THE INFLUENCE OF SPELEOTHERAPY ON BRONCHI PASSAGE IN CHILDREN WITH BRONCHIAL ASTHMA USING A PHARMACO-FUNCTIONAL TEST WITH SALBUTAMOL.

OBJECTIVE: The aim: To investigate the reaction of the bronchi to inhalation of salbutamol in children with different severity of bronchial asthma under the conditions of speleotherapy. PATIENTS AND METHODS: Materials and methods: 40 children aged 6-15 years were examined, 20 of them had an intermittent course of the disease, 20 had a mild course, and the children were in the inter-relapse period. Determining the function of external respiration (FER) with a pharmaco-functional test (PFT) with salbutamol was carried out in the dynamics of observation before and after treatment and compared with the indicators of 40 healthy children. Speleotherapy was performed based on the children's department of the Ukrainian Allergological Hospital of the village Solotvino. RESULTS: Results: A decrease in increased bronchial tone and restoration of bronchial patency at all levels of the bronchi in all patients with an intermittent course of the disease and a partial decrease in bronchial hyperreactivity with the improvement of bronchial patency in children with a mild course of bronchial asthma under the influence of speleotherapy was established. CONCLUSION: Conclusions: Thus, speleotherapy contributes to a positive reaction of the bronchi to inhalation of salbutamol, which is reflected in the normalization of disturbed bronchial tone and the restoration of bronchial patency at all levels of the bronchi, in all patients with an intermittent course and partially with a mild course of the disease.

Efficacy of salmeterol and magnesium isoglycyrrhizinate combination treatment in rats with chronic obstructive pulmonary disease.

The most classic treatment recommended in the current chronic obstructive pulmonary disease (COPD) guidelines is glucocorticoid and ß2 receptor agonist combination, such as salmeterol xinafoate and fluticasone propionate (Sal/Flu), causing many adverse reactions due to hormones. Magnesium isoglycyrrhizinate (MgIG) is an anti-inflammatory glycyrrhizic acid preparation for treating chronic inflammation, contributing to its structure is similar to steroidal anti-inflammatory drugs. In this study, we successfully established COPD rat model by endotracheal-atomized lipopolysaccharide exposure and cigarette smoke induction, as characterized by lung function decline. We discovered that salmeterol xinafoate/MgIG combination could alleviated lung inflammation infiltration, airway wall thickness (AWT) and the secretion of bronchial mucin MUC5AC of COPD rats more than salmeterol xinafoate, MgIG, or salmeterol xinafoate and fluticasone propionate treatment did, as well as reduced inflammatory cells (white blood cells, neutrophils and lymphocytes) accumulation in bronchoalveolar lavage fluid and decreased TNF-α, IL-6 and IL-1ß production in the serum of COPD rats. Finally, we found that Moreover, the mechanism involved might be related to the suppression of JAK/STAT signaling pathway. Overall, our studies suggested that MgIG might be a potential alternative adjuvant drug for fluticasone propionate for the clinical treatment of patients with COPD.

Reducing Unnecessary Treatments for Acute Bronchiolitis Through an Integrated Care Pathway.

OBJECTIVES: To analyze the impact of an integrated care pathway on reducing unnecessary treatments for acute bronchiolitis. METHODS: We implemented an evidence-based integrated care pathway in primary care (PC) centers and the referral emergency department (ED). This is the third quality improvement cycle in the management of acute bronchiolitis implemented by our research team. Family and provider experiences were incorporated by using design thinking methodology. A multifaceted plan that included several quality improvement initiatives was adopted to reduce unnecessary treatments. The primary outcome was the percentage of infants prescribed salbutamol. Secondary outcomes were prescribing rates of other medications. The main control measures were hospitalization and unscheduled return rates. Salbutamol prescribing rate data were plotted on run charts. RESULTS: We included 1768 ED and 1092 PC visits, of which 913 (51.4%) ED visits and 558 (51.1%) PC visits occurred in the postintervention period. Salbutamol use decreased from 7.7% (interquartile range [IQR] 2.8-21.4) to 0% (IQR 0-1.9) in the ED and from 14.1% (IQR 5.8-21.6) to 5% (IQR 2.7-8) in PC centers. In the ED, the overall epinephrine use rate fell from 9% (95% confidence interval [CI], 7.2-11.1) to 4.6% (95% CI, 3.4-6.1) (P < .001). In PC centers, overall corticosteroid and antibiotic prescribing rates fell from 3.5% (95% CI, 2.2-5.4) to 1.1% (95% CI, 0.4-2.3) (P =.007) and from 9.5% (95% CI; 7.3-12.3) to 1.7% (95% CI, 0.9-7.3) (P <.001), respectively. No significant variations were noted in control measures. CONCLUSIONS: An integrated clinical pathway that incorporates the experiences of families and clinicians decreased the use of medications in the management of bronchiolitis.

Magnesium sulphate for treating acute bronchiolitis in children up to two years of age.

