bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Rattles, Purrs and Whistles as Predictors of Later Wheeze
Authors: Mehrotra Anjuli , Lasley Mary V. 
Published: October 2008

Turner SW, Craig LCA, Harbor PJ, et al. Arch Dis Child. 2008;93(8):701–704
PURPOSE OF THE STUDY. To determine how different respiratory sounds in 2-year-olds (whistles, purrs, and rattles) characterized as wheeze by parents predicted wheeze and asthma diagnosis at 5 years of age. A better understanding of parental descriptions of respiratory symptoms may lead to a more accurate diagnosis of asthma.
STUDY POPULATION. The study subjects were children followed at 2 time points: at ages 2 and 5 years. They were recruited randomly before birth irrespective of history of parental asthma and allergy.
METHODS. Two thousand pregnant women were recruited randomly at 12 weeks’ gestation, initially as part of a longitudinal birth cohort designed to relate dietary exposure in early life to asthma outcomes in childhood. Parents filled out questionnaires by mail regarding respiratory symptoms when their children were aged 2 and 5 years. Questions included, “Has your child ever suffered from asthma?” and “Has this been diagnosed by a doctor?” Current wheeze was defined as wheezing that has occurred over the last 12 months. If present, parents were asked to categorize the wheeze by sound, describing it as a whistle, rattle, purr, or other sound. If “other sound” was designated, the subjects were excluded from the analysis.
RESULTS. A total of 210 children wheezed as determined by the questionnaire at 2 years of age, and 77% (162) of the parents of these children also returned a questionnaire when the child was 5 years old. Wheeze persisted in 62 of these subjects. At 5 years of age, children with “whistle” at age 2 were more likely to have current wheeze (73% [11 of 15]) with physician-confirmed asthma (67% [10 of 15]). They were also more likely to be on asthma treatment (40% [6 of 15]). This was compared with “rattle,” which only translated to a 34% (33 of 97) incidence of current wheeze at age 5 and 42% (43 of 97) with physician-confirmed asthma, with 11% (11 of 97) on asthma therapy. A description of “purr” at age 2 had similar outcomes to that of rattle. Children with whistle at 2 years of age were more likely to have mothers with asthma, whereas children with rattle and purr were more likely to be exposed to environmental tobacco smoke.
CONCLUSIONS. Parents often interpret any respiratory sound as “wheeze.” When respiratory sounds are further characterized as whistle, rattle, or purr, a parent using the terminology “whistle” to describe his or her child's wheeze was a good predictor of persisting symptoms and was associated with future asthma treatment. Use of terms “rattle” and “purr” did not predict future wheeze particularly well.
REVIEWER COMMENTS. In pediatric medicine, physicians must rely on parents for the history. For children with respiratory symptoms, parents often do not understand or know what “wheeze” means. Having parents use terms such as whistle, rattle, or purr to characterize the noise they hear may help physicians make a diagnosis of asthma, especially if the term whistle is used.
Atopic Sensitization and the International Variation of Asthma Symptom Prevalence in Children
Authors: Kelso John M. 
Published: October 2008

Weinmayr G, Weiland SK, Björkstén B, et al. Am J Respir Crit Care Med. 2007;176(6):565–574
PURPOSE OF THE STUDY. The International Study of Asthma and Allergies in Childhood (ISAAC I) found that the prevalence of asthma symptoms varies &gt;15-fold among various countries. ISAAC II was designed to identify why such differences occur.
STUDY POPULATION. Studied were a random sample of 8- to 12-year-old children (n = 54 439) in 22 countries worldwide.
METHODS. Data were collected by parental questionnaires (n = 54 439) and skin-prick tests (n = 31 759). Economic development was assessed by gross national income per capita.
RESULTS. Prevalence of current wheeze (wheeze during the last year) ranged from 0.8% (Ecuador) to 25.6% (Brazil). The prevalence of skin-prick test reactivity ranged from 1.7% (Ghana) to 45.3% (Hong Kong). The association between current wheeze and skin-prick test reactivity was stronger in affluent countries (odds ratio: 4.0 [95% confidence interval: 3.5–4.6]) than nonaffluent countries (odds ratio: 2.2 [95% confidence interval: 1.5–3.3]). The population attributable fraction (PAF), or fraction of current wheeze attributable to skin-prick test reactivity, ranged from 0% (Turkey) to 59.6% (Hong Kong). Overall, the combined PAFs were substantially higher in affluent countries (40.7%) than in nonaffluent countries (20.3%).
CONCLUSIONS. The authors concluded that the link between atopic sensitization and asthma symptoms in children differs strongly between populations and increases with economic development.
REVIEWER COMMENTS. The variation in rates of asthma and allergy around the world are striking, and the fact that the relationship between allergy and asthma seems related to the level of economic development in any given country is fascinating. The authors speculated that this may be a result of exposures or other factors that are different for children in more or less affluent countries that make it more or less likely that allergy would lead to asthma. Such factors could include greater exposure to helminth infections or different commensal bacteria in poorer countries and higher rates of urbanization and obesity in wealthier countries.
Pediatric Prescribing of Asthma Drugs in the UK: Are We Sticking to the Guideline?
Authors: Kelso John M. 
Published: October 2008

Cohen S, Taitz J, Jaffé A. Arch Dis Child. 2007;92(10):847–849
PURPOSE OF THE STUDY. Similar to those in the United States, there are asthma-treatment guidelines in the United Kingdom, which were published in 1993 and updated in 1995, 1997, 2003, and 2005. The authors wondered whether the prescribing habits of physicians reflect recommendations in these guidelines.
STUDY POPULATION. The population studies was persons in the United Kingdom National Health Service Information database, which includes all prescriptions dispensed by community pharmacists and dispensing doctors.
METHODS. Prescriptions for children were reviewed for the years 2000–2006.
RESULTS. From 2000 to 2006, the number of prescriptions for bronchodilator syrups decreased 60% from 302 500 to 121 000. The use of steroid-alone inhalers declined 22% from 1 968 000 to 1 525 000, whereas the use of combination steroid/long-acting β-agonist (LABA) inhalers increased sevenfold from 50 000 to 350 000. The percentage of total steroid inhalers prescribed as combination inhalers increased from 2% to 20%.
CONCLUSIONS. The authors concluded that the increase in the number of combination inhalers prescribed is not consistent with the guideline recommendations that combination inhalers should only be introduced in those patients with asthma that is not controlled on adequate doses of inhaled steroids.
REVIEWER COMMENTS. The authors noted that inhaled bronchodilators have fewer adverse effects and that, although the use of the oral bronchodilators has declined, there are still a large number of prescriptions being written for them. On the basis of other studies, they estimated that only 5% to 10% of children with asthma would qualify for treatment with combined inhaled-steroid/LABA inhalers, yet 20% are prescribed such medications. I suspect that these findings would be the same in the United States. It is useful to reinforce that that there is virtually no indication for treatment with oral bronchodilators, and only children whose condition has failed to respond to treatment with low- to medium-dose inhaled steroids alone should be treated with inhaled-steroid/LABA combinations.
Linoleic Acid Metabolites and Transepidermal Water Loss in Children With Atopic Dermatitis
Authors: Lester Mitchell R. 
Published: October 2008

Yang YH, Wang LC, Lee JH, Chiang BL. Ann Allergy Asthma Immunol. 2008;100(1):66–73
PURPOSE OF THE STUDY. To investigate whether n-6 essential fatty acid (EFA) deficits account for atopic dermatitis (AD) by affecting transepidermal water loss (TEWL).
STUDY POPULATION. Children between the ages of 2 and 17 years with AD (n = 35), asthma or allergic rhinitis (AS/AR group, n = 35), or no atopic disease (n = 31) were studied. The AD group did not have allergic airway disease.
METHODS. Synthesis of the n-6 EFA from linoleic acid (LA) involves alternating steps of desaturation and elongation with serial conversion to γ-linoleic acid (GLA), dihommo-γ-linoleic acid (DGLA), and arachidonic acid (AA). Fasting blood samples were obtained with immediate serum separation and freezing to prevent changes in fatty acid composition of serum lipids. Analysis of lipid content was performed by gas chromatography/mass spectrometry. Measurement of TEWL on the right volar forearm was reported as loss of grams of water per square meter of skin per hour. Nonparametric tests were used to evaluate differences between the groups.
RESULTS. Although not statistically significant, patients in the AD and AS/AR groups had higher LA and lower AA levels than controls. Patients with AD but not AS/AR had statistically lower GLA (P = .04) and DGLA (P = .03) levels than control subjects. There were no differences between the 2 groups of atopic patients. Ratios of GLA/LA, DGLA/LA, and AA/LA were lower in the AD group than controls (P &lt; .01 for each). However, in the AS/AR group, only the GLA/LA and DGLA/LA ratios were statistically lower than in controls. TEWL had a significant negative correlation with GLA and DGLA (P = .001) and near-significant negative correlation with AA (P = .06). In subjects with AD, TEWL and the Scoring Atopic Dermatitis (SCORAD) index were correlated (P &lt; .001). The SCORAD index had a significant correlation with GLA and DGLA (P &lt; .001) but not AA (P = .06).
CONCLUSIONS. AD is associated with a defect in n-6 EFA metabolism. LA metabolites are involved in the maintenance of the epidermal water barrier.
REVIEWER COMMENTS. Antimicrobial protein defects, filaggrin defects, and fatty acid defects are among the newer areas of research on the underlying pathogenesis of AD. Because human epidermis lacks the capacity to convert LA to GLA or DGLA to AA, it is likely that those LA metabolites are synthesized elsewhere and transported to the epidermis. Serum levels of n-6 EFAs, as reported here, presumably reflect epidermal concentrations. It follows, therefore, that dietary supplementation of GLA or topical application of LA metabolites may have therapeutic benefit.
Cigarette Smoke Exposure Impairs Dendritic Cell Maturation and T Cell Proliferation in Thoracic Lymph Nodes of Mice
Authors: Sharma Hemant P. , Matsui Elizabeth C. 
Published: October 2008

