Should atelectasis be considered a pulmonary complication and indicator of poor prognosis in cystic fibrosis?

OBJECTIVE: This study examined whether bronchoscopy leads to clinicoradiological improvement in cystic fibrosis (CF) and the predictive factors. The study also investigated whether pulmonary atelectasis is a poor prognostic factor in CF. METHODS: This multicenter, case-control, observational, retrospective study included two groups of patients with CF: a case group (patients with persistent atelectasis who were followed-up at least for 2 years) and a control group (patients without atelectasis matched 1:1 by sex and age [±3 years]). We recorded demographic data, lung function test results, pulmonary complications, comorbidities, treatments (including bronchoscopies, surgery and transplantation), and deaths. RESULTS: Each group included 55 patients (case group: 20 men, mean age 25.4 ± 10.4 years; control group: 20 men, mean age 26.1 ± 11.4 years). Bronchoscopy did not lead to clinicoradiological improvement. Allergic bronchopulmonary aspergillosis (ABPA) was more frequent in the case group. Patients in the case group more frequently used inhaled steroids, their pre-atelectasis lung function was statistically worse, and they had more exacerbations during follow-up. CONCLUSION: Moderate-to-severe pulmonary disease and ABPA can favor atelectasis. Pulmonary atelectasis can be a poor prognostic factor in CF because it increases exacerbations. Despite our results, we recommend enhancing treatment, including bronchoscopy, to prevent persistent atelectasis.

Molecular diagnosis of cystic fibrosis by RNA obtained from nasal epithelial cells.

BACKGROUND: The diagnosis of cystic fibrosis (CF) is established when characteristic clinical signs are coupled with biallelic CFTR pathogenic variants. No previously reported non-canonical splice site variants have to be considered as variants of uncertain significance unless their effect on splicing has been validated. METHODS: Two variants identified by next-generation sequencing were evaluated. We assayed their effects on splicing employing RNA analysis and real-time expression quantification from RNA obtained from the nasal epithelial cells of a patient with clinically suspected CF and of two patients with milder phenotypes (CFTR-related disorders). RESULTS: The variant c.164+2dup causes skipping of exon 2 (p.(Ser18_Glu54del)) and exon 2 plus 3 (p.(Ser18Argfs*16)) in CFTR mRNA. Exon 2 expression in the patient heterozygous for c.164+2dup was decreased to 7 % of the exon 2 expression in the controls. The synonymous variant c.1584G>A causes a partial skipping of exon 11. The exon 11 expression in the two patients heterozygous for this variant was 22 % and 42 % of that of the controls, respectively. CONCLUSION: We conclude that variant c.164+2dup affects mRNA processing and can be considered a CF-causing variant. The results of the functional assay also showed that the p.(Glu528=) variant, usually categorized as a neutral variant based on epidemiological data, partially affects mRNA processing in our patients. This finding would allow us to reclassify the variant as a CFTR-related variant with incomplete penetrance. RNA obtained from nasal epithelial cells is an easy and accurate tool for CFTR functional studies in patients with unclassified splice variants.

Fibrosis quística: epidemiología, clínica, diagnóstico y tratamiento / Cystic fibrosis: Epidemiology, clinical manifestations, diagnosis and treatment

La fibrosis quística es una enfermedad genética y multisistémica. La principal comorbilidad en la edad adulta es la afectación respiratoria, con la presencia de bronquiectasias, infección bronquial crónica y obstrucción al flujo aéreo. Hasta hace una década los tratamientos estaban dirigidos a favorecer el drenaje de secreciones, reducir las exacerbaciones respiratorias, controlar la infección bronquial crónica y enlentecer el deterioro funcional, pero con la llegada de los moduladores del gen cystic fibrosis transmembrane conductance regulator (CFTR) el paradigma de la fibrosis quística se ha modificado. Este novedoso tratamiento da un paso más frente al tratamiento de esta enfermedad, es capaz de mejorar la producción de proteína CFTR defectuosa y aumentar su expresión en la superficie celular, para así conseguir un mejor funcionamiento del intercambio iónico fluidificando las secreciones respiratorias y reduciendo la obstrucción al flujo aéreo. Además, en la actualidad hay diferentes líneas de investigación orientadas a corregir el defecto genético causante de la fibrosis quística (AU)

Cystic fibrosis is a genetic and multisystemic disease. The main comorbidity in adulthood is respiratory involvement, with the presence of bronchiectasis, chronic bronchial infection and airflow obstruction. Until a decade ago, treatments were aimed at favoring secretion drainage, reducing respiratory exacerbations, controlling chronic bronchial infection and slowing functional deterioration, but with the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, the cystic fibrosis paradigm has changed. This novel treatment goes a step further in the management of this disease, it is able to improve the production of defective CFTR protein and increase its expression on the cell surface, thus achieving a better functioning of ion exchange, fluidizing respiratory secretions and reducing airflow obstruction. In addition, there are currently different lines of research aimed at correcting the genetic defect that causes cystic fibrosis (AU)

Cystic fibrosis: Epidemiology, clinical manifestations, diagnosis and treatment. / Fibrosis quística: epidemiología, clínica, diagnóstico y tratamiento.