BACKGROUND: Acute bronchiolitis is a significant burden on children, their families and healthcare facilities. It mostly affects children younger than two years of age. Treatment involves adequate hydration, humidified oxygen supplementation, and nebulisation of medications, such as salbutamol, epinephrine, and hypertonic saline. The effectiveness of magnesium sulphate for acute bronchiolitis is unclear. OBJECTIVES: To assess the effects of magnesium sulphate in acute bronchiolitis in children up to two years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, CINAHL, and two trials registries to 30 April 2020. We contacted trial authors to identify additional studies. We searched conference proceedings and reference lists of retrieved articles. Unpublished and published studies were eligible for inclusion. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs, comparing magnesium sulphate, alone or with another treatment, with placebo or another treatment, in children up to two years old with acute bronchiolitis. Primary outcomes were time to recovery, mortality, and adverse events. Secondary outcomes were duration of hospital stay, clinical severity score at 0 to 24 hours and 25 to 48 hours after treatment, pulmonary function test, hospital readmission within 30 days, duration of mechanical ventilation, and duration of intensive care unit stay. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We used GRADE methods to assess the certainty of the evidence. MAIN RESULTS: We included four RCTs (564 children). One study received funding from a hospital and one from a university; two studies did not report funding sources. Comparator interventions differed among all four trials. Studies were conducted in Qatar, Turkey, Iran, and India. We assessed two studies to be at an overall low risk of bias, and two to be at unclear risk of bias, overall. The certainty of the evidence for all outcomes and comparisons was very low except for one: hospital re-admission rate within 30 days of discharge for magnesium sulphate versus placebo. None of the studies measured time to recovery, duration of mechanical ventilation, duration of intensive care unit stay, or pulmonary function. There were no events of mortality or adverse effects for magnesium sulphate compared with placebo (1 RCT, 160 children). The effects of magnesium sulphate on clinical severity are uncertain (at 0 to 24 hours: mean difference (MD) on the Wang score 0.13, 95% confidence interval (CI) -0.28 to 0.54; and at 25 to 48 hours: MD on the Wang score -0.42, 95% CI -0.84 to -0.00). Magnesium sulphate may increase hospital re-admission rate within 30 days of discharge (risk ratio (RR) 3.16, 95% CI 1.20 to 8.27; 158 children; low-certainty evidence). None of our primary outcomes were measured for magnesium sulphate compared with hypertonic saline (1 RCT, 220 children). Effects were uncertain on the duration of hospital stay in days (MD 0.00, 95% CI -0.28 to 0.28), and on clinical severity on the Respiratory Distress Assessment Instrument (RDAI) score at 25 to 48 hours (MD 0.10, 95% CI -0.39 to 0.59). There were no events of mortality or adverse effects for magnesium sulphate, with or without salbutamol, compared with salbutamol (1 RCT, 57 children). Effects on the duration of hospital stay were uncertain (magnesium sulphate: 24 hours (95% CI 25.8 to 47.4), magnesium sulphate + salbutamol: 20 hours (95% CI 15.3 to 39.0), and salbutamol: 24 hours (95% CI 23.4 to 76.9)). None of our primary outcomes were measured for magnesium sulphate + epinephrine compared with no treatment or normal saline + epinephrine (1 RCT,120 children). Effects were uncertain for the duration of hospital stay in hours (MD -0.40, 95% CI -3.94 to 3.14), and for RDAI scores (0 to 24 hours: MD -0.20, 95% CI -1.06 to 0.66; and 25 to 48 hours: MD -0.90, 95% CI -1.75 to -0.05). AUTHORS' CONCLUSIONS: There is insufficient evidence to establish the efficacy and safety of magnesium sulphate for treating children up to two years of age with acute bronchiolitis. No evidence was available for time to recovery, duration of mechanical ventilation and intensive care unit stay, or pulmonary function. There was no information about adverse events for some comparisons. Well-designed RCTs to assess the effects of magnesium sulphate for children with acute bronchiolitis are needed. Important outcomes, such as time to recovery and adverse events should be measured.

Cervical stitch (cerclage) in combination with other treatments for preventing spontaneous preterm birth in singleton pregnancies.

