Understanding the Gaps in the Reporting of COPD Exacerbations by Patients: A Review.

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with loss of lung function, poor quality of life, loss of exercise capacity, risk of serious cardiovascular events, hospitalization, and death. However, patients underreport exacerbations, and evidence suggests that unreported exacerbations have similar negative health implications for patients as those that are reported. Whilst there is guidance for physicians to identify patients who are at risk of exacerbations, they do not help patients recognise and report them. Newly developed tools, such as the COPD Exacerbation Recognition Tool (CERT) have been designed to achieve this objective. This review focuses on the underreporting of COPD exacerbations by patients, the factors associated with this, the consequences of underreporting, and potential solutions.

Consensus on mild asthma management: results of a modified Delphi study.

OBJECTIVE: In order to understand the role of regular controller inhaled corticosteroids (ICS) versus as-needed ICS-formoterol in managing mild asthma, we performed a modified Delphi procedure. METHODS: Opinions from 16 respiratory experts to three surveys and during a virtual scientific workshop helped to develop final consensus statements (pre-defined as 70% agreement). RESULTS: Thirteen participants completed all rounds (response rate 81%). At the end of the procedure, there was final consensus on: regular daily ICS being the recommended treatment approach in mild persistent asthma, with better symptom control and robust long-term clinical data compared with as-needed ICS-formoterol (85%); to avoid noncompliance, frequently seen in mild asthma patients, regular ICS dosing should be accompanied by ongoing education on treatment adherence (100%); treatment aims should be targeting asthma control (92%) and reduction of exacerbation risk (85%). No consensus was reached on whether GINA or national guidelines most influence prescribing decisions. CONCLUSIONS: It is important to encourage patients to be adherent and to target both asthma control and exacerbation risk reduction. There is robust clinical evidence to support proactive regular dosing with ICS controller therapy plus as-needed short-acting beta-agonists for the management of patients with mild asthma.

The role of modeling studies in asthma management and clinical decision-making: a Delphi survey of physician knowledge and perceptions.

OBJECTIVE: To investigate the knowledge and perceptions of physicians on the role of modeling studies in asthma, using a modified Delphi procedure. METHODS: Group opinions among a panel of respiratory experts were obtained using two online questionnaires and a virtual scientific workshop. A consensus was pre-defined as agreement by >75% of participants. RESULTS: From 26 experts who agreed to participate, 22 completed both surveys. At the end of the process, the panel rated their own understanding of modeling as good (77%) but that among physicians in general as poor (77%). Participants agreed that data from modeling studies should be used, at least sometimes, to inform treatment guidelines (91%) and could be useful for guiding clinical decisions (100%). Perceived barriers to using modeling studies were 'A lack of understanding' (81%) and 'A lack of standardized methodology' (82%). Based on data from two modeling studies, no consensus was reached on physicians recommending regular inhaled corticosteroids (ICS) versus as-needed therapy for patients with mild asthma, whereas 77% agreed that they would recommend regular ICS over maintenance and reliever therapy for ≥80% of their patients with moderate asthma. No consensus was reached on the value of modeling data in relation to empirical data. CONCLUSION: There is overall support among respiratory experts for the usefulness of modeling data to guide asthma treatment guidelines and clinical decision making. More publications on modeling data using robust models and accessible terminology will aid the understanding of physicians in general and help clarify the evidence-based value of modeling studies.

Meta-analysis and cost-effectiveness analysis of intranasal corticosteroid treatment in allergic rhinitis with ocular symptoms.

BACKGROUND: Intranasal corticosteroid (INCS) has a beneficial effect on ocular symptoms in allergic rhinitis (AR). To our knowledge, the cost-effectiveness of available INCS for AR with ocular symptoms is yet to be demonstrated. OBJECTIVE: To evaluate the cost-effectiveness of INCSs including Budesonide (BANS), Mometasone furoate (MFNS), Triamcinolone (TANS), and Fluticasone furoate (FFNS) on ocular symptoms associated with AR in the Thai context. METHODS: The percentage of effectiveness in improving total ocular symptoms score (TOSS) was derived from the result of a meta-analysis that estimated the SMD of each INCS treatment compared to placebo as clinical input parameters. A cost-effectiveness analysis based on a decision-tree model to assess one-year costs and outcomes from a Thai societal perspective. The outcomes were to compare incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analyses (PSA) were also conducted to capture parameter uncertainties. RESULTS: 13 eligible RCTs with a total of 3,722 patients with SAR were included in the analysis. The percentage of effectiveness of FFNS, MFNS, TANS, and BANS was 59.89%, 45.60%, 24.89%, and 16.00%, respectively. The ICER of FFNS, MFNS, and TANS is THB-6,539.92, 4,593.83, and 1,401.24 compared to BANS. CECA result showed the probability of using FFNS is considered cost-effective in 87.50% of cases from zero value followed by MFNS (0.80%), TANS (5.40%), and BANS (6.30%). With a threshold greater than THB20,000, FFNS is considered a cost-effective strategy. CONCLUSIONS: FFNS is a cost-effective option compared to alternative INCSs in Thailand for treating AR with ocular symptoms.

Direct healthcare costs associated with management of asthma: comparison of two treatment regimens in Indonesia, Thailand and Vietnam.

OBJECTIVE: Daily inhaled corticosteroid (ICS) and long-acting beta-2-agonist (LABA) combinations comprising either regular maintenance therapy with ICS/LABA plus as-needed short-acting beta-2-agonist (SABA) or ICS-formoterol combinations used as maintenance and reliever therapy (MART) are recommended for moderate asthma. This analysis compares the direct costs of twice-daily fluticasone propionate/salmeterol (FP/salm) and budesonide/formoterol MART in three Southeast Asian countries. METHODS: A literature review identified three randomized trials in patients with asthma (≥ 12 years) comparing regular twice-daily FP/salm with as-needed SABA versus MART in moderate asthma: AHEAD (NCT00242775/17 countries/2309 patients), COMPASS (AstraZeneca study SD-039-0735/16 countries/3335 patients), and COSMOS (AstraZeneca study SD-039-0691/16 countries/2143 patients). Economic analyses, conducted from a healthcare sector perspective (medication costs + healthcare utilization costs), applied unit costs from countries where healthcare costs are publicly available: Indonesia, Thailand and Vietnam. Results are expressed in British pound sterling (GBP/patient/year). RESULTS: Annual exacerbation rates were low and differences between treatment strategies were small (range, FP/salm: 0.31-0.38, MART: 0.24-0.25) although statistically significant in favor of MART. Total average (minimum-maximum) direct costs (in GBP/patient/year) across the three studies were £187 (£137-£284), £158 (£125-£190), and £151 (£141-£164) for those who used FP/salm, and £242 (£217-£267), £284 (£237-£340) and £266 (£224-£315) for MART in Indonesia, Thailand and Vietnam, respectively. On average, total direct costs/patient/year with FP/salm were 22.8%, 44.6% and 43.0% lower than with MART for Indonesia, Thailand and Vietnam, respectively. CONCLUSIONS: In the three countries evaluated, total treatment costs with regular twice-daily FP/salm were consistently lower than with budesonide/formoterol MART due to lower direct healthcare costs.

Treatment patterns among non-active users of maintenance asthma medication in the United Kingdom: a retrospective cohort study in the Clinical Practice Research Datalink.

Objective: To describe patient characteristics, treatment patterns and healthcare utilization (HCU) of non-active users of maintenance asthma medications in the United Kingdom.Methods: Retrospective, cohort analysis of patients with asthma, aged ≥ 6 years who were non-active users of maintenance therapy (no prescription for inhaled corticosteroids (ICS), combined ICS/long-acting beta agonists (ICS/LABA) or 'other' bronchodilatory therapies in last 12 months) were identified in the Clinical Practice Research Datalink (2012-2015) and followed-up for 2 years after a new prescription for an asthma maintenance medication (index date). Patient characteristics, most common maintenance treatment sequences and HCU were described.Results: 55,293 patients were identified (ICS: 46,297, ICS/LABA: 8,367; Other: 629). Mean age was 37 years and 56% were female. During follow-up, the most common treatment sequences across groups implied intermittent use, comprising periods of maintenance therapy interspersed with maintenance-free periods. During year 1 and year 2 of follow-up, the proportion of patients prescribed OCS was 19% and 13%, prescribed ≥ 4 short-acting bronchodilators (SABD) was 24% and 19%, having ≥ 3 asthma-related primary care consultations/year was 59% and 36% and experiencing ≥ 1 exacerbation/year was 15% and 11%, respectively.Conclusions: In previously non-active users of asthma maintenance medication subsequently commenced on maintenance therapy, intermittent use was common during the 2-year follow-up despite the potential need for regular use as evidenced by patient HCU and SABD usage patterns. This highlights the need for regular patient assessment and education on medication adherence to ensure appropriateness of prescribing to maintain asthma control.

Direct healthcare cost comparison of Fluticasone propionate/Salmeterol vs Budesonide/Formoterol Maintenance And Reliever Therapy for moderate/severe asthma: Results from Thailand.

BACKGROUND: Inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) for moderate/severe asthma i.e. regular Fluticasone propionate/Salmeterol (FP/Salm) with as-needed short acting beta-2 agonist (SABA) or ICS/Formoterol Maintenance And Reliever Therapy (MART) are the recommended options. OBJECTIVE: To compare healthcare cost between regular FP/Salm with as-needed SABA vs MART in Thailand. METHODS: Direct healthcare cost data from 3 published randomized trials in asthma patients aged ≥12 years comparing regular twice-daily FP/Salm with as-needed SABA vs Budesonide/Formoterol (BUD/Form) MART in moderate/severe asthma were considered: AHEAD (NCT00242775/17 countries/2309 patients), COMPASS (AstraZeneca study SD-0390735/16 countries/3335 patients), and COSMOS (AstraZeneca study SD-039-0691/16 countries/2143 patients). Total direct treatment cost comparison/patient/year was calculated as a combination from 1) medication costs plus 2) healthcare utilization costs i.e. cost for health care visit, emergency room visit, and hospitalization. Unit costs referred from National drug information and Health Intervention and Technology Assessment (HITAP), Ministry of Public Health. RESULTS: Annual medication costs of FP/Salm + SABA were lower than MART in all studies with average cost as 182.01 vs 347.21 USD. Average annual healthcare utilization costs were 17.51 vs 13.01 USD in FP/Salm + SABA and MART, respectively. In overall, total direct treatment costs/patient/year with FP/Salm was 199.53 vs 360.22 USD of MART. Percent saving of total direct treatment costs by FP/Salm + SABA was 45% lower than with MART. CONCLUSIONS: In moderate/severe asthma patients, total direct treatment costs with regular twice-daily FP/Salm with as-needed SABA were lower than with BUD/Form MART primarily due to lower medication costs. Healthcare cost should be considered for asthma care in Thailand.

Pharmacological Basis of Differences in Dose Response, Dose Equivalence, and Duration of Action of Inhaled Corticosteroids.

INTRODUCTION: Asthma treatment guidelines classify inhaled corticosteroid (ICS) regimens as low, medium, or high dose. However, efficacy and safety are not independently assessed accordingly. Moreover, differences in ICS duration of action are not considered when a dose regimen is selected. We investigated the efficacy and safety implications of these limitations for available ICS molecules. METHODS: Published pharmacodynamic and pharmacokinetic parameters were used, alongside physiological and pharmacological principles, to estimate the efficacy and safety of available ICS molecules. Extent and duration of glucocorticoid receptor (GR) occupancy in the lung (efficacy) and cortisol suppression (systemic exposure and safety) were estimated. RESULTS: Some ICS regimens (e.g., fluticasone furoate, fluticasone propionate, and ciclesonide) rank high for efficacy but low for systemic exposure, contrary to how ICS dose equivalence is currently viewed. Differences in dose-response relationships for efficacy and systemic exposure were unique for each ICS regimen and reflected in their therapeutic indices. Notably, even low doses of most ICSs can generate high GR occupancy (≥ 90%) across the entire dose interval at steady state, which may explain previously reported difficulties in obtaining dose responses within the clinical dose range and observations that most clinical benefit typically occurs at low doses. The estimated post dose duration of lung GR occupancy for ICS molecules was categorized as 4-6 h (short), 14-16 h (medium), 25-40 h (long), or > 80 h (ultra-long), suggesting potentially large differences in anti-inflammatory duration of action. CONCLUSION: In a real-world clinical setting where there may be poor adherence to prescribed therapy, our findings suggest a significant therapeutic advantage for longer-acting ICS molecules in patients with asthma.

Patients with asthma often rely on inhaled corticosteroids to manage their symptoms by controlling lung inflammation. Inhaled corticosteroids can be used at low, medium, or high doses; however, the effectiveness, safety, and how long the effects last for a particular inhaled corticosteroid molecule are not considered when choosing them. This study investigated the safety and efficacy of different inhaled corticosteroid molecules. Leveraging published data on the mode of anti-inflammatory action and the rates these molecules are absorbed and eliminated from the body, we estimated their effectiveness and safety profiles, including duration of action in the lungs and systemic exposure levels. Some inhaled corticosteroid molecules such as fluticasone furoate, fluticasone propionate, and ciclesonide were found to exhibit high anti-inflammatory effectiveness in the lungs with minimal systemic exposure, contrasting the perceived similarities among currently used drug molecules. Anti-inflammatory duration of the unwanted systemic effect in the rest of the body was unique for each inhaled corticosteroid molecule. Notably, even the lowest doses of most inhaled corticosteroids were found to be effective in the lungs when taken as prescribed, supporting previous observations that clinical benefits are mostly realized at lower doses. Furthermore, estimated post dose durations of effectiveness for different inhaled corticosteroid molecules varied widely among different molecules, with some lasting a few hours and others lasting more than 80 h, suggesting significant differences in their duration of action. Overall, these findings demonstrate the potential advantage of using longer-acting inhaled corticosteroids, particularly for patients with asthma who may face challenges in adhering to prescribed regimens.

Exploring Clinical Remission in Moderate Asthma - Perspectives from Asia, the Middle East, and South America.

INTRODUCTION: Clinical remission is a relatively new concept in asthma but recent research initiatives suggest it could be an ambitious and achievable therapeutic target for patients with asthma. METHODS: In this modified Delphi study (comprising two online surveys, completed either side of a virtual scientific workshop), the opinions of a panel of respiratory physicians were evaluated to summarize perspective statements on key therapeutic outcomes and criteria for on-treatment clinical remission in patients with moderate asthma. An agreement threshold was pre-defined as agreement by ≥ 75% of participants. RESULTS: Surveys 1 and 2 were completed by 20 and 18 participants, respectively. Most participants (95%) agreed with the concept of clinical remission in moderate asthma and that this should be a desirable treatment goal (90%). Based on a composite measure of 4-6 desirable therapeutic outcomes, current understanding of clinical remission was considered as 12 months with no exacerbations, no oral corticosteroids, no daytime or night-time asthma symptoms (Asthma Control Test score ≥ 20 or Asthma Control Questionnaire score ≤ 0.75), stable lung function, and no treatment-related adverse events. No agreement was reached on the role of relievers in defining therapeutic outcomes or on the wider use of biomarkers and airway hyperresponsiveness for defining asthma remission in clinical practice. CONCLUSIONS: In line with recent consensus statements from the United States and Europe, there was a high level of agreement on the elements of clinical remission among a panel of respiratory physicians from Asia, the Middle East, and South America. Extension of the concept of clinical remission to patients with moderate asthma was considered aligned with the potential of clinical remission as a goal of therapy.

Association between Increased Risk of Pneumonia with ICS in COPD: A Continuous Variable Analysis of Patient Factors from the IMPACT Study.

INTRODUCTION: Despite the proven benefits of inhaled corticosteroid (ICS)-containing triple therapy for chronic obstructive pulmonary disease (COPD), clinicians limit patient exposure to ICS due to the risk of pneumonia. However, there are multiple factors associated with the risk of pneumonia in patients with COPD. This post hoc analysis of IMPACT trial data aims to set the risks associated with ICS into a context of specific patient-related factors that contribute to the risk of pneumonia. METHODS: The 52-week, double-blind IMPACT trial randomized patients with symptomatic COPD and ≥1 exacerbation in the prior year 2:2:1 to once-daily fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI), FF/VI or UMEC/VI. Annual rate of on-treatment pneumonias in the intent-to-treat population associated with age, body mass index (BMI), percent predicted forced expiratory volume in 1 s (FEV1) and blood eosinophil count (BEC) was evaluated. RESULTS: This analysis revealed that the annual rate of pneumonia showed the lowest risk at the age of 50 years. The 95% confidence intervals (CI) between ICS-containing and non-ICS containing treatments diverged in ages > 63 years, suggesting a significantly increased ICS-related risk in older patients. In contrast, the annual rate of pneumonia rose in both groups below BMI of 22.5 kg/m2, but above that, there was no relationship to pneumonia rate and no differential effect between the two groups. The relationship between BEC and pneumonia was flat up to > 300/µL cells with ICS-containing treatment and then rose. In contrast, the rate of pneumonia with non-ICS containing treatment appeared to increase at a lower level of BEC (~ 200/µL). CONCLUSIONS: There was little evidence of a differential effect of older age, lower BMI, lower FEV1 and BEC on the pneumonia rate between ICS-containing and non-ICS containing treatments. This analysis points to the need for a balanced approach to risk versus benefit in the use of ICS-containing treatments in COPD. CLINICAL TRIAL REGISTRATION: IMPACT ClinicalTrials.gov number, NCT02164513.

Delphi Consensus on Clinical Applications of GOLD 2023 Recommendations in COPD Management: How Aligned are Recommendations with Clinical Practice?

INTRODUCTION: The objective of this Delphi study was to understand and assess the level of consensus among respiratory experts on the clinical application of GOLD 2023 recommendations in management of patients with chronic obstructive pulmonary disease (COPD). METHODS: The study comprised two online surveys and a participant meeting with 34 respiratory experts from 16 countries. Responses of 73 questions were recorded using a Likert scale ranging from 0 (disagreement) to 9 (agreement). The consensus threshold was 75%. RESULTS: Survey 1 and survey 2 had 34 and 32 participants, respectively; and 25 attended the participant meeting. Consensus was reached on survey 1: 28/42; survey 2: 18/30 close-ended questions. A consensus was reached on the clinical relevance of most updates in definitions and diagnosis of COPD. Mixed results for the treatment recommendations by GOLD were noted: 74% agreed with the recommendation to initiate treatment with dual bronchodilators for group E patients; 63% agreed for including inhaled corticosteroids (ICS)/long-acting ß2 agonist(LABA)/ Long-acting muscarinic receptor antagonists (LAMA) as a treatment option for GOLD B patients. Also, consensus lacked on removing ICS + LABA as an initial therapeutic option, in countries with challenges in access to other treatment option;. 88% agreed that they use GOLD recommendations in their daily clinical practice. CONCLUSIONS: This Delphi study demonstrated a high level of consensus regarding key concepts of GOLD 2023 report, with most participants favoring recent updates in definitions, diagnosis, management, and prevention of COPD. More evidence on the etiotype based management and treatment options for group B and E are required which could further strengthen clinical application of the GOLD report.

The goal of this Delphi study was to understand and assess the level of alignment among the respiratory experts on the application of key changes and recommendations proposed by the GOLD 2023 report in their routine clinical practice for the management of patients with chronic obstructive pulmonary disease (COPD). There were two online surveys in this study, and experts from 16 countries (primarily focused on developing countries) were invited to participate. Using the Delphi method, expert representatives shared their insights with the aim of optimizing patient care. The alignment was assessed in six well-defined themes: 1) Overall view on GOLD/other recommendations; 2) Assessing patients with COPD; 3) Initial pharmacological treatment in patients with COPD; 4) Vaccination for patients with COPD; 5) Follow-up pharmacological treatment in patients with COPD; and 6) Survival evidence in patients with COPD. Participants expressed a high level of agreement regarding key concepts of the GOLD 2023 report, with most of them agreeing with recent updates in definitions, diagnosis, management, and prevention of COPD. The results also highlighted the need to publish GOLD reports in multiple languages and in a shorter, pocket-sized format to increase awareness and adaptation among healthcare providers.

Understanding the Burden of Respiratory Syncytial Virus in Older Adults in Latin America: An Expert Perspective on Knowledge Gaps.

Respiratory syncytial virus (RSV) is a significant global health concern and major cause of hospitalization, particularly among infants and older adults. The clinical impact of RSV is well characterized in infants; however, in many countries, the burden and risk of RSV in older populations are overlooked. In Latin America, there are limited data on RSV epidemiology and disease management in older adults. Therefore, the impact of RSV in this region needs to be addressed. Here, current insights on RSV infections in older populations in Latin America, including those with underlying health conditions, are discussed. We also outline the key challenges limiting our understanding of the burden of RSV in Latin America in a worldwide context and propose an expert consensus to improve our understanding of the burden of RSV in the region. By so doing, we aim to ultimately improve disease management and outcomes of those at risk and to alleviate the impact on healthcare systems.A graphical plain language summary is available with this article.

APPaRENT 3: Asthma Patients' and Physicians' Perspectives on the Burden and Management of Asthma in Seven Countries.

INTRODUCTION: Asthma management is strongly dependent on physician and patient beliefs and perceptions about the disease and its long-term treatment. The APPaRENT 3 study was conducted to explore factors influencing treatment choice and to understand patients' and physicians' attitudes and perspectives on the use of controller inhalers in regular versus flexible dosing for asthma management. METHODS: This cross-sectional survey of patients with asthma and treating physicians was conducted in seven countries: Indonesia, Malaysia, Philippines, Thailand, Vietnam (patient survey only), Saudi Arabia, and the United Arab Emirates. Assessment was carried out through an online/face-to-face questionnaire, where patients' viewpoints were focused on their attitudes and beliefs about asthma and treatment adherence, whereas physicians' viewpoints were gathered on their attitudes and beliefs about asthma management, knowledge of and adherence to asthma treatment guidelines, and asthma treatment regimens. RESULTS: Overall, 1400 patients (mean age, 34 years) and 599 physicians (mean age, 43 years) were included in the survey. Physicians similarly prioritised symptom control (39%) and exacerbation reduction (40%) in moderate asthma, whereas patients prioritised symptom control (41%) over exacerbation reduction (22%). Although both groups (physicians, 86%; patients, 84%) perceived asthma as well-controlled, poor management was evident based on Asthma Control Test (ACT) scores (mean, 15.7; standard deviation, 4.14; 82% had an ACT score < 20) and high symptom burden (39% reported nighttime awakenings or early mornings ≥ 2 nights/week). Most patients (76%) with moderate asthma were prescribed regular dosing, with the most common treatment being inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA) with as-needed inhaled short-acting ß2-agonist (SABA; 20%). Among patients on maintenance and reliever therapy, 93% of patients received a separate inhaled reliever. CONCLUSIONS: Despite high symptom burden, patients overestimated their level of asthma control. Physicians prioritised controlling symptoms and reducing exacerbations as treatment goals for moderate asthma, often prescribing regular dosing with ICS/LABA with as-needed inhaled SABA.

Managing asthma depends a lot on what doctors and patients think about the illness and its long-term treatment. This study looked into what influences treatment decisions and what patients and doctors think about using inhalers regularly or on an as-needed basis to manage asthma across seven countries (Indonesia, Malaysia, Philippines, Thailand, Vietnam [patient survey only], Saudi Arabia, and the United Arab Emirates). In this study, patients with asthma and doctors managing asthma completed an online/face-to-face questionnaire. The study aimed to understand what patients think about asthma and their treatment plan. Meanwhile, the doctors were asked what they think about managing asthma and how much they apply clinical guidelines for treating patients with asthma. Doctors believed it is equally important to control symptoms and prevent worsening of symptoms in patients with moderate asthma, while patients cared more about controlling symptoms than preventing worsening of symptoms. While doctors and patients both regarded asthma as well-controlled, many patients had low Asthma Control Test scores and experienced a lot of symptoms, suggesting that they are poor perceivers of asthma control. Most patients with moderate asthma were given regular treatment, usually with inhaled corticosteroid combined with long-acting ß₂-agonist along with as-needed short-acting ß₂-agonist as a reliever. Most patients who were prescribed the same inhaler for regular use and as a reliever also had a separate inhaler for quick relief of symptoms. This study shows the need for patients and doctors to have better conversations about asthma, its treatments, and what to expect from them.

Association Between Adult Antibiotic Use, Microbial Dysbiosis and Atopic Conditions - A Systematic Review.

Background: Strong associations between early antibiotic exposure and increased risk of childhood allergies have been established. Antibiotics have the potential to induce microbial dysbiosis that may be linked to allergic conditions. This review examines the limited available evidence on the associations between adult antibiotic use, microbial dysbiosis and atopic conditions. Methods: A systematic literature search was conducted using PubMed and Embase for relevant studies, published between 01-01-2000 and 08-17-2022. We searched for associations between antibiotic use, microbial dysbiosis, and allergic conditions in adults, defined as over 13 years of age for the purposes of this review. Results: Twenty-one studies were analyzed, with the inclusion of four narrative reviews as scarce relevant literature was found when stricter selection criteria were employed. Relevant studies predominantly focused on asthma. Significant microbial differences were observed in most measures between healthy subjects and subjects with allergic conditions. However, no system-wise and strain-wise associations were evident. Notably, at the phyla level, the Bacillota and Pseudomonadota phyla were associated with asthmatics, while the Actinobacteria phylum was linked to healthy controls. Asthmatics tends to reflect upregulation in the Bacillota and Pseudomonadota phyla in both airway and gut microbiomes. Conclusion: No compelling evidence could be found between adult antibiotic exposure, consequent microbial dysbiosis, and allergic conditions in adults. Our review is limited by scarce literature and therefore remains inconclusive. However, potential implications of antibiotic use impacting on allergic conditions justify additional research and heightened pharmacovigilance in this area.

SABAs as Reliever Medications in Asthma Management: Evidence-Based Science.

The role of as-needed inhaled short-acting ß2-agonists (SABAs) in the management of asthma has become a subject of debate due to differing opinions in the professional community relating to the use of SABAs. In this article, we summarize the current position of SABAs when used as reliever medications and examine the challenges to appropriate use including a critique of the data that have led to the condemnation of SABA used as a reliever. We consider the evidence for the appropriate use of SABA as a reliever together with practical solutions to ensure such use, including identifying patients at risk of misusing their SABA relievers and managing issues of inhaler technique and treatment adherence. We conclude that inhaled corticosteroid (ICS)-based maintenance treatment with SABA used as-needed as a reliever is an effective and safe treatment for patients with asthma, with no scientific evidence of a causal link between SABA use as a reliever and mortality or serious adverse events (including exacerbations). Increased SABA use warns of a deterioration in asthma control, and patients at risk of misusing their ICS and SABA medication should be rapidly identified to ensure they are receiving adequate ICS-based controller therapy. Appropriate use of ICS-based controller therapy and as-needed SABA should be encouraged and promoted with educational activities.

Clinical Concepts for Triple Therapy Use in Patients with COPD: A Delphi Consensus.

Purpose: Role of triple therapy in chronic obstructive pulmonary disease (COPD) management is supported by growing evidence, but consensus is lacking on various aspects. We conducted a Delphi survey in respiratory experts on the effects of triple therapy on exacerbation reduction, early optimization, pneumonia risk, and mortality benefits in COPD management. Methods: The study comprised 2-round online surveys and a participant meeting with 21 respiratory experts from 10 countries. The 31-statement questionnaire was prepared using Decipher software after literature review. Responses were recorded using Likert scale ranging from 1 (disagreement) to 9 (agreement) with a consensus threshold of 75%. Results: All experts participated in both surveys and 14/21 attended participant meeting. Consensus was reached on 13/31 questions in first survey and 4/14 in second survey on: mortality benefits of triple therapy; comparable pneumonia risk between single inhaler triple therapy (SITT) and multiple inhaler triple therapy (81%); preference of SITT for patients with high eosinophil count (95%); exacerbation risk reduction and healthcare cost benefits with early initiation of SITT post exacerbation-related hospitalization (<30 days) (86%). No consensus was reached on first line SITT use after first exacerbation resulting in COPD diagnosis (62%). Conclusion: This study demonstrated that there is consensus among experts regarding many of the key concepts about appropriate clinical use and benefits of triple therapy in COPD. More evidence is required for evaluating the benefits of early optimisation of triple therapy.

DElaying Disease Progression In COPD with Early Initiation of Dual Bronchodilator or Triple Inhaled PharmacoTherapy (DEPICT): A Predictive Modelling Approach.

INTRODUCTION: Clinical studies demonstrate an accelerated decline in lung function in patients with moderate chronic obstructive pulmonary disease (COPD) (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grade 2) versus severe and very severe COPD (GOLD grades 3 and 4). This predictive modelling study assessed the impact of initiating pharmacotherapy earlier versus later on long-term disease progression in COPD. METHODS: The modelling approach used data on decline in forced expiratory volume in 1 s (FEV1) extracted from published studies to develop a longitudinal non-parametric superposition model of lung function decline with progressive impact of exacerbations from 0 per year to 3 per year and no ongoing pharmacotherapy. The model simulated decline in FEV1 and annual exacerbation rates from age 40 to 75 years in COPD with initiation of long-acting anti-muscarinic antagonist (LAMA)/long-acting beta2-agonist (LABA) (umeclidinium (UMEC)/vilanterol (VI)) or triple (inhaled corticosteroid (ICS)/LAMA/LABA; fluticasone furoate (FF)/UMEC/VI) therapy at 40, 55 or 65 years of age. RESULTS: Model-predicted decline in FEV1 showed that, compared with 'no ongoing' therapy, initiation of triple or LAMA/LABA therapy at age 40, 55 or 65 years preserved an additional 469.7 mL or 236.0 mL, 327.5 mL or 203.3 mL, or 213.5 mL or 137.5 mL of lung function, respectively, by the age of 75. The corresponding average annual exacerbation rates were reduced from 1.57 to 0.91, 1.06 or 1.23 with triple therapy or to 1.2, 1.26 and 1.4 with LAMA/LABA therapy when initiated at 40, 55 or 65 years of age, respectively. CONCLUSIONS: This modelling study suggests that earlier initiation of LAMA/LABA or triple therapy may have positive benefits in slowing disease progression in patients with COPD. Greater benefits were demonstrated with early initiation therapy with triple versus LAMA/LABA.

Safety of SABA Monotherapy in Asthma Management: a Systematic Review and Meta-analysis.

INTRODUCTION: Short-acting ß2-agonist (SABA) reliever overuse is common in asthma, despite availability of inhaled corticosteroid (ICS)-based maintenance therapies, and may be associated with increased risk of adverse events (AEs). This systematic literature review (SLR) and meta-analysis aimed to investigate the safety and tolerability of SABA reliever monotherapy for adults and adolescents with asthma, through analysis of randomized controlled trials (RCTs) and real-world evidence. METHODS: An SLR of English-language publications between January 1996 and December 2021 included RCTs and observational studies of patients aged ≥ 12 years treated with inhaled SABA reliever monotherapy (fixed dose or as needed) for ≥ 4 weeks. Studies of terbutaline and fenoterol were excluded. Meta-analysis feasibility was dependent on cross-trial data comparability. A random-effects model estimated rates of mortality, serious AEs (SAEs), and discontinuation due to AEs (DAEs) for as-needed and fixed-dose SABA treatment groups. ICS monotherapy and SABA therapy were compared using a fixed-effects model. RESULTS: Forty-two studies were identified by the SLR for assessment of feasibility. Final meta-analysis included 24 RCTs. Too few observational studies (n = 2) were available for inclusion in the meta-analysis. One death unrelated to treatment was reported in each of the ICS, ICS + LABA, and fixed-dose SABA groups. No other treatment-related deaths were reported. SAE and DAE rates were < 4%. DAEs were reported more frequently in the SABA treatment groups than with ICS, potentially owing to worsening asthma symptoms being classified as an AE. SAE risk was comparable between SABA and ICS treatments. CONCLUSIONS: Meta-analysis of data from RCTs showed that deaths were rare with SABA reliever monotherapy, and rates of SAEs and DAEs were comparable between SABA reliever and ICS treatment groups. When used appropriately within prescribed limits as reliever therapy, SABA does not contribute to excess rates of mortality, SAEs, or DAEs.

Primary Care Management of Asthma Exacerbations or Attacks: Impact of the COVID-19 Pandemic.

The COVID-19 pandemic has brought a renewed focus on appropriate management of chronic respiratory conditions with a heightened awareness of respiratory symptoms and the requirement for differential diagnosis between an asthma attack and COVID-19 infection. Despite early concerns in the pandemic, most studies suggest that well-managed asthma is not a risk factor for more severe COVID-related outcomes, and that asthma may even have a protective effect. Advice on the treatment of asthma and asthma attacks has remained unchanged. This article describes some challenges faced in primary care asthma management in adults and in teenagers, particularly their relevance during a pandemic, and provides practical advice on asthma attack recognition, classification, treatment and continuity of care. Acute attacks, characterised by increased symptoms and reduced lung function, are often referred to as exacerbations of asthma by doctors and nurses but are usually described by patients as asthma attacks. They carry a significant and underestimated morbidity and mortality burden. Many patients experiencing an asthma attack are assessed in primary care for treatment and continuing management. This may require remote assessment by telephone and home monitoring devices, where available, during a pandemic. Differentiation between an asthma attack and a COVID-19 infection requires a structured clinical assessment, taking account of previous medical and family history. Early separation into mild, moderate, severe or life-threatening attacks is helpful for continuing good management. Most attacks can be managed in primary care but when severe or unresponsive to initial treatment, the patient should be appropriately managed until transfer to an acute care facility can be arranged. Good quality care is important to prevent further attacks and must include a follow-up appointment in primary care, proactive regular dosing with daily controller therapy and an understanding of a patient's beliefs and perceptions about asthma to maximise future self-management.

Pharmacology Versus Convenience: A Benefit/Risk Analysis of Regular Maintenance Versus Infrequent or As-Needed Inhaled Corticosteroid Use in Mild Asthma.

INTRODUCTION: This study compared the bronchoprotective and benefit/risk profiles of various inhaled corticosteroid (ICS) dosing regimens in mild asthma. METHODS: A pharmacokinetic/pharmacodynamic model was developed and validated describing the relationship between ICS dose and time-course for airway bronchoprotection, [provocative concentration of adenosine monophosphate (AMP) causing ≥ 20% decline in forced expiratory volume in 1 s (FEV1) (AMP PC20)], for fluticasone furoate (FF), fluticasone propionate (FP) and budesonide (BUD). For regular ICS maintenance therapy (100% and 50% adherence) and infrequent or as-needed use (dosing 3-4 times per week), treatment effectiveness was expressed as percent time during 28 days when bronchoprotection exceeded either the threshold for a treatment-related bronchoprotective effect (AMP PC20 ≥ 0.25 doubling dose) or the threshold for a clinically significant bronchoprotective effect (AMP PC20 ≥ 1.0 doubling dose). This value was divided by the total ICS dose administered expressed in prednisolone equivalents to give a therapeutic index (TI). RESULTS: The model-predicted time course of ICS-induced bronchoprotection with regular daily maintenance dosing and 100% adherence showed that all ICS at the highest recommended doses for mild asthma exceeded the threshold for clinically significant bronchoprotective effect for all or most of the 28-day dosing period, mean (90% CI); 100% (96.1-100), 99.9% (8.0-100) and 100% (58.2-100) with TI values of 16.9, 6.6 and 5.4 for FF 100 µg OD, FP 200 µg BID and BUD 200 µg BID, respectively. For simulated poor adherence (50%) to regular daily maintenance therapy, corresponding mean (90% CI) values were; 75.7% (39.4-89.1), 52.3% (0.7-69.2) and 51.3% (28.6-58.3) with TI values of 25.7, 6.9 and 5.6. For simulated infrequent/as needed use the corresponding values were; 77.0% (37.6-87.0), 25.5% (0.0-38.0) and 26.2% (14.3-31.5) with TI values of 26.1, 6.7 and 5.7. For all regimen/scenarios, FF had the most sustained efficacy and favourable TI followed by FP and BUD. CONCLUSIONS: At doses recommended for mild asthma, all ICS regimens provide sustained bronchoprotective efficacy when dosed regularly with high adherence. With poor adherence or use 3-4 times per week (infrequent/as needed), longer-acting ICS molecules will more likely provide sustained protection and a better TI versus shorter duration of action molecules (FF > FP ≥ BUD). These data highlight the benefits of using ICS as regular daily maintenance dosing in mild asthma and the potential risks of under-treatment with ICS (which may occur with ICS/formoterol as-needed approach in mild persistent asthma) associated with reduced levels of bronchoprotection.