Targeting the Beta-2-Adrenergic Receptor and the Risk of Developing Alzheimer's Disease: A Retrospective Inception Cohort Study.

BACKGROUND: Animal studies suggested that ß2-Adrenergic receptors (ß2AR) may be a potential target for the treatment of Alzheimer's disease (AD). OBJECTIVE: This retrospective inception cohort study aimed to assess the association between antagonists and agonists of the ß2AR and the risk of starting treatment for AD in older adults. METHODS: A retrospective inception cohort study was conducted among older adults who initiated either non-selective ßAR antagonists or selective ß2AR agonists using the University Groningen IADB.nl prescription database (study period 1994-2019). For each exposed cohort, two reference cohorts (A and B) were matched on age at index date. The main outcome was defined as at least two prescriptions for cholinesterase inhibitors (rivastigmine, galantamine, and donepezil) and/or memantine. Cox proportional hazard regression models were used to estimate hazard ratios (HR). RESULTS: The risk of developing AD was elevated among patients exposed to non-selective ßAR antagonists (A: aHR 3.303, 95% CI 1.230-8.869, B: aHR 1.569, 95% CI 0.560-4.394) and reduced among patients exposed to selective ß2AR agonists (A: aHR 0.049, 95% CI 0.003-0.795, B: aHR 0.834, 95% CI 0.075-9.273) compared to reference patients. CONCLUSION: These findings suggest that exposure to non-selective ßAR antagonists is associated with an increased risk for developing AD whereas there may be a decreased risk for developing AD after exposure to selective ß2AR agonists.

Therapeutics effects of inhaled magnesium sulfate combined with adrenergic beta-2 agonist on children with acute asthma: Systematic review and meta-analysis.

AIM: To review the evidence on the effectiveness of inhaled magnesium sulfate (MgSO4) combined with beta-2 (B2) agonist as compared to inhaled B2 agonist alone in treating pediatric patients with moderate to severe asthma attacks METHODS: The search was conducted on five electronic databases namely the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, PubMed, Science Direct, and Google Scholar. RESULTS: Eight trials were included in the review. All studies involved a total of 1585 children aged 2-17 years with moderate to severe asthma attacks. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials. Three studies that assessed the effect of inhaled MgSO4 as adjunctive therapy on vital signs revealed no effect of inhaled MgSO4 on vital signs (SMD -0.11, 95% CI 0.27-0.04, p = 0.16, I2 = 68%). Two studies that assessed the effect of inhaled MgSO4 as adjunctive therapy on asthma severity score (ASS) revealed no effect of inhaled MgSO4 on ASS (SMD 0.22, 95% CI 0.01-0.44, Z = 2.01, p = 0.04, I2 = 88%). Two studies that assessed the effect of inhaled MgSO4 as adjunctive therapy on peak expiratory flow rate (PEFR) revealed a large effect of B2 agonist alone on PEFR (SMD 2.02, 95% CI 0.83-3.2, p < 0.001, I2 = 98%). CONCLUSION: This review does not support the use of inhaled MgSO4 as adjunctive therapy to B2 agonist for asthmatic children.

Patient-reported outcomes of dual bronchodilator fixed-dose combination versus bronchodilator monotherapy in individuals with COPD.

Background: This study compared real-world patient-reported outcomes (PROs) measured by the Clinical COPD Questionnaire (CCQ), the London Chest Activities of Daily Living (LCADL) scale, and the Work Productivity and Activity Impairment (WPAI) questionnaire between individuals with COPD initiating LAMA/LABA fixed-dose combination (FDC) dual therapy versus either long-acting muscarinic antagonist (LAMA) or long-acting beta2-agonist (LABA) monotherapy. Methods: Individuals with COPD aged ≥40 years initiating a LAMA/LABA FDC dual therapy or a LAMA or LABA monotherapy (index date = first prescription date) between January 1, 2016 and December 31, 2016 were identified from a large US administrative claims database. Individuals were excluded if they were prescribed an inhaled corticosteroid (ICS) or ICS/LABA two months prior to the index date or were diagnosed with cystic fibrosis, idiopathic pulmonary fibrosis, or asthma. The cohorts were propensity score matched (PSM) 1:1 for COPD severity using baseline measures. Each participant completed a survey. Results: Surveys were completed by 399 participants in the dual therapy cohort, and 718 participants in the monotherapy cohort. Following PSM, 379 participants remained in each cohort for analysis (monotherapy: 369 LAMA and 10 LABA). The dual therapy cohort reported fewer COPD-related symptoms (CCQ symptom score 2.75 vs 2.97, respectively, P=0.023), and, fewer limitations in leisure activities (LCADL leisure score 4.78 vs 5.17, respectively, P=0.021) versus the monotherapy cohort. No significant differences were found in the WPAI. A greater percentage of participants in the dual therapy cohort stayed on index therapy (63.1%) when compared with the monotherapy cohort (30.3%, P<0.0001). Conclusions: Only 30% of the participants prescribed monotherapy, usually with a LAMA, remained on index therapy alone at the time of survey administration. In the dual therapy cohort, 63% of the participants remained on the index medication and had fewer COPD-related symptoms and fewer limitations in leisure activities compared with participants in the monotherapy cohort.

Anaphylaxis Caused by Benzalkonium in a Nebulizer Solution

Benzalkonium chloride (BAC) is commonly used as a bactericidal preservative in nebulizer solutions, and can cause paradoxical onchoconstriction following nebulizing therapy in some asthmatics. We describe a case of anaphylactic shock in a 23-yr-old asthmatic woman following an intradermal skin test with a salbutamol solution containing BAC. Since she complained of cough and dyspnea after inhalation therapy with a nebulizer solution, we conducted an intradermal skin test using the same solution, which contained BAC. About 10 min later, the patient reported dizziness, palpitations, and dyspnea. On examination, tachycardia, tachypnea, and hypotension were found. She was resuscitated with a subcutaneous injection of epinephrine and an infusion of saline. One month later, we conducted a bronchial provocation test with BAC, and she showed a positive response.