Pretreatment Alveolar Nitric Oxide Levels Predict Improvement of Pulmonary Function 1 Year Following Anti-Asthma Treatments in Patients with Inhaled Corticosteroid-Naïve Asthma

2022 ◽  
pp. 1-11
Author(s):  
Kensuke Fukumitsu ◽  
Hirono Nishiyama ◽  
Yoshihiro Kanemitsu ◽  
Norihisa Takeda ◽  
Ryota Kurokawa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Function ◽  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Poor Responders ◽  
Newly Diagnosed ◽  
Inhaled Corticosteroid ◽  
Factors Associated ◽  
Long Acting ◽  
Continuous Use

<b><i>Introduction:</i></b> Inhaled corticosteroids (ICS) are fundamental agents to subside airway inflammation and improve forced expiratory volume in 1 s (FEV<sub>1</sub>) among asthmatics. Alveolar concentrations of nitric oxide (CANO), as well as the classical fraction of exhaled nitric oxide (FeNO50), are associated with the pathophysiology of asthma. However, the association between pretreatment CANO levels and response to anti-asthma treatments, including ICS, remains unknown. <b><i>Methods:</i></b> We retrospectively analyzed 107 patients newly diagnosed with asthma. ICS in combination with long-acting β<sub>2</sub>-agonists (ICS/LABA) was initiated. FEV<sub>1</sub> and FeNO levels were evaluated at diagnosis and were followed up at 6 and 12 months after the treatment intervention. CANO levels were estimated using various expiratory flows of FeNO measurements. Factors associated with annual changes in FEV<sub>1</sub> (ΔFEV<sub>1</sub>) were analyzed. Patients with a ΔFEV<sub>1</sub> &#x3c;–20 mL were defined as “poor-responders.” <b><i>Results:</i></b> FEV<sub>1</sub>, FeNO50, and CANO levels significantly improved by anti-asthma treatments. The average ΔFEV<sub>1</sub> was 85 (176) mL. Eighty-two patients continuously took ICS/LABA treatment. Higher pretreatment CANO levels and continuous use of LABA were independent predictive factors for the improvement of FEV<sub>1</sub> on multivariate analysis. The decline in FeNO50 and CANO levels by the anti-asthma treatments was significantly greater in 81 responders than in 26 poor-responders. CANO, but not FeNO50, levels at 12 months were significantly higher in poor-responders than in responders (<i>p</i> = 0.009). <b><i>Conclusion:</i></b> Levels of CANO, but not FeNO50, predict changes in pulmonary function in ICS-naïve asthmatics. Meanwhile, persistently high levels of CANO may be related to poor responsiveness to treatments assessed by ΔFEV<sub>1</sub>.

scholarly journals Predictors of Loss of Asthma Control Induced by Corticosteroid Withdrawal

2006 ◽  
Vol 13 (3) ◽  
pp. 129-133 ◽  
Author(s):  
Jose Belda ◽  
Krishnan Parameswaran ◽  
Catherine Lemière ◽  
Dennis Kamada ◽  
Paul M O'Byrne ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Asthma Control ◽  
Eosinophil Count ◽  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Exhaled Nitric Oxide ◽  
Baseline Risk ◽  
Blood Eosinophil ◽  
Inhaled Corticosteroid ◽  
Sputum Eosinophil

BACKGROUND: Asthma guidelines recommend reducing the dose of inhaled corticosteroids after establishing control.OBJECTIVE: To identify predictors of loss of control and the kinetics of symptoms, and inflammatory and physiological measurements when inhaled corticosteroids are reduced in patients with stable asthma.PATIENTS AND METHODS: In a single-blind study, the daily dose of inhaled corticosteroid was reduced by one-half at intervals of 20±2 days in 17 adults with controlled asthma until loss of asthma control occurred or until the corticosteroid was replaced with placebo for 20 days. The patients recorded symptoms and peak expiratory flow each day, and forced expiratory volume in 1 s (FEV1), the provocative concentration of methacholine causing a 20% fall in FEV1(PC20), exhaled nitric oxide, and eosinophils in sputum and blood were measured every 10 days. A loss of asthma control was defined as a worsening of the symptoms score of at least 20%, and either a decrease in FEV1of at least 15% or a decrease in PC20of at least fourfold.RESULTS: Two patients had a respiratory infection and were withdrawn from the study. In eight patients, asthma became uncontrolled after a mean of 33 days (range 13 to 48 days). This was accurately reflected by a worsening of all parameters. The first parameter to change was the sputum eosinophil percentage (20 days before the loss of asthma control). Significant changes in exhaled nitric oxide, FEV1and methacholine PC20were observed only when the symptoms became uncontrolled. A high blood eosinophil count at baseline (risk ratio of 2.5, 95% CI 1.0 to 6.5) and an increase in sputum eosinophil count after the reduction of corticosteroids were predictors of loss of asthma control.CONCLUSION: In patients whose asthma is controlled on inhaled corticosteroid, it is prudent not to reduce the dose further if the blood eosinophils are increased or if the sputum eosinophils increase by as little as 1% after the reduction of corticosteroids.

scholarly journals Maintained therapeutic effect of revefenacin over 52 weeks in moderate to very severe Chronic Obstructive Pulmonary Disease (COPD)

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
James F. Donohue ◽  
Edward Kerwin ◽  
Sanjay Sethi ◽  
Brett Haumann ◽  
Srikanth Pendyala ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Health Outcomes ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Open Label ◽  
Double Blind ◽  
Obstructive Pulmonary Disease ◽  
Long Acting

Abstract Background Revefenacin is a long-acting muscarinic antagonist that was recently approved for the nebulized treatment of chronic obstructive pulmonary disease (COPD). Although shorter duration studies have documented the efficacy of revefenacin in COPD, longer-term efficacy has not been described. In a recent 52-week safety trial, revefenacin was well tolerated and had a favorable benefit-risk profile. Here we report exploratory efficacy and health outcomes in patients receiving revefenacin 175 μg or 88 μg daily during the 52-week trial. Methods In this randomized, parallel-group, 52-week trial (NCT02518139), 1055 participants with moderate to very severe COPD received revefenacin 175 μg or 88 μg in a double-blind manner, or open-label active control tiotropium. Results Over the 52-week treatment period, both doses of revefenacin, as well as tiotropium, elicited significant (all p < 0.0003) improvements from baseline in trough forced expiratory volume in 1 s (FEV1). The trough FEV1 profile (least squares mean change from baseline) for revefenacin 175 μg ranged from 52.3–124.3 mL and the trough FEV1 profile for tiotropium ranged from 79.7–112.8 mL. In subgroup comparisons, the effect of revefenacin on trough FEV1 was comparable in patients taking concomitant long-acting β-agonists, with or without inhaled corticosteroids, with patients who were not taking these medications. There were statistically significant (p < 0.05) improvements in all measured health status outcomes (evaluated using St. George’s Respiratory Questionnaire, COPD Assessment Test, Clinical COPD Questionnaire and Baseline and Transition Dyspnea Index) from 3 months onward, in all treatment arms. Conclusions Significant sustained improvements from baseline in trough FEV1 and respiratory health outcomes were demonstrated for 175-μg revefenacin over 52 weeks, further supporting its use as a once-daily bronchodilator for the nebulized treatment of patients with COPD. Trial registration NCT02518139; Registered 5 August 2015.

scholarly journals Combination of ICSs and LABAs Should Be Used in the Management of Patients with COPD — The Con Argument

2004 ◽  
Vol 11 (3) ◽  
pp. 224-226
Author(s):  
Jeremy Road
Keyword(s):  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Randomized Controlled ◽  
The Past ◽  
Related Quality ◽  
Health Related ◽  
Long Acting

The management of patients with symptomatic chronic obstructive pulmonary disease (COPD) has become more clear in the past several years. New medications have been developed and their efficacy has been evaluated using important outcomes in addition to forced expiratory volume in 1 s (FEV1), such as health-related quality of life (HRQL), frequency of exacerbations and dyspnea scores. I will review five welldesigned, randomized, controlled trials that have advanced our knowledge about the use of inhaled corticosteroids (ICSs), long-acting beta2-agonists (LABAs) and their combination.

β 2-Adrenoceptor polymorphism and bronchoprotective sensitivity with regular short- and long-acting β2-agonist therapy

1999 ◽  
Vol 96 (3) ◽  
pp. 253-259 ◽  
Author(s):  
B. J. LIPWORTH ◽  
I. P. HALL ◽  
I. AZIZ ◽  
K. S. TAN ◽  
A. WHEATLEY
Keyword(s):  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Double Blind ◽  
Geometric Means ◽  
Once Daily ◽  
Regular Treatment ◽  
Parallel Group ◽  
Long Acting ◽  
To Receive ◽  
Β2 Agonist

The aim of the present study was to investigate bronchoprotective sensitivity in patients receiving regular treatment with short- and long-acting β2-agonists and to evaluate any possible association with genetic polymorphism. Thirty-eight patients with stable mild to moderate asthma and receiving inhaled corticosteroids were randomized in a parallel group, double-blind, double-dummy fashion to receive 2 weeks of treatment with either formoterol (12μg once daily, 6μg twice daily or 24μg twice daily) or terbutaline (500μg four times daily). Bronchoprotection against methacholine challenge (as a provocative dose to produce a 20% fall in forced expiratory volume in 1.0 ;s: PD20) was measured at baseline (unprotected) after an initial 1 week run-in without β2-agonist, and at 1 ;h after the first and last doses of each treatment. The PD20 values were log-transformed and calculated as change from baseline. Percentage desensitization of log PD20 for first- versus last-dose bronchoprotection was calculated and analysed according to effects of treatment and β2-adrenoceptor polymorphism at codon 16 or 27. The mean degree of desensitization for bronchoprotection was comparable with all four treatments and there were no significant differences in absolute PD20 values after 2 weeks of chronic dosing. The PD20 values were (as μg of methacholine, geometric means±S.E.M.): formoterol, 12μg once daily, 99±42μg; formoterol, 6μg twice daily, 107±44μg; formoterol, 24μg twice daily, 108±45μg; terbutaline, 500μg four times daily, 88±37μg. All patients receiving formoterol, 24μg twice daily, exhibited a loss of protection greater than 30% which was unrelated to polymorphism at codon 16 or 27. For codon 16, the use of lower doses of formoterol (12μg once daily or 6μg twice daily) showed wider variability in the propensity for protection loss in patients who were heterozygous, in contrast to a more uniform protection loss seen with homozygous glycine patients. The amount of protection loss was not significantly related to polymorphism at codon 16 or 27, expressed as values (mean±S.E.M.) for percentage desensitization according to each genotype (pooled treatments): Gly-16, 66±11%; Het-16, 53±8%; Arg-16, 69±18%; Glu-27, 68±12%; Het-27, 58±8%; Gln-27, 52±12%. The results of this preliminary study showed that bronchoprotective desensitization occurred readily in response to short- or long-acting β2-agonist exposure irrespective of β2-adrenoceptor polymorphism at codon 16 or 27. Further studies with larger patient numbers are required to further evaluate the effects of polymorphisms with lower doses of regular formoterol.

scholarly journals Efficacy and safety of a budesonide/formoterol reliever therapy regimen in mild-moderate asthma: A randomised controlled trial

2021 ◽  
Author(s):  
◽  
Joanna Hardy
Keyword(s):  
Low Dose ◽  
Inhaled Corticosteroids ◽  
Controlled Trial ◽  
Beta Agonist ◽  
Inhaled Corticosteroid ◽  
Moderate Asthma ◽  
Fast Onset ◽  
Systemic Glucocorticoids ◽  
Long Acting ◽  
Randomised Controlled

<p>Background Inhaled corticosteroids taken regularly reduce exacerbation risk in patients with mild asthma. In clinical practice however, adherence to inhaled corticosteroids is poor and the burden of disease from exacerbations is substantive. In this thesis I explore an alternative approach, that of an inhaled corticosteroid/formoterol combination used as sole reliever therapy, that potentially overcomes the problem of poor adherence. I report the results of my research, known as the PeRsonalised Asthma Combination Therapy: with Inhaled Corticosteroid And fast-onset Long acting beta agonist (PRACTICAL) study.   Research aims To investigate the efficacy and safety of as-needed budesonide/formoterol, an inhaled corticosteroid (ICS)/fast-onset long-acting beta agonist (LABA) combination, as compared with maintenance budesonide (ICS) plus as-needed terbutaline, a short-acting beta-agonist (SABA), in adult patients with mild-moderate asthma.  Methods This research was performed as a 52-week, open-label, parallel-group, multicentre, phase III randomised controlled trial of adults aged 18-75 with mild to moderate asthma using SABA for symptom relief, with or without low to moderate doses of maintenance ICS in the previous 12 weeks. Participants were randomly assigned (1:1) to either: (i) budesonide/formoterol Turbuhaler, an ICS/fast-onset LABA, 200/6 micrograms (μg), one inhalation as needed for relief of symptoms, or (ii) budesonide Turbuhaler, an ICS, 200µg, one inhalation twice daily, plus terbutaline Turbuhaler, a SABA, 250µg, two inhalations as needed. Participants and investigators were not masked to group assignment. Participants were seen for six study visits: randomisation, and at weeks 4, 16, 28, 40 and 52. The primary outcome was rate of severe exacerbations per patient per year, with severe exacerbations defined as the use of systemic glucocorticoids for at least three days because of asthma, or a hospitalisation or emergency department visit because of asthma requiring systemic glucocorticoids.   Findings Between May 4, 2016 and Dec 22, 2017, 890 participants were assigned to treatment. The analysis included 885 of 890 randomised participants; 437 assigned to budesonide/formoterol as needed and 448 to budesonide maintenance plus terbutaline as needed. 70% of participants were using ICS at entry. The annualised severe exacerbation rate was lower with as-needed budesonide/formoterol than with maintenance budesonide (absolute rate 0.119 vs 0.172; relative rate, 0.69 [95% confidence interval [CI], 0.48 to 1.00]; p=0.049). The Asthma Control Questionnaire-5 score with budesonide/formoterol was not significantly different from budesonide maintenance (mean difference, 0.06; 95% CI -0.005 to 0.12).   Conclusion This research has demonstrated that in adults with mild to moderate asthma in the real-world setting, budesonide/formoterol reliever therapy was more effective at preventing severe exacerbations than maintenance low-dose budesonide plus as-needed terbutaline without a clinically important worsening in asthma control.   The evidence presented in this thesis supports the 2019 Global Initiative for Asthma recommendation that inhaled corticosteroid/formoterol reliever therapy is an alternative regimen to maintenance low-dose inhaled corticosteroid and SABA reliever for the prevention of severe exacerbations for patients with mild to moderate asthma.</p>

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