Author's response to 'CAP and HCAP are different? An unresolved question

Dear Editor, We thank the authors for the interest in our recent publication and for their useful comments. Unfortunately we consider the comparison with the publication from Giannella et al1 poorly appropriate in many aspects. The main strength of our work is the multicentre prospective case–control study design (match by age, gender and period of hospitalisation). Although severity scores were not used for matching, we considered this design the most appropriate to describe healthcare-associated pneumonia (HCAP) features. In fact, the Giannella group performed an observational prospective study only on patients admitted to internal medicine departments: these elements (study design and patients) could justify a different population composition and, consequently, different microbiological and clinical findings. In fact, in comparison..

Multiple inert gases elimination tecnique(MIGET)and gas exchange in obstructive respiratory diseases

Among the traditional causes of arterial hypoxemia and hypercapnia, ventilation-perfusion ratio (VA/Q) inequality is the most important mechanism of gas exchange impairment in respiratory diseases. In the mild 1970s a new technique, named “multiple inert gases elimination technique” (MIGET), was developed able to study VA/Q distributions. The first study of present thesis, (“Adenosine 5’-monophosphate (AMP) challenge in mild asthma: cellular and gas exchange responses”), is focused on the comparative evaluation, in mild asthma, of the effects of two different challenge tests (AMP and methacholine [MCh]) on lung function, including VA/Q relationships, and induced sputum. Results showed similar spirometric and gas exchange responses (severe bronchonstriction, VA/Q and PaO2 worsening) after both tests but a neutrophils increase in the sputum only after AMP challenge, supporting the hypothesis that indirect agents of bronchoconstriction (AMP) offer a better estimate of airway inflammation than direct agents (Mch). The second study (“Effects of nebulized salbutamol on pulmonary gas exchange during COPD exacerbations and in stable conditions”) investigated the effects of salbutamol on ventilation-perfusion (VA/Q) inequalities in COPD patients during exacerbations (E) and in stable clinical condition (S). In both phases of the study we observed similar spirometric (increased FEV1 and IC) and hemodynamic (increased cardiac output and decreased mean arterial pressure) responses to salbutamol. By contrast, patients showed at phase S more marked and prolonged negative effects on gas exchange (hypoxemia and VA/Q mismatch) than during E, likely as effect of pulmonary vasodilatation. In conclusion, this effect was more evident in stable condition as pulmonary vasculature tone is more relaxed and liable to vasodilatation than during exacerbations (hypoxic pulmonary vasoconstriction)

Short-term Airway Clearance Management in people with stable Bronchiectasis

Introducción La expectoración crónica es uno de los síntomas respiratorios más prevalentes en personas con bronquiectasias y se asocia con un peor estado clínico y un fuerte impacto en la vida social. A pesar de que el uso de técnicas de drenaje de secreciones (DS) y agentes hiperosmolares es recomendado para facilitar el manejo diario de la tos productiva en pacientes con bronquiectasias, la calidad de su evidencia es todavía bajamoderada y su grado de recomendación varía de débil a fuerte. Por este motivo, se requiere evaluar en profundidad nuevos enfoques terapéuticos a corto plazo que faciliten el DS y que no hayan sido investigados hasta la fecha, para poder diseñar futuros ensayos clínicos a largo plazo con mayor nivel de garantía. Por consiguiente, el objetivo de esta tesis fue investigar que enfoque terapéutico a corto plazo facilita en mayor medida el DS en personas adultas diagnosticadas de bronquiectasias en periodo de estabilidad clínica, al igual que averiguar cómo interpretar correctamente los beneficios clínicos de estas intervenciones.Métodos Dos ensayos clínicos aleatorizados y cruzados se llevaron a cabo para comparar la efectividad a corto plazo de tres técnicas espiratorias lentas de DS (drenaje autógeno, espiración lenta con glotis abierta en decúbito infralateral [ETLGOL] y presión espiratoria positiva temporal [TPEP]) y tres soluciones salinas para inhalar (suero hipertónico [SH], suero hipertónico con ácido hialurónico [SH+AH] y suero isotónico [SI]) en personas con bronquiectasias. El objetivo primario en ambos ensayos clínicos fue el peso húmedo de la cantidad de esputo expectorada durante las sesiones. Además, se realizó un análisis ad‐hoc utilizando las muestras de esputo de ambos ensayos clínicos para examinar la fiabilidad de la cantidad de esputo durante 24 horas, así como la diferencia importante mínima (DIM) después de una sesión de DS en bronquiectasias. Finalmente, se examinó mediante un estudio de viabilidad/factibilidad el potencial uso de los ruidos respiratorios adventicios analizados de forma computacional como herramienta de evaluación de los efectos a corto plazo del DS en pacientes con bronquiectasias.Resultados (1) Las técnicas de drenaje autógeno y ELTGOL favorecieron en mayor grado la expectoración durante las sesiones que la técnica TPEP en personas con bronquiectasias en estabilidad clínica; siendo el drenaje autógeno la técnica preferida por los participantes; (2) la solución SH+AH fue tan efectiva como la solución de SH y mejor que la solución de SI facilitandola expectoración; sin embargo presentó un mejor perfil de seguridad que el SH en personas conbronquiectasias en periodo de estabilidad clínica y por esto fue la técnica de elección por los participantes; (3) el peso húmedo de la cantidad de esputo expectorada durante 24 horas presentó una fiabilidad aceptable; sin embargo su nivel de concordancia fue ligeramente amplio, especialmente para niveles de expectoración elevados. Además, se estimó que una reducción de al menos 6,4 g. en la cantidad de esputo expectorada durante las 24 horas posteriores a una intervención de DS, o un cambio relativo de alrededor del ‐17% con respecto al nivel basal, es la DIM; (4) el uso de los ruidos respiratorios adventicios analizados de forma computacional fue una herramienta viable/factible y parece ser que el número de crujidos espiratorios graves es la mejor variable para utilizar en futuros estudios.Conclusión Los hallazgos de esta tesis resaltan cuáles son los enfoques terapéuticos de DS a corto plazo más efectivos en personas con bronquiectasias en periodo de estabilidad clínica. Por lo tanto, el próximo paso es diseñar y realizar ensayos clínicos a largo plazo que analicen los efectos de estos enfoques terapéuticos en personas con bronquiectasias.Background Daily sputum expectoration is one of the most common respiratory symptoms in people with bronchiectasis. It is associated with poor health outcomes and negative impacts on social life. Although the use of airway clearance techniques (ACTs) and hyperosmolar agents is recommended to more easily manage chronic productive cough, the quality of evidence is still low-moderate and the level of recommendation ranges from weak to strong in bronchiectasis. However, there is a need to evaluate in-depth the short-term effects of airway clearance therapeutic approaches that are so far under-investigated in bronchiectasis in order to design optimal long-term future trials in this field. Therefore, the aims of this thesis were to investigate what is the short-term effectiveness of airway clearance therapeutic approaches in adults with clinically stable bronchiectasis and how to correctly interpret the clinical benefits observed after these interventions. Methods Two randomised, three-way crossover trials were conducted to compare the short-term effectiveness of three slow-expiratory ACTs (autogenic drainage, slow-expiration with glottis opened in lateral posture [ELTGOL] and temporary positive expiratory pressure [TPEP]) and three inhaled saline solutions (hypertonic saline [HS], hyaluronic acid + HS [HA + HS] and isotonic saline [IS]) in people with bronchiectasis. Wet sputum weight during sessions was selected as the primary outcome in both trials. Moreover, an ad hoc analysis was performed using the sputum samples of both studies to evaluate the reliability of 24-hour sputum weight and the minimal important difference (MID) after short-term airway clearance sessions in bronchiectasis. Finally, a feasibility study was conducted to examine the potential use of computerised adventitious respiratory sounds (ARS) as an outcome measure to assess the short-term effects of airway clearance sessions in bronchiectasis. <br /

Feasibility of computerized adventitious respiratory sounds to assess the effects of airway clearance techniques in patients with bronchiectasis

Objective: To examine the feasibility of adventitious respiratory sound (ARS) as an outcome measure to assess the effects of airway clearance techniques (ACTs) in outpatients with bronchiectasis. Methods: ARS were registered pre/post four ACTs sessions. Clinical outcomes included: number of crackles (coarse and fine), number of wheezes (monophonic and polyphonic), wheezes occupation rate (%) and sputum quantity. Feasibility outcomes of ARS included: reasons for exclusion, suitability, safety, equipment and time required, magnitude of change after intervention and sample size estimation. Results: Seven patients (49.7 ± 20.5 years; FEV1 69.3 ± 15.8% predicted) were included. Recordings from four patients were excluded due to excessive environment noise. All ARS measurements were completed without any adverse events. An electronic stethoscope was acquired and the time spent to complete each assessment was 6 ± 3.5 min. The largest changes were observed for number of expiratory coarse crackles [effect size (95%CI) ES = 0.40 (0.01–0.79)], which correlated moderately with sputum quantity (r = 0.56), and inspiratory monophonic wheezes [ES = 0.61 (0.22–1.00)]. The estimated sample size for a full crossover trial was 46. Conclusions: ARS is feasible to assess the effects of ACTs in patients with bronchiectasis. Expiratory coarse crackles seem to be the most appropriate ARS parameter, but this finding needs to be confirmed in an adequately powered trial.publishe

What is important for people with nontuberculous mycobacterial disease? An EMBARC-ELF patient survey

Experiencias de los pacientes; Enfermedad pulmonarExperiències dels pacients; Malaltia pulmonarPatient experiences; Lung diseasePatients' experiences of NTM pulmonary disease highlight important and unmet needs for better pharmacological treatment and education of medical staffEuropean Respiratory Society (EMBARC Clinical Research Collaboration

Development and initial validation of the bronchiectasis exacerbation and symptom tool (BEST)

BACKGROUND: Recurrent bronchiectasis exacerbations are related to deterioration of lung function, progression of the disease, impairment of quality of life, and to an increased mortality. Improved detection of exacerbations has been accomplished in chronic obstructive pulmonary disease through the use of patient completed diaries. These tools may enhance exacerbation reporting and identification. The aim of this study was to develop a novel symptom diary for bronchiectasis symptom burden and detection of exacerbations, named the BEST diary. METHODS: Prospective observational study of patients with bronchiectasis conducted at Ninewells Hospital, Dundee. We included patients with confirmed bronchiectasis by computed tomography, who were symptomatic and had at least 1 documented exacerbation of bronchiectasis in the previous 12\u2009months to participate. Symptoms were recorded daily in a diary incorporating cough, sputum volume, sputum colour, dyspnoea, fatigue and systemic disturbance scored from 0 to 26. RESULTS: Twenty-one patients were included in the study. We identified 29 reported (treated exacerbations) and 23 unreported (untreated) exacerbations over 6-month follow-up. The BEST diary score showed a good correlation with the established and validated questionnaires and measures of health status (COPD Assessment Test, r =\u20090.61, p =\u20090.0037, Leicester Cough Questionnaire, r =\u2009-\u20090.52,p =\u20090.0015, St Georges Respiratory Questionnaire, r =\u20090.61,p &lt;\u20090.0001 and 6\u2009min walk test, r =\u2009-\u20090.46,p =\u20090.037). The mean BEST score at baseline was 7.1 points (SD 2.2). The peak symptom score during exacerbation was a mean of 16.4 (3.1), and the change from baseline to exacerbation was a mean of 9.1 points (SD 2.5). Mean duration of exacerbations based on time for a return to baseline symptoms was 15.3\u2009days (SD 5.7). A minimum clinically important difference of 4 points is proposed. CONCLUSIONS: The BEST symptom diary has shown concurrent validity with current health questionnaires and is responsive at onset and recovery from exacerbation. The BEST diary may be useful to detect and characterise exacerbations in bronchiectasis clinical trials

Comparison of different sets of immunological tests to identify treatable immunodeficiencies in adult bronchiectasis patients

Immunological tests; BronchiectasisPruebas inmunologicas; BronquiectasiasProves immunològiques; BronquiectasiesBackground The reported prevalence of immunodeficiencies in bronchiectasis patients is variable depending on the frequency and extent of immunological tests performed. European Respiratory Society guidelines recommend a minimum bundle of tests. Broadening the spectrum of immunological tests could increase the number of patients diagnosed with an immunodeficiency and those who could receive specific therapy. The primary objective of the present study was to assess the performance of different sets of immunological tests in diagnosing any, primary, secondary or treatable immunodeficiencies in adults with bronchiectasis. Methods An observational, cross-sectional study was conducted at the Bronchiectasis Program of the Policlinico University Hospital in Milan, Italy, from September 2016 to June 2019. Adult outpatients with a clinical and radiological diagnosis of bronchiectasis underwent the same immunological screening during the first visit when clinically stable consisting of: complete blood count; immunoglobulin (Ig) subclass tests for IgA, IgG, IgM and IgG; total IgE; lymphocyte subsets; and HIV antibodies. The primary endpoint was the prevalence of patients with any immunodeficiencies using five different sets of immunological tests. Results A total of 401 bronchiectasis patients underwent the immunological screening. A significantly different prevalence of bronchiectasis patients diagnosed with any, primary or secondary immunodeficiencies was found across different bundles. 44.6% of bronchiectasis patients had a diagnosis of immunodeficiency when IgG subclasses and lymphocyte subsets were added to the minimum bundle suggested by the guidelines. Conclusion A four-fold increase in the diagnosis of immunodeficiencies can be found in adults with bronchiectasis when IgG subclasses and lymphocyte subsets are added to the bundle of tests recommended by guidelines

ROSE: radiology, obstruction, symptoms and exposure – a Delphi consensus definition of the association of COPD and bronchiectasis by the EMBARC Airways Working Group

Consensus; COPD; Clinical practiceConsenso; EPOC; Práctica clínicaConsens; MPOC; Pràctica clínicaIntroduction The coexistence of COPD and bronchiectasis seems to be common and associated with a worse prognosis than for either disease individually. However, no definition of this association exists to guide researchers and clinicians. Methods We conducted a Delphi survey involving expert pulmonologists and radiologists from Europe, Turkey and Israel in order to define the “COPD– [bronchiectasis] BE association”. A panel of 16 experts from EMBARC selected 35 statements for the survey after reviewing scientific literature. Invited participants, selected on the basis of expertise, geographical and sex distribution, were asked to express agreement on the statements. Consensus was defined as a score of ≥6 points (scale 0 to 9) in ≥70% of answers across two scoring rounds. Results 102 (72.3%) out of 141 invited experts participated in the first round. Their response rate in the second round was 81%. The final consensus definition of “COPD–BE association” was: “The coexistence of (1) specific radiological findings (abnormal bronchial dilatation, airways visible within 1 cm of pleura and/or lack of tapering sign in ≥1 pulmonary segment and in >1 lobe) with (2) an obstructive pattern on spirometry ([forced expiratory volume in 1 s] FEV1/[forced vital capacity] FVC <0.7), (3) at least two characteristic symptoms (cough, expectoration, dyspnoea, fatigue, frequent infections) and (4) current or past exposure to smoke (≥10 pack-years) or other toxic agents (biomass, etc.)”. These criteria form the acronym “ROSE” (Radiology, Obstruction, Symptoms, Exposure). Conclusions The Delphi process formulated a European consensus definition of “COPD–BE association”. We hope this definition will have broad applicability across clinical practice and research in the future

Ten Issues for Updating in Community-Acquired Pneumonia: An Expert Review

Aetiology; Community acquired pneumonia; Radiologic findingsEtiologia; Pneumònia adquirida a la comunitat; Troballes radiològiquesEtiología; Neumonía adquirida en la comunidad; Hallazgos radiológicosCommunity-acquired pneumonia represents the third-highest cause of mortality in industrialized countries and the first due to infection. Although guidelines for the approach to this infection model are widely implemented in international health schemes, information continually emerges that generates controversy or requires updating its management. This paper reviews the most important issues in the approach to this process, such as an aetiologic update using new molecular platforms or imaging techniques, including the diagnostic stewardship in different clinical settings. It also reviews both the Intensive Care Unit admission criteria and those of clinical stability to discharge. An update in antibiotic, in oxygen, or steroidal therapy is presented. It also analyzes the management out-of-hospital in CAP requiring hospitalization, the main factors for readmission, and an approach to therapeutic failure or rescue. Finally, the main strategies for prevention and vaccination in both immunocompetent and immunocompromised hosts are reviewed

The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN

Primary ciliary dyskinesia; Rare genetic disorder; Lung diseasesDiscinesia ciliar primaria; Trastorno genético raro; Enfermedades pulmonaresDiscinesia ciliar primària; Trastorn genètic rar; Malalties pulmonarsPrimary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients