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Biomedical subjects

Wanda Phipatanakul

Publications and source records attributed to Wanda Phipatanakul.

15 recordsLinked to original sources

Reframing the asthma microbiome: Multikingdom, multisite, and multiomic perspectives.

The field of asthma microbiome research has shifted rapidly in recent years. Advances in sequencing technology have led to an increased ability to characterize multikingdom microbial species and integration with host -omics profiling to enhance future translational applications. Traditional bacteria-centric, cross-sectional studies are giving way to mechanistic frameworks that incorporate fungi, viruses, and host-immune interactions. In this state-of-the-art review of emerging concepts in microbiome asthma research, we first propose a structured framework to consider microbiome studies across 5 major domains-microbial kingdom, site of sampling, integration with host -omics, clinical outcome domain, and translational relevance-in order to synthesize recent high-impact human microbiome studies in asthma. We highlight emerging evidence that fungal and viral communities contribute independently to asthma risk and that human microbial communities are linked to distinct inflammatory and immune pathways shaped by host genetic susceptibility.

Asthma↗

Assessment of adrenal suppression in children with asthma treated with inhaled corticosteroids: use of dehydroepiandrosterone sulfate as a screening test.

BACKGROUND: Inhaled corticosteroids (ICs) are considered first-line therapy for persistent asthma. At medium to high doses, ICs can suppress the hypothalamic-pituitary-adrenal (HPA) axis. Various provocative stimuli have been used to evaluate HPA axis function, but they are labor intensive and time-consuming. Dehydroepiandrosterone sulfate (DHEA-S) is a corticotropin-dependent adrenal androgen precursor that is suppressible in patients treated with ICs. OBJECTIVES: To evaluate DHEA-S as a possible marker for HPA axis dysfunction in children treated with ICs. METHODS: Children with moderate-to-severe persistent asthma and a history of medium- to high-dose IC exposure for at least 6 months were evaluated using low-dose and standard high-dose cosyntropin stimulation testing to assess adrenal function, and DHEA-S levels were compared with the results. RESULTS: Thirteen (59%) of 22 patients exhibited an abnormal cortisol response to cosyntropin. Age- and sex-specific mean DHEA-S z scores were significantly lower in cosyntropin abnormal responders (-1.2822) compared with normal responders (0.2964) (P = .008). The receiver operating characteristic curve for DHEA-S z scores had an area of 0.786 (95% confidence interval, 0.584-0.989), reaching 100% sensitivity with a DHEA-S z score of -1.5966 or less and 100% specificity with a DHEA-S z score greater than 0.0225. CONCLUSIONS: Most children develop biochemical evidence of adrenal suppression after treatment with medium to high doses of ICs. The presence of low DHEA-S levels can be used as a screening test to identify the child who needs more formal testing of the HPA axis.

Administration, Inhalation↗

Comparison of nebulized ipratropium bromide with salbutamol vs salbutamol alone in acute asthma exacerbation in children.

BACKGROUND: Despite multiple doses of beta2-agonists in the treatment of acute asthma exacerbation, significant residual airways obstruction often remains. OBJECTIVE: To determine whether the addition of inhaled ipratropium bromide to salbutamol provides improvement in lung function and clinical asthma symptoms in young children with acute asthma exacerbation. METHODS: This study was a prospective, double-blind randomized control trial of children aged 3 to 15 years who presented with an acute asthma exacerbation at the emergency department or outpatient clinic of Thammasat University Hospital, Pathumthani, Thailand, between September 2001 and February 2003. Subjects were randomized to receive 3 doses of nebulized salbutamol mixed with isotonic sodium chloride solution (control) or ipratropium bromide (treatment) every 20 minutes. Additional doses of salbutamol were given every 30 minutes as needed. Asthma outcome measures were evaluated 40, 70, 100, and 120 minutes after baseline. Primary outcomes were the differences in percent change in asthma clinical score and percent change in peak expiratory flow rate (PEFR) from baseline. Secondary outcomes included change in percent predicted PEFR. RESULTS: Of 74 children randomized and enrolled in the trial, 71 had complete data for analysis. Thirty-three children were in the control group and 38 were in the treatment group. Both the percent change in PEFR and the change in percent predicted PEFR at any time were higher in the treatment group, but these findings were not statistically significantly different. The number of subjects with at least a 100% percent predicted PEFR at any time point was greater in the treatment group. CONCLUSION: Although this study did not demonstrate a significant advantage in clinical score and PEFR, the trend toward additional effect of ipratropium bromide was consistent with previous studies.

