Lung allograft transbronchial cryobiopsy for critical ventilated patients: a randomised trial.

BACKGROUND: Transbronchial lung cryobiopsy is an emerging technique for diagnosing pulmonary rejection. However, no prospective studies of this procedure for critically ill lung transplant recipients who require mechanical ventilation in the intensive care unit (ICU) have been performed. METHODS: From March 2017 to January 2020, we performed a prospective, randomised, comparative study to assess the diagnostic yield, histological quality and safety of transbronchial lung biopsy using biopsy forceps, a 1.9-mm cryoprobe or a 2.4-mm cryoprobe. RESULTS: 89 out of 129 consecutive transbronchial biopsy procedures (forceps group, 28 procedures; 1.9-mm cryoprobe group, 31 procedures; 2.4-mm cryoprobe group, 30 procedures) were randomised. Compared with lung samples from the forceps and 1.9-mm cryoprobe groups, lung samples from the 2.4-mm cryoprobe group allowed the most definitive diagnoses (p<0.01 and p=0.02, respectively), the most diagnoses of acute lung rejection (p<0.01 and p=0.01, respectively) and the most diagnoses of rejection severity (p<0.01 and p<0.01, respectively). These samples were larger (p<0.01 and p=0.04, respectively), had the most adequate alveolar tissue (p<0.01 and p=0.02, respectively), had more vessels per procedure (p<0.01 and p=0.01, respectively) and had no significant crush artefacts. Moderate bleeding was observed in 23% of cases (p=0.01 and p=0.08, respectively). No severe bleeding was observed. CONCLUSIONS: Transbronchial lung biopsy using a 2.4-mm cryoprobe allows the safe collection of lung tissue samples from critically ill lung transplant recipients who require mechanical ventilation in the ICU and has good diagnostic performance.

Validation of a Spanish version of the Leicester Cough Questionnaire in cystic fibrosis.

Cough is a main symptom in cystic fibrosis (CF). We aim to validate a Spanish version of the Leicester Cough Questionnaire (LCQ-Sp) to measure the impact of cough in CF bronchiectasis. A prospective longitudinal multicentre study was performed. Internal consistency and score changes over a 15-day period in stable state were assessed to analyse reliability. Concurrent validity was analysed by correlation with Saint George's Respiratory Questionnaire (SGRQ) and convergent validity by assessing the association with clinical variables. Changes in scores between stable state and the first exacerbation were assessed to analyse responsiveness. 132 patients (29.73 ± 10.52 years) were enrolled in four hospitals. Internal consistency was high for the total score and good for the three domains (Cronbach's α 0.81-0.93). The test-retest reliability showed an intraclass correlation coefficient of 0.86 for the total score. The correlation between LCQ-Sp and SGRQ scores was -0.74. The LCQ-Sp score negatively correlated with sputum volume, and the mean score decreased at the beginning of exacerbations (16.04±3.81 vs 13.91±4.29) with a large effect size. The LCQ-Sp is a reliable, repeatable and responsive instrument to assess the impact of cough in CF bronchiectasis and is responsive to change in the event of exacerbations.

New opacities in lung allograft after transbronchial cryobiopsy.

BACKGROUND: The occurrence of radiological opacities post-transbronchial cryobiopsy may pose serious difficulties in differential diagnosis and management of lung allografts. This prospective study evaluated the frequency, characteristics, and evolution of new lung opacities after performing transbronchial cryobiopsy. METHODS: From February 2018 to June 2018, 22 of 51 consecutive patients with an indication for transbronchial cryobiopsy underwent computed tomography (CT) of the thorax before and at 1, 4, and 8 weeks post-cryobiopsy. New CT images, required by the transplant team, were also evaluated during the next 6 months. Histological findings of transbronchial cryobiopsy and microbiological studies on bronchoalveolar lavage were evaluated as risk factors for opacities. RESULTS: After obtaining 112 cryobiopsy samples, 46 opacities >10 mm, including ground-glass, solid, cavitated, or a combination of these lesions were observed in 20 (91%) patients on post-cryobiopsy CT. All ground-glasses opacities on CT disappeared at 4 weeks. A single cavitated opacity persisted at 6 months. The remaining opacities disappeared or were decreased to <10 mm by 8 weeks. No correlations of the number, type, or evolution of opacities with the number or volume of cryobiopsy samples obtained, or with the histological diagnosis, type of transplant, or microbiologic culture results were observed. CONCLUSION: New pulmonary opacities >10 mm occur frequently after transbronchial cryobiopsy; a few may persist beyond 6 months. CT studies are recommended before implementing transbronchial cryobiopsy, whenever possible.

