Asthma Flare-ups in Children

Short-term increases in inhaled steroid doses do not prevent asthma flare-ups in children

NIH-funded findings challenge common practice of increasing doses at early signs of worsening symptoms.

Researchers have found that temporarily increasing the dosage of inhaled steroids when asthma symptoms begin to worsen does not effectively prevent severe flare-ups, and may be associated with slowing a child’s growth, challenging a common medical practice involving children with mild-to-moderate asthma.

The study, funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, will appear online on March 3 in the New England Journal of Medicine (NEJM) to coincide with its presentation at a meeting of the 2018 Joint Congress of the American Academy of Allergy, Asthma & Immunology (AAAAI) and the World Allergy Organization (WAO) in Orlando, Florida. It will appear in print on March 8th.

Asthma flare-ups in children are common and costly, and to prevent them, many health professionals recommend increasing the doses of inhaled steroids from low to high at early signs of symptoms, such as coughing, wheezing, and shortness of breath. Until now, researchers had not rigorously tested the safety and efficacy of this strategy in children with mild-to-moderate asthma.

“These findings suggest that a short-term increase to high-dose inhaled steroids should not be routinely included in asthma treatment plans for children with mild-moderate asthma who are regularly using low-dose inhaled corticosteroids,” said study leader Daniel Jackson, M.D., associate professor of pediatrics at the University of Wisconsin School of Medicine and Public Health, Madison, and an expert on childhood asthma. “Low-dose inhaled steroids remain the cornerstone of daily treatment in affected children.”

The research team studied 254 children 5 to 11 years of age with mild-to-moderate asthma for nearly a year. All the children were treated with low-dose inhaled corticosteroids (two puffs from an inhaler twice daily). At the earliest signs of asthma flare-up, which some children experienced multiple times throughout the year, the researchers continued giving low-dose inhaled steroids to half of the children and increased to high-dose inhaled steroids (five times the standard dose) in the other half, twice daily for seven days during each episode.

Though the children in the high-dose group had 14 percent more exposure to inhaled steroids than the low-dose group, they did not experience fewer severe flare-ups. The number of asthma symptoms, the length of time until the first severe flare-up, and the use of albuterol (a drug used as a rescue medication for asthma symptoms) were similar between the two groups.

Unexpectedly, the investigators found that the rate of growth of children in the short-term high-dose strategy group was about 0.23 centimeters per year less than the rate for children in the low-dose strategy group, even though the high-dose treatments were given only about two weeks per year on average. While the growth difference was small, the finding echoes previous studies showing that children who take inhaled corticosteroids for asthma may experience a small negative impact on their growth rate. More frequent or prolonged high-dose steroid use in children might increase this adverse effect, the researchers caution.

The study did not include children with asthma who do not take inhaled steroids regularly, nor did it include adults.

“This study allows caregivers to make informed decisions about how to treat their young patients with asthma,” said James Kiley, Ph.D., director of the NHLBI’s Division of Lung Diseases. “Trials like this can be used in the development of treatment guidelines for children with asthma.”

This work was supported by the following NHLBI grants: HL098102, HL098075, HL098090, HL098177, HL098098, HL098107, HL098112, HL098103, HL098115, HL098096. The NHLBI-funded study, Step Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (STICS) (NCT02066129), is part of the NHLBI AsthmaNet program, a nationwide clinical research network that explores new approaches in treating asthma from childhood to adulthood.

Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at https://www.nhlbi.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases.

Patient, Physician, and Health-System Factors Influencing the Quality of Antidepressant and Sedative Prescribing for Older, Community-Dwelling Adults.

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Patient, Physician, and Health-System Factors Influencing the Quality of Antidepressant and Sedative Prescribing for Older, Community-Dwelling Adults.

Health Serv Res. 2016 Dec 26;:

Authors: Extavour RM, Perri M

Abstract
OBJECTIVE: To identify determinants of potentially inappropriate (PI) antidepressant and anxiolytic/sedative prescribing for older, community-dwelling adults.
DATA SOURCES/STUDY SETTING: Office visits from the 2010 National Ambulatory Medical Care Survey.
STUDY DESIGN: A cross-sectional study measuring associations between various patient and physician factors and prescribing of PI antidepressants, and PI sedatives among elderly, using Beers 2012/2015 criteria, a clinical decision model, and multivariate logistic regressions.
DATA COLLECTION: Visits by older adults (?65 years) involving medications were extracted to identify visits with antidepressants and sedatives.
PRINCIPAL FINDINGS: Black race, asthma, depression, osteoporosis, payment type, consultation time, and computer systems with prescribing support were associated with reduced odds of PI antidepressant prescribing among users. Income, chronic renal failure, diabetes, and obesity were associated with reduced odds of PI sedative prescribing. Female sex, white race, depression, increasing number of medications, and physician specialty were associated with increased odds of PI sedative prescribing.
CONCLUSIONS: Various patient and health-system factors influence the quality of antidepressant and sedative prescribing for older community-dwelling adults. Longer consultations and the use of computer systems with prescribing support may minimize potentially inappropriate antidepressant prescribing. As medication numbers increase, exposure to PI sedatives is more likely, requiring medication review and monitoring.

