Background We investigate bronchopulmonary colonization patterns in Spanish people with CF (pwCF), gathering clinical, demographic, and microbiological data to supplement nine years of registry information, comparing 2021 findings with a similar multicenter study conducted in 2013. Methods Sixteen CF units from 14 hospitals across Spain participated, each randomly recruiting around 20 patients. Patients provided sputum samples for culture. The clinical, demographical, microbiological, and treatment data from the previous year were recorded. Results Overall, 326 patients (48.5% females) were recruited: 185 adult and 141 pediatrics, with a median age [q3–q1] of 30 [38–24] and 12 [16–6] years, respectively. p.Phe508del mutation was present in 30.6% and 46.4% of patients with homozygosis or heterozygosis, respectively. Median FEV1 (%) was significantly lower in adults (62%, range 75–43%) compared with pediatrics (90%, range 104–81%) (p<0.001). Pancreatic insufficiency was observed in 77.3%, carbohydrate metabolism alteration in 27.3%, and CF-related diabetes in 19.6% of patients. Lower prevalence of Staphylococcus aureus and Pseudomonas aeruginosa colonization were noted compared to 2013, along with a significantly lower correlation in lung function among pwCF colonized by P. aeruginosa (p<0.001). Half of pwCF (51%) exhibited a single pathogen in culture, two in 30%, and three or more in 2.4%. Co-colonization of P. aeruginosa and S. aureus (36.1%) was the most prevalent combination. High resistance rates were observed in P. aeruginosa and methicillin resistant S. aureus isolates. Conclusions We provide a valuable and representative current insight into the observed evolution in the clinical, demographic, and microbiological aspects in recent years among pwCF in Spain.

Background:Lysosomal storage diseases (LSD) are inherited diseases caused by mutations affecting genes encoding the function of lysosomal enzymes. Acid sphingomyelinase deficiency (ASMD) is an ultra-rare, progressive, and often fatal LSD with an estimated prevalence of 1-in-50,000-250,000 individuals. The PrevASMD study established the ASMD prevalence in Spain at 35 patients. Almost all present asymptomatic interstitial lung disease (ILD), since >90 % patients with chronic visceral ASMD have radiographic evidence of ILD. Objective:This case series aims to emphasize the importance of ASMD in adult and pediatric patients with ILD, and to underline the consideration of pulmonary involvement as a key feature of the multisystemic manifestation of ASMD. Methods:This case series describes seven adult and pediatric cases of ASMD in Spain. All presented with pulmonary function impairment. Data were collected on clinical presentation, diagnostic workup, pulmonary function tests, imaging studies, and patient outcomes during follow up. Results:Sphingomyelin accumulation in ASMD leads to multi-systemic disease involving spleen, liver, lungs, bone marrow, and lymph nodes. Almost all patients presented with asymptomatic ILD, but not all of them exhibited respiratory symptoms and not all were referred to pulmonologists. Periodic assessments included pulmonary function testing (forced vital capacity and diffusing capacity for carbon monoxide), O2 saturation, and exercise tolerance testing. Conclusion:ASMD patients presented with different target organ involvement, with lung involvement contributing significantly to patient morbi-mortality. ASMD diagnostic suspicion among pulmonologists treating ILD is thus crucial, as multidisciplinary monitoring of ILD as a feature of ASMD can ensure its correct management and follow-up.

