Persistent airway obstruction after virus infection is not associated with airway inflammation

BACKGROUND: This study examined the contribution of airway inflammation to the delayed lung function recovery that occurs in some people following virus-induced asthma exacerbations. METHODS: Subjects (n = 40) were recruited at hospital admission for acute asthma exacerbation. Respiratory virus infection was diagnosed by viral nucleic acid detection and/or cell culture, using induced sputum, nasal, or throat swabs. Data collected included lung function, answers to common cold and asthma control questionnaires, and induced sputum cellular profiles. Subjects were reexamined 4 to 6 weeks postexacerbation and were compared with stable asthmatic subjects (n = 26) who had been recruited from ambulatory care clinics. RESULTS: Persistent airway obstruction, defined as lung function improvement at follow-up (ie, change in FEV1 percent predicted [Delta%FEV1]) of <15%, was observed in 10 subjects (25%). Airway recovery (Delta%FEV1, > or = 15%) was observed in the remaining subjects (30 subjects; 75%). During the acute episode, the airway-recovery group had increased total cell count (p = 0.019), increased number of neutrophils (p = 0.005), and increased percentage of neutrophils (p = 0.0043) compared to the group of stable subjects with asthma. Postexacerbation, the airway-recovery group had reduced numbers of neutrophils and an increased percentage of eosinophils. In contrast, during exacerbation, subjects with persistent airway obstruction showed no differences in inflammatory cell counts compared to stable subjects with asthma, nor did cell counts change postexacerbation. Symptoms improved in both groups postexacerbation. However, in the persistent-airway-obstruction group, asthma remained uncontrolled. CONCLUSION: Persistent airway obstruction and uncontrolled asthma are observed in some people after viral asthma exacerbations. These abnormalities are not associated with inflammatory cell influx into the airway lining fluid during the exacerbation and may reflect the involvement of noncellular elements. Further work should explore other mechanisms leading to incomplete airway recovery.     

Efficacy of dexamethasone injection for acute bronchiolitis in hospitalized children: a randomized, double-blind, placebo-controlled trial

Controversy over the efficacy of systemic corticosteroids for acute bronchiolitis initiated this study. We conducted a randomized, double-blind, placebo-controlled trial to examine the efficacy of single dexamethasone injection for the treatment of acute bronchiolitis in young hospitalized children. The study, performed at the pediatric wards of a University Hospital and its affiliated hospital in Thailand, included 174 previously healthy children under 2 years of age, hospitalized with acute bronchiolitis. Each child received either a single intramuscular injection of 0.6 mg/kg dexamethasone or a placebo in addition to regular management. The primary outcome was the time from study entry to resolution of respiratory distress, determined by a clinical score derived from the respiratory rate, occurrence of wheezing, chest retraction, and oxygen saturation. Survival analysis using the Kaplan-Meier method and a log-rank test were performed. A single-dose, dexamethasone injection versus placebo produced a significant: (1) decrease in the time needed for resolution of respiratory distress (hazard ratio 1.56; 95% CI, 1.14-2.13; P = 0.005), (2) decrease in the mean duration of symptoms of 11.8 hr (95% CI, 3.9-19.7; P = 0.004), (3) decrease in the mean duration of oxygen therapy of 14.9 hr (95% CI, 5.3-24.4; P = 0.003), and (4) decrease in the mean length of hospital stay of 13.4 hr (95%CI, 2.6-24.2; P = 0.02). In conclusion, a single injection of dexamethasone yielded a significant clinical benefit for the treatment of previously healthy, young children hospitalized with acute bronchiolitis.     

Adherence rate to inhaled corticosteroids and their impact on asthma control

Background:  Poor asthma control is associated to high morbidity. The objective of this study was to assess the association between adherence rates to beclomethasone dipropionate (BDP) and the degree of asthma control.
Methods:  A cohort concurrent study was carried out for 12 months with 122 asthmatic patients, aged 3–12 years, randomly selected in a pediatric pulmonology outpatient clinic, who received BDP free of charge. Adherence rates were verified by pharmacy records. Clinical control was assessed through a scoring system comprised four variables (nocturnal and morning symptoms, limitation of physical activities and exacerbations). Total score was 16 points. Patients whose score was below or equal to two were considered controlled (group 1), and patients whose score was above or equal to three were considered uncontrolled (group 2). For patients able to perform spirometry, we considered as controlled the patients with forced expiratory volume in 1 s (FEV₁) equal to or above 80% of the predicted value, and as uncontrolled the patients with FEV₁ below 80%.
Results:  Fewer than half (40.3% maximum) of the 122 patients maintained asthma control. Median adherence rate of groups 1 and 2 were 85.5% and 33.8%, ( P  < 0.001) in the 4th month, 90.0% and 48.0% ( P  < 0.001) in the 8th month and 84.4% and 47.0% in the 12th month ( P  < 0.001), respectively.
Conclusion:  In all periods, there were statistically significant differences in adherence rates for maintaining or not maintaining the asthma control. Optimal asthma control entailed adherence rate higher than 80%. Strategies for reducing asthma morbidity should include a regular monitoring of adherence to inhaled steroids.     

INFANTILE PYODERMA GANGRENOSUM

A six month old female infant with pyoderma gangrenosum is reported. Pyoderma gangrenosum in an infant is rare. The child responded to pulse therapy with intravenous dexamethasone and intralesional triamcinolone acetonide.     

系统性红斑狼疮患者的血液学异常及治疗

目的:探讨系统性红斑狼疮(SLE)患者的血液学异常变化及其对药物治疗的反应。方法:对142例SLE患者外周血、骨髓象及应用糖皮质激素、免疫抑制剂治疗后变化情况进行总结分析。结果:142例中血象异常者121例,以血液学异常为首发症状就诊者32例(26.45%),其中误诊为血液系统疾病9例(7.44%)。在142例中45例行骨髓细胞学检查,发现骨髓增生活跃或明显活跃35例(77.78%),增生低下者10例(22.22%)。结论:SLE易累及血液系统,其特点是血液学改变多样性,缺乏特异性,容易误诊漏诊。SLE患者经糖皮质激素及免疫抑制剂治疗,其外周血和骨髓象均有不同程度的改善。     

Ocular distribution, bactericidal activity and settling characteristics of TobraDex® ST ophthalmic suspension compared with TobraDex® ophthalmic suspension

Introduction

TobraDex® ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.1%; Alcon Laboratories Inc, Fort Worth, Tex) is frequently used for inflammatory ocular conditions where a risk of bacterial ocular infection exists. A new formulation, TobraDex® ST ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.05%, Alcon), utilises a novel suspension technology to reduce viscosity and help prevent settling in the container.

Methods

A rabbit model that closely mimics the human eye and a clinical study with cataract patients was used to compare the pharmacokinetics and tissue permeability of TobraDex ST and TobraDex. An in-vitro model was used to assess the bactericidal activity using the rabbit tear concentrations of tobramycin 10 minutes after a single topical dose.

Results

Concentrations of both tobramycin and dexamethasone were greater in the tear film and ocular tissues of rabbits treated with TobraDex ST. There was an 8.3-fold increase in tobramycin concentration in the rabbit tear film 10 minutes after dosing with TobraDex ST compared with TobraDex. Concentrations of tobramycin and dexamethasone in ocular tissues from rabbits exposed to TobraDex ST were up to 12.5-fold greater relative to TobraDex. The in-vitro bactericidal activity (>99.9% kill, 3-log reduction) of TobraDex ST toward tobramycin-resistant and methicillin-resistant Staphylococcus aureus occurred in 90 minutes. TobraDex ST killed Streptococcus pneumoniae 3-log in 5 minutes. TobraDex had no activity toward tobramycin-resistant, methicillin-resistant S. aureus and required approximately 120 minutes for 3-log reduction of S. pneumoniae. In humans, the mean ratio of dexamethasone levels in the aqueous humour at 1 hour was 1.17 in favour of TobraDex ST.

Conclusion

TobraDex ST demonstrated improved suspension formulation characteristics, enhanced pharmacokinetic distribution and improved bactericidal characteristics, and may provide a useful alternative as compared to TobraDex.     

Obesity and hypertension among children after treatment for acute lymphoblastic leukemia

BACKGROUND: The purpose was to determine the prevalence and treatment-related risk factors for obesity and hypertension among childhood acute lymphoblastic leukemia (ALL) survivors treated with contemporary therapy. METHODS: In a single-center longitudinal study, serial body mass indices (BMI) and blood pressure (BP) measurements of children ages 2-20 at time of ALL diagnosis and enrolled on pediatric cooperative group trials from 1993-2003 were abstracted from medical records and converted to population-referenced z-scores. RESULTS: Among 165 study participants, BMI z-scores increased significantly between diagnosis (median age 4.8 years) and therapy completion. At the end of therapy, 17.0% of survivors were overweight (BMI of 25-29, or 85-94% for age), 21.2% were obese (BMI >or=30, or >or=95% for age), and 15.3% had BP meeting stage 1+ hypertension thresholds (systolic or diastolic BP >or=140/90 mm Hg, or 95% for age and height plus 5 mm Hg). These proportions were found to be unchanged 2-3 years later. In multivariate analysis, the highest level of corticosteroid exposure was associated with both obesity (odds ratio [OR] 6.0; 95% confidence interval [95% CI], 1.2-28.5) as well as stage 1+ hypertension (OR 2.4; 95% CI, 1.2-5.1) compared with the lowest level. Females also were more likely to have increased BMI and elevated BP compared with males. Treatment intensity and cranial radiotherapy were not found to be associated with BMI or BP changes. CONCLUSIONS: Despite reductions in the use of cranial radiotherapy, contemporary childhood survivors of ALL remain at an increased risk of obesity and hypertension at least several years after the completion of treatment, with those exposed to higher doses of corticosteroids at greater risk.     

