Assistive technologies for home NIV in patients with COPD: feasibility and positive experience with remote-monitoring and volume-assured auto-EPAP NIV mode.

BACKGROUND: Outcomes for patients with chronic obstructive pulmonary disease (COPD) with persistent hypercapnic respiratory failure are improved by long-term home non-invasive ventilation (NIV). Provision of home-NIV presents clinical and service challenges. The aim of this study was to evaluate outcomes of home-NIV in hypercapnic patients with COPD who had been set-up at our centre using remote-monitoring and iVAPS-autoEPAP NIV mode (Lumis device, ResMed). METHODS: Retrospective analysis of a data set of 46 patients with COPD who commenced remote-monitored home-NIV (AirView, ResMed) between February 2017 and January 2018. Events including time to readmission or death at 12 months were compared with a retrospectively identified cohort of 27 patients with hypercapnic COPD who had not been referred for consideration of home-NIV. RESULTS: The median time to readmission or death was significantly prolonged in patients who commenced home-NIV (median 160 days, 95% CI 69.38 to 250.63) versus the comparison cohort (66 days, 95% CI 21.9 to 110.1; p<0.01). Average time to hospital readmission was 221 days (95% CI, 47.77 to 394.23) and 70 days (95% CI, 55.31 to 84.69; p<0.05), respectively. Median decrease in bicarbonate level of 4.9 mmol/L (p<0.0151) and daytime partial pressure of carbon dioxide 2.2 kPa (p<0.032) in home-NIV patients with no required increase in nurse home visits is compatible with effectiveness of this service model. Median reduction of 14 occupied bed days per annum was observed per patient who continued home-NIV throughout the study period (N=32). CONCLUSION: These findings demonstrate the feasibility and provide initial utility data for a technology-assisted service model for the provision of home-NIV therapy for patients with COPD.

Circulating Truncated Alpha-1 Antitrypsin Glycoprotein in Patient Plasma Retains Anti-Inflammatory Capacity.

Alpha-1 antitrypsin (AAT) is an acute phase protein that possesses immune-regulatory and anti-inflammatory functions independent of antiprotease activity. AAT deficiency (AATD) is associated with early-onset emphysema and chronic obstructive pulmonary disease. Of interest are the AATD nonsense mutations (termed null or Q0), the majority of which arise from premature termination codons in the mRNA coding region. We have recently demonstrated that plasma from an AATD patient homozygous for the Null Bolton allele (Q0bolton ) contains AAT protein of truncated size. Although the potential to alleviate the phenotypic consequences of AATD by increasing levels of truncated protein holds therapeutic promise, protein functionality is key. The goal of this study was to evaluate the structural features and anti-inflammatory capacity of Q0bolton-AAT. A low-abundance, truncated AAT protein was confirmed in plasma of a Q0bolton-AATD patient and was secreted by patient-derived induced pluripotent stem cell-hepatic cells. Functional assays confirmed the ability of purified Q0bolton-AAT protein to bind neutrophil elastase and to inhibit protease activity. Q0bolton-AAT bound IL-8 and leukotriene B4, comparable to healthy control M-AAT, and significantly decreased leukotriene B4-induced neutrophil adhesion (p = 0.04). Through a mechanism involving increased mRNA stability (p = 0.007), ataluren treatment of HEK-293 significantly increased Q0bolton-AAT mRNA expression (p = 0.03) and Q0bolton-AAT truncated protein secretion (p = 0.04). Results support the rationale for treatment with pharmacological agents that augment levels of functional Q0bolton-AAT protein, thus offering a potential therapeutic option for AATD patients with rare mutations of similar theratype.

The BLT1 Inhibitory Function of α-1 Antitrypsin Augmentation Therapy Disrupts Leukotriene B4 Neutrophil Signaling.

Leukotriene B4 (LTB4) contributes to many inflammatory diseases, including genetic and nongenetic forms of chronic obstructive pulmonary disease. α-1 Antitrypsin (AAT) deficiency (AATD) is characterized by destruction of lung parenchyma and development of emphysema, caused by low AAT levels and a high neutrophil burden in the airways of affected individuals. In this study we assessed whether AATD is an LTB4-related disease and investigated the ability of serum AAT to control LTB4 signaling in neutrophils. In vitro studies demonstrate that neutrophil elastase is a key player in the LTB4 inflammatory cycle in AATD, causing increased LTB4 production, and associated BLT1 membrane receptor expression. AATD patients homozygous for the Z allele were characterized by increased neutrophil adhesion and degranulation responses to LTB4. We demonstrate that AAT can bind LTB4 and that AAT/LTB4 complex formation modulates BLT1 engagement and downstream signaling events, including 1,4,5-triphosphate production and Ca(2+) flux. Additionally, treatment of ZZ-AATD individuals with AAT augmentation therapy decreased plasma LTB4 concentrations and reduced levels of membrane-bound neutrophil elastase. Collectively, these results provide a mechanism by which AAT augmentation therapy impacts on LTB4 signaling in vivo, and not only reinforces the utility of this therapy for resolving inflammation in AATD, but supports useful future clinical applications in treatment of other LTB4-related diseases.

Alpha-1 antitrypsin augmentation therapy corrects accelerated neutrophil apoptosis in deficient individuals.