BACKGROUND: Preterm birth (PTB) remains the foremost global cause of perinatal morbidity and mortality. Thus, the prevention of spontaneous PTB still remains of critical importance. In an attempt to prevent PTB in singleton pregnancies, cervical cerclage, in combination with other treatments, has been advocated. This is because, cervical cerclage is an intervention that is commonly recommended in women with a short cervix at high risk of preterm birth but, despite this, many women still deliver prematurely, as the biological mechanism is incompletely understood. Additionally, previous Cochrane Reviews have been published on the effectiveness of cervical cerclage in singleton and multiple pregnancies, however, none has evaluated the effectiveness of using cervical cerclage in combination with other treatments. OBJECTIVES: To assess whether antibiotics administration, vaginal pessary, reinforcing or second cerclage placement, tocolytic, progesterone, or other interventions at the time of cervical cerclage placement prolong singleton gestation in women at high risk of pregnancy loss based on prior history and/or ultrasound finding of 'short cervix' and/or physical examination. History-indicated cerclage is defined as a cerclage placed usually between 12 and 15 weeks gestation based solely on poor prior obstetrical history, e.g. multiple second trimester losses due to painless dilatation. Ultrasound-indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation for transvaginal ultrasound cervical length < 20 mm in a woman without cervical dilatation. Physical exam-indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation because of cervical dilatation of one or more centimetres detected on physical (manual) examination. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (26 September 2019), and reference lists of retrieved studies. SELECTION CRITERIA: We included published, unpublished or ongoing randomised controlled trial (RCTs). Studies using a cluster-RCT design were also eligible for inclusion in this review but none were identified. We excluded quasi-RCTs (e.g. those randomised by date of birth or hospital number) and studies using a cross-over design. We also excluded studies that specified addition of the combination therapy after cervical cerclage because the woman subsequently became symptomatic. We included studies comparing cervical cerclage in combination with one, two or more interventions with cervical cerclage alone in singleton pregnancies. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts of all retrieved articles, selected studies for inclusion, extracted data, assessed risk of bias, and evaluated the certainty of the evidence for this review's main outcomes. Data were checked for accuracy. Standard Cochrane review methods were used throughout. MAIN RESULTS: We identified two studies (involving a total of 73 women) comparing cervical cerclage alone to a different comparator. We also identified three ongoing studies (one investigating vaginal progesterone after cerclage, and two investigating cerclage plus pessary). One study (20 women), conducted in the UK, comparing cervical cerclage in combination with a tocolytic (salbutamol) with cervical cerclage alone in women with singleton pregnancy did not provide any useable data for this review. The other study (involving 53 women, with data from 50 women) took place in the USA and compared cervical cerclage in combination with a tocolytic (indomethacin) and antibiotics (cefazolin or clindamycin) versus cervical cerclage alone - this study did provide useable data for this review (and the study authors also provided additional data on request) but meta-analyses were not possible. This study was generally at a low risk of bias, apart from issues relating to blinding. We downgraded the certainty of evidence for serious risk of bias and imprecision (few participants, few events and wide 95% confidence intervals). Cervical cerclage in combination with an antibiotic and tocolytic versus cervical cerclage alone (one study, 50 women/babies) We are unclear about the effect of cervical cerclage in combination with antibiotics and a tocolytic compared with cervical cerclage alone on the risk of serious neonatal morbidity (RR 0.62, 95% CI 0.31 to 1.24; very low-certainty evidence); perinatal loss (data for miscarriage and stillbirth only - data not available for neonatal death) (RR 0.46, 95% CI 0.13 to 1.64; very low-certainty evidence) or preterm birth < 34 completed weeks of pregnancy (RR 0.78, 95% CI 0.44 to 1.40; very low-certainty evidence). There were no stillbirths (intrauterine death at 24 or more weeks). The trial authors did not report on the numbers of babies discharged home healthy (without obvious pathology) or on the risk of neonatal death. AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence to evaluate the effect of combining a tocolytic (indomethacin) and antibiotics (cefazolin/clindamycin) with cervical cerclage compared with cervical cerclage alone for preventing spontaneous PTB in women with singleton pregnancies. Future studies should recruit sufficient numbers of women to provide meaningful results and should measure neonatal death and numbers of babies discharged home healthy, as well as other important outcomes listed in this review. We did not identify any studies looking at other treatments in combination with cervical cerclage. Future research needs to focus on the role of other interventions such as vaginal support pessary, reinforcing or second cervical cerclage placement, 17-alpha-hydroxyprogesterone caproate or dydrogesterone or vaginal micronised progesterone, omega-3 long chain polyunsaturated fatty acid supplementation and bed rest.

Reducing Albuterol Use in Children With Bronchiolitis.

OBJECTIVES: In 2014, the American Academy of Pediatrics published bronchiolitis guidelines recommending against the use of bronchodilators. For the winter of 2015 to 2016, we aimed to reduce the proportion of emergency department patients with bronchiolitis receiving albuterol from 43% (previous winter rate) to <35% and from 18% (previous winter rate) to <10% in the inpatient setting. METHODS: A team identified key drivers of albuterol use and potential interventions. We implemented changes to our pathway and the associated order set recommending against routine albuterol use and designed education to accompany the pathway changes. We monitored albuterol use through weekly automated data extraction and reported results back to clinicians. We measured admission rate, length of stay, and revisit rate as balancing measures for the intervention. RESULTS: The study period included 3834 emergency department visits and 1119 inpatient hospitalizations. In the emergency department, albuterol use in children with bronchiolitis declined from 43% to 20% and was <3 SD control limits established in the previous year, meeting statistical thresholds for special cause variation. Inpatient albuterol use decreased from 18% to 11% of patients, also achieving special cause variation and approaching our goal. The changes in both departments were sustained through the entire bronchiolitis season, and admission rate, length of stay, and revisit rates remained unchanged. CONCLUSIONS: Using a multidisciplinary group that redesigned a clinical pathway and order sets for bronchiolitis, we substantially reduced albuterol use at a large children's hospital without impacting other outcome measures.

A Respiratory Therapist-Driven Asthma Pathway Reduced Hospital Length of Stay in the Pediatric Intensive Care Unit.

BACKGROUND: Asthma is a common reason for admissions to the pediatric intensive care unit (PICU). Since June 2014, our institution has used a pediatric asthma clinical pathway for all patients, including those in PICU. The pathway promotes respiratory therapist-driven bronchodilator weaning based on the Modified Pulmonary Index Score (MPIS). This pathway was associated with decreased hospital length of stay (LOS) for all pediatric asthma patients; however, the effect on PICU patients was unclear. We hypothesized that the implementation of a pediatric asthma pathway would reduce hospital LOS for asthmatic patients admitted to the PICU. METHODS: We retrospectively reviewed the medical records of all pediatric asthma subjects 2-17 y old admitted to our PICU before and after pathway initiation. Primary outcome was hospital LOS. Secondary outcomes were PICU LOS and time on continuous albuterol. Data were analyzed using the chi-square test for categorical data, the t test for normally distributed data, and the Mann-Whitney test for nonparametric data. RESULTS: A total of 203 eligible subjects (49 in the pre-pathway group, 154 in the post group) were enrolled. There were no differences between groups for age, weight, gender, home medications, cause of exacerbation, medical history, or route of admission. There were significant decreases in median (interquartile range) hospital LOS (4.4 [2.9-6.6] d vs 2.7 [1.6-4.0] d, P < .001), median PICU LOS (2.1 [1.3-4.0] d vs 1.6 [0.8-2.4] d, P = .003), and median time on continuous albuterol (39 [25-85] h vs 27 [13-42] h, P = .001). Significantly more subjects in the post-pathway group were placed on high-flow nasal cannula (32% vs 6%, P = .001) or noninvasive ventilation (10% vs 4%, P = .02). CONCLUSION: The implementation of an asthma pathway was associated with decreased hospital LOS, PICU LOS, and time on continuous albuterol. There was also an increase in the use of high-flow nasal cannula and noninvasive ventilation after the implementation of this clinical pathway.

