Impact of PIF, Inhalation Technique and Medication Adherence on Health Status and Exacerbations in COPD : Protocol of a Real-World Observational Study (PIFotal COPD Study)

ACKNOWLEDGEMENTS The authors thank Evgeni Dvortsin for his valuable contribution in the initial development of the project. Funding. This study was co-funded by Boehringer Ingelheim and GPRI. The study sponsor is GPRI, who will also be performing the data collection and analysis. Boehringer Ingelheim is the funding and scientific partner, and is funding the journal’s Rapid Service fee.Peer reviewedPublisher PD

Clinical recommendations for dry powder inhaler use in the management of COPD in primary care

Acknowledgements The study sponsor was the General Practitioners Research Institute; data collection and analysis were performed by General Practitioners Research Institute. Boehringer Ingelheim was the funding and scientific partner. The members of the PIFotal study group would like to acknowledge Dr. Jaco Voorham from Data to Insights Research Solutions for his assistance with the statistical analyses, Dr Wilma Zijlema for her assistance with the review, drafting and editing of the paper, and Dr. Hans Wouters for his contribution to the project administration in the initial phase of the project. They would also like to thank all contributing researchers: Maria João Barbosa, Ana Margarida Cruz, Liliana Silva, Duarte Araújo, Eurico Silva, Daniel Castro, João Ramires, Ana Fernandes, Catarina Carvalho, Raquel Castro, Jerzy Zientek, Ewa Pasko, Witold Drzastwa, Tomasz Kachel, Kornelia Ciekalska, Krzysztof Wytrychowski, Bernard Panaszek, Krzysztof Kowal, Ebian Brill, Willemien Feenstra, Geert Struik, Hans Schuurman, Mariette van Oostrum, Hennie Holwerda Meekma, Boudewijn Dierick, George Amofa, Esther Kuipers, Lennard Ringnalda, Boris Tyndall, Mark Drenth, Peter Mast, Hilbert Talsma, Raoul Wolfs, Cobie Hoogeboom, Hanneke van Andel, Paul Stoutenberg, Nancy van de Laak, Tessa Hillaert, Laura Holtzer, Natascha Fehrmann, Anniek Makkinga – Maassen van den Brink, Annemarie Hilbink, Erik Feenstra, Murat Tek, Sabrina Burer, Jan van Ginkel, Rinze Boersma, Alyssa Bonger, Miguel Roman Rodriguez, Marina García Pardo, Alejandra Valero Suau, Laura López Velasco, Cecilia Amato, Francisco Palmer Simó, Alberto Abenza, Rosa Llull Vila, Bartolomé Llompart Van Belzen, Silvia Jimeno Martínez, Francesc Moranta Ribas, Margarita Perelló Oliver, Yolanda Gómez López, Patricia Ibañez Gómez, María Nieves Mendieta Lagos, Laura Bueno López, Virginia María Mirabal Sánchez, Ana Delia Rodríguez Delgado, Nils Fischer, Alicia González Sansó, Nayra Ramírez Mendoza, Valeria Gazzaneo, Paula Merced Guillama Rodríguez, Virginia Naranjo Guerrero, Jose Angel Suarez Caballero, Isidoro Souto Bethencourt, Juan R. Dominguez Beatell, Elena Vanesa Rojas Manrique, Maria Jose Sanz Orejas, Cary Perez Lorenzo, Jesús Antonio Pérez Jiménez, Silvia 480 Lara Afonso Trujillo, Bartolomé Dominguez Del Río Boada, Stavroula Papageorgakopoulou, Eleytheria Vakouti, Claire Gkatzoudi, Thodoris Krasanakis, Dimitris Kounalakis , Izoldi Bouloukaki , Nikolaos Tsakountakis, Emmanouela Chronaki, Katherine Mary Borg and Kamila Abutalieva for their time and efforts to perform the study measurements and complete patient inclusion, even in the challenging times of the pandemic. Finally, they would like to thank the participants who generously gave their time to participate in the study.Peer reviewedPublisher PD

Sufficient inspiratory effort for a dry powder inhaler - do we have to measure it, or can we observe it? : Post hoc analysis of the PIFotal study.

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Suboptimal Peak Inspiratory Flow and Critical Inhalation Errors are Associated with Higher COPD-Related Healthcare Costs

Purpose: To assess the relationship between suboptimal Peak Inspiratory Flow (sPIF), inhalation technique errors, and non-adherence, with Healthcare Resource Utilisation (HCRU) in Chronic Obstructive Pulmonary Disease (COPD) patients receiving maintenance therapy via a Dry Powder Inhaler (DPI). Patients and methods: The cross-sectional, multi-country PIFotal study included 1434 COPD patients (≥40 years) using a DPI for maintenance therapy. PIF was measured with the In-Check DIAL G16, and sPIF was defined as a typical PIF lower than required for the device. Inhalation technique was assessed by standardised evaluation of video recordings and grouped into 10 steps. Patients completed the "Test of Adherence to Inhalers" questionnaire. HCRU was operationalised as COPD-related costs for primary healthcare, secondary healthcare, medication, and total COPD-related costs in a 1-year period. Results: Participants with sPIF had higher medication costs compared with those with optimal PIF (cost ratio [CR]: 1.07, 95% CI [1.01, 1.14]). Multiple inhalation technique errors were associated with increased HCRU. Specifically, "insufficient inspiratory effort" with higher secondary healthcare costs (CR: 2.20, 95% CI [1.37, 3.54]) and higher total COPD-related costs (CR: 1.16, 95% CI 1.03-1.31). "no breath-hold following the inhalation manoeuvre (<6 s)" with higher medication costs (CR: 1.08, 95% CI [1.02, 1.15]) and total COPD-related costs (CR 1.17, 95% CI [1.07, 1.28]), and "not breathing out calmly after inhalation" with higher medication costs (CR: 1.19, 95% CI [1.04, 1.37]). Non-adherence was not significantly associated with HCRU. Conclusion: sPIF and inhalation technique errors were associated with higher COPD-related healthcare utilisation and costs in COPD patients on DPI maintenance therapy

Factors associated with health status and exacerbations in COPD maintenance therapy with dry powder inhalers

Funding Information: J.K. reports grants, personal fees and non-financial support from AstraZeneca, GSK and Boehringer Ingelheim; grants and personal fees from Chiesi Pharmaceuticals and TEVA; grants from Mundipharma; personal fees from MSD and COVIS Pharma; and also holds 72.5% of shares in the General Practitioners Research Institute. H.W. has received grants from Boehringer Ingelheim, which is the financial and scientific partner of GPRI for the submitted study, and from AstraZeneca, Novartis and Chiesi for scientific projects in the area of COPD/asthma. S.B.-A. has received grants from TEVA, and personal fees from TEVA, Boehringer Ingelheim, AstraZeneca, GSK, Sanofi and Mylan. J.C.d.S. reports or personal fees from AstraZeneca, Bial, Boehringer Ingelheim, GSK, Medinfar, Mundipharma and Sanofi. B.C. received honorarium from GSK and Sanofi. J.v.C., L.D., I.v.G.-P., I.v.d.H., Y.J., M.K., B.M., K.S., N.S., M.H., B.M. and M.T.L. were employed by General Practitioners Research Institute (GPRI) at the time of the study. In the past three years (2019–2021), GPRI conducted investigator- and sponsor-initiated research funded by non-commercial organizations, academic institutes, and pharmaceutical companies (including AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, Novartis, and Teva). R.D. has received grants and personal fees from TEVA, Boehringer Ingelheim, AstraZeneca, GSK, Chiesi, Focus Care, and Glenmark. R.G. has received personal fees from AstraZeneca, GSK and Chiesi. E.D. holds 27.5% of shares in the General Practitioners Research Institute. M.G.P. receives grants from AstraZeneca, GSK and Boehringer Ingelheim. A.G. and A.d.l.H. are employees of Boehringer Ingelheim. F.L. received grants and personal fees from GSK, personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Menarini International, Novartis, Orion, and Trudell International, outside the submitted work. T.M. is an Assoicate Editor at npj Primary Care Respiratory Medicine. J.M. received grants from Boehringer Ingelheim, during the conduct of the study; and grants from AstraZeneca, Chiesi, Novartis, and GSK, outside the submitted work. D.P. reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Theravance and Zentiva (Sanofi Generics); grants from the British Lung Foundation, Respiratory Effectiveness Group, UK National Health Service, and AKL Research and Development Ltd; personal fees from Cipla, GlaxoSmithKline, Kyorin, Merck, Mundipharma, Airway Vista Secretariat, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc, Strategic North Limited, Synapse Research Management Partners S.L., Talos Health Solutions, and WebMD Global LLC; non-financial support from Efficacy and Mechanism Evaluation programme and Health Technology Assessment; stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); and 5% shareholding in Timestamp, which develops adherence monitoring technology. M.R.-R. receives grants and personal fees from AstraZeneca and GSK; and personal fees from Boehringer Ingelheim, Chiesi, Menarini, Mundipharma, Novartis, Pfizer, TEVA and BIAL. I.T. reports grants and personal fees from GSK, AstraZeneca, Boehringer Ingelheim, Menarini, Novartis, Chiesi and Elpen. O.U. reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Edmond Pharma, Chiesi and GSK; grants from Edmond Pharma; and personal fees from Napp, Mundipharma, Sandoz, Takeda, Cipla, COVIS, Novartis, Mereobiopharma, Orion, and Menarini. S.B.-A. and T.M. are Associate Editors at npj Primary Care Respiratory Medicine, and I.T. is Editor in Chief. These authors were not involved in the journal’s review of, or decisions related to, this manuscript.Peer reviewedPublisher PD

On the notion of home and the goals of palliative care

The notion of home is well known from our everyday experience, and plays a crucial role in all kinds of narratives about human life, but is hardly ever systematically dealt with in the philosophy of medicine and health care. This paper is based upon the intuitively positive connotation of the term “home.” By metaphorically describing the goal of palliative care as “the patient’s coming home,” it wants to contribute to a medical humanities approach of medicine. It is argued that this metaphor can enrich our understanding of the goals of palliative care and its proper objectives. Four interpretations of “home” and “coming home” are explored: (1) one’s own house or homelike environment, (2) one’s own body, (3) the psychosocial environment, and (4) the spiritual dimension, in particular, the origin of human existence. Thinking in terms of coming home implies a normative point of view. It represents central human values and refers not only to the medical-technical and care aspects of health care, but also to the moral context

Suboptimal peak inspiratory flow and critical inhalation errors are associated with higher COPD-related healthcare costs

Acknowledgements The members of the PIFotal study group would like to acknowledge Dr. Judith Cohen and Dr. Wilma Zijlema for their assistance with the review, drafting, and editing of the paper, and Dr. Hans Wouters for his contribution to the project administration in the initial phase of the project. They would also like to thank all contributing researchers: Maria João Barbosa, Ana Margarida Cruz, Liliana Silva, Duarte Araújo, Eurico Silva, Daniel Castro, João Ramires, Ana Fernandes, Catarina Carvalho, Raquel Castro, Jerzy Zientek, Ewa Pasko, Witold Drzastwa, Tomasz Kachel, Kornelia Ciekalska, Krzysztof Wytrychowski, Bernard Panaszek, Krzysztof Kowal, Ebian Brill, Willemien Feenstra, Geert Struik, Hans Schuurman, Mariette van Oostrum, Hennie Holwerda Meekma, Boudewijn Dierick, George Amofa, Esther Kuipers, Lennard Ringnalda, Boris Tyndall, Mark Drenth, Peter Mast, Hilbert Talsma, Raoul Wolfs, Cobie Hoogeboom, Hanneke van Andel, Paul Stoutenberg, Nancy van de Laak, Tessa Hillaert, Laura Holtzer, Natascha Fehrmann, Anniek Makkinga – Maassen van den Brink, Annemarie Hilbink, Erik Feenstra, Murat Tek, Sabrina Burer, Jan van Ginkel, Rinze Boersma, Alyssa Bonger, Miguel Roman Rodriguez, Marina García Pardo, Alejandra Valero Suau, Laura López Velasco, Cecilia Amato, Francisco Palmer Simó, Alberto Abenza, Rosa Llull Vila, Bartolomé Llompart Van Belzen, Silvia Jimeno Martínez, Francesc Moranta Ribas, Margarita Perelló Oliver, Yolanda Gómez López, Patricia Ibañez Gómez, María Nieves Mendieta Lagos, Laura Bueno López, Virginia María Mirabal Sánchez, Ana Delia Rodríguez Delgado, Nils Fischer, Alicia González Sansó, Nayra Ramírez Mendoza, Valeria Gazzaneo, Paula Merced Guillama Rodríguez, Virginia Naranjo Guerrero, Jose Angel Suarez Caballero, Isidoro Souto Bethencourt, Juan R. Dominguez Beatell, Elena Vanesa Rojas Manrique, Maria Jose Sanz Orejas, Cary Perez Lorenzo, Jesús Antonio Pérez Jiménez, Silvia Lara Afonso Trujillo, Bartolomé Dominguez Del Río Boada, Stavroula Papageorgakopoulou, Eleytheria Vakouti, Claire Gkatzoudi, Thodoris Krasanakis, Dimitris Kounalakis , Izoldi Bouloukaki, Nikolaos Tsakountakis, Emmanouela Chronaki, Katherine Mary Borg and Kamila Abutalieva for their time and efforts to perform the study measurements and complete patient inclusion, even in the challenging times of the pandemic. Finally, they would like to thank the participants who generously gave their time to participate in the study. Funding The study sponsor is the General Practitioners Research Institute; data collection and analysis were performed by the General Practitioners Research Institute. Boehringer Ingelheim is the funding and scientific partnerPeer reviewedPublisher PD

Perceptions on home-administration of biologics in the context of severe asthma: an international qualitative study

BACKGROUND: Biologics are an effective therapy for severe asthma. Home administration of biologics by patients is likely to facilitate their accessibility. Yet little is known about patients' and health care providers' (HCPs) perceptions regarding home administration of biologics. OBJECTIVE: The aim of this study is to create more insight into the perceptions and experiences of patients and HCPs regarding home administration of biologics in the context of the treatment of severe asthma. METHODS: A qualitative international study was performed in the Netherlands, United States, Australia, and United Kingdom. In each country, 2 focus groups were held with potential/recent and long-term users of biologics at home. Prior to the focus groups, patients were prompted with themes on online forums. For triangulation purposes, interviews were held with HCPs to discuss salient findings from forums and focus groups. Data were analyzed with qualitative content analysis. RESULTS: In total, 75 patients participated in the forums, of which 40 participated in the focus groups. Furthermore, 12 HCPs were interviewed. The following overarching themes were identified: living with severe asthma; practical aspects of using biologics; the role of HCPs regarding biologics; social support from family, friends, and others; effectiveness of biologics and other treatments; side effects of biologics. CONCLUSIONS: This study showed that, for those using biologics for severe asthma, the benefits of home administration of biologics usually outweigh inconvenience and side effects. Guided practice, accessible support contact, and monitoring including social support should be central in the transition from hospital to home administration of asthma biologics

Clinical recommendations for dry powder inhaler use in the management of COPD in primary care

Over 1400 patients using dry powder inhalers (DPIs) to deliver COPD maintenance therapies were recruited across Europe and Australia. Their peak inspiratory flow (PIF) was measured, inhaler technique was observed, and adherence to treatment assessed. From relating the findings with patient health status, and thereby identifying critical errors, key clinical recommendations for primary care clinicians were determined, namely – measure PIF before prescribing a DPI to ensure inhalation manoeuvre ability is well-matched with the device. Some patients could benefit from inhalation training whereas others should have their DPI changed for one better suited to their inspiratory ability or alternatively be prescribed an active device (such as a soft mist inhaler or pressurized metered dose inhaler). Observing the inhalation technique was valuable however this misses suboptimal PIF (approaching one fourth of patients with a satisfactory observed manoeuvre had a suboptimal PIF for their DPI). Assess adherence as deliberate non-adherence can point to a mismatch between a patient and their inhaler (deliberate non-adherence was significantly associated with PIFs below the minimum for the DPI). In-person observation of inhalation technique was found to be inferior to video rating based on device-specific checklists. Where video assessments are not possible, observation training for healthcare professionals would therefore be valuable particularly to improve the ability to identify the critical errors associated with health status namely ‘teeth and lips sealed around mouthpiece’, ‘breathe in’ and ‘breathing out calmly after inhalation’. However, it is recommended that observation alone should not replace PIF measurement in the DPI selection process. Trial registration: https://clinicaltrials.gov/ct2/show/NCT04532853

Identifying critical inhalation technique errors in Dry Powder Inhaler use in patients with COPD based on the association with health status and exacerbations: findings from the multi-country cross-sectional observational PIFotal study

Abstract Background Correct inhaler use depends on a complex interplay of factors, including device preparation and generating sufficient inspiratory flow. It is currently unknown which inhalation technique errors can be considered critical in Chronic Obstructive Pulmonary Disease (COPD) patients on Dry Powder Inhaler (DPI) maintenance therapy. Objective To investigate the association between inhalation technique errors and health status or exacerbations in patients with COPD. Additionally, the association between the number of errors and COPD outcomes was determined. Methods The PIFotal study is a cross-sectional multi-country observational study in a primary care setting, including 1434 COPD patients aged ≥ 40 years (50.1% female; mean age 69.2 yrs) using a DPI for their maintenance therapy. Inhalation technique was video recorded and scored by two independent researchers using inhaler-specific checklists. Health status was assessed with two questionnaires; the Clinical COPD Questionnaire (CCQ) and the COPD Assessment Test (CAT). The number of moderate and severe exacerbations in the past 12 months was recorded. Critical errors were identified based on their association with health status or exacerbations through multi-level prediction models adjusted for identified confounding. Results Errors in inhalation technique steps ‘Breathe in’, ‘Hold breath’, and ‘Breathe out calmly after inhalation’ were significantly associated with poorer CCQ and CAT outcomes and thus deemed critical. None of the errors were significantly associated with moderate exacerbations. Patients with errors ‘Preparation’, ‘Hold inhaler in correct position during inhalation’, and ‘Breathe in’ had significantly more severe exacerbations, and therefore these errors were also deemed critical. 81.3% of patients with COPD made at least one critical error. Specific combinations of errors were associated with worse outcomes. The more inhalation technique errors identified, the poorer the health status and the higher the exacerbation rate. Conclusion In this study, we identified multiple critical inhalation technique errors in COPD patients using DPIs each associated with poorer outcomes. Explorative analysis revealed that specific combinations of errors may be of clinical relevance, especially those related to the inhalation manoeuvre. COPD outcomes worsened with increasing error count. These results warrant further prospective longitudinal studies to establish the effect of correcting these errors on COPD control. Trial registration https://clinicaltrials.gov/ct2/show/NCT04532853 (31/08/2020