Pharmacotherapies for COPD

This review article summarizes the main treatments for chronic obstructive pulmonary disease, their mechanisms, and the key evidence from trials supporting their use. Drug classes covered were short acting beta agonists (SABA), short acting muscarinic antagonists (SAMA), long acting beta agonists (LABA), long acting antimuscarinics (LAMA), inhaled corticosteroids (ICS), LABA/ ICS combinations, specific phosphodiesterase (PDE4) inhibitors, non-specific PDE inhibitors, mucolytics, and oxygen. Non-specific therapies, such as opiates for relief of dyspnoea and therapies for smoking cessation, are also covered briefly. For each class of drug, mechanisms of action are described, key clinical trial results are reported, and available agents compared. Finally, the place of each drug in therapy is compared between current worldwide guidelines

The role of iron in pulmonary pathology

Respiratory disease accounts for a large proportion of emergency admissions to hospital and diseaseassociated mortality. Genetic association studies demonstrate a link between iron metabolism and pulmonary disease phenotypes. IREB2 is a gene that produces iron regulatory protein 2 (IRP2), which has a key role in iron homeostasis. This review addresses pathways involved in iron metabolism, particularly focusing on the role of IREB2. In addition to this, environmental factors also influence phenotypic variation in respiratory disease, for example inhaled iron from cigarette smoke is deposited in the lung and causes tissue damage by altering iron homeostasis. The effects of cigarette smoke are detailed in this article, particularly in relation to lung conditions that favour the upper lobes, such as emphysema and lung cancer. Clinical applications of iron homeostasis are also discussed in this review, especially looking at the pathophysiology of chronic obstructive pulmonary disease, lung cancer, pulmonary infections and acute respiratory distress syndrome. Promising new treatments involving iron are also covered

The prevalence of bronchiectasis in patients with alpha-1 antitrypsin deficiency: initial report of EARCO

Alpha-1 antitrypsin deficiency; Emphysema; PrevalenceDeficiència d'alfa-1 antitripsina; Emfisema; PrevalençaDeficiencia de alfa-1 antitripsina; Enfisema; PrevalenciaBackground Although bronchiectasis has been recognised as a feature of some patients with Alpha1-Antitrypsin deficiency the prevalence and characteristics are not widely known. We wished to determine the prevalence of bronchiectasis and patient characteristics. The first cohort of patients recruited to the EARCO (European Alpha1 Research Collaboration) International Registry data base by the end of 2021 was analysed for radiological evidence of both emphysema and bronchiectasis as well as baseline demographic features. Results Of the first 505 patients with the PiZZ genotype entered into the data base 418 (82.8%) had a reported CT scan. There were 77 (18.4%) with a normal scan and 38 (9.1%) with bronchiectasis alone. These 2 groups were predominantly female never smokers and had lung function in the normal range. The remaining 303 (72.5%) ZZ patients all had emphysema on the scan and 113 (27%) had additional evidence of bronchiectasis. Conclusions The data indicates the bronchiectasis alone is a feature of 9.1% of patients with the PiZZ genotype of Alpha1-antitrypsin deficiency but although emphysema is the dominant lung pathology bronchiectasis is also present in 27% of emphysema cases and may require a different treatment strategy.The International EARCO registry is funded by unrestricted grants of Grifols, CSL Behring, Kamada, pH Pharma and Takeda to the European Respiratory Society (ERS)

Experience-based co-design to improve a pulmonary rehabilitation programme

PURPOSE The purpose of this paper is to investigate patient perspectives on attending pulmonary rehabilitation (PR). This qualitative case study identifies the benefits and challenges to attending PR and presents areas of improvements as recommended by patients. DESIGN/METHODOLOGY/APPROACH A qualitative case study of a UK case study based on a PR programme based on undertaking focus groups (=3) and interviews (=15) with current and former patients. FINDINGS The findings report patient perspectives of the challenges and benefits of attending a PR programme along with recommendations on how the service could be improved. RESEARCH LIMITATIONS/IMPLICATIONS The authors focussed solely on a UK PR programme, so the findings might not be applicable to other countries if PR is organised and provided in a unique way or setting. PRACTICAL IMPLICATIONS This paper provides valuable insights to patient perspectives offrom patients attending PR programmes, which are useful to those running and designing these services. ORIGINALITY/VALUE The findings identify the benefits and challenges for patients attending PR programmes and suggest areas where improvements can be made

Long-term effect of α1-antitrypsin augmentation therapy on the decline of FEV1 in deficient patients: an analysis of the AIR database

