Anti-IL-5 and anti-IL-5R biologics for severe asthma. Are there any differences in their effects?

OBJECTIVE: The aim of this retrospective multicentre study is to describe the clinical characteristics of patients diagnosed with severe eosinophilic asthma receiving anti-IL-5/anti-IL-5Rα therapies and to compare their effectiveness. METHODS: We collected and analysed results separately for anti-IL-5 and anti-IL-5Rα therapies from January 2016 until December 2021 in multidisciplinary severe asthma units. We collected demographic and clinical data, treatment with previous anti-IgE and/or anti-IL-5 agents, and comorbidities. We compared the number of exacerbations and admissions to the hospital, daily oral corticosteroid intake, pulmonary function tests, and Asthma Control Test scores before and after 12 months of therapy. 261 patients were included: 176 patients in the anti-IL-5 group and 85 in the anti-IL-5Rα group. RESULTS: Both groups led to statistically significant reductions in asthma exacerbations, hospital admissions, and visits to the Emergency Room. Although both groups showed a significant reduction in blood eosinophiliccount, we found a difference, although not significant, in the magnitude of reduction as benralizumab was able to decrease eosinophil counts to zero. Patients in the anti-IL-5 group achieved higher ACT scores after treatment, although this improvement was seen in both treatment groups. CONCLUSION: The anti-IL-5 and anti-IL-5Rα biologics have shown similar effectiveness despite having different mechanisms of action. The anti-IL-5 group appeared to be better than benralizumab at improving ACT scores and FEV1/FVC and at reducing the number of inhalers. Although these differences were not statistically significant, it is not clear whether they may have clinical relevance and they might highlight the need for further head-to-head studies comparing these treatments.

Inhaled bronchodilators use and clinical course of adult inpatients with Covid-19 pneumonia in Spain: A retrospective cohort study.

BACKGROUND: In the current coronavirus health crisis, inhaled bronchodilators(IB) have been suggested as a possible treatment for patients hospitalized. Patients with evidence of Covid-19 pneumonia worldwide have been prescribed these medications as part of therapy for the disease, an indication for which this medications could be ineffective taken on account the pathophysiology and mechanisms of disease progression. OBJECTIVE: The main objective was to evaluate whether there is an association between IB use and length of stay. Primary end points were the number of days that a patient stayed in the hospital and death as a final event in a time to event analysis. Pneumonia severity, oxygen requirement, involved drugs, comorbidity, historical or current respiratory diagnoses and other drugs prescribed to treat coronavirus pneumonia were also evaluated. METHODS: A descriptive, observational, cross-sectional study was performed in this tertiary hospital in Madrid (Spain). Data were obtained regarding patients hospitalized with Covid-19, excluding those who were intubated. The primary and secondary outcomes such as duration of hospitalization and death were compared in patients who received IB with those in patients who did not. RESULTS: 327 patients were evaluated, mean age was 64.4 ± 15.8 years. Median length of hospitalization stay was 10 days. Of them 292 (89.3%) overcame the disease, the remaining 35 died. Patients who had received IB did not have less mortality rate (odds ratio 0.839; 95% CI: 0.401 to 1.752) and less hospitalization period when compared with patients who did not received IB (odds ratio 1.280; 95% CI: 0.813 to 2.027). There was no significant association between IB use and recovery or death. Hypertension and diabetes were the most common comorbidities. The prevalence of chronic respiratory disease in our cohort was low (21.1%). Anticholinergics were the IB more frequently prescribed for Covid-19 pneumonia. Better response in patients treated with inhaled corticosteroids was not observed. CONCLUSION: Off-label indication of inhaled-bronchodilators for Covid-19 patients are common in admitted patients. Taken on account our results, the use of IB for coronavirus pneumonia apparently is not associated with a significantly patient's improvement. Our study confirms the hypothesis that inhaled bronchodilators do not improve clinical outcomes or reduce the risk of Covid-19 mortality. This could be due to the fact that the virus mainly affects the lung parenchyma and the pulmonary vasculature and probably not the airway. More researches are necessary in order to fill the gap in evidence for this new indication.

Changes in structural lung disease in cystic fibrosis children over 4 years as evaluated by high-resolution computed tomography.

OBJECTIVES: To compare the worsening of structural lung disease on high-resolution computed tomography (HRCT) with changes in spirometry results in cystic fibrosis (CF) patients, and analyse factors associated with the worsening of structural lung disease over time. METHODS: A total of 31 CF subjects (mean age 11.03 ± 3.67 years old) were prospectively evaluated by two HRCT and spirometry tests performed 4 years apart. HRCT abnormalities were scored using the Bhalla scoring system. Comparisons between changes on HRCT and spirometry were made for all patients, and also for groups categorized by age, sex, genotypic alterations and lung obstruction. RESULTS: The mean HRCT Bhalla scoring, forced expiratory volume in 1 s (FEV1 %pred.) and forced vital capacity (FVC %pred.) were 7.92 ± 3.59, 87.76 ± 20.52 and 96.54 ± 15.12, respectively. There was a significant deterioration in the Bhalla score (p < 0.01) and in certain categories: severity of bronchiectasis, peribronchial thickening, mucous plugging and bronchial divisions. Females had a more pronounced worsening of the Bhalla score than males (p = 0.048). No change over time was found in FEV1 and FVC. Only sex was associated with a deterioration in HRCT. CONCLUSIONS: HRCT Bhalla scoring changes statistically significantly over 4 years, but spirometry results do not. Worsening on HRCT is more evident in females. KEY POINTS: • HRCT Bhalla scoring changes significantly over 4 years, spirometry results do not. • Females experience faster respiratory deterioration than males. • Spirometry results are not associated with deterioration in HRCT.

Reasons for initiation of proton pump inhibitor therapy for hospitalised patients and its impact on outpatient prescription in primary care.

BACKGROUND: Proton-pump-inhibitors are often prescribed unnecessarily in hospitals, which in turn induces their prescriptions after discharge. OBJECTIVE: To evaluate patients starting treatment with proton-pump-inhibitors during hospitalisation and proportion of inappropriate prescriptions. Patient risk factors and whether initiation in hospital induced their continuation in ambulatory care were also analyzed. METHODS: An observational, cross-sectional study in a tertiary hospital (1350 beds) was carried out on the first Tuesday in February 2015. Pharmacists screened admitted patients treated with proton-pump-inhibitors using an electronic prescription program (FarmaTools®-5.0). They also checked patients' home medications before admission by accessing a primary care program (Horus®). Authorized indications according to Spanish-Medicines-Agency and those recommended in Spanish-Clinical-Practice-Guidelines were considered appropriate. Hospital-medical-records were checked to know whether proton-pump-inhibitors were prescribed at discharge. RESULTS: Three hundred seventy nine patients were analysed. Two hundred ninety four of them were prescribed proton-pump-inhibitors (77.6%). Treatment was initiated during admission for 143 patients (48.6%, 95% CI: 42.8-54.5). Of them, 91 (63.6%, 95% CI: 55.2-71.5) were inappropriate, mainly due to its inclusion unnecessarily in protocols associated with surgeries or diseases (56 cases of 91, 61.5%). Additional inappropriate indications were surgical stress ulcer prophylaxis for surgeries without bleeding risks (19.8%) and polypharmacy without drugs that increase the risk of bleeding (18.7%). Of 232 discharge reports assessed, in 153 (65.9%, 95% CI: 59.5-72), proton-pump-inhibitor continuation was recommended, of them, 51 (33.3%) were initiated at admission. CONCLUSION: In hospitalized patients there is a high prevalence of prescription of proton-pump-inhibitors unnecessarily. The superfluous use is often associated with the prescription of treatment protocols. Those treatments started in the hospital generally did not contribute to over-use existing primary care, most of them were removed at discharge.

The role of environmental pollution in the development of pulmonary exacerbations in cystic fibrosis: a narrative review.

Cystic fibrosis is the most common autosomal recessive disease in the Caucasian race. Its course is chronic and progressive, with pulmonary involvement being associated with greater morbidity and mortality. One of the factors most related to worse prognosis in these patients is respiratory exacerbations. Although limited, there is evidence demonstrating that increased exposure to environmental pollution, both acute and chronic, is associated with an increase in these exacerbations. It is crucial to fully understand this relationship in order to attempt to improve the respiratory health of these patients. That is why the available evidence is reviewed and measures are established to reduce exposure to pollutants.

[Renal involvement in adults with cystic fibrosis: study of 89 patients]. / Afectación renal en adultos con fibrosis quística: estudio de 89 pacientes.

INTRODUCTION: We are assisting to an increase in survival rates among individuals with cystic fibrosis (CF). Until now, renal involvement was a minority issue, but with the rise in life expectancy, we will likely see an increase in its prevalence. Our main objective was to assess renal function in CF and study risk factors associated with its deterioration. METHODS: A cross-sectional, retrospective study was conducted, including adults with CF. Clinical, respiratory function, microbiological, blood and urine analysis, and major chronic treatments received were collected. RESULTS: Eighty nine patients with a mean age of 35±12 years were analyzed. Mean serum creatinine levels were 0.8±0.2mg/dL. 10.6% had a glomerular filtration rate less than 90mL/min/1.73m2. No patient showed albuminuria. In multivariate model, only age was an independent risk factor for reduced glomerular filtration (OR: 0.344; 95%CI: 0.004-0.017; P=.002). CONCLUSIONS: 11% of CF adults show decreased glomerular filtration, with age being the sole independent risk factor. Vigilance for this uncommon condition is crucial.

