Airway Obstruction Worsens in Young Adults with Asthma Who Become Obese.

BACKGROUND: Few studies have examined how developing obesity in early adulthood affects the course of asthma. OBJECTIVE: We analyzed lung function and asthma impairment and risk among nonobese children with asthma, comparing those who were obese in young adulthood with those who remained nonobese. METHODS: We carried out the post hoc analysis of 771 subjects with mild to moderate asthma who were not obese (pediatric definition, body mass index [BMI] < 95th percentile) when enrolled in the Childhood Asthma Management Program at ages 5-12 years. The subjects were then followed to age 20 years or more. For visits at ages 20 years or more, spirometry values as percent predicted and recent asthma symptom scores and prednisone exposure were compared between 579 subjects who were nonobese at all visits and 151 who were obese (adult definition of BMI ≥ 30 kg/m(2)) on at least 1 visit (median number of visits when obese = 4, IQR 2-7). RESULTS: Compared with participants who were nonobese (BMI 23.4 ± 2.6 kg/m(2)), those who became obese (BMI 31.5 ± 3.8 kg/m(2)) had significant decreases in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) (P < .0003) and FEV1 (P = .001), without differences in FVC (P = .15) during visits at ages 20 years or more. For each unit increase of BMI, FEV1 percent predicted decreased by 0.29 (P = .0009). The relationship between BMI and lung function was not confounded by sex or BMI at baseline. Asthma impairment (symptom scores) and risk (prednisone use) did not differ between the 2 groups. CONCLUSION: Becoming obese in early adulthood was associated with increased airway obstruction, without impact on asthma impairment or risk.

Classification of childhood asthma phenotypes and long-term clinical responses to inhaled anti-inflammatory medications.

BACKGROUND: Although recent studies have identified the presence of phenotypic clusters in asthmatic patients, the clinical significance and temporal stability of these clusters have not been explored. OBJECTIVE: Our aim was to examine the clinical relevance and temporal stability of phenotypic clusters in children with asthma. METHODS: We applied spectral clustering to clinical data from 1041 children with asthma participating in the Childhood Asthma Management Program. Posttreatment randomization follow-up data collected over 48 months were used to determine the effect of these clusters on pulmonary function and treatment response to inhaled anti-inflammatory medication. RESULTS: We found 5 reproducible patient clusters that could be differentiated on the basis of 3 groups of features: atopic burden, degree of airway obstruction, and history of exacerbation. Cluster grouping predicted long-term asthma control, as measured by the need for oral prednisone (P < .0001) or additional controller medications (P = .001), as well as longitudinal differences in pulmonary function (P < .0001). We also found that the 2 clusters with the highest rates of exacerbation had different responses to inhaled corticosteroids when compared with the other clusters. One cluster demonstrated a positive response to both budesonide (P = .02) and nedocromil (P = .01) compared with placebo, whereas the other cluster demonstrated minimal responses to both budesonide (P = .12) and nedocromil (P = .56) compared with placebo. CONCLUSION: Phenotypic clustering can be used to identify longitudinally consistent and clinically relevant patient subgroups, with implications for targeted therapeutic strategies and clinical trials design.

Effect of vitamin D and inhaled corticosteroid treatment on lung function in children.

RATIONALE: Low vitamin D levels are associated with asthma and decreased airway responsiveness. Treatment with inhaled corticosteroids improves airway responsiveness and asthma control. OBJECTIVES: To assess the effect of vitamin D levels on prebronchodilator FEV(1), bronchodilator response, and responsiveness to methacholine (PC(20), provocative concentration of methacholine producing a 20% decline in FEV(1)) in patients with asthma treated with inhaled corticosteroids. METHODS: We measured 25-hydroxyvitamin D levels in the serum of children with persistent asthma at the time of enrollment in the Childhood Asthma Management Program. We divided subjects into the vitamin D sufficiency (>30 ng/ml), insufficiency (20-30 ng/ml), and deficiency (<20 ng/ml) groups. Covariates included age, treatment, sex, body mass index, race, history of emergency department visits, hospitalizations, and season that vitamin D specimen was drawn. Our main outcome measures were change in prebronchodilator FEV(1), bronchodilator response, and PC(20) from enrollment to 8-12 months. MEASUREMENTS AND MAIN RESULTS: Of the 1,024 subjects, 663 (65%) were vitamin D sufficient, 260 (25%) were insufficient, and 101 (10%) were deficient. Vitamin D-deficient subjects were more likely to be older, African American, and have a higher body mass index compared with the vitamin D-sufficient and insufficient subjects. In the inhaled corticosteroid treatment group, prebronchodilator FEV(1) increased from randomization to 12 months by 140 ml in the vitamin D-deficient group and prebronchodilator FEV(1) increased by 330 ml in the vitamin D insufficiency group and by 290 ml in the vitamin D sufficiency group (P = 0.0072), in adjusted models. CONCLUSIONS: In children with asthma treated with inhaled corticosteroids, vitamin D deficiency is associated with poorer lung function than in children with vitamin D insufficiency or sufficiency.

