Experience With Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Disease

Introduction: Elexacaftor/tezacaftor/ivacaftor (ETI) was used through the early access programme in Spain from December 2019 in cystic fibrosis (CF) patients with homozygous or heterozygous F508del mutation with advanced lung disease. Methodology: Multicentre, ambispective, observational, study in which 114 patients in follow-up in 16 national CF units were recruited. Clinical data, functional tests, nutritional parameters, quality of life questionnaires, microbiological isolates, number of exacerbations, antibiotic treatments and side effects were collected. The study also compared patients with homozygous and heterozygous F508del mutations. Results: Of the 114 patients, 85 (74.6%) were heterozygous for F508del mutation, and the mean age was 32.2±9.96 years. After 30 months of treatment, lung function measured by FEV1% showed improvement from 37.5 to 48.6 (p<0.001), BMI increased from 20.5 to 22.3 (p<0.001), and all isolated microorganisms decreased significantly. The total number of exacerbations was also significantly reduced from 3.9 (±2.9) to 0.9 (±1.1) (p<0.001). All items in the CFQ-R questionnaire showed improvement, except for the digestive domain. Oxygen therapy use decreased by 40%, and only 20% of patients referred for lung transplantation remained on the active transplant list. ETI was well-tolerated, with only 4 patients discontinuing treatment due to hypertransaminemia. Conclusions: ETI decreases the number of exacerbations, increases lung function and nutritional parameters, decrease in all isolated microorganisms, for 30 months of treatment. There is an improvement in the CFQ-R questionnaire score except for the digestive item. It is a safe and well-tolerated drug. (AU)

Experience With Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Disease.

INTRODUCTION: Elexacaftor/tezacaftor/ivacaftor (ETI) was used through the early access programme in Spain from December 2019 in cystic fibrosis (CF) patients with homozygous or heterozygous F508del mutation with advanced lung disease. METHODOLOGY: Multicentre, ambispective, observational, study in which 114 patients in follow-up in 16 national CF units were recruited. Clinical data, functional tests, nutritional parameters, quality of life questionnaires, microbiological isolates, number of exacerbations, antibiotic treatments and side effects were collected. The study also compared patients with homozygous and heterozygous F508del mutations. RESULTS: Of the 114 patients, 85 (74.6%) were heterozygous for F508del mutation, and the mean age was 32.2±9.96 years. After 30 months of treatment, lung function measured by FEV1% showed improvement from 37.5 to 48.6 (p<0.001), BMI increased from 20.5 to 22.3 (p<0.001), and all isolated microorganisms decreased significantly. The total number of exacerbations was also significantly reduced from 3.9 (±2.9) to 0.9 (±1.1) (p<0.001). All items in the CFQ-R questionnaire showed improvement, except for the digestive domain. Oxygen therapy use decreased by 40%, and only 20% of patients referred for lung transplantation remained on the active transplant list. ETI was well-tolerated, with only 4 patients discontinuing treatment due to hypertransaminemia. CONCLUSIONS: ETI decreases the number of exacerbations, increases lung function and nutritional parameters, decrease in all isolated microorganisms, for 30 months of treatment. There is an improvement in the CFQ-R questionnaire score except for the digestive item. It is a safe and well-tolerated drug.

Real Life With Tezacaftor and Ivacaftor in Adult Patients With Cystic Fibrosis: Spanish Multicenter Study

No disponible

[Risk and Mortality Factors for Pleural Effusions Requiring Diagnostic Thoracentesis]. / Factores de riesgo y mortalidad de los derrames pleurales que precisan de una toracocentesis diagnóstica.

Introduction: Occurrence of malignant pleural effusion (PE) is known to be associated with a poor prognosis, but the mortality of patients with non-malignant effusions has not been sufficiently studied. Our objective was to describe the clinical course and explore risk factors associated with all-cause mortality at 1, 5 and 10 years in patients who develop a PE. Methods: Retrospective observational study of patients undergoing diagnostic thoracentesis during the decade 2008-2017 in a pulmonology service. Demographic, biochemical, pathological and evolutionary variables were evaluated. The etiology of the effusions was determined using standardized criteria. Results: Pleural fluid samples from 358 patients with a mean age of 68.9 years (SD 15.1 years), 69.2% males, were analyzed. Malignant (29.4%), parapneumonic (19.8%) and secondary to heart failure (18.9%) effusions predominated. Patients with malignant and heart failure related PE had 1-year mortality rates of 60.0% and 30.8%, respectively, and 85% and 64.7% at 5 years. Male gender (hazard ratio [HR] 1.46; 95% CI: 1.03-2.07), positive cytology for malignancy (HR 1.66; 95% CI: 1.03-2.68) and effusion recurrence (HR 1.61; 95% CI: 1.17-2.21) were associated with a worse prognosis and 5-year mortality. Conclusions: Patients undergoing thoracentesis for effusion have a high short and long-term mortality. In our series of hospitalized patients with PE, the factors associated with higher mortality at 1 and 5 years were age, male sex, recurrence of PE, and coexistence of malignancy.

