Insights into interventions in managing COPD patients: lessons from the TORCH and UPLIFT® studies

Influencing the progression of COPD has long been an elusive goal of drug therapy. Directly or indirectly, this has again been investigated in two of the largest, long-term drug trials in COPD: Towards a Revolution in COPD Health (TORCH) and Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT®). Neither trial achieved statistical significance in their respective primary outcomes; however, both make considerable contributions to understanding of how the progression of COPD may be influenced. The objective of this article is to review the data from these different trials with a view to what can be learnt about the management of COPD. The long-term improvements in lung function, health-related quality of life, and possibly survival from the use of long-acting bronchodilators in these trials suggest an influence on progression of the disease. With the more optimistic view of benefits from drug treatment of COPD that these trials provide, a review of prescribing practices is warranted

Alpha-1 antitrypsin (AAT) augmentation therapy in individuals with the PI*MZ genotype: a pro/con debate on a working hypothesis

Deficiència d'alfa-1 antitripsina; Genotip; Malaltia pulmonarDeficiencia de alfa-1 antitripsina; Genotipo; Enfermedad pulmonarAlpha-1 antitrypsin deficiency; Genotype; Pulmonary diseaseAlpha-1 antitrypsin deficiency (AATD) is a significantly under-diagnosed genetic condition caused by reduced levels and/or functionality of alpha-1 antitrypsin (AAT), predisposing individuals to lung, liver or other systemic diseases. The management of individuals with the PI*MZ genotype, characterized by mild or moderate AAT deficiency, is less clear than of those with the most common severe deficiency genotype (PI*ZZ). Recent genetic data suggest that the PI*MZ genotype may be significantly more prevalent than currently thought. The only specific treatment for lung disease associated with severe AATD is the intravenous infusion of AAT augmentation therapy, which has been shown to slow disease progression in PI*ZZ individuals. There is no specific evidence for the clinical benefit of AAT therapy in PI*MZ individuals, and the risk of emphysema development in this group remains controversial. As such, current guidelines do not support the use of AAT augmentation in PI*MZ individuals. Here, we discuss the limited data on the PI*MZ genotype and offer pro and con perspectives on pursuing an AAT-specific therapeutic strategy in PI*MZ individuals with lung disease. Ultimately, further research to demonstrate the safety, risk/benefit balance and efficacy of AAT therapy in PI*MZ individuals is needed.Medical writing assistance for this manuscript was funded by CSL Behring; the role of the funder was to support medical writing assistance only

Use of Computed Tomography Lung Densitometry as an Outcome Measure for Emphysema Progression: The Case of Losartan

Tomography; Emphysema; OutcomesTomografía; Enfisema; ResultadosTomografia; Emfisema; Resultat

Chronic bronchial infection in stable COPD: To treat or not to treat

Chronic bronchial infection; COPDInfección bronquial crónica; EPOCInfecció bronquial crònica; MPO

Clinical and functional characteristics of individuals with alpha‑1 antitrypsin deficiency: EARCO international registry

Trial registration www. clini caltr ials. gov (ID: NCT04180319)Background Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. Methods The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 μM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. Results A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). Conclusions EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function.GrifolsCSL BehringKamadapH PharmaTakeda to the European Respiratory Society (ERS)

Stepwise management of COPD: what is next after bronchodilation?

Dyspnoea; Eosinophils; Inhaled corticosteroidsDisnea; Eosinófilos; Corticosteroides inhaladosDispnea; Eosinòfils; Corticoides inhalatsInhaled bronchodilator therapy with long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) in combination is currently the mainstay of treatment for chronic obstructive pulmonary disease (COPD). Treatment guidelines recommend the addition of inhaled corticosteroids (ICS) to LABA/LAMA only in patients with a history of frequent/severe exacerbations and high blood eosinophil counts, or in those with concomitant asthma. Despite this, real-world data suggest that clinicians are not adhering to this guidance and that ICS are frequently overused. This is possibly due to the incorrect assumption that when LABA/LAMA therapy is not sufficient, adding an ICS to the treatment regimen is the logical next step. In this narrative review, we describe global and country-specific guideline recommendations from Germany, Spain, and Japan and compare these with real-world data on LABA/LAMA and ICS use in clinical practice. We also provide a clinical guide to the use of add-on therapies with LABA/LAMA for different patient phenotypes, including (1) patients still symptomatic (but not exacerbating) despite LABA/LAMA treatment; (2) patients still exacerbating despite LABA/LAMA treatment who have high blood eosinophil counts; and (3) patients still exacerbating despite LABA/LAMA treatment who do not have high blood eosinophils or concomitant asthma

