BACKGROUND: Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise approaches in asthmatic children, there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years. This study aimed to compare the safety and efficacy of salmeterol/fluticasone (SFC) vs. montelukast (MON), or combination of montelukast and fluticasone (MFC) in children and adolescents aged 4 to 18 years with bronchial asthma. METHODS: A systematic search was conducted in MEDLINE, EMBASE, the Cochrane Library, China BioMedical Literature Database, Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, and Wanfang for randomized controlled trials (RCTs) published from inception to May 24, 2021. Interventions are as follows: SFC vs. MON, or combination of MFC, with no limitation of dosage or duration. Primary and secondary outcome measures were as follows: the primary outcome of interest was the risk of asthma exacerbation. Secondary outcomes included risk of hospitalization, pulmonary function, asthma control level, quality of life, and adverse events (AEs). A random-effects (I2 ≥ 50%) or fixed-effects model (I2 < 50%) was used to calculate pooled effect estimates, comparing the outcomes between the intervention and control groups where feasible. RESULTS: Of the 1006 articles identified, 21 studies met the inclusion criteria with 2643 individuals; two were at low risk of bias. As no primary outcomes were similar after an identical treatment duration in the included studies, meta-analysis could not be performed. However, more studies favored SFC, instead of MON, owing to a lower risk of asthma exacerbation in the SFC group. As for secondary outcome, SFC showed a significant improvement of peak expiratory flow (PEF)%pred after 4 weeks compared with MFC (mean difference [MD]: 5.45; 95% confidence interval [CI]: 1.57-9.34; I2 = 95%; P = 0.006). As for asthma control level, SFC also showed a higher full-controlled level (risk ratio [RR]: 1.51; 95% CI: 1.24-1.85; I2 = 0; P < 0.001) and higher childhood asthma control test score after 4 weeks of treatment (MD: 2.30; 95% CI: 1.39-3.21; I2 = 72%; P < 0.001) compared with MFC. CONCLUSIONS: SFC may be more effective than MFC for the treatment of asthma in children and adolescents, especially in improving asthma control level. However, there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma. Further research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs. PROSPERO REGISTRATION NUMBER CRD42019133156.
Acetates ; Administration, Inhalation ; Adolescent ; Adrenal Cortex Hormones/therapeutic use* ; Albuterol/therapeutic use* ; Anti-Asthmatic Agents/therapeutic use* ; Asthma/drug therapy* ; Child ; Cyclopropanes ; Drug Therapy, Combination ; Fluticasone/therapeutic use* ; Humans ; Quinolines ; Salmeterol Xinafoate/therapeutic use* ; Sulfides

PURPOSE: Asthma control in older asthmatics is often less effective, which may be attributed to small airway dysfunction and poor inhalation technique. We compared the efficacy of 2 inhalers (fluticasone propionate/formoterol treatment using a pressurized metered-dose inhaler [p-MDI group] vs. fluticasone propionate/salmeterol treatment using a dry powder inhaler [DPI group]) in older asthmatics.METHODS: We conducted a 12-week, randomized, open-label, parallel-designed trial in older patients (over 55 years old) with moderate-to-severe asthma, and compared the efficacy and safety for asthma control between the 2 groups. Subgroup analyses on disease duration and air trapping were performed. Clinical parameters, including changes in lung function parameters, inhaler technique and adherence, were compared with monitoring adverse reactions between the 2 groups.RESULTS: A total of 68 patients underwent randomization, and 63 (30 in the p-MDI group and 33 in the DPI group) completed this study. The p-MDI group was non-inferior to the DPI group with regard to the rate of well-controlled asthma (53.3% vs. 45.5%, P < 0.001; a predefined non-inferiority limit of 17%). In subgroup analyses, the proportion of patients who did not reach well-controlled asthma in the p-MDI group was non-inferior to that in the DPI group; the difference was 12.7% among those with a longer disease duration (≥ 15 years) and 17.5% among those with higher air-trapping (RV/TLC ≥ 45%), respectively (a predefined non-inferiority limit of 17%, P < 0.001). No significant differences were observed in lung function parameters, inhalation techniques, adherence and adverse reactions between the 2 groups.CONCLUSION: These results suggest that the p-MDI group may be comparable to the DPI group in the management of older asthmatics in aspects of efficacy and safety.
Airway Management ; Asthma ; Dry Powder Inhalers ; Fluticasone ; Humans ; Inhalation ; Lung ; Medication Adherence ; Metered Dose Inhalers ; Nebulizers and Vaporizers ; Random Allocation

