The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report revised the combined assessment, merged the C and D groups into the E group, and revised the initial inhalation therapy recommendation.
This study aimed to analyze the future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease (COPD) in various groups based on the GOLD 2017 and GOLD 2023 reports.
This is a multicenter and retrospective study.
Stable COPD patients from the database setup by 12 hospitals were enrolled. The patients were divided into Groups A, B, C, D, and E according to the GOLD 2017 and GOLD 2023 reports. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS subgroups. Data on exacerbation and death during 1 year of follow-up were collected.
A total of 4623 patients were classified into Group A (15.0%), Group B (37.8%), Group C (7.3%), Group D (39.9%), and Group E (47.2%). The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies in Groups A and C. Patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of exacerbation and frequent exacerbation than patients treated with LAMA or LABA + ICS in Groups B, D, and E. The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies after combining Groups A with C.
Patients in Group A should be recommended to undergo mono-LAMA, while patients in Groups B and E should be recommended treatment with LABA + LAMA, which is consistent with the GOLD 2023 report. However, it is worth considering merging Groups A and C into a single group and recommending mono-LAMA as the initial inhalation therapy.

UNASSIGNED: Although β2-adrenoceptor (β2AR) agonists have been associated with a lower risk of Parkinson\'s disease (PD), the findings are inconclusive and may reflect confounding by indication. We studied the association between inhaled β2AR agonists and risk of PD in persons with asthma or chronic obstructive pulmonary disease (COPD).
UNASSIGNED: The nested case-control study was conducted within a register-based Finnish Parkinson\'s disease study (FINPARK) and included 1406 clinically verified PD cases diagnosed during 1999-2015, who also had asthma/COPD >3 years before PD. PD cases were matched with up to seven controls by age, sex, duration of asthma/COPD, pulmonary diagnosis, and region (N = 8630). Cumulative and average annual exposure to short- and long-acting β2AR agonists before a 3-year lag period was assessed with quartiles of defined daily doses (DDDs). Adjusted odds ratios (aORs) were calculated with 95% confidence intervals (CIs) using conditional logistic regression.
UNASSIGNED: Cumulative exposure to either short- or long-acting β2AR agonists was not associated with a risk of PD. With average annual exposure, a decreased risk was observed only for the highest quartile of long-acting β2AR agonists (aOR 0.75; 95% CI 0.58-0.97). In the stratified analysis the lowest risk estimates were observed among those with both asthma and COPD diagnoses. The suggestion of an inverse association was seen for the highest quartile of long-acting β2AR agonists in asthma.
UNASSIGNED: Higher levels of exposure to β2AR agonists were not consistently associated with a reduced risk of PD. The inverse association in the highest category of average annual exposure to long-acting β2AR agonists may be explained by unmeasured confounding, such as disease severity or smoking.

Despite ample evidence underpinning the efficacy of β2-agonists in asthma and chronic obstructive pulmonary disease (COPD), the occurrence of β1- and β2-adrenoceptors in the heart suggests that β2-agonists may have deleterious cardiac effects. We investigated the association between new users of long-or short-acting β2-agonists (LABA or SABA) or ICS (inhaled corticosteroids)/LABA and major adverse cardiovascular events (MACE).
A nested case-control analysis was conducted using the UK Clinical Practice Research Datalink of patients with asthma, COPD or asthma-COPD overlap with initial treatment of LABA, SABA, ICS/LABA, ICS, long-or short-acting muscarinic antagonist (LAMA or SAMA) between 01 January 1998 and 31 July 2018. The primary outcome was MACE, defined as the first occurrence of stroke, heart failure, myocardial infarction, arrhythmia, or cardiovascular death. Each case was matched with up to 10 controls on age, sex, date of cohort-entry, and duration of follow-up. The risk of MACE associated with β2-agonists was estimated using conditional logistic regression after controlling for potential confounders.
The cohort included 180,567 new users of β2-agonists, ICS, SAMA, or LAMA. Among asthmatics, β2-agonists were not associated with the risk of MACE (SABA vs ICS: HR 1.29 [0.96-1.73]; ICS/LABA vs ICS, HR 0.75 [0.33-1.73]). In contrast, among COPD patients, LABA (HR, 2.38 [1.04-5.47]), SABA (HR, 2.02 [1.13-3.59]) and ICS/LABA (HR, 2.08 [1.04-4.16]) users had an increased risk of MACE compared with SAMA users. Among patients with asthma-COPD overlap, SABA (HR, 2.57 [1.26-5.24]) was associated with an increased risk of MACE compared with ICS.
In conclusion, initiation of LABA, SABA, or ICS/LABA in COPD or SABA in asthma-COPD overlap is associated with increased risk of MACE. No associations were observed among patients with asthma.

BACKGROUND: Long-acting muscarinic antagonists (LAMA) are used for long-term treatment of bronchial asthma in adults. Its use in the management of pediatric bronchial asthma, however, is currently not approved in Japan. Nonetheless, there have been a few reports of its use in children, particularly in cases of severe bronchial asthma or those without atopic disease that are refractory to existing treatment protocols. We report the progress of LAMA in infantile asthma patients.
METHODS: Three out of four patients had LAMA introduced at 3 to 5 years of age after being diagnosed with asthma at 1 to 3 years old. Three patients had non-IgE-related asthma and an underlying disease, such as Apert and Noonan syndrome, while one patient had severe IgE-related asthma without a pre-existing disease. In all cases, conventional long-term medications such as medium to high-dose inhaled corticosteroids and long-acting beta-agonists, were given. However, severe bronchial asthma persisted, with some patients having uncontrolled secretions. Since uncontrolled severe-persistent bronchial asthma results in repeated hospitalization and intensive care unit admission, we introduced LAMA, specifically 2.5μg/day of tiotropium (Tio). After the introducing Tio, none of the patients had an acute exacerbation that required hospitalization and the frequency of wheezing was reduced. LAMA was administered for up to 19 months, with no adverse events.
CONCLUSIONS: The results of this series suggest that LAMA is an effective and safe option for uncontrolled infantile asthma.

Chronic obstructive pulmonary disease (COPD) is a medical condition characterised by persistent respiratory symptoms and airflow limitation. For the long-term management of COPD, inhaled therapies are the main approach to maintenance treatment. In order to improve treatment efficacy and tolerability for patients with COPD, recent clinical trials have focused on the withdrawal of inhaled corticosteroids (ICSs), the use of which has been associated with adverse outcomes, including pneumonia. In this case report, a patient with Global Initiative for Chronic Obstructive Lung Disease grade 3 COPD was switched from a combined inhaled therapy of a long-acting beta-agonist (LABA) and ICS to a combination of a LABA and a long-acting muscarinic antagonist (tiotropium/olodaterol) during hospitalisation for an acute exacerbation of COPD in April 2016. He was subsequently maintained in a stable condition, and was able to live and travel independently. This case report of successful ICS withdrawal suggests that, for moderate-to-severe COPD, if it is assessed individually, dual therapy of LABA and long-acting muscarinic antagonist can be highly effective and well-tolerated. Treatment compliance and lifestyle modifications have been shown to be critical in optimising treatment outcomes.

The relative scale adjusts for baseline variability and therefore may lead to findings that can be generalized more widely. It is routinely used for the analysis of binary outcomes but only rarely for continuous outcomes. Our objective was to compare relative vs absolute scale pooled outcomes using data from a recently published Cochrane systematic review that reported only absolute effects of inhaled β2-agonists on exercise-induced decline in forced-expiratory volumes in 1 s (FEV1).
From the Cochrane review, we selected placebo-controlled cross-over studies that reported individual participant data (IPD). Reversal in FEV1 decline after exercise was modeled as a mean uniform percentage point (pp) change (absolute effect) or average percent change (relative effect) using either intercept-only or slope-only, respectively, linear mixed-effect models. We also calculated the pooled relative effect estimates using standard random-effects, inverse-variance-weighting meta-analysis using study-level mean effects.
Fourteen studies with 187 participants were identified for the IPD analysis. On the absolute scale, β2-agonists decreased the exercise-induced FEV1 decline by 28 pp., and on the relative scale, they decreased the FEV1 decline by 90%. The fit of the statistical model was significantly better with the relative 90% estimate compared with the absolute 28 pp. estimate. Furthermore, the median residuals (5.8 vs. 10.8 pp) were substantially smaller in the relative effect model than in the absolute effect model. Using standard study-level meta-analysis of the same 14 studies, β2-agonists reduced exercise-induced FEV1 decline on the relative scale by a similar amount: 83% or 90%, depending on the method of calculating the relative effect.
Compared with the absolute scale, the relative scale captures more effectively the variation in the effects of β2-agonists on exercise-induced FEV1-declines. The absolute scale has been used in the analysis of FEV1 changes and may have led to sub-optimal statistical analysis in some cases. The choice between the absolute and relative scale should be determined based on biological reasoning and empirical testing to identify the scale that leads to lower heterogeneity.

Introduction: Asthma is one of the most common airway diseases that nearly all pediatricians will encounter in their clinical practice. Using spirometry to compare a patient\'s forced expiratory volume in one second (FEV1) both pre- and post-bronchodilator administration is the ideal way to document a paradoxical bronchodilator response.Case Study: Here, we present a patient who experienced paradoxical responses to short acting beta-2 agonists (SABAs; albuterol and levalbuterol).Results: This patient responded to an anti-cholinergic agent (ipratropium bromide) with both subjective as well as objective response.Conclusion: This case highlights the need to include paradoxical response to SABAs in the differential of a patient with poorly controlled asthma. It also provides an example of successful treatment of a pediatric patient with a class of medications previously reserved for adults with chronic obstructive pulmonary disease.

Associations between parental asthma and prenatal exposure to asthma medications with offspring autism spectrum disorder (ASD) have been reported. However, the associations might be confounded by unmeasured (genetic and shared environmental) familial factors.
We investigated the association between (a) maternal/paternal asthma and offspring ASD, and (b) prenatal exposures to β2-agonists, other asthma medications and offspring ASD using cases and controls selected from the population as well as biological relatives with different degrees of relatedness.
We included all children (N = 1 579 263) born in Sweden 1992-2007. A nested case-control design was used to compare 22 894 ASD cases identified from the National Patient Register to (a) 228 940 age-, county- and sex-matched controls randomly selected from the population, (b) their eligible full-siblings (n = 1267), (c) half-siblings (n = 1323), (d) full-cousins (n = 11 477) and (e) half-cousins (n = 3337). Conditional logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for ASD in children differentially exposed to parental asthma or prenatal asthma medications.
Maternal asthma was associated with increased risk of offspring ASD (OR 1.43, 95% CI 1.38-1.49); there was a weaker association for paternal asthma (OR 1.17, 95% CI 1.11-1.23). The risk of offspring ASD in mothers with asthma showed similar estimates when adjusting for shared familial factors among paternal half-siblings (OR 1.20, 95% CI 0.80-1.81), full-cousins (OR 1.28, 95% CI 1.16-1.41) and half-cousins (OR 1.30, 95% CI 1.10-1.54), albeit with wider confidence intervals. Prenatal exposure to asthma medications among subjects whose mothers had asthma was not associated with subsequent ASD.
In this large observational study, parental asthma was associated with slightly elevated risk of ASD in offspring. More specifically, the increased risk by maternal asthma did not seem to be confounded by familial factors. There was no evidence of an association between asthma medications during pregnancy and offspring ASD.

Salbutamol is a β2 adrenergic agonist widely prescribed in patients with obstructive and restrictive lung diseases. The main side effects associated with its use are tachycardia and tremor. Myoclonus is an involuntary, irregular, abrupt, brief and sudden muscular contraction, which can be generalized, focal or multifocal. We report the case of a 61-year-old patient presenting with myoclonus difficult to treat who showed improvement only after the definitive discontinuation of the β2 adrenergic agonist. We describe the clinical findings, the interventions, and the outcomes related to the onset of myoclonus secondary to the use of salbutamol, as well as the possible genesis and importance of this adverse effect. We used the CARE guidelines to delineate the clinical case. Although myoclonus secondary to the use of different drugs has been described in the literature, as far as we know this is the fourth report of salbutamol-induced myoclonus to date.

A 22-year-old woman presented with symptoms and signs consistent with acute severe asthma. After significant doses of beta-agonist, she developed a significant lactic acidosis. Significant issues arose in this patient\'s history with regards to purchase of medications, compliance and follow-up with respiratory service. Beta-adrenergic receptors when stimulated have been hypothesised to increase lipolysis, producing free fatty acids, which inhibit the conversion of pyruvate to coenzyme A within the Krebs cycle. Additional pyruvate is generated through stimulation of glycolysis and glycogenolysis through simultaneous catecholamine surge. This increased pyruvate load is shunted through anaerobic glycolysis, producing increased lactate. Steroid use during an asthma attack enhances the beta-2 receptor sensitivity, further potentiating lactate production. The hyperadrenergic state in this young asthmatic likely resulted in pyruvate and therefore lactate rise and thus metabolic acidosis as mentioned before. This piece highlights a physiological phenomenon that may occur in the context of iatrogenic hyperadrenergism.