fluticasone and Body-Weight

The effect on linear growth of daily long-term inhaled corticosteroid therapy in preschool-aged children with recurrent wheezing is controversial.. We sought to determine the effect of daily inhaled corticosteroid given for 2 years on linear growth in preschool children with recurrent wheezing.. Children aged 2 and 3 years with recurrent wheezing and positive modified Asthma Predictive Index scores were randomized to a 2-year treatment period of chlorofluorocarbon-delivered fluticasone propionate (176 μg/d) or masked placebo delivered through a valved chamber with a mask and then followed for 2 years off study medication. Height growth determined by means of stadiometry was compared between treatment groups.. In the study cohort as a whole, the fluticasone group did not have significantly less linear growth than the placebo group (change in height from baseline difference, -0.2 cm; 95% CI, -1.1 to 0.6) 2 years after discontinuation of study treatment. In post hoc analyses children 2 years old who weighed less than 15 kg at enrollment and were treated with fluticasone had less linear growth compared with those treated with placebo (change in height from baseline difference, -1.6 cm; 95% CI, -2.8 to -0.4; P = .009).. Linear growth was not significantly different in high-risk preschool-aged children with recurrent wheezing treated with 176 μg/d chlorofluorocarbon-delivered fluticasone compared with placebo 2 years after fluticasone is discontinued. However, post hoc subgroup analyses revealed that children who are younger in age and of lesser weight relative to the entire study cohort had significantly less linear growth, possibly because of a higher relative fluticasone exposure.

Topics: Age Factors; Androstadienes; Anti-Asthmatic Agents; Asthma; Body Height; Body Weight; Child, Preschool; Cohort Studies; Double-Blind Method; Female; Fluticasone; Humans; Male; Respiratory Sounds

Eosinophilic esophagitis is an increasingly recognized disorder with distinctive endoscopic, histologic, and allergic features. Although several therapies are advocated, no placebo-controlled trials have been conducted. We aimed to determine the efficacy of swallowed fluticasone propionate (FP) in the treatment of eosinophilic esophagitis.. We conducted a randomized, double-blind, placebo-controlled trial of swallowed FP in pediatric patients with active eosinophilic esophagitis. Thirty-six patients were randomly assigned to receive either 880 mug of FP (21 patients) or placebo (15 patients) divided twice daily for 3 months. The primary end point was histologic remission, defined by a peak eosinophil count of

Topics: Adolescent; Age Factors; Androstadienes; Body Height; Body Weight; CD8-Positive T-Lymphocytes; Child; Child, Preschool; Double-Blind Method; Eosinophilia; Esophagitis; Female; Fluticasone; Humans; Hyperplasia; Infant; Male

Hecogenin is a steroidal sapogenin plays important role in treatment of variety of inflammatory diseases. We have investigated the anti-inflammatory effects of Hecogenin (50 µg/animal) (HG), Fluticasone (50 µg/animal) (FC) and Hecogenin+Fluticasone (HG+FC) combination (25 µg/animal, each) on various inflammatory models. The anti-inflammatory effect of HG, FC and HG+FC combination was studied on % inhibition of dry weight of granuloma tissue, Δ ear weight, myeloperoxidase assay, serum pro-inflammatory cytokines, colon weight to length ratio, macroscopic lesions, adhesion score, diarrhoea score and histopathological analysis of ear and colon tissue on Cotton pellets induced granuloma in rats, Croton oil induced ear edema in mice and TNBS induced granuloma in rats. Topical administration of HG and its combination with FC showed significant decrease (p<0.001) in the % inhibition of dry weight of granuloma tissue, Δ ear weight, myeloperoxidase level, serum pro-inflammatory cytokines levels, colon weigh to length ratio as compared with Cotton pellets treated with acetone groups and Croton oil treated animals. Further histopathological analysis of ear tissue showed significant decrease in dermal thickness and epidermal hyperplasia and colon tissue showed reduction of edema, infiltration of inflammatory cells and normalization of crypt structure compared to DC animals. Thus, the findings of present study suggest the possible role of HG in the treatment of inflammation by reducing the dose of FC in combination with HG.

Topics: Animals; Anti-Inflammatory Agents; Body Weight; Colon; Cytokines; Disease Models, Animal; Fluticasone; Inflammation; Mice; Peroxidase; Rats; Rats, Wistar; Sapogenins

The most significant adverse effect of inhaled steroid administration in children is suppression of hypothalamic-pituitary-adrenal axis responsiveness and suppression of growth. This study evaluates the effects of inhaled corticosteroids on the growth plates in infant rats. Rats aged 10 days were divided into five groups. Low and high doses of budesonide and fluticasone propionate (50-200-250 mcg/day) were applied with a modified spacer for 10 days. The rat's tibias were then removed and the effects of the steroids on the growth plates were compared. Growth cartilage chondrocyte proliferation and apoptosis rates; IGF-1 and glucocorticoid receptor levels; and resting, proliferative, hypertrophic, and total zone (TZ) measurements were compared using immunohistochemical-staining methods. With high doses of fluticasone, growth plates were affected much more than with high doses of budesonide (p = 0.01). Fluticasone, particularly at a dose of 250 mcg, inhibited the growth plate with an intensive negative impact on all parameters.

Topics: Administration, Inhalation; Animals; Animals, Suckling; Body Weight; Budesonide; Cell Division; Chondrocytes; Dose-Response Relationship, Drug; Fluticasone; Growth Plate; Hypertrophy; Hypothalamo-Hypophyseal System; Insulin-Like Growth Factor I; Osteogenesis; Pituitary-Adrenal System; Random Allocation; Rats; Rats, Wistar; Receptors, Glucocorticoid; Tibia

Long-term inhaled corticosteroids are the preferred treatment for asthma, but their safety still controversial. The aim of the present study was to explore the effects of inhaled corticosteroids on bone age and growth in children with asthma.. Seventy-three children with asthma received inhaled fluticasone treatment at a starting dosage of 250 μg/d for 3 months, when the dosage was reduced by a third. Three months later, the patients were treated with fluticasone at a dosage of 125 μg/d for 6 months. Bone age, heights and weights were measured before and one year of treatment.. The increase in the heights, weights and RUS (radius, ulna and short finger bones) bone age of the children with asthma after one year of treatment was not significantly different from healthy children. There were no significant differences in body mass index (BMI) before and after one year of treatment, however the level of carpal bone age [-0.2(-0.6,0.8) years] was delayed after therapy compared to before treatment [-0.5(-1.0,0.6) years] (P<0.05).. Treatment with inhaled corticosteroids for 1 year may suppress the level of carpal bone age, but the level of RUS bone age, heights, weights and BMI are not affected. It is necessary to monitor the growth of children with asthma who receive long-term inhaled corticosteroid treatment.

Topics: Administration, Inhalation; Age Determination by Skeleton; Androstadienes; Asthma; Body Height; Body Mass Index; Body Weight; Bone Development; Child; Child, Preschool; Female; Fluticasone; Humans; Male

Asthma needs continuous treatment often for years. In humans, some drugs are administered via aerosol, therefore they come in contact with both respiratory and olfactory mucosa. We explored the possibility that antiasthma corticosteroid treatment could influence the olfactory function by passage through the nose. A group of mice was exposed twice daily for 42 days to fluticasone propionate aerosol and was compared with a control group. Olfactory behavior, respiratory mechanics, histology, and immunoreactivity in the olfactory system were assessed. Fluticasone-treated mice were slower in retrieving a piece of hidden food, but both groups were similarly fast when the food was visible. When a clearly detectable odor was present in the environment, all mice behaved in a similar way. Respiratory mechanics indices were similar in all mice except for the viscose resistance, which was reduced in fluticasone-treated mice. Olfactory mucosa of fluticasone-treated mice was thicker than that of controls. Slight but consistent differences in staining were present for Olfactory Marker Protein but not for other proteins. A mild impairment of olfactory function is present in mice chronically treated with fluticasone aerosol, apparently accompanied by slight modifications of the olfactory receptor cells, and suggests monitoring of olfactory function modifications in long-term steroid users.

Topics: Aerosols; Androstadienes; Animals; Behavior, Animal; Body Weight; Female; Fluticasone; Immunohistochemistry; Mice; Olfactory Bulb; Olfactory Mucosa; Organ Size; Respiratory Mechanics; Steroids; Vomeronasal Organ

Fluticasone proprionate (FP) is increasingly used to treat very young children with asthma. Its safety in terms of effects on the hypothalamic pituitary axis (HPA) and growth in this age group is uncertain.. Eleven children (median (range) age 10 (5.6-24.3) months) presenting with recurrent wheeze and family history of asthma were studied prospectively for a period of 18 months. Children received daily-inhaled FP 250 microg via a spacer device. No other corticosteroid therapy was administered prior to or during the study. A Short Standard Synacthen Test (SST) (125 microg) was performed pretreatment, and after 6 and 18 months. Weight (Wt), height (Ht), and body mass index (BMI) were measured at 3-6 monthly intervals.. Fasting early morning and peak cortisol levels remained within the normal reference range with therapy. There were no changes in Ht SDS, whereas both Wt SDS (baseline 0.05 (-2.17 to 0.52) vs. +18 months 0.68 (-0.5 to 1.36) P < 0.02) and BMI SDS (-0.22 (-1.73 to 0.75) vs. 0.86 (0.03 to 1.99) P < 0.005) increased after 18 months of treatment.. Daily treatment with inhaled FP 250 microg in young children with asthma appears to have no adverse effects on the HPA or on linear growth, however, treatment is associated with increases in body Wt and BMI in young children.