Predictors of symptoms are different from predictors of severe exacerbations from asthma in children.

BACKGROUND: Asthma therapy is typically prescribed and titrated based on patient or parent self-report of symptoms. No longitudinal studies have assessed the relationship between symptoms and severe asthma exacerbations in children. The goal of our study was (1) to assess the association of asthma symptoms with severe asthma exacerbations and (2) to compare predictors of persistent asthma symptoms and predictors of severe asthma exacerbations. METHODS: The Childhood Asthma Management Program was a multicenter clinical trial of 1,041 children randomized to receive budesonide, nedocromil, or placebo (as-needed ß-agonist). We conducted a post hoc analysis of diary cards that were completed by subjects on a daily basis to categorize subjects as having persistent vs intermittent symptoms. We defined a severe asthma exacerbation as an episode requiring ≥ 3 days use of oral corticosteroids, hospitalization, or ED visit due to asthma based on self-report at study visits every 4 months. RESULTS: While accounting for longitudinal measures, having persistent symptoms from asthma was significantly associated with having severe asthma exacerbations. Predictors of having persistent symptoms compared with intermittent symptoms included not being treated with inhaled corticosteroids, lower FEV(1)/FVC ratio, and a lower natural logarithm of provocative concentration of methacholine producing a 20% decline in FEV(1) (lnPC(20)). Predictors of having one or more severe asthma exacerbations included younger age, history of hospitalization or ED visit in the prior year, ≥ 3 days use of oral corticosteroids in the prior 3 months, lower FEV(1)/FVC ratio, lower lnPC(20), and higher logarithm to the base 10 eosinophil count; treatment with inhaled corticosteroids was predictive of having no severe asthma exacerbations. CONCLUSIONS: Patients with persistent symptoms from asthma were more likely to experience severe asthma exacerbations. Nevertheless, demographic and laboratory predictors of having persistent symptoms are different from predictors of severe asthma exacerbations. Although symptoms and exacerbations are closely related, their predictors are different. The current focus of the National Asthma Education and Prevention Program guidelines on the two separate domains of asthma control, impairment and risk, are supported by our analysis.

Association of VEGF polymorphisms with childhood asthma, lung function and airway responsiveness.

Vascular endothelial growth factor (VEGF) is an angiogenic factor implicated in asthma severity. The objective of the present study was to determine whether VEGF single nucleotide polymorphisms (SNPs) are associated with asthma, lung function and airway responsiveness. The present authors analysed 10 SNPs in 458 white families in the Childhood Asthma Management Program (CAMP). Tests of association with asthma, lung function and airway responsiveness were performed using PBAT software (Golden Helix, Inc. Bozeman, MT, USA; available at www.goldenhelix.com). Family and population-based, revpeated measures analysis of airflow obstruction were conducted. Replication studies were performed in 412 asthmatic children and their parents from Costa Rica. Associations with asthma, lung function and airway responsiveness were observed in both cohorts. SNP rs833058 was associated with asthma in both cohorts. This SNP was also associated with increased airway responsiveness in both populations. An association of rs4711750 and its haplotype with forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) ratio in both cohorts was observed. Longitudinal analysis in CAMP confirmed an association of rs4711750 with FEV(1)/FVC decline over approximately 4.5 yrs of observation. VEGF polymorphisms are associated with childhood asthma, lung function and airway responsiveness in two populations, suggesting that VEGF polymorphisms influence asthma susceptibility, airflow obstruction and airways responsiveness.