Administration, Inhalation↗

Environmental factors and childhood asthma.

Indoor allergens are potent triggers for acute and chronic pediatric asthma. Environmental control measures of these allergens should be considered first-line treatment measures. Allergen avoidance can produce changes in disease activity and symptoms that can be beneficial before any medical intervention is implemented. In addition to allergen avoidance, studies evaluating other exposures, such as endotoxin and diet, in the pathogenesis of asthma are in progress. Understanding the complex relationships between exposure and allergy/asthma development is vitally important to the development of potentially more effective primary and secondary prevention strategies.

Air Pollution, Indoor↗

Use of a fish oil-based lipid emulsion to treat essential fatty acid deficiency in a soy allergic patient receiving parenteral nutrition.

The treatment of essential fatty acid deficiency (EFAD) in a 17-year-old male following allogeneic bone marrow transplantation is described. His transplant was complicated by gastrointestinal bleeding that precluded the use of enteral feedings. Due to a severe soy allergy, he could not tolerate any intravenous fat emulsions marketed in the US. After months of receiving fat-free parenteral nutrition and intermittent use of enteral feeds, he developed signs and symptoms consistent with EFAD, including a rash and an elevated plasma triene:tetraene ratio of 0.231 (0.013-0.05). After receiving FDA approval, a parenteral fish oil emulsion was administered to provide fat calories and sufficient alpha-linolenic and linoleic acid to correct his EFAD. Therapy was initiated at 0.2 g/kg/day and advanced to 0.67 g/kg/day, providing approximately 45 mg/kg/day of linoleic acid. After 10 days of therapy, his rash disappeared and his triene:tetraene ratio improved to 0.07. By day 17 the ratio normalized to 0.047. This suggests that using a fish oil emulsion with minimal linoleic acid may be safely used as the sole source of fat calories and may be an option to prevent or treat EFAD in subjects allergic to soy that require a parenteral source of fat.

Adolescent↗

Allergic rhinoconjunctivitis: epidemiology.

Allergic rhinoconjunctivitis has been studied much less frequently than asthma using epidemiologic approaches. Population-based studies are difficult to conduct because of misclassification arising from the reliance on self-reported questionnaires that use terms such as allergic rhinitis or hay fever to establish the diagnosis. In addition, many epidemiologic studies focus on diagnostic skin testing or allergen-specific IgE antibodies (RASTs) as an objective outcome to assess for hay fever. These techniques are helpful but not perfect measures for predicting hay fever outcomes in epidemiologic studies. It is generally accepted, however, that allergic rhinoconjunctivitis is one of the most common of chronic diseases and is the most common atopic disorder. This article reviews the definition of allergic rhinoconjunctivitis, the epidemiology of this disorder from infancy into adulthood, and environmental risk factors for development of sensitization to certain allergens.

Age of Onset↗

Mouse exposure and wheeze in the first year of life.

BACKGROUND: Studies have found that exposure to mice is highly prevalent among children with asthma living in urban areas. OBJECTIVE: To examine the relationship between exposure to mice and wheeze in the first year of life. METHODS: We conducted an ongoing prospective birth cohort study of 498 children with a history of allergy or asthma in at least 1 parent living in metropolitan Boston (the Home Allergens and Asthma Study). RESULTS: In a multivariate analysis, infants whose parents reported exposure to mice in the household had nearly twice the odds of developing any wheeze in the first year of life as children without exposure (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.14-2.95; P = .01). Other variables associated with wheeze in the first year of life included low birth weight (OR, 1.77; 95% CI, 1.06-2.95; P = .03), having at least 1 lower respiratory tract illness (OR, 5.59; 95% CI, 3.46-9.04; P < .001), exposure to high levels of endotoxin at age 2 to 3 months (fourth quartile compared with first quartile: OR, 2.32; 95% CI, 1.19-4.54; P = .01), and exposure to cockroach allergen of 0.05 U/g of dust or more at age 2 to 3 months (OR, 1.83; 95% CI, 1.09-3.08; P = .02). CONCLUSION: Among children with a parental history of asthma or allergies, exposure to mice is associated with wheeze in the first year of life, independent of other factors.