Cardiovascular Events in Patients with Severe Asthma-A Retrospective Study of Two Cohorts: Asthma Type T2 Treated with Biologics and Non-Type T2.

Background: The prevalence of cardiovascular events (CVEs) in patients with asthma varies amongst studies, with little evidence as to their prevalence in patients treated with monoclonal antibodies (mAbs). In this retrospective, observational study, we aimed to evaluate the prevalence of CVEs in patients with T2 and non-T2 asthma and to identify risk factors associated with CVEs. Methods: A total of 206 patients with severe asthma were included. Demographic variables, respiratory comorbidities and cardiovascular risk factors were collected, along with respiratory function, laboratory parameters and respiratory pharmacotherapy, including treatment with mAbs. Results: A total of 10.7% of the patients had any CVE from the date of asthma diagnosis, with a higher risk in those patients with chronic obstructive pulmonary disease (odds ratio [OR] = 5.36, 95% CI 1.76-16.31; p = 0.003), arterial hypertension (OR = 2.71, 95% CI 1.13-6.55; p = 0.026) and dyslipidaemia (OR = 9.34, 95% CI 3.57-24.44; p < 0.001). No association between mAb treatment and a CVE or between time of mAb treatment and the event was found. No significant differences were observed between the T2 and non-T2 cohort. After a multivariate analysis, dyslipidaemia was identified as an independent risk factor (OR = 13.33, 95% CI 4.49-39.58; p < 0.001), whereas regular use of inhaled corticosteroids was associated with a reduced risk of a CVE (OR = 0.103, 95% CI 0.021-0.499; p = 0.005). Further research is needed to fully understand the relationship between severe asthma and CVEs. Conclusions: This study suggests that patients with severe asthma experience a higher percentage of CVEs compared with the general population.

Influenza vaccination mitigates severe complications in hospitalized patients: A ten-year observational study, Spain, 2009-2019.

BACKGROUND: Influenza epidemics annually impact a substantial portion of adults worldwide, leading to numerous hospitalizations and fatalities. While the primary goal of vaccination is to prevent influenza virus infection, breakthrough infections can still occur despite vaccination. Evaluating the vaccine effectiveness in preventing severe cases among hospitalized patients is crucial for enhancing vaccination strategies. METHODS: This single-center, observational, cross-sectional, and retrospective study analyzed data from 1,357 patients admitted to La Paz University Hospital for influenza infection between 2009 and 2019. Patients' demographics, clinical variables, comorbidities, vaccination status, and influenza-related outcomes were assessed. Logistic regression analysis was performed to determine the vaccine-independent protective effects. RESULTS: Influenza vaccination independently prevented severe complications, including pneumonia, bacterial superinfection, acute respiratory distress syndrome, and multiple organ failure in hospitalized patients (odds ratio = 0.61, 95% confidence interval: 0.47-0.76). Vaccinated patients had significantly lower intensive care unit admission rates (odds ratio = 0.42, 95% confidence interval: 0.18-0.92). However, there were no significant differences in mortality rates between vaccinated and unvaccinated patients (P = .385). CONCLUSIONS: Our study provides robust evidence supporting the influenza vaccine protective effect against severe outcomes in hospitalized patients during epidemic flu. Vaccination is associated with a significant reduction in severe complications and intensive care unit admissions, emphasizing its importance as a preventive measure. Improving vaccination coverage, especially in specific comorbidities and age groups, could further enhance the vaccine effectiveness in preventing severe influenza cases.

Impact of systemic corticosteroids on hospital length of stay among patients with COVID-19.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic has posed a threat to hospital capacity due to the high number of admissions, which has led to the development of various strategies to release and create new hospital beds. Due to the importance of systemic corticosteroids in this disease, we assessed their efficacy in reducing the length of stay (LOS) in hospitals and compared the effect of 3 different corticosteroids on this outcome. METHODS: We conducted a real-world, controlled, retrospective cohort study that analysed data from a hospital database that included 3934 hospitalised patients diagnosed with COVID-19 in a tertiary hospital from April to May 2020. Hospitalised patients who received systemic corticosteroids (CG) were compared with a propensity score control group matched by age, sex and severity of disease who did not receive systemic corticosteroids (NCG). The decision to prescribe CG was at the discretion of the primary medical team. RESULTS: A total of 199 hospitalized patients in the CG were compared with 199 in the NCG. The LOS was shorter for the CG than for the NCG (median = 3 [interquartile range = 0-10] vs. 5 [2-8.5]; p = 0.005, respectively), showing a 43% greater probability of being hospitalised ≤ 4 days than > 4 days when corticosteroids were used. Moreover, this difference was only noticed in those treated with dexamethasone (76.3% hospitalised ≤ 4 days vs. 23.7% hospitalised > 4 days [p < 0.001]). Serum ferritin levels, white blood cells and platelet counts were higher in the CG. No differences in mortality or intensive care unit admission were observed. CONCLUSIONS: Treatment with systemic corticosteroids is associated with reduced LOS in hospitalised patients diagnosed with COVID-19. This association is significant in those treated with dexamethasone, but no for methylprednisolone and prednisone.

