Long-acting Bronchodilators Research Articles

New Perspectives on Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide; many recent advances have been made in many aspects of the disease. The aim of this article is to illustrate and discuss some of these advances in the management of different types of patients. Large-scale trials have confirmed that long-acting bronchodilator therapy, particularly using the combination of LABA/LAMA, remains the mainstay of COPD treatment, with special attention being paid to careful selection of inhaler devices. The initial choice of pharmacological therapy is based on the GOLD ABCD grouping of patients. It is very important to stress that there is a need to implement a management cycle because COPD is a chronic disease with varying clinical course and a high number of potential comorbidities that may affect morbidity and mortality. Therefore, regular reevaluation of the patient is mandatory. This allows identification of characteristics aimed at maximizing the benefits for a specific patient or a subset of patients. Within this context, the role of the blood eosinophil count as a marker of inhaled corticosteroids response to prevent future exacerbations in patients who, despite appropriate bronchodilator therapy, still suffer from them has been proven to be a useful simple biomarker in medication selection. These advances support the concept of precision medicine, with the goal that patients get the right medicine at the right time for the right reason. Finally, recent studies have shown that early life events may be of critical relevance for the development of COPD. With this as a background, concepts to identify individuals at risk and early identification of cases have become an important objective of current research with the hope of maximizing the effects of therapy and the possibility of impacting disease progression.

Prescription Pathways from Initial Medication Use to Triple Therapy in Older COPD Patients: A Real-World Population Study

Background and objective Triple therapy with an inhaled corticosteroid (ICS), a long-acting β2-agonist bronchodilator (LABA) and a long-acting muscarinic antagonist (LAMA) is recommended as step-up therapy for chronic obstructive pulmonary disease (COPD) patients who continue to have persistent symptoms and increased risk of exacerbation despite treatment with dual therapy. We sought to evaluate different treatment pathways through which COPD patients were escalated to triple therapy. Methods We used population health databases from Ontario, Canada to identify individuals aged 66 or older with COPD who started triple therapy between 2014 and 2017. Median time from diagnosis to triple therapy was estimated using the Kaplan-Meier method. We classified treatment pathways based on treatments received prior to triple therapy and evaluated whether pathways differed by exacerbation history, blood eosinophil counts or time period. Results Among 4108 COPD patients initiating triple therapy, only 41.2% had a COPD exacerbation in the year prior. The three most common pathways were triple therapy as initial treatment (32.5%), LAMA to triple therapy (29.8%), and ICS + LABA to triple therapy (15.4%). Median time from diagnosis to triple therapy was 362 days (95% confidence interval:331–393 days) overall, but 14 days (95% CI 12–17 days) in the triple therapy as initial treatment pathway. This pathway was least likely to contain patients with frequent or severe exacerbations (22.0% vs. 31.5%, p < 0.001) or with blood eosinophil counts ≥300 cells/µL (18.9% vs. 22.0%, p < 0.001). Conclusion Real-world prescription of triple therapy often does not follow COPD guidelines in terms of disease severity and prior treatments attempted.

Optimization of Long-Acting Bronchodilator Dose Ratios Using Isolated Guinea Pig Tracheal Rings for Synergistic Combination Therapy in Asthma and COPD

The co-administration of a long-acting β2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA), has been shown to be beneficial in the management of non-communicable chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). The resulting relaxation of the airways can be synergistically enhanced, reducing symptoms and optimizing lung function. This provides an insight into more effective treatments. In this study, the LABAs formoterol fumarate dihydrate (FOR) and indacaterol maleate (IND) were each associated with tiotropium bromide monohydrate (TIO) to assess their synergistic potential. This was done using an appropriate ex vivo model of isolated perfused guinea pig tracheal rings, and pharmacological models of drug interaction. Among the dose ratios studied for both types of combination, a higher synergistic potential was highlighted for FOR/TIO 2:1 (w/w). This was done through three steps by using multiple additions of drugs to the organ baths based on a non-constant dose ratio and then on a constant dose ratio, and by a single addition to the organ baths of specific amounts of drugs. In this way, the synergistic improvement of the relaxant effect on the airways was confirmed, providing a basis for improving therapeutic approaches in asthma and COPD. The synergy found at this dose ratio should now be confirmed on a preclinical model of asthma and COPD by assessing lung function.

A descriptive cohort study of withdrawal from inhaled corticosteroids in COPD patients

Inhaled corticosteroid (ICS) therapy is widely prescribed without a history of exacerbations and consensus guidelines suggest withdrawal of ICS in these patients would reduce the risk of side effects and promote cost-effective prescribing. The study describes the prescribing behaviour in the United Kingdom (UK) in relation to ICS withdrawal and identifies clinical outcomes following withdrawal using primary and secondary care electronic health records between January 2012 and December 2017. Patients with a history ≥12 months’ exposure who withdrew ICS for ≥6 months were identified into two cohorts; those prescribed a long-acting bronchodilator maintenance therapy and those that were not prescribed any maintenance therapy. The duration of withdrawal, predictors of restarting ICS, and clinical outcomes were compared between both patient cohorts. Among 76,808 patients that had ≥1 prescription of ICS in the study period, 11,093 patients (14%) withdrew ICS therapy at least once during the study period. The median time without ICS was 9 months (IQR 7–14), with the majority (71%) receiving subsequent ICS prescriptions after withdrawal. Patients receiving maintenance therapy with a COPD review at withdrawal were 28% less likely to restart ICS (HR: 0.72, 95% CI 0.61, 0.85). Overall, 69% and 89% of patients that withdrew ICS had no recorded exacerbation event or COPD hospitalisation, respectively, during the withdrawal. This study provides evidence that most patients withdrawing from ICS do not experience COPD exacerbations and withdrawal success can be achieved by carefully planning routine COPD reviews whilst optimising the use of available maintenance therapies.

Impact of asthma control on quality of life in an outpatient setting in Brazil

Introduction The goal of asthma therapy is asthma control. As a chronic disease, asthma may cause considerable physical, emotional and social restrictions impacting quality of life. The aim of this study was to analyze control of asthma symptoms in an outpatient setting in Brazil and its impact on quality of life. Methods A pilot cross-sectional study was performed in two public centers in the metropolitan region of São Paulo, Brazil. Control of asthma symptoms was assessed according to GINA guidelines, and quality of life was analyzed by the Mini Quality of Life Questionnaire (mini-AQLQ). Results A total of 47 adult patients with asthma were analyzed. Asthma was controlled in 8 patients (17.0%), partially controlled in 26 patients (55.3%) and uncontrolled in 13 patients (27.7%). Patients with controlled asthma showed better mini-AQLQ scores (4.99 ± 1.10) as compared to those with partly controlled (3.66 ± 1.10) and uncontrolled asthma (2.59 ± 0.64; p < 0.001 for both). Most patients (85.1%) were taking inhaled corticosteroids (ICS) and long-acting bronchodilators (LABA) as controller treatment. Conclusions Better asthma control had a positive impact on Health-Related Quality of Life (HRQoL) contributing to a better disease management. Few patients reached full asthma control in our specialty ambulatory center, suggesting further initiatives are required to improve the quality of asthma care in Brazil.

Molecular Clustering Analysis of Blood Biomarkers in World Trade Center Exposed Community Members with Persistent Lower Respiratory Symptoms.

The destruction of the World Trade Center (WTC) on September 11, 2001 (9/11) released large amounts of toxic dusts and fumes into the air that exposed many community members who lived and/or worked in the local area. Many community members, defined as WTC survivors by the federal government, developed lower respiratory symptoms (LRS). We previously reported the persistence of these symptoms in patients with normal spirometry despite treatment with inhaled corticosteroids and/or long-acting bronchodilators. This report expands upon our study of this group with the goal to identify molecular markers associated with exposure and heterogeneity in WTC survivors with LRS using a selected plasma biomarker approach. Samples from WTC survivors with LRS (n = 73, WTCS) and samples from healthy control participants of the NYU Bellevue Asthma Registry (NYUBAR, n = 55) were compared. WTCS provided information regarding WTC dust exposure intensity. Hierarchical clustering of the linear biomarker data identified two clusters within WTCS and two clusters within NYUBAR controls. Comparison of the WTCS clusters showed that one cluster had significantly increased levels of circulating matrix metalloproteinases (MMP1, 2, 3, 8, 12, 13), soluble inflammatory receptors (receptor for advanced glycation end-products-RAGE, Interleukin-1 receptor antagonist (IL-1RA), suppression of tumorigenicity (ST)2, triggering receptor expressed on myeloid cells (TREM)1, IL-6Ra, tumor necrosis factor (TNF)RI, TNFRII), and chemokines (IL-8, CC chemokine ligand- CCL17). Furthermore, this WTCS cluster was associated with WTC exposure variables, ash at work, and the participant category workers; but not with the exposure variable WTC dust cloud at 9/11. A comparison of WTC exposure categorial variables identified that chemokines (CCL17, CCL11), circulating receptors (RAGE, TREM1), MMPs (MMP3, MMP12), and vascular markers (Angiogenin, vascular cell adhesion molecule-VCAM1) significantly increased in the more exposed groups. Circulating biomarkers of remodeling and inflammation identified clusters within WTCS and were associated with WTC exposure.

Characteristics of Patients with Chronic Obstructive Pulmonary Disease Treated with Long-Acting Bronchodilators in a Real-World Setting in Singapore: A Single-Center Observational Study.

IntroductionThere is limited real-world evidence regarding clinical practice for chronic obstructive pulmonary disease (COPD) in Singapore. We compared baseline clinical characteristics and evaluated outcomes in patients with COPD who initiated treatment with either a long-acting muscarinic antagonist (LAMA) or a LAMA and a long-acting β2-agonist (LAMA+LABA).MethodsThis was a single-center observational study at Changi General Hospital, Singapore. Routine clinical data (hospital visits, case management, lung function, laboratory/imaging results, medication orders) were collected and compiled into a data warehouse. Eligible patients with COPD were ≥40 years old and newly prescribed LAMA or LAMA+LABA during the enrollment period. Patient characteristics in the baseline period (6 months) were compared between treatments. Clinical worsening was measured as a composite endpoint, defined as the first of a change in maintenance treatment class or a moderate-to-severe exacerbation during follow-up (12 months).ResultsIn total, 261 patients were included in the baseline period (LAMA: 73; LAMA+LABA: 188). In the baseline period, patients receiving LAMA+LABA versus LAMA had significantly lower body mass index, higher COPD Assessment Test score and worse lung function, and numerically higher exacerbation history. Prevalence of comorbidities was similar between treatment groups. In follow-up, high rates of clinical worsening were observed regardless of treatment regimen (LAMA: 38/73 [52%]; LAMA+LABA: 86/188 [46%]). Median time-to-clinical worsening was 340 days for the LAMA cohort and the raw median 154 days (interquartile range: 44–225) for the LAMA+LABA cohort. Median medication dispensation rate (0.86; interquartile range: 0.56–1.00) was similar between treatments.ConclusionPatients initiating treatment with LAMA+LABA had more severe COPD than patients prescribed LAMA. The proportion of patients experiencing clinical worsening was similarly high in both cohorts, suggesting that early identification and treatment optimization are necessary.

Fernand Widal Syndrome: About 16 Cases (Moroccan Series)

Fernand Widal syndrome is a condition with an often severe triad of asthma, intolerance to acetylsalicylic acid and nasosinus polyposis. Aim of the work: to determine the clinical peculiarities of the patients carrying this syndrome in our context.Patients and methods: we carried out a retrospective study carried out over a period of five years at the service of respiratory diseases of the University Hospital of Casablanca, collecting 16 cases of patients carrying this triad. Result: The average age was 44.2 years, with a female predominance (75% of cases). All patients had atopy, mainly rhinitis and conjunctivitis. In 62.5% of the cases, asthma was moderate to severe with moderate to severe obstructive airways in 60% of cases. Five patients had a history of hospitalization for severe exacerbation of asthma in one medical facility and four others in intensive care unit with intubation in three patients. All patients were on inhaled corticosteroids and long-acting bronchodilators using antileukotrienes. Despite optimal medical treatment and polyp surgery in patients with locally resistant rhinitis, 38% of rhinitis cases and 56.6% of severe asthma cases were poorly controlled. In conclusion, patients with SFW have difficult-to-control asthma and rhinitis under optimal medical treatment, sometimes requiring desensitization with aspirin and the emergence of new therapies.

Features and significance of the early bronchodilatation effect of the first dose of a long-acting bronchodilator alone and in fixed combination in the treatment of chronic obstructive pulmonary disease

The early bronchodilatory effects of the first dose of long-acting anticholinergics (glycopyrronium and tiotropium) were compared with those of a fixed double combination of long-acting bronchodilators of various classes (indacaterol/glycopyrronium) in patients with stable chronic obstructive pulmonary disease. The possibility of using the results of an early bronchodilatory response to predict their effectiveness in the basic therapy of chronic obstructive pulmonary disease is evaluated. A total of 176 patients with chronic obstructive pulmonary disease were examined. The patients were randomized into three groups. The first group (n = 66) took glycopyrronium, the second group (n = 60) received a combination of indacaterol/glycopyrronium, and the third group (n = 50, control) took tiotropium. Broncholytic tests with the listed drugs were evaluated. The early bronchodilatory effect of the first dose of 110/50 mcg indacaterol/glycopyrronium was manifested by significant bronchodilation (p 0.001) from 30 min, reached its maximum value 60 min after drug intake, and persisted after a 28-day course of treatment. The combination of indacaterol/glycopyrronium provided rapid and prolonged bronchodilation in patients with stable chronic obstructive pulmonary disease, demonstrating advantages over the isolated use of glycopyrronium and tiotropium. Maximization of bronchodilation by the sequential use of glycopyrronium and salbutamol leads to an increase in the volume of forced exhalation in the first second on the 90th min, comparable with the results of indacaterol/glycopyrronium on the 60th min after drug intake, which indicates the clinical feasibility of maximizing bronchodilation with drugs both separately and in combination. Based on a direct positive correlation between the initial value of the forced expiratory volume in the first second and the value on day 28 of indacaterol/glycopyrronium therapy, an equation for predicting the individual effectiveness of the drug during treatment is derived.

The Impact of an Electronic Health Record Intervention on Spirometry Completion in Patients with Chronic Obstructive Pulmonary Disease

Spirometry is necessary to diagnose chronic obstructive pulmonary disease (COPD), yet a large proportion of patients are diagnosed and treated without having received testing. This study explored whether the effects of interventions using the electronic health record (EHR) to target patients diagnosed with COPD without confirmatory spirometry impacted the incidence rates of spirometry referrals and completions. This retrospective before and after study assessed the impact of provider-facing clinical decision support that identified patients who had a diagnosis of COPD but had not received spirometry. Spirometry referrals, completions, and results were ascertained 1.5 years prior to and 1.5 years after the interventions were initiated. Inhaler prescriptions by class were also tallied. There were 10,949 unique patients with a diagnosis of COPD who were eligible for inclusion. 4,895 patients (44.7%) were excluded because they had completed spirometry prior to the cohort start dates. The pre-intervention cohort consisted of 2,622 patients, while the post-intervention cohort had 3,392. Spirometry referral rates pre-intervention were 20.2% compared to 31.6% post-intervention (p < 0.001). Spirometry completion rates rose from 13.2% pre-intervention to 19.3% afterwards (p < 0.001). 61.7% (585 of 948) had no evidence of airflow obstruction. After excluding patients with a diagnosis of asthma, 25.8% (126 of 488) patients who had no evidence of airflow obstruction had prescriptions for long-acting bronchodilators or inhaled steroids. A concerted EHR intervention modestly increased spirometry referral and completion rates in patients with a diagnosis of COPD without prior spirometry and decreased misclassification of disease.

Duplicate Prescription Rates of Long-Acting Bronchodilator Inhalers.

Background: Long-acting bronchodilator inhalers are widely used with or without inhaled corticosteroids (ICs) by patients with lung diseases. In Israel alone, there are 21 inhalers containing long-acting β2 agonists (LABAs) and/or long-acting muscarinic antagonists (LAMAs). Some patients are treated incorrectly with several inhalers of the same pharmacologic group. Methods: Electronic data of LABA and/or LAMA inhalers purchased during a period of 1 year were extracted in one district of Clalit Health Services in Israel. Patients who were treated with two or more inhalers from the same pharmacologic group were compared with patients without duplicate treatment. Inhaler purchases during the 12 months before and after the first duplicate purchase were compared with the purchases by patients without duplication of treatment. New diagnoses were compared to identify possible side effects. Results: Of the 13,528 patients who were treated with LABA and/or LAMA inhalers, 244 (1.8%) purchased at least two different inhalers from the same pharmacologic group. Inhaler purchases were 3.8 times higher in the duplication group during the 12 months before the first duplication. Inhaler purchase increased by 28% in the duplication group compared with a 4.5% increase in the nonduplication group (p < 0.001) during the following year. The risk for duplicated consumption was significantly higher in patients with a chronic obstructive pulmonary disease (COPD) diagnosis, males, and persons aged between 61 and 80 years. Conclusions: Nearly 2% of the patients treated with long-acting bronchodilators consumed different medications of the same pharmacologic group even when adherence was satisfactory. COPD patients are at higher risk for inhaler duplication. Clinical Trial Registration Number: 0151-20-COM1.

New insights into the optimal management of COPD: extracts from CHEST 2021 annual meeting (October 17–20, 2021)

ABSTRACT Introduction Discordance between real-world prescribing patterns and global treatment guidelines for the treatment of chronic obstructive pulmonary disease (COPD) with inhaled single or dual long-acting bronchodilator maintenance therapy is increasingly being reported in the literature, particularly with regard to addition of inhaled corticosteroids (ICS). Patient-related factors, e.g. inhalation technique and inspiratory flow, are key to disease control in COPD. Treatment discordance and patient-related factors can lead to high-cost side effects and sub-optimal treatment benefit; furthermore, the COVID-19 pandemic has led to new challenges in COPD management. Areas Covered This article summarizes a series of presentations sponsored by Boehringer Ingelheim and delivered at the annual CHEST congress 2021 (October 17–20, 2021) that explored new insights into the optimal management of COPD. Expert Opinion/Commentary There is a concerning high degree of discordance with GOLD recommendations. Dual therapy without addition of ICS does not increase exacerbation risk and could reduce pneumonia risk, and unnecessary prescription of triple therapy has financial implications. Clinic-based spirometry may not reflect the home setting, and training is required; inhalers that operate independently of users’ inhalation profiles should be considered. Integration of digital healthcare solutions into clinical studies is suggested in the post-COVID setting, although further evaluation is required.

ОТДЕЛЬНЫЕ АСПЕКТЫ ЛЕЧЕНИЯ ПАЦИЕНТОВ С ВПЕРВЫЕ ВЫЯВЛЕННЫМ ТУБЕРКУЛЕЗОМ ЛЕГКИХ С МНОЖЕСТВЕННОЙ ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТЬЮ В СОЧЕТАНИИ И ХРОНИЧЕСКОЙ ОБСТРУКТИВНОЙ БОЛЕЗНЬЮ ЛЕГКИХ: В ФОКУСЕ ИНГАЛЯЦИОННЫЕ ГЛЮКОКОРТИКОСТЕРОИДЫ

Introduction. The problem of treating tuberculosis (TB) remains relevant, due to the growth of drug-resistant forms of mycobacterium tuberculosis and an increase in the incidence of TB in persons with comorbid bronchopulmonary pathology, which requires comprehensive management of this category of patients, with mandatory drug correction of concomitant pathology. Aim. The aim of this study was to assess the effect of inhaled glucocorticosteroids (budesonide / formoterol 160 / 4.5 in an Inhaler device) on the efficacy of TB therapy in patients with newly diagnosed multidrug-resistant tuberculosis (MDR) who developed in the presence of chronic obstructive pulmonary disease (COPD). Material and methods. A simple, prospective, comparative study in accordance with the inclusion criteria included 40 patients admitted to an anti-tuberculosis dispensary with newly diagnosed MDR tuberculosis with COPD. The diagnosis of TB and COPD was confirmed using radiographic, functional and laboratory research methods. Group 1, age Me (25; 75) 55.5 (46; 58) years - 22 patients with MDR + COPD tuberculosis who, simultaneously with TB chemotherapy, received a short-acting M-anticholinergic blocker, 2 inhalations 4 times a day, group 2, age 54.5 (51; 58) years - 18 patients with MDR + COPD tuberculosis, simultaneously with TB chemotherapy received a combination of ICS with a long-acting bronchodilator (beta-2-agonist (LABA)), budesonide + formoterol 160 / 4.5 μg dose - 2 inhalations 2 times a day (in an inhaler device). Duration of observation is 9 months. Results and discussion. After 9 months of observation, closure of decay cavities in 63.6% in group 1 and 83.3% in group 2 (χ² = 0.3; p = 0.581), smear negativity in 90.9% of cases in group 1 and in 100, 0% in group 2, respectively (χ² = 0.04 p = 0.834), abacillated 63.3% and 100.0% in groups 1 and 2, respectively (χ² = 0.46; p = 0.496). Against the background of the use of ICS in the intensive phase of TB chemotherapy simultaneously with antibiotic therapy, there was a decrease in the time of abacillation and closure of decay cavities in comparison with the group that did not receive ICS. At the same time in broncholics, the use of ICS made it possible to quickly stop the broncho-obstructive syndrome, improve the quality of life and compliance with long-term anti-tuberculosis therapy. An additional nonspecific anti-inflammatory effect of ICS promoted the active resorption of infiltrative changes and the cure of a specific process, reducing the duration of the main course of treatment, including in patients with MDR. Conclusion. Patients of the anti-tuberculosis dispensary with concomitant bronchopulmonary pathology need complex treatment aimed at correcting comorbid conditions, simultaneously with chemotherapy for tuberculosis. The use of ICS in addition to long-acting bronchodilators (LABA, LDAH) in patients with COPD for the correction of broncho-obstructive syndrome in the intensive phase of TB treatment can reduce the time of smear negativity, abacillation and closure of decay cavities.

Establishing Quality of Life in Southern Taiwan COPD Patients Using Long-Acting Bronchodilator.

BackgroundTo assess the health-related quality of life (HRQoL) of Taiwan patients with different stages of chronic obstructive pulmonary disease (COPD) and using different combination therapies and to explore the factors affecting HRQoL in these patients.MethodsThis cross-sectional study included outpatient participants aged 35 years old and older who were receiving long-acting bronchodilator treatment in one of two hospitals in Southern Taiwan. Participants were categorized according to their Global Initiative for Obstructive Lung Disease (GOLD) classification as either their COPD group, based on symptoms and exacerbation risk, or their COPD stage, based on spirometry results. Patients’ HRQoL was assessed using the St. George’s Respiratory Questionnaire score (SGRQ), World Health Organization Quality of Life Quality of Life-BREF (WHOQOL-BREF), and EQ-5D-5L. The total scores of the SGRQ, WHOQOL-BREF, EQ-5D utility index, and EQ-VAS were presented as mean ± standard deviation (SD) among different combination treatments. Univariate and multivariate analyses were used to explore the association of patients’ baseline characteristics and environmental factors with HRQoL.ResultsA total of 218 patients were enrolled in the study. The distribution of patients using GOLD group classification were as follows: 73.39% in group A, 20.19% group B, 1.83% group C and 4.59% group D. Triple therapy patients mostly showed a lower quality of life than other combination therapies, regardless of the GOLD classification system. However, only the SGRQ scores of GOLD groups A and B were significantly different when using different drug combinations (p-value = 0.0072 and 0.0430, respectively). The COPD assessment test (CAT) score, a questionnaire to assess impact of COPD on health status, was found to be associated with all the questionnaires.ConclusionThe HRQoL is impaired in patients with COPD, and it deteriorates with an increase of severity. The CAT was the strongest predictor of HRQoL.

New Versus Old: The Impact of Changing Patterns of Inhaled Corticosteroid Prescribing and Dosing Regimens in Asthma Management.

Inhaled corticosteroid (ICS)-containing therapies are the mainstay of pharmacological management of asthma. They can be administered alone or in combination with a long-acting bronchodilator, depending on asthma severity, and may also be supplemented with short-acting bronchodilators for as-needed rescue medication. Adherence to asthma therapies is generally poor and characterized by underuse of ICS therapies and over-reliance on short-acting bronchodilators, which leads to poor clinical outcomes. This article reviews efficacy versus systemic activity profiles for various dosing regimens of budesonide (BUD) and fluticasone propionate (FP). We performed a structured literature review of BUD and FP regular daily dosing, and BUD/formoterol (FOR) as-needed dosing, to explore the relationship between various dosing patterns of ICS regimens and the risk–benefit profile in terms of the extent of bronchoprotection and cortisol suppression. In addition, we explored how adherence could potentially affect the risk–benefit profile, in patients with mild, moderate, and moderate-to-severe asthma. With a specific focus on BUD or FP-containing treatments, we found that regular daily ICS and ICS/long-acting β2-agonist (LABA) dosing had a greater degree of bronchoprotection than as-needed BUD/FOR dosing or BUD/FOR maintenance and reliever therapy (MART) dosing, and still maintained low systemic activity. We also found that the benefits of regular daily ICS dosing regimens were diminished when adherence was low (50%); the shorter duration of bronchoprotection observed was similar to that seen with typical as-needed BUD/FOR usage. These findings have implications for aiding clinicians with selecting the most suitable treatment option for asthma management, and subsequent implications for the advice clinicians give their patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02092-7.

Differential Outcomes Following 4 Weeks of Aclidinium/Formoterol in Patients with COPD: A Reanalysis of the ACTIVATE Study

RationaleIt is difficult to predict the effects of long-acting bronchodilators (LABD) on lung function, exercise capacity and physical activity in patients with chronic obstructive pulmonary disease (COPD). Therefore, the multidimensional response to LABD was profiled in COPD patients participating in the ACTIVATE study and randomized to LABD.MethodsIn the ACTIVATE study, patients were randomized to aclidinium bromide/formoterol fumarate (AB/FF) or placebo for four weeks. The primary outcomes included (1) lung function as measured by functional residual capacity (FRC), residual volume (RV), and spirometric outcomes; (2) exercise performance as measured by a constant work rate cycle ergometry test (CWRT); and (3) physical activity (PA) using an activity monitor. Self-organizing maps (SOMs) were used to create an ordered representation of the patients who were randomly assigned to four weeks of AB/FF and cluster them into different outcome groups.ResultsA total of 250 patients were randomized to AB/FF (n = 126) or placebo (n = 124). Patients in the AB/FF group (39.6% women) had moderate-to-severe COPD, static hyperinflation (FRC: 151.4 (27.7)% predicted) and preserved exercise capacity. Six clusters with differential outcomes were identified. Patients in clusters 1 and 2 had significant improvements in lung function compared to the remaining AB/FF-treated patients. Patients in clusters 1 and 3 had significant improvements in CWRT time, and patients in clusters 2, 3 and 6 had significant improvements in PA compared to the remaining AB/FF-treated patients.ConclusionIndividual responses to 4 weeks of AB/FF-treatment in COPD are differential and the degree of change differs across domains of lung function, exercise capacity and PA. These results indicate that clinical response to LABD therapy is difficult to predict and is non-linear, and show doctors that it is important to look at multiple outcomes simultaneously when evaluating the clinical response to LABD therapy.Clinical Trial RegistrationThe original ACTIVATE study was registered on ClinicalTrials.gov, registration number NCT02424344.

Concordance between reported medication taking behavior and prescription instructions for patients with chronic obstructive pulmonary disease visiting community pharmacies

BackgroundUnderstanding types and frequency of medication taking discrepancies could help design pharmacist interventions to improve adherence, outcomes, and prescribing. ObjectiveThis study aimed to assess concordance between participants' descriptions of chronic obstructive pulmonary disease (COPD) medication taking behaviors and prescription instructions. MethodsContinued analysis of previously collected data. Dispensing data from 35 community pharmacies identified participants at the age of ≥ 40 years, with ≥ 1 COPD maintenance medication in the past year and self-reported COPD. Participants completed a survey of demographics, corticosteroid/antibiotic drug use, and symptom scores. Participants listed each medication and described medication taking behavior. COPD severity was classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) ABCD categories from exacerbation history and symptoms. Aggregate proportion days covered (PDC) for any 1 maintenance medicine was calculated using 12-month dispensing data. Discrepancies between medication taking and instructions were classified: (1) overuse, (2) underuse, or (3) discontinued by participant (without prescriber knowledge). Descriptive statistics summarized survey results. Chi-square compared discrepancies among long-acting bronchodilators (LABDs), inhaled corticosteroids (ICS), and short-acting bronchodilators (SABDs). ResultsMost participants (N = 709; 27.6% urban, 70.5% rural) were highly symptomatic (GOLD groups B/D = 89.9%) and high risk (groups C/D = 59.2%). Median medication number was 4. Concordance of ICS and LABD taking behavior with prescriber instructions was 80.6% and 81.8%, respectively (P > 0.05). PDC averaged 0.46 ± 0.37; only 28.7% were adherent (i.e., PDC ≥ 0.80). ICS underuse (11.8%) exceeded LABD (5.5%). LABD discontinuation (7.4%) exceeded ICS (2.7%) or SABD (0.6%). SABD overuse (9.3%) exceeded ICS (3.4%) or LABD (4.3%) (P < 0.5 all comparisons). ConclusionAlthough most were highly symptomatic, high risk, and frequently described correct medication taking behavior, overall adherence was very low. Discrepancies included overuse, underuse, and self-discontinuation. Nonadherence and medication taking discrepancies may increase symptoms, exacerbations, and additional medication prescribing. Potential pharmacist strategies include regularly assessing adherence and differentiating intentional versus nonintentional nonadherence to identify and implement patient-specific interventions to encourage medication taking as prescribed.

Explainable Machine Learning Model for Predicting First-Time Acute Exacerbation in Patients with Chronic Obstructive Pulmonary Disease.

Background: The study developed accurate explainable machine learning (ML) models for predicting first-time acute exacerbation of chronic obstructive pulmonary disease (COPD, AECOPD) at an individual level. Methods: We conducted a retrospective case–control study. A total of 606 patients with COPD were screened for eligibility using registry data from the COPD Pay-for-Performance Program (COPD P4P program) database at Changhua Christian Hospital between January 2017 and December 2019. Recursive feature elimination technology was used to select the optimal subset of features for predicting the occurrence of AECOPD. We developed four ML models to predict first-time AECOPD, and the highest-performing model was applied. Finally, an explainable approach based on ML and the SHapley Additive exPlanations (SHAP) and a local explanation method were used to evaluate the risk of AECOPD and to generate individual explanations of the model’s decisions. Results: The gradient boosting machine (GBM) and support vector machine (SVM) models exhibited superior discrimination ability (area under curve [AUC] = 0.833 [95% confidence interval (CI) 0.745–0.921] and AUC = 0.836 [95% CI 0.757–0.915], respectively). The decision curve analysis indicated that the GBM model exhibited a higher net benefit in distinguishing patients at high risk for AECOPD when the threshold probability was <0.55. The COPD Assessment Test (CAT) and the symptom of wheezing were the two most important features and exhibited the highest SHAP values, followed by monocyte count and white blood cell (WBC) count, coughing, red blood cell (RBC) count, breathing rate, oral long-acting bronchodilator use, chronic pulmonary disease (CPD), systolic blood pressure (SBP), and others. Higher CAT score; monocyte, WBC, and RBC counts; BMI; diastolic blood pressure (DBP); neutrophil-to-lymphocyte ratio; and eosinophil and lymphocyte counts were associated with AECOPD. The presence of symptoms (wheezing, dyspnea, coughing), chronic disease (CPD, congestive heart failure [CHF], sleep disorders, and pneumonia), and use of COPD medications (triple-therapy long-acting bronchodilators, short-acting bronchodilators, oral long-acting bronchodilators, and antibiotics) were also positively associated with AECOPD. A high breathing rate, heart rate, or systolic blood pressure and methylxanthine use were negatively correlated with AECOPD. Conclusions: The ML model was able to accurately assess the risk of AECOPD. The ML model combined with SHAP and the local explanation method were able to provide interpretable and visual explanations of individualized risk predictions, which may assist clinical physicians in understanding the effects of key features in the model and the model’s decision-making process.

Comparative efficacy of interferential therapy, bronchodilators, and body positioning on asthma control and quality of life of patients with bronchial asthma: A study protocol

Interferential Therapy (IFT) is the application of two medium frequency currents to the skin to stimulate and activate different systems in the body using specific frequencies and frequency ranges. The aim in applying IFT is to reduce myalgia in the chest and upper back, reduce muscular fatigue, and induce mucus expectoration. This study is designed to test the efficacy of IFT in reducing the symptoms frequently experienced by patients with bronchial asthma. Forty-eight (48) patients aged 18 and above with bronchial asthma attending the respiratory clinic at the Lagos State University Teaching Hospital, Ikeja (LASUTH) will be assessed for eligibility. The study design will be a double-blinded, randomized control trial with four intervention groups and four parallel placebo control groups. IFT will be administered as an intervention to patients on short and longacting bronchodilators in an assigned fundamental body position for 20 minutes. Six continuous outcome variables at different points will be utilized as outcome measures. A baseline Pulmonary Function Test (PFT) will be conducted on entry into the study while quality of life and asthma control will be evaluated every two (2) weeks during the study. Data obtained will be analyzed using descriptive and inferential statistics of repeated ANOVA; P&lt;0.05. The study outcome will compare the efficacy of IFT on bronchial asthma, identify its effect in different body positions, and compare the relationship between its application and the bronchodilator medication frequently used by the patients.

First Maintenance Therapy for Chronic Obstructive Pulmonary Disease: Retrospective Analyses of US and UK Healthcare Databases.

IntroductionInhaled corticosteroids (ICS) are often prescribed inappropriately alongside long-acting bronchodilators for chronic obstructive pulmonary disease (COPD). We aimed to investigate if prescribing habits in the US and UK differ from recommendations for initiation of COPD maintenance therapy.MethodsWe used healthcare data from the US IBM® MarketScan® and UK Clinical Practice Research Datalink databases to assess exacerbations and comorbidities in patients with COPD initiating first maintenance therapy (1MT) between 2015 and 2018. Patients with a recorded asthma diagnosis prior to initiation of 1MT were excluded. We evaluated time from recorded diagnosis of COPD until initiation of 1MT, and treatment regimen at 1MT (long-acting muscarinic antagonist [LAMA], long-acting β2-agonist [LABA], ICS, as monotherapy or in combination).ResultsIn the US and UK, median (IQR) time between recorded COPD diagnosis and 1MT was 158 (12; 839) and 29 (1; 521) days, respectively. Among the 53,473 US patients and 8786 UK patients who initiated 1MT, 50.9% and 32.4% had ≥ 1 exacerbation in the previous year. In the US, 20% of patients initiated LAMA, 1% LABA, 13% LAMA/LABA, and 66% an ICS-containing regimen (49% LABA/ICS, 13% ICS, and 4% LAMA/LABA/ICS). In the UK, 53% of patients initiated LAMA, 4% LABA, 16% LAMA/LABA, and 27% an ICS-containing regimen (14% LABA/ICS, 9% ICS, and 4% LAMA/LABA/ICS).ConclusionsAt 1MT, two-thirds of patients in the US received ICS-containing therapies, with almost half on LABA/ICS. In contrast, less than one-third received ICS-containing therapy in the UK and more than half of patients received LAMA. In both countries, more patients received ICS-containing therapies at initiation of 1MT than would be expected based on their exacerbation history, suggesting overprescribing.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41030-021-00179-0.