerisme-Beaty E et al., The Journal of Allergy and Clinical Immunology 124, 2: 207-212 (2009) August
8. Filaggrin gene defects and risk of developing allergic sensitisation and allergic disorders.
Systematic review and meta-analysis to investigate whether filaggrin gene defects, present in up to one in 10 western Europeans and North Americans, increase the risk of developing allergic sensitization and allergic disorders. 24 studies were included from genetic epidemiological studies (family, case-control) of the association between filaggrin gene defects and allergy. The odds of developing allergic sensitisation was 1.91 (95% confidence interval 1.44 to 2.54) in the family studies and 1.57 (1.20 to 2.07) in the case-control studies. Filaggrin gene defects increase the risk of developing allergic sensitization, atopic eczema, and allergic rhinitis. Evidence of the relation between filaggrin gene mutations and atopic eczema was strong, with people manifesting increased severity and persistence of disease. Filaggrin gene mutations also increased the risk of asthma in people with atopic eczema.
Editor's comment: Restoring skin barrier function in filaggrin deficient people in early life may help prevent the development of sensitisation and halt the development and progression of allergic disease.
van den Oord R and Sheikh A, BMJ 2009; 339: b2433 (2009) 9 July
Also see editorial on Gene defects and allergy. Van Bever, H et al., BMJ 2009; 339: b1203.
9. Mina, an IL 4 repressor, controls T helper type 2 bias.
Mina, a member of the jumonji C (JmjC) protein family, is a genetic determinant of TH2 bias. Mina specifically bound to and repressed the IL4 promoter. Mina overexpression in transgenic mice impaired IL4 expression, whereas its knockdown in primary CD4+ T cells led to IL4 derepression. These findings collectively provide mechanistic insight into an IL-4-regulatory pathway that controls helper T cell differentiation and genetic variation in TH2 bias.
Editor's comment: Mina a genetic determinant of the TH2 bias, could affect susceptibility to infectious, autoimmune and allergic diseases.
Okamoto M et al., Nature Immunology 10, 8: 872-879 (2009) August
10. Sleep-disordered breathing linked to behavior problems.
To investigate if sleep-disordered breathing (SDB) are linked to behavior problems, 194 asthmatic children, aged 4-10, who were participating in an urban school-based asthma intervention program were studied. An amended version of the Sleep-Related Breathing Disorder Questionnaire (SRBDQ) was used to assess snoring and sleepiness, with a score of more than 0.33 indicating SDB. Behavior problems were assessed with the caregiver-completed Behavior Problem Index (BPI), which includes eight behavioral subdomains. The researchers found that 33% of the children experienced SDB and were more likely to have significant behavioral problems than the asthmatic children without SDB, as indicated by respective scores on the BPI of 13.7 vs 8.8, with a higher score indicating greater behavioral problems.
Editor's comment: SBD is associated with a significantly increased risk for behavior problems among asthmatic children.
Fagnano M et al., Pediatrics 124, 1: 218-225 (2009) July
11. Prevalence of obstructive sleep apnea-hypopnea in severe versus moderate asthma.
Complete overnight home polysomnography was performed in 26 patients with severe asthma consecutively recruited to a difficult-to-treat asthma program, 26 patients consecutively recruited with moderate asthma, and 26 controls without asthma of similar age and body mass index. Flow rates and Juniper asthma control and quality of life questionnaires were also obtained. Obstructive sleep apnea-hypopnea, defined by an Apnea-Hypopnea Index ≥15 events/h of sleep scored using Chicago criteria, was present in 23 of 26 (88%) patients with severe asthma, 15 of 26 (58%) patients with moderate asthma, and 8 of 26 (31%) controls without asthma ( χ2: P < .001). Obstructive sleep apnea-hypopnea was significantly more prevalent among patients with severe compared with moderate asthma and more prevalent for both asthma groups than controls without asthma. These observations suggest potential pathophysiologic interactions between obstructive sleep apnea-hypopnea and asthma severity and control.
Editor's comment: This paper indicates a direct link between obstructive sleep apnea and degree of asthma control.
Julien J et al., The Journal of Allergy and Clinical Immunology, 124, 2: 371-376 (2009) August
12. The role of bacterial infections in hand eczema (HE).
Bacterial swabs were taken at three different visits from the hands and nares in 50 patients with HE and 50 controls to determine the prevalence of Staphylococcus aureus in patients with HE compared with controls and to relate presence of S. aureus, subtypes and toxin production to severity of HE. Staphylococcus aureus was subtyped by spa typing and assigned to clonal complexes, and isolates were tested for exotoxin-producing S. aureus strains. The Hand Eczema Severity Index was used for severity assessment. Staphylococcus aureus was found on the hands in 24 patients with HE and four controls (P < 0·001), and the presence of S. aureus was related to increased severity of the eczema (P < 0·001).
Editor's comment: S. aureus could be an important cofactor for persistence of HE.
Haslund P et al., British Journal of Dermatology, Early View 3 July 2009 Published online.