Comorbidities of patients in tiotropium clinical trials : comparison with observational studies of patients with chronic obstructive pulmonary disease

Acknowledgments The authors are fully responsible for all content and editorial decisions made, were involved at all stages of manuscript development, and have approved the final version for publication. Editorial assistance, supported financially by Boehringer Ingelheim and Pfizer, was provided by Godfrey Lisk of PAREXEL International during the preparation of this manuscript. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited.Peer reviewedPublisher PD

Nine controversial questions about augmentation therapy for alpha-1 antitrypsin deficiency: a viewpoint

Alpha-1 antitrypsin deficiencyDeficiencia de alfa-1 antitripsinaDeficiència d'alfa-1 antitripsinaAugmentation therapy with intravenous alpha-1 antitrypsin is the only specific treatment for alpha-1 antitrypsin deficiency (AATD)-associated emphysema. This treatment has been available and remained basically unchanged for more than 35 years, but many questions persist regarding its indications, regimen of administration and efficacy. Because AATD is a rare disease, it has not been possible to conduct randomised, placebo-controlled trials that are adequately powered for the usual outcomes analysed in non-AATD-related COPD, such as lung function decline, exacerbations, symptoms or quality of life. New outcomes such as lung densitometry measured by computed tomography are more sensitive for identifying emphysema progression but are not widely accepted by regulatory agencies. In addition, clinical manifestations, severity and the natural history of lung disease associated with AATD are very heterogeneous, which means that individual prediction of prognosis is challenging. Therefore, the indication for augmentation is sometimes a dilemma between initiating treatment in individuals who may not develop significant lung disease or in whom disease will not progress and delaying it in patients who will otherwise rapidly and irreversibly progress. Other areas of debate are the possible indication for augmentation in patients with severe AATD and respiratory diseases other than emphysema, such as bronchiectasis or asthma, and the use of therapy after lung transplant in AATD patients. All these uncertainties imply that the indication for treatment must be personalised in expert reference centres after in-depth discussion of the pros and cons of augmentation with the patient

Optimizing bronchodilation in the prevention of COPD exacerbations

The natural disease course of chronic obstructive pulmonary disease (COPD) is often punctuated by exacerbations: acute events of symptom worsening associated with significant morbidity and healthcare resource utilizationreduced quality of lifeand increased risk of hospitalization and death. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommend that patients at risk of exacerbations ( GOLD Groups C and D) receive a long-acting muscarinic antagonist (LAMA) or a long-acting beta(2)- agonist (LABA)/LAMA combination, respectively, as preferred initial treatments. The latter recommendation is based on recent trial evidence demonstrating the superior efficacy of a fixed-dose LABA/LAMA over an inhaled corticosteroid (ICS)/LABA in exacerbation prevention. ICS in combination with a LABA is also indicated for prevention of exacerbations, but the use of ICS is associated with an increased risk of adverse events such as pneumonia, and offers limited benefits beyond those provided by LABA or LAMA monotherapy. In this review, we examine evidence from a number of pivotal studies of LABAs and LAMAs, administered as monotherapy or as part of dual or triple combination therapy, with a specific focus on their effect on exacerbations. We also discuss a new proposed treatment paradigm for the management of COPD that takes into account this recent evidence and adopts a more cautious approach to the use of ICS. In alignment with GOLD 2017, we suggest that ICS should be reserved for patients with concomitant asthma or in whom exacerbations persist despite treatment with LABA/LAMA.Novartis Pharma AG (Basel, Switzerland)Hosp Univ Vall dHebron, CIBER Enfermedades Resp CIBERES, Pneumol Dept, Barcelona, SpainUniv Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USASouth Texas Vet Hlth Care Syst, San Antonio, TX USAUniv Fed Sao Paulo, Escola Paulista Med, Resp Div, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Resp Div, Sao Paulo, BrazilNovartis Pharma AG (Basel, Switzerland)Web of Scienc