Variants in TGFB1, dust mite exposure, and disease severity in children with asthma.

RATIONALE: Polymorphisms in the gene for transforming growth factor-beta1 (TGFB1) have been associated with asthma, but not with airway responsiveness or disease exacerbations in subjects with asthma. OBJECTIVES: To test for association between single nucleotide polymorphisms (SNPs) in TGFB1 and markers of asthma severity in childhood. METHODS: We tested for the association between nine SNPs in TGFB1 and indicators of asthma severity (lung function, airway responsiveness, and disease exacerbations) in two cohorts: 416 Costa Rican parent-child trios and 465 families of non-Hispanic white children in the Childhood Asthma Management Program (CAMP). We also tested for the interaction between these polymorphisms and exposure to dust mite allergen on asthma severity. MEASUREMENTS AND MAIN RESULTS: The A allele of promoter SNP rs2241712 was associated with increased airway responsiveness in Costa Rica (P = 0.0006) and CAMP (P = 0.005), and the C allele of an SNP in the promoter region (rs1800469) was associated with increased airway responsiveness in both cohorts (P

Clinical predictors and outcomes of consistent bronchodilator response in the childhood asthma management program.

BACKGROUND: Among asthmatic subjects, bronchodilator response (BDR) to inhaled beta(2)-adrenergic agonists is variable, and the significance of a consistent response over time is unknown. OBJECTIVE: We assessed baseline clinical variables and determined the clinical outcomes associated with a consistently positive BDR over 4 years in children with mild-to-moderate persistent asthma. METHODS: In the 1041 participants in the Childhood Asthma Management Program, subjects with a change in FEV(1) of 12% or greater (and 200 mL) after inhaled beta(2)-agonist administration at each of their yearly follow-up visits (consistent BDR) were compared with those who did not have a consistent BDR. RESULTS: We identified 52 children with consistent BDRs over the 4-year trial. Multivariable logistic regression modeling demonstrated that lower baseline prebronchodilator FEV(1) values (odds ratio, 0.71; P < .0001), higher log10 IgE levels (odds ratio, 1.97; P = .002), and lack of treatment with inhaled corticosteroids (odds ratio, 0.31; P = .009) were associated with a consistent BDR. Individuals who had a consistent BDR had more hospital visits (P = .007), required more prednisone bursts (P = .0007), had increased nocturnal awakenings caused by asthma (P < .0001), and missed more days of school (P = .03) than nonresponders during the 4-year follow-up. CONCLUSIONS: We have identified predictors of consistent BDR and determined that this phenotype is associated with poor clinical outcomes.

Airway responsiveness in mild to moderate childhood asthma: sex influences on the natural history.

RATIONALE: Airway responsiveness is a prognostic marker for asthma symptoms in later life. OBJECTIVES: To evaluate characteristics responsible for persistence of airway responsiveness in children with asthma. METHODS: A total of 1,041 children, initially aged 5-12 years, with mild to moderate persistent asthma enrolled in the Childhood Asthma Management Program (CAMP) were studied prospectively for 8.6 +/- 1.8 years with methacholine challenges yearly. MEASUREMENTS AND MAIN RESULTS: Least squares geometric mean models were fit to determine effects of sex and age on airway responsiveness (provocative concentration producing 20% decrease in FEV(1) [PC(20)]). Multiple linear regression analysis was performed to determine factors at baseline and over time, which were associated with PC(20) at end of follow-up. A total of 7,748 methacholine challenges were analyzed. PC(20) increased with age, with boys having greater increase after age 11 years than girls (P < 0.001). The divergence coincided with the mean age for Tanner stage 2. Postpubertal girls had greater airway responsiveness, even after adjustment for FEV(1) and other potential confounders. Although multivariable regression analyses noted a variety of factors that influenced airway responsivness in both sexes, a history of hay fever (beta= -0.30, P = 0.005), respiratory allergy (beta= -0.32, P = 0.006), or recent inhaled corticosteroid usage (beta= -0.18, P = 0.02) were associated with decrements in final log PC(20) only in girls. CONCLUSIONS: Airway responsiveness (PC(20)) is more severe in the postpubertal female with asthma than in males. Although there are factors associated with airway responsiveness in both males and females, sex-specific factors may contribute to new insights into asthma pathogenesis.