Anti-asthmatic activity of alkaloid compounds from Pericarpium Citri Reticulatae (Citrus reticulata 'Chachi').

Pericarpium Citri Reticulatae (PCR, Citrus reticulata 'Chachi', Guangchenpi in Chinese) is one of the most famous Chinese citrus herbal medicines. The in vivo anti-asthmatic activity of 'Chachi' PCR was investigated using a histamine-induced experimental asthma model in Guinea pigs. Two alkaloid-type compounds, synephrine and stachydrine, were analyzed and identified in the 'Chachi' PCR alkaloid fraction. The alkaloid fraction and synephrine protected Guinea pigs against histamine-induced experimental asthma in a dose-dependent manner. The respective application of high, middle, and low doses of the 'Chachi' PCR alkaloid fraction significantly increased specific airway resistance by 284%, 328%, and 355%, and decreased dynamic compliance by 57%, 67%, and 75%. A similar change was observed for synephrine. The expression of eosinophils in bronchoalveolar lavage fluid (BALF) and serum IgE, IL-4, and IL-5 levels in histamine-induced experimental asthmatic Guinea pigs were significantly downregulated by the 'Chachi' PCR alkaloid fraction and synephrine compared to the control group, whereas stachydrine did not impart a statistically significant effect on the expression of tested inflammatory cells (leucocytes, eosinophils, neutrophils, and lymphocytes), immunoglobulin (IgE), or cytokines (IL-4 and IL-5). Pathological changes in lung tissues in each treatment group included the infiltration of inflammatory cells around the bronchia.

Effects of a PICU Status Asthmaticus De-Escalation Pathway on Length of Stay and Albuterol Use.

OBJECTIVES: Evaluate the effects of an asthma de-escalation clinical pathway on selected outcomes for patients admitted to a PICU with status asthmaticus. DESIGN: Time series quality improvement trial. SETTING: PICU in a tertiary care children's hospital. PATIENTS: Children age 2-18 years old with a known diagnosis of asthma presenting with status asthmaticus. INTERVENTION: One-hundred five admissions to a PICU for status asthmaticus were treated according to a new de-escalation pathway between August 15, 2015, and August 30, 2016. This group was compared with a prepathway group of 141. MEASUREMENTS AND MAIN RESULTS: Primary outcome was variability in PICU length of stay. Secondary outcomes were median PICU length of stay, median hospital length of stay, and median duration a patient received continuous nebulized albuterol. The effectiveness of the intervention was tracked using control charts. The postpathway group demonstrated decreased variability of PICU length of stay and time receiving continuous albuterol. Statistically significant decreases were seen in median PICU length of stay (16 vs 13 hr; p = 0.0009), median duration a child spent receiving continuous nebulized albuterol (10.8 vs 7.3 hr; p = 0.0008), and median hospital length of stay (37 vs 31 hr; p = 0.02). Total number of asthma assessments completed by respiratory therapists increased from 741 to 1,087. CONCLUSIONS: Implementation of a PICU asthma de-escalation pathway demonstrated statistical decrease in the reported measures for children with status asthmaticus. Although the clinical significance of these changes may be debatable, the results demonstrate that efforts to standardize asthma care in the PICU setting is an area in need of further study.

Honey for acute cough in children.

BACKGROUND: Cough causes concern for parents and is a major cause of outpatient visits. Cough can impact quality of life, cause anxiety, and affect sleep in children and their parents. Honey has been used to alleviate cough symptoms. This is an update of reviews previously published in 2014, 2012, and 2010. OBJECTIVES: To evaluate the effectiveness of honey for acute cough in children in ambulatory settings. SEARCH METHODS: We searched CENTRAL (2018, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (2014 to 8 February 2018), Embase (2014 to 8 February 2018), CINAHL (2014 to 8 February 2018), EBSCO (2014 to 8 February 2018), Web of Science (2014 to 8 February 2018), and LILACS (2014 to 8 February 2018). We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform (WHO ICTRP) on 12 February 2018. The 2014 review included searches of AMED and CAB Abstracts, but these were not searched for this update due to lack of institutional access. SELECTION CRITERIA: Randomised controlled trials comparing honey alone, or in combination with antibiotics, versus no treatment, placebo, honey-based cough syrup, or other over-the-counter cough medications for children aged 12 months to 18 years for acute cough in ambulatory settings. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six randomised controlled trials involving 899 children; we added three studies (331 children) in this update.We assessed two studies as at high risk of performance and detection bias; three studies as at unclear risk of attrition bias; and three studies as at unclear risk of other bias.Studies compared honey with dextromethorphan, diphenhydramine, salbutamol, bromelin (an enzyme from the Bromeliaceae (pineapple) family), no treatment, and placebo. Five studies used 7-point Likert scales to measure symptomatic relief of cough; one used an unclear 5-point scale. In all studies, low score indicated better cough symptom relief.Using a 7-point Likert scale, honey probably reduces cough frequency better than no treatment or placebo (no treatment: mean difference (MD) -1.05, 95% confidence interval (CI) -1.48 to -0.62; I² = 0%; 2 studies; 154 children; moderate-certainty evidence; placebo: MD -1.62, 95% CI -3.02 to -0.22; I² = 0%; 2 studies; 402 children; moderate-certainty evidence). Honey may have a similar effect as dextromethorphan in reducing cough frequency (MD -0.07, 95% CI -1.07 to 0.94; I² = 87%; 2 studies; 149 children; low-certainty evidence). Honey may be better than diphenhydramine in reducing cough frequency (MD -0.57, 95% CI -0.90 to -0.24; 1 study; 80 children; low-certainty evidence).Giving honey for up to three days is probably more effective in relieving cough symptoms compared with placebo or salbutamol. Beyond three days honey probably had no advantage over salbutamol or placebo in reducing cough severity, bothersome cough, and impact of cough on sleep for parents and children (moderate-certainty evidence). With a 5-point cough scale, there was probably little or no difference between the effects of honey and bromelin mixed with honey in reducing cough frequency and severity.Adverse events included nervousness, insomnia, and hyperactivity, experienced by seven children (9.3%) treated with honey and two children (2.7%) treated with dextromethorphan (risk ratio (RR) 2.94, 95% Cl 0.74 to 11.71; I² = 0%; 2 studies; 149 children; low-certainty evidence). Three children (7.5%) in the diphenhydramine group experienced somnolence (RR 0.14, 95% Cl 0.01 to 2.68; 1 study; 80 children; low-certainty evidence). When honey was compared with placebo, 34 children (12%) in the honey group and 13 (11%) in the placebo group complained of gastrointestinal symptoms (RR 1.91, 95% CI 1.12 to 3.24; I² = 0%; 2 studies; 402 children; moderate-certainty evidence). Four children who received salbutamol had rashes compared to one child in the honey group (RR 0.19, 95% CI 0.02 to 1.63; 1 study; 100 children; moderate-certainty evidence). No adverse events were reported in the no-treatment group. AUTHORS' CONCLUSIONS: Honey probably relieves cough symptoms to a greater extent than no treatment, diphenhydramine, and placebo, but may make little or no difference compared to dextromethorphan. Honey probably reduces cough duration better than placebo and salbutamol. There was no strong evidence for or against using honey. Most of the children received treatment for one night, which is a limitation to the results of this review. There was no difference in occurrence of adverse events between the honey and control arms.