Alpha-1 antitrypsin (AAT) deficiency (AATD) is characterized by neutrophil-driven lung destruction and early emphysema in a low AAT, and high neutrophil elastase environment in the lungs of affected individuals. In this study, we examined peripheral blood neutrophil apoptosis and showed it to be accelerated in individuals with AATD by a mechanism involving endoplasmic reticulum stress and aberrant TNF-α signaling. We reveal that neutrophil apoptosis in individuals homozygous for the Z allele (PiZZ) is increased nearly 2-fold compared with healthy controls and is associated with activation of the external death pathway. We demonstrate that in AATD, misfolded AAT protein accumulates in the endoplasmic reticulum of neutrophils, leading to endoplasmic reticulum stress and the expression of proapoptotic signals, including TNF-α, resulting in increased apoptosis and defective bacterial killing. In addition, treatment of AATD individuals with AAT augmentation therapy decreased neutrophil ADAM-17 activity and apoptosis in vivo and increased bacterial killing by treated cells. In summary, this study demonstrates that AAT can regulate neutrophil apoptosis by a previously unidentified and novel mechanism and highlights the role of AAT augmentation therapy in ameliorating inflammation in AATD.

Official conceptualizations of person-centered care: which person counts?

Numerous studies have indicated that a "psycho-social" person-centered care approach, involving the delivery of a compassionate, respectful model of care, leads to a high quality of life, particularly for older people living in residential care. This has prompted policy-makers to endorse this approach. Yet, some commentators have argued that the model of person-centered care in official government policies equates to a "consumer-based" rather than a psycho-social approach, as it focuses solely on offering service-users more choice and on promoting independence. However, as such arguments are made in the absence of any empirical analysis, it is unclear both whether such a distinction exists in practice, and, if so, how this alternative model developed. This study explores the development of minimum standards for residential care settings for older people in Ireland in order to address this gap in our understanding of person-centered care. Findings confirm that a consumer-driven model of person-centered care underpins the Irish Standards; residential care is portrayed as a hotel-like service and residents as discerning consumers, which may be unsuitable for older people in residential care with limited capacity to make key choices. Analysis indicates that this model can be seen both as an extension of consumer-driven policies endorsed by many neo-liberal governments, and also of policy-makers' fears of losing their autonomy when they reach the "Fourth Age". This study is particularly illuminating, given the similarities between the Irish care system with England, Scotland, Wales, Northern Ireland and Australia.

Expanded, but not regulated: ambiguity in home-care policy in Ireland.

This article argues that home-care policy in Ireland was ambiguous throughout the first decade of the 21st century: policy-makers expanded home care, but failed to develop policies to govern this expanded provision. As a result, home care became more widely available in the absence of a framework to govern access to services and to regulate care providers. We analysed official policy documents, statistics and policy critiques published between 2000 and 2010 in order to understand this incongruity between the expansion of home-care services and the failure to develop policies to govern access to and quality of services. The key factors that motivated home-care expansion in the Irish case were: (1) problems in the acute hospital sector and the perception of home care as a partial solution to these (political blame avoidance) and (2) significant GDP growth (until 2007) that provided politicians with the means to fund expansion in home-care services (political credit claiming). The key factors that inhibited the development of a policy framework to govern home-care services were: (1) weak governance structures in health services and decision-making at national level based on short-term political gain; (2) Ireland's adherence to the liberal welfare state model and concern about uncontrollable care costs in the face of population ageing; (3) until 2010, paucity of attention to home-care issues in the Irish media and (4) weak provider interest representation. The recent budgetary cutbacks in Ireland bring into sharp relief the political expediency of an unregulated domiciliary care sector and absence of entitlements to home care. We conclude that the forces that drive expanded provision are different from drivers of policy to govern home care and that weakness of governance structures and political advantages of the absence of regulation are the main reasons for the lack of standards and entitlement rules.

'It is nice to see someone coming in': exploring the social objectives of Meals-on-Wheels.

Despite the fact that Meals-on-Wheels have both nutritional and social aspects, research on the social objectives of the service is lacking. This study set out to develop an understanding of the social objectives of Meals-on-Wheels and to explore the extent to which they are met by Ireland's Meals-on-Wheels services. A literature review suggested that Meals-on-Wheels services can potentially meet three social objectives: (a) providing meals recipients with social contact, (b) helping to restimulate an interest in meals and regularising mealtimes, and (c) helping to develop acceptance of the service. Interviews were conducted with 66 meals recipients to explore these themes and augment them as necessary. Study results show that meals recipients derive limited social contact from the service; regularising mealtimes was not important to most recipients; and many were reluctant to accept the service. The three objectives are therefore minimally met within the Irish system at present.

Living in institutional care: residents' experiences and coping strategies.

Insights into daily living in residential care settings are rare. This article draws on a qualitative dataset (semi-structured interviews and recordings of residents' council meetings) that gives a glimpse of the experiences and coping strategies of (older) people living in residential care. The data highlight the range of unmet needs of the residents, similar to the categories of physiological, safety, love, esteem, and self-actualization needs in Maslow's hierarchy of needs theory. Our analysis indicates that "higher" and "lower" needs are closely intertwined and mutually reinforcing and should therefore be accorded equal emphasis by professionals (including social workers) employed within residential care settings.