The comparison of diphenhydramine HCl and Nedocromil sodium in prevention of abdominal postoperative adhesion formation in rat models: an experimental study.

BACKGROUND: The purpose of this study was to determine the effects of diphenhydramine HCl and Nedocromil sodium for the prevention of postsurgical adhesion formation in rat model. METHODS: Sixty adult female rats were anesthetized by 5mg/kg ketamine hydrochloride. After opening the abdominal wall, a 2 cm(2) peritoneal layer was excised from the left abdominal wall and 10 longitudinal incisions of 2 to 3 cm in length were made on the right parietal peritoneum. The abdominal wall was closed with 4/0 atraumatic continuous nylon sutures. Group I was the control group, group II was given 10mg/kg diphenhydramine HCl, group III was given 100mg/kg Nedocromil sodium, and group IV was administered both drugs in the above doses. All the drugs were instilled into the peritoneal cavity after abdominal closure except Nedocromil sodium which was administered in two separate doses 30 min before surgery and just after abdominal closure. Relaparatomy was performed 2 weeks after the initial surgery and abdominal adhesions were scored. Kruskal-Wallis and Mann-Whitney U-test were used for the statistical evaluation. RESULTS: The mean+/-S.D. (median) of adhesion scores were 2.5+/-0.90 (2.0), 1.58+/-0.99 (1.0), 0.92+/-0.86 (1.0) and 1.75+/-0.75 (2.0) in group I, II, III and IV, respectively. There were significant differences between the scores of groups I and II (P=0.033), groups I and III (P<0.001), and groups I and IV (P=0.033). CONCLUSION: Both diphenhydramine HCl and Nedocromil sodium reduced postoperative abdominal adhesions separately and in combination with each other in our study. Average score of adhesion formation was lowest in the group that was administered Nedocromil sodium. More research is needed in order to discover any positive effect of these drugs as antiadhesive agents in humans.

The influence of mechanical processing of dry powder inhaler carriers on drug aerosolization performance.

The influence of processing on the performance of carrier material used in dry powder inhalers was investigated. alpha-Lactose monohydrate crystals were processed by ball milling for cumulative time durations and their properties evaluated. As expected, milling reduced the median particle diameter while increasing fine particulate (<10 microm) and amorphous levels. Recrystallization of these partially amorphous samples resulted in a reduction in fines, elimination of amorphous material with little change in median diameter. To study the effects of processing on aerosolization performance, blends of lactose monohydrate with a model drug (nedocromil sodium trihydrate), were evaluated using an in vitro multistage liquid impinger (MSLI) model. In general, milling and storage of the carriers at high humidity (prior to blending) had a significant (ANOVA, p < 0.05) effect on the fine particle fractions (FPF; <6.8 microm). These effects were attributed predominantly to the fines content, showing a strong correlation between increased fines and FPF (R(2) = 0.974 and 0.982 for milled and recrystallized samples, respectively). However, this relationship only existed up to 15% fines concentration, after which agglomerate-carrier segregation was observed and FPF decreased significantly. These results suggest that, after processing, high-dose drug formulation performance is dominated by the presence of fines.

Anti-inflammatory pharmacotherapy for wheezing in preschool children.

Accumulating evidence indicates that there are at least two phenotypes of wheezing in preschool years with distinct natural history. Frequent wheezing in the first 3 years of life with risk factors for asthma (e.g., eczema, maternal asthma) predicts symptoms in older age, while infrequent viral-associated wheezing without risk factors for asthma has a benign prognosis. This systematic review summarizes evidence on the use of anti-inflammatory medications in preschool children with wheezing. Literature search was performed using Medline and the Cochrane Library. Retrieved articles were critically appraised. Episodic use of high-dose inhaled corticosteroids (>1,600 mcg/day of beclomethasone) may ameliorate severity of intermittent viral-associated wheezing. Maintenance inhaled corticosteroids can control symptoms in children with frequent wheezing associated with risk factors for asthma. Inhaled corticosteroids do not alter the natural history of wheezing even when started early in life and could have a negative impact on linear growth rate. Short courses of oral corticosteroids have been proposed as an effective measure to control exacerbations of symptoms although there is little evidence supporting their use. Some studies support the administration of non-steroidal anti-inflammatory medications (leukotriene pathway modifiers, cromones, methylxanthines) for mild frequent wheezing. Maintenance inhaled corticosteroids is the most effective measure for controlling frequent wheezing in preschool children, especially when accompanied by risk factors for asthma. This treatment does not affect the natural history of wheezing, although deceleration of linear growth rate is the most commonly recognized systemic adverse effect.

