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Maria Hollmen,1 Tom Bromilow,2 Adam B Smith,2 Stuart Mealing,2 Damian Lewis,2 Liam Galvin,3 Steve Jones,3 Luís Pacheco,4 Stéphane Soulard,4 Antoine Froidure5,6 1Faculty of Medicine, University of Helsinki, Helsinki, Finland; 2York Health Economics Consortium (YHEC), York, UK; 3European Pulmonary Fibrosis & Related Disorders Federation, Overijse, Belgium; 4Boehringer Ingelheim, Amsterdam, the Netherlands; 5Service de Pneumologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium; 6Institut de Recherche Expérimentale et Clinique, UCLouvain, Ottignies-Louvain-la-Neuve, BelgiumCorrespondence: Maria Hollmen, Faculty of Medicine, University of Helsinki, Helsinki, Finland, Email maria.hollmen@helsinki.fiIntroduction: Idiopathic Pulmonary Fibrosis (IPF) is a rare disease that causes shortness of breath, dry cough, and tiredness. While there is no cure for IPF, current therapeutic treatments aim to slow lung degeneration while managing side effects. There is little known about patient experience and attitude with regards to their disease and medication.Purpose: To understand the perceptions, behaviors and drivers of treatment decision-making among patients, caregivers and pulmonologists in IPF.Patients and Methods: Online surveys to patients with IPF, caregivers and pulmonologists were developed and administered in Belgium, Finland, France, Greece (pulmonologists only), the Netherlands, Ireland and the United Kingdom between November 2021 and January 2022.Results: A total of 111 patients, 22 caregivers and 140 pulmonologists participated. Half (47%) of patients rated their disease as “severe”, while pulmonologists reported that a quarter of their patients had a low Forced Vital Capacity (FVC) (below 50% of the predicted value). Between 21% and 42% of the patients do not take an IPF medication (patients’ perception) or antifibrotic (physicians’ perception). Pulmonologists reported that a total of 58% of their patients were receiving antifibrotic medication, any IPF medication, while around 53%, 55%, 35% and 73% of the patients limited their exposure (sometimes or often) to the sun due to IPF, considered taking medication against diarrhea, nausea/vomiting and heartburn, respectively. Treatment adherence was relatively high (81%), in line with the caregivers’ view and the pulmonologists’ expectations. Overall, cultural, clinical or socio-demographic factors impacted patients’ perceptions or behaviors.Conclusion: This study shows there is a significant proportion of IPF patients who remain untreated, a misalignment of disease severity between patients and their physicians and patient background impacts behavior. Overall, more in-depth patient–physician communication is needed to improve treatment experience.Keywords: online survey, antifibrotic, adherence, behavior, lung disease, outcomes research

Maria Hollmen,1 Marlies Wijsenbeek,2 Tom Bromilow,3 Adam B Smith,3 Stuart Mealing,3 Damian Lewis,3 Liam Galvin,4 Steve Jones,4 Guus Asijee,5 Stéphane Soulard,5 Antoine Froidure6,7 1Faculty of Medicine, University of Helsinki, Helsinki, Finland; 2Centre of Excellence for Interstitial Lung Diseases and Sarcoidosis, Department of Respiratory Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; 3York Health Economics Consortium (YHEC), York, UK; 4European Pulmonary Fibrosis & Related Disorders Federation, Overijse, Belgium; 5Boehringer Ingelheim, Amsterdam, the Netherlands; 6Service de Pneumologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium; 7Institut de Recherche Expérimentale et Clinique, UCLouvain, BelgiumCorrespondence: Maria Hollmen, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8 P.O. Box 63, Helsinki, 00014, Uusimaa, Finland, Email maria.hollmen@hus.fiPurpose: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and ultimately fatal lung disease that, while rare, has seen incidence rise over time. There is no cure for IPF other than a lung transplant, though two antifibrotic (AF) drugs do exist to slow disease progression. While these drugs are efficacious, they are both associated with differing profiles of adverse events. This study aimed to elicit patient, caregiver and pulmonologist preferences on the treatment profiles of AFs via a discrete choice experiment (DCE).Patients and Methods: The DCE and associated survey were distributed across 7 European countries, and bespoke DCEs were developed for patients/caregivers and pulmonologists. After collaboration with European Pulmonary Fibrosis & Related Disorders Federation (EU-PFF) and expert pulmonologists, respectively, a patient/caregiver DCE with 5 attributes and a pulmonologist DCE with 6 attributes were finalized. The DCEs had a blocked approach to reduce participant burden and were distributed on an online survey platform. Preferences were estimated through conditional multinomial logit regression analysis.Results: Ninety-five patients, 22 caregivers and 115 pulmonologists fully completed their respective DCEs. Overall, patients and caregivers preferred management of treatment-related adverse events over both survival benefits and disease progression. Nearly all preference levels were found to be significantly different from their reference level. In contrast, pulmonologists showed a greater preference for control of lung function and exacerbations over adverse events. Although there were relative differences between the univariate subgroups in terms of the preference weights, most of these were not statistically significant.Conclusion: The outcomes from this study suggest that while patients and caregivers had similar preferences for characteristics of IPF treatments, pulmonologists did not share those same preferences. Patients and caregivers preferred safety, while pulmonologists preferred efficacy. These differences should be considered by clinicians to better involve the patient in treatment decision-making for IPF.Keywords: treatment preferences, online survey, outcomes research, lung disease

Background: Health-related quality of life (HRQoL) assessments and estimates of prognosis are needed for comprehensive care and planning of subsequent treatment in patients with idiopathic pulmonary fibrosis (IPF). We investigated HRQoL and its association with survival using a disease-specific tool in patients with IPF., Methods: The patients were recruited from the real-life FinnishIPF study in 2015. HRQoL was assessed with the King's Brief Interstitial Lung Disease (K-BILD) questionnaire every six months for 2.5 years. Dyspnoea was assessed with the modified Medical Research Council (mMRC) dyspnoea scale. Survival was registered until 31 December 2022. Patient survival according to the K-BILD total score was evaluated using the Kaplan‒Meier method. The Friedman test was used to compare the K-BILD total scores longitudinally, and the Mann‒Whitney U test was used to compare the mMRC groups. P values < 0.05 were considered statistically significant., Results: The median K-BILD total score (n = 245) was 51.6. At baseline, patients in the highest HRQoL quartile (K-BILD scores 58.9-100) had a longer median survival time (5.3 years) than did those with scores of 51.7-58.8 (3.1 years), 45.7-51.6 (2.3 years), and 0.0-45.6 (1.8 years). A decrease in the K-BILD total score of ≥ 5 units in the preceding 12 or 24 months showed a trend towards poorer survival, although statistical significance was not reached. Ninety-four patients survived more than 2.5 years and had available K-BILD data at all time points. The K-BILD total score remained higher in patients with a baseline mMRC of 0-1 than in those with a mMRC of 2-4, and the total score decreased only modestly in both groups (median of 3.3 and 4.8 units in patients with mMRC scores of 0-1 and 2-4, respectively)., Conclusions: In IPF, a reduced HRQoL is associated with impaired survival. A K-BILD total score less than approximately 50 units is associated with a median survival of approximately two years. In addition to assessing the treatment needs of patients with IPF using K-BILD, a decreased score may be useful for facilitating advance care planning and transplantation assessment., (© 2024. The Author(s).)

Chronic inflammation plays a crucial role in coronary artery disease (CAD), but differences in specific cytokine profiles between acute coronary syndrome (ACS) and stable CAD remain unknown. We investigated cytokine differences between these two manifestations of CAD. The study included 308 patients with angiographically detected, hemodynamically significant CAD: 150 patients undergone angiography for ACS, 158 patients undergone angiography for stable CAD. To assess dynamic changes, 116 patients had index angiogram at least 3 months earlier. We measured the serum concentrations of 48 circulating cytokines. The ACS group had decreased interleukin (IL) 4 (p = 0.005), and increased IL-8 (p = 0.008), hepatocyte growth factor (HGF) (p < 0.001) and macrophage colony-stimulating factor (M-CSF) (p = 0.002) levels compared with the stable CAD group. Multivariable logistic regression revealed increased levels of HGF (OR 18.050 [95% CI 4.372-74.517], p < 0.001), M-CSF (OR 2.257 [1.375-3.705], p = 0.001) and IL-6 (OR 1.586 [1.131-2.224], p = 0.007), independently associated with ACS. In the post-angiography group, only diminished platelet-derived growth factor-BB levels in ACS-manifested patients were observed (OR 0.478, [0.279-0.818], p = 0.007). Cytokine profiles differ between ACS and stable CAD. Such differences seem to be mainly reversible within 3 months after ACS. Thus, targeting one or two cytokines only might not offer one-size fits all-therapeutic approach for CAD-associated inflammation.Trial registration: NCT03444259., (© 2024. The Author(s).)

Background: Research on health-related quality of life (HRQoL) is crucial for developing comprehensive palliative care in idiopathic pulmonary fibrosis (IPF). Objectives: To study IPF patients' HRQoL compared with general population and its association with dyspnea in a longitudinal follow-up. Design: Assessment of IPF patients' HRQoL by a generic tool. Comparison of baseline data with the general population and a 30-month follow-up with 6 months intervals. Setting/Subjects: In total, 246 IPF patients were recruited from the Finnish nationwide real-life study, FinnishIPF. Measurements: Modified Medical Research Council (MMRC) dyspnea scale for dyspnea and the generic HRQoL tool 15D for the total and dimensional HRQoL were used. Results: At baseline, the mean 15D total score was lower (0.786, standard deviation [SD] 0.116) in IPF patients than in the general population (0.871, SD 0.043) ( p  < 0.001) and among the IPF patients with MMRC ≥2 compared with those with MMRC <2 ( p  < 0.001). In patients with MMRC ≥2, significant impairment compared with general population existed in 11 dimensions of HRQoL, such as breathing, usual activities, and sexual activity, whereas this was true in only 4 dimensions in MMRC <2 category. Mental function was not impaired in either group. During the follow-up, 15D total score decreased in both MMRC categories ( p  < 0.001) but stayed constantly worse in the MMRC ≥2 group. Seven and two dimensions of HRQoL significantly declined in the categories of MMRC <2 and MMRC ≥2, respectively. Conclusions: Patients with IPF, especially if dyspnea limits everyday life, suffer from widely impaired HRQoL, although self-assessed mental capability is preserved. Integrated palliative care is supported to face the multiple needs of IPF patients.

Multidisciplinary meeting (MDM) is a core element in the diagnosis of interstitial lung diseases (ILD). The aim of the study was to investigate the implementation and key elements related to ILD MDMs in Finnish specialized care, which is characterized by long travel distances and a large number of small centers treating patients suffering from ILDs. An electronic questionnaire was sent to ILD experts working at five academic centers of Finland regarding the implementation of ILD MDMs with the focus on utilization of virtual communication. Responses were received from all academic centers of Finland ( n  = 5) whose catchment areas cover all of Finland. ILD MDMs were organized in each center approximately every two weeks and the core participants included a radiologist, respiratory physicians, junior staff, pathologist and a rheumatologist. All non-academic centers could refer their patients to be evaluated in ILD MDM of an academic center. Virtual communication was utilized by all academic centers in the implementation of ILD MDMs, being most common among small centers located in Eastern and Northern Finland. Virtual access to ILD MDM of an academic center was available in most parts of Finland, enabling small centers to benefit from the ILD expertise of academic centers., Competing Interests: JS reports congress/travel costs from Boehringer Ingelheim, GlaxoSmithKline and Novartis Finland Oy, and lecturer’s fees from Chiesi, all outside the submitted work. HN reports grants for scientific work from the Foundation of the Finnish Anti-Tuberculosis Association and the North Savo Regional Fund of the Finnish Cultural Foundation, lecturers´ fees from Boehringer Ingelheim and Roche and congress/travel support from Boehringer-Ingelheim, Sanofi-Genzyme, Chiesi and Duodecim, all outside the submitted work. UH reports consulting and lecture fees from Johnson and Johnson and Boehringer Ingelheim, and congress travel costs from Chiesi and Roche. HH reports lecture fees from Boehringer Ingelheim and Chiesi, outside the submitted work. MK has nothing to disclose. MH reports lecture fees and payments for research purposes from Boehringer Ingelheim. MP reports personal lecture fee, congress travel costs and advisory board membership at Boehringer Ingelheim, lecture fee from Roche, congress travel cost from Orion Pharma, outside the submitted work. RK reports consulting and lecture fees from Boehringer Ingelheim, Roche and MSD, and virtual congress costs from Roche and Novartis., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Study Objectives: As sleep latency is an important factor in the diagnosis of many disorders, it is important to know whether the patient's self-reported evaluation of sleep latency corresponds with an objectively measured evaluation. Some studies indicate that patients usually overestimate their sleep latency. We sought to determine how comorbidities affect the patient's ability to assess their sleep latency., Methods: This was a retrospective study of 240 patients who had a polysomnography recorded at our sleep unit or at home in 2017-2020. Data on comorbidities were collected from hospital records., Results: Mean objective sleep latency (29.5 minutes, standard deviation [SD] 35.5) was significantly lower than self-reported sleep (37.4 minutes, SD 41.6) ( P < .001). The patients who overestimated their sleep latency had higher mean apnea-hypopnea index (18.8 events/h, SD 21.6, vs 13.4 events/h, SD 12.8; P = .04) and higher mean sleep efficiency (81.7%, SD 13.6%, vs 75.2%, SD 13.9%; P = .004) than those who underestimated their sleep latency. There were significantly more patients with migraine in the overestimation group than in the underestimation group (20/159 patients vs 3/81 patients; P = .035). This difference was not observed in patients with headache without migraine ( P = 1.000)., Conclusions: We hypothesize that migraine is markedly associated with overestimation of sleep latency. This overestimation was not observed in patients with other headache types. Further studies are needed to explore the relation between migraine and sleep onset misperception., Citation: Rantanen O, Hollmen M, Bachour A. Migraine may disturb sleep perception during sleep onset: a retrospective data analysis. J Clin Sleep Med . 2022;18(9):2113-2117., (© 2022 American Academy of Sleep Medicine.)