Robbins CS, Franco F, Mouded M, Cernadas M, Shapiro SD. J Immunol. 2008;180(10):6623–6628
PURPOSE OF THE STUDY. Airborne antigens are processed and presented by respiratory tract dendritic cells (DCs). The purpose of this study was to determine the consequences of cigarette-smoke exposure on DC function in mice.
METHODS. Mice were exposed to cigarette smoke 5 days per week for 1 month. There was also a control group of mice unexposed to smoke. Mice then underwent intratracheal injection of ovalbumin-fluorescein isothiocyanate (FITC) or ovalbumin and were killed at varying time points thereafter depending on the aspect of DC function being studied (migration, maturation, or T-cell activation). Lung cells were isolated, and the numbers of DCs were determined in exposed and unexposed mice by flow cytometry. Migration of lung DCs to thoracic lymph nodes (TLNs) was assessed by measuring CD11c+FITC+ cells. Maturation of TLN DCs after ovalbumin exposure was then determining by assessing expression of cell-surface costimulatory molecules (CD80, CD86, MHCII, CD40). T-cell proliferation was assessed by measuring T-cell–derived cytokine production by TLN cells in vitro. The staining profile was assessed to measure T-cell proliferation in vivo.
RESULTS. The number of lung DCs was decreased among mice exposed to cigarette smoke. Exposed mice did not exhibit decreased migration of lung DCs to TLNs, as evidenced by similar numbers of TLN CD11c+FITC+ cells as in unexposed mice. Although no differences were observed in migration, smoking suppressed DC maturation in the lymph nodes as demonstrated by decreased cell-surface expression of MHC class II and the costimulatory molecules CD80 and CD86. T-cell proliferation was impaired in smoke-exposed mice, evidenced by reduced interleukin 2 production from CD4 T cells as compared with controls. T-cell proliferation was also decreased in vivo: smoke-exposed mice had a lower percentage of T cells undergoing ≥6 cycles or cell division compared with controls.
CONCLUSIONS. These findings suggest that cigarette smoke is associated with defects in DC maturation and suppressed thoracic lymph node CD4+ T-cell proliferation in mice.
REVIEWER COMMENTS. This study suggests that cigarette-smoke exposure in mice leads to impaired DC maturation and thereby diminished T-cell clonal expansion in the TLNs. The findings imply that, although the T-cell effector program remains intact, fewer cells might be available to perform those duties. The authors asserted that the observed effects on DC function might serve as a potential mechanism for cigarette smoke causing impaired tumor surveillance. In addition, it is suggested that impaired CD4+ T-cell function might predispose patients with obstructive lung disease to infections and exacerbations. Additional studies will help to elucidate the specific mechanisms by which cigarette-smoke exposure exerts its harmful immunologic effects.
Intermittent Therapy for Flare Prevention and Long-term Disease Control in Stabilized Atopic Dermatitis: A Randomized Comparison of 3-Times-Weekly Applications of Tacrolimus Ointment Versus Vehicle
Authors: Spergel Jonathan M. 
Published: October 2008