Impact of systemic corticosteroids on length of hospitalization among patients with COVID-19. / [Artículo traducido] Impacto de los corticoides sistémicos en el tiempo de hospitalización en pacientes con COVID-19.

OBJECTIVE: The COVID-19 pandemic has posed a threat to hospital capacity due to the high number of admissions, which has led to the development of various strategies to release and create new hospital beds. Due to the importance of systemic corticosteroids in this disease, we assessed their efficacy in reducing the length of stay (LOS) in hospitals and compared the effect of 3 different corticosteroids on this outcome. MéTHOD: We conducted a real-world, controlled, retrospective cohort study that analysed data from a hospital database that included 3934 hospitalised patients diagnosed with COVID-19 in a tertiary hospital from April to May 2020. Hospitalised patients who received systemic corticosteroids (CG) were compared with a propensity score control group matched by age, sex and severity of disease who did not receive systemic corticosteroids (NCG). The decision to prescribe CG was at the discretion of the primary medical team. RESULTS: A total of 199 hospitalized patients in the CG were compared with 199 in the NCG. The LOS was shorter for the CG than for the NCG (median=3 [interquartile range=0-10] vs. 5 [2-8.5]; p=0.005, respectively), showing a 43% greater probability of being hospitalised ≤4 days than >4 days when corticosteroids were used. Moreover, this difference was only noticed in those treated with dexamethasone (76.3% hospitalised ≤4 days vs. 23.7% hospitalised >4 days [p<0.001]). Serum ferritin levels, white blood cells and platelet counts were higher in the CG. No differences in mortality or intensive care unit admission were observed. CONCLUSIONS: Treatment with systemic corticosteroids is associated with reduced LOS in hospitalised patients diagnosed with COVID-19. This association is significant in those treated with dexamethasone, but no for methylprednisolone and prednisone.

Krebs von den Lungen-6 (KL-6) Levels in Post-COVID Follow-Up: Differences According to the Severity of COVID-19.

To evaluate KL-6 levels in medium-term post-COVID and to compare them in three groups categorised by the severity of COVID-19, we conducted a real-world, retrospective, cohort study. Data from the COVID-19 episode and follow-up during the post-COVID phase were extracted from the COVID@HULP and POSTCOVID@HULP databases, respectively. For the post-COVID period we included demographics, medical history, symptoms, quality of life, physical activity, anxiety and depression status and laboratory results. Patients were categorised into three groups based on the severity of COVID-19: Group 1 (inpatient critical), Group 2 (inpatient non-critical) and Group 3 (hospitalised at home). KL-6 was measured during the follow-up of the three groups. In all, 802 patients were included (Group 1 = 59; Group 2 = 296; Group 3 = 447 patients). The median age was 59 years (48-70), and 362 (45.2%) were males. At admission, fibrinogen and ferritin levels were lower in Group 3 than in the other groups (p < 0.001). Follow-up data were obtained 124 days (97-149) after the diagnosis of COVID-19. The median levels of fibrinogen, ferritin and KL-6 at follow-up were 336 mg/dL (276-413), 80.5 ng/mL (36-174.3) and 326 U/mL (240.3-440.3), respectively. KL-6 levels were lower in Group 3 than in the other groups (298 U/mL (231.5-398) vs. 381.5 U/mL (304-511.8) (Group 1) and 372 U/mL (249-483) (Group 2) (p < 0.001)). KL-6 was associated with ferritin (p < 0.001), fibrinogen (p < 0.001), D-dimer (p < 0.001) and gamma-glutamyl transferase (p < 0.001). KL-6 levels are less elevated at medium-term post-COVID follow-up in patients with mild COVID-19 than in those with moderate or severe disease. KL-6 is associated with systemic inflammatory, hepatic enzyme and thrombosis biomarkers.

Relationship between air pollution exposure and the progression of idiopathic pulmonary fibrosis in Madrid: Chronic respiratory failure, hospitalizations, and mortality. A retrospective study.

Introduction: Air pollution has a significant impact on the morbidity and mortality of various respiratory diseases. However, this has not been widely studied in diffuse interstitial lung diseases, specifically in idiopathic pulmonary fibrosis. Objective: In this study we aimed to assess the relationship between four major air pollutants individually [carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and nitrogen oxides (NOx)] and the development of chronic respiratory failure, hospitalization due to respiratory causes and mortality in patients with idiopathic pulmonary fibrosis. Methods: We conducted an exploratory retrospective panel study from 2011 to 2020 in 69 patients with idiopathic pulmonary fibrosis from the pulmonary medicine department of a tertiary hospital. Based on their geocoded residential address, levels of each pollutant were estimated 1, 3, 6, 12, and 36 months prior to each event (chronic respiratory failure, hospital admission and mortality). Data was collected from the air quality monitoring stations of the Community of Madrid located <3.5 km (2.2 miles) from each patient's home. Results: The increase in average values of CO [OR 1.62 (1.11-2.36) and OR 1.84 (1.1-3.06)], NO2 [OR 1.64 (1.01-2.66)], and NOx [OR 1.11 (1-1.23) and OR 1.19 (1.03-1.38)] were significantly associated with the probability of developing chronic respiratory failure in different periods. In addition, the averages of NO2, O3, and NOx were significantly associated with the probability of hospital admissions due to respiratory causes and mortality in these patients. Conclusion: Air pollution is associated with an increase in the probability of developing chronic respiratory failure, hospitalization due to respiratory causes and mortality in patients with idiopathic pulmonary fibrosis.

Air pollution exposure and its effects on idiopathic pulmonary fibrosis: clinical worsening, lung function decline, and radiological deterioration.

Introduction: Major urban pollutants have a considerable influence on the natural history of lung disease. However, this effect is not well known in idiopathic pulmonary fibrosis (IPF). Aim: This study aimed to investigate the effects of air pollution on clinical worsening, lung function, and radiological deterioration in patients with IPF. Methods: This exploratory retrospective cohort study included 69 patients with IPF, monitored from 2011 to 2020. Data on air pollution levels, including carbon monoxide (CO), nitrogen dioxide (NO2), particulate matter ≤ 2.5 µM (PM2.5), ozone (O3), and nitrogen oxides (NOx), were collected from the nearest air quality monitoring stations (<3.5 km from the patients' homes). Patient outcomes such as clinical worsening, lung function decline, and radiological deterioration were assessed over various exposure periods (1, 3, 6, 12, and 36 months). The statistical analyses were adjusted for various factors, including age, sex, smoking status, and treatment. Results: There was an association between higher O3 levels and an increased likelihood of clinical worsening over 6 and 36 months of exposure (odds ratio [OR] and 95% confidence interval [CI] = 1.16 [1.01-1.33] and OR and 95% CI = 1.80 [1.07-3.01], respectively). Increased CO levels were linked to lung function decline over 12-month exposure periods (OR and 95% CI 1.63 = [1.01-2.63]). Lastly, radiological deterioration was significantly associated with higher CO, NO2, and NOx levels over 6-month exposure periods (OR and 95% CI = 2.14 [1.33-3.44], OR and 95% CI = 1.76 [1.15-2.66] and OR and 95% CI = 1.16 [1.03-1.3], respectively). Conclusion: This study suggests that air pollution, specifically O3, CO, NO2, and NOx, could affect clinical worsening, lung function, and radiological outcomes in patients with IPF. These findings highlight the potential role of air pollution in the progression of IPF, emphasizing the need for further research and air quality control measures to mitigate its effects on respiratory health.

Acute lower intestinal bleeding: feasibility and diagnostic performance of CT angiography.

PURPOSE: To assess the diagnostic performance of computed tomographic (CT) angiography as the initial diagnostic examination for patients presenting to the emergency room with acute lower intestinal bleeding. MATERIALS AND METHODS: The study was reviewed and approved by the ethics committee, and written informed consent was obtained from each patient or their closest relative when the clinical condition precluded consent by the patient. This prospective study comprised 47 patients (27 men, 20 women; mean age, 68 years) with acute lower gastrointestinal tract bleeding who were referred to undergo emergency colonoscopy for evaluation. CT angiography was performed in all patients shortly after arrival to the emergency room. Findings identified at CT angiography included active extravasation (ongoing hemorrhage) or hyperattenuating intraluminal contents on noncontrast material-enhanced images (recent hemorrhage). Presence and location of bleeding and likely cause of hemorrhage were determined and compared with the standard of reference (angiography, colonoscopy, or surgical findings). Data collected were analyzed with a statistical software package. Sensitivity, specificity, and positive and negative predictive values of CT angiography in depicting ongoing or recent hemorrhage were calculated and compared with those of standard of reference. RESULTS: CT angiography demonstrated active bleeding in 14 patients and intraluminal hyperattenuating material in six patients. The sensitivity, specificity, positive predictive value, and negative predictive value of CT angiography in depicting active or recent bleeding were 100% (19 of 19), 96% (27 of 28), 95% (19 of 20), and 100% (27 of 27), respectively. Findings of CT angiography and the standard of reference were concordant for determining definite or potential cause of bleeding in 44 of 47 patients (93% accuracy). CONCLUSION: CT angiography performed in the emergency setting in patients with acute lower intestinal bleeding is feasible and correctly depicts the presence and location of active or recent hemorrhage, as well as the potential cause, in the majority of patients.

Adherence to inhalers in patients with severe asthma treated with anti-interleukin-5 biologics.

OBJECTIVE: Given poor medication adherence in severe asthma is difficult to  evaluate in daily practice, using at least two methods concurrently is recommended. We aimed to determine the prevalence of nonadherence  to  inhalers using the Test of Adherence to Inhalers questionnaire and the medication possession ratio obtained from the pharmacy refill data in patients with severe asthma treated with anti-interleukin-5 biologics and to evaluate their concordance. METHOD: This was a cross-sectional retrospective observational study of 53  patients with severe asthma recruited from the severe asthma unit of a tertiary  hospital in Madrid from June to December 2020. We registered demographic data, comorbidities and concomitant therapy for  sthma. Nonadherence was defined as pharmacy refill data < 80% and/or Test of Adherence to Inhalers questionnaire results < 50. Concordance was assessed by determining the Cohen's kappa statistic. Results: The median age was 61 years (interquartile range 51.8-67.0), and 33  (61%) were women. According to the pharmacy refill data lack of  adherence to the primary inhaler was 58.5%. However, when using the Test of  Adherence to Inhalers questionnaire, it was 22.6%. Combining both methods,  17% of patients were considered to have nonadherence to inhalers. Likewise,  when identifying nonadherence by either of these methods, it reached a  prevalence of 64.2%. The pharmacy refill data and Test of Adherence to  Inhalers questionnaire agreed in 53.1% and disagreed in 46.9% of patients (k  = 0.137; 95% confidence interval -0.057 to 0.331; p = 0.318). CONCLUSIONS: We observed a higher prevalence of non-adherence to inhalers  in patients with severe asthma treated with anti-interleukin-5 biologics. The  agreement between the Test of Adherence to Inhalers questionnaire and the  pharmacy refill data is lower when evaluating nonadherence in patients with  severe asthma treated with anti-interleukin-5 biologics. The pharmacy refill  data detect a higher proportion of nonadherence compared with the Test of  Adherence to Inhalers questionnaire.

OBJETIVO: Dado que la mala adherencia a la medicación en el asma grave es  difícil de evaluar en la práctica diaria, se recomienda utilizar al menos dos métodos simultáneamente. El objetivo es determinar la prevalencia de la  falta de adherencia a los inhaladores mediante el cuestionario Test de  Adherencia a los Inhaladores y la ratio de posesión de la medicación obtenida a  partir de los datos de dispensación de la farmacia en pacientes con asma  grave tratados con biológicos anti interleucina 5 y evaluar su concordancia.Método: Estudio observacional retrospectivo transversal de 53 pacientes con  asma grave reclutados en la unidad de asma grave de un hospital terciario de  Madrid de junio a diciembre de 2020. Se registraron datos demográficos, comorbilidades y el tratamiento concomitante para el asma. La  falta de adherencia se definió como una ratio de posesión de la medicación <  80% y/o un valor en los resultados del cuestionario Test de Adherencia a los  Inhaladores < 50. La concordancia se evaluó con el coeficiente kappa de  Cohen. RESULTADOS: La mediana de edad fue de 61 años (rango intercuartílico 51,8- 67,0), y 33 (61%) eran mujeres. Según la ratio de posesión de la medicación,  la falta de adherencia al inhalador primario fue del 58,5%. Sin embargo, al  utilizar el cuestionario Test de Adherencia a los Inhaladores, ésta fue del  22,6%. Combinando ambos métodos, se consideró que el 17% de los  pacientes presentaban no adherencia a los inhaladores. Asimismo, al identificar  la no adherencia por cualquiera de estos métodos, se alcanzó una  prevalencia del 64,2%. El cuestionario Test de Adherencia a los Inhaladores y  la ratio de posesión de la medicación coincidieron en el 53,1% y discreparon en  el 46,9% de los pacientes (k = 0,137; intervalo de confianza del 95% ­0,057 a 0,331; p = 0,318). CONCLUSIONES: Se observó una alta prevalencia de no adherencia a los inhaladores en los pacientes con asma grave tratados con biológicos anti interleucina 5. La concordancia entre el cuestionario Test de Adherencia a los Inhaladores y la ratio de posesión de la medicación es menor cuando se  evalúa la no adherencia en pacientes con asma grave tratados con biológicos  anti interleucina 5. La ratio de posesión de la medicación detecta una mayor  proporción de no adherencia en comparación con el cuestionario Test de  Adherencia a los Inhaladores.