Allergens↗

Effect of environmental intervention on mouse allergen levels in homes of inner-city Boston children with asthma.

BACKGROUND: Recent studies have suggested that mouse allergen exposure and sensitization are common in urban children with asthma. The effectiveness of environmental intervention in reducing mouse allergen exposure has not been established. OBJECTIVE: To evaluate whether environmental intervention of mouse extermination and cleaning results in a reduction in mouse allergen levels. METHODS: Eighteen homes of children with positive mouse allergen skin test results and at least mild persistent asthma in urban Boston, MA, with evidence of mouse infestation or exposure were randomized in a 2:1 ratio (12 intervention and 6 control homes). The intervention homes received an integrated pest management intervention, which consisted of filling holes with copper mesh, vacuuming and cleaning, and using low-toxicity pesticides and traps. Dust samples were collected and analyzed for major mouse allergen (Mus m 1) and cockroach allergen (Bla g 1) at baseline and 1, 3, and 5 months after the intervention was started and compared with control homes. RESULTS: Mouse allergen levels were significantly decreased compared with control homes by the end of the intervention period at month 5 in the kitchen and bedroom (kitchen intervention, 78.8% reduction; control, 319% increase; P = .02; bedroom intervention, 77.3% reduction; control, 358% increase; P < .01; and living room intervention, 67.6% reduction; control, 32% reduction; P = .07). CONCLUSIONS: Mouse allergen levels were significantly reduced during a 5-month period using an integrated pest management intervention.

Adolescent↗

Endotoxin exposure and eczema in the first year of life.

OBJECTIVE: Exposure to endotoxin in early life has been proposed as a factor that may protect against the development of allergic diseases such as eczema. The objective of this study was to examine the relation between endotoxin exposure in early life and eczema in the first year of life in children with parental history of asthma or allergies. METHODS: This study used a prospective birth cohort study of 498 children who had a history of allergy or asthma in at least 1 parent and lived in metropolitan Boston. A subset of 401 living rooms had house dust samples adequate for analysis of endotoxin. RESULTS: In multivariate analyses adjusting for gender, income, and season of birth, endotoxin levels in the living room at 2 to 3 months of age was inversely associated with physician- or nurse-diagnosed eczema in the first year of life (odds ratio [OR] for each quartile increment: 0.76; 95% confidence interval [CI]: 0.61-0.96). Exposure to a dog in the home at age 2 to 3 months was also inversely associated with eczema in the first year of life, but the CI widened when endotoxin was included in the multivariate model (OR: 0.54; 95% CI: 0.27-1.09). Other variables associated with eczema in the first year of life included paternal history of eczema (OR: 1.91; 95% CI: 1.03-3.55) and maternal specific immunoglobulin E positivity to > or =1 allergen (OR: 1.61; 95% CI: 1.01-2.56). CONCLUSIONS: Among children with parental history of asthma or allergies, exposure to high levels of endotoxin in early life may be protective against eczema in the first year of life. In these children, paternal history of eczema and maternal sensitization to at least 1 allergen are associated with an increased risk of eczema in the first year of life.

Analysis of Variance↗

Low-normal gestational age as a predictor of asthma at 6 years of age.

BACKGROUND: Perinatal factors, including gestational age and birth weight, influence the development of atopy in early life. However, the role of these factors in the development of asthma in later life among children who do not develop perinatal respiratory disease remains unclear. METHODS: Four hundred fifty-four infants who had a history of allergy or asthma in at least 1 parent, were born in the 36th week of gestation or later, and did not develop perinatal respiratory distress were monitored for at least 6 years. Associations between predictor variables and asthma and wheeze were assessed with multivariate logistic regression and repeated-event analyses. RESULTS: Although we previously observed a relationship between low birth weight and persistent wheeze in the first 1 year of life, we did not observe similar associations between low birth weight and asthma at 6 years of age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 0.40-2.73). However, a strong relationship was found between low-normal gestational age and asthma at 6 years of age (OR: 4.7; 95% CI: 2.1-10.5). The effects of low-normal gestational age were significantly greater among boys than among girls (boys: OR: 8.15; 95% CI: 2.98-22.3; girls: OR: 1.90; 95% CI: 0.38-13.83). Longitudinal analysis of the relationship between gestational age and wheeze during the 6 years of observation confirmed these gender differences. CONCLUSIONS: Among children at high risk of developing atopic disease, late prematurity might be an important additional determinant of asthma later in life, and these effects are gender specific.

