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- Does Use of Inhaled Corticosteroid for Management of Asthma in Children Make Them Shorter Adults? [JOURNAL ARTICLE]
- Pediatr Allergy Immunol Pulmonol 2013 Jun; 26(2):99-101.
The purpose of this review is to discuss the effect of daily inhaled corticosteroids (ICSs) on the height of children with asthma. The effect of ICSs on growth and height is dependent on the dose and the therapeutic index of the ICS; however, the effect on final adult height was not clear until recently. New data suggest that if growth suppression occurs with the use of ICSs in children, it is sustained, but not cumulative over the years. The observed reduction in the final adult height is small and does not outweigh the benefits of ICSs, and the growth effect may be minimized by use of newer ICSs and other approaches for management of asthma in children with mild to moderate asthma.
- Determining the Relative Burden of Childhood Asthma at the Local Level by Surveying School Nurses. [JOURNAL ARTICLE]
- Pediatr Allergy Immunol Pulmonol 2013 Jun; 26(2):76-80.
Schools are effective venues for providing pediatric asthma education programs. Resources are limited, however, so ideally, these programs should be provided to schools with the highest prevalence. National and state asthma surveillance data cannot be extrapolated to local geographic areas. The objective of this study was to survey local schools on Long Island to obtain this information. Survey forms were mailed to the school nurses at every school in Nassau and Suffolk Counties, New York, in 2004, 2006, 2008, and 2010 asking for the number of children with asthma and the number who had permission to access rescue medication in the school. School nurses completed and returned the forms. We analyzed data from elementary and high schools separately, as high-school students often carry their medications with them without obtaining permission. Of the 3,327 surveys sent, 2,060 (61.9%) were returned and 1,807 (54.3%) could be included in the analyses. Overall, asthma prevalence increased from 7.6% in 2004 to 8.7% in 2010. This mirrored the New York State and national trends, although the rates we found were generally lower. The rate of asthmatic children with permission to access rescue medication in school was about the same throughout the study period (39.7% in 2004 and only 42.3% in 2010). Both rates were lower in elementary schools in low socioeconomic areas. These methods allowed us to compare the burden of childhood asthma in individual responder schools in a relatively large geographic area.
- Provider Perceptions of Parent Health Literacy and Effect on Asthma Treatment Recommendations and Instructions. [JOURNAL ARTICLE]
- Pediatr Allergy Immunol Pulmonol 2013 Jun; 26(2):69-75.
Little is known about how pediatric providers assess parental health literacy, how concordant they are with validated measures of health literacy, and how these perceptions may influence treatment recommendations, how instructions are given or how reliable they perceive parents to be in carrying out instructions. Two hundred and eighty-one parents of 6-12-year-old asthma patients attending a pediatric clinic visit were recruited to a cross-sectional study of health literacy and asthma outcomes. Fourteen pediatric healthcare providers participated. Parents completed surveys that included 2 measures of health literacy: the Test of Function Health Literacy in Adults (TOFHLA) and the Rapid Estimate of Adult Literacy in Medicine (REALM). Immediately postvisit, pediatric providers completed a brief survey asking their assessment of the parent's health literacy and how it impacted treatment instructions and recommendations. Kappa statistics tested concordance; chi square and logistic regression tested associations among provider ratings, rating concordance, and demographic factors. Six providers were interviewed regarding the bases for their ratings. Providers' perceptions influenced asthma treatment recommendations (p=0.001) and how treatment instructions were given (p=0.001). Providers indicated that their perceptions were shaped by parent's verbal communication skills and patterns of past behavior related to children's asthma management. Data from 277 parents indicated that most had adequate health literacy with a lower percentage scored as adequate by the REALM versus the TOFHLA. Pediatric provider estimates of parental health literacy had low concordance with the validated measures. Providers were more likely to designate whites as adequately health literate. Pediatric asthma providers' perceptions of parents' health literacy can influence treatment recommendations and instructional practices.
- Differential regulation of inflammation and immunity in mild and severe experimental asthma. [Journal Article]
- Mediators Inflamm 2013.:808470.
This study aimed at exploring innate and adaptive immunity in allergic asthma by investigation of mRNA expression of pattern recognition receptors, T-cell-specific cytokines, and transcription factors. Mouse models for mild and severe asthma, with similar pathological characteristics observed in humans, were used to study the involved inflammatory markers as a first step in the development of phenotype-directed treatment approaches. In the mild model, mice were sensitized to ovalbumin-Imject Alum and challenged with ovalbumin. In the severe model, mice were sensitized to trinitrophenyl-conjugated ovalbumin and challenged with trinitrophenyl-ovalbumin/IgE immune complex. Pulmonary airway inflammation and mRNA expression of Toll-like receptors (TLRs), NOD-like receptors (NLRs), T cell cytokines, and transcription factors in lung tissue were examined. Different mRNA expression profiles of TLRs, NLRs, T cell cytokines, and transcription factors were observed. In the mild model, Il10 showed the largest increase in expression, whereas in the severe model, it was Inf γ with the largest increase. Expression of Tbet was also significantly increased in the severe model. Inflammation and immunity are differentially regulated in mild and severe experimental asthma. This preclinical data may help in directing clinical research towards a better understanding and therapy in mild and severe asthmatic patients.
- Modulation of IL-8 Boosted by Mycoplasma pneumoniae lysate in Human Airway Epithelial Cells. [JOURNAL ARTICLE]
- J Clin Immunol 2013 Jun 19.
Mycoplasma pneumoniae, a major cause of community-acquired pneumonia, has been recognized as a trigger for asthma inception and exacerbation. The epithelial cells on the respiratory tract parasitized by M. pneumoniae exhibit a number of cytopathic effects as a result of local inflammation and stimulated host immune response. We investigated the interactions of signaling molecules regulating the release of IL-8 by the direct stimulation of M. pneumoniae lysate (MPL) in human airway epithelial cells. In human airway epithelial cells, MPL-induced IL-8 proteins were decreased by monoclonal anti-TLR2 antibody in a dose-dependent fashion, and significantly blocked by siRNA TLR2. The pharmacologic inhibitors of ERK, U0126 and PD98059, effectively reduced IL-8 expression and the active forms of ERK signaling molecules, as detected by anti-phosphorylated p44/42 antibody. The region spanning from -132 to +41 in the IL-8 promoter demonstrated the highest luciferase activity against MPL and the mutations of NF-κB and NF-IL6 entirely diminished the activity. After investigating transfections of the NF-κB and NF-IL6 reporter vectors, NF-IL6 activation was significantly induced by MPL stimulation, which was considerably decreased by U0126 and monoclonal anti-TLR2 antibody. These results indicate that MPL-induced IL-8 increase is transcriptionally regulated by NF-IL6 more than by NF-κB. Additionally, the activation of NF-IL6 is influenced by TLR2 and ERK signaling pathways in airway epithelial cells.
- Laboratory animals and respiratory allergies: The prevalence of allergies among laboratory animal workers and the need for prophylaxis. [Journal Article]
- Clinics (Sao Paulo) 2013 Jun; 68(6)
Subjects exposed to laboratory animals are at a heightened risk of developing respiratory and allergic diseases. These diseases can be prevented by simple measures such as the use of personal protective equipment. We report here the primary findings of the Laboratory Animals and Respiratory Allergies Study regarding the prevalence of allergic diseases among laboratory animal workers, the routine use of preventive measures in laboratories and animal facilities, and the need for prevention programs.Animal handlers and non-animal handlers from 2 Brazilian universities (University of São Paulo and State University of Campinas) answered specific questionnaires to assess work conditions and symptoms. These subjects also underwent spirometry, a bronchial challenge test with mannitol, and skin prick tests for 11 common allergens and 5 occupational allergens (rat, mouse, guinea pig, hamster, and rabbit).Four hundred fifty-five animal handlers (32±10 years old [mean±SD], 209 men) and 387 non-animal handlers (33±11 years old, 121 men) were evaluated. Sensitization to occupational allergens was higher among animal handlers (16%) than non-animal handlers (3%, p<0.01). Accessibility to personal protective equipment was measured at 85% (median, considering 73 workplaces of the animal handler group). Nineteen percent of the animal handlers indicated that they wear a respirator at all times while handling animals or working in the animal room, and only 25% of the animal handlers had received an orientation about animal-induced allergies, asthma, or rhinitis.In conclusion, our data indicate that preventive programs are necessary. We suggest providing individual advice to workers associated with institutional programs to promote a safer work environment.
- Effect of antigen binding affinity and effector function on the pharmacokinetics and pharmacodynamics of anti-IgE monoclonal antibodies. [Journal Article]
- MAbs 2012 Nov 1; 4(6):724-31.
Modulating the binding affinities to IgE or changing the FcγR binding properties of anti-IgE antibodies offers an opportunity to enhance the therapeutic potential of anti-IgE antibodies, but the influence of increased affinity to IgE or reduced Fc effector function on the pharmacological properties of anti-IgE therapies remains unclear. Our studies were designed to characterize the pharmacokinetics, pharmacodynamics and immune-complex distribution of two high-affinity anti-IgE monoclonal antibodies, high-affinity anti-IgE antibody (HAE) 1 and 2, in mice and monkeys. HAE1, also known as PRO98498, is structurally similar to omalizumab (Xolair®), a humanized anti-IgE IgG1 marketed for the treatment of asthma, but differs by 9 amino acid changes in the complementarity-determining region resulting in a 23-fold improvement in affinity. HAE2 is similar to HAE1, but its Fc region was altered to reduce binding to Fcγ receptors. As expected given the decreased binding to Fcγ receptors, systemic exposure to pre-formed HAE2:IgE complexes in mice was greater (six-fold) and distribution to the liver lower (four-fold) compared with HAE1:IgE complexes. In monkeys, systemic exposure to HAE1 was similar to that previously observed for omalizumab in this species, but required comparatively lower serum drug concentrations to suppress free IgE levels. HAE2 treatment resulted in greater exposure and greater increase of total IgE, relative to HAE1, because of decreased clearance of HAE2:IgE complexes. Overall, these data suggest that increased binding affinity to IgE may provide a more effective therapeutic for asthma patients, and that retaining FcγR binding of the anti-IgE antibody is important for elimination of anti-IgE:IgE complexes.
- Spatiotemporally resolved air exchange rate as a modifier of acute air pollution-related morbidity in Atlanta. [JOURNAL ARTICLE]
- J Expo Sci Environ Epidemiol 2013 Jun 19.
Epidemiological studies frequently use central site concentrations as surrogates of exposure to air pollutants. Variability in air pollutant infiltration due to differential air exchange rates (AERs) is potentially a major factor affecting the relationship between central site concentrations and actual exposure, and may thus influence observed health risk estimates. In this analysis, we examined AER as an effect modifier of associations between several urban air pollutants and corresponding emergency department (ED) visits for asthma and wheeze during a 4-year study period (January 1999-December 2002) for a 186 ZIP code area in metro Atlanta. We found positive associations for the interaction between AER and pollution on asthma ED visits for both carbon monoxide (CO) and nitrogen oxides (NOx), indicating significant or near-significant effect modification by AER on the pollutant risk-ratio estimates. In contrast, the interaction term between particulate matter (PM)2.5 and AER on asthma ED visits was negative and significant. However, alternative distributional tertile analyses showed PM2.5 and AER epidemiological model results to be similar to those found for NOx and CO (namely, increasing risk ratios (RRs) with increasing AERs when ambient PM2.5 concentrations were below the highest tertile of their distribution). Despite the fact that ozone (O3) was a strong independent predictor of asthma ED visits in our main analysis, we found no O3-AER effect modification. To our knowledge, our findings for CO, NOx, and PM2.5 are the first to provide an indication of short-term (i.e., daily) effect modification of multiple air pollution-related risk associations with daily changes in AER. Although limited to one outcome category in a single large urban locale, the findings suggest that the use of relatively simple and easy-to-derive AER surrogates may reflect intraurban differences in short-term exposures to pollutants of ambient origin.Journal of Exposure Science and Environmental Epidemiology advance online publication, 19 June 2013; doi:10.1038/jes.2013.32.
- Parental psychological distress during pregnancy and wheezing in preschool children: The Generation R Study. [JOURNAL ARTICLE]
- J Allergy Clin Immunol 2013 Jun 15.
BACKGROUND:Maternal psychological distress during pregnancy might affect fetal lung development and subsequently predispose children to childhood asthma.
OBJECTIVE:We sought to assess the associations of maternal psychological distress during pregnancy with early childhood wheezing.
METHODS:We performed a population-based prospective cohort study among 4848 children. We assessed maternal and paternal psychological distress at the second trimester of gestation and 3 years after delivery and maternal psychological distress at 2 and 6 months after delivery by using the Brief Symptom Inventory questionnaire. Wheezing in the children was annually examined by using questionnaires from 1 to 4 years. Physician-diagnosed ever asthma was reported at 6 years.
RESULTS:Mothers with psychological distress during pregnancy had increased odds of wheezing in their children from 1 to 4 years of life (overall distress: odds ratio [OR], 1.60 [95% CI, 1.32-1.93]; depression: OR, 1.46 [95% CI, 1.20-1.77]; and anxiety: OR, 1.39 [95% CI, 1.15-1.67]). We observed similar positive associations with the number of wheezing episodes, wheezing patterns, and physician-diagnosed asthma at 6 years. Paternal distress during pregnancy and maternal and paternal distress after delivery did not affect these results and were not associated with childhood wheezing.
CONCLUSION:Maternal psychological distress during pregnancy is associated with increased odds of wheezing in their children during the first 6 years of life independent of paternal psychological distress during pregnancy and maternal and paternal psychological distress after delivery. These results suggest a possible intrauterine programming effect of maternal psychological distress leading to respiratory morbidity.
- Long Term Exposure to PM10 and NO2 in Association with Lung Volume and Airway Resistance in the MAAS Birth Cohort. [JOURNAL ARTICLE]
- Environ Health Perspect 2013 Jun 18.