INTRODUCTION:There is scarce information about the most used mucolytic drug in bronchiectasis N-acetylcysteine (N-AC). Our objective was to analyze the effect of N-AC with respect to some outcomes in bronchiectasis. METHODS:Ambispective, longitudinal, observational, multi-center (43 centers) study of a cohort of 2461 adult patients diagnosed with bronchiectasis. Those patients treated in a stable situation with at least 600mg/d of N-AC (368; 15%) for at least 6 months were compared with patients not receiving this treatment. The variables analyzed and compared were those available two years before and after treatment. ANCOVA analysis was used to analyze the effect of N-AC as the inter-group difference of the basal intra-group difference for each variable, adjusted for relevant covariables. RESULTS:The N-AC group showed a full adjusted improvement of 27% in exacerbations, 17% in hospitalizations, and 31% in total exacerbation rates compared with the no-N-AC group. Moreover, a decrease in the volume of sputum production of 59.7% was observed as well as a decrease of 12% of patients with bronchial infection by Pseudomonas aeruginosa (PA). The use of 1200mg/d (n=116) resulted in only a mild, albeit significative improvement in the exacerbation rate compared with the use of 600mg/d (-11% in absolute number). Both doses were well tolerated. CONCLUSION:N-AC (in most cases at a dose of 600mg/d) is safe and effective and sufficient to reduce both the number of exacerbations and hospitalizations and the purulence and volume of sputum, as well as the isolation rate of PA in patients with bronchiectasis.

Rationale: The baseline value of eosinophils in peripheral blood (BEC) has been associated with different degrees of severity, prognosis and response to treatment in patients with bronchiectasis. It is not known, however, if this basal value remains constant over time. Objectives: The aim of this study was to assess whether the BEC remains stable in the long term in patients with bronchiectasis. Methods and measurements Patients from the RIBRON registry of bronchiectasis diagnosed by computed tomography with at least 2 BEC measurements one year apart were included in the study. Patients with asthma and those taking anti-eosinophilic drugs were excluded. Reliability was assessed using the intra-class correlation coefficient (ICC). A patient with a BEC of at least 300 cells/uL or less than 100 cells/uL was considered eosinophilic or eosinopenic, respectively. Group changes over time were also calculated. Main results: Seven hundred and thirteen patients were finally included, with a mean age of 66.5 (13.2) years (65.8 % women). A total of 2701 BEC measurements were performed, with a median number of measurements per patient of 4 (IQR: 2-5) separated by a median of 12.1 (IQR: 10.5-14.3) months between two consecutive measurements. The ICC was good (>0.75) when calculated between two consecutive measurements (approximately one year apart) but had dropped significantly by the time of the next annual measurements. Similarly, the change from an eosinophilic or eosinopenic patient to a non-eosinophilic or non-eosinopenic patient, respectively, was less than 30 % during the first year with respect to the baseline value but was close to 50 % in later measurements. Conclusions: Given the significant changes observed in the baseline value of the BEC over time, its monitoring is necessary in patients with bronchiectasis in order to more reliably assess its usefulness.

INTRODUCTION:Inhaled antibiotics are used in the treatment of various respiratory diseases, including cystic fibrosis (CF), non-CF bronchiectasis, and ventilator-associated pneumonia. While some of these drugs are marketed as ready-to-use formulations, others require prior manipulation, such as dilution or reconstitution procedures that are often not standardized. Furthermore, certain antibiotics are only approved for intravenous administration, making it necessary to develop specific protocols for their preparation and use via the inhaled route. Their biochemical properties may also compromise patient safety and tolerability. The aim of this study was to assess how frequently preparation methods and biochemical parameters of inhaled antibiotic solutions are described in the scientific literature. Additionally, we explored their prevalence of use in our country and evaluated their biochemical characteristics to assess tolerability. METHODS:A literature review was conducted using the MEDLINE database to identify studies describing the dilutions used for the administration of inhaled antibiotics. In addition, a nationwide survey was carried out to assess the dilutions currently used in hospital clinical practice. Biochemical analyses were performed in parallel to determine the pH, osmolality, and sodium and chloride ion concentrations of the solutions employed. Excipients present in each formulation were recorded based on information from the product's summary of characteristics. RESULTS:The literature review identified 533 full-text publications describing 737 different inhaled antibiotic mixtures. Of these, 476 were not standardized. Only 190 mixtures included precise dilution instructions, while just 31 provided data on pH and 28 on osmolality. The national survey revealed a high prevalence of inhaled antibiotic use among participating hospitals, with 22 centres (64.7%) reporting the use of intravenous formulations administered via inhalation. Laboratory analyses showed that some of the evaluated dilutions fell outside the acceptable tolerability range, particularly those involving reconstitution of dry powders or dilution of concentrated intravenous solutions. CONCLUSION:There is limited information in the scientific literature regarding preparation methods and the biochemical characteristics of inhaled antibiotic solutions. Off-label use of intravenous formulations for inhalation is widespread, and some of the dilutions used exhibit biochemical parameters outside the recommended tolerability range, which may compromise both the safety and effectiveness of treatment.

