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  1. Norhaya MR, Yap TM, Zainudin BM
    Respirology, 1999 Mar;4(1):77-81.
    PMID: 10339734 DOI: 10.1046/j.1440-1843.1999.00153.x
    The effect of adding inhaled salmeterol to inhaled corticosteroids was studied in patients with poorly controlled nocturnal asthma. In a double-blind, cross-over study, 20 patients were randomized to receive either salmeterol 50 micrograms twice daily or placebo via a Diskhaler after a 1-week run-in period. After 4 weeks of treatment, patients were subsequently crossed over to receive the other treatment for a further 4 weeks with a 2-week wash-out period in between. The response to treatment was assessed by peak expiratory flow rates (PEF) measured in the morning and evening, symptom scores of asthma, number of bronchodilators used, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at regular intervals. Patients' preference for the Diskhaler or metered-dose inhaler was assessed at the last visit. The results showed that morning PEF was significantly higher while on salmeterol than on placebo (296.9 +/- 70.2 vs 274.6 +/- 77.4 L/min). Evening PEF showed a trend towards a higher value while on salmeterol than on placebo (321.1 +/- 73.4 vs 288.7 +/- 79.4 L/min), but the difference was not significant. There was no statistically significant improvement in symptom scores, number of rescue bronchodilators used and FEV1 or FVC between the two treatment groups. The occurrence of side effects in terms of tremors and palpitations between treatment and placebo were similar. There were more patients who preferred Diskhaler to metered-dose inhaler (70% vs 30%). We conclude that salmeterol 50 micrograms twice daily produces significant improvement in morning PEF and is well tolerated in patients with nocturnal asthma. Diskhaler is a device which is easy to use and preferred to a metered-dose inhaler.
    Study site: Respiratory Clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
    Matched MeSH terms: Bronchodilator Agents/therapeutic use*
  2. Loh LC, Puah SH, Ho CV, Chow CY, Chua CY, Jayaram J, et al.
    J Asthma, 2005 Dec;42(10):853-8.
    PMID: 16393724
    Measurement of disability and breathlessness in asthma is important to guide treatment. Using an incentive spirometer, Triflo II (Tyco Healthcare, Mansfield, MA, USA), we developed a three-minute respiratory exercise test (3-MRET) to score the maximal breathing capacity (MBC) and perception of dyspnea (POD) index by means of repetitive inspiratory efforts achieved within 3 minutes. POD index was calculated based on the ratio of breathlessness on visual analogue scale over MBC score. In 175 normal healthy subjects and 158 asthmatic patients of mild (n = 26), moderate (n = 78), and severe (n = 54), severity, the mean (95% CI) MBC scores in mild, moderate, and severe asthma patients were 168 (145-192), 153 (136-169), and 125 (109-142) respectively, and 202 (191-214) in normal subjects (p < 0.001). The mean POD index in mild, moderate, and severe asthma patients was 16 (9-23), 25 (14-37), and 57 (14-100), respectively, and 6 (4-7) in normal subjects (p < 0.001). Intraclass correlation coefficients for MBC score and POD index in 17 asthmatic and 20 normal subjects were high. In 14 asthmatic patients randomized to receiving nebulized beta2-agonist or saline in a cross-over, double-blind study, % forced expiratory volume in one second (FEV1) change correlated with % change in MBC score [r(s) = 0.49, p < 0.01] and POD index [r(s)-0.46, p = 0.012]. In 21 asthmatic and 26 normal subjects, the MBC score and POD index correlated with the walking distance and walking POD index of the six-minute walking test (6MWT). We conclude that 3MRET is discriminative between asthmatic patients of varying severity and normal subjects, is reproducible, is responsive to bronchodilator effect, and is comparable with 6MWT. Taken together, it has the potential to score disability and POD in asthma simply and effectively.
    Matched MeSH terms: Bronchodilator Agents/therapeutic use
  3. Chye JK, Lim CT, Leong HL, Wong PK
    Ann Acad Med Singap, 1999 Mar;28(2):193-8.
    PMID: 10497665
    This study aims to determine the prevalence of and risk factors associated with retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants. All premature VLBW infants, admitted into the neonatal intensive care unit of the University Hospital Kuala Lumpur, were screened from 4 weeks of life. Perinatal and neonatal data were retrieved from the infants' medical notes. Between August 1994 and July 1996, 100 infants had their eyes examined serially. Of the 15 (15%) infants with ROP, all were less than 31 weeks gestation, and only 1 infant had birth weight above 1250 g. Five (5%) infants had severe ROP; 4 infants underwent cryotherapy for stage 3 threshold disease. Infants with ROP, as compared to infants without ROP, had lower birth weight [mean (SEM) 993 (50) g versus 1205 (22) g, P < 0.001], lower gestational age [mean (SEM) 28.0 (0.4) weeks versus 30.1 (0.2) weeks, P < 0.001], higher rates of patent ductus arteriosus and chronic lung disease, greater number of radiographic examinations and episodes of late-onset suspected/confirmed sepsis, and required longer duration of supplemental oxygen, ventilation, xanthine, antibiotics and intralipid use, but were slower to establish full enteral feeds. On multivariate logistic regression analysis, birth weight < or = 1000 g [OR 2.38, 95% CI 1.25, 4.55, P = 0.009] and gestational age < or = 28 weeks [OR 2.86, 95% CI 1.47, 5.56, P = 0.002] were significant predictors of increased risk of this disease. In conclusion, ROP is strongly associated with smaller, more immature and sicker neonates. Prevention of prematurity would help reduce the incidence of this disease.
    Matched MeSH terms: Bronchodilator Agents/therapeutic use
  4. Liam CK, Lim KH, Wong CM
    Asian Pac J Allergy Immunol, 2000 Sep;18(3):135-40.
    PMID: 11270467
    This study aimed to evaluate dry powder inhaler naive asthmatic patients' perception and preference of the Accuhaler, a multidose dry powder inhaler and the pressurized metered dose inhaler (pMDI). After the first instruction, 66.7% of 48 patients enrolled in the study could demonstrate the correct use of the Accuhaler. When the patients were asked to compare the pMDI and the Accuhaler after using the Accuhaler to administer salmeterol for 4 weeks, the Accuhaler scored significantly better than the pMDI for the following features: knowing how many doses are left, presence of an attached cover, taste, instruction for use, attractiveness, ease of use, ease of holding, shape, and comfortable mouthpiece. The pMDI scored better to the Accuhaler in terms of size. More patients preferred the Accuhaler than the pMDI; the presence of a dose counter and perceived ease of use were the main reasons cited for their preference for the Accuhaler.
    Study site: Asthma Clinic, University of Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
    Matched MeSH terms: Bronchodilator Agents/therapeutic use
  5. Liam CK, Goh CT, Isahak M, Lim KH, Wong CM
    Asian Pac J Allergy Immunol, 2001 Jun;19(2):79-83.
    PMID: 11699724
    The objective of this study was to determine the relationship between asthma symptoms and the degree of airway obstruction as measured by the forced expiratory volume in one second (FEV1) and peak expiratory flow rate (PEFR) in a group of 64 asthmatic patients with clinically stable disease attending a university-based urban asthma clinic. Asthma symptoms did not correlate with the degree of airway obstruction as measured by prebronchodilator PEFR (total asthma symptom score vs PEFR: r = -0.214, p = 0.104, n = 59) and only correlated poorly with prebronchodilator FEV1 (total asthma symptom score vs FEV1: r = -0.256, p = 0.041, n = 64). These results lend support to the recommendation that airway obstruction should be measured objectively when assessing patients with chronic persistent asthma.
    Study site: Asthma clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
    Matched MeSH terms: Bronchodilator Agents/therapeutic use
  6. Ni H, Moe S, Soe Z, Myint KT, Viswanathan KN
    Cochrane Database Syst Rev, 2018 Dec 11;12:CD011594.
    PMID: 30536566 DOI: 10.1002/14651858.CD011594.pub2
    BACKGROUND: Several dual bronchodilator combinations of long-acting beta2-agonist (LABA) and long-acting muscarinic antagonist (LAMA) have been approved for treatment of stable chronic obstructive pulmonary disease (COPD). The current GOLD (Global Initiative for Chronic Obstructive Lung Disease) recommendations suggest the use of LABA/LAMA combinations in people with group B COPD with persistent symptoms, group C COPD with further exacerbations on LAMA therapy alone and group D COPD with or without inhaled corticosteroids (ICS). Fixed-dose combination (FDC) of aclidinium/formoterol is one of the approved LABA/LAMA therapies for people with stable COPD.

    OBJECTIVES: To assess the efficacy and safety of combined aclidinium bromide and long-acting beta2-agonists in stable COPD.

    SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov, World Health Organization (WHO) trials portal, United States Food and Drug Administration (FDA) and manufacturers' websites as well as the reference list of published trials up to 12 October 2018.

    SELECTION CRITERIA: Parallel-group randomised controlled trials (RCTs) assessing combined aclidinium bromide and LABAs in people with stable COPD.

    DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane for data collection and analysis. The primary outcomes were exacerbations requiring a short course of an oral steroid or antibiotic, or both; quality of life measured by a validated scale and non-fatal serious adverse events (SAEs). Where the outcome or study details were not reported, we contacted the study investigators or pharmaceutical company trial co-ordinators (or both) for missing data.

    MAIN RESULTS: We identified RCTs comparing aclidinium/formoterol FDC versus aclidinium, formoterol or placebo only. We included seven multicentre trials of four to 52 weeks' duration conducted in outpatient settings. There were 5921 participants, whose mean age ranged from 60.7 to 64.7 years, mostly men with a mean smoking pack-years of 46.4 to 61.3 of which 43.9% to 63.4% were current smokers. They had a moderate-to-severe degree of COPD with a mean postbronchodilator forced expiratory volume in one second (FEV1) between 50.5% and 61% of predicted normal and the baseline mean FEV1 of 1.23 L to 1.43 L. We assessed performance and detection biases as low for all studies whereas selection, attrition and reporting biases were either low or unclear.FDC versus aclidiniumThere was no evidence of a difference between FDC and aclidinium for exacerbations requiring steroids or antibiotics, or both (OR 0.95, 95% CI 0.71 to 1.27; 2 trials, 2156 participants; moderate-certainty evidence); quality of life measured by St George's Respiratory Questionnaire (SGRQ) total score (MD -0.92, 95% CI -2.15 to 0.30); participants with significant improvement in SGRQ score (OR 1.17, 95% CI 0.97 to 1.41; 2 trials, 2002 participants; moderate-certainty evidence); non-fatal SAE (OR 1.19, 95% CI 0.79 to 1.80; 3 trials, 2473 participants; moderate-certainty evidence); hospital admissions due to severe exacerbations (OR 0.62, 95% CI 0.29 to 1.29; 2 trials, 2156 participants; moderate-certainty evidence) or adverse events (OR 0.95, 95% CI 0.76 to 1.18; 3 trials, 2473 participants; moderate-certainty evidence). Compared with aclidinium, FDC improved symptoms (Transitional Dyspnoea Index (TDI) focal score: MD 0.37, 95% CI 0.07 to 0.68; 2 trials, 2013 participants) with a higher chance of achieving a minimal clinically important difference (MCID) of at least one unit improvement (OR 1.34, 95% CI 1.11 to 1.62; high-certainty evidence); the number needed to treat for an additional beneficial outcome (NNTB) being 14 (95% CI 9 to 39).FDC versus formoterolWhen compared to formoterol, combination therapy reduced exacerbations requiring steroids or antibiotics, or both (OR 0.78, 95% CI 0.62 to 0.99; 3 trials, 2694 participants; high-certainty evidence); may decrease SGRQ total score (MD -1.88, 95% CI -3.10 to -0.65; 2 trials, 2002 participants; low-certainty evidence; MCID for SGRQ is 4 units); increased TDI focal score (MD 0.42, 95% CI 0.11 to 0.72; 2 trials, 2010 participants) with more participants attaining an MCID (OR 1.30, 95% CI 1.07 to 1.56; high-certainty evidence) and an NNTB of 16 (95% CI 10 to 60). FDC lowered the risk of adverse events compared to formoterol (OR 0.78, 95% CI 0.65 to 0.93; 5 trials, 3140 participants; high-certainty evidence; NNTB 22). However, there was no difference between FDC and formoterol for hospital admissions, all-cause mortality and non-fatal SAEs.FDC versus placeboCompared with placebo, FDC demonstrated no evidence of a difference in exacerbations requiring steroids or antibiotics, or both (OR 0.82, 95% CI 0.60 to 1.12; 2 trials, 1960 participants; moderate-certainty evidence) or hospital admissions due to severe exacerbations (OR 0.55, 95% CI 0.25 to 1.18; 2 trials, 1960 participants; moderate-certainty evidence), although estimates were uncertain. Quality of life measure by SGRQ total score was significantly better with FDC compared to placebo (MD -2.91, 95% CI -4.33 to -1.50; 2 trials, 1823 participants) resulting in a corresponding increase in SGRQ responders who achieved at least four units decrease in SGRQ total score (OR 1.72, 95% CI 1.39 to 2.13; high-certainty evidence) with an NNTB of 7 (95% CI 5 to 12). FDC also improved symptoms measured by TDI focal score (MD 1.32, 95% CI 0.96 to 1.69; 2 studies, 1832 participants) with more participants attaining at least one unit improvement in TDI focal score (OR 2.51, 95% CI 2.02 to 3.11; high-certainty evidence; NNTB 4). There were no differences in non-fatal SAEs, adverse events and all-cause mortality between FDC and placebo.Combination therapy significantly improved trough FEV1 compared to aclidinium, formoterol or placebo.

    AUTHORS' CONCLUSIONS: FDC improved dyspnoea and lung function compared to aclidinium, formoterol or placebo, and this translated into an increase in the number of responders on combination treatment. Quality of life was better with combination compared to formoterol or placebo. There was no evidence of a difference between FDC and monotherapy or placebo for exacerbations, hospital admissions, mortality, non-fatal SAEs or adverse events. Studies reported a lower risk of moderate exacerbations and adverse events with FDC compared to formoterol; however, larger studies would yield a more precise estimate for these outcomes.

    Matched MeSH terms: Bronchodilator Agents/therapeutic use
  7. Mohd Rhazi NA, Muneswarao J, Abdul Aziz F, Ibrahim B, Kamalludin A, Soelar SA
    J Asthma, 2023 Aug;60(8):1608-1612.
    PMID: 36650693 DOI: 10.1080/02770903.2023.2169930
    INTRODUCTION: Anti-inflammatory reliever (AIR) with or without regular maintenance delivered through Turbuhaler® has been widely recommended in the GINA strategy document. These patients are not prescribed with additional reliever inhalers, but dependent on Turbuhaler® during acute asthma episodes. The peak inspiratory flow rate (PIFR) is crucial in drug delivery from a dry powder inhaler (DPI) such as Turbuhaler®. Despite its increasing usage, there are some concerns that patients on Turbuhaler® are not able to achieve adequate PIFR during acute exacerbation of asthma.

    OBJECTIVE: This study aimed to assess the PIFR at resistance settings that matched Turbuhaler® in patients with acute exacerbation of asthma.

    METHODOLOGY: A six-month cross-sectional study was conducted at the Emergency Department (ED) of Hospital Sultanah Bahiyah and Hospital Kulim, Kedah, Malaysia. Adult patients diagnosed with mild to moderate acute exacerbations of asthma were recruited. The PIFRs were measured using the In-Check DIAL G16 that was set to simulate the resistance of Turbuhaler® (R3). The PIFRs were assessed before (pre) and after (post) the initial bronchodilator (BD) treatment at the ED. The minimal required PIFR was defined as flow rates ≥ 30 L/min while a PIFR of 60 L/min was considered as optimal.

    RESULTS: A total of 151 patients (81 females and 70 males) were recruited. The mean age was 37.5 years old with a range between 18 and 79 years old. The results showed that 98% (n = 148) of patients managed to achieve the minimal PIFR required for pre-BD. The mean PIFR pre-BD was 60 ± 18.5 L/min and post-BD was 70 ± 18.5 L/min. Furthermore, more than half (54%, n = 82) of the patients recorded PIFR ≥ 60 L/min during pre-BD, and about three-quarters (71%, n = 92) achieved PIFR ≥ 60 L/min post-BD. The PIFR showed a moderate correlation with peak expiratory flow rate (PEFR) (r = 0.55, 95% CI: 0.43-0.65, p 

    Matched MeSH terms: Bronchodilator Agents/therapeutic use
  8. Loh LC, Kanabar V, D'Amato M, Barnes NC, O'Connor BJ
    Asian Pac J Allergy Immunol, 2005 Dec;23(4):189-96.
    PMID: 16572738
    Sputum induction with nebulized hypertonic saline is increasingly being used to evaluate airway inflammation. We investigated the procedure-associated risk in 16 asthmatics that were still symptomatic despite on high doses of regular corticosteroid (CS) therapy (7 on daily inhaled CS > or = 800 microg budesonide or equivalent; 9 on additional daily oral CS) and their sputum cellular profile. For comparison, 12 mild stable asthmatics and 10 normal healthy subjects were included. All subjects inhaled 3%, 4% and 5% hypertonic saline sequentially via ultrasonic nebulizer as a means to induce sputum. Maximal percentage fall of Forced Expiratory Volume on One Second (FEV1) during sputum induction was significantly greater in CS-dependent asthmatics (median % [IQR]: 16.0 [11.0-32.3]) than in mild asthmatics (5.3 [4.2-10.8], p = 0.002] and in normal subjects (4.6 [3.4-6.4]), p = 0.0001). The maximal percentage FEV1 fall was inversely correlated with baseline FEV1 (Rs= -0.69; p < 0.0001). Compared to mild asthmatics, induced sputum from CS-dependant asthmatics had proportionately fewer eosinophils (2.2 [0.8-7.0] versus 23.3% [10.7-46.3], p = 0.003) and greater neutrophils (64.2 [43.9-81.2] versus 28.7 [19.0-42.6], p = 0.009). Sputum neutrophils showed a significant inverse correlation to FEV1 (Rs = -0.51, p = 0.01). We concluded that sputum induction using nebulized hypertonic saline should be performed with caution in CS-dependant asthmatics. The airway cellular profile observed suggests that the immunopathology underlying CS-dependant asthmatics may be different or a consequence of CS therapy.
    Matched MeSH terms: Bronchodilator Agents/therapeutic use*
  9. Howe TA, Jaalam K, Ahmad R, Sheng CK, Nik Ab Rahman NH
    J Emerg Med, 2011 Dec;41(6):581-9.
    PMID: 19272745 DOI: 10.1016/j.jemermed.2008.10.017
    STUDY OBJECTIVE: To determine if the slope of Phase II and Phase III, and the alpha angle of the expiratory capnographic waveform, as measured via computer-recognizable algorithms, can reflect changes in bronchospasm in acute asthmatic non-intubated patients presenting to the emergency department (ED).
    METHODS: In this prospective study carried out in a university hospital ED, 30 patients with acute asthma were monitored with clinical severity scoring and peak flow measurements, and then had a nasal cannula attached for sidestream sampling of expired carbon dioxide. The capnographic waveform was recorded onto a personal computer card for analysis. The patients were treated according to departmental protocols. After treatment, when they had improved enough for discharge, a second set of results was obtained for capnographic waveform recording. The pre-treatment and post-treatment results were then compared with paired-samples t-test analysis.
    RESULTS: On the capnographic waveform pre- and post-treatment, there was a significant difference in the slope of Phase III (p < 0.001) and alpha angle (p < 0.001), but not in the Phase II slope (p = 0.35). There was significant change in peak flow meter reading, but it was poorly correlated with all the capnographic indices.
    CONCLUSION: The study provides some preliminary data showing that capnographic waveform indices can indicate improvement in airway diameter in acute asthmatics in the ED. Capnographic waveform analysis presents several advantages in that it is effort-independent, and provides continuous monitoring of normal tidal respiration. With further refined studies, it may serve as a new method of monitoring non-intubated asthmatics in the ED.
    Study site: Emergency department, Hospital Universiti Sains Malaysia (HUSM), Kubang Kerian, Kelantan, Malaysia
    Matched MeSH terms: Bronchodilator Agents/therapeutic use
  10. Koh HP, Shamsudin NS, Tan MMY, Mohd Pauzi Z
    J Clin Pharm Ther, 2021 Aug;46(4):1129-1138.
    PMID: 33768601 DOI: 10.1111/jcpt.13410
    WHAT IS KNOWN AND OBJECTIVE: Nebulizer use has been suspended in Malaysian public health facilities due to the potential to aggravate COVID-19 nosocomial transmission. Currently, our facility uses the pressurized metered-dose inhaler (pMDI) bronchodilator with Venturi mask modified spacer (VMMS) in patients visiting the Emergency Department (ED) for mild to moderate exacerbation of asthma and chronic obstructive pulmonary disease (COPD). We sought to assess the outcomes and acceptance of pMDI-VMMS in the outpatient ED of a tertiary hospital in Malaysia.

    METHODS: We analysed the total visits and discharge rates during periods of using the nebulizer and current pMDI-VMMS methods. The acceptance of pMDI-VMMS by patients and assistant medical officers (AMOs) were assessed by questionnaire.

    RESULTS AND DISCUSSION: We analysed 3184 ED visits and responses from 103 patients and 32 AMOs. The direct discharge rate was similar for both nebulizer (n = 2162, 92.5%) and pMDI-VMMS method (n = 768, 90.7%) (p-value = 0.120). Twenty-eight patients (27.2%) favoured the pMDI-VMMS over the nebulizer, whereas 36 patients (35.0%) had no preference for either method. Sixty-four patients (62.1%) felt that the current pMDI-VMMS method was better or at least as effective in relieving their symptoms as a nebulizer. The current method was favoured over the nebulizer by twenty-seven AMOs (84.4%). Twenty-eight (87.5%) AMOs suggested that the current method was more effective than the nebulizer.

    WHAT IS NEW AND CONCLUSION: The bronchodilator delivered via pMDI-VMMS appeared to be comparable to nebulizer in treating mild to moderate asthma and COPD exacerbations in the outpatient ED. Most patients and AMOs accepted the use of pMDI-VMMS in the outpatient ED during the current COVID-19 pandemic. The Venturi mask modified spacer can be a cheap and effective alternative to the commercial spacer in a resource-limited situation.

    Matched MeSH terms: Bronchodilator Agents/therapeutic use
  11. Ni H, Soe Z, Moe S
    Cochrane Database Syst Rev, 2014 Sep 19;2014(9):CD010509.
    PMID: 25234126 DOI: 10.1002/14651858.CD010509.pub2
    BACKGROUND: Bronchodilators are the mainstay for symptom relief in the management of stable chronic obstructive pulmonary disease (COPD). Aclidinium bromide is a new long-acting muscarinic antagonist (LAMA) that differs from tiotropium by its higher selectivity for M3 muscarinic receptors with a faster onset of action. However, the duration of action of aclidinium is shorter than for tiotropium. It has been approved as maintenance therapy for stable, moderate to severe COPD, but its efficacy and safety in the management of COPD is uncertain compared to other bronchodilators.

    OBJECTIVES: To assess the efficacy and safety of aclidinium bromide in stable COPD.

    SEARCH METHODS: We identified randomised controlled trials (RCT) from the Cochrane Airways Group Specialised Register of trials (CAGR), as well as www.clinicaltrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), US Food and Drug Administration (FDA) website and Almirall Clinical Trials Registry and Results. We contacted Forest Laboratories for any unpublished trials and checked the reference lists of identified articles for additional information. The last search was performed on 7 April 2014 for CAGR and 11 April 2014 for other sources.

    SELECTION CRITERIA: Parallel-group RCTs of aclidinium bromide compared with placebo, long-acting beta2-agonists (LABA) or LAMA in adults with stable COPD.

    DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed the risk of bias, and extracted data. We sought missing data from the trial authors as well as manufacturers of aclidinium. We used odds ratios (OR) for dichotomous data and mean difference (MD) for continuous data, and reported both with their 95% confidence intervals (CI). We used standard methodological procedures expected by The Cochrane Collaboration. We applied the GRADE approach to summarise results and to assess the overall quality of evidence.

    MAIN RESULTS: This review included 12 multicentre RCTs randomly assigning 9547 participants with stable COPD. All the studies were industry-sponsored and had similar inclusion criteria with relatively good methodological quality. All but one study included in the meta-analysis were double-blind and scored low risk of bias. The study duration ranged from four weeks to 52 weeks. Participants were more often males, mainly Caucasians, mean age ranging from 61.7 to 65.6 years, and with a smoking history of 10 or more pack years. They had moderate to severe symptoms at randomisation; the mean post-bronchodilator forced expiratory volume in one second (FEV1) was between 46% and 57.6% of the predicted normal value, and the mean St George's Respiratory Questionnaire score (SGRQ) ranged from 45.1 to 50.4 when reported.There was no difference between aclidinium and placebo in all-cause mortality (low quality) and number of patients with exacerbations requiring a short course of oral steroids or antibiotics, or both (moderate quality). Aclidinium improved quality of life by lowering the SGRQ total score with a mean difference of -2.34 (95% CI -3.18 to -1.51; I(2) = 48%, 7 trials, 4442 participants) when compared to placebo. More patients on aclidinium achieved a clinically meaningful improvement of at least four units decrease in SGRQ total score (OR 1.49; 95% CI 1.31 to 1.70; I(2) = 34%; number needed to treat (NNT) = 10, 95% CI 8 to 15, high quality evidence) over 12 to 52 weeks than on placebo. Aclidinium also resulted in a significantly greater improvement in pre-dose FEV1 than placebo with a mean difference of 0.09 L (95% CI 0.08 to 0.10; I(2) = 39%, 9 trials, 4963 participants). No trials assessed functional capacity. Aclidinium reduced the number of patients with exacerbations requiring hospitalisation by 4 to 20 fewer per 1000 over 4 to 52 weeks (OR 0.64; 95% CI 0.46 to 0.88; I(2) = 0%, 10 trials, 5624 people; NNT = 77, 95% CI 51 to 233, high quality evidence) compared to placebo. There was no difference in non-fatal serious adverse events (moderate quality evidence) between aclidinium and placebo.Compared to tiotropium, aclidinium did not demonstrate significant differences for exacerbations requiring oral steroids or antibiotics, or both, exacerbation-related hospitalisations and non-fatal serious adverse events (very low quality evidence). Inadequate data prevented the comparison of aclidinium to formoterol or other LABAs.

    AUTHORS' CONCLUSIONS: Aclidinium is associated with improved quality of life and reduced hospitalisations due to severe exacerbations in patients with moderate to severe stable COPD compared to placebo. Overall, aclidinium did not significantly reduce mortality, serious adverse events or exacerbations requiring oral steroids or antibiotics, or both.Currently, the available data are insufficient and of very low quality in comparisons of the efficacy of aclidinium versus tiotropium. The efficacy of aclidinium versus LABAs cannot be assessed due to inaccurate data. Thus additional trials are recommended to assess the efficacy and safety of aclidinium compared to other LAMAs or LABAs.

    Matched MeSH terms: Bronchodilator Agents/therapeutic use*
  12. Jayasooriya S, Stolbrink M, Khoo EM, Sunte IT, Awuru JI, Cohen M, et al.
    Int J Tuberc Lung Dis, 2023 Sep 01;27(9):658-667.
    PMID: 37608484 DOI: 10.5588/ijtld.23.0203
    BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs).METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards.RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available.CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.
    Matched MeSH terms: Bronchodilator Agents/therapeutic use
  13. Liam CK
    Med J Malaysia, 2000 Jun;55(2):285-92; quiz 293.
    PMID: 19839165
    Matched MeSH terms: Bronchodilator Agents/therapeutic use
  14. Kelly AM, Holdgate A, Keijzers G, Klim S, Graham CA, Craig S, et al.
    Respirology, 2018 07;23(7):681-686.
    PMID: 29394524 DOI: 10.1111/resp.13259
    BACKGROUND AND OBJECTIVE: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common presentation to emergency departments (ED) but data regarding its epidemiology and outcomes are scarce. We describe the epidemiology, clinical features, treatment and outcome of patients treated for AECOPD in ED.

    METHODS: This was a planned sub-study of patients with an ED diagnosis of AECOPD identified in the Asia, Australia and New Zealand Dyspnoea in Emergency Departments (AANZDEM) study. The AANZDEM was a prospective, interrupted time series cohort study conducted in 46 ED in Australia, New Zealand, Singapore, Hong Kong and Malaysia over three 72-h periods in May, August and October 2014. Primary outcomes were patient epidemiology, clinical features, treatment and outcomes (hospital length of stay (LOS) and mortality).

    RESULTS: Forty-six ED participated. There were 415 patients with an ED primary diagnosis of AECOPD (13.6% of the overall cohort; 95% CI: 12.5-14.9%). Median age was 73 years, 60% males and 65% arrived by ambulance. Ninety-one percent had an existing COPD diagnosis. Eighty percent of patients received inhaled bronchodilators, 66% received systemic corticosteroids and 57% of those with pH < 7.30 were treated with non-invasive ventilation (NIV). Seventy-eight percent of patients were admitted to hospital, 7% to an intensive care unit. In-hospital mortality was 4% and median LOS was 4 days (95% CI: 2-7).

    CONCLUSION: Patients treated in ED for AECOPD commonly arrive by ambulance, have a high admission rate and significant in-hospital mortality. Compliance with evidence-based treatments in ED is suboptimal affording an opportunity to improve care and potentially outcomes.

    Matched MeSH terms: Bronchodilator Agents/therapeutic use
  15. Ismail TS
    Med J Malaysia, 2009 Sep;64(3):250-5; quiz 256.
    PMID: 20527283 MyJurnal
    Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in COPD patients and place a large burden on healthcare resources. COPD patients with frequent exacerbations have accelerated decline in lung function, poorer health status and are at higher risk of mortality. The mainstay of treatment includes increasing short acting bronchodilator therapy and systemic glucocorticosteroids with or without antibiotics. Non invasive ventilation is indicated in those with respiratory failure with acidosis or hypercapnia. Preventive strategies to reduce exacerbations include smoking cessation, immunisation against influenza and S. pneumonia, chronic maintenance inhaled pharmacotherapy, pulmonary rehabilitation and self management education.
    Matched MeSH terms: Bronchodilator Agents/therapeutic use
  16. Chongmelaxme B, Chaiyakunapruk N, Dilokthornsakul P
    J Med Econ, 2019 Jun;22(6):554-566.
    PMID: 30663455 DOI: 10.1080/13696998.2019.1572014
    Aims: Non-adherence is associated with poor clinical outcomes among patients with asthma. While cost-effectiveness analysis (CEA) is increasingly used to inform value assessment of the interventions, most do not take into account adherence in the analyses. This study aims to: (1) Understand the extent of studies considering adherence as part of the economic analyses, and (2) summarize the methods of incorporating adherence in the economic models. Materials and methods: A literature search was performed from the inception to February 2018 using four databases: PubMed, EMBASE, NHS EED, and the Tufts CEA registry. Decision model-based CEA of asthma were identified. Outcomes of interest were the number of studies incorporating adherence in the economic models, and the incorporating methods. All data were extracted using a standardized data collection form. Results: From 1,587 articles, 23 studies were decision model-based CEA of asthma, of which four CEA (17.4%) incorporated adherence in the analyses. Only the method of incorporating adherence by adjusting treatment effectiveness according to adherence levels was demonstrated in this review. Two approaches were used to derive the associations between adherence and effectiveness. The first approach was to apply a mathematical formula, developed by an expert panel, and the second was to extrapolate the associations from previous published studies. The adherence-adjusted effectiveness was then incorporated in the economic models. Conclusions: A very low number of CEA of asthma incorporated adherence in the analyses. All the CEA adjusted treatment effectiveness according to adherence levels, applied to the economic models.
    Matched MeSH terms: Bronchodilator Agents/therapeutic use
  17. Janbaz KH, Arif J, Saqib F, Imran I, Ashraf M, Zia-Ul-Haq M, et al.
    BMC Complement Altern Med, 2014 Feb 22;14:71.
    PMID: 24559094 DOI: 10.1186/1472-6882-14-71
    BACKGROUND: Isodon rugosus is used in folk Pakistan traditional practices to cure ailments related to gastrointestinal, respiratory and cardiovascular problems. Present study was undertaken to validate these folkloric uses.

    METHODS: A crude methanol extract of the aerial parts of Isodon rugosus (Ir.Cr.) was used for both in vitro and in vivo experiments. The plant extract was tested on isolated rabbit jejunum preparations for possible presence of spasmolytic activity. Moreover, isolated rabbit tracheal and aorta preparations were used to ascertain the relaxant effects of the extract. Acetylcholinesterase and butyrylcholinesterase inhibitory activities of Ir.Cr were also determined as well as its antioxidant activity. The in vivo antiemetic activity of the extract was evaluated by using the chick emesis model, while the analgesic and antipyretic activities were conducted on albino mice.

    RESULTS: The application of the crude extract of I. rugosus to isolated rabbit jejunum preparations exhibited relaxant effect (0.01-0.3 mg/ml). The Ir.Cr also relaxed K+(80 m M)-induced spastic contractions in isolated rabbit jejunum preparations and shifted the Ca+2 concentration response curves towards right (0.01-0.3 mg/ml). Similarly, the extract, when applied to the isolated rabbit tracheal preparations relaxed the carbachol (1 μM)--as well as K+ (80 mM)-induced contractions in a concentration range of 0.01-1.0 mg/ml. Moreover, it also relaxed (0.01-3.0 mg/ml) the phenylephrine (1 μM)- and K+ (80 mM)-induced contractions in isolated rabbit aorta preparations. The Ir.Cr (80 mg/kg) demonstrated antipyretic activity on pyrogen-induced pyrexia in rabbits as compared to aspirin as standard drug. The Ir.Cr also exhibited anti-oxidant as well as inhibitory effect on acetyl- and butyryl-cholinesterase and lipoxygenase (0.5 mg/ml).

    CONCLUSIONS: The observed relaxant effect on isolated rabbit jejunum, trachea and aorta preparations caused by Ir.Cr is possibly to be mediated through Ca+2 channel blockade and therefore may provided scientific basis to validate the folkloric uses of the plant in the management of gastrointestinal, respiratory and cardiovascular ailments. The observed antioxidant activity as well as the lipoxygenase inhibitory activity may validate its traditional use in pain and inflammations.

    Matched MeSH terms: Bronchodilator Agents/therapeutic use
  18. Townend J, Minelli C, Mortimer K, Obaseki DO, Al Ghobain M, Cherkaski H, et al.
    Eur Respir J, 2017 06;49(6).
    PMID: 28572124 DOI: 10.1183/13993003.01880-2016
    Poverty is strongly associated with mortality from COPD, but little is known of its relation to airflow obstruction.In a cross-sectional study of adults aged ≥40 years from 12 sites (N=9255), participating in the Burden of Obstructive Lung Disease (BOLD) study, poverty was evaluated using a wealth score (0-10) based on household assets. Obstruction, measured as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) (%) after administration of 200 μg salbutamol, and prevalence of FEV1/FVC
    Matched MeSH terms: Bronchodilator Agents/therapeutic use
  19. Lai CK, De Guia TS, Kim YY, Kuo SH, Mukhopadhyay A, Soriano JB, et al.
    J Allergy Clin Immunol, 2003 Feb;111(2):263-8.
    PMID: 12589343
    Few data on asthma management are available for the Asia-Pacific region.
    Matched MeSH terms: Bronchodilator Agents/therapeutic use
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