Topics: Administration, Inhalation; Androstadienes; Asthma; Biomarkers; Body Height; Body Mass Index; Body Weight; Bronchodilator Agents; Child Development; Child, Preschool; Cohort Studies; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Infant; Longitudinal Studies; Male; Pituitary-Adrenal System; Prospective Studies; Respiratory Sounds

Inhaled corticosteroids (ICS), for years used in the therapy of low-moderate bronchial asthma, reduce the rate of asthmatic attack with improved pulmonary functioning and quality of life. Clinical trials have been addressed mainly to study the efficacy rather than the safety of drugs, so that the side effects of these drugs have not yet been accurately defined. Clinical experience shows that growth delay appears in the first months of therapy with ICS. The aim of the study was to evaluate the influence of the therapy with spacer-administered inhaled corticosteroid on short-term auxological development in prepubertal children.. In a group of children with low asthma, height and weight have been evaluated before and after six months of inhaled therapy with dipropionate fluticasone at a dose of 100 microg per day.. Twenty-five patients (19 males and 6 females; age 5.5+/-1.6 years; range: 2.6-7.8 years) showed a regular growth during the six months of therapy (mean height 0.8 standard deviation score [SDS] before therapy and 0.8 SDS after therapy), while 21 (17 males and 4 females; age 10.0+/-1.5 years; range 8.0-12.7 years) showed an increment of growth rate (mean height from 0.5 SDS to 0.7 SDS, respectively).. Spacer-administered low dose fluticasone does not negatively influence short-term growth rate, regardless of the age of the patients.

Topics: Administration, Inhalation; Androstadienes; Asthma; Body Height; Body Weight; Bronchodilator Agents; Child; Child, Preschool; Female; Fluticasone; Growth; Humans; Male; Quality of Life; Time Factors; Treatment Outcome

Neurotrophic factors and receptors are upregulated in the respiratory tract of humans and rodents infected by the respiratory syncytial virus, leading to airway inflammation and hyperreactivity. The contribution of neurotrophic pathways to the recruitment of immuno-inflammatory cells and their response to anti-inflammatory therapy remains unclear. We sought to determine whether selective nerve growth factor inhibition prevents the immuno-inflammatory response against infection, and explored the effect of inhaled corticosteroids on virus-induced neurotrophic upregulation and the consequent recruitment of immuno-inflammatory cells into the airways. We tried to inhibit the recruitment of lymphocytes and monocytes into the airways of infected weanling rats using immunologic inhibition of nerve growth factor with a specific blocking antibody, or chemical inhibition of receptor tyrosine kinase with K252a. The anti-inflammatory activity of inhaled corticosteroids was studied in infected rats treated with budesonide, fluticasone, or vehicle. Immunological or chemical inhibition of nerve growth factor or its high-affinity receptor tyrosine kinase pathway inhibited the recruitment of inflammatory cells triggered by nociceptive irritation of infected rat airways, thereby reducing local and systemic immuno-inflammatory responses against the virus. Neurotrophic upregulation in infected airways was not affected by inhaled corticosteroids. As a logical consequence, these commonly used drugs were also unable to stop the recruitment of immune and inflammatory effector cells into infected airways. Overexpression of neurotrophic factors and receptors in airways infected by respiratory syncytial virus is critical for the development of airway inflammation and hyperreactivity, which is resistant to the anti-inflammatory effect of inhaled corticosteroids.

Topics: Administration, Inhalation; Androstadienes; Animals; Body Weight; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Budesonide; Carbazoles; Drug Resistance; Enzyme Inhibitors; Female; Fluticasone; Indole Alkaloids; Male; Nerve Growth Factors; Pneumonia; Rats; Rats, Inbred F344; Receptor Protein-Tyrosine Kinases; Respiratory Syncytial Virus Infections; Steroids; Up-Regulation

