FIDEPOC: Consensus on Inspiratory Flow and Lung Deposition as Key Decision Factors in COPD Inhaled Therapy.

Purpose: The pharmacological treatment of chronic obstructive pulmonary disease (COPD) is largely based on inhaled bronchodilators. Inspiratory flow and lung deposition are key parameters to be considered in inhaled therapy; however, the relationship between these two parameters, the patient specificities, and the suitability of the inhaler type for COPD management has not been fully addressed. The present study follows a Delphi Panel methodology to find expert consensus on the role of inspiratory flow and lung deposition as key decision factors in COPD inhaled therapy. Methods: A two-round Delphi Panel, consisting of 38 statements (items) and completed by 57 Spanish pulmonologists, was carried out to measure the experts' consensus degree with each item. Results: A high degree of consensus was reached on most of the items consulted, among these inspiratory flow or inspiratory capacity should be periodically considered when choosing an inhalation device and to ensure the suitability of the inhaler used; the outflow velocity and particle size of the different devices should be considered to ensure adequate lung deposition; an active device (pressurized metered-dose inhalers (pMDI) or soft mist inhalers (SMI)) should be used in patients with low inspiratory flow to achieve adequate lung deposition; and, the use of dry powder inhalers (DPI) should be re-evaluated in patients with severe obstruction and severe exacerbations. Conclusion: This study shows the relevance of inspiratory flow and the degree of particle deposition in the lung in the choice of an inhalation device for COPD management, as well as the convenience of an SMI type device in cases of low inspiratory flow. Moreover, it highlights the scarcity of information on the specific features of inhalation devices in COPD guidelines.

Lung Deposition and Inspiratory Flow Rate in Patients with Chronic Obstructive Pulmonary Disease Using Different Inhalation Devices: A Systematic Literature Review and Expert Opinion.

BACKGROUND: Our aim was to describe: 1) lung deposition and inspiratory flow rate; 2) main characteristics of inhaler devices in chronic obstructive pulmonary disease (COPD). METHODS: A systematic literature review (SLR) was conducted to analyze the features and results of inhaler devices in COPD patients. These devices included pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), and a soft mist inhaler (SMI). Inclusion and exclusion criteria were established, as well as search strategies (Medline, Embase, and the Cochrane Library up to April 2019). In vitro and in vivo studies were included. Two reviewers selected articles, collected and analyzed data independently. Narrative searches complemented the SLR. We discussed the results of the reviews in a nominal group meeting and agreed on various general principles and recommendations. RESULTS: The SLR included 71 articles, some were of low-moderate quality, and there was great variability regarding populations and outcomes. Lung deposition rates varied across devices: 8%-53% for pMDIs, 7%-69% for DPIs, and 39%-67% for the SMI. The aerosol exit velocity was high with pMDIs (more than 3 m/s), while it is much slower (0.84-0.72 m/s) with the SMI. In general, pMDIs produce large-sized particles (1.22-8 µm), DPIs produce medium-sized particles (1.8-4.8 µm), and 60% of the particles reach an aerodynamic diameter <5 µm with the SMI. All inhalation devices reach central and peripheral lung regions, but the SMI distribution pattern might be better compared with pMDIs. DPIs' intrinsic resistance is higher than that of pMDIs and SMI, which are relatively similar and low. Depending on the DPI, the minimum flow inspiratory rate required was 30 L/min. pMDIs and SMI did not require a high inspiratory flow rate. CONCLUSION: Lung deposition and inspiratory flow rate are key factors when selecting an inhalation device in COPD patients.

Relationship Between Clinical Control, Respiratory Symptoms and Quality of Life for Patients with COPD.

Background: The concept of clinical control has been proposed as an instrument for evaluating patients with COPD. However, the possible association between clinical control, reduced symptom severity and HRQoL has yet to be confirmed. Methods: This multicentre, prospective and observational study was carried out in 15 pulmonology clinics in Spain. The patients were followed up for six months, with a baseline visit (V0), followed by visits at three months (V1) and six months (V2). Clinical control was determined at V1, with the application of both clinical criteria and the COPD assessment test (CAT). All patients reported their symptoms by a validated symptom diary (E-RS) using a portable device, and their HRQoL was assessed using the EQ5D questionnaire. The relationship between clinical control and E-RS and HRQoL during follow-up was assessed with t-test. Results: A total of 126 patients were screened. After application of the inclusion/exclusion criteria, 93 were finally included (mean age 66 ± 8 years, 84.9% male), with a mean FEV1 predicted of 49.8% ± 16.5%. Of these patients, 44 (47.3%) achieved clinical control at V1, according to CAT criteria, and 50 (53.8%), according to clinical criteria. The E-RS scores differed between controlled and uncontrolled patients at all time points, both according to CAT (mean differences of -4.6, -5.6 and -6.2 units at V0, V1 and V2, respectively, p<0.005 for all comparisons) and to clinical criteria (mean differences of -3.3, -5-6 and -4.99 units, respectively, p<0.005 for all comparisons). The controlled patients also presented a significantly better HRQoL, measured by the EQ5D questionnaire (mean difference 0.13 and 0.10 at V2 by CAT or clinical criteria, respectively, p<0.05). Conclusion: Clinical control in patients with COPD, whether measured by CAT or by clinical criteria, is associated with a lower symptom load and a better HRQoL.

Effects of long-term azithromycin therapy on airway oxidative stress markers in non-cystic fibrosis bronchiectasis.

BACKGROUND AND OBJECTIVE: To explore the effect of long-term therapy with azithromycin in regards to airway oxidative stress markers in exhaled breath condensate (EBC) of adult patients with stable non-cystic fibrosis (CF) bronchiectasis. METHODS: Open-label prospective study of 30 patients randomized to azithromycin 250 mg three times per week during 3 months (16 patients) or control (14 patients). Primary outcome were changes in nitric oxide, 8-isoprostane, pH, nitrites and nitrates in EBC. Secondary outcomes were changes in exacerbation rates, dyspnoea (Borg scale), sputum volume (cc), sputum colour (15-point scale), bacterial infection, health-related quality of life (St George's Respiratory Questionnaire), lung function and radiological extension. RESULTS: Azithromycin produced a significant decrease in sputum volume (8.9 (1.8) mL vs 2.1 (3.4) mL) and number of exacerbations (0.1 (0.6) vs 1.2 (0.9)). Dyspnoea (0.4 (0.1) vs 0.1 (0.2)) and health-related quality of life also improved after therapy. However, oxidative stress markers in EBC, systemic inflammatory markers as well as functional respiratory tests did not differ from the control group after therapy. A post-hoc analysis comparing patients infected or not with Pseudomonas aeruginosa revealed that these effects were more pronounced in infected patients. In this subgroup, treatment was followed by a significant reduction in sputum volume, number of exacerbations, dyspnoea and St George's Respiratory Questionnaire total score. Of all airway oxidative stress markers, only nitrates in EBC were reduced after therapy. CONCLUSIONS: Long-term azythromicin treatment has some clinical benefits in patients with non-CF stable bronchiectasis, but it does not affect airway oxidative stress markers.

Coste económico del paciente asmático en España (estudio AsmaCost) / Economic Cost of Treating the Patient With Asthma in Spain: The Asma Cost Study

IntroducciónSe ha realizado un estudio del consumo de recursos y de los costes derivados, tanto sanitarios como no sanitarios, en el paciente asmático en España.Pacientes y métodosSe trata de un estudio prospectivo y observacional de cohortes, en pacientes asmáticos adultos, diagnosticados según los criterios de GINA/GEMA y seguidos durante 12 meses. Se recogieron datos sobre recursos sanitarios (consumo de medicamentos, consultas médicas, visitas a urgencias, ingresos hospitalarios y pruebas) y no sanitarios (desplazamientos de los pacientes y pérdidas de jornadas laborales).ResultadosParticiparon 627 pacientes de toda España, con asma intermitente (21,2%), leve (24,6%), moderada (27,6%) y grave (26,6%). Desde la perspectiva de la sociedad (incluyendo los recursos no sanitarios), el coste anual de un paciente con asma asciende a 1.726€ (intervalo de confianza [IC] del 95%, 1.314–2.154). El 11,2% del gasto corresponde a recursos no sanitarios. Para el Sistema Nacional de Salud el gasto por paciente es de 1.533€ (IC del 95%, 1.133–1.946). El coste es superior en los pacientes mayores de 65 años (2.079€) y en aquéllos con asma de mayor gravedad (959; 1.598; 1.553, y 2.635€ para asma intermitente, leve, moderada y grave, respectivamente). De acuerdo con estos resultados, se estima que el coste anual del asma en España es de 1.480 millones de euros (IC del 95%, 382–2.565 millones) y de 3.022 millones de euros (IC del 95%, 2.472–3.535 millones) considerando el diagnóstico por hiperreactividad bronquial y sólo sintomático, respectivamente.ConclusionesEl coste anual medio del paciente asmático adulto en España asciende a 1.726 y a 1.533€ desde la perspectiva de la sociedad y del Sistema Nacional de Salud, respectivamente(AU)