Breneman D, Fleisher AB, Abramovitis A, et al. J Am Acad Dermatol. 2008;58(6):990–999
PURPOSE OF THE STUDY. To examine the usefulness of regular intermittent therapy instead of treating flares for the approach of atopic dermatitis (AD).
STUDY POPULATION. A total of 383 patients were randomly assigned to the stabilization phase, and 288 patients were controlled on tacrolimus ointment. There were 68 children (aged 2–16 years) and 57 adults (&gt;16 years) in the tacrolimus arm and 37 children and 35 adults in the vehicle arm. Eighty-five percent had moderate AD, and 15% had severe AD.
METHODS. Adult and pediatric patients with moderate-to-severe AD who were clear of disease after up to 16 weeks of treatment with tacrolimus ointment were randomly assigned in a double-blind fashion to 3-times-weekly treatment with either tacrolimus ointment (0.03% or 0.1%) or vehicle for 40 weeks. The primary end point was the number of flare-free treatment days. Relapses were treated with open-labeled tacrolimus.
RESULTS. There were 288 patients who entered the randomization phase. The largest reasons for not finishing the stabilization phase were voluntary patient withdrawal for 95 patients and loss to follow-up for 55 patients. Only 16 (4.2%) patients were withdrawn for lack of efficacy. A total of 125 patients were randomly assigned to tacrolimus, and 72 patients were assigned to vehicle. The mean number of flare-free treatment days was 177 for the tacrolimus group and 134 for the vehicle group (P = .003). Median time to first relapse was 169 days for the tacrolimus group and 43 for the vehicle group (P = .037).
CONCLUSIONS. Maintenance therapy with tacrolimus ointment was associated with significantly more flare-free days compared with vehicle and a significantly longer time until first disease relapse.
REVIEWER COMMENTS. This article examined the possibility of proactive treatment of AD instead of reacting to flares. The principle is similar to the use of maintenance medication for asthma. Similar results were seen with topical fluticasone propionate (Berth-Jones J, Damstra RJ, Golsch S, et al. BMJ. 2003;326[7403]:1367). One significant limitation is that the study only included patients who responded to topical tacrolimus. The question now is whether it can be generalized to all patients with AD or patients not controlled with daily topical therapies.
Sustained Efficacy and Safety of Pimecrolimus Cream 1% When Used Long-term (up to 26 Weeks) to Treat Children With Atopic Dermatitis
Authors: Park Audrey Y. , Spergel Jonathan M. 
Published: October 2008

Langley RG, Eichenfield LF, Lucky AW, Boguniewicz M, Barbier N, Cherill R. Pediatr Dermatol. 2008;25(3):301–307
PURPOSE OF THE STUDY. To evaluate the efficacy and safety of pimecrolimus cream 1% (Elidel [Novartis, East Hanover, NJ]) used for 26 weeks in children with atopic dermatitis (AD)
STUDY POPULATION. This was a prospective study of 403 children aged 2 to 17 years with AD (mean age at enrollment: 6.7 years) recruited from multiple academic centers in the United States.
METHODS. Pooled data were assessed from 20-week, open-label (OL) extensions of 2 previously reported 6-week, double-blind (DB) phase studies in which patients were randomly assigned 2:1 to pimecrolimus or vehicle. During the OL phase, all patients were treated with pimecrolimus. During the DB phase, no other AD treatments except emollients were allowed. The efficacy parameters included the Investigator's Global Assessment (IGA), Eczema Area and Severity Index, and severity of pruritus scores. Safety assessment consisted primarily of monitoring adverse events. Patients were evaluated on days 8, 15, 22, 29, 43, 71, 99, 141, and 183.
RESULTS. Overall, 60.3% of the patients had moderately severe AD (IGA: 3) at study entry. Twice as many in the control group discontinued during the DB phase compared with the treated group (25% vs 11.4%). The main reason for the higher discontinuation rate in the control group was unsatisfactory therapeutic effect (15.4% vs 2.6%). Eighty-four percent completed the OL phase with similar rates of completion between the groups. At day 43, 34.8% of the pimecrolimus-treated patients versus 18.4% in the vehicle groups (P &lt; .001) had clear or almost clear (IGA: 0 or 1) disease. Pimecrolimus was significantly more effective (P &lt; .0001) in treating the face and neck compared with the body during both DB and OL phases. In the pimecrolimus group, 56.5% of the patients had mild or absent pruritus by day 43 compared with 33.8% of those in the control group. The incidence of adverse events, including infections and complaints of a burning sensation with application, was not statistically different between groups during either phase of the study.
CONCLUSIONS. Treatment of AD with pimecrolimus was effective, particularly for the face and neck areas, and well tolerated.
REVIEWER COMMENTS. Given the black-box warning and concern with using topical calcineurin inhibitors, this article reemphasized that pimecrolimus is efficacious for children with AD. Particularly, it should be considered for use on the face and neck, which are difficult to treat with higher potency topical corticosteroids because of the risk of local adverse effects such as atrophy. The minimal adverse events associated with pimecrolimus support previous studies that had longer durations of treatment (up to 2 years).
Transient Tachypnea of the Newborn May Be an Early Clinical Manifestation of Wheezing Symptoms
Authors: Lin Joann H. 
Published: October 2008