PMID: 28024315 [PubMed – as supplied by publisher]

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Ponciretin attenuates ethanol-induced gastric damage in mice by inhibiting inflammatory responses.

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Ponciretin attenuates ethanol-induced gastric damage in mice by inhibiting inflammatory responses.

Int Immunopharmacol. 2016 Dec 22;43:179-186

Authors: Kang GD, Kim DH

Abstract
BACKGROUND: Poncirin (PO) and isosakuranetin (or ponciretin [PT]) are compounds found in fruits of the genus Citrus. They are frequently used in traditional Chinese medicine for the treatment of inflammation and asthma. Therefore, we examined their anti-gastritis effects in vitro and in vivo.
METHODS: The anti-inflammatory effects of PO and PT were examined using ethanol- or LPS-stimulated KATO III cells. Gastritis was induced in ICR mice via intragastric injection of absolute ethanol. Levels of inflammatory markers were measured by enzyme-linked immunosorbent assay, immunoblotting, and quantitative polymerase chain reaction.
RESULTS: Treatment with PT or PO inhibited the secretion of interleukin (IL)-8 and tumor necrosis factor (TNF) in ethanol- or LPS-stimulated KATO III cells. They also reduced the activation of nuclear factor kappa B (NF-?B). Pre-treatment with PT or PO significantly protected against ethanol-induced hemorrhagic gastritis, characterized by edema, tissue erosions, and mucosal friability in mice. Treatment with PT or PO suppressed ethanol-induced NF-?B activation and the release of TNF, IL-8, and IFN-?. The protective effect of PT was greater than that of PO and comparable to ranitidine, a positive control.
CONCLUSION: PT may attenuate ethanol-induced gastritis by inhibiting the infiltration of immune cells, including neutrophils, via the regulation of CXCL4 (or IL-8) secretion and the activation NF-?B.

PMID: 28013186 [PubMed – as supplied by publisher]

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Ventilation/perfusion ratio and right to left shunt in healthy newborn infants.

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Ventilation/perfusion ratio and right to left shunt in healthy newborn infants.

J Clin Monit Comput. 2016 Dec 23;:

Authors: Dassios T, Ali K, Rossor T, Greenough A

Abstract
Oxygenation impairment can be assessed non-invasively by determining the degree of right-to-left shunt and ventilation/perfusion (VA/Q) inequality. These indices have been used in sick newborn infants, but normative values have not been reported which are essential to determine the magnitude of the abnormality. We, therefore, aimed to measure the shunt and VA/Q in infants with no history of respiratory conditions and determine if there was any effect of supine or prone position and the reproducibility of the data. Data were analysed from infants who had undergone a hypoxic challenge and in a subset who had been assessed in the supine or prone position. Transcutaneous oxygen saturations (SpO2) were recorded at fractions of inspired oxygen (FIO2) of 0.21 and 0.15. Two independent raters used a computer software algorithm which analysed and fitted paired data for FIO2 and SpO2 and derived a curve which represented the best fit for each infant’s data and calculated the shunt and VA/Q. The raters ability to interpret the SpO2 value which corresponded to a given FIO2 was compared. The downwards displacement of the FIO2 versus SpO2 curve was used to estimate the degree of right-to-left shunt and the rightwards shift of the curve was used to calculate the VA/Q ratio. The mean (SD) gestational age of the 145 infants was 39 (1.6) weeks, their birth weight was 2990 (578) gms and median (range) postnatal age at measurement 3 (1-8) days. The mean (SD) VA/Q ratio was 0.95 (0.21). None of the infants had a right-to-left shunt. No significant differences were found in VA/Q in the supine compared to the prone position. The intraclass correlation coefficient of VA/Q between two independent raters was 0.968 (95% CI 0.947-0.980), p?<?0.001. Right-to-left shunt and VA/Q ratio in healthy newborn infants were similar in the prone compared to the supine position.

PMID: 28012013 [PubMed – as supplied by publisher]

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Interventions To Help Asthma Clinical Adherence

Conditions:   Asthma/Drug Therapy;   Medication Adherence/Statistics & Numerical Data;   Reminder Systems;   Humans;   Hispanic Americans;   Communication Barriers;   Child
Interventions:   Device: SmartInhaler with reminder function turned on;   Device: SmartInhaler
Sponsors:   University of California, San Francisco;   Academic Pediatric Association
Not yet recruiting – verified December 2016

View full post on ClinicalTrials.gov: asthma | Studies received in the last 14 days

Allergic Sensitization at School Age is a Systemic Low-grade Inflammatory Disorder.

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Allergic Sensitization at School Age is a Systemic Low-grade Inflammatory Disorder.

Allergy. 2016 Dec 19;:

Authors: Chawes BL, Stokholm J, Schoos AM, Rahman N, Brix S, Bisgaard H

Abstract
BACKGROUND: Systemic low-grade inflammation has been demonstrated in a range of the frequent noncommunicable diseases (NCDs) proposing a shared mechanism, but is largely unexplored in relation to allergic sensitization. We therefore aimed to investigate the possible association with childhood allergic sensitization.
METHODS: High sensitivity C-reactive protein (hs-CRP), interleukin-1? (IL-1?), IL-6, tumor necrosis factor-? (TNF-?) and chemokine (C-X-C motif) ligand 8 (CXCL8) were measured in plasma at age 6mo (N=214) and 7yrs (N=277) in children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000 ) birth cohort. Allergic sensitization against common inhalant and food allergens was determined longitudinally at age ½, 1½, 4 and 6yrs by specific-IgE assessments and skin prick tests. Associations between inflammatory biomarkers and sensitization phenotypes were tested with logistic regression and principle component analyses (PCA).
RESULTS: Adjusted for gender, recent infections and a CRP genetic risk-score, hs-CRP at 7yrs was associated with concurrent elevated specific-IgE against any allergen (adjusted OR (aOR) =1.40; 95% CI, 1.14-1.72; p=0.001), aeroallergens (aOR, 1.43; 1.15-1.77; p=0.001), food allergens (aOR, 1.31; 95% CI, 1.02-1.67; p=0.04), sensitization without any clinical allergy symptoms (aOR=1.40; 1.06-1.85; p=0.02), and with similar findings for skin prick tests. The other inflammatory markers were not univariantly associated with sensitization, but multi-parametric PCA suggested a specific inflammatory response among sensitized children. Inflammatory markers at age 6mo were not associated with subsequent development of sensitization phenotypes.
CONCLUSIONS: Elevated hs-CRP is associated with allergic sensitization in school-aged children suggesting systemic low-grade inflammation as a phenotypic characteristic of this early onset NCD. This article is protected by copyright. All rights reserved.

PMID: 27992959 [PubMed – as supplied by publisher]

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Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies.

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Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies.

Front Pharmacol. 2016;7:299

Authors: Thompson MD, Capra V, Clunes MT, Rovati GE, Stankova J, Maj MC, Duffy DL

Abstract
Genetic variants associated with asthma pathogenesis and altered response to drug therapy are discussed. Many studies implicate polymorphisms in genes encoding the enzymes responsible for leukotriene synthesis and intracellular signaling through activation of seven transmembrane domain receptors, such as the cysteinyl leukotriene 1 (CYSLTR1) and 2 (CYSLTR2) receptors. The leukotrienes are polyunsaturated lipoxygenated eicosatetraenoic acids that exhibit a wide range of pharmacological and physiological actions. Of the three enzymes involved in the formation of the leukotrienes, arachidonate 5 lipoxygenase 5 (ALOX5), leukotriene C4 synthase (LTC4S), and leukotriene hydrolase (LTA4H) are all polymorphic. These polymorphisms often result in variable production of the CysLTs (LTC4, LTD4, and LTE4) and LTB4. Variable number tandem repeat sequences located in the Sp1-binding motif within the promotor region of the ALOX5 gene are associated with leukotriene burden and bronchoconstriction independent of asthma risk. A 444A > C SNP polymorphism in the LTC4S gene, encoding an enzyme required for the formation of a glutathione adduct at the C-6 position of the arachidonic acid backbone, is associated with severe asthma and altered response to the CYSLTR1 receptor antagonist zafirlukast. Genetic variability in the CysLT pathway may contribute additively or synergistically to altered drug responses. The 601 A > G variant of the CYSLTR2 gene, encoding the Met201Val CYSLTR2 receptor variant, is associated with atopic asthma in the general European population, where it is present at a frequency of ?2.6%. The variant was originally found in the founder population of Tristan da Cunha, a remote island in the South Atlantic, in which the prevalence of atopy is approximately 45% and the prevalence of asthma is 36%. In vitro work showed that the atopy-associated Met201Val variant was inactivating with respect to ligand binding, Ca(2+) flux and inositol phosphate generation. In addition, the CYSLTR1 gene, located at Xq13-21.1, has been associated with atopic asthma. The activating Gly300Ser CYSLTR1 variant is discussed. In addition to genetic loci, risk for asthma may be influenced by environmental factors such as smoking. The contribution of CysLT pathway gene sequence variants to atopic asthma is discussed in the context of other genes and environmental influences known to influence asthma.

PMID: 27990118 [PubMed – in process]

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Single Injection Adductor Canal Block Versus Continuous Adductor Canal Infusion for Total Knee Arthroplasty

Conditions:   Total Knee Arthroplasty;   Pain, Postoperative;   Adductor Canal Block
Interventions:   Procedure: Multimodal Peripheral Nerve Block Injection;   Procedure: Single Shot Adductor Canal Block
Sponsor:   Wake Forest School of Medicine
Not yet recruiting – verified December 2016

View full post on ClinicalTrials.gov: asthma | Studies received in the last 14 days