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.

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.

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.

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.

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).

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.

Clinical picture and treatment of 2212 patients with common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is an antibody deficiency with an equal sex distribution and a high variability in clinical presentation. The main features include respiratory tract infections and their associated complications, enteropathy, autoimmunity, and lymphoproliferative disorders. OBJECTIVE: This study analyzes the clinical presentation, association between clinical features, and differences and effects of immunoglobulin treatment in Europe. METHODS: Data on 2212 patients with CVID from 28 medical centers contributing to the European Society for Immunodeficiencies Database were analyzed retrospectively. RESULTS: Early disease onset (<10 years) was very frequent in our cohort (33.7%), especially in male subjects (39.8%). Male subjects with early-onset CVID were more prone to pneumonia and less prone to other complications suggesting a distinct disease entity. The diagnostic delay of CVID ranges between 4 and 5 years in many countries and is particularly high in subjects with early-onset CVID. Enteropathy, autoimmunity, granulomas, and splenomegaly formed a set of interrelated features, whereas bronchiectasis was not associated with any other clinical feature. Patient survival in this cohort was associated with age at onset and age at diagnosis only. There were different treatment strategies in Europe, with considerable differences in immunoglobulin dosing, ranging from 130 up to 750 mg/kg/mo. Patients with very low trough levels of less than 4 g/L had poor clinical outcomes, whereas higher trough levels were associated with a reduced frequency of serious bacterial infections. CONCLUSION: Patients with CVID are being managed differently throughout Europe, affecting various outcome measures. Clinically, CVID is a truly variable antibody deficiency syndrome.

Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score.

Bronchiectasis is a multidimensional disease and, therefore, its severity or prognosis cannot be adequately quantified by analysing one single variable. The objective of the present study was to develop a multidimensional score that classifies the severity of bronchiectasis according to its prognosis. This is an observational multicentre study including 819 patients diagnosed with non-cystic fibrosis bronchiectasis using high-resolution computed tomography. 397 subjects were selected at random to construct the score while the remaining 422 were used for its validation. The outcome was 5-year all-cause mortality after radiological diagnosis. A logistic regression analysis was used to select the variables included in the final score. The final seven-point score incorporated five dichotomised variables: forced expiratory volume in 1 s % predicted (F, cut-off 50%, maximum value 2 points); age (A, cut-off 70 years, maximum value 2 points); presence of chronic colonisation by Pseudomonas aeruginosa (C, dichotomic, maximum value 1 point); radiological extension (E, number of lobes affected, cut-off two lobes, maximum value 1 point); and dyspnoea (D, cut-off grade II on the Medical Research Council scale, maximum value 1 point) to construct the FACED score. The validation cohort confirmed the score's validity. We conclude that this easy-to-use multidimensional grading system proved capable of accurately classifying the severity of bronchiectasis according to its prognosis.

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.

Herpetic tracheitis and polybacterial pneumonia in an immunocompetent young man is herpes tracheitis involved in the pathogenesis of bacterial pneumonia?

We report a 28-year-old immunocompetent man that after a course of corticoids developed a severe pneumonia in right lower lobe. A fiber-optic bronchoscopy showed a white membrane easily bloody on contact with bronchoscopy tube at trachea level. The tracheal biopsy showed typical cytopathological lesions of herpes simplex virus (HSV) and polymerase chain reaction was positive for type 1 HSV. Streptococcus viridans and Fusobacterium necrophorum grew in right bronchial secretion cultures. Clinical improvement was achieved after prolonged antibiotic therapy and before initiating treatment with acyclovir. Herpetic tracheitis could have been involved in the aspiration of oropharyngeal material that leaded to the development of this bacterial pneumonia.

[Diagnoses and diagnostic procedures in 500 consecutive patients with clinical suspicion of interstitial lung disease]. / Diagnósticos y procedimientos en 500 pacientes consecutivos con sospecha clínica de enfermedad pulmonar intersticial.

OBJECTIVE: To determine the diagnostic yield achieved with the application of current recommendations for evaluating patients with suspected interstitial lung disease (ILD) and the procedures that must be applied to reach a definitive diagnosis. PATIENTS AND METHODS: Over a 10-year period, 500 consecutive patients attending an ILD outpatient clinic who showed features of diffuse lung involvement were assessed with a single diagnostic protocol. Results were introduced in a dedicated database and diagnoses for idiopathic interstitial pneumonia were established according to a recent consensus classification. RESULTS: A definitive diagnosis was reached in 427 (85%) patients: in 125 without invasive procedures and in 302 with invasive procedures. In 73 (14.6%) cases a definitive diagnosis was not reached, and patients were placed in the group of unclassifiable interstitial pneumonia. Idiopathic interstitial pneumonia was the predominant group with 193 (39%) patients. The main specific entities included sarcoidosis with 93 (19%) patients, usual interstitial pneumonia with 84 (17%) patients, and hypersensitivity pneumonitis with 75 (15%) patients. Thirty (6%) patients were diagnosed with an illness other than ILD (false ILD). In 332 patients, we performed a total of 433 invasive procedures: transbronchial biopsy in 252 (direct diagnostic yield, 38%, or if used also to exclude other specific diagnosis, 50%), bronchoalveolar lavage in 260 (yield, 5%), and open lung biopsy in 141 (yield, 93%). Hence, following the current diagnostic approach, a definitive diagnosis was established for 85% of patients, for 25% solely on clinical grounds and imaging criteria and for 60% on the basis of invasive procedures. Diagnosis by open lung biopsy was still required for 141 (28%) patients. CONCLUSIONS: The diagnostic yield was high when the recommended study protocol was followed. A quarter of the diagnoses were reached with clinical criteria alone, but another quarter could only be made after open lung biopsy.

[Diagnosis and treatment of bronchiectasis. Spanish Society of Pneumology and Thoracic Surgery]. / Diagnóstico y tratamiento de las bronquiectasias. SEPAR.

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.

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.

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.

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.