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Archives: Medical Journal Reviews

Medical Journal Review

Posted: September 2009

Reviewed by Juan Carlos Ivancevich, MD, in collaboration with Richard Lockey, MD, WAO Web Editor-in-Chief.

1. Dose-response relationship of inhaled corticosteroids (ICS) and cataracts
A systematic review and meta-analysis is reported of four case-control studies of cataracts and ICS use, with a total of 46,638 cases and 146,378 controls. The primary outcome was risk of cataracts. There was a significant relationship between risk of cataracts and ICS dose, with a random effects pooled odds ratio for risk of cataracts per 1000 µg increase in daily beclomethasone dose of 1.25 (95% CI: 1.14-1.37). The risk of cataracts was increased by approximately 25% for each 1000 µg per day increase in the dose of beclomethasone or equivalent.
Editor's comment: These findings reinforce the importance of prescribing the least amount of an ICS to control asthma and screening for the presence of cataracts in older subjects with asthma and COPD.
Weatherall, M. et al., Dose-response relationship of inhaled corticosteroids and cataracts: A systematic review and meta-analysis, Respirology, 983-990, Published Online August 2, 2009.

2. Probiotic effects on incidence and duration of cold and influenza-like symptoms (ILS) in children
This DBPC (double-blind, placebo-controlled) study on 326 healthy children (3-5 years) reports on the effects of probiotic consumption during the winter season. Subjects were assigned randomly to receive placebo (N = 104), Lactobacillus acidophilus NCFM (North Carolina Food Microbiology) (N = 110), or L acidophilus NCFM in combination with Bifidobacterium animalis subsp lactis Bi-07 (N = 112), treated twice daily for 6 months. Single and combination probiotics relative to placebo significantly reduced the incidence and duration of fever, cough and rhinorrhea, antibiotic use and days absent from child care.
Editor's comment: Daily dietary probiotic supplementation may be a safe and effective way to reduce cold and ILS symptoms in children 3 to 5 years of age.
Leyer G. et al., Probiotic Effects on Cold and Influenza-Like Symptom Incidence and Duration in Children, Pediatrics, 124(2):e172-e179.

3. Unmet needs in severe chronic upper airway disease (SCUAD)
SCUAD defines patients whose symptoms are inadequately controlled despite optimal, i.e., effective, safe, and acceptable, pharmacologic treatment based on guidelines. These patients have an impaired quality-of-life, social function, sleep, and school/work performance. Severe uncontrolled allergic rhinitis, nonallergic rhinitis, chronic rhinosinusitis, aspirin exacerbated respiratory disease, and occupational airway diseases are defined as SCUADs. The group of experts who wrote this paper believes that SCUADs should be considered differently from mild chronic upper airway diseases. It reviews the state-of- the-art literature, highlighting gaps in knowledge, and proposes several areas for the better understanding, prevention, and management of SCUADs.
Editor's comment: This paper hopefully will prompt the pharmaceutical industry to increase research for SCUAD.
Bousquet J. et al., Unmet needs in severe chronic upper airway disease (SCUAD), JACI 24(3): 428-433.

4. Obesity, Waist Size, and Prevalence of Current Asthma in Cohort Study
The authors report data on 88,304 women, over age 18, who participated in The California Teachers Study. Information on waist size, BMI, asthma diagnoses, smoking, and other variables were collected in 1995, 1997, 2000, and 2005. Of the 88,304 women, 11,500 were obese (BMI 30 kg/m² or higher) in 1995, including 1334 who were extremely obese (BMI of 40 kg/m² or higher). The women who were obese at baseline were more than twice as likely to have adult-onset asthma as women with a normal weight (BMI less than 25 kg/m²); those who were extremely obese were more than three times more susceptible to adult-onset asthma. Women with a waist circumference of more than 88 cm were significantly more likely to have adult-onset asthma than their thinner counterparts, even with a normal BMI.
Editor's comment: This paper suggests an association between obesity and waist size and asthma prevalence, the latter even with a normal BMI.
Von Behren J. et al., Obesity, Waist Size, and Prevalence of Current Asthma in the California Teachers Study Cohort, Thorax, Published online first: 25 August 2009.

5. Hypochlorite bleach, atopic sensitization, and respiratory symptoms in adults
This paper reports 3626 participants of the European Community Respiratory Health Survey II in 10 countries who used bleach as a domestic cleaning agent and for whom data were available on specific serum IgE to four environmental allergens. Frequency of bleach use and information on respiratory symptoms were obtained by interviews. House dust mite and cat allergens in mattress dust were measured. Associations between the frequency of bleach use and health outcomes were evaluated. The use of bleach was associated with less atopic sensitization (odds ratio [OR], 0.75; 95% CI, 0.63-0.89). Dose-response relationships (P < .05) were apparent for the frequency of bleach use and sensitization rates.
Editor's comment: People who clean their homes with hypochlorite bleach are less likely to be atopic but more likely to have respiratory symptoms.
Zock J-P et al., Domestic use of hypochlorite bleach, atopic sensitization, and respiratory symptoms in adults, JACI, Published online 10 August 2009

6. PS increases effect of TRP on childhood asthma incidence
These researchers identified 2,497 children aged 5-9 years with no history of asthma or wheeze at entry (2002-2003) into a prospective cohort study to investigate whether low socioeconomic status or high parental stress (PS) modified the effect of traffic-related air pollution (TRP) and in utero tobacco smoke exposure on new onset asthma. The primary outcome was a parental report of doctor-diagnosed new onset asthma during 3 years of follow-up. The risk of asthma attributable to TRP was significantly higher for subjects with high PS (HR 1.51; 95% CI 1.16-1.96) than with low PS (HR 1.05, 95% CI 0.74-1.49; P value 0.05). Stress also was associated with adverse effects of in utero tobacco smoke.
Editor's comment: The results suggest that children from stressful households are more susceptible to the effects of TRP and in utero tobacco smoke.
Shankardass K. et al., PNAS 106(30): 12406-12411.

7. Arginase: key enzyme in the pathophysiology of allergic asthma
Ex vivo and in vivo studies in animal models and asthmatic patients indicate that arginase may play a central role in allergen-induced early and late bronchial obstructive reactions, airway hyperresponsiveness (AHR), airway inflammation and airway remodelling. Increased arginase activity in the airways induces reduced bioavailability of L-arginine to constitutive (cNOS) and inducible (iNOS) nitric oxide synthases, causing a deficiency of bronchodilatation and anti-inflammatory NO, as well as increased formation of peroxynitrite, which may be involved in allergen-induced airways obstruction, AHR and inflammation. Reduced NO production, enhanced synthesis of L-ornithine, and increased arginase activity may promote cell proliferation and collagen deposition.
Editor's comment: Arginase inhibitors may have therapeutic potential to treat acute and chronic asthma.
Maarsingh H. et al., Arginase: a key enzyme in the pathophysiology of allergic asthma opening novel therapeutic perspectives, Br J Pharmacol. Early view, published online 24 August 2009.

8. T-helper Type 2-driven Inflammation Defines Major Subphenotypes of Asthma
The authors classified subjects with asthma based on high or low expression of IL-13-inducible genes using microarray and PCR analyses of airway epithelial brushings from 42 patients with mild-to-moderate asthma and 28 healthy controls. They investigated its clinical implications through cytokine expression in bronchial biopsies, markers of inflammation and remodelling, responsiveness to inhaled corticosteroids, and reproducibility. Two evenly sized and distinct subgroups were identified,"Th2-high" and "Th2-low" asthma, differing significantly in expression of IL-5 and IL-13 in bronchial biopsies and in hyperresponsiveness, serum IgE, eosinophilia, subepithelial fibrosis, and airway mucin gene expression (all P < 0.03). Inhaled corticosteroid effectiveness is restricted to Th2-high asthma.
Editor's comment: Current models do not adequately explain non-Th2-driven asthma.
Woodruff P et al., T-helper Type 2-driven Inflammation Defines Major Subphenotypes of Asthma, Am J Respir Crit Care Med 180(5): 388-395.

9. Allergic status of schoolchildren with food allergy to eggs, milk or wheat in infancy.
The investigators conducted a large-scale survey to investigate the allergic status of schoolchildren who avoided eggs, milk or wheat because of an immediate-type allergic reaction at < 1-yr-old. A questionnaire was distributed to the parents of 14,669 schoolchildren aged 7 to 15 years in 30 schools in Kyoto. 13,215 responded (90.1%). Of the children who had allergies as infants, 5.4% were avoiding foods at the age of 7 and 3% at the age of 15. More than 80% became tolerant by school age, but the prevalence of bronchial asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis and food allergy were significantly higher in this group.
Editor´s comment: Food avoiders in infancy have a higher risk of allergic diseases and allergy to other foods at school age.
Kusunoki T. et al., Allergic status of schoolchildren with food allergy to eggs, milk or wheat in infancy, Pediatr Allergy Immunol, Early View, published online 21 August 2009.

10. HDM-SLIT - The Role for TGF-beta and Functional Regulatory T Cells
A detailed immunological investigation of House Dust Mite Sublingual Immunotherapy (HDM-SLIT) was performed in a 12-month randomized DBPC (Double-blind, Placebo-Controlled) study in 30 HDM-allergic subjects, with one-year open extension in 9 patients on SLIT. Allergen-induced CD4+ T cell division and IL-5 production were significantly decreased on SLIT. sTGF-betaRII blocked immunotherapy-induced suppression of allergen-specific T cell proliferation, decreased allergen-specific CD4+ T cell proliferation and increased IL-10 secretion and serum Der p 2-specific IgG4. Regulatory T cells function was demonstrated by suppression of allergen-specific effector T cell proliferation and cytokine production. SLIT significantly decreased the rhinitis symptom score, total asthma score, and Juniper QoL score.
Editor´s comment: TGF-beta mediates the immunological suppression seen early in clinically-effective HDM-SLIT. It also increases regulatory T cells with suppressor function.
O'Hehir R et al., House Dust Mite Sublingual Immunotherapy - The Role for TGF-beta and Functional Regulatory T Cells, Am J Respir Crit Care Med, published ahead of print 20 August 2009.

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