Optimization of Transbronchial Cryobiopsy in Lung Transplant Recipients.

BACKGROUND: Previous studies suggest that transbronchial lung biopsy using a cryoprobe is superior to transbronchial lung biopsy using forceps for evaluating lung grafts, although the technique can be associated an increase in complications. Because cryoprobe experience is limited, assessment of a greater number of cases is warranted. This prospective study evaluates the diagnostic yield, complications, and risk factors associated with the cryoprobe technique. METHODS: From April 2013 to April 2016, 321 consecutive cryoprobe transbronchial biopsies were indicated in single or bilateral lung transplant patients with acute or chronic clinical lung injury or in asymptomatic patients before hospital discharge after lung transplantation. RESULTS: With a mean of 4.32 lung parenchyma specimens per procedure, adequate alveolar lung parenchyma was obtained in 96.6% (84.27 ± 44.14 mm2) of cases. Obtaining at least 4 samples increased the histological diagnostic certainty (P < .001). Moderate to severe bleeding was observed in 7.48% of patients and was significantly more frequent in patients with unilateral transplantation (odds ratio, 0.10; 95% confidence interval, 0.02-0.30; P < .001) and in those with high blood pressure during scanning (odds ratio, 0.31; 95% confidence interval, 0.12-0.86; P = .019). Pneumothorax was observed in 7.7% of the patients, but only 3.7% of these patients required pleural drainage. CONCLUSIONS: Obtaining 4 or more cryobiopsy samples is valuable and safe for lung allograft monitoring. Being a recipient of a unilateral lung transplant or having arterial hypertension during bronchoscopy seem to be risk factors associated with increased bleeding.

Primary immunodeficiency diseases in lung disease: warning signs, diagnosis and management.

BACKGROUND: Pulmonary complications are common in primary immunodeficiency diseases (PID) and contribute to morbidity and mortality in these patients. However, their varied presentation and a general lack of awareness of PID in this setting make early diagnosis and treatment difficult. The aim of this study was to define the warning signs of PID in patients with respiratory manifestations, the necessary diagnostic tests, and the therapeutic management of both children and adults. METHODS: A review of the literature was performed, and 43 PID interdisciplinary specialists were consulted. RESULTS: This document identifies the pulmonary and extrapulmonary manifestations that should prompt a suspicion of PID, the immunological and respiratory tests that should be included in the diagnostic process according to the level of care, recommendations regarding the use of immunoglobulin replacement therapy according to the specific immunodeficiency, and the minimum recommended immunological and pulmonary monitoring in these patients. CONCLUSIONS: This document is the first to combine scientific evidence with the opinion of a broad panel of experts specializing in the treatment of patients with immunodeficiencies. It aims to provide a useful tool for all practitioners who are regularly involved in the management of these patients.

Detection of Bacteriophage Particles Containing Antibiotic Resistance Genes in the Sputum of Cystic Fibrosis Patients.

Cystic fibrosis (CF) is a chronic disease in which the bacterial colonization of the lung is linked to an excessive inflammatory response that leads to respiratory failure. The microbiology of CF is complex. Staphylococcus aureus is the first bacterium to colonize the lungs in 30% of pediatric CF patients, and 80% of adult patients develop a chronic Pseudomonas aeruginosa infection, but other microorganisms can also be found. The use of antibiotics is essential to treat the disease, but antibiotic performance is compromised by resistance mechanisms. Among various mechanisms of transfer of antibiotic resistance genes (ARGs), the recently been reported bacteriophages are the least explored in clinical settings. To determine the role of phages in CF as mobile genetic elements (MGEs) carrying ARGs, we evaluated their presence in 71 CF patients. 71 sputum samples taken from these patients were screened for eight ARGs (blaTEM, blaCTX-M-1-group, blaCTX-M-9-group, blaOXA-48, blaVIM, mecA, qnrA, and qnrS) in the bacteriophage DNA fraction. The phages found were also purified and observed by electron microscopy. 32.4% of CF patients harbored ARGs in phage DNA. ß-lactamase genes, particularly blaVIM and blaTEM, were the most prevalent and abundant, whereas mecA, qnrA, and qnrS were very rare. Siphoviridae phage particles capable of infecting P. aeruginosa and Klebsiella pneumoniae were detected in CF sputum. Phage particles harboring ARGs were found to be abundant in the lungs of both CF patients and healthy individuals and could contribute to the colonization of multiresistant strains.

The role of transbronchial cryobiopsy in lung transplantation.

AIMS: Lung transplant monitoring is usually performed with forceps transbronchial biopsies. These types of biopsy show limited reliability and a high degree of variability, owing to insufficient material and compression artefact, which lead to misinterpretation and, eventually, inappropriate treatment of the transplanted patients. The following study was undertaken to assess the diagnostic yield, histological quality and safety of cryobiopsy (CB) in comparison with conventional forceps biopsy (FB) for sampling lung tissue in transplant recipients. METHODS AND RESULTS: From January to December 2011, 81 consecutive transbronchial biopsies (41 FBs and 40 CBs) were indicated in single or bilateral lung transplantation recipients with clinical acute or chronic lung injury. Lung samples obtained by CB were larger (8.5 ± 6.5 mm in the FB group versus 22.1 ± 12.5 mm in the CB group; P < 0.0001) and had no crush artefacts (P = 0.002), allowing us to increase the diagnostic yield of acute (P = 0.0657) and chronic (P = 0.0053) cellular rejection. DISCUSSION: Transbronchial cryoprobe bronchoscopy allows the harvesting of larger and more expanded lung tissue samples, increasing the diagnostic yield in the monitoring of the lung allograft by means of a safe procedure.

The annual prognostic ability of FACED and E-FACED scores to predict mortality in patients with bronchiectasis.

Both FACED and E-FACED scores have shown good short-term prognostic value for predicting mortality in bronchiectasis http://ow.ly/albl30i11bv.

Long-term benefits of airway clearance in bronchiectasis: a randomised placebo-controlled trial.

Keeping airways clear of mucus by airway clearance techniques seems essential in bronchiectasis treatment, although no placebo-controlled trials or any studies lasting longer than 3 months have been conducted. We evaluate the efficacy of the ELTGOL (slow expiration with the glottis opened in the lateral posture) technique over a 1-year period in bronchiectasis patients with chronic expectoration in a randomised placebo-controlled trial.Patients were randomised to perform the ELTGOL technique (n=22) or placebo exercises (n=22) twice-daily (ClinicalTrials.gov, NCT01578681). The primary outcome was sputum volume during the first intervention and 24 h later. Secondary outcomes included sputum volume during the intervention and 24 h later at month 12, exacerbations, quality of life, sputum analyses, pulmonary function, exercise capacity, systemic inflammation, treatment adherence, and side effects.Sputum volume during intervention and 24 h later was higher in the ELTGOL group than in the placebo group both at the beginning and end of the study. Patients in the ELTGOL group had fewer exacerbations (p=0.042) and a clinically significant improvement in the St George's Respiratory Questionnaire score (p<0.001) and the Leicester Cough Questionnaire score compared with the placebo group (p<0.001).Twice-daily ELTGOL technique over 1 year in bronchiectasis patients facilitated secretion removal and was associated with fewer exacerbations, improved quality of life, and reduced cough impact.

Spanish Guidelines on the Evaluation and Diagnosis of Bronchiectasis in Adults. / Normativa sobre la valoración y el diagnóstico de las bronquiectasias en el adulto.

In 2008, the Spanish Society of Pulmonology (SEPAR) published the first guidelines in the world on the diagnosis and treatment of bronchiectasis. Almost 10 years later, considerable scientific advances have been made in both the treatment and the evaluation and diagnosis of this disease, and the original guidelines have been updated to include the latest scientific knowledge on bronchiectasis. These new recommendations have been drafted following a strict methodological process designed to ensure the quality of content, and are linked to a large amount of online information that includes a wealth of references. These guidelines cover aspects ranging from a consensual definition of bronchiectasis to an evaluation of the natural course and prognosis of the disease. The topics of greatest interest and some new areas are addressed, including epidemiology and economic costs of bronchiectasis, pathophysiological aspects, the causes (placing particular emphasis on the relationship with other airway diseases such as chronic obstructive pulmonary disease and asthma), clinical and functional aspects, measurement of quality of life, radiological diagnosis and assessment, diagnostic algorithms, microbiological aspects (including the definition of key concepts, such as bacterial eradication or chronic bronchial infection), and the evaluation of severity and disease prognosis using recently published multidimensional tools.

Spanish Guidelines on Treatment of Bronchiectasis in Adults. / Normativa sobre el tratamiento de las bronquiectasias en el adulto.

In 2008, the Spanish Society of Pulmonology (SEPAR) published the first guidelines in the world on the diagnosis and treatment of bronchiectasis. Almost 10 years later, considerable scientific advances have been made in both the treatment and the evaluation and diagnosis of this disease, and the original guidelines have been updated to include the latest therapies available for bronchiectasis. These new recommendations have been drafted following a strict methodological process designed to ensure quality of content, and are linked to a large amount of online information that includes a wealth of references. The guidelines are focused on the treatment of bronchiectasis from both a multidisciplinary perspective, including specialty areas and the different healthcare levels involved, and a multidimensional perspective, including a comprehensive overview of the specific aspects of the disease. A series of recommendations have been drawn up, based on an in-depth review of the evidence for treatment of the underlying etiology, the bronchial infection in its different forms of presentation using existing therapies, bronchial inflammation, and airflow obstruction. Nutritional aspects, management of secretions, muscle training, management of complications and comorbidities, infection prophylaxis, patient education, home care, surgery, exacerbations, and patient follow-up are addressed.

Antibiotic resistance and population structure of cystic fibrosis Pseudomonas aeruginosa isolates from a Spanish multi-centre study.

The first Spanish multi-centre study on the microbiology of cystic fibrosis (CF) was conducted from 2013 to 2014. The study involved 24 CF units from 17 hospitals, and recruited 341 patients. The aim of this study was to characterise Pseudomonas aeruginosa isolates, 79 of which were recovered from 75 (22%) patients. The study determined the population structure, antibiotic susceptibility profile and genetic background of the strains. Fifty-five percent of the isolates were multi-drug-resistant, and 16% were extensively-drug-resistant. Defective mutS and mutL genes were observed in mutator isolates (15.2%). Considerable genetic diversity was observed by pulsed-field gel electrophoresis (70 patterns) and multi-locus sequence typing (72 sequence types). International epidemic clones were not detected. Fifty-one new and 14 previously described array tube (AT) genotypes were detected by AT technology. This study found a genetically unrelated and highly diverse CF P. aeruginosa population in Spain, not represented by the epidemic clones widely distributed across Europe, with multiple combinations of virulence factors and high antimicrobial resistance rates (except for colistin).

Clinical impact of chronic obstructive pulmonary disease on non-cystic fibrosis bronchiectasis. A study on 1,790 patients from the Spanish Bronchiectasis Historical Registry.

BACKGROUND: Few studies have evaluated the coexistence of bronchiectasis (BE) and chronic obstructive pulmonary disease (COPD) in series of patients diagnosed primarily with BE. The aim of this study was to analyse the characteristics of patients with BE associated with COPD included in the Spanish Bronchiectasis Historical Registry and compare them to the remaining patients with non-cystic fibrosis BE. METHODS: We conducted a multicentre observational study of historical cohorts, analysing the characteristics of 1,790 patients who had been included in the registry between 2002 and 2011. Of these, 158 (8.8%) were registered as BE related to COPD and were compared to the remaining patients with BE of other aetiologies. RESULTS: Patients with COPD were mostly male, older, had a poorer respiratory function and more frequent exacerbations. There were no differences in the proportion of patients with chronic bronchial colonisation or in the isolated microorganisms. A significantly larger proportion of patients with COPD received treatment with bronchodilators, inhaled steroids and intravenous antibiotics, but there was no difference in the use of long term oral or inhaled antibiotherapy. During a follow-up period of 3.36 years, the overall proportion of deaths was 13.8%. When compared to the remaining aetiologies, patients with BE associated with COPD presented the highest mortality rate. The multivariate analysis showed that the diagnosis of COPD in a patient with BE as a primary diagnosis increased the risk of death by 1.77. CONCLUSION: Patients with BE related to COPD have the same microbiological characteristics as patients with BE due to other aetiologies. They receive treatment with long term oral and inhaled antibiotics aimed at controlling chronic bronchial colonisation, even though the current COPD treatment guidelines do not envisage this type of therapy. These patients' mortality is notably higher than that of remaining patients with non-cystic fibrosis BE.

Etiology of Bronchiectasis in a Cohort of 2047 Patients. An Analysis of the Spanish Historical Bronchiectasis Registry. / Etiología de las bronquiectasias en una cohorte de 2.047 pacientes. Análisis del registro histórico español.

INTRODUCTION: Bronchiectasis is caused by many diseases. Establishing its etiology is important for clinical and prognostic reasons. The aim of this study was to evaluate the etiology of bronchiectasis in a large patient sample and its possible relationship with demographic, clinical or severity factors, and to analyze differences between idiopathic disease, post-infectious disease, and disease caused by other factors. METHODS: Multicenter, cross-sectional study of the SEPAR Spanish Historical Registry (RHEBQ-SEPAR). Adult patients with bronchiectasis followed by pulmonologists were included prospectively. Etiological studies were based on guidelines and standardized diagnostic tests included in the register, which were later included in the SEPAR guidelines on bronchiectasis. RESULTS: A total of 2,047 patients from 36 Spanish hospitals were analyzed. Mean age was 64.9years and 54.9% were women. Etiology was identified in 75.8% of cases (post-Infection: 30%; cystic fibrosis: 12.5%; immunodeficiencies: 9.4%; COPD: 7.8%; asthma: 5.4%; ciliary dyskinesia: 2.9%, and systemic diseases: 1.4%). The different etiologies presented different demographic, clinical, and microbiological factors. Post-infectious bronchiectasis and bronchiectasis caused by COPD and asthma were associated with an increased risk of poorer lung function. Patients with post-infectious bronchiectasis were older and were diagnosed later. Idiopathic bronchiectasis was more common in female non-smokers and was associated with better lung function, a higher body mass index, and a lower rate of Pseudomonas aeruginosa than bronchiectasis of known etiology. CONCLUSIONS: The etiology of bronchiectasis was identified in a large proportion of patients included in the RHEBQ-SEPAR registry. Different phenotypes associated with different causes could be identified.

Utility of Bronchoalveolar Lavage for the Diagnosis of Asbestos-Related Diseases. / Utilidad del lavado broncoalveolar en el diagnóstico de enfermedades relacionadas con el amianto.

INTRODUCTION: Bronchoalveolar lavage (BAL) analysis has been proposed as an objective technique for confirming asbestos exposure. However, the reliability and diagnostic yield of this procedure has not been studied in Spain. The aim of this study was to assess the usefulness of the analysis of asbestos bodies (AB) in bronchoalveolar lavage (BAL) for the diagnosis of asbestos-related diseases (ARD). METHODS: BAL samples from 72 patients (66 male, mean age 66 years) undergoing bronchoscopy were analyzed. Lung tissue from 23 of these patients was also analyzed. Asbestos exposure was assessed by anamnesis and a review of the patient's medical records. BAL and lung samples were processed and AB count was determined by light microscopy. The accepted threshold value to diagnose asbestos-related diseases was 1 AB/ml BAL or 1000 AB/gr dry tissue. RESULTS: Thirty-nine patients reported exposure to asbestos. Of these, 13 (33%) presented AB values above 1 AB/ml BAL. In the 33 non-exposed patients, 5 (15%) presented AB values above 1 AB/ml BAL. There was a significant difference between the AB levels of exposed and non-exposed patients (P=.006). The ROC curve showed that a value of 0.5 AB/ml BAL achieved the most satisfactory sensitivity, 46%, and a specificity of 83%. The correlation between AB levels in BAL and lung was 0.633 (P=.002). CONCLUSIONS: BAL study provides objective evidence of exposure to asbestos. The good correlation between the AB counts in BAL and lung tissue indicates that both techniques are valid for the analysis of asbestos content.

Prognosis of Good syndrome: mortality and morbidity of thymoma associated immunodeficiency in perspective.

Good syndrome (GS) or thymoma-associated immunodeficiency, is a rare condition that has only been studied in retrospective case series. General consensus was that GS has a worse prognosis than other humoral immunodeficiencies. In this study, physicians of GS patients completed two questionnaires with a two year interval with data on 47 patients, 499 patient years in total. Results on epidemiology, disease characteristics, and outcome are presented. Mean age at diagnosis was 60years and median follow-up from onset of symptoms was 9years. There was a high frequency of respiratory tract infections due to encapsulated bacteria. Median survival was 14years. Survival was reduced compared to age-matched population controls (5-year survival: 82% versus 95%, p=0.008). In this cohort survival was not associated with gender (HR 0.9, 95% CI 0.3-3.0), autoimmune diseases (HR 2.9, 95% CI 0.8-10.1) or immunosuppressive use (HR 0.3, 95% CI: 0.1-1.2).

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.