Iron overload damages many organs. Unfortunately, therapeutic iron chelators also have undesired toxicity and may deliver iron to microbes. Here we show that a mutant form (K3Cys) of endogenous lipocalin 2 (LCN2) is filtered by the kidney but can bypass sites of megalin-dependent recapture, resulting in urinary excretion. Because K3Cys maintains recognition of its cognate ligand, the iron siderophore enterochelin, this protein can capture and transport iron even in the acidic conditions of urine. Mutant LCN2 strips iron from transferrin and citrate, and delivers it into the urine. In addition, it removes iron from iron overloaded mice, including models of acquired (iron-dextran or stored red blood cells) and primary (Hfe -/- ) iron overload. In each case, the mutants reduce redox activity typical of non-transferrin-bound iron. In summary, we present a non-toxic strategy for iron chelation and urinary elimination, based on manipulating an endogenous protein:siderophore:iron clearance pathway., Competing Interests: J.B. and A.Q. declare patent applications with Columbia University for the use of LCN2 (Scn or NGAL). R.K.S., P.B.R. and R.J.A. declare patent applications with Fred Hutchinson Cancer Research Center for the use of Scn (NGAL). All the other authors declare no competing financial interest.

Kidney damage induces the expression of a myriad of proteins in the serum and in the urine. The function of these proteins in the sequence of damage and repair is now being studied in genetic models and by novel imaging techniques. One of the most intensely expressed proteins is lipocalin2, also called NGAL or Siderocalin. While this protein has been best studied by clinical scientists, only a few labs study its underlying metabolism and function in tissue damage. Structure-function studies, imaging studies and clinical studies have revealed that NGAL-Siderocalin is an endogenous antimicrobial with iron scavenging activity. This review discusses the "iron problem" of kidney damage, the tight linkage between kidney damage and NGAL-Siderocalin expression and the potential roles that NGAL-Siderocalin may serve in the defense of the urogenital system. This article is part of a Special Issue entitled: Cell Biology of Metals., (Copyright © 2012. Published by Elsevier B.V.)

Pim-1 is an oncogenic serine/threonine kinase with poorly defined function in epithelial cancers. In this study, we determined 1) associations of Pim-1 expression with clinicopathological parameters including responsiveness to irradiation in squamocellular cancers of head and neck and 2) how Pim-1 expression is controlled subsequent to irradiation. Moderate to high expression of Pim-1 correlated to poor response to radiation therapy (P = .003). It is also associated to the expression of epidermal growth factor receptor (EGFR, P < .0001), which has been shown to be activated by irradiation. In radioresistant tumors, irradiation promoted nuclear translocation of Pim-1 (P < .005). When directly testing EGFR dependence of Pim-1 expression, up-regulation and nuclear translocation of Pim-1 could be induced through stimulation of EGFR with its ligands EGF or transforming growth factor alpha. Both ligand- and irradiation-induced changes in Pim-1 expression and localization could be inhibited by the monoclonal anti-EGFR antibody cetuximab and by the tyrosine kinase inhibitor gefitinib also targeting EGFR. These results suggest that irradiation-induced activation of EGFR upregulates Pim-1, and Pim-1 may be used as a novel predictive marker of radiation response in patients with squamocellular cancers of head and neck.