Rosa Girón

Diagnóstico y tratamiento de las bronquiectasias

Bronchiectasis is the end result of several different diseases that share principles of management. The clinical course usually involves chronic bronchial infection and inflammation, which are associated with progression. The cause of bronchiectasis should always be investigated, particularly when it can be treated. We recommend evaluating etiology, symptoms, bronchial colonization and infection, respiratory function, inflammation, structural damage, nutritional status, and quality of life in order to assess severity and to monitor clinical course. Care should be supervised by specialized units, at least in cases of chronic bronchial infection, recurrent exacerbations, or when there is a cause that is likely to respond to treatment. Improving symptoms and halting progression are the goals of management, which is based on treatment of the underlying cause and of acute or chronic infections and on the drainage of secretions. Complications that arise must also be treated. Antibiotic prescription is guided by how well infection is being controlled, and this is indicated by the color of sputum and a reduction in the number of exacerbations. We recommend inhaled antibiotics in cases of chronic bronchial infection that does not respond to oral antibiotics, when these cause side effects, or when the cause is Pseudomonas species or other bacteria resistant to oral antibiotics. Inhaled administration is also advisable to treat initial colonization by Pseudomonas species.

Diagnosis and Treatment of Bronchiectasis

Bronchiectasis is the end result of several different diseases that share principles of management. The clinical course usually involves chronic bronchial infection and inflammation, which are associated with progression. The cause of bronchiectasis should always be investigated, particularly when it can be treated. We recommend evaluating etiology, symptoms, bronchial colonization and infection, respiratory function, inflammation, structural damage, nutritional status, and quality of life in order to assess severity and to monitor clinical course. Care should be supervised by specialized units, at least when there is a history of chronic bronchial infection, recurrent exacerbations, or a cause that is likely to respond to treatment. Improving symptoms and halting progression are the goals of management, which is based on treatment of the underlying cause and of acute or chronic infections and on the drainage of secretions. Complications that arise must also be treated. Antibiotic prescription is guided by monitoring how well infection is being controlled, and this is indicated by the color of sputum and a reduction in the number of exacerbations. We recommend inhaled antibiotics when bronchial infection is chronic and does not respond to oral antibiotics or when these cause side effects, or when the cause is Pseudomonas species or other bacteria resistant to oral antibiotics. Inhaled administration is also advisable to treat initial colonization by Pseudomonas species.

Inhaled antibiotics for the treatment of chronic bronchopulmonary Pseudomonas aeruginosa infection in cystic fibrosis: systematic review of randomised controlled trials

Introduction: Inhaled antibiotics are probably the safest and most effective therapy for Pseudomonas aeruginosa chronic lung infection in cystic fibrosis (CF) patients. Areas covered: To summarise the available evidence, a systematic review of the three currently available inhaled antibiotics (aztreonam lysine (AZLI), colistin (COL) and tobramycin (TOB)) was performed. The three AZLI placebo-controlled studies showed that the improvements in FEV1 and mean sputum P. aeruginosa density were statistically significant better than with placebo. The two COL placebo-controlled studies involved few patients but showed that COL was better than placebo in terms of maintenance of some pulmonary function parameters. The tobramycin inhalation solution (TIS) and tobramycin inhalation powder studies showed that the efficacy of both formulations was similar but significantly better than placebo. In the comparative studies, TIS showed more efficacy than COL solution, colistin inhalation powder showed non-inferiority to TIS and AZLI was superior to TIS. Expert opinion: Placebo-controlled and comparative clinical trials have shown that clinical evidence of inhaled antibiotics is very different. The choice of treatment for each individual CF patient must be based on the features of the drug (clinical evidence on efficacy and safety), the inhalation system and the patient characteristics. Development of new inhaled antibiotics will allow new end points of efficacy and therapy regimens to be assessed.

Patógenos multirresistentes en la fibrosis quística

La infección pulmonar es una de las causas más importantes de morbilidad y mortalidad en el paciente con fibrosis quística (FQ). La evolución en el tiempo, su calidad de vida y sus expectativas de supervivencia son proporcionales al número anual de exacerbaciones y a la carga de microorganismos en las secreciones respiratorias1,2. El particular nicho ecológico del pulmón en los pacientes con FQ, el incremento de la edad y los tratamientos antimicrobianos prolongados determinan que, con elevada frecuencia, se encuentren microorganismos multirresistentes que hacen aún más difícil el control de la progresión de la colonización y el deterioro de la función pulmonar. En este sentido, es importante definir y conocer los patrones de sensibilidad de los microorganismos que habitualmente colonizan la vía aérea del paciente con FQ, los aspectos clínicos relacionados con la colonización por patógenos multirresistentes y las opciones terapéuticas específicas para cada situación. El diagnóstico microbiológico y la detección de estos patógenos en las muestras respiratorias son imprescindibles para un correcto control y seguimiento de estos pacientes. En abril de 2001 la Fundación Sira Carrasco para la ayuda a la FQ reunió en Madrid a pediatras, neumólogos y microbiólogos para dar a conocer, entre otros, un documento que sirviese de reflexión y guía de información sobre estos patógenos. La importancia de los microorganismos multirresistentes en la FQ se había constatado en una encuesta realizada con anterioridad3, en la que el 86% de los representantes de las diferentes unidades de FQ de España manifestaron que la multirresistencia era un problema acuciante, que podría condicionar el futuro de los tratamientos antimicrobianos y la calidad de vida de estos pacientes. En el presente trabajo se recogen los aspectos más sobresalientes de dicho documento, analizando el concepto de multirresistencia, su aplicación particular a los patógenos en la FQ, los factores que determinan su aparición, su repercusión clínica y algunos aspectos relacionados con el seguimiento microbiológico de los pacientes con aislamientos multirresistentes. Concepto de multirresistencia

Estudio multicéntrico de prevalencia de micobacterias ambientales en pacientes con fibrosis quística

Objetivo Evaluar la prevalencia de micobacterias ambientales (MA) en pacientes con fibrosis quistica (FQ). Pacientes y metodos Se ha realizado un estudio prospectivo de 2 anos de duracion en pacientes con FQ mayores de 6 anos, procedentes de 6 unidades monograficas. En las muestras respiratorias, recogidas cada 6 meses, se efectuo una tincion de auramina-rodamina, ademas de cultivos en medios solido y liquido. Si se detectaba una tincion o cultivo positivo para MA, se recogian 1 o 2 esputos mas y se hacia un seguimiento estricto para valorar la necesidad de tratamiento especifico. Se consideraron las siguientes variables clinicas: edad, sexo, insuficiencia pancreatica, diabetes, uso de aerosolterapia antibiotica y de azitromicina de forma continua, tratamientos con corticoides inhalados o por via oral de forma prolongada. Resultados Participaron en el estudio 220 pacientes (119 mujeres), con una edad media de 22,62 anos (rango: 6-74). El 23,6% recibia azitromicina. Se cultivaron para la deteccion de micobacterias 1.303 muestras de esputo (rango por paciente: 4-68), de las que la tincion de auramina fue positiva en 17 casos y el cultivo en 48, correspondientes a 17 pacientes (7,72%). En 88 muestras el cultivo estaba contaminado. En ningun caso se aislo Mycobacterium tuberculosis . Las MA aisladas fueron: M. avium complex (n = 10), M. abscessus (n = 6) y M. fortuitum (n = 1). Cinco de los 9 pacientes que presentaron mas de un aislamiento tuvieron deterioro clinico y se les indico tratamiento especifico. No hubo diferencias entre las variables clinicas de los pacientes con y sin aislamientos de MA. Conclusiones La prevalencia de MA en pacientes con FQ no fue muy alta (7,72%), quiza debido a la interferencia de la azitromicina sobre el crecimiento de MA. Hay que vigilar estrechamente a los pacientes con aislamientos repetidos.

Annual direct medical costs of bronchiectasis treatment Impact of severity, exacerbations, chronic bronchial colonization and chronic obstructive pulmonary disease coexistence

Patients with bronchiectasis (BE) present exacerbations that increase with severity of the disease. We aimed to determine the annual cost of BE treatment according to its severity, determined by FACED score, as well as the parameters associated with higher costs. Multicentre historical cohorts study with patients from six hospitals in Spain. The costs arising during the course of a year from maintenance treatment, exacerbations, emergency visits and hospital admissions were analysed. In total, 456 patients were included (56.4% mild BE, 26.8% moderate BE and 16.9% severe BE). The mean cost was €4671.9 per patient, which increased significantly with severity. In mild BE, most of the costs were due to bronchodilators and inhaled steroids; in severe BE, most were due to exacerbations and inhaled antibiotics. Forced expiratory volume in 1 second (FEV1%), age, colonization by Pseudomonas aeruginosa and the number of admissions were independently related to higher costs. The highest costs were found in patients with BE associated with chronic obstructive pulmonary disease, with the most exacerbations and with chronic bronchial colonization by Pseudomonas aeruginosa (PA). In conclusion, BE patients gave rise to high annual costs, and these were doubled on each advance in severity on the FACED score. FEV1%, age, colonization by PA and the number of admissions were independently related to higher costs.

The Multiple Faces of Non-Cystic Fibrosis Bronchiectasis: A Cluster Analysis Approach

RATIONALE The clinical presentation and prognosis of non-cystic fibrosis bronchiectasis are both very heterogeneous. OBJECTIVES To identify different clinical phenotypes for non-cystic fibrosis bronchiectasis and their impact on prognosis. METHODS Using a standardized protocol, we conducted a multicenter observational cohort study at six Spanish centers with patients diagnosed with non-cystic fibrosis bronchiectasis before December 31, 2005, with a 5-year follow-up from the bronchiectasis diagnosis. A cluster analysis was used to classify the patients into homogeneous groups by means of significant variables corresponding to different aspects of bronchiectasis (clinical phenotypes): age, sex, body mass index, smoking habit, dyspnea, macroscopic appearance of sputum, number of exacerbations, chronic colonization with Pseudomonas aeruginosa, FEV1, number of pulmonary lobes affected, idiopathic bronchiectasis, and associated chronic obstructive pulmonary disease. Survival analysis (Kaplan-Meier method and log-rank test) was used to evaluate the comparative survival of the different subgroups. MEASUREMENTS AND MAIN RESULTS A total of 468 patients with a mean age of 63 (15.9) years were analyzed. Of these, 58% were females, 39.7% had idiopathic bronchiectasis, and 29.3% presented with chronic Pseudomonas aeruginosa colonization. Cluster analysis showed four clinical phenotypes: (1) younger women with mild disease, (2) older women with mild disease, (3) older patients with severe disease who had frequent exacerbations, and (4) older patients with severe disease who did not have frequent exacerbations. The follow-up period was 54 months, during which there were 95 deaths. Mortality was low in the first and second groups (3.9% and 7.6%, respectively) and high for the third (37%) and fourth (40.8%) groups. The third cluster had a higher proportion of respiratory deaths than the fourth (77.8% vs. 34.4%; P < 0.001). CONCLUSIONS Using cluster analysis, it is possible to separate patients with bronchiectasis into distinct clinical phenotypes with different prognoses.

Prevalence and factors associated with isolation of Aspergillus and Candida from sputum in patients with non-cystic fibrosis bronchiectasis.

Background: Information on the role of fungi in non-cystic fibrosis (CF) bronchiectasis is lacking. Objectives: Our aim was to determine the prevalence of and factors associated with the isolation and persistence of fungi from sputum in these patients. Methods: We performed a multicenter observational study comprising adult patients with non-CF bronchiectasis. Persistence of Aspergillus spp. and Candida albicans was defined as the presence of ≥2 positive sputum cultures taken at least 6 months apart within a period of 5 years. Results: A total of 252 patients (62.7% women with a mean ± SD age of 55.3 ± 16.7 years) were included in the study. All patients had at least 1 sputum sample cultured for fungi, with a mean ± SD of 7 ± 6 cultures per patient. Eighteen (8.7%) and 71 (34.5%) patients had persistent positive cultures for Aspergillus spp. and C. albicans, respectively. Patients with persistence of Aspergillus spp. and C. albicans were older and had more daily purulent sputum. In addition, patients with persistent C. albicans had worse postbronchodilator forced expiratory volume in the first second (FEV1), more frequent cystic bronchiectasis, and more hospital-treated exacerbations. They were also more frequently treated with long-term antibiotics. Multivariate analysis showed that daily purulent sputum (OR = 3.75, p = 0.045) and long-term antibiotics (OR = 2.37, p = 0.005) were independently associated with persistence of Aspergillus spp. and C. albicans, respectively. Conclusions: Isolation and persistence of Aspergillus spp. and C. albicans are frequent in patients with non-CF bronchiectasis. Daily purulent sputum and chronic antibiotic treatment were associated with persistence of Aspergillus spp. and C. albicans, respectively.

Bronchial reactivity indices are determinants of health-related quality of life in patients with stable asthma

Background A very weak relationship has been reported between the health-related quality of life (HRQL) of patients with asthma and their degree of airway hyper-responsiveness (AHR), evaluated in terms of sensitivity. However, this relationship still has not been sufficiently explored for bronchial reactivity indices. Objectives To analyse the relationship between bronchial reactivity and sensitivity with the HRQL of patients with stable asthma, identifying the functional parameters that determine HRQL. Methods In 103 consecutive patients with stable asthma, HRQL was evaluated using the Asthma Quality of Life Questionnaire (AQLQ). Patients underwent spirometry and non-specific bronchial provocation with methacoline. Sensitivity (PD20) and reactivity (dose–response slope (DRS), continuous index of responsiveness (CIR) and bronchial reactivity index (BRI)) of the dose–response curve were analysed. Results BRI presented significant differences with different degrees of asthma severity. Although patients with AHR showed poorer quality of life than patients without AHR, the AQLQ total score was not related to PD20 but rather to DRS (r=−0.784), CIR (r=−0.712) and BRI (r=−0.776). The indices of bronchial reactivity reached a negative correlation with all the domains of the AQLQ. In a multiple linear regression model, BRI, DRS, FIV1 (forced inspiratory volume in 1 s) and VCIN (inspiratory vital capacity) were identified as independent predictors of the AQLQ total score (r2=0.742, p<0.001). Conclusion In patients with stable asthma, bronchial reactivity is associated with HRQL. This could justify incorporating bronchial reactivity indices in bronchial provocation analyses.

Validation of a Spanish version of the Leicester Cough Questionnaire in non-cystic fibrosis bronchiectasis

The Leicester Cough Questionnaire (LCQ) has been validated in non-cystic fibrosis bronchiectasis (NCFBC). The present study aimed to create and validate a Spanish version of the LCQ (LCQ-Sp) in NCFBC. The LCQ-Sp was developed following a standardized protocol. For reliability, we assessed internal consistency and the change in score over a 15-day period in stable state. For responsiveness, we assessed the change in scores between visit 1 and the first exacerbation. For validity, we evaluated convergent validity through correlation with the Saint George’s Respiratory Questionnaire (SGRQ) and discriminant validity. Two hundred fifty-nine patients (118 mild bronchiectasis, 90 moderate bronchiectasis and 47 severe bronchiectasis) were included. Internal consistency was high for the total scoring and good for the different domains (Cronbach’s α: 0.86–0.91). The test–retest reliability shows an intraclass correlation coefficient of 0.87 for the total score. The mean LCQ-Sp score at visit 1 decreased at the beginning of an exacerbation (15.13 ± 4.06 vs. 12.24 ± 4.64; p < 0.001). The correlation between LCQ-Sp and SGRQ scores was −0.66 (p < 0.01). The differences in the LCQ-Sp total score between the different groups of severity were significant (p < 0.001). The LCQ-Sp discriminates disease severity, is responsive to change when faced with exacerbations and is reliable for use in bronchiectasis.