Lung structure and function; COPD and smokingEstructura y función pulmonar; EPOC y tabaquismoEstructura i funció pulmonar; MPOC i tabaquismeBackground Patients with ZZ (Glu342Lys) α-1-antitrypsin deficiency (ZZ-AATD) who received augmentation therapy with α-1-antitrypsin (AAT) in randomised controlled trials over 2–3 years failed to show a significant reduction of the annual decline of forced expiratory volume in 1 s (FEV1). Methods To compare the trajectory of FEV1 change during 4 or more years in ZZ-AATD patients with emphysema receiving or not receiving intravenous augmentation therapy, a retrospective analysis of FEV1 values entered in the Alpha-1 International Registry (AIR) of ZZ-AATD patients from five different European countries (Germany, UK, Spain, Italy and the Netherlands) was performed. The post-bronchodilator FEV1 % predicted values for baseline and follow-up over time from patients were analysed using linear mixed effects models. Results Data of 374 patients were analysed: 246 untreated and 128 treated with intravenous AAT augmentation therapy. The mean±sd follow-up duration of the untreated group was 8.60±3.34 years and 8.59±2.62 years for the treated group. The mixed effects model analysis showed a mean FEV1 decline of −0.931% predicted per year (95% CI −1.144 to −0.718) in the untreated group and a decline of −1.016% predicted per year (95% CI −1.319 to −0.7145) in the treated group. The likelihood ratio test showed no difference between the two groups (p=0.71). Conclusion In our study population, we could not detect a significant difference in the annual decline of FEV1 by AAT augmentation treatment over a mean period of 8.6 years. Other approaches are needed to validate any benefit of augmentation therapy.This study was supported by Stichting AIR

Adapting to domiciliary non-invasive ventilation in chronic obstructive pulmonary disease:a qualitative interview study

Background: Domiciliary non-invasive ventilation may be used in palliative care of patients with chronic obstructive pulmonary disease, although there is uncertainty regarding effect on quality of life. Aim: Explore experiences of domiciliary non-invasive ventilation in chronic obstructive pulmonary disease, to understand decision-making processes and improve future palliative care. Design: Qualitative interview study, based on constructivist grounded theory, and using the framework method for data management and analysis. Participants: 20 chronic obstructive pulmonary disease patients, 4 carers and 15 healthcare professionals. Results: Most patients had very severe chronic obstructive pulmonary disease. Data were categorised into four domains – clinical, technical, socio-economic and experiential. Healthcare professionals felt uncertain regarding clinical evidence, emphasising social support and tolerance as deciding factors in non-invasive ventilation use. Conversely, patients reported symptomatic benefit, which generally outweighed negative experiences and led to continued use. Healthcare professionals felt that patients chose to be on non-invasive ventilation; however, most patients felt that they had no choice as healthcare professionals recommended non-invasive ventilation or their poor health mandated it. Conclusions: Our study identifies ‘adapting to non-invasive ventilation’ as the central process enabling long-term use in palliative care, although the way in which this is approached by healthcare professionals and patients does not always converge. We present ideas emerging from the data on potential interventions to improve patient experience and adaptation. </jats:sec

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

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

Tuberculosis incidence correlates with sunshine : an ecological 28-year time series study

Birmingham is the largest UK city after London, and central Birmingham has an annual tuberculosis incidence of 80 per 100,000. We examined seasonality and sunlight as drivers of tuberculosis incidence. Hours of sunshine are seasonal, sunshine exposure is necessary for the production of vitamin D by the body and vitamin D plays a role in the host response to tuberculosis. Methods: We performed an ecological study that examined tuberculosis incidence in Birmingham from Dec 1981 to Nov 2009, using publicly-available data from statutory tuberculosis notifications, and related this to the seasons and hours of sunshine (UK Meteorological Office data) using unmeasured component models. Results: There were 9,739 tuberculosis cases over the study period. There was strong evidence for seasonality, with notifications being 24.1% higher in summer than winter (p<0.001). Winter dips in sunshine correlated with peaks in tuberculosis incidence six months later (4.7% increase in incidence for each 100 hours decrease in sunshine, p<0.001). Discussion and Conclusion: A potential mechanism for these associations includes decreased vitamin D levels with consequent impaired host defence arising from reduced sunshine exposure in winter. This is the longest time series of any published study and our use of statutory notifications means this data is essentially complete. We cannot, however, exclude the possibility that another factor closely correlated with the seasons, other than sunshine, is responsible. Furthermore, exposure to sunlight depends not only on total hours of sunshine but also on multiple individual factors. Our results should therefore be considered hypothesis-generating. Confirmation of a potential causal relationship between winter vitamin D deficiency and summer peaks in tuberculosis incidence would require a randomized-controlled trial of the effect of vitamin D supplementation on future tuberculosis incidence