Liem JJ, Huq SI, Ekuma O, Becker AB, Kozyrskyj AL. J Pediatr. 2007;151(1):29–33
PURPOSE OF THE STUDY. To identify risk factors associated with transient tachypnea of the newborn (TTN) and its possible association with wheezing symptoms in early childhood.
STUDY POPULATION. Data were collected from the Population Health Research Data Repository at the Manitoba Centre for Health Policy. This was a retrospective evaluation of 12 763 children who were born at term. In this cohort, children with physician-determined bronchiolitis, acute bronchitis, chronic bronchitis, asthma, or need for prescription asthma medications were identified as having wheezing syndromes.
METHODS. Children diagnosed with TTN at birth were identified, and Cox proportional hazards regression analysis for time to first event of hospitalization, physician visit, or prescription for an asthma medication up to 7 years of age was performed. Hazard ratios were compared with those of healthy newborns.
RESULTS. A total of 308 (2.4%) of the study children developed TTN. Risk factors for development of TTN included maternal asthma, birth weight of ≥4500 g, male gender, and urban location. Infants with TTN at birth had a significantly increased risk of having a wheezing disorder in early childhood (adjusted hazard ratio: 1.17 [95% confidence interval: 1.02–1.34]).
CONCLUSIONS. TTN is associated with the development of wheezing syndromes in early childhood.
REVIEWER COMMENTS. TTN is generally believed to resolve in 2 to 5 days with no increased risk of pulmonary complications. The findings in this study suggest otherwise, with maternal asthma a risk factor for development of TTN. Nevertheless, the spectrum of wheezing disorders is broad, especially in this study where they evaluated onset of symptoms before 7 years of age, and not every young child with wheezing eventually develops childhood asthma. Additional studies to examine the association between TTN and wheezing before the age of 3 years may help determine if TTN plays a critical role in early pulmonary development.
IFATS Collection: Adipose Stromal Cells Adopt a Proangiogenic Phenotype Under the Influence of Hypoxia
Authors: Thangarajah Hariharan , Vial Ivan N. , Chang Edwin , El-Ftesi Samyra , Januszyk Michael , Chang Edward I. , Paterno Josemaria , Neofytou Evgenios , Longaker Michael T. , Gurtner Geoffrey C. 
Published: October 2008

Abstract
Evolving evidence suggests a possible role for adipose stromal cells (ASCs) in adult neovascularization, although the specific cues that stimulate their angiogenic behavior are poorly understood. We evaluated the effect of hypoxia, a central mediator of new blood vessel development within ischemic tissue, on proneovascular ASC functions. Murine ASCs were exposed to normoxia (21% oxygen) or hypoxia (5%, 1% oxygen) for varying lengths of time. Vascular endothelial growth factor (VEGF) secretion by ASCs increased as an inverse function of oxygen tension, with progressively higher VEGF expression at 21%, 5%, and 1% oxygen, respectively. Greater VEGF levels were also associated with longer periods in culture. ASCs were able to migrate towards stromal cell-derived factor (SDF)-1, a chemokine expressed by ischemic tissue, with hypoxia augmenting ASC expression of the SDF-1 receptor (CXCR4) and potentiating ASC migration. In vivo, ASCs demonstrated the capacity to proliferate in response to a hypoxic insult remote from their resident niche, and this was supported by in vitro studies showing increasing ASC proliferation with greater degrees of hypoxia. Hypoxia did not significantly alter the expression of endothelial surface markers by ASCs. However, these cells did assume an endothelial phenotype as evidenced by their ability to tubularize when seeded with differentiated endothelial cells on Matrigel. Taken together, these data suggest that ASCs upregulate their proneovascular activity in response to hypoxia, and may harbor the capacity to home to ischemic tissue and function cooperatively with existing vasculature to promote angiogenesis.