fluticasone nasal spray (two sprays in each nostril once daily). Olfactory function was evaluated at baseline and again at three months, and results were quantified as patient TDI (threshold, discrimination, and identification) scoreRESULTS: Olfactory function improved in 74 of 134 patients (55.2%). Etiology of olfactory disorder, sex, and age had statistically significant influence on the improvement rate of olfactory function, among which etiology of olfactory loss was the most important. However, initial severity and duration of olfactory loss had no statistically significant influence on the improvement rate. The TDI score at three months of olfactory training showed remarkable improvement, primarily because of improvements in the discrimination and identification components.CONCLUSION: The present study showed that olfactory training with intranasal corticosteroid was beneficial to improve olfactory function in patients with olfactory dysfunction, particularly in postviral infection patients.]]>
Adult ; Discrimination (Psychology) ; Fluticasone ; Humans ; Methods ; Odors ; Olfaction Disorders ; Regeneration

OBJECTIVE: To study the clinical effect of different combinations of fluticasone propionate (Flu), montelukast sodium (Mon) and ketotifen (Ket) in the treatment of children with cough variant asthma (CVA). METHODS: A total of 280 children with CVA who were admitted to the department of respiratory medicine from June 2015 to January 2018 were randomly divided into Flu+Mon+Ket, Flu+Mon, Flu+Ket, Mon+Ket, Flu, Mon and Ket groups, with 40 children in each group. The children in each group were given corresponding drug(s), and the course of treatment was 3 months for all groups. The condition of cough, cough symptom score, pulmonary function and adverse drug reactions were evaluated after 2 and 3 months of treatment. The children were followed up to observe recurrence. RESULTS: After treatment, cough symptom score tended to decrease in all 7 groups, with increases in percentage of forced expiratory volume in 1 second (FEV1%) and percentage of predicted peak expiratory flow (PEF%). After 2 months of treatment, the Flu+Mon+Ket group had a significantly lower cough symptom score and significantly higher FEV1% and PEF% than the other groups (P<0.05). After 2 and 3 months of treatment, the Ket group had a significantly higher cough symptom score and significantly lower FEV1% and PEF% than the other groups (P<0.05). After 3 months of treatment, there were no significant differences in cough symptom score, FEV1% and PEF% among the other groups (P>0.05). There was a low incidence rate of adverse events in all 7 groups, and there was no significant difference among the 7 groups (P>0.05). The Ket group had a significantly higher recurrence rate of cough than the other groups (P<0.001), while there was no significant difference in this rate among the other groups (P>0.0024). CONCLUSIONS For children with CVA, a combination of Flu, Mon and Ket has a better clinical effect than a combination of two drugs and a single drug at 2 months of treatment and is safe. After 3 months of treatment, Flu or Mon alone has a similar effect to drug combination. Ket alone has a poor clinical effect and a high recurrence rate after drug withdrawal.
Acetates ; Androstadienes ; Anti-Asthmatic Agents ; Asthma ; drug therapy ; Child ; Cough ; drug therapy ; Drug Combinations ; Fluticasone ; Humans ; Ketotifen ; Quinolines

PURPOSE: To compare the surgical outcomes and intraocular pressure (IOP) reduction after trabeculectomy in patients with primary open-angle glaucoma (POAG) according to treatment with three different postoperative topical steroids. METHODS: A total of 84 eyes of 84 patients who had undergone trabeculectomy for POAG and were followed-up at least 1 year were included in this study. According to the postoperative topical steroid treatment, the patients were divided into three groups involving 0.5% loteprednol etabonate (LE), 1% rimexolone (RMX), and 1% prednisolone acetate (PDA). The mean IOP change, mean number of topical anti-glaucoma medication changes, 1-year success rate, and complication percentage were compared among the three groups. RESULTS: There were significant reductions in the IOP and number of anti-glaucoma medications during the postoperative 1-year follow-up in all of the groups (all, p < 0.05), but there were no differences among the three groups. Postoperative 1-year success rates (68.2% in the LE group, 67.0% in the RMX group, and 65.9% in the PDA group; p = 0.88) and complication percentages of trabeculectomy were not significantly different among the three groups. CONCLUSIONS: There were no statistical differences in the 1-year success rate, complication percentage, visual acuity, IOP, and number of anti-glaucoma medications among treatment regimens. LE and RMX were as effective and safe as PDA after trabeculectomy in patients with POAG.
Follow-Up Studies ; Glaucoma, Open-Angle ; Humans ; Intraocular Pressure ; Loteprednol Etabonate ; Prednisolone ; Steroids ; Trabeculectomy ; Visual Acuity

Gonococcal conjunctivitis is rare in adults and, if not treated properly, can cause corneal perforation. Gonococcal conjunctivitis typically presents with a severe mucopurulent discharge, similar to that associated with viral conjunctivitis. Here, we describe a case of monocular gonococcal conjunctivitis, including its clinical characteristics and slit-lamp images, which was initially misdiagnosed as epidemic conjunctivitis. A 20-year-old man was referred to our hospital with no improvement in monocular infection and purulent ocular discharge after 2-wk treatment using antibiotic and 0.1% fluorometholone eye drops at the local ophthalmic clinic. Initially, 0.5% loteprednol eye drops were used since we suspected viral conjunctivitis. Following this treatment, conjunctival infection worsened and a yellow-white ocular discharge covered the conjunctiva and cornea surface. Additional history taking revealed that the patient had sexual contact with a prostitute 1 wk prior to symptom presentation and, after the encounter, he took antibiotics for genital discharge at the local urology clinic, but self-discontinued treatment. A Gram staining showed gram-negative diplococci and culture of collected ocular discharge from the palpebral conjunctiva revealed growth of Neisseria gonorrhoeae, confirming gonococcal conjunctivitis. Following this, the patient was systemically treated with 3rd generation cephalosporin antibiotics. After 3-d treatment, conjunctival infection and purulent ocular discharge had significantly improved. When clinical symptoms are aggravated following steroid eye drop treatment for suspected monocular viral conjunctivitis, gonococcal conjunctivitis must be considered as a differential diagnosis
Adult* ; Anti-Bacterial Agents ; Cephalosporins ; Conjunctiva ; Conjunctivitis* ; Conjunctivitis, Viral ; Cornea ; Corneal Perforation ; Diagnosis, Differential ; Fluorometholone ; Humans ; Loteprednol Etabonate ; Male* ; Neisseria gonorrhoeae ; Ophthalmic Solutions ; Sex Workers ; Urology ; Young Adult

PURPOSE: To compare the effects of anti-inflammatory agents, specifically bromfenac, loteprednol, and prednisolone, on the permeability of cultured human trabecular meshwork cell (HTMC) monolayers. METHODS: HTMCs were cultured until confluency in the inner chamber of Transwell, then exposed to 1/1,000 or 1/500 diluted commercial 0.1% bromfenac, 0.5% loteprednol, and 1% prednisolone for 24 hours. The permeabilities of carboxyfluorescein through the HTMC monolayer were measured with a spectrofluorometer after 2 hours in the outer chamber. Cellular viabilities were assessed with an 3-[4,5–dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Bromfenac and loteprednol diluted at 1/1,000 or 1/500 did not significantly affect the cellular survival (p > 0.05). Bromfenac did not affect the permeability via the HTMC monolayer (p > 0.05) and loteprednol decreased the permeability (p < 0.05). In addition, 1/2,000 prednisolone also decreased the permeability (p < 0.05). CONCLUSIONS: Among the anti-inflammatory agents, the non-steroidal anti-inflammatory agent bromfenac did not affect the permeability, while loteprednol and prednisolone decreased the permeability through the HTMC monolayer. Thus, loteprednol and prednisolone may decrease the trabecular outflow.
Anti-Inflammatory Agents* ; Humans ; Loteprednol Etabonate ; Permeability* ; Prednisolone ; Trabecular Meshwork*

PURPOSE: To compare the effects of anti-inflammatory agents, specifically bromfenac, loteprednol, and prednisolone, on the permeability of cultured human trabecular meshwork cell (HTMC) monolayers. METHODS: HTMCs were cultured until confluency in the inner chamber of Transwell, then exposed to 1/1,000 or 1/500 diluted commercial 0.1% bromfenac, 0.5% loteprednol, and 1% prednisolone for 24 hours. The permeabilities of carboxyfluorescein through the HTMC monolayer were measured with a spectrofluorometer after 2 hours in the outer chamber. Cellular viabilities were assessed with an 3-[4,5–dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Bromfenac and loteprednol diluted at 1/1,000 or 1/500 did not significantly affect the cellular survival (p > 0.05). Bromfenac did not affect the permeability via the HTMC monolayer (p > 0.05) and loteprednol decreased the permeability (p < 0.05). In addition, 1/2,000 prednisolone also decreased the permeability (p < 0.05). CONCLUSIONS: Among the anti-inflammatory agents, the non-steroidal anti-inflammatory agent bromfenac did not affect the permeability, while loteprednol and prednisolone decreased the permeability through the HTMC monolayer. Thus, loteprednol and prednisolone may decrease the trabecular outflow.
Anti-Inflammatory Agents* ; Humans ; Loteprednol Etabonate ; Permeability* ; Prednisolone ; Trabecular Meshwork*