Cost of Hospitalizations due to Exacerbation in Patients with Non-Cystic Fibrosis Bronchiectasis.

BACKGROUND: Knowing the cost of hospitalizations for exacerbation in bronchiectasis patients is essential to perform cost-effectiveness studies of treatments that aim to reduce exacerbations in these patients. OBJECTIVES: To find out the mean cost of hospitalizations due to exacerbations in bronchiectasis patients, and to identify factors associated with higher costs. METHODS: Prospective, observational, multicenter study in adult bronchiectasis patients hospitalized due to exacerbation. All expenses from the patients' arrival at hospital to their discharge were calculated: diagnostic tests, treatments, transferals, home hospitalization, admission to convalescence centers, and hospitals' structural costs for each patient (each hospital's tariff for emergencies and 70% of the price of a bed for each day in a hospital ward). RESULTS: A total of 222 patients (52.7% men, mean age 71.8 years) admitted to 29 hospitals were included. Adding together all the expenses, the mean cost of the hospitalization was EUR 5,284.7, most of which correspond to the hospital ward (86.9%), and particularly to the hospitals' structural costs. The adjusted multivariate analysis showed that chronic bronchial infection by Pseudomonas aeruginosa, days spent in the hospital, and completing the treatment with home hospitalization were factors independently associated with a higher overall cost of the hospitalization. CONCLUSIONS: The mean cost of a hospitalization due to bronchiectasis exacerbation obtained from the individual data of each episode is higher than the cost per process calculated by the health authorities. The most determining factor of a higher cost is chronic bronchial infection due to P. aeruginosa, which leads to a longer hospital stay and the use of home hospitalization.

Comorbilidad infecciosa en la EPOC / Infectious comorbidity in COPD

La infección respiratoria es la comorbilidad infecciosa más frecuente y característica de los pacientes conenfermedad pulmonar obstructiva crónica (EPOC). Esta infección respiratoria origina 2 cuadros clínicos. Elprimero y más común se asociaría a una agudización, aunque no todas las agudizaciones son de causa infecciosa;su porcentaje estaría entre el 50 y el 70% de estos procesos. El segundo cuadro clínico corresponderíaa la presencia de una neumonía, ya que, como se sabe, la EPOC es la comorbilidad más frecuenteasociada al desarrollo de una neumonía.De los agentes infecciosos causantes de agudizaciones, el 50-60% de los casos corresponderían a bacterias,que son los microorganismos que más se han estudiado y cuyo papel con las últimas investigaciones cadadía es más notorio. Dentro de las bacterias habría que destacar el hecho que cada vez se están aislando enagudizaciones un número mayor de casos de Pseudomonas aeruginosa y microorganismos más agresivos.Un segundo grupo que causa agudizaciones infecciosas serían los virus, que parece que pueden tener unpapel relevante en estos procesos, aunque menos determinante que el de las bacterias. En muchos casospueden predisponer a una infección bacteriana posterior.La neumonía comunitaria (NAC) es una entidad muy común en pacientes con EPOC y es conocido que entreel 25 y el 50% de los pacientes que ingresan con una NAC tienen una EPOC. Pese a ello, la EPOC no se haconsiderado un factor de riesgo de mala evolución en los pacientes con NAC, como quedó demostrado en elPneumonia Severity Index, en el que la EPOC no estaba entre las comorbilidades asociadas a mortalidad alos 30 días. Aunque recientemente ha habido algunos estudios que sí la asociaban a una mayor mortalidad,este hecho todavía es cuestionable y esta posible mejor evolución podría deberse al empleo de corticoidessistémicos en la gran mayoría de estos cuadros(AU)

Respiratory infection is the most frequent and characteristic infectious comorbidity in patients withchronic obstructive pulmonary disease (COPD) and can lead to two clinical scenarios. The fi rst and mostcommon is exacerbation, although not all exacerbations are caused by infections, which account for 50-70% of these processes. The second scenario is pneumonia, since COPD is the most frequent comorbidityassociated with the development of pneumonia.Of the infectious agents causing exacerbations, 50-60% of cases correspond to bacteria, which are the mostwidely studied microorganisms and whose role is becoming increasingly notorious. Among bacteria, agreater number of Pseudomonas aeruginosa and more aggressive microorganisms are being isolated inexacerbations. A second cause of infectious exacerbations are viruses, which seem to play an importantrole in these processes, although less so than bacteria. Viral infections seem to predispose many patients toa subsequent bacterial infection.Community-acquired pneumonia (CAP) is highly common in patients with COPD and between 25 and 50%of patients hospitalized with this diagnosis have COPD. Nevertheless, COPD has not been considered as arisk factor for poor outcome in patients with CAP and the Pneumonia Severity Index (PSI) showed thatCOPD was not among the comorbidities associated with mortality at 30 days. Although some studies haverecently associated COPD with increased mortality, this association is questionable and the possibleimproved outcome could be due to the use of systemic corticosteroids in most patients with COPD(AU)