Adherence and persistence in allergen immunotherapy (APAIT): A reporting checklist for retrospective studies.

BACKGROUND: Adherence is essential for the long-term efficacy of allergen immunotherapy (AIT) and has been evaluated in numerous retrospective studies. However, there are no published guidelines for best practice in measuring and reporting adherence or persistence to AIT, which has resulted in substantial heterogeneity among existing studies. The 'adherence and persistence in AIT (APAIT)' checklist has been developed to guide the reporting, design and interpretation of retrospective studies that evaluate adherence or persistence to AIT in clinical practice. METHODS: Five existing checklists, focussing on study protocol design, the use of retrospective databases/patient registries, and the appraisal and reporting of observational studies, were identified and merged. Relevant items were selected and tailored to be specific to AIT. The content of the checklist was discussed by 11 experts from Europe, the United States and Canada, representing allergy, healthcare and life sciences, and health technology appraisal. RESULTS: The APAIT checklist presents a set of items that should either be included or at least considered, when reporting retrospective studies that assess adherence or persistence to AIT. Items are organized into four categories comprising study objective, design and methods, data analysis, and results and discussion. The checklist highlights the need for clarity and transparency in reporting and emphasizes the importance of considering potential sources of bias in retrospective studies evaluating adherence or persistence to AIT. CONCLUSIONS: The APAIT checklist provides a pragmatic guide for reporting retrospective adherence and persistence studies in AIT. Importantly, it identifies potential sources of bias and discusses how these influence outcomes.

Tobacco industry ownership of pharmaceutical companies: an international survey of people with respiratory disease.

The 2021 purchase of the respiratory pharmaceutical company Vectura by Phillip Morris International has been criticised by the public health and medical community, as a conflict of interest, with little input to date, from the patient community or the public. To address this gap, the COPD Foundation, along with global partners, surveyed 1196 people with chronic respiratory disease. 70% were bothered by a tobacco company making an inhaler to treat lung conditions and 48% reported that they would want to switch inhalers if they knew that a tobacco company made or sold their inhaler devices. Patients care about who makes the therapies used to treat their diseases.

A Social Return on Investment Analysis of Improving the Management of Chronic Obstructive Pulmonary Disease Within the Spanish National Healthcare System.

Purpose: To define a set of proposals that would improve the current management of chronic obstructive pulmonary disease (COPD) within the Spanish National Healthcare System (SNHS) from a comprehensive multidisciplinary perspective and to assess the impact of its implementation from clinical, healthcare, economic, and social perspectives. Patients and Methods: A group of 20 stakeholders related to COPD (healthcare professionals, patients, and informal caregivers, among others) participated in an online Delphi process to agree on a set of 15 proposals that would improve the current management of COPD within the SNHS in four areas: diagnosis, risk stratification, management of exacerbations, and management of stable COPD. A one-year forecast-type social return on investment (SROI) analysis was used to estimate the impact that implementing the set of proposals would have in relation to the investment required. A sensitivity analysis was used to test the strength of the model when varying assumption-based data-points. Results: The hypothetical implementation of the complete set of 15 proposals would require a €668 million investment and would generate a €2079 million social impact concerning savings for the SNHS and quality of life improvements for patients and their informal caregivers, among others. Accordingly, for every euro invested in the set of proposals, a social return of €3.11 would be generated (€2.71 in the worst-case scenario and €3.62 in the best-case scenario) of both tangible (32.56%) and intangible nature (67.44%). Conclusion: Altogether, implementing this set of 15 proposals would generate a positive social impact, threefold the required investment. The results may inform decisions relative to healthcare policy and practice regarding COPD management within the SNHS, further contributing to reduce the large burden of COPD.

Development and Validation of Patient-Reported Outcome Measures (PROM) and Patient-Reported Experience Measures (PREM) in Home Respiratory Therapies: Oxygen Therapy, CPAP Treatment, Mechanical Ventilation, and Aerosol Therapy.

Introduction: Home respiratory therapies (HRT) are treatments aimed at diseases that are generally chronic and that have a significant impact on the biopsychosocial aspects of patients' lives. No validated patient-reported outcome measures (PROM) and patient-reported experience measures (PREM) are available to assess the impact of these treatments on quality of life (QoL) in HRT. The objective of this work was to identify and validate PROMs and PREMs in HRT. Methods: The process was divided into 5 stages: review of the literature, patient interviews, qualitative validation workshops, cognitive validation, and psychometric validation. For the identification of PROM and PREM, consensus techniques were used with patients, caregivers, specialist doctors, and therapists. The evaluation was based on items that were collected from questionnaires on diseases commonly treated with HRT techniques in clinical practice. The psychometric validation was analyzed by a team of psychologists trained in the methodology. Results: For the literature review, 20 articles met the inclusion and exclusion criteria. After patient interviews, the research team selected 40 PROM items for each treatment from the total of 51 PROM questionnaires found for respiratory diseases. For the validation workshops, the list of selected items had to be reduced to a final number of 15. After the workshops, 8 preliminary questionnaires were drawn up (4 PROMs and 4 PREMs). A second validation round was then held and the questionnaires were modified with the list of PREMs and PROMs resulting from the whole process. The psychometric validation of PROM and PREM questionnaires for each of the therapies consisted of an exploratory factor analysis (EFA) and a confirmatory factor analysis (CFA). Overall, 1299 questionnaires answered by 650 patients were obtained. Conclusions: A preliminary set of PREMs and PROMs associated with HRT with good reliability indexes was developed: Cronbach's alpha and Composite Reliability Index (CRI). These are questionnaires with a 5-point Likert scale that the patient can quickly complete and which provide excellent scores for acceptability, reliability, and validity in psychometric tests. This may offer HRT units a robust basis for better monitoring of patient outcomes and needs and improve healthcare quality and clinical outcomes.

Introducción: Las terapias respiratorias domiciliarias (TRD) son tratamientos dirigidos a patologías, generalmente crónicas, que tienen un impacto significativo en los aspectos biopsicosociales de la vida del paciente. No hay PROM y PREM validados informados por los pacientes para evaluar el impacto de los tratamientos en sí mismos en la calidad de vida (CdV) en la TRD. El objetivo de este trabajo es identificar y validar las PROM y PREM en las TRD. Métodos: Se ha realizado un proceso de cinco etapas: investigación bibliográfica, entrevistas a pacientes, talleres de validación cualitativa, validación cognitiva y validación psicométrica. Para la identificación de PRO y PRE se utilizaron técnicas de consenso con pacientes, cuidadores, médicos especialistas y terapeutas. Se basó en ítems recogidos de cuestionarios relacionados con patologías prevalentes tratadas con TRD y que se utilizan en la práctica clínica. Para la validación psicométrica, un equipo de psicólogos metodólogos realizó los análisis. Resultados: Para la revisión bibliográfica, 20 artículos cumplieron con los criterios de inclusión y exclusión. Después de las entrevistas con los pacientes, el equipo de investigación seleccionó 40 ítems PRO para cada terapia de un total de 51 cuestionarios PRO encontrados para enfermedades respiratorias. Con los talleres de validación se tuvo que reducir la lista de ítems seleccionados a una lista final de 15. Después de los talleres se realizaron 8 cuestionarios preliminares (4 PRO y 4 PRE). Luego de una segunda validación, los cuestionarios fueron modificados con la lista de PRE y PRO resultante de todo el proceso. La validación psicométrica de los cuestionarios PROM y PREM en cada una de las terapias consistió en un análisis factorial exploratorio (EFA) y un análisis factorial confirmatorio (AFC). Se obtuvieron 1.299 cuestionarios respondidos por 650 pacientes. Conclusiones: Se ha desarrollado un primer conjunto de PREM y PROM relacionados con la TRD, con buenos índices de fiabilidad: alfa de Cronbach y Composite Reliability Index (CRI). Se trata de cuestionarios con una escala de 5 puntos Likert que el paciente puede completar rápidamente con excelentes puntuaciones de aceptabilidad, fiabilidad y validez en las pruebas psicométricas. Los servicios de TRD ahora podrían tener una base para un mejor seguimiento de los resultados y las necesidades de los pacientes y, por lo tanto, para mejorar la calidad de la atención médica y los resultados clínicos.

Daily Impact of COPD in Younger and Older Adults: Global Online Survey Results from over 1,300 Patients.

The daily impact of chronic obstructive pulmonary disease (COPD) on younger patients is often underappreciated. To assess this, we investigated the disease burden experienced by younger and older patients. A panel of questions was developed in conjunction with the European Federation of Allergy and Airways Diseases Patients' Associations and Boehringer Ingelheim. The online survey was conducted by Instar Research. Data were collected from eight countries in Europe, plus China, Japan and the United States. All patients were receiving COPD maintenance therapy. Patients were stratified by age (45-54, 55-64, ≥65 years). Data were analyzed from 1,375 patients from Europe (925), China (150), Japan (100) and the US (200); 365 were aged 45-54, 440 aged 55-64, and 570 aged ≥65 years. Mean age was 61.8 years; 771 (56%) were male. A significantly higher proportion of patients aged 45-54 years reported "poor" or "very poor" wellbeing (35% vs. 28%; p < 0.05) and "high impact" on 8 of the 11 daily activities and requirements for adjusting activities assessed (all p < 0.05), compared with patients aged ≥65 years. Significantly more patients aged 45-54 versus ≥65 years associated their COPD with feeling "anxious", "stressed", "sad", or "overwhelmed" (all p < 0.05). Younger patients with COPD reported a higher impact on their daily activities, wellbeing and requirement for adjusting their activities due to their symptoms than older patients. Our findings highlight the importance of optimizing treatment for younger patients with COPD and suggest that clinicians should not overlook the burden of disease in these patients.

Candidate chemosensory cells in the porcine stomach.

A continuous chemosensory monitoring of the ingested food is of vital importance for adjusting digestive processes according to diet composition. Although any dysfunction of this surveillance system may be the cause of severe gastrointestinal disorders, information about the cellular and molecular basis of chemosensation in the gastrointestinal tract is limited. The porcine alimentary canal is considered as an appropriate model for the human gastrointestinal tract. Therefore, in this study we have investigated the gastric mucosa of swine for cells which express gustatory transduction elements such as TRPM5 or PLCß2, and thus may represent candidate "chemosensors". It was found that the porcine stomach indeed contains cells expressing gustatory marker molecules; however, the morphology and topographic distribution of putative chemosensory cells varied significantly from that in mice. Whereas in the murine stomach these cells were clustered at a distinct region near the gastric entrance, no such compact cell cluster was found in the pig stomach. These results indicate substantial differences regarding the phenotype of candidate chemosensory cells of mice and swine and underline the importance of choosing the most suitable model organisms.

Candidate chemosensory cells in the stomach mucosa of young postnatal mice during the phases of dietary changes.

The complex physiology of the gastrointestinal (GI) tract must permanently be adjusted according to the composition of ingested food, which requires continuous monitoring by appropriate sensory systems. Sensing the dietary constituents is thought to be mediated by chemosensory cells residing in the mucosa of the GI tract. We have examined the appearance and differentiation of candidate chemosensory cells at distinct postnatal stages and visualized cells that express gustducin or TRPM5. Two critical stages have been considered: the suckling period when the neonates are nourished exclusively on milk and the weaning period when the diet gradually changes to solid food. At early postnatal stages, only a few gustducin- or TRPM5-expressing cells have been found; they display an immature morphology. At the time of weaning, numerous gustducin- or TRPM5-positive cells are present in the gastric mucosa and are isomorphic to adult candidate chemosensory cells. The typical accumulation of gustducin and TRPM5 cells at the border between the forestomach and corpus region and the characteristic tissue fold or "limiting ridge" have not been observed at early postnatal stages but are complete at the time of weaning. The appearance of candidate chemosensory cells at the strategic position occurs within the last few days before weaning but after the formation of the limiting ridge. Thus, both the topographic arrangement of the cells and the limiting ridge seem to be important features for the processing of solid food in the mouse stomach.

T1R3 is expressed in brush cells and ghrelin-producing cells of murine stomach.

Various digestive and enteroendocrine signaling processes are constantly being adapted to the chemical composition and quantity of the chyme contained in the diverse compartments of the gastrointestinal tract. The chemosensory monitoring that underlies the adaptive capacity of the gut is thought to be performed by so called brush cells that share morphological and molecular features with gustatory sensory cells. A substantial population of brush cells is localized in the gastric mucosa. However, no chemosensory receptors have been found to be expressed in these cells so far, challenging the concept that they serve a chemosensory function. The canonical chemoreceptors for the detection of macronutrients are taste receptors belonging to the T1R family; these have been identified in several tissues in addition to the gustatory system including the small intestine. We demonstrate the expression of the T1R subtype T1R3, which is essential for the detection of both sugars and amino acids in the gustatory system, in two distinct cell populations of the gastric mucosa. One population corresponds to open-type brush cells, emphasizing the notion that they are a chemosensory cell type; T1R3 immunoreactivity in these cells is restricted to the apical cell pole, which might provide the basis for the detection of luminal macronutrient compounds. The second gastric T1R3-positive population consists of closed-type endocrine cells that produce ghrelin. This finding suggests that ghrelin-releasing cells, which lack access to the stomach lumen, might receive chemosensory input from macronutrients in the circulation via T1R3.

Expression of adiponectin receptor 1 in olfactory mucosa of mice.

AdipoR1 and AdipoR2 are receptors for the adipocyte-derived hormone adiponectin, which is an important regulator of glucose and lipid metabolism, and which has also been implicated in the control of food intake and energy homeostasis. In the present study, we have demonstrated that AdipoR1 is expressed in mature sensory neurons of the olfactory mucosa of mice, in a pattern reminiscent of the olfactory marker protein. AdipoR1 expression levels in the olfactory mucosa have been observed to increase gradually during late embryogenesis until adulthood. No local expression of adiponectin has been detected in nasal tissues, indicating that serum adiponectin is the ligand for AdipoR1 in olfactory sensory neurons. As the serum adiponectin concentration is regulated depending on adipose tissue mass, with a reduction of adiponectin levels being seen in obesity, AdipoR1 function in the olfactory epithelium seems to be directly linked to the nutritional status of the body, suggesting a potential modulatory role for AdipoR1 in the adjustment of the olfactory system to energy balance requirements.

A cluster of gustducin-expressing cells in the mouse stomach associated with two distinct populations of enteroendocrine cells.

In the gastrointestinal (GI) tract, a variety of digestive processes are continually adapted to the changing composition of ingested foods, which requires a precise chemosensory monitoring of luminal contents. Gustducin-expressing brush cells scattered throughout the GI mucosa are considered candidate sensory cells for accomplishing this task. In this study, we have investigated a large cluster of gustducin-positive cells which is located exactly at the boundary between the fundic and the oxyntic mucosa of the mouse stomach, at the so-called "limiting ridge". In close association with the candidate chemosensory cluster, we found two populations of enteroendocrine cells: one population containing the satiety regulating hormone ghrelin, the other population comprising serotonin-secreting enterochromaffin cells. The particular arrangement of gustducin-expressing cells and enteroendocrine cells at the limiting ridge suggests a direct interplay between these cell types with immediate implications, not only for digestive processes in the stomach, but also for parameters controlling the satiety status.

Olfactory receptors and signalling elements in the Grueneberg ganglion.

The Grueneberg ganglion (GG) is a cluster of neurones present in the vestibule of the anterior nasal cavity. Although its function is still elusive, recent studies have shown that cells of the GG transcribe the gene encoding the olfactory marker protein (OMP) and project their axons to glomeruli of the olfactory bulb, suggesting that they may have a chemosensory function. Chemosensory responsiveness of olfactory neurones in the main olfactory epithelium (MOE) and the vomeronasal organ (VNO) is based on the expression of either odorant receptors or vomeronasal putative pheromone receptors. To scrutinize its presumptive olfactory nature, the GG was assessed for receptor expression by extensive RT-PCR analyses, leading to the identification of a distinct vomeronasal receptor which was expressed in the majority of OMP-positive GG neurones. Along with this receptor, these cells expressed the G proteins Go and Gi, both of which are also present in sensory neurones of the vomeronasal organ. Odorant receptors were expressed by very few cells during prenatal and perinatal stages; a similar number of cells expressed adenylyl cyclase type III and G(olf/s), characteristic signalling elements of the main olfactory system. The findings of the study support the notion that the GG is in fact a subunit of the complex olfactory system, comprising cells with either a VNO-like or a MOE-like phenotype. Moreover, expression of a vomeronasal receptor indicates that the GG might serve to detect pheromones.

A novel population of neuronal cells expressing the olfactory marker protein (OMP) in the anterior/dorsal region of the nasal cavity.

The olfactory marker protein (OMP) is expressed in mature chemosensory neurons in the nasal neuroepithelium. Here, we report the identification of a novel population of OMP-expressing neurons located bilaterally in the anterior/dorsal region of each nasal cavity at the septum. These cells are clearly separated from the regio olfactoria, harboring the olfactory sensory neurons. During mouse development, the arrangement of the anterior OMP-cells undergoes considerable change. They appear at about stage E13 and are localized in the nasal epithelium during early stages; by epithelial budding, ganglion-shaped clusters are formed in the mesenchyme during the perinatal phase, and a filiform layer directly underneath the nasal epithelium is established in adults. The anterior OMP-cells extend long axonal processes which form bundles and project towards the brain. The data suggest that the newly discovered group of OMP-cells in the anterior region of the nasal cavity may serve a distinct sensory function.