New pharmacotherapy options for noninfectious posterior uveitis

Introduction: Noninfectious posterior uveitis is a leading cause of visual impairment. Although conventional immunosuppressive agents have been successfully used, these are nonspecific and their long-term use may induce significant adverse effects. The purpose of this article is to identify recent advances and future therapeutic options in noninfectious posterior uveitis.

Areas covered: A MEDLINE database search was conducted through May 2014 using the terms: uveitis, treatment, intravitreal and corticosteroid, biological. To provide ongoing and future perspectives in treatment options, also clinical trials as registered at ClinicalTrials.gov were included.

Expert opinion: For individuals who do not respond to conventional immunotherapy, two major lines of treatments can be identified as focus in recent years: i) the intraocular application of anti-inflammatory drugs and ii) the introduction of new agents, for example, biologicals and small-molecule inhibitors. Whereas intravitreal treatments have the beauty of avoiding systemic side effects, new agents are gaining increased importance because of their highly targeted molecular effects. Even when current treatment strategies are still hampered by the paucity of randomized controlled trials, promising progress and continuous efforts are undertaken to close this gap. Still, a critical evaluation of new agents has to be made because ‘new’ agents are almost exclusively based on experience in other autoimmune disorders.     

Serum thymus and activation‐regulated chemokine as disease activity and response biomarker in alopecia areata

Serum thymus and activation‐regulated chemokine/CCL17 (sTARC) is known as a good indicator for atopic dermatitis severity. Herein, we investigate whether sTARC correlates with severity and therapeutic response for alopecia areata (AA) in our 121 patients. The sTARC mean of AA totalis and universalis was significantly higher than mild AA. Next, we compared sTARC of diffuse AA (n = 14) and severity‐controlled patchy AA (n = 32) and found that sTARC in diffuse AA (564.2 ± 400.0 pg/mL) was significantly higher than that of the patchy type (344.0 ± 239.8 pg/mL), suggesting a potential role of TARC in active progression of diffuse AA. Ten patients with diffuse AA were treated with i.v. corticosteroid pulse therapy. Then, we tested whether sTARC can predict prognosis after the pulse therapy and found that baseline sTARC in the poor responders (1025.5 ± 484.8 pg/mL) was significantly higher than that in the good responders (complete remission at 24 months after the pulse therapy, 347.8 ± 135.7 pg/mL), indicating sTARC as a response biomarker in the corticosteroid pulse therapy for diffuse AA. Finally, to investigate TARC production in the affected hair follicles, we performed immunohistochemical double staining of TARC and CD68 using scalp skin specimens of diffuse AA with high titers of sTARC. The results showed their co‐localization in the infiltrating cells around the AA hair follicles, suggesting that TARC is mainly produced from CD68⁺ histiocytes. In conclusion, sTARC is a disease activity and response biomarker in AA, providing new insight beyond the T‐helper 1/2 paradigm to solve the immunological pathogenesis of AA.     

Current and emerging strategies for the management of sarcoidosis

Sarcoidosis is a systemic inflammatory disorder of unknown etiology. Although any organ may be involved, the lungs are most frequently affected. The clinical course of the disease is highly variable, with up to two-thirds of untreated patients experiencing spontaneous remission within 12 – 24 months of onset of symptoms. When therapy is required, corticosteroids are considered standard, but studies demonstrating their ability to modify the long-term outcome in this disease are lacking. Often, the myriad of adverse side effects of corticosteroids necessitate the addition of immunosuppressants, cytotoxic agents or biologic therapies to maintain disease remission. Unfortunately, optimal therapeutic regimens have not been described. Patients who do not respond to therapy often experience progressive fibrotic changes and end-organ damage, which ultimately may result in significant morbidity or death. Agents commonly used to treat patients with sarcoidosis and emerging therapeutic options are discussed.