Psycho-demographic profile in severe asthma and effect of emotional mood disorders and hyperventilation syndrome on quality of life.

BACKGROUND: Severe asthma affects a small population but carries a high psychopathological risk. Therefore, the psychodemographic profile of these patients is of interest. A substantial prevalence of anxiety, depression, alexithymia and hyperventilation syndrome in severe asthma is known, but contradictory results have been observed. These factors can also affect patients' quality of life. For this reasons, our purpose is to evaluate the psychodemographic profile of patients with severe asthma and assess the prevalence of anxiety, depression, alexithymia and hyperventilation syndrome and their impact on the quality of life of patients with severe asthma. METHODS: A cross-sectional study of 63 patients with severe asthma. Their psychodemographic profile was evaluated using the Hospital Anxiety and Depression Scale (HADS), Toronto Alexithymia Scale (TAS-20), Nijmegen questionnaire and Asthma Control Test (ACT) to determine the state of anxiety and depression, alexithymia, hyperventilation syndrome and control of asthma, respectively. Quality of life was assessed with the Mini Asthma Quality of Life Questionnaire (Mini-AQLQ). RESULTS: The mean age was 60 ± 13.6 years. Personal psychopathological histories were found in 65.1% of participants, and 8% reported previous suicidal attempts. The rate of anxiety and/or depression (HADS ≥ 11) was 68.3%. These patients present higher scores on the TAS-20 (p < 0.001) for the level of dyspnea (p = 0.021), and for emotional function (p = 0.017) on the Mini-AQLQ, compared with patients without anxiety or depression. Alexithymia (TAS-20 ≥ 61) was observed in 42.9% of patients; these patients were older (p = 0.037) and had a higher HADS score (p = 0.019) than patients with asthma without alexithymia. On the other hand, patients with hyperventilation syndrome (Nijmegen ≥ 23) scored higher on the HADS (p < 0.05), on the Mini-AQLQ (p = 0.002) and on the TAS-20 (p = 0.044) than the group without hyperventilation syndrome. Quality of life was related to anxiety-depression symptomatology (r = - 0.302; p = 0.016) and alexithymia (r = - 0.264; p = 0.036). Finally, the Mini-AQLQ total score was associated with the Nijmegen questionnaire total score (r = - 0.317; p = 0.011), and the activity limitation domain of the Mini-AQLQ correlated with the ACT total score (r = 0.288; p = 0.022). CONCLUSIONS: The rate of anxiety, depression, alexithymia and hyperventilation syndrome is high in patients with severe asthma. Each of these factors is associated with a poor quality of life.

Off-label use of inhaled bronchodilators in hospitalised patients in Spain: a multicentre observational study.

BACKGROUND: Off-label prescription of inhaled bronchodilators (IB) is frequent, despite the fact that they can be ineffective and increase avoidable healthcare costs. OBJECTIVE: To analyse the frequency of off-label prescription of IB in hospitalised patients. Indications and level of evidence, involved drugs, medical specialties prescribing off-label IB and patients' adherence to IBs were also evaluated. METHOD: A descriptive, observational, cross-sectional study was performed in four tertiary hospitals in Spain. The main outcome measure was the number of patients prescribed off-label IBs. Prescriptions were checked against the European Medicines Agency-approved indications. The level of evidence supporting off-label prescription of IBs (according to MICROMEDEX 2.0) was also analysed. Patients were interviewed to test differences (off-label vs on-label) in adherence and knowledge about their inhaled therapy. RESULTS: 217 patients were prescribed IBs, 92 of whom were givend off-label IBs (54.7% men, mean age 73.9±12.9 years). The most common off-label prescriptions for IBs were: unspecified dyspnoea (not related to COPD or asthma) (27.2%), respiratory infections (23.9%) and heart failure (22.8%). 76.8% of patients did not have evidence supporting them. Beta2-agonist+corticosteroids and anticholinergics were most commonly prescribed off-label. Internal Medicine was the main medical specialty involved. There were no differences between off-label and on-label users in terms of patients' knowledge about treatment and adherence. CONCLUSION: Off-label indications for IBs are common in hospitalised patients and are generally indicated without scientific support. Dyspnoea not related to COPD or asthma, respiratory infections and heart failure were the main off-label indications, most frequently treated with anticholinergics and beta2-agonists+corticosteroids, for which their efficacy and safety has not been proved. Our results show that prescribing needs to be improved to follow the evidence that exists. Moreover, further research focused on off-label indications is needed to clarify whether they are effective, safe and cost-effective.

Lung volume reference values for women and men 65 to 85 years of age.

RATIONALE: In elderly subjects, static lung volumes are interpreted using prediction equations derived from primarily younger adult populations. OBJECTIVES: To provide reference equations for static lung volumes for European adults 65 to 85 years of age and to compare the predicted values of this sample with those from other studies including middle-aged adults. We compare the lung volumes by plethysmography and helium dilution in elderly subjects. METHODS: Reference equations were derived from a randomly selected sample from the general population of 321 healthy never-smoker subjects 65 to 85 years of age. Spirometry and lung volume determinations by plethysmography and multibreath helium equilibration method were performed following the American Thoracic Society/European Respiratory Society recommendations. Reference values and lower and upper limits of normal were derived using a piecewise polynomial model. MEASUREMENTS AND MAIN RESULTS: Plethysmography provided higher values than the dilutional method for all lung volumes, with wide limits of agreement. In addition to height, our reference equations confirm the age- and body size dependence of lung volumes in older subjects. Practically all the estimations performed by extrapolating reference equations of middle-aged adults overpredicted the true lung volumes of our healthy elderly volunteers. Middle-aged reference equations classify subjects as being below the total lung capacity lower limit of normal between 17.9 and 62.5% of the women and between 12.5 and 42.2% of the men of the current study. CONCLUSIONS: These results underscore the importance of using prediction equations appropriate to the origin, age, and height characteristics of the subjects being studied.

Daily physical activity in patients with chronic obstructive pulmonary disease is mainly associated with dynamic hyperinflation.

RATIONALE: Although the major limitation to exercise performance in patients with COPD is dynamic hyperinflation, little is known about its relation to daily physical activity. OBJECTIVES: To analyze the contribution of dynamic hyperinflation, exercise tolerance, and airway oxidative stress to physical activity in patients with COPD. METHODS: In a cross-sectional study, we included 110 patients with moderate to very severe COPD. Daily physical activity was measured using a triaxial accelerometer providing a mean of 1-minute movement epochs as vector magnitude units (VMU). Patients performed the 6-minute walk test, incremental exercise test with measurement of breathing pattern and operating lung volumes, and constant-work rate test at 75% of maximal work rate. MEASUREMENTS AND MAIN RESULTS: Using the GOLD stage and BODE index, we determined arterial blood gases, lung volumes, diffusing capacity, and biomarkers in exhaled breath condensate. Daily physical activity was lower in the 89 patients who developed dynamic hyperinflation than in the 21 who did not (n =161 [SD 70] vs. n = 288 [SD 85] VMU; P = 0.001). Physical activity was mainly related to distance walked in 6 minutes (r = 0.72; P = 0.001), Vo(2) (r = 0.63; P = 0.001), change in end-expiratory lung volume during exercise (r = -0.73; P = 0.001), endurance time (r = 0.61; P = 0.001), and 8-isoprostane in exhaled breath condensate (r = -0.67; P = 0.001). In a multivariate linear regression analysis using VMU as a dependent variable, dynamic hyperinflation, change in end-expiratory lung volume, and distance walked in 6 minutes were retained in the prediction model (r(2) = 0.84; P = 0.001). CONCLUSIONS: Daily physical activity of patients with COPD is mainly associated with dynamic hyperinflation, regardless of severity classification.

A Phase 3 Study to Compare Delafloxacin With Moxifloxacin for the Treatment of Adults With Community-Acquired Bacterial Pneumonia (DEFINE-CABP).

BACKGROUND: The clinical and economic burden of community-acquired bacterial pneumonia (CABP) is significant and is anticipated to increase as the population ages and pathogens become more resistant. Delafloxacin is a fluoroquinolone antibiotic approved in the United States for the treatment of adults with acute bacterial skin and skin structure infections. Delafloxacin's shape and charge profile uniquely impact its spectrum of activity and side effect profile. This phase 3 study compared the efficacy and safety of delafloxacin with moxifloxacin for the treatment of CABP. METHODS: A randomized, double-blind, comparator-controlled, multicenter, global phase 3 study compared the efficacy and safety of delafloxacin 300 mg twice daily or moxifloxacin 400 mg once daily in adults with CABP. The primary end point was early clinical response (ECR), defined as improvement at 96 (±24) hours after the first dose of study drug. Clinical response at test of cure (TOC) and microbiologic response were also assessed. RESULTS: In the intent-to-treat analysis population (ITT), ECR rates were 88.9% in the delafloxacin group and 89.0% in the moxifloxacin group. Noninferiority of delafloxacin compared with moxifloxacin was demonstrated. At TOC in the ITT population, the success rates were similar between groups. Treatment-emergent adverse events that were considered at least possibly related to the study drug occurred in 65 subjects (15.2%) in the delafloxacin group and 54 (12.6%) in the moxifloxacin group. CONCLUSIONS: Intravenous/oral delafloxacin monotherapy is effective and well tolerated in the treatment of adults with CABP, providing coverage for Gram-positive, Gram-negative, and atypical pathogens. CLINICALTRIALSGOV IDENTIFIER: NCT03534622.