Several topical corticosteroids are available as anti-inflammatory treatment for asthma. Their comparative effects on allergic inflammation and airway remodeling are unclear.. We compared the effects of ciclesonide with those of fluticasone propionate in a Brown Norway rat model of chronic allergic asthma.. Rats sensitized and exposed to ovalbumin (OVA) were treated with dry powder vehicle, ciclesonide, or fluticasone (0.01, 0.03, and 0.1 mg/kg administered intratracheally) 24 hours and 1 hour before each of 6 OVA exposures. In a second protocol we administered 0.1 mg/kg ciclesonide or fluticasone only after the third OVA exposure.. Ciclesonide at all doses inhibited the allergen-induced increase in airway eosinophils and T cells, reduced goblet cell hyperplasia, and decreased 5-bromo-2'-deoxyuridine-immunoreactive airway smooth muscle (ASM) and epithelial cells. At 0.03 and 0.1 mg/kg ciclesonide, bronchial hyperresponsiveness (BHR) was also inhibited. Fluticasone did not attenuate allergen-induced BHR, despite inhibiting airway eosinophils and T cells, goblet cell hyperplasia, and 5-bromo-2'-deoxyuridine-immunoreactive ASM and epithelial cells. Fluticasone (0.1 mg/kg) caused a significant reduction in body weight (9%) compared with ciclesonide (0.1 mg/kg). Ciclesonide did not change plasma corticosterone levels, whereas fluticasone (0.1 mg/kg) reduced them. In the second protocol both fluticasone and ciclesonide inhibited BHR, bronchial inflammation, goblet cell hyperplasia, and ASM proliferation.. Ciclesonide potently inhibited chronic allergic inflammation, remodeling, and BHR without having an effect on body weight and the hypothalamic-pituitary-adrenal axis. Fluticasone prevented airway inflammation but not BHR, but both fluticasone and ciclesonide are effective at reversal of BHR, inflammation, and remodeling features.

Topics: Administration, Inhalation; Allergens; Androstadienes; Animals; Anti-Allergic Agents; Body Weight; Corticosterone; Dose-Response Relationship, Drug; Eosinophils; Epithelial Cells; Fluticasone; Male; Muscle, Smooth; Ovalbumin; Pregnenediones; Rats; Rats, Inbred BN; Respiratory Hypersensitivity; Respiratory System; T-Lymphocytes

To determine broadband ultrasound attenuation (BUA) and speed of sound (SOS) on the os caicis in asthmatic children. To correlate these findings with sex, age, weight and height, topical steroid intake, and asthma severity grade (ASG).. 178 children (ASG 1 - 3)/(98 m, 80 f; mean age 11.9 +/- 3.1 y) were consecutively chosen from 4/00 to 9/01. Children with any other chronic disease were excluded. BUA and SOS were measured using SAHARA (Hologic lnc. Waltham, USA). Regional normative BUA and SOS data of 3 299 children (obtained with the same system), were used to calculate age-, weight- and height-matched standard-deviation-scores (SDS) for both sexes. Asthma severity grade and steroidal intake were determined. The highest topical steroid dosage was 500 micro g Fluticasone or 800 micro g Budesonide per day.. 10/178 children were small and 7/178 tall per age (5.6 %/3.9 %), 11/178 children were light (6.2 %) and 9 heavy per age (5.0 %). 19 and 45 children had reduced BUA and SOS values, respectively. The following rates of reduced values were observed: girls: BUA 15.0 % (12/80), SOS 25.0 % (20/80); boys: BUA 7.1 %, SOS 25.5 % (7/98 and 25/98). Sexual differences were not significant. Reduced SOS-values were associated with higher severity and occurred significantly more frequent at children under steroidal intake (0.09 vs. 0.25 [BUA] and - 0.37 vs. - 0.07 [SOS]).. Following our results an increase incidence of reduced speed of sound occurs in asthmatic children which is attributed to asthma severity and seems to be negatively influenced even by topically applied low dose steroids. This could be attributed to a steroid induced collagen synthesis deficiency followed by a reduced bone elasticity. Further studies, especially using a longitudinal study design are required to verify these findings.

Topics: Adolescent; Adrenal Cortex Hormones; Age Factors; Androstadienes; Anti-Inflammatory Agents; Asthma; Body Height; Body Weight; Bronchodilator Agents; Budesonide; Child; Female; Fluticasone; Humans; Male; Multivariate Analysis; Sex Factors; Ultrasonography

In one of two cases of systemic effects of high-dose inhaled corticosteroid treatment with fluticasone propionate, adrenal suppression was demonstrated in a young man, and in the other retarded growth and severe general effects were observed in connection with infection in a child. These cases illustrate the risk of systemic effects of inhaled corticosteroids, and the importance of using the lowest possible maintenance dose.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Body Height; Body Weight; Child; Child, Preschool; Fluticasone; Growth; Humans; Male; Pituitary-Adrenal System