Cystic fibrosis is a genetic and multisystemic disease. The main comorbidity in adulthood is respiratory involvement, with the presence of bronchiectasis, chronic bronchial infection and airflow obstruction. Until a decade ago, treatments were aimed at favoring secretion drainage, reducing respiratory exacerbations, controlling chronic bronchial infection and slowing functional deterioration, but with the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, the cystic fibrosis paradigm has changed. This novel treatment goes a step further in the management of this disease, it is able to improve the production of defective CFTR protein and increase its expression on the cell surface, thus achieving a better functioning of ion exchange, fluidizing respiratory secretions and reducing airflow obstruction. In addition, there are currently different lines of research aimed at correcting the genetic defect that causes cystic fibrosis.

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.

Impact and characteristics of hospital-acquired influenza over 10 seasons in a third-level university hospital.

OBJECTIVES: To analyze the characteristics of patients with nosocomial flu, to compare them with patients with community-acquired influenza to study possible differences and to identify possible risk factors associated with this type of flu. PATIENTS AND METHODS: Observational, cross-sectional and retrospective study of hospitalized patients with a microbiological confirmation of influenza in a third-level university hospital over 10 seasons, from 2009 to 2019. Nosocomial influenza was defined as that infection whose symptoms began 72h after hospital admission, and its incidence, characteristics and consequences were further analyzed. RESULTS: A total of 1260 hospitalized patients with a microbiological diagnosis of influenza were included, which 110 (8.7%) were nosocomial. Patients with hospital-acquired influenza were younger (71.74±16.03 years, P=0.044), had a longer hospital stay (24.25±20.25 days, P<0.001), had more frequently a history of chronic pulmonary pathologies (P=0.010), immunodeficiency (P<0.001), and were associated with greater development of bacterial superinfection (P<0.001), respiratory distress (P=0.003), and admission to the intensive care unit (ICU) (P<0.001). In the multivariate logistic regression analysis, the following characteristics were identified as independent risk factors: immunodeficiency (ORa=2.33; 95% CI: 1.47-3.60); ICU admission (ORa=4.29; 95% CI: 2.23-10.91); bacterial superinfection (ORa=1.64; 95% CI: 1.06-2.53) and respiratory distress (ORa=3.88; 95% CI: 1.23-12.23). CONCLUSIONS: Nosocomial influenza is more common in patients with a history of immunodeficiency. In addition, patients with hospital-acquired influenza had an increased risk of bacterial superinfection, admission to the ICU, and development of respiratory distress.

Influenza vaccination for flu infection in hospitalised patients / Vacunación antigripal en pacientes hospitalizados por gripe

Objectives: The objectives of this study are (1) to analyse which group of admitted patients with risk factors is most ­vaccinated, (2) to find out whether vaccinated patients admitted for flu have fewer complications, and (3) to check whether there are differences in demographic and therapeutic characteristics between vaccinated and unvaccinated patients who have been admitted. Patients and methods: This is a single-centre, observational, cross-sectional, and retrospective study of patients admitted for flu at La Paz University Hospital in the 2013–2014 and 2014–2015 seasons, with an analysis of the variables included in the clinical history and mandatory declaration documents. Results: A total of 179 patients were ­admitted for influenza infection in the two seasons studied, of whom 65 (36.3%) patients were vaccinated. Patients with chronic heart disease were significantly more vaccinated than other risk groups. Furthermore, the average age of vaccinated patients was significantly higher than that of unvaccinated patients. We did not find any other significant differences in the remaining ­variables when comparing the two groups, nor did we find any less development of complications in the admitted and ­vaccinated patients. Conclusion: It is important to emphasise vaccination campaigns, increase vaccination coverage, and raise awareness of vaccination among all patients with chronic diseases.(AU)

Objetivos: 1) analizar qué grupo de pacientes con factores de riesgo que ingresa se vacuna más; 2) averiguar si los ­enfermos con gripe hospitalizados que han sido vacunados tienen menor número de complicaciones, y 3) comprobar si existen diferencias en cuanto a las características demográficas y terapéuticas al comparar a los pacientes ingresados vacunados y no vacunados. Pacientes y métodos: Estudio unicéntrico, observacional, transversal y retrospectivo de los pacientes ingresados por gripe en el Hospital Universitario La Paz en las temporadas 2013–2014 y 2014–2015, con análisis de las variables recogidas en el documento del historial clínico y de los documentos de declaración obligatoria. Resultados: 179 pacientes ingresaron por gripe en las dos temporadas estudiadas, de los cuales estaban vacunados 65 (36.3%). Se vacunaron más, de forma significativa, los pacientes con enfermedades cardiacas crónicas frente al resto de grupos de riesgo. La edad media de los vacunados era significativamente mayor. No encontramos otras diferencias significativas en el resto de las variables al comparar los dos grupos, tampoco un menor desarrollo de complicaciones en los pacientes ­ingresados y vacunados. Conclusiones: Es importante hacer hincapié en las campañas de vacunación, es necesario aumentar la cobertura vacunal en, y concienciar sobre la vacunación a, los enfermos con patologías crónicas.(AU)

Factors associated with poor long-term adherence after completing a pulmonary rehabilitation programme in patients with chronic obstructive pulmonary disease.

BACKGROUND: Although pulmonary rehabilitation programmes (PRPs) benefit patients with chronic obstructive pulmonary disease (COPD), poor adherence to these programmes is common. OBJECTIVE: This study aimed to analyse the factors associated with poor long-term adherence after completing a PRP. METHOD: We conducted a retrospective study of 70 patients with COPD who performed an 8-week outpatient PRP that included 24 sessions of aerobic training, skeletal muscle resistance exercises, physiotherapy and COPD education. The study classified the patients into 2 groups: (1) long-term adherence and (2) long-term non-adherence to the PRP. We considered long-term non-adherence when the patient did not attend the 32 weeks follow-up visit after beginning the PRP. We measured the degree of dyspnoea, quality of life, physical activity, anxiety-depression status, submaximal exercise capacity and COPD exacerbations in both groups. RESULTS: The patients' median age was 69.6 [63.8-75.0] years, and 71.4% were men. The median forced expiratory volume in 1 second was 60.0 [47.7-68.0] % of that predicted. We observed total COPD exacerbations and severe COPD exacerbations in the last year in 32 (45.7%) and 22 (31.4%) patients, respectively. Dyspnoea, physical activity and quality of life significantly improved after completing the PRP. Long-term non-adherence to the PRP was observed in 32 (45.7%) patients. In the single regression model, severe COPD exacerbations (p = 0.04) and dyspnoea (p = 0.03) were associated with long-term non-adherence to the PRP. In the multiple regression model, only severe COPD exacerbations remained as an associated factor (OR 2.7; 95% CI 1.1-8,1; p = 0.04). CONCLUSION: Approximately half of patients who complete PRPs present long-term non-adherence to the programme. Severe COPD exacerbations are associated with long-term non-adherence.

¿Son importantes los dispositivos de inhalación en antibioterapia? / Are Inhalation Devices Important in Antibiotic Treatment?

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Imágenes quísticas pulmonares en paciente con infección por SARS-CoV-2 / Lung cysts in a patient with SARS-CoV-2

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Lung cysts in a patient with SARS-CoV-2 / Imágenes quísticas pulmonares en paciente con infección por SARS-CoV-2

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Síndrome antisintetasa: análisis de 11 casos / Antisynthetase syndrome: Analysis of 11 cases

Introducción: El síndrome antisintetasa (ASA) se caracteriza por manifestaciones clínicas como miositis, fiebre, manos de mecánico y enfermedad pulmonar intersticial (EPI) asociadas a la positividad ante anticuerpos antisintetasa. La presencia de EPI será la que, en gran medida, marcará la respuesta al tratamiento y el pronóstico. Pacientes y métodos: Se describen 11 pacientes con ASA y afectación pulmonar en seguimiento en una consulta monográfica de Neumología de un hospital de tercer nivel. Resultados: Nueve pacientes presentaron positividad para anticuerpos anti-Jo y 2 para anti-PL12. Cuatro pacientes mostraron en TCAR patrón NINE, 4 NIU, uno NOC y 2 en vidrio deslustrado. El 73% se acompañaron de bronquiectasias y bronquiolectasias y el 27%, de panalización. Funcionalmente resalta la DLCO, con hasta el 45% con un test de la marcha positivo. Destaca la corticodependencia, con necesidad en muchas ocasiones de tratamiento inmunodepresor, tanto en exacerbaciones como de forma crónica. Todos los pacientes mantuvieron buen pronóstico hasta el momento. Conclusiones: Los pacientes con EPI deberían tener al menos una determinación de anticuerpos antisintetasa para así identificar esta enfermedad, de mejor pronóstico que otras afecciones intersticiales como la fibrosis pulmonar idiopática (AU)

Introduction: Antisynthetase syndrome (ASS) is characterised by a series of clinical manifestations such as myositis, fever, mechanic’s hands and diffuse interstitial lung disease (ILD), all associated with positivity to antisynthetase antibodies. The presence of ILD will be that, to a great extent it will mark the response to treatment and prognosis. Patients and methods: Eleven cases of patients with ASS and pulmonary involvement in monitoring at a Pulmonary monographic consult in a third level hospital consult are described. Results: Nine patients presented positivity to anti-Jo antibody and 2 to anti-PL12. Four patients’ HRCT pattern showed NSIP, four UIP, one COP and 2 ground-glass opacity. A percentage of 73 were accompanied by bronchiectasis and bronchiolectasis and 27% honeycombing. Functional exploration was mainly affected by DLCO with up to 45% of the positive walking test. Corticodependence is highlighted, often requiring immunosuppressive treatment both chronically and in exacerbations. All patients maintain good prognosis so far. Conclusions: Patients with interstitial lung disease should have at least a determination of antisynthetase antibodies in order to identify this disease, better prognosis than other interstitial diseases such as idiopathic pulmonary fibrosis (AU)

Antisynthetase syndrome: Analysis of 11 cases. / Síndrome antisintetasa: análisis de 11 casos.

INTRODUCTION: Antisynthetase syndrome (ASS) is characterised by a series of clinical manifestations such as myositis, fever, mechanic's hands and diffuse interstitial lung disease (ILD), all associated with positivity to antisynthetase antibodies. The presence of ILD will be that, to a great extent it will mark the response to treatment and prognosis. PATIENTS AND METHODS: Eleven cases of patients with ASS and pulmonary involvement in monitoring at a Pulmonary monographic consult in a third level hospital consult are described. RESULTS: Nine patients presented positivity to anti-Jo antibody and 2 to anti-PL12. Four patients' HRCT pattern showed NSIP, four UIP, one COP and 2 ground-glass opacity. A percentage of 73 were accompanied by bronchiectasis and bronchiolectasis and 27% honeycombing. Functional exploration was mainly affected by DLCO with up to 45% of the positive walking test. Corticodependence is highlighted, often requiring immunosuppressive treatment both chronically and in exacerbations. All patients maintain good prognosis so far. CONCLUSIONS: Patients with interstitial lung disease should have at least a determination of antisynthetase antibodies in order to identify this disease, better prognosis than other interstitial diseases such as idiopathic pulmonary fibrosis.

Lipomatosis cardiaca masiva, hallazgo en la autopsia de un paciente con muerte súbita / Massive cardiac lipomatosis, an autopsy finding in a patient with sudden death

La sustitución grasa de las células miocárdicas es un proceso degenerativo que afecta en mayor medida al ventrículo derecho y se encuentra en el 50% de las personas ancianas. El problema se origina cuando esta degeneración se produce en grado masivo, planteando la necesidad de realizar el diagnóstico diferencial con otras enfermedades. Se presenta el caso de un paciente que falleció de forma súbita y en su autopsia se encontró esta dolencia como única explicación del desenlace (AU)

The fat replacement of myocardial cells is a degenerative process that usually affects the right ventricle and is found in 50% of the elderly. The problem arises when this degeneration occurs to a massive degree, a differential diagnosis with other pathologies being necessary. We present the case of a patient who died suddenly and a massive cardiac lipomatosis was found on autopsy, as the only explanation of the outcome (AU)

[Massive cardiac lipomatosis, an autopsy finding in a patient with sudden death]. / Lipomatosis cardiaca masiva, hallazgo en la autopsia de un paciente con muerte súbita.

The fat replacement of myocardial cells is a degenerative process that usually affects the right ventricle and is found in 50% of the elderly. The problem arises when this degeneration occurs to a massive degree, a differential diagnosis with other pathologies being necessary. We present the case of a patient who died suddenly and a massive cardiac lipomatosis was found on autopsy, as the only explanation of the outcome.