Analysis of Variance↗

Montelukast improves asthma control in asthmatic children maintained on inhaled corticosteroids.

BACKGROUND: Because of potential toxicities of inhaled corticosteroid (ICS) use in pediatric asthma, alternative or steroid-sparing therapy is desirable. There are no previous studies evaluating montelukast's steroid-sparing effects in children with asthma. OBJECTIVE: To evaluate whether (1) montelukast as add-on therapy improves asthma symptom control and (2) montelukast provides steroid-sparing effects in children with asthma treated with low to moderate doses of ICS therapy. METHODS: In a double-blind, placebo-controlled trial, 36 children ages 6 to 14 years with symptomatic asthma maintained on a stable low to moderate dose of ICSs were randomly assigned to receive montelukast or matching placebo for 24 weeks after a run-in period of 2 weeks (period I). During the trial, subjects kept daily asthma diary cards and monthly spirometry was performed. After a 4 week add-on period (period II), the subjects completed a 20-week (period III) ICS tapering period based on a predetermined protocol. RESULTS: In period II, the difference in the number of rescue-free days was significantly higher in the montelukast group (P = 0.0001), and the number of rescue-free days per week was also significantly higher in montelukast-treated subjects compared with placebo subjects (P = 0.002). In period III, the percentage reduction in ICS dose was not significant between montelukast and placebo (P = 0.10), but the montelukast group experienced an average 17% decrease in ICS dose and the control group experienced an average 64% increase in ICS dose. CONCLUSIONS: Montelukast treatment significantly increased the number of rescue-free days in symptomatic children with asthma.

Acetates↗

Rodent allergens.

Rodent allergens play a significant role in the pathogenesis of asthma and allergic rhinitis, and are potent causes of acute and chronic symptoms. This has long been apparent in occupational settings, particularly in the laboratory, but has been most recently studied and found to be important in home environments. These allergens have been suggested as uniquely important among inner-city children with asthma. Furthermore, rodents have become increasingly popular as pets. With recent awareness of significant exposure in a variety of settings, hypersensitivity to rodents has become increasingly important. This review focuses on the importance of rodent allergens, concentrating on mouse and rat, but including other potentially important rodents such as gerbil, hamster, and rabbit. It also discusses the pathogenesis, diagnosis, prevention, and management of rodent allergy.

Allergens↗

The efficacy of montelukast in the treatment of cat allergen-induced asthma in children.

BACKGROUND: Montelukast is a leukotriene antagonist approved for the treatment of childhood asthma in children age 2 years and older. There are limited studies on its effects on allergic asthma in children. OBJECTIVE: We sought to evaluate montelukast's effects on upper and lower airway responses to intense cat allergen exposure. METHODS: In a double-blind, placebo-controlled, cross-over trial 18 subjects aged 6 to 14 years with cat-induced asthma were randomly assigned to receive 1 week each of either montelukast or placebo, followed by a 1-hour cat challenge in an environmental exposure unit. Upper and lower respiratory tract symptoms were rated, and spirometry and acoustic rhinometry were performed. Challenges were stopped early if the subject became too uncomfortable or had a greater than 50% decrease in FEV1. RESULTS: Overall changes in FEV1 were significantly different with montelukast treatment and remained significant after adjusting for allergen level (P =.02; adjusted P =.01). Lower respiratory tract symptom scores were significantly reduced with montelukast versus placebo (P =.007) but lost significance after adjusting for allergen level (P =.16). Challenge length was significantly longer with montelukast versus placebo (P <.001) and remained significant after adjusting for allergen level (P =.019). Montelukast did not significantly affect upper respiratory responses, as measured by means of symptom scores (P =.43) and changes in acoustic rhinometry (P =.078). CONCLUSIONS: Montelukast was significantly more effective than placebo in attenuating lower respiratory responses and extending challenge length when cat-sensitive children with mild persistent asthma were exposed to high levels of cat allergen.

Acetates↗