PURPOSE: Recent studies have shown that the cysteinyl leukotriene (cysLT) of exhaled breath condensate (EBC) could be predictive of inflammatory status and effectiveness of treatment in allergic disease. The aim of this study was to evaluate the inflammation and therapeutic effectiveness of cysLT in EBC in pediatric patients with allergic rhinitis (AR). METHODS: We enrolled 34 healthy children (median age, 4 years 10 months) and 67 AR children (median age, 5 years 1 month). All of the AR patients received intranasal steroid (fluticasone furoate) once daily for 2 weeks. After 2 week of fluticasone furoate treatment, they were classified into 2 groups: the fluticasone furoate (F) and montelukast (M) groups. We treated each group for another 8 weeks. To evaluate the therapeutic effectiveness, we used symptom score (SS) and EBC leukotriene E4 (LTE4). EBC samples were collected with RTube. Each parameter was checked at 0, 2, and 10 weeks of therapy. RESULTS: Most of the AR patients showed clinical improvement with 2- and 10-week fluticasone therapy (F group: 0-week SS, 5.6; 2-week SS, 3.6; 10-week SS, 2.1; P<0.01; M group: 0-week SS, 4.8; 2-week SS, 3.2; 10-week SS, 1.9: P<0.01). LTE4 levels were higher in AR patients than in control subjects (0 week: 87 pg/mL vs. 18 pg/mL) and were reduced after 2 weeks of fluticasone treatment (F group: 90→51.6 pg/mL, P<0.01; M group: 84→46.1 pg/mL, P<0.01). After 10 weeks of treatment, there was no significant difference in the LTE4 level between the F and M groups. CONCLUSION: LTE4 in EBC may be useful for evaluating inflammation and therapeutic effectiveness in patients with allergic rhinitis.
Child* ; Fluticasone ; Humans ; Inflammation* ; Leukotriene E4* ; Rhinitis, Allergic*

Chronic obstructive pulmonary disease (COPD) is a type of progressive, obstructive lung disease characterized by long-term poor airflow. The symptoms of COPD may be relieved and its progression delayed by fluticasone (FTS), salmeterol (SM), and tiotropium (TTP). The aim of this study is to investigate pharmacokinetic (PK) characteristics of inhaled FTS, SM, and TTP after co-administration. An open-label, single-arm, three-period, simple ascending dose study was conducted in 10 healthy male subjects. A single dose of FTS/SM (250/50 µg) and TTP (18 µg) were concomitantly inhaled in period 1, and the dose of each drug was escalated to two- and three-fold in periods 2 and 3, respectively, with a 2-week washout between periods. Activated charcoal was co-administered before and after inhalation to block gastrointestinal absorption. Blood samples for PK analysis were collected up to 24 hours. PK parameters were obtained by non-compartmental analysis. FTS, SM, and TTP rapidly reached maximum plasma concentration after inhalation (0.08–3.00 h, 0.03–0.10 h and 0.03–0.10 h, respectively) and were eliminated with mean half-lives of 9.29–10.44 h, 6.09–12.39 h and 0.25–47.42 h, respectively. PK assessment of the lowest dose of TTP was limited due to relatively low systemic exposure compared to the lower limit of quantification. In conclusion, PK characteristics of FTS, SM, and TTP by pulmonary absorption were evaluated after concurrent inhalation. FTS and SM showed dose-proportional PK profiles between 250–750 µg and 50–150 µg, respectively, while TTP presented dose-proportionality in the early phase exposure between 18-54 µg.
Charcoal ; Fluticasone* ; Gastrointestinal Absorption ; Humans ; Inhalation* ; Lung Diseases, Obstructive ; Male ; Pharmacokinetics ; Plasma ; Pulmonary Disease, Chronic Obstructive ; Respiratory Tract Absorption ; Salmeterol Xinafoate* ; Tiotropium Bromide*