Drugs for discoid lupus erythematosus.

BACKGROUND: Discoid lupus erythematosus (DLE) is a chronic form of cutaneous lupus, which can cause scarring. Many drugs have been used to treat this disease and some (such as thalidomide, cyclophosphamide and azathioprine) are potentially toxic. This is an update of a Cochrane Review first published in 2000, and previously updated in 2009. We wanted to update the review to assess whether any new information was available to treat DLE, as we were still unsure of the effectiveness of available drugs and how to select the most appropriate treatment for an individual with DLE. OBJECTIVES: To assess the effects of drugs for discoid lupus erythematosus. SEARCH METHODS: We updated our searches of the following databases to 22 September 2016: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We also searched five trials databases, and checked the reference lists of included studies for further references to relevant trials. Index Medicus (1956 to 1966) was handsearched and we approached authors for information about unpublished trials. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) of drugs to treat people with DLE in any population group and of either gender. Comparisons included any drug used for DLE against either another drug or against placebo cream. We excluded laser treatment, surgery, phototherapy, other forms of physical therapy, and photoprotection as we did not consider them drug treatments. DATA COLLECTION AND ANALYSIS: At least two reviewers independently extracted data onto a data extraction sheet, resolving disagreements by discussion. We used standard methods to assess risk of bias, as expected by Cochrane. MAIN RESULTS: Five trials involving 197 participants were included. Three new trials were included in this update. None of the five trials were of high quality.'Risk of bias' assessments identified potential sources of bias in each study. One study used an inappropriate randomisation method, and incomplete outcome data were a concern in another as 15 people did not complete the trial. We found most of the trials to be at low risk in terms of blinding, but three of the five did not describe allocation concealment.The included trials inadequately addressed the primary outcome measures of this review (percentage with complete resolution of skin lesions, percentage with clearing of erythema in at least 50% of lesions, and improvement in patient satisfaction/quality of life measures).One study of fluocinonide cream 0.05% (potent steroid) compared with hydrocortisone cream 1% (low-potency steroid) in 78 people reported complete resolution of skin lesions in 27% (10/37) of participants in the fluocinonide cream group and in 10% (4/41) in the hydrocortisone group, giving a 17% absolute benefit in favour of fluocinonide (risk ratio (RR) 2.77, 95% CI 0.95 to 8.08, 1 study, n = 78, low-quality evidence). The other primary outcome measures were not reported. Adverse events did not require discontinuation of the drug. Skin irritation occurred in three people using hydrocortisone, and one person developed acne. Burning occurred in two people using fluocinonide (moderate-quality evidence).A comparative trial of two oral agents, acitretin (50 mg daily) and hydroxychloroquine (400 mg daily), reported two of the outcomes of interest: complete resolution was seen in 13 of 28 participants (46%) on acitretin and 15 of 30 participants (50%) on hydoxychloroquine (RR 0.93, 95% CI 0.54 to 1.59, 1 study, n = 58, low-quality evidence). Clearing of erythema in at least 50% of lesions was reported in 10 of 24 participants (42%) on acitretin and 17 of 25 (68%) on hydroxychloroquine (RR 0.61, 95% CI 0.36 to 1.06, 1 study, n = 49, low-quality evidence). This comparison did not assess improvement in patient satisfaction/quality of life measures. Participants taking acitretin showed a small increase in serum triglyceride, not sufficient to require withdrawal of the drug. The main adverse effects were dry lips (93% of the acitretin group and 20% of the hydroxychloroquine group) and gastrointestinal disturbance (11% of the acitretin group and 17% of the hydroxychloroquine group). Four participants on acitretin withdrew due to gastrointestinal events or dry lips (moderate-quality evidence).One trial randomised 10 people with DLE to apply a calcineurin inhibitor, pimecrolimus 1% cream, or a potent steroid, betamethasone 17-valerate 0.1% cream, for eight weeks. The study reported none of the primary outcome measures, nor did it present data on adverse events.A trial of calcineurin inhibitors compared tacrolimus cream 0.1% with placebo (vehicle) over 12 weeks in 14 people, but reported none of our primary outcome measures. In the tacrolimus group, five participants complained of slight burning and itching, and for one participant, a herpes simplex infection was reactivated (moderate-quality evidence).Topical R-salbutamol 0.5% cream was compared with placebo (vehicle) over eight weeks in one trial of 37 people with DLE. There was a significant improvement in pain and itch in the salbutamol group at two, four, six, and eight weeks compared to placebo, but the trial did not record a formal measure of quality of life. None of the primary outcome measures were reported. Changes in erythema did not show benefit of salbutamol over placebo, but we could not obtain from the trial report the number of participants with clearing of erythema in at least 50% of lesions. There were 15 events in the placebo group (experienced by 12 participants) and 24 in the salbutamol group (experienced by nine participants). None of the adverse events were considered serious (moderate-quality evidence). AUTHORS' CONCLUSIONS: Fluocinonide cream may be more effective than hydrocortisone in clearing DLE skin lesions. Hydroxychloroquine and acitretin appear to be of equal efficacy in terms of complete resolution, although adverse effects might be more frequent with acitretin, and clearing of erythema in at least 50% of lesions occurred less often in participants applying acitretin. Moderate-quality evidence found adverse events were minor on the whole. There is not enough reliable evidence about other drugs used to treat DLE. Overall, the quality of the trials and levels of uncertainty were such that there is a need for further trials of sufficient duration comparing, in particular, topical steroids with other agents.

The effect of nebulised magnesium sulphate in the management of childhood moderate asthma exacerbations as adjuvant treatment

BACKGROUND: After the bronchodilator effect of magnesium was shown, the use of magnesium in treatment of asthma exacerbations became common. With the results of recent studies, the use of intravenous magnesium in severe asthma exacerbations took its place. We aimed to examine the effects of adding isotonic magnesium sulphate instead of isotonic saline into nebulised salbutamol on the Modified Pulmonary Index Score (MPIS) and the hospitalisation rate in moderate asthma exacerbations. METHODS: Our study population included 100 children age between 3 and 15 years with asthma admitted to emergency department due to moderate asthma exacerbations. The patients were randomised to placebo or magnesium, with 50 patients in each arm. All patients received 1mg/kg of systemic methylprednisolone at the beginning of treatment and thereafter received either nebulised salbutamol (0.15mg/kg/dose) and 1ml magnesium sulphate (15%)+1.5ml isotonic saline on three occasions at roughly 20min intervals (Magnesium group) or nebulised salbutamol (0.15mg/kg/dose) and 2.5ml isotonic saline mixture on three occasions at roughly 20min intervals (Placebo group). The MPIS of patients on 0th min, 20th min, 40th and 120th min were calculated and compared. The primary outcome was to compare MPIS values at the end of 120th min. RESULTS: Both groups have similar demographic, allergic characteristics and baseline MPIS scores. When the MPIS scores in the 120th min and admission rates in the 200th min, there was no significant difference between the two groups. CONCLUSIONS: The use of nebulised magnesium sulphate in moderate asthma exacerbation as adjuvant treatment showed no benefit to standard treatment in our study

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The effect of nebulised magnesium sulphate in the management of childhood moderate asthma exacerbations as adjuvant treatment.

BACKGROUND: After the bronchodilator effect of magnesium was shown, the use of magnesium in treatment of asthma exacerbations became common. With the results of recent studies, the use of intravenous magnesium in severe asthma exacerbations took its place. We aimed to examine the effects of adding isotonic magnesium sulphate instead of isotonic saline into nebulised salbutamol on the Modified Pulmonary Index Score (MPIS) and the hospitalisation rate in moderate asthma exacerbations. METHODS: Our study population included 100 children age between 3 and 15 years with asthma admitted to emergency department due to moderate asthma exacerbations. The patients were randomised to placebo or magnesium, with 50 patients in each arm. All patients received 1mg/kg of systemic methylprednisolone at the beginning of treatment and thereafter received either nebulised salbutamol (0.15mg/kg/dose) and 1ml magnesium sulphate (15%)+1.5ml isotonic saline on three occasions at roughly 20min intervals (Magnesium group) or nebulised salbutamol (0.15mg/kg/dose) and 2.5ml isotonic saline mixture on three occasions at roughly 20min intervals (Placebo group). The MPIS of patients on 0th min, 20th min, 40th and 120th min were calculated and compared. The primary outcome was to compare MPIS values at the end of 120th min. RESULTS: Both groups have similar demographic, allergic characteristics and baseline MPIS scores. When the MPIS scores in the 120th min and admission rates in the 200th min, there was no significant difference between the two groups. CONCLUSIONS: The use of nebulised magnesium sulphate in moderate asthma exacerbation as adjuvant treatment showed no benefit to standard treatment in our study.

Effect of Traditional Chinese Medicine on Inflammatory Mediators in Pediatric Asthma.

Objective. To observe the effects of empirical prescriptions of traditional Chinese medicine (TCM) on inflammatory mediators in pediatric asthma and to explore the underlying molecular mechanism in the treatment of asthma. Methods. A total of 182 children with asthma were randomly placed into either the TCM group (n = 97) or the salbutamol and montelukast (SM) group (n = 85). Patients in the TCM group were treated with a series of empirical prescriptions of TCM, while those in the SM group received salbutamol and montelukast. Both groups received their respective treatment for 12 weeks. There were 35 patients in TCM group and 34 patients in SM group providing venous blood. Real-time PCR was used to determine the mRNA expression levels of interleukin- (IL-) 10, IL-17, matrix metalloproteinase-9 (MMP-9), and transforming growth factor ß1 (TGF-ß1) in peripheral blood mononuclear cells before and after treatment. Enzyme-linked immunosorbent assay was used to measure the levels of IL-10, IL-17, MMP-9, and TGF-ß1 in peripheral blood before and after treatment. Results. The mRNA expression of TGF-ß1 in the SM group was downregulated (P = 0.00) after treatment. No significant differences were found between the TCM group and the SM group after treatment (P > 0.05). In the TCM group, the levels of IL-10, IL-17, and MMP-9 significantly decreased after treatment (P = 0.01, 0.04, and 0.03, resp.). In the SM group, IL-17, MMP-9, and TGF-ß1 levels significantly decreased after treatment (P = 0.00, 0.03, and 0.00, resp.). There was no significant difference between the two groups regarding the levels of IL-10, IL-17, TGF-ß1, and MMP-9 (P > 0.05). The difference of the level of IL-17 was negatively correlated with the change of C-ACT score in TCM group and SM group. Conclusion. TCM has a regulatory effect on the balance of some inflammatory mediators in pediatric asthma.

Salbutamol in paediatrics: pharmacology, prescribing and controversies.

Salbutamol has become a key drug in respiratory medicine since it was first developed by Sir David Jack et al in 1968, 5000 years after the ß agonist ephedrine was first used in its raw form, as the Ma Huang herb in Chinese medicine to treat asthma. It is one of the most commonly encountered medicines in paediatric practice and the authors have found that an understanding of its pharmacology in clinical practice is incredibly helpful. In this article, we discuss its pharmacology and pharmacodynamics, practical prescribing points and some unresolved issues surrounding its use, which should serve to provide an essential working knowledge for the busy paediatrician.

Long-acting beta2-agonist in addition to tiotropium versus either tiotropium or long-acting beta2-agonist alone for chronic obstructive pulmonary disease.

BACKGROUND: Long-acting bronchodilators, comprising long-acting beta2-agonists (LABA) and long-acting anti-muscarinic agents (LAMA, principally tiotropium), are commonly used for managing persistent symptoms of chronic obstructive pulmonary disease (COPD). Combining these treatments, which have different mechanisms of action, may be more effective than the individual components. However, the benefits and risks of combining tiotropium and LABAs for the treatment of COPD are unclear. OBJECTIVES: To compare the relative effects on markers of quality of life, exacerbations, symptoms, lung function and serious adverse events in people with COPD randomised to LABA plus tiotropium versus tiotropium alone; or LABA plus tiotropium versus LABA alone. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of trials and ClinicalTrials.gov up to July 2015. SELECTION CRITERIA: We included parallel-group, randomised controlled trials of three months or longer comparing treatment with tiotropium in addition to LABA against tiotropium or LABA alone for people with COPD. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and then extracted data on trial quality and the outcome results. We contacted study authors for additional information. We collected information on adverse effects from the trials. MAIN RESULTS: This review included 10 trials on 10,894 participants, mostly recruiting participants with moderate or severe COPD. All of the trials compared tiotropium in addition to LABA to tiotropium alone, and four trials additionally compared LAMA plus LABA with LABA alone. Four studies used the LABA olodaterol, three used indacaterol, two used formoterol, and one used salmeterol.Compared to tiotropium alone, treatment with tiotropium plus LABA resulted in a slightly larger improvement in mean health-related quality of life (St George's Respiratory Questionnaire (SGRQ) (mean difference (MD) -1.34, 95% confidence interval (CI) -1.87 to -0.80; 6709 participants; 5 studies). The MD was smaller than the four units that is considered clinically important, but a responder analysis indicated that 7% more participants receiving tiotropium plus LABA had a noticeable benefit (greater than four units) from treatment in comparison to tiotropium alone. In the control arm in one study, which was tiotropium alone, the SGRQ improved by falling 4.5 units from baseline and with tiotropium plus LABA the improvement was a fall of a further 1.3 units (on average). Most of the data came from studies using olodaterol. High withdrawal rates in the trials increased the uncertainty in this result, and the GRADE assessment for this outcome was therefore moderate. There were no significant differences in the other primary outcomes (hospital admission or mortality).The secondary outcome of pre-bronchodilator forced expiratory volume in one second (FEV1) showed a small mean increase with the addition of LABA over the control arm (MD 0.06, 95% CI 0.05 to 0.07; 9573 participants; 10 studies), which showed a change from baseline ranging from 0.03 L to 0.13 L with tiotropium alone. None of the other secondary outcomes (exacerbations, symptom scores, serious adverse events, and withdrawals) showed any statistically significant differences between the groups. There was moderate heterogeneity for both exacerbations and withdrawals.This review included data on four LABAs: two administered twice daily (salmeterol, formoterol) and two once daily (indacaterol, olodaterol). The results were largely from studies of olodaterol and there was insufficient information to assess whether the other LABAs were equivalent to olodaterol or each other.Comparing LABA plus tiotropium treatment with LABA alone, there was a small but significant improvement in SGRQ (MD -1.25, 95% CI -2.14 to -0.37; 3378 participants; 4 studies). The data came mostly from studies using olodaterol and, although the difference was smaller than four units, this still represented an increase of 10 people with a clinically important improvement for 100 treated. There was also an improvement in FEV1 (MD 0.07, 95% CI 0.06 to 0.09; 3513 participants; 4 studies), and in addition an improvement in exacerbation rates (odds ratio (OR) 0.80, 95% CI 0.69 to 0.93; 3514 participants; 3 studies). AUTHORS' CONCLUSIONS: The results from this review indicated a small mean improvement in health-related quality of life and FEV1 for participants on a combination of tiotropium and LABA compared to either agent alone, and this translated into a small increase in the number of responders on combination treatment. In addition, adding tiotropium to LABA reduced exacerbations, although adding LABA to tiotropium did not. Hospital admission and mortality were not altered by adding LABA to tiotropium, although there may not be enough data. While it is possible that this is affected by higher attrition in the tiotropium group, one would expect that participants withdrawn from the study would have had less favourable outcomes; this means that the expected direction of attrition bias would be to reduce the estimated benefit of the combination treatment. The results were largely from studies of olodaterol and there was insufficient information to assess whether the other LABAs were equivalent to olodaterol or each other.

Glycopyrronium once-daily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD: the GLISTEN study, a randomised controlled trial.

BACKGROUND: The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear. The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting ß2 agonist (LABA). METHODS: This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily. The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks. An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone. RESULTS: 773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial. At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) -7 mL (SE 17.4) with a lower limit for non-inferiority of -60 mL. There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001). At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff -2.154, p=0.02). GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff -0.72 puffs/day, p<0.001). Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively. CONCLUSIONS: GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP. Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP. TRIAL REGISTRATION NUMBER: NCT01513460.

Obesity and bronchodilator response in black and Hispanic children and adolescents with asthma.

BACKGROUND: Obesity is associated with poor asthma control, increased asthma morbidity, and decreased response to inhaled corticosteroids. We hypothesized that obesity would be associated with decreased bronchodilator responsiveness in children and adolescents with asthma. In addition, we hypothesized that subjects who were obese and unresponsive to bronchodilator would have worse asthma control and would require more asthma controller medications. METHODS: In the Study of African Americans, Asthma, Genes, and Environments (SAGE II) and the Genes-environments and Admixture in Latino Americans (GALA II) study, two identical, parallel, case-control studies of asthma, we examined the association between obesity and bronchodilator response in 2,963 black and Latino subjects enrolled from 2008 to 2013 using multivariable logistic regression. Using bronchodilator responsiveness, we compared asthma symptoms, controller medication usage, and asthma exacerbations between nonobese (< 95th% BMI) and obese (≥ 95th% BMI) subjects. RESULTS: The odds of being bronchodilator unresponsive were 24% (OR, 1.24; 95% CI, 1.03-1.49) higher among obese children and adolescents compared with their not obese counterparts after adjustment for age, race/ethnicity, sex, recruitment site, baseline lung function (FEV1/FVC), and controller medication. Bronchodilator-unresponsive obese subjects were more likely to report wheezing (OR, 1.38; 95% CI, 1.13-1.70), being awakened at night (OR, 1.34; 95% CI, 1.09-1.65), using leukotriene receptor inhibitors (OR, 1.33; 95% CI, 1.05-1.70), and using inhaled corticosteroid with long-acting ß2-agonist (OR, 1.37; 95% CI, 1.05-1.78) than were their nonobese counterpart. These associations were not seen in the bronchodilator-responsive group. CONCLUSIONS: Obesity is associated with bronchodilator unresponsiveness among black and Latino children and adolescents with asthma. The findings on obesity and bronchodilator unresponsiveness represent a unique opportunity to identify factors affecting asthma control in blacks and Latinos.

A Systematic Review of the Efficacy and Safety of a Fixed-Dose Combination of Umeclidinium and Vilanterol for the Treatment of COPD.

BACKGROUND: COPD guidelines recommend the combined use of inhaled long-acting ß2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) if symptoms are not improved by a single agent. This systematic review tested the hypothesis that the bronchodilator effect of the LABA/LAMA combination, umeclidinium (UMEC)/vilanterol (VIL), would translate into better outcomes without incurring increased adverse events (AEs). METHODS: This was a systematic review of randomized, placebo-controlled or crossover trials (> 4 weeks) involving UMEC/VIL compared with its monocomponents, tiotropium, or fluticasone/salmeterol. Primary outcomes were trough FEV1, serious adverse events (SAEs), and serious cardiovascular events (SCVEs). RESULTS: Eleven trials from 10 studies (9,609 patients) showed that UMEV/VIL provided superior improvements in lung function compared with UMEC, VIL, tiotropium, and fluticasone propionate/salmeterol (mean trough FEV1, 60, 110, 90, and 90 mL, respectively; P < .0001). Also, UMEC/VIL had a greater likelihood of demonstrating a minimal clinically important difference on the Transition Dyspnea Index compared with UMEC and VIL (number needed to treat for benefit [NNTB] = 14 and 10, respectively). UMEC/VIL therapy significantly reduced the risk of COPD exacerbations compared with UMEC and VIL (NNTB = 42 and 41, respectively). On the contrary, we noted no significant differences between UMEC/VIL and tiotropium with respect to dyspnea, health status, or risk of COPD exacerbation. Regarding safety issues, the incidence of AEs, SAEs, SCVEs, and mortality on treatment was similar across treatments, suggesting reduced safety concerns with the use of the UMEC/VIL combination. CONCLUSIONS: Once-daily inhaled UMEC/VIL showed superior efficacy compared with its monocomponents, tiotropium, and fluticasone/combination in patients with moderate to severe COPD.