Protective effects of nedocromil sodium and sodium cromoglycate on gastroduodenal ulcers: a comparative study in rats.

Stabilization of mast cells plays a key mechanism to protect gastrointestinal tract from injury. This study presents a comparative evaluation of mast cell stabilizers nedocromil sodium (NDS) and sodium cromoglycate (SCG) in experimental gastric and duodenal ulcers in rats. Wistar rats of either sex were used in this study. Both NDS and SCG, in the doses of 10, 30 and 100 mg/kg were given intraperitoneally for gastric secretion studies and by gavage for antiulcer studies. Acid secretion studies were undertaken in pylorus-ligated rats. Gastric lesions were induced by water immersion restraint stress (WIRS), indomethacin and ethanol whereas duodenal ulcers were produced by cysteamine. The level of glutathione (GSH) and gastric wall mucus were measured in glandular stomach of rats following ethanol-induced gastric lesions. SCG was more effective than NDS in preventing WIRS- and indomethacin-induced gastric lesions whereas reverse was true in ethanol- and cysteamine-induced ulcers. All the 3 doses of SCG offered almost equal protection against WIRS-induced gastric lesions whereas only medium and high dose of NDS provided significant protection in this model of ulcer. NDS significantly inhibited cysteamine-induced duodenal ulcers whereas SCG failed to do so. Pretreatment with NDS or SCG significantly and dose-dependently protected gastric mucosa against ethanol-induced injury, while the former drug appeared to be more effective. The cytoprotective effects of these two drugs were accompanied by the attenuation of ethanol-induced depletion of gastric wall mucus and GSH. The differential effects of NDS and SCG against various gastric lesions rationalize the possible benefits of a combined therapy (NDS+SCG) for the treatment of complex gastroduodenal ulcers.

Efficacy and safety of mometasone furoate vs nedocromil sodium as prophylactic treatment for moderate/severe seasonal allergic rhinitis.

BACKGROUND: The preventive use of medications has been proposed to be effective in the treatment of seasonal rhinitis. OBJECTIVE: To evaluate the efficacy and safety of mometasone furoate and nedocromil sodium nasal sprays as prophylactic treatment for moderate to severe seasonal allergic rhinitis (SAR). PATIENTS: Sixty-one patients were recruited from 3 referral allergy centers. Inclusion criteria were history of SAR for 2 years or longer, sensitization to relevant local pollen (grasses, Parietaria, and olive), and age older than 12 years. METHODS: An open-label, randomized, parallel-group, "real-life" study design was used. Patients received mometasone furoate nasal spray once daily or nedocromil sodium nasal spray 3 times daily starting 2 to 4 weeks before the pollen season and continuing for up to 4 months. Instructions regarding the use of additional medications were given. Diary cards recording symptoms, use of medication, and adverse events were kept by the patients. RESULTS: All 61 patients completed the study. The prophylactic use of mometasone furoate vs nedocromil sodium led to significantly more days without symptoms (75.1% vs 54.5%; P < .001). The mometasone furoate group also had lower nasal symptom scores (mean, 1.4 vs 2.9; median, 0 vs 2; P < .001) and was more satisfied (93.1% vs 43.5%; P < .001). No serious adverse event was recorded, and there was no difference between the treatments in any adverse event. CONCLUSIONS: Prophylactic administration of mometasone furoate before the pollen season is safe and may lead to improved control of SAR compared with the use of nedocromil sodium.

Pharmacologic inhibition of mast cell degranulation prevents left ventricular remodeling induced by chronic volume overload in rats.

BACKGROUND: Left ventricular (LV) hypertrophy and dilation are important compensatory responses to chronic volume overload; however, the mechanisms responsible for this LV remodeling have not been well characterized. Previous observations that the number of myocardial mast cells are increased in congestive heart failure (CHF) suggested the hypothesis that mast cells might be involved in the ventricular remodeling induced by a chronic volume overload. METHODS AND RESULTS: Accordingly, the intent of this study was to determine the contribution of mast cells to LV remodeling, dysfunction, and morbidity/mortality secondary to CHF in the infrarenal aortocaval fistula model of sustained volume overload. To this end, LV end-diastolic pressure, size, and function (ie, isovolumetric pressure-volume relations in the blood-perfused isolated heart) were assessed in both nedocromil sodium treated and untreated rats at 8 weeks after fistula and compared with age-matched controls. Nedocromil, a mast cell-stabilizing drug, effectively prevented the LV dilation and decreased contractility seen in the untreated fistula group in a dose-dependent fashion, resulting in a significant reduction in the incidence of morbidity/mortality from CHF. CONCLUSION: The ability of mast cell stabilization to prevent ventricular dilation induced by chronic volume overload identifies a key role for mast cells in the regulation of myocardial remodeling.

Safety and application of induced sputum analysis in childhood asthma.

BACKGROUND: The value of sputum induction in pediatric asthma lies in its potential to directly and noninvasively assess airway inflammation in children, because bronchoscopy and biopsy carry some risk. The Childhood Asthma Management Program (CAMP) study was designed to evaluate the long-term effects of budesonide and nedocromil compared with placebo in children with mild to moderate asthma across 8 centers. OBJECTIVE: At the Denver CAMP site, we sought to evaluate the safety of sputum induction, to determine differences in airway inflammation between treatment groups by using induced sputum analysis, and to examine correlations between other biomarkers and sputum eosinophils. METHODS: Sputum induction was performed, and exhaled nitric oxide, circulating eosinophil counts, and serum eosinophil cationic protein were obtained at treatment discontinuation and after washout. Spirometry and a methacholine challenge were also performed according to the CAMP protocol. RESULTS: Ninety of 117 children provided an adequate sputum sample for analysis. In 9 subjects (3 nedocromil and 6 placebo), sputum induction resulted in bronchospasm. These subjects had greater disease severity, as measured by a lower median prebronchodilator FEV 1 percentage predicted (85.0% vs 96.0%; P =.024) and FEV 1 /FVC ratio (70.0% vs 79.0%; P =.0008); greater bronchodilator reversibility (16.5% vs 6.8%; P =.004); higher serum IgE (1390.0 vs 495.0 ng/mL; P =.017) and circulating eosinophil count (757.0 vs 282.0/mm 3; P =.04); greater use of prednisone (1.9 vs 0.9 courses per 100 person-years; P =.05); and greater supplemental inhaled steroid doses (85.3 vs 0 mg; P =.016). At treatment discontinuation, budesonide-treated patients had a lower median (1st, 3rd quartile) sputum percentage eosinophil (SPEos) (0.2% [0%, 1.2%] vs 0.8% [0.2%, 4.6%]; P =.03) compared with those treated with placebo; no significant difference was noted between nedocromil- and placebo-treated patients. Higher SPEos at the time of treatment discontinuation was associated with asthma worsening that required rescue prednisone (n = 23) during the washout period compared with patients who remained stable (3.6% [0.4%, 6.4%] vs 0.6% [0.2%, 3.2%] SPEos; P =.023). Finally, greater SPEos was associated with atopy, higher bronchodilator reversibility, lower FEV 1 /FVC ratio, higher exhaled nitric oxide levels, circulating eosinophils, sputum and serum eosinophil cationic protein, more prednisone courses during the treatment period, and greater asthma severity. CONCLUSIONS: Sputum induction is a relatively noninvasive and safe procedure that can provide information on eosinophilic inflammation and treatment response and is also associated with several measures of asthma control. However, this procedure still remains a research tool in asthma because of its requirements for technical expertise.

Comparative effect of triamcinolone, nedocromil and montelukast on asthma control in children: A randomized pragmatic study.

Asthma severity can be judged by measurements of symptoms, lung function, and medication requirements. The objective was to compare the effect of a 4-wk monotherapy with low-dose triamcinolone, montelukast and nedocromil on asthma control, lung function, eosinophil blood count, and bronchial hyper-reactivity in children with mild to moderate asthma allergic to dust mite. Two hundred fifty-six children, aged 6-18 yr, with mild to moderate asthma, participated in an 8-wk study. This was a three-arm, randomized no blinding or placebo pragmatic trial comparing the effect of triamcinolone acetonide (400 microg/day), inhaled nedocromil and montelukast sodium on clinical parameters of asthma [score, forced expiratory volume in 1 s (FEV(1))], PC20H, and eosinophil blood count. Two hundred forty-six children completed the study. After 4 wk of treatment with triamcinolone and montelukast, FEV(1) and PC20H significantly increased, and mean total symptoms score and mean number of eosinophil count in serum significantly decreased. Triamcinolone had a stronger effect on PC20H than montelukast. Nedocromil improved total asthma symptoms score and lung function. There was a reduction in the daytime and night-time symptom scores after treatment with all three drugs. Triamcinolone and montelukast had a stronger effect on asthma symptoms than nedocromil. There were statistically significant differences in reduction of nocturnal asthma symptoms between the triamcinolone and nedocromil groups (p < 0.001) and between montelukast and nedocromil (p = 0.001) groups, but not between the triamcinolone and montelukast groups. There was a reduction in beta-agonists use after treatment with all three drugs, with the strongest effect of triamcinolone. The study showed the strongest effect of low-dose inhaled steroids on clinical symptoms, lung function, bronchial hyper-reactivity and eosinophil blood count when compared to other asthma medications.

Evaluation of preoperative and postoperative prophylactic regimens for prevention and treatment of diffuse lamellar keratitis.

PURPOSE: To investigate preoperative and postoperative prophylactic treatment with different pharmacological agents before flap cutting and exposure to a diffuse lamellar keratitis (DLK) causative agent. SETTING: Magill Research Center for Vision Correction, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: The study comprised 48 eyes of 24 Dutch-belted rabbits. Three days before a corneal flap was cut and the corneal interface was exposed to Pseudomonas aeruginosa lipopolysaccharide endotoxin, a DLK causative agent, the eyes were randomly assigned to treatment with a mast-cell stabilizer, a nonsteroidal antiinflammatory drug (NSAID), or a corticosteroid or left without treatment as controls. The treatment was maintained throughout the 1-week follow-up. Slitlamp examinations and photographs were performed at 1, 3, 5, and 7 days; DLK was graded by a masked observer from 0 (no DLK) to IV. Corneal interface scrapings were performed in selected eyes on day 7. RESULTS: At the end of the follow-up, 36 eyes were available for evaluation. At 1 week, 100% of the control eyes and the eyes treated with the mast-cell stabilizer developed DLK; in the NSAID-treated and corticosteroid-treated eyes, the DLK rate was 86% and 70%, respectively. At 1 day, the severity of DLK was significantly lower in eyes treated with the mast-cell stabilizer (0.44) and at 7 days, it was significantly lower in corticosteroid-treated eyes (0.3) than in the control group (1.5 and 1.4, respectively) (P<.05, Wilcoxon test). Corneal interface scraping from an eye with grade III DLK showed numerous inflammatory cells. CONCLUSIONS: Preoperative and postoperative treatment with corticosteroids significantly reduced the severity of DLK compared to the untreated control eyes in this animal model. Treatment with a mast-cell stabilizer and an NSAID had less effect on the postoperative course of DLK.

[Strategies for the prevention and treatment of allergies in children and adolescents]. / Wie Sie Allergien in Schach halten: Von der Stillberatung bis zur Steroidtherapie.

Over and beyond the avoidance of allergies, prophylactic measures can also prevent the development of lower airway disease from upper airway disease, for example, bronchial asthma from allergic rhinitis. A further protective effect can be achieved by reducing both prenatal and postnatal allergens. A major concept of prevention--not merely of pulmonary function changes and the development of allergies--is the avoidance of exposure to passive smoking. With regard to pharmacotherapeutic agents, both official approval for their use by the respective age group, and the dearth of study-based data need to be taken into account. To ensure the successful application of inhalative agents, the use of appropriate inhalation aids as also ensuring the correct inhalation technique are urgently recommended, particularly in the case of children and adolescents.