ObjectiveThis analysis of the cost of asthma in Spain includes both direct health care costs and indirect costs arising from illness.Patients and MethodsProspective, 12-month observational cohort study of adult patients with asthma diagnosed according to the guidelines of the Global Initiative for Asthma (GINA) and the adapted Spanish criteria (GEMA). We recorded information on health care resources utilized (medications, medical visits, emergency care, hospital admissions, and tests) and indirect costs (patient travel or transfer costs and workdays lost).ResultsA total of 627 patients throughout Spain were studied. Of these, 21.2% had intermittent asthma, 24.6% mild asthma, 27.6% moderate asthma, and 26.6% severe asthma. The total societal cost of asthma (including indirect costs) was €1726 (95% confidence interval [CI], €1314–€2154) per patient annually. Indirect costs accounted for 11.2% of the total. The cost to the National Health Service was €1533 (95% CI, €1133–€1946) per patient annually. The cost of asthma was higher for patients older than 65 years (€2079) and for those with more severe disease (€959 for intermittent asthma; €1598, mild asthma; €1553, moderate asthma; and €2635 severe asthma). Based on these findings, the total annual cost of asthma in Spain is estimated to be €1480 million (95% CI, €382–€2565 million) for patients with demonstrated bronchial hyperreactivity and €3022 million (95% CI, €2472–€3535 million) for patients diagnosed based on symptoms alone.ConclusionsThe average annual cost of asthma in adults in Spain comes to €1726 per patient, considering both direct and indirect costs. The average annual cost per patient to the National Health Service is €1533(AU)

[Economic cost of treating the patient with asthma in Spain: the AsmaCost study]. / Coste económico del paciente asmático en España (estudio AsmaCost).

OBJECTIVE: This analysis of the cost of asthma in Spain includes both direct health care costs and indirect costs arising from illness. PATIENTS AND METHODS: Prospective, 12-month observational cohort study of adult patients with asthma diagnosed according to the guidelines of the Global Initiative for Asthma (GINA) and the adapted Spanish criteria (GEMA). We recorded information on health care resources utilized (medications, medical visits, emergency care, hospital admissions, and tests) and indirect costs (patient travel or transfer costs and workdays lost). RESULTS: A total of 627 patients throughout Spain were studied. Of these, 21.2% had intermittent asthma, 24.6% mild asthma, 27.6% moderate asthma, and 26.6% severe asthma. The total societal cost of asthma (including indirect costs) was euro1726 (95% confidence interval [CI], euro1314-euro2154) per patient annually. Indirect costs accounted for 11.2% of the total. The cost to the National Health Service was euro1533 (95% CI, euro1133-euro1946) per patient annually. The cost of asthma was higher for patients older than 65 years (euro2079) and for those with more severe disease (euro959 for intermittent asthma; euro1598, mild asthma; euro1553, moderate asthma; and euro2635 severe asthma). Based on these findings, the total annual cost of asthma in Spain is estimated to be euro1480 million (95% CI, euro382-euro2565 million) for patients with demonstrated bronchial hyperreactivity and euro3022 million (95% CI, euro2472-euro3535 million) for patients diagnosed based on symptoms alone. CONCLUSIONS: The average annual cost of asthma in adults in Spain comes to euro1726 per patient, considering both direct and indirect costs. The average annual cost per patient to the National Health Service is euro1533.