[New clinical guidelines for COPD - a paradigm shift: A review].

Chronic obstructive pulmonary disease is now one of the most common noncommunicable diseases and the main causes of morbidity, disability and mortality in the world. In recent years, new approaches to epidemiology, diagnosis, classification (categorization), evaluation of phenotypes, as well as characterization and assessment of the severity of сhronic obstructive pulmonary disease exacerbations have emerged. Modern approaches to starting and subsequent drug therapy have changed significantly. This is largely due to the results of recently conducted major clinical trials, demonstrated high efficacy of triple fixed combinations, including inhaled glucocorticosteroids, long-acting beta-agonists and long-acting anticholinergic drugs. The use of non-medication methods (smoking cessation, physical activity and respiratory rehabilitation) and modern approaches to the treatment of respiratory failure and antibiotic therapy remain important. In terms of their significance, all these updates have a significant impact on real clinical practice and can be considered as a novel paradigm of the approaches to the diagnosis and management of this disease.

Pulmonary MRI with hyperpolarized xenon-129 demonstrates novel alterations in gas transfer across the air-blood barrier in asthma.

BACKGROUND: Individuals with asthma can vary widely in clinical presentation, severity, and pathobiology. Hyperpolarized xenon-129 (Xe129) MRI is a novel imaging method to provide 3-D mapping of both ventilation and gas exchange in the human lung. PURPOSE: To evaluate the functional changes in adults with asthma as compared to healthy controls using Xe129 MRI. METHODS: All subjects (20 controls and 20 asthmatics) underwent lung function measurements and Xe129 MRI on the same day. Outcome measures included the pulmonary ventilation defect and transfer of inspired Xe129 into two soluble compartments: tissue and blood. Ten asthmatics underwent Xe129 MRI before and after bronchodilator to test whether gas transfer measures change with bronchodilator effects. RESULTS: Initial analysis of the results revealed striking differences in gas transfer measures based on age, hence we compared outcomes in younger (n = 24, ≤ 35 years) versus older (n = 16, > 45 years) asthmatics and controls. The younger asthmatics exhibited significantly lower Xe129 gas uptake by lung tissue (Asthmatic: 0.98% ± 0.24%, Control: 1.17% ± 0.12%, P = 0.035), and higher Xe129 gas transfer from tissue to the blood (Asthmatic: 0.40 ± 0.10, Control: 0.31% ± 0.03%, P = 0.035) than the younger controls. No significant difference in Xe129 gas transfer was observed in the older group between asthmatics and controls (P > 0.05). No significant change in Xe129 transfer was observed before and after bronchodilator treatment. CONCLUSIONS: By using Xe129 MRI, we discovered heterogeneous alterations of gas transfer that have associations with age. This finding suggests a heretofore unrecognized physiological derangement in the gas/tissue/blood interface in young adults with asthma that deserves further study.

The value of bronchodilator response in FEV1 and FeNO for differentiating between chronic respiratory diseases: an observational study.

BACKGROUND: There is no uniform standard for a strongly positive bronchodilation test (BDT) result. In addition, the role of bronchodilator response in differentiating between asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) in patients with a positive BDT result is unclear. We explored a simplified standard of a strongly positive BDT result and whether bronchodilator response combined with fractional exhaled nitric oxide (FeNO) can differentiate between asthma, COPD, and ACO in patients with a positive BDT result. METHODS: Three standards of a strongly positive BDT result, which were, respectively, defined as post-bronchodilator forced expiratory volume in 1-s responses (ΔFEV1) increasing by at least 400 mL + 15% (standard I), 400 mL (standard II), or 15% (standard III), were analyzed in asthma, COPD, and ACO patients with a positive BDT result. Receiver operating characteristic curves were used to determine the optimal values of ΔFEV1 and FeNO. Finally, the accuracy of prediction was verified by a validation study. RESULTS: The rates of a strongly positive BDT result and the characteristics between standards I and II were consistent; however, those for standard III was different. ΔFEV1 ≥ 345 mL could predict ACO diagnosis in COPD patients with a positive BDT result (area under the curve [AUC]: 0.881; 95% confidence interval [CI] 0.83-0.94), with a sensitivity and specificity of 90.0% and 91.2%, respectively, in the validation study. When ΔFEV1 was < 315 mL combined with FeNO < 28.5 parts per billion, patients with a positive BDT result were more likely to have pure COPD (AUC: 0.774; 95% CI 0.72-0.83). CONCLUSION: The simplified standard II can replace standard I. ΔFEV1 and FeNO are helpful in differentiating between asthma, COPD, and ACO in patients with a positive BDT result.

Prevalence and Risk Factors of Chronic Obstructive Pulmonary Disease Among Users of Primary Health Care Facilities in Morocco.

Background: Chronic obstructive pulmonary disease (COPD) is a major public health problem. In Morocco, few studies have focused on COPD in primary health care facilities, whose main mission is prevention. The aim of our work is thus to assess the prevalence of COPD and to study the factors associated with this silent disease among users of health care facilities in Morocco. Methods: This is a cross-sectional observational study of participants aged 40 and over. Data were collected by questionnaire. Pulmonary function testing was conducted using a spirometer before and after administration of a bronchodilator. COPD was defined as fixed ratio of the post-bronchodilator forced expiratory volume in 1 second / forced vital capacity less than 0.7. Logistic regression models were applied to define factors associated with COPD. Results: From 550 participants aged 40 and over, we selected only 477 patients with exploitable spirometry results for inclusion in the final analysis. The mean age of participants was 54.91±11.92 years, and the female/male ratio was 1.59. The prevalence of COPD was 6.7% (95% CI; 4.6 to 9.3%), and was higher in men than in women (11.4% vs 3.8%, p=0.002). The prevalence of COPD increased significantly with age, from 3.3% in those aged 40 to 49 to 16.9% in those aged 70 and over (p=0.001). Current smokers had a higher prevalence of COPD than former and never smokers. Age, smoking, asthma diagnosis and childhood hospitalization for lung disease were risk factors associated with the development of COPD. Only 6.25% of participants identified as having COPD had previously been diagnosed with COPD. Conclusion: COPD remains largely under-diagnosed among primary care consultants in Morocco. Efforts for early detection and promotion of prevention of the main risk factors need to be intensified in order to reduce the burden of this silent pathology on a national scale.

Sexual dysfunction in women with chronic obstructive lung disease.

OBJECTIVE: To determine the prevalence of sexual dysfunction in women with COPD and the factors related to its presence. METHODS: Cross-sectional observational study during 2021, including women with COPD diagnosed by spirometry through convenience sampling. Data on age, smoking status, spirometric data, comorbidities and medications used were collected. A sexual health questionnaire was administered. RESULTS: The study included 101 women with a mean age of 59.7 (11.3) years. All had experienced a change in sexual activity, with 44% attributing it to COPD. Among them, 51.5% experienced dyspnea during coitus. The prevalence of sexual dysfunction was 52.5%. Women with sexual dysfunction were older and had a lower Tiffeneau index. Furthermore, they consumed alcohol more frequently and had hypertension and cerebrovascular disease, and less often, they had diabetes and heart failure. However, they scored lower on the Charlson index corrected for age. Patients with sexual dysfunction used inhaled triple therapy less frequently. CONCLUSIONS: Sexual dysfunction is common in women with COPD. Further studies are needed to investigate its causes, mechanisms, and potential treatments.

Effect of Individual Patient Characteristics and Treatment Choices on Reliever Medication Use in Moderate-Severe Asthma: A Poisson Analysis of Randomised Clinical Trials.

INTRODUCTION: Even though increased use of reliever medication, including short-acting beta agonists (SABA), provides an indirect measure of symptom worsening, there have been limited efforts to assess how different patterns of reliever use correlate with symptom control and future risk of exacerbations. Here, we evaluate the effect of individual baseline characteristics on reliever use in patients with moderate-severe asthma on regular maintenance therapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). METHODS: A drug-disease model describing the number of 24-h puffs and overnight occasions was developed with data from five clinical studies (N = 6212). The model was implemented using a nonlinear mixed effects approach and a Poisson function, considering clinical and demographic baseline characteristics. Goodness of fit and model predictive performance were assessed. Heatmaps were created to summarise the effect of concurrent baseline factors on reliever utilisation. RESULTS: The final model accurately described individual patterns of reliever use, which is significantly increased with time since diagnosis, smoking, higher Asthma Control Questionnaire (ACQ-5) score and higher body mass index (BMI) at baseline. Whilst the number of puffs decreases slowly after an initial drop relative to the start of treatment, exacerbating patients utilise significantly more reliever than those who do not exacerbate. The mean effect of FP/SAL (median dose: 250/50 µg BID) on reliever use was slightly higher than that of BUD/FOR (median dose: 160/4.5 µg BID), i.e. a 75.3% vs 69.3% reduction in reliever use, respectively. CONCLUSIONS: The availability of individual-level patient data in conjunction with a parametric approach enabled the characterisation of interindividual differences in the patterns of reliever use in patients with moderate-severe asthma. Taken together, individual demographic and clinical characteristics, as well as exacerbation history, can be considered an indicator of the degree of asthma control. High SABA reliever use suggests suboptimal clinical management of patients on maintenance therapy.

In this study, we tried to understand how patients with moderate to severe asthma use their quick-relief inhalers (like albuterol), how it relates to their symptoms and the risk of having asthma attacks. To evaluate whether differences in reliever inhaler use between patients are associated with factors like smoking or their asthma symptoms at the beginning of treatment, we gathered data from five clinical studies (n = 6212 patients). These data allowed us to create a model that predicts how often patients use their reliever inhalers (expressed as number of puffs in 24 h) during maintenance therapy with inhaled corticosteroids alone or in combination with long-acting beta agonists. The final model showed that reliever inhaler use is higher in patients who have been diagnosed with asthma for > 10 years, are smokers, have higher asthma symptom scores, and are obese or extremely obese. Patients who had asthma attacks also used their reliever inhalers more often. In addition, to understand how relief inhalers are used in real-life situations, we also created heatmaps that include a wide range of patient characteristics. By using individual patient data together with this model, we have learned that smoking, asthma control, BMI, long history of asthma and previous asthma attacks significantly influence reliever use. This information can help physicians and healthcare professionals understand know how well someone's asthma is managed. A patient who uses their reliever inhaler often is likely not to have their asthma well controlled by their regular medications.

Biological Anti-IL-5/IL-5R Therapeutics for Chronic Obstructive Pulmonary Disease (COPD) with Specific Treatable Traits: A Real-World Retrospective Analysis.

Introduction: We describe the use of anti-IL-5 monoclonal antibodies from a COPD clinic, a source other than traditional clinical trials. The objectives were to characterize the patient subgroup prescribed anti-IL-5 monoclonal antibodies and to report potential benefits. Methods: This is a retrospective case series study of 17 patients treated in a COPD subspecialty clinic. All patients had a diagnosis of COPD (post-bronchodilator FEV1/FVC <0.7) and had been prescribed an anti-IL-5 biologic for at least 8 months. Acute exacerbations of COPD (AECOPDs) were collected as reported in electronic medical records. Results: All patients (17) enrolled were treated with biologics for ≥8 months, and 13 (76%) for ≥1 year. Patients were characterized by severe disease traits, FEV1 <50% predicted, recurrent exacerbations (3.5 moderate-to-severe AECOPDs in the year before treatment), high peripheral blood eosinophil counts (≥250 cells/µL in the previous year), all on inhaled triple therapy, and only 1 patient with a diagnosis of asthma prior to smoking. There was a statistically significant decrease in the exacerbation rate compared with baseline after 8 and 12 months of anti-IL-5 treatment, respectively, yielding the equivalent of a 2-3x reduction in exacerbation rate. Absolute FEV1 decreased, and the decline in FEV1 % of predicted reached statistical significance (p<0.05); CAT score improved (p<0.05). Discussion: This real-world evidence data aligns with existing studies suggesting the potential benefit of anti-IL-5 treatment for specific patients with COPD and therefore advocates for further investigation of RCTs on the use of anti-IL-5 biologics for well-characterized patients with COPD.

[Effects of type 2 inflammation on bronchodilator responsiveness of large and small airways in chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the impact of type 2 inflammation markers blood eosinophils (EOS) and fractional exhaled nitric oxide (FeNO) on bronchodilator responsiveness (BDR) in patients with chronic obstructive pulmonary disease (COPD). METHODS: This study was conducted among 389 patients with an established diagnosis of COPD in our hospital from October, 2019 to October, 2023, who all underwent bronchial dilation test (BDT) of the large and small airways. Based on smoking history, blood EOS, and FeNO, these patients were divided group A (blood EOS < 300/µL + FeNO < 35 ppb + smoking history < 20 pack-years), group B (blood EOS < 300/µL+FeNO < 35 ppb+smoking history ≥20 pack-years), group C (blood EOS ≥300/µL or FeNO≥35 ppb+smoking history ≥20 pack-years), and group D (blood EOS ≥300/µL or FeNO ≥35 ppb+smoking history < 20 pack-years) for analyzing the relationship between clinical indexes and BDR. RESULTS: BDR evaluation based on forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and maximum mid-expiratory flow (MMEF) yielded consistent results, all showing a younger mean age, higher FeNO levels, and higher blood EOS counts and percentages in patients positive for BDT (P < 0.05). The improvement value and improvement rate of FEV1 were significantly lower in group A than in group D. The improvement value and improvement rate of FEV1 as well as the improvement rate of MMEF were significantly lower in group B than in group D. In the overall patients, age and FeNO were significantly correlated with the improvement value and improvement rate of FEV1 and the improvement rate of MMEF (P < 0.05). CONCLUSION: Type 2 inflammation markers have different effects on BDR in the large and small airways of COPD patients, and their clinical significance needs further investigation.

Systematic literature review of traits and outcomes reported in randomised controlled trials of asthma with regular dosing of inhaled corticosteroids with short-acting ß2-agonist reliever, as-needed ICS/formoterol, or ICS/formoterol maintenance and reliever therapy.

INTRODUCTION: Asthma treatments based solely on diagnostic label do not benefit patients equally. To identify patient traits that may be associated with improved treatment response to regular inhaled corticosteroid (ICSs) dosing with short-acting ß2-agonist reliever or ICS/formoterol-containing therapy, a systematic literature review (SLR) was conducted. METHODS: Searches of databases including MEDLINE and Embase identified randomised controlled trials (RCTs) of patients with asthma, aged ≥12 years, published 1998-2022, containing ≥1 regular ICS dosing or ICS/formoterol-containing treatment arm, and reporting patient traits and outcomes of interest. Relevant data was extracted and underwent a feasibility assessment to determine suitability for meta-analysis. RESULTS: The SLR identified 39 RCTs of 72,740 patients and 90 treatment arms, reporting 11 traits and 11 outcomes. Five patient traits (age, body mass index, FEV1, smoking history, asthma control) and five outcomes (exacerbation rate, lung function, asthma control, adherence, time to first exacerbation) were deemed feasible for inclusion in meta-analyses due to sufficient comparable reporting. Subgroups of clinical outcomes stratified by levels of patient traits were reported in 16 RCTs. CONCLUSION: A systematic review of studies of regular ICS dosing with SABA or ICS/formoterol-containing treatment strategies in asthma identified consistent reporting of five traits and outcomes, allowing exploration of associations with treatment response. Conversely, many other traits and outcomes, although being potentially relevant, were inconsistently reported and limited subgroup reporting meant analyses of treatment response for subgroups of traits was not possible. We recommend more consistent measurement and reporting of clinically relevant patient traits and outcomes in respiratory RCTs.

Disfunções respiratórias felinas: caracterizando e diferenciando a asma e bronquite felinas / Feline respiratory dysfunctions: characterizing and differentiating feline asthma and bronchitis / Disfunciones respiratorias felinas: caracterización y diferenciación del asma y bronquitis felinas

As doenças respiratórias são consideradas doenças graves e potencialmente deletérias. Dentre elas, a asma e a bronquite crônica caracterizam-se como disfunções respiratórias que ameaçam constantemente o bem-estar dos gatos. Os pacientes apresentam mudanças na estrutura respiratória, reversíveis ou não, devido ao extenso quadro inflamatório, que obstrui o fluxo de ar, permite o acúmulo de muco e reduz o lúmen das vias aéreas. Os gatos acometidos apresentam tosses, respiração ruidosa, dispneia, e, em muitos casos, assumem posição ortopneica. O diagnóstico pode ser obtido através de exames de rotina, uso de radiografias torácicas, coleta e análise de fluidos broncoalveolares, e testes alergênicos. O manejo terapêutico baseia-se, combinado ou não, no uso de drogas como broncodilatadores, antiinflamatórios esteroidais, mucolíticos, antibióticos, agentes inalatórios e mudanças ambientais com objetivo de redução da exposição aos possíveis agentes alergênicos responsáveis pela incitação do quadro respiratório.

Respiratory diseases are considered serious and potentially harmful diseases. Among them, asthma and chronic bronchitis are characterized as respiratory disorders that constantly threaten the well-being of cats. The patients present changes in the respiratory structure, reversible or not, due to the extensive inflammatory condition, which obstructs the air flow, allows the accumulation of mucus and reduces the lumen of the airways. Affected cats have coughs, wheezing, dyspnoea, and in many cases assume an orthopneic position. The diagnosis can be obtained through routine exams, use of chest x-rays, collection and analysis of bronchoalveolar fluids, and allergen testing. Therapeutic management is based, combined or not, on the use of drugs such as bronchodilators, steroidal anti-inflammatory, mucolytics, antibiotics, inhalational agents and environmental changes in order to reduce exposure to possible allergenic agents responsible for the incitation of the respiratory condition.

Las enfermedades respiratorias son consideradas enfermedades graves y potencialmente dañinas. Entre ellos, el asma y la bronquitis crónica se caracterizan por ser trastornos respiratorios que amenazan constantemente el bienestar de los gatos. Los pacientes presentan cambios en la estructura respiratoria, reversibles o no debido al cuadro inflamatorio extenso, que obstruye el flujo de aire, permite la acumulación de moco y reduce la luz de las vías respiratorias. Los gatos afectados presentan tos, respiración ruidosa, disnea y, en muchos casos, adoptan una posición ortopneica. El diagnóstico se puede obtener mediante exámenes de rutina, uso de radiografías de tórax, recolección y análisis de líquidos broncoalveolares, y pruebas de alérgenos. El manejo terapéutico se basa, combinado o no, en el uso de fármacos como broncodilatadores, antiinflamatorios esteroides, mucolíticos, antibióticos, agentes inhalatorios y cambios ambientales con el objetivo de reducir la exposición a posibles agentes alergénicos responsables de incitar la afección respiratoria.

Response to Various Biologics in Patients with Both Asthma and Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Patients can have features of both chronic obstructive pulmonary disease (COPD) and asthma. However, there is still no consensus how to precisely define this patient population. In addition, there are little data on the effectiveness of biologics in these patients. METHOD: Presence of COPD was defined by a smoking history of ≥10 pack years (PY), a postbronchodilator FEV1/FVC ratio < lower limit of normal (LLN) and FEV1 < 80% predicted, a carbon monoxide diffusion capacity (DLCO) < LLN, and dyspnoea on exertion as a leading symptom. Presence of asthma was defined by high type 2 biomarkers (blood eosinophils ≥300 cells/µL and/or FeNO ≥50 ppb), typical clinical features of asthma (including nocturnal respiratory symptoms), and a documented history of a clinical benefit from inhaled and/or oral glucocorticoid treatment. We analysed data from 20 patients fulfilling the criteria for both COPD and asthma who were newly treated with a biologic due to recurrent exacerbations despite high-dose inhaled triple therapy. RESULTS: Median values before treatment with a biologic were as follows: 40 PY, FEV1 42% predicted, DLCO 45% predicted, 475 eosinophils/µL blood, FeNO 48 ppb. Median duration of biologic treatment (mepolizumab, benralizumab, dupilumab, omalizumab, or tezepelumab) was 12 months. There were significant improvements in exacerbations (most prominent effect), asthma control, and lung function during biologic treatment. CONCLUSIONS: Various types of biologics approved for severe asthma treatment can be effective in patients with both COPD and asthma. We propose an easy-to-use definition of these patients for routine clinical practice.

Epigenomic response to albuterol treatment in asthma-relevant airway epithelial cells.

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 × 10-8). Albuterol predominantly induced a hypomethylation effect on CpGs captured by the EPIC array across the genome (probability of hypomethylation: 76%, p value = 3.3 × 10-5). 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 × 10-14 ≤ p ≤ 6.60 × 10-5). 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.

How can the findings of the EMAX trial on long-acting bronchodilation in chronic obstructive pulmonary disease be applied in the primary care setting?

This review addresses outstanding questions regarding initial pharmacological management of chronic obstructive pulmonary disease (COPD). Optimizing initial treatment improves clinical outcomes in symptomatic patients, including those with low exacerbation risk. Long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) dual therapy improves lung function versus LAMA or LABA monotherapy, although other treatment benefits have been less consistently observed. The benefits of dual bronchodilation in symptomatic patients with COPD at low exacerbation risk, and its duration of efficacy and cost effectiveness in this population, are not yet fully established. Questions remain on the impact of baseline symptom severity, prior treatment, degree of reversibility to bronchodilators, and smoking status on responses to dual bronchodilator treatment. Using evidence from EMAX (NCT03034915), a 6-month trial comparing the LAMA/LABA combination umeclidinium/vilanterol with umeclidinium and salmeterol monotherapy in symptomatic patients with COPD at low exacerbation risk who were inhaled corticosteroid-naïve, we describe how these findings can be applied in primary care.

Management goals and stable phase management of patients with chronic obstructive pulmonary disease in the Japanese respiratory society guideline for the management of chronic obstructive pulmonary disease 2022 (6th edition).

Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction on spirometry and symptoms such as dyspnea on exertion and chronic cough with sputum production, thus making it a significant healthcare issue worldwide. Japanese patients with COPD have unique characteristics compared to patients in Western countries, including older age and lower exacerbation frequency. The Japanese Respiratory Society (JRS) published the 6th edition of the COPD guideline in June 2022. This article introduces the management goals of COPD and describes its management during the stable phase, as outlined in the guideline. Management goals include improving the current status, such as the symptoms, quality of life (QOL), exercise tolerance, and physical activity, and reducing future risks through prevention of exacerbation and suppression of disease progression to prevent shortening of healthy life expectancy. Management plans should include avoidance of causative substances, assessment of disease severity, and personalized treatment plans. Pharmacotherapy using inhalation bronchodilators is a key component of the treatment of stable COPD. Bronchodilators, including short- and long-acting dilators, are commonly used to relieve symptoms and improve QOL. Inhaled corticosteroids (ICSs) are used in combination with long-acting bronchodilators, especially in patients with asthma and COPD overlap, or those experiencing frequent exacerbation of eosinophilia. Combination therapy with a long-acting muscarinic antagonist (LAMA), a long-acting beta 2 agonist (LABA), and ICS is expected to improve QOL and respiratory function and reduce mortality and exacerbation compared to the LAMA + LABA combination. Non-pharmacological therapies, including smoking cessation and pulmonary rehabilitation, should also be considered.

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.

Lung function deficits and bronchodilator responsiveness at 12 years of age in children born very preterm compared with controls born at term.

INTRODUCTION: Very preterm birth is associated with lung function impairment later in life, but several aspects have not been studied. We aimed to comprehensively assess lung function at school age in very preterm infants and term controls, with special emphasis on bronchopulmonary dysplasia (BPD), sex, and bronchodilator response. METHODS: At 12 years of age, 136 children born very preterm (85 with and 51 without BPD) and 56 children born at term performed spirometry, body plethysmography, impulse oscillometry, measurement of diffusion capacity, and multiple breath washout, before and after bronchodilator inhalation. RESULTS: Airway symptoms and a diagnosis of asthma were more common in children born very preterm. These children had more airflow limitation, seen as lower forced expiratory volume in 1 s (FEV1 ) (p < .001), FEV1 /forced vital capacity (FVC) (p = .011), and mean forced expiratory flow between 25% and 75% of FVC (p < .001), and a higher total and peripheral airway resistance compared with term-born controls. There was no difference in total lung capacity but air trapping and lung clearance index were higher in children born very preterm. Diffusion capacity was lower in children born very preterm, especially in those with a diagnosis of BPD. In most other tests, the differences between preterm-born children with or without BPD were smaller than between children born preterm versus at term. Boys born preterm had more lung function deficits than preterm-born girls. In children born very preterm, airway obstruction was to a large extent reversible. CONCLUSION: At 12 years of age, children born very preterm had lower lung function than children born at term in most aspects and there was only little difference between children with or without BPD. Airway obstruction improved markedly after bronchodilator inhalation.

The rs2601796 variant in ADCY9 gene is associated with severe asthma and less bronchodilator response.

Asthma is a respiratory disease caused by the interaction of genetic and environmental factors. The adenylyl cyclase type 9 (ADCY9) enzyme produces the cyclic-adenosinemonophosphate (cAMP), important mediator involved in bronchodilation and immunomodulatory response. The aim of this study was to investigate if rs2601796 and rs2532019 variants in the ADCY9 gene are associated with asthma and lung function. The study comprised 1,052 subjects. Logistic regressions were done using PLINK 1.9 adjusted by sex, age, BMI, smoke and principal components. Bronchodilator responsiveness was assessed using the percentage of difference in FEV1 before and after the bronchodilator use. The in silico analysis for gene expression was performed in the GTEx Portal. The variant rs2601796 (AA/AG genotype) was positively associated with asthma severity (OR: 1.60 IC95%: 1.08-2.39) and with obstruction in individuals with severe asthma (OR: 3.10, IC95%: 1.11-8.62). Individuals with severe asthma and the AA/AG genotype of rs2601796 had less responsiveness to bronchodilators and also a lower expression of ADCY9 in lung and whole blood. The variant rs2532019 (TT/GT genotype) also downregulated the ADCY9 gene expression, but no significant association with the studied phenotypes was found. Thus, the variant in ADCY9 was associated with worse asthma outcomes, including a lower response to bronchodilators, likely due to the impact on its gene expression rate. This variant may be useful in the future to assist in personalized management of patients with asthma.

Efficacy and safety of aclidinium/formoterol versus monotherapies and aclidinium versus placebo in Chinese and other Asian patients with moderate-to-severe COPD: The AVANT Phase 3 study.

AVANT was a Phase 3, 24-week, randomized, parallel-group, double-blind, double-dummy, placebo-controlled study to assess the efficacy and safety of aclidinium/formoterol 400 µg/12 µg combination vs monotherapies and aclidinium vs placebo (1:1:1:1) in Asian patients (∼70% of whom were Chinese) with moderate-to-severe stable chronic obstructive pulmonary disease. Endpoints were analyzed hierarchically to incorporate type I error control. At Week 24, aclidinium/formoterol demonstrated improvements from baseline in 1-h morning post-dose forced expiratory volume in 1 s (FEV1) vs aclidinium (least squares [LS] mean 92 mL; 95% confidence interval [CI] 60, 124 mL; p < 0.001), and in trough FEV1 vs formoterol (LS mean 85 mL; 95% CI 53, 117 mL; p < 0.001). Furthermore, aclidinium provided improvements in trough FEV1 vs placebo (LS mean 134 mL; 95% CI 103, 166 mL; p < 0.001). There was an improvement in transition dyspnea index focal score at Week 24 for aclidinium/formoterol vs placebo (LS mean 0.8; 95% CI 0.2, 1.3; p = 0.005) but not for aclidinium vs placebo (LS mean 0.4; 95% CI -0.1, 1.0; p = 0.132). Improvements in St George's Respiratory Questionnaire total scores occurred for aclidinium/formoterol vs placebo (LS mean -4.0; 95% CI -6.7, -1.4; p = 0.003) and aclidinium vs placebo (LS mean -2.9; 95% CI -5.5, -0.3; p = 0.031). Aclidinium/formoterol and aclidinium were well tolerated and safety findings were consistent with known profiles; rates of treatment-emergent adverse events (AEs) (aclidinium/formoterol: 54.8%; aclidinium: 47.4%; placebo: 53.9%), serious AEs (7.2, 7.9, and 7.8%, respectively), and AEs leading to discontinuation of study medication (2.3, 1.5, and 2.2%, respectively) were similar between groups.