Introduction Current bronchiectasis guidelines advise against the use of inhaled corticosteroids (ICS) except in patients with associated asthma, allergic bronchopulmonary aspergillosis (ABPA) and/or chronic obstructive pulmonary disease (COPD). This study aimed to describe the use of ICS in patients with bronchiectasis across Europe. Methods Patients with bronchiectasis were enrolled into the European Bronchiectasis Registry from 2015 to 2022. Patients were grouped into ICS users and non-users at baseline and clinical characteristics associated with ICS use were investigated. Patients were followed up for clinical outcomes of exacerbation, hospitalisation and mortality for up to 5 years. We evaluated if elevated blood eosinophil counts (above the laboratory upper limit of normal) modified the effect of ICS on exacerbations. Results 19 324 patients were included for analysis and 10 109 (52.3%) were recorded as being prescribed ICS at baseline. After exclusion of patients with a history of asthma, COPD and/or ABPA, 3174/9715 (32.7%) patients with bronchiectasis were prescribed ICS. Frequency of ICS use varied across countries, ranging from 17% to 85% of included patients. ICS users had more severe disease, with significantly worse lung function, higher Bronchiectasis Severity Index scores and more frequent exacerbations at baseline (p<0.0001). Overall, ICS users did not have a reduced risk of exacerbation or hospitalisation during follow-up, but a significant reduction in exacerbation frequency was observed in the subgroup of ICS users with elevated blood eosinophil counts (relative risk 0.70, 95% CI 0.59 to 0.84, p<0.001). Conclusion ICS use is common in bronchiectasis, including in those not currently recommended ICS according to bronchiectasis guidelines. ICS use may be associated with reduced exacerbation frequency in patients with elevated blood eosinophils.

BACKGROUND:We aimed to elucidate the cystic fibrosis (CF) microbiota composition (shotgun metagenomics) and functionality (short-chain fatty acids, SCFAs). METHODS:Fecal and sputum samples were recruited from 39 clinically stable CF subjects. RESULTS:Bacillota and Pseudomonadota were dominant in both gut and lung compartments, whereas Ascomycota were the most abundant fungi in feces, and Basidiomycota, especially Malassezia globosa, in sputum. Viruses accounted for 0.4 % of the relative abundance in the gut and 0.6 % in lungs. Mycobacteroides abscessus was genetically identified in 10 individuals, although only 2 had positive cultures. Patients with higher levels of Pseudomonas filamentous phages had negative cultures for P. aeruginosa. The protozoan Toxoplasma gondii was detected in all sputum samples, accounting for 0.25 % of the metagenomic reads, with further PCR-confirmation in 50 % of subjects, including children. No correlation was found between SCFA and lung function or microbial composition. The resistome of the fecal compartment was higher than that of the lungs, and a greater abundance of SCFAs in the intestine was associated with poorer lung function. CONCLUSIONS:Patients with normal-mild lung function had higher alpha diversity in the respiratory microbiota; however, beta diversity in the stool was statistically different compared with the group with poorer lung function. Although there were no differences in SCFA concentrations, butyrate-producing bacteria were more abundant in the sputum of the group with better lung function. In fecal samples, resistome to tetracyclines, glycopeptides, and aminoglycosides predominated, whereas in sputum an enrichment of ARGs related to tetracyclines, beta-lactams, and macrolides was observed.

Introduction: Blood eosinophil counts (BEC) have been related to the severity of bronchiectasis and its response to inhaled corticosteroids. However, only the baseline BEC has been used to assess this relationship and it is known that BEC could change over time. The objective of this study is to analyse the association of persistent eosinophilia or eosinopenia with outcomes in bronchiectasis. Methods: Multicentre, prