Expert review of respiratory medicine最新文献

Background: Dyspnea is a critical component of chronic obstructive pulmonary disease (COPD). We report the effect of ensifentrine, a novel PDE3/PDE4 inhibitor, on dyspnea using pooled data from the Phase 3 ENHANCE-1/2 trials.

Methods: The pooled population (ensifentrine, n = 975; placebo, n = 574) included patients aged 40-80 years with post-bronchodilator FEV₁/FVC <0.7, FEV₁ 30-70% predicted, mMRC Dyspnea Scale score ≥2, and a smoking history ≥10 pack-years. Patients taking dual LAMA/LABA or LAMA/LABA/ICS triple therapy were excluded. Dyspnea measures included the Transition Dyspnea Index (TDI), Evaluating Respiratory Symptoms (E-RS), and rescue medication use.

Results: After 24 weeks, ensifentrine significantly improved TDI scores (least-squares mean difference, 0.97; 95% CI, 0.64, 1.30; p < 0.001) and across all TDI subdomains. Ensifentrine-treated patients were more likely to be TDI responders at week 24 (p < 0.001), which was consistent across clinically relevant subgroups. Ensifentrine-treated patients had improved E-RS breathlessness subdomain scores (p = 0.053) and reduced rescue medication use (p = 0.002).

Conclusion: Ensifentrine produced clinically meaningful improvements in multiple dyspnea measures in patients with symptomatic, moderate-to-severe COPD. A limitation of this study was the exclusion of patients taking dual LAMA/LABA and LAMA/LABA/ICS triple therapy.

Clinical trial registration: www.clinicaltrials.gov identifiers are ENHANCE-1: NCT04535986; ENHANCE-2: NCT04542057.

Background: Various bronchoscopic lung volume reduction (BLVR) methods have been developed to treat chronic obstructive pulmonary disease (COPD). The efficacy and safety of these interventions remain unclear. This study assessed the efficacy and safety of various BLVR interventions in COPD patients.

Methods: PubMed and Embase were searched from inception to 21 October 2023. The primary outcomes assessed included the 6-min walking distance (6MWD), St. George Respiratory Questionnaire (SGRQ) score, lung function, and adverse events (AE). A frequentist approach with a random-effects model was used for a network meta-analysis.

Results: Twelve randomized controlled trials (RCTs) with 1646 patients were included in this meta-analysis. Patients treated with an endobronchial valve (EBV) achieved a minimum clinically important difference (MCID) in 6MWD and SGRQ at 6 months. Patients treated with coils achieved MCID in the SGRQ score at 12 months. Patients with aspiration valve system and bronchoscopic thermal vapor ablation (BTVA) achieved MCID in the SGRQ score at 6 months.

Conclusions: In COPD patients, EBV should be considered first, while being wary of pneumothorax. Coil and BTVA are potential therapeutic alternatives. Although BTVA demonstrates a safer procedural profile than coils, additional studies are imperative to clarify its efficacy.

Introduction: In the management of chronic obstructive pulmonary disease (COPD), inhalation therapy plays a pivotal role. However, clinicians often face the dilemma of choosing between single and multiple inhaler therapies for their patients. This choice is critical because it can affect treatment efficacy, patient adherence, and overall disease management.

Areas covered: This article examines the advantages and factors to be taken into consideration when selecting between single and multiple inhaler therapies for COPD.

Expert opinion: Both single and multiple inhaler therapies must be considered in COPD management. While single inhaler therapy offers simplicity and convenience, multiple inhaler therapy provides greater flexibility and customization. Clinicians must carefully evaluate individual patient needs and preferences to determine the most appropriate inhaler therapy regimen. Through personalized treatment approaches and shared decision-making, clinicians can optimize COPD management and improve patient well-being. Nevertheless, further research is required to compare the effectiveness of single versus multiple inhaler strategies through rigorous clinical trials, free from industry bias, to determine the optimal inhaler strategy. Smart inhaler technology appears to have the potential to enhance adherence and personalized management, but the relative merits of smart inhalers in single inhaler regimens versus multiple inhaler regimens remain to be determined.

Introduction: Home oxygen therapy is one of the few interventions that can improve survival in patients with chronic obstructive pulmonary disease (COPD) when administered appropriately, although it may cause side effects and be an unnecessary burden for some patients.

Areas covered: This narrative review summarizes the current literature on the assessment of hypoxemia, different types of home oxygen therapy, potential beneficial and adverse effects, and emerging research on home oxygen therapy in COPD. A literature search was performed using MEDLINE and EMBASE up to January 2024, with additional articles being identified through clinical guidelines.

Expert opinion: Hypoxemia is common in patients with more severe COPD. Long-term oxygen therapy is established to prolong survival in patients with chronic severe resting hypoxemia. Conversely, in the absence of chronic severe resting hypoxemia, home oxygen therapy has an unclear or conflicting evidence base, including for palliation of breathlessness, and is generally not recommended. However, beneficial effects in some patients cannot be precluded. Evidence is emerging on the optimal daily duration of oxygen use, the role of high-flow and auto-titrated oxygen therapy, improved informed decision-making, and telemonitoring. Further research is needed to validate novel oxygen delivery systems and monitoring tools and establish long-term effects of ambulatory oxygen therapy in COPD.

Introduction: Small airway disease (SAD) represents a common and critical feature of Chronic Obstructive Pulmonary Disease (COPD). Introduced in the '60s, SAD has gradually gained increasing interest as assessment methodologies have improved. Chronic exposure to smoking and noxious particles or gases induces inflammation and remodeling, leading to airway obstruction and SAD, eventually resulting in complete airway loss.

Areas covered: A literature search up to June 2024 was performed in PubMed to identify articles on SAD and airway diseases mainly COPD, but also to the extent that it seemed relevant in the uncontrolled/severe asthma field, where SAD is better studied. We provide clinicians and translational scientists with a comprehensive analysis of the existing literature on SAD in COPD, concentrating on the underlying pathophysiological mechanisms, diagnostic techniques, and current pharmacological approaches targeting airflow obstruction in small airways.

Expert opinion: Small airways are the primary site for the onset and progression of airflow obstruction in patients with COPD, with significant clinical consequences associated with poor lung function, hyperinflation, and impaired quality of life. The early identification of individuals with subclinical SAD may allow us to prevent its further progress from airway loss and potential development of emphysema and choose the appropriate therapeutic approach.

Introduction: Chronic nocturnal noninvasive ventilation (NIV) improves outcomes in COPD patients with chronic hypercapnic respiratory failure. The aim of chronic NIV in COPD is to control chronic hypercapnic respiratory insufficiency and reduce symptoms of nocturnal hypoventilation, thereby improving quality of life. Chronic NIV care is more and more offered exclusively at home, enabling promising outcomes in terms of patient and caregiver satisfaction, hospital care consumption and cost reduction. Yet, to achieve and maintain optimal ventilation, during adaptation and follow-up, effective feasible (home) monitoring poses a significant challenge.

Areas covered: Comprehensive monitoring of COPD patients receiving chronic NIV requires integrating data from ventilators and assessment of the patient's status including gas exchange, sleep quality, and patient-reported outcomes. The present article describes the physiological background of monitoring during NIV and aims to provide an overview of existing methods for monitoring, assessing their reliability and clinical relevance.

Expert opinion: Patients on chronic NIV are 'ideal' candidates for home monitoring; the advantages of transforming hospital to home care are huge for patients and caregivers and for healthcare systems facing increasing patient numbers. Despite the multitude of available monitoring methods, identifying and characterizing the most relevant parameters associated with optimal patient well-being remains unclear.

Background: Several methods exist to reduce the number of arterial blood gases (ABGs). One method, Roche v-TAC, has been evaluated in different patient groups. This paper aggregates data from these studies, in different patient categories using common analysis criteria.

Research design and methods: We included studies evaluating v-TAC based on paired arterial and peripheral venous blood samples. Bland-Altman analysis compared measured and calculated arterial values of pH, PCO₂, and PO₂. Subgroup analyses were performed for normal, chronic hypercapnia and chronic base excess, acute hyper- and hypocapnia, and acute and chronic base deficits.

Results: 811 samples from 12 studies were included. Bias and limits of agreement for measured and calculated values: pH 0.001 (-0.029 to 0.031), PCO₂ -0.08 (-0.65 to 0.49) kPa, and PO₂ 0.04 (-1.71 to 1.78) kPa, with similar values for all sub-group analyses.

Conclusion: These data suggest that v-TAC analysis may have a role in replacing ABGs, avoiding arterial puncture. Substantial data exist in patients with chronic hypercapnia and chronic base excess, acute hyper- and hypocapnia, and in patients with relatively normal acid-base status, with similar bias and precision across groups and across study data. Limited data exist for patients with acute and chronic base deficits.

Introduction: The hallmark of most patients with severe asthma is type 2 inflammation, driven by innate and adaptive immune responses leading to either allergic or non-allergic eosinophilic infiltration of airways. The cellular and molecular pathways underlying severe type 2 asthma can be successfully targeted by specific monoclonal antibodies.

Areas covered: This review article provides a concise overview of the pathophysiology of type 2 asthma, followed by an updated appraisal of the mechanisms of action and therapeutic efficacy of currently available biologic treatments used for management of severe type 2 asthma. Therefore, all reported information arises from a wide literature search performed on PubMed.

Expert opinion: The main result of the recent advances in the field of anti-asthma biologic therapies is the implementation of a personalized medicine approach, aimed to achieve clinical remission of severe asthma. Today this accomplishment is made possible by the right choice of the most beneficial biologic drug for the pathologic traits characterizing each patient, including type 2 severe asthma and its comorbidities.

Introduction: Asthma is a common chronic respiratory disease affecting 262 million people globally, causing half a million deaths each year. Poor asthma outcomes are frequently due to non-adherence to medication, poor engagement with asthma services, and a lack of objective diagnostic tests. In recent years, technologies have been developed to improve diagnosis, monitoring, and care.

Areas covered: Technology has impacted asthma care with the potential to improve patient outcomes, reduce healthcare costs, and provide personalized management. We focus on current evidence on home diagnostics and monitoring, remote asthma reviews, and digital smart inhalers. PubMed, Ovid/Embase, Cochrane Library, Scopus and Google Scholar were searched in November 2023 with no limit by year of publication.

Expert opinion: Advanced diagnostic technologies have enabled early asthma detection and personalized treatment plans. Mobile applications and digital therapeutics empower patients to manage their condition and improve adherence to treatments. Telemedicine platforms and remote monitoring devices have the potential to streamline asthma care. AI algorithms can analyze patient data and predict exacerbations in proof-of-concept studies. Technology can potentially provide precision medicine to a wider patient group in the future, but further development is essential for implementation into routine care which in itself will be a major challenge.