Salbutamol dry powder inhaler: efficacy, tolerability, and acceptability study

Dry powder inhaler (DPI) devices are frequently used in children over 5 years of age in order to avoid coordination difficulties often seen with the use of pressurized metered dose inhalers (pMDI). This study assessed the efficacy, tolerability, and acceptability of salbutamol delivered via two delivery systems, in a population of pediatric patients. The primary aim of the study was to investigate the bronchodilator efficacy of a single dose (100 microg) of salbutamol administered via a dry powder inhaler (Clickhaler) compared to a similar dose administered by a pressurized metered dose inhaler via a large-valved holding chamber (VHC) to children with asthma. The study comprised two phases: the first comparator phase, followed by an open 4-week treatment period. Sixty-one children with a mean (SD) age of 11.3 years (2.9) (range, 6-17) and mild or moderate asthma completed the study. The primary efficacy endpoint, forced expiratory volume in 1 sec (FEV1), indicated that there was no clinically or statistically significant difference between the bronchodilator effects of salbutamol delivered via either device, with a maximum posttreatment percentage change in FEV1 (SD) of 12.4% (10.0) and 14.15 (9.3) for Clickhaler and pMDI plus VHC, respectively. Most patients rated the Clickhaler as easy to use (97%) and liked the device (84%). Both treatments were well--tolerated. These results support the suitability of salbutamol Clickhaler as an acceptable, well-tolerated, and effective alternative to a pMDI plus VHC in mild to moderate asthmatic children over age 6 years.     

Variations in bronchiolitis management between five New Zealand hospitals: Can we do better?

OBJECTIVES: To determine the current management of bronchiolitis by five major New Zealand hospitals and to identify areas for improvement. METHODS: Lists of infants under 1 year of age admitted with bronchiolitis during 1998 were obtained from the casemix offices of the five largest New Zealand hospitals with paediatric services. Hospital records from a random sample of these admissions were reviewed. RESULTS: Out of the 409 infants admitted overnight, 8% had been born less than or=32 weeks gestation and 53% were aged younger than 6 months. Overall, 59% received oxygen, 21% had nasogastric fluids, 22% had intravenous fluids, 34% were prescribed antibiotics, 42% received bronchodilators and 60% had a chest radiograph. Respiratory secretions were collected for viral studies from 58% of infants and, in 59%, respiratory syncytial virus was detected. Significant variations in management were detected between hospitals. The overall proportion of infants requiring oxygen, intravenous or nasogastric fluids (65%) was significantly higher than that found in a 1986-1988 Christchurch study where only 25% received one or more of these interventions (P < 0.001). CONCLUSIONS: Opportunities exist to rationalize bronchiolitis management in New Zealand with potential cost savings, particularly by reducing the number of chest radiographs and prescribing of unnecessary antibiotics and bronchodilators.     

Underdiagnosis and undertreatment of COPD in primary care settings

OBJECTIVE: The aim of this study was to improve the detection of COPD in a primary care setting and to evaluate the subsequent management of these patients by general practitioners. METHODOLOGY: A two-step protocol was followed: patients were screened for airway obstruction and their subsequent management status reviewed. Screening spirometry was performed in 56 primary care settings (23 hospitals and 33 general practices). Inclusion criteria for screening subjects were: (i) > or =40-year-old smokers (both current and past smokers) and/or (ii) > or =40-year-old patients with respiratory symptoms of chronic cough and sputum. Patients with a previously diagnosed respiratory disease were excluded. In the second part of the study, the diagnosis and the subsequent management status of subjects with airway obstructive changes (FEV1/FVC <70%) were sought from their physician using a questionnaire 2 months after detection. RESULTS: A total of 1168 patients were screened, with 128 not analysed because of incomplete data, leaving 1040 patients. The percentages of current smokers, ex-smokers, and non-smokers among all analysed subjects were 41.7%, 29.8% and 28.5%, respectively. Airway obstructive changes (FEV1/FVC <70%) were found in 27.0% (n = 281) of all analysed subjects. Questionnaires for 194 subjects (with positive screening tests) were sent back by the participating physicians. Eighty-one per cent (n = 158) of the 194 subjects had COPD and 13.4% (n = 26) had asthma. Sixty-one per cent (n = 96) of the subjects with moderate to severe COPD according to international guidelines (FEV1 <80% predicted). However, 31.3% (n = 30) did not receive any clinical intervention (smoking cessation advice and/or drug administration). CONCLUSIONS: Screening spirometry in outpatients in a primary care setting can identify many COPD patients. However, COPD management appears to be poor in Japan.     

口服福莫特罗与其（R，R）对映体的支气管扩张和抗炎活性比较

目的:比较口服福莫特罗(rac-FMT)和(R,R)-福莫特罗(R,R-FMT)的支气管扩张和抗炎作用。方法:分别采用抗原气雾攻击致敏豚鼠和小鼠,观察豚鼠的肺功能变化以及小鼠肺内炎症细胞的集聚反应。结果:模型组豚鼠在抗原激发后1-30min的气道阻力(R_L)平均值增加101％±34％,动态肺顺应性(C_(dyn))降低42％±7％。rac-FMT 0.5,1.0和2.0 mg/g,R,R-FMT 0.25,0.5和1.0mg/kg灌胃给药(ig)呈剂量依赖抑制抗原引起的支气管收缩反应,rac-FMT的ID_(50)(95％可信限)分别为0.96(0.86-1.07)和1.59(1.32-1.92)mg/g;R,R-FMT分别为0.52(0.45-0.59)和0.43(0.37-0.51)mg/g。rac-FMT抑制抗原攻击引起的致敏小鼠肺内总炎症细胞和嗜 酸性粒细胞聚集,ID_(50)(95％C1)分别为1.48(1.22-1.81)和0.80(0.62-1.04)mg/g;RR-FMT分别为0.80(0.57-1.13)和0.60(0.43-0.83)mg/g。结论:R,R-FMT保护豚鼠哮喘模型抗原攻击引起的R_1和C_(dyn)变化,抑制致敏小鼠的气道炎症,其作用强于rac-FMT约2倍。     

The perception of asthma

Subjective scores of 'wheeze' or 'tightness in the chest' were compared with the forced expiratory volume in 1 s (FEV₁) in 40 asthmatic children before and after administration of nebulized salbutamol. Symptom scores were poor predictors of the degree of airways obstruction. Many children underestimated their improvement after salbutamol.
The results suggest that reliance on the child's perception of his symptoms and his response to a bronchodilator may result in incorrect assessment and inappropriate treatment.     

Bronchodilator responsiveness testing using raised volume forced expiration in recurrently wheezing infants

We hypothesized that a new test of infant lung function, less affected by shifts in lung volume, might better detect bronchodilator effects. Using the raised volume forced expiration technique (RVFET), the effect of a bronchodilator on lung function was studied in 22 infants with a history of recurrent wheeze and five healthy infants. Forced expiratory volume in 0.75 s (FEV_0.75), forced expiratory vital capacity (FVC), and forced expiratory flow at 75% of FVC (FEF_75%) were measured by forcing expiration, using an inflatable jacket from a lung volume set by an inspiratory pressure of 20 cm H₂O. A minimum of five measurements were made at baseline and following the administration of 500 μg of salbutamol from a metered dose inhaler via a small volume metal spacer. Changes in lung function in the group of 25 infants who received salbutamol were compared to seven infants who received placebo aerosol. No significant changes occurred in measures of lung function following salbutamol administration when compared to baseline or placebo despite a significant increase in heart rate. A shift in lung volume is unlikely the reason why infants do not demonstrate a change in forced expiration following bronchodilator administration. Pediatr Pulmonol. 1998; 26:35–41. © 1998 Wiley-Liss, Inc.     

Treatment of COVID‐19 with pentoxifylline: Could it be a potential adjuvant therapy?

The world is facing a viral pandemic of a new coronavirus called COVID‐19. Pentoxifylline is a methyl‐xanthine derivative and it inhibits the phosphodiesterase IV (PDE IV). This drug is known for its unique features as an immunomodulatory and anti‐inflammatory agent, also it could have antiviral affects. This is a scoping review, in which all related articles on COVID‐19 and the probable benefits of Pentoxifylline against COVID‐19 pathogenesis, in Medline, Scopus, Web of Sciences, and Google Scholar up to 20 March 2020 with proper keywords including: pentoxifylline, Pentoxil, COVID‐19, coronavirus, treatment, anti‐inflammatory, immunomodulatory, antifibrosis, oxygenation, circulation, bronchodilator, ARDS, and organ failure. We found many confirmatory data on proper efficacy of pentoxifylline on controlling COVID‐19 and its consequences. The antiviral, anti‐inflammatory, anti‐oxidative, immune‐modulatory, bronchodilator and respiratory supportive effects and protective roles in organ failures of PTX, along with its main functions means better circulation‐oxygenation properties, low price and safety, make it a promising drug to be considered for COVID‐19 treatment, especially as an adjuvant therapy in combination with other drugs.     

Efficacy of salbutamol and ipratropium bromide in decreasing bronchial hyperreactivity in children with cystic fibrosis.

A proportion of patients with cystic fibrosis (CF) suffer from increased airway hyperreactivity but their response to bronchodilators is variable. Adrenergic agents may produce an increase, no change or a decrease in forced expiratory volume in 1 second (FEV1). We hypothesized that the variable response might be related to poor aerosol distribution caused by the presence of secretions. Therefore, in 11 children with CF and airway hyperreactivity the influence of pretreatment with either 0.9% saline, salbutamol, or ipratropium bromide on the methacholine challenge test was evaluated in a double-blind, randomized, cross-over study. FEV1 (mean +/- S.E.) did not change following pretreatment with saline, salbutamol, or ipratropium (1.64 +/- 0.22, 1.63 +/- 0.16 and 1.67 +/- 0.19, respectively). All patients demonstrated airway hyperreactivity with a PC20 below 8 mg/mL (geometric mean, 0.41 mg/mL) after saline pretreatment. Salbutamol inhalation significantly increased the PC20 to 1.24 mg/mL (P less than 0.01), but ipratropium bromide was found to be even more effective than salbutamol (PC20 = 7.37 mg/mL) (P less than 0.0001). We conclude that the variable response to bronchodilator is not secondary to impaired aerosol distribution since ipratropium bromide effectively blocked the response to methacholine. The improvement in PC20 without a change in baseline FEV1 following salbutamol suggests that the adrenergic agent altered the contractile mechanism of smooth muscle.     

Beta2-ADR haplotypes/polymorphisms associate with bronchodilator response and total IgE in grass allergy

Association and linkage studies of beta2-adrenergic receptor (beta2-ADR) polymorphisms in relation to the expression of asthmatic phenotypes and immune regulatory mechanisms have shown inconsistent results. In order to analyse the relevance of particular combinations of single nucleotide polymorphisms (SNPs) or haplotypes of beta2-ADR gene to bronchial asthma, bronchodilator response and total immunoglobulin E (IgE) we determined by direct DNA sequencing five SNPs (in positions: -47, -20, 46, 79, 252) in a group of 180 Caucasian subjects (110 patients with grass allergy and 70 nonatopic controls). The eight different beta2-ADR haplotypes were identified, with three the most common of them representing 92% of the studied cohort. Significantly higher (pcor = 0.0045) bronchodilator response was observed in patients with homozygotic genotype 46A/A in comparison with respective homo- and hetero-zygotes. There was no significant difference in bronchodilator response when beta2-ADR haplotypes were analysed. Significantly higher (pcor = 0.0005) total IgE levels were found in patients with beta2-ADR haplotype -47T/-20T/46A/79C/252G and homozygotic carriers of 46A (pcor = 0.0015) and 79C (pcor = 0.003) genotypes. No significant associations were found in regards to asthmatic phenotype and atopy. These results indicate that depending on phenotype studied, either an individual beta2-ADR SNP or beta2-ADR haplotype might affect disease manifestation.