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Clinical Epigenetics Oct 2023Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and...
BACKGROUND
Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and bronchodilator drug response (BDR), no study has assessed whether albuterol could induce changes in the airway epithelial methylome. We aimed to characterize albuterol-induced DNAm changes in airway epithelial cells, and assess potential functional consequences and the influence of genetic variation and asthma-related clinical variables.
RESULTS
We followed a discovery and validation study design to characterize albuterol-induced DNAm changes in paired airway epithelial cultures stimulated in vitro with albuterol. In the discovery phase, an epigenome-wide association study using paired nasal epithelial cultures from Puerto Rican children (n = 97) identified 22 CpGs genome-wide associated with repeated-use albuterol treatment (p < 9 × 10). Albuterol predominantly induced a hypomethylation effect on CpGs captured by the EPIC array across the genome (probability of hypomethylation: 76%, p value = 3.3 × 10). DNAm changes on the CpGs cg23032799 (CREB3L1), cg00483640 (MYLK4-LINC01600), and cg05673431 (KSR1) were validated in nasal epithelia from 10 independent donors (false discovery rate [FDR] < 0.05). The effect on the CpG cg23032799 (CREB3L1) was cross-tissue validated in bronchial epithelial cells at nominal level (p = 0.030). DNAm changes in these three CpGs were shown to be influenced by three independent genetic variants (FDR < 0.05). In silico analyses showed these polymorphisms regulated gene expression of nearby genes in lungs and/or fibroblasts including KSR1 and LINC01600 (6.30 × 10 ≤ p ≤ 6.60 × 10). Additionally, hypomethylation at the CpGs cg10290200 (FLNC) and cg05673431 (KSR1) was associated with increased gene expression of the genes where they are located (FDR < 0.05). Furthermore, while the epigenetic effect of albuterol was independent of the asthma status, severity, and use of medication, BDR was nominally associated with the effect on the CpG cg23032799 (CREB3L1) (p = 0.004). Gene-set enrichment analyses revealed that epigenomic modifications of albuterol could participate in asthma-relevant processes (e.g., IL-2, TNF-α, and NF-κB signaling pathways). Finally, nine differentially methylated regions were associated with albuterol treatment, including CREB3L1, MYLK4, and KSR1 (adjusted p value < 0.05).
CONCLUSIONS
This study revealed evidence of epigenetic modifications induced by albuterol in the mucociliary airway epithelium. The epigenomic response induced by albuterol might have potential clinical implications by affecting biological pathways relevant to asthma.
Topics: Child; Humans; DNA Methylation; Epigenomics; Asthma; Albuterol; Epigenesis, Genetic; Bronchodilator Agents; Epithelial Cells; Genome-Wide Association Study
PubMed: 37784136
DOI: 10.1186/s13148-023-01571-0 -
Current Allergy and Asthma Reports Dec 2021Several genome-wide association studies (GWASs) of bronchodilator response (BDR) to albuterol have been published over the past decade. This review describes current... (Review)
Review
PURPOSE OF REVIEW
Several genome-wide association studies (GWASs) of bronchodilator response (BDR) to albuterol have been published over the past decade. This review describes current knowledge gaps, including pharmacogenetic studies of albuterol response in minority populations, effect modification of pharmacogenetic associations by age, and relevance of BDR phenotype characterization to pharmacogenetic findings. New approaches, such as leveraging additional "omics" data to focus pharmacogenetic interrogation, as well as developing polygenic risk scores in asthma treatment responses, are also discussed.
RECENT FINDINGS
Recent pharmacogenetic studies of albuterol response in minority populations have identified genetic polymorphisms in loci (DNAH5, NFKB1, PLCB1, ADAMTS3, COX18, and PRKG1), that are associated with BDR. Additional studies are needed to replicate these findings. Modification of the pharmacogenetic associations for SPATS2L and ASB3 polymorphisms by age has also been published. Evidence from metabolomic and epigenomic studies of BDR may point to new pharmacogenetic targets. Lastly, a polygenic risk score for response to albuterol has been developed but requires validation in additional cohorts. In order to expand our knowledge of pharmacogenetics of BDR, additional studies in minority populations are needed. Consideration of effect modification by age and leverage of other "omics" data beyond genomics may also help uncover novel pharmacogenetic loci for use in precision medicine for asthma treatment.
Topics: Albuterol; Bronchodilator Agents; Genome-Wide Association Study; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide
PubMed: 34958416
DOI: 10.1007/s11882-021-01023-w -
Ethiopian Journal of Health Sciences May 2023Patients with chronic obstructive pulmonary disease (COPD) experience an increased risk of perioperative pulmonary complications. The aim of this study was to evaluate... (Randomized Controlled Trial)
Randomized Controlled Trial
The Effect of Albuterol Spray on Hypoxia and Bronchospasm in Patients with Chronic Obstructive Pulmonary Disease (COPD) under General Anesthesia: A bouble-Blind Randomized Clinical Trial.
BACKGROUND
Patients with chronic obstructive pulmonary disease (COPD) experience an increased risk of perioperative pulmonary complications. The aim of this study was to evaluate the effect of albuterol spray on hypoxia and bronchospasm in patients with COPD under general anesthesia.
METHODS
This single-center, double-blind, parallel-group, randomized clinical trial was performed on 120 smoking patients with COPD who were referred to 5 Azar Educational Hospital in Gorgan, Northern Iran, in 2021. Twenty minutes before general anesthesia and also after completion of surgery and before extubation, 60 patients in the intervention group were inhaled with 2 puffs of albuterol spray. In the control group, patients were inhaled with 2 puffs of placebo spray. In perioperative period, the occurrence of wheezing, bronchospasm, coughing, hemodynamic changes, postoperative shivering, dyspnea, and nausea and vomiting were evaluated in all patients. The Consolidated Standards of Reporting Trials (CONSORT) checklist was used to report important aspects of this study.
RESULTS
The mean age of the patients was 52.34 ±8.95 years, and 115 (95.8%) of them were males while the rest were females. The difference between systolic blood pressure before induction of anesthesia (after administration of albuterol spray) between the group receiving albuterol spray and the group not receiving it was statistically significant (p=0.04). Also, the difference between the mean arterial oxygen saturation before tracheal extubation (after re-administration of albuterol spray) between the albuterol spray group and the non-albuterol group was statistically significant (p = 0.03). Wheezing and recurrent cough after induction of anesthesia and after extubation (after albuterol spray administration) was lower in the albuterol group than in the control group (p<0.05). No significant side effects were detected in the albuterol-treated group.
CONCLUSION
According to the results of this study, it seems that the prophylactic use of albuterol spray is useful in reducing the incidence of wheezing and recurrent cough before induction of anesthesia in COPD patients with smoking.
Topics: Male; Female; Humans; Adult; Middle Aged; Albuterol; Bronchial Spasm; Bronchodilator Agents; Cough; Respiratory Sounds; Pulmonary Disease, Chronic Obstructive; Anesthesia, General; Hypoxia; Double-Blind Method
PubMed: 37576161
DOI: 10.4314/ejhs.v33i3.12 -
Journal of Feline Medicine and Surgery Sep 2023Feline inflammatory airway diseases, including (but not limited to) asthma, chronic bronchitis and bronchiectasis, are common and incurable disorders. These diseases... (Review)
Review
PRACTICAL RELEVANCE
Feline inflammatory airway diseases, including (but not limited to) asthma, chronic bronchitis and bronchiectasis, are common and incurable disorders. These diseases require lifelong therapy and may result in substantial morbidity and, in some cases, mortality. Goals of therapy include reduction or resolution of clinical signs and the underlying pathologic processes driving those clinical signs. Inhalational therapy has the advantage of topical delivery of drugs to target tissues at higher doses with fewer systemic effects than oral medications. There are multiple options for delivery devices, and proper selection and training on the use of these devices - including acclimation of the cat to the device - can maximize therapeutic efficacy.
AIM
As inhalational therapy is uncommonly used by many veterinarians and owners, this review article provides a foundation on the selection and use of devices and inhalant medications for specific feline inflammatory airway diseases. Cats present a unique challenge with respect to the use of inhalers, and easy-to-follow steps on acclimating them to the devices are provided. The review also discusses the mechanics of inhalational therapy and helps clarify why certain medications, such as albuterol (salbutamol), fluticasone or budesonide, are chosen for certain diseases. The ultimate aim is that the practitioner should feel more comfortable managing common airway diseases in cats.
EVIDENCE BASE
In compiling their review, the authors searched the veterinary literature for articles in English that discuss inhalational therapy in cats, and which focus primarily on inhaled glucocorticoids and bronchodilators. While most literature on inhalational therapy in cats is based on experimental feline asthma models, there are some studies demonstrating successful treatment in cats with naturally occurring inflammatory airway disease.
Topics: Cats; Animals; Humans; Asthma; Albuterol; Bronchitis, Chronic; Emotions; Veterinarians; Cat Diseases
PubMed: 37675792
DOI: 10.1177/1098612X231193054 -
European Journal of Pediatrics Sep 2023Numerous studies have shown that quality improvement methods can reduce the use of medications in the management of bronchiolitis. Our objective is to identify factors... (Observational Study)
Observational Study
Numerous studies have shown that quality improvement methods can reduce the use of medications in the management of bronchiolitis. Our objective is to identify factors related to the overuse of salbutamol in the treatment of bronchiolitis before and after an improvement initiative. Observational study of sociodemographic and clinical factors associated with the use of salbutamol in children diagnosed with bronchiolitis. This was a secondary analysis of a prospective cohort study conducted at 135 primary care (PC) centers and eight pediatric emergency departments (ED) in the Osakidetza/Basque Health Service (Spain) in two epidemic seasons between which a bronchiolitis integrated care pathway (BICP) had been implemented: pre-intervention season from October 2018 to March 2019 and post-intervention season from October 2019 to March 2020. Generalized linear mixed models were used to estimate association of studied variables on use of salbutamol over the two seasons. Four thousand one hundred thirty-four ED attendances and 8573 PC visits were included, of which 1936 (46.8%). And 4067 (47.4%) occurred in the post-intervention period respectively. Six independent risk factors were associated with overuse of salbutamol in both seasons: age ≥ 1 year, aOR 2.32 (2.01 to 2.68) in PC centers, and aOR 6.84 (4.98 to 9.39) in EDs; being seen in the last third of the bronchiolitis season, aOR 1.82 (1.51 to 2.18) in PC centers and aOR 1.78 (1.19 to 2.64) in EDs; making more than one visit to the PC center, aOR 4.18 (3.32 to 5.27) or the ED, aOR 2.06 (1.59 to 2.66); being seen by a general practitioner, aOR 1.97 (1.58 to 2.46) in PC centers; and having a more severe episode, aOR 3.01 (1.89 to 4.79) in EDs. Conclusion:There are factors associated with salbutamol overuse in children diagnosed with bronchiolitis in PC and emergency settings that persist after the deployment of quality improvement initiatives. What is Known: • Quality improvement initiatives have been shown to decrease the use of non-evidence-based treatments and testing in bronchiolitis. • The magnitude and pattern of change in the use of medications linked to the quality improvement initiatives are not uniform across the same health service. What is New: • Children diagnosed with bronchiolitis ≥ 1 year of age, seen in the last third of the bronchiolitis season, attending more than once, treated by a general practitioner, and/or with more severe episodes are more likely to be treated with salbutamol. • These factors may remain present despite the implementation of improvement initiatives focused on reducing the use of medications in the management of bronchiolitis.
Topics: Child; Humans; Infant; Albuterol; Bronchiolitis; Emergency Service, Hospital; Prospective Studies; Risk Factors; Child, Preschool
PubMed: 37452844
DOI: 10.1007/s00431-023-05111-z -
Respiratory Medicine Oct 2023Bronchial thermoplasty is an effective intervention to improve respiratory symptoms and to reduce the rate of exacerbations in uncontrolled severe asthma. A reduction in...
INTRODUCTION
Bronchial thermoplasty is an effective intervention to improve respiratory symptoms and to reduce the rate of exacerbations in uncontrolled severe asthma. A reduction in airway smooth muscle is arguably the most widely discussed mechanisms accounting for these clinical benefits. Yet, this smooth muscle reduction should also translate into an impaired response to bronchodilator drugs. This study was designed to address this question.
METHODS
Eight patients with clinical indication for thermoplasty were studied. They were uncontrolled severe asthmatics despite optimal environmental control, treatment of comorbidities, and the use of high-dose inhaled corticosteroids and long-acting β-agonists. Lung function measured by spirometry and respiratory mechanics measured by oscillometry were examined pre- and post-bronchodilator (salbutamol, 400 μg), both before and at least 1 year after thermoplasty.
RESULTS
Consistent with previous studies, thermoplasty yielded no benefits in terms of baseline lung function and respiratory mechanics, despite improving symptoms based on two asthma questionnaires (ACQ-5 and ACT-5). The response to salbutamol was also not affected by thermoplasty based on spirometric readouts, including forced expiratory volume in 1 s (FEV), forced vital capacity (FVC), and FEV/FVC ratio. However, a significant interaction was observed between thermoplasty and salbutamol for two oscillometric readouts, namely reactance at 5 Hz (X) and reactance area (Ax), showing an attenuated response to salbutamol after thermoplasty.
CONCLUSIONS
Thermoplasty attenuates the response to a bronchodilator. We argue that this result is a physiological proof of therapeutic efficacy, consistent with the well-described effect of thermoplasty in reducing the amount of airway smooth muscle.
Topics: Humans; Bronchodilator Agents; Bronchial Thermoplasty; Asthma; Albuterol; Adrenal Cortex Hormones; Forced Expiratory Volume
PubMed: 37422022
DOI: 10.1016/j.rmed.2023.107340 -
Therapeutic Advances in Respiratory... 2024This summary describes the results of a clinical study called MANDALA that was published in the in 2022. In the MANDALA study, researchers looked at a new asthma rescue... (Review)
Review
This summary describes the results of a clinical study called MANDALA that was published in the in 2022. In the MANDALA study, researchers looked at a new asthma rescue inhaler that contains both and in a single inhaler (known as , AIRSUPRA™). This summary describes the results for people aged 18 yearsand older who took part in the study.
Topics: Humans; Asthma; Albuterol; Drug Combinations; Administration, Inhalation; Bronchodilator Agents; Budesonide; Adult; Middle Aged; Male; Female; Nebulizers and Vaporizers; Treatment Outcome; Adolescent; Young Adult; Aged; Anti-Asthmatic Agents
PubMed: 38698565
DOI: 10.1177/17534666241232264 -
MMW Fortschritte Der Medizin Oct 2022
Topics: Albuterol; Bronchodilator Agents; Humans; Physical Examination
PubMed: 36253705
DOI: 10.1007/s15006-022-2011-8 -
American Journal of Therapeutics 2019
Topics: Acidosis, Lactic; Albuterol; Asthma; Bronchodilator Agents; Female; Humans; Lactic Acid; Middle Aged; Severity of Illness Index
PubMed: 30664522
DOI: 10.1097/MJT.0000000000000843 -
Hospital Pediatrics Sep 2023Management guidelines for bronchiolitis advocate for supportive care and exclude those with high-risk conditions. We aim to describe and compare the management of...
OBJECTIVE
Management guidelines for bronchiolitis advocate for supportive care and exclude those with high-risk conditions. We aim to describe and compare the management of standard-risk and high-risk patients with bronchiolitis.
METHODS
This retrospective study examined patients <2 years of age admitted to the general pediatric ward with an International Classification of Diseases, 10th Revision discharge diagnosis code of bronchiolitis or viral syndrome with evidence of lower respiratory tract involvement. Patients were defined as either standard- or high-risk on the basis of previously published criteria. The frequencies of diagnostic and therapeutic interventions were compared.
RESULTS
We included 265 patients in this study (122 standard-risk [46.0%], 143 high-risk [54.0%]). Increased bronchodilator use was observed in the standard-risk group (any albuterol dosing, standard-risk 65.6%, high-risk 44.1%, P = .003). Increased steroid use was observed in the standard-risk group (any steroid dosing, standard-risk 19.7%, high-risk 14.7%, P = .018). Multiple logistic regression revealed >3 doses of albuterol, hypertonic saline, and chest physiotherapy use to be associated with rapid response team activation (odds ratio [OR] >3 doses albuterol: 8.36 [95% confidence interval (CI): 1.99-35.10], P = .048; OR >3 doses hypertonic saline: 13.94 [95% CI: 4.32-44.92], P = .001); OR percussion and postural drainage: 5.06 [95% CI: 1.88-13.63], P = .017).
CONCLUSIONS
A varied approach to the management of bronchiolitis in both standard-risk and high-risk children occurred institutionally. Bronchodilators and steroids continue to be used frequently despite practice recommendations and regardless of risk status. More research is needed on management strategies in patients at high-risk for severe disease.
Topics: Humans; Child; Infant; Retrospective Studies; Bronchodilator Agents; Albuterol; Bronchiolitis; Steroids
PubMed: 37534416
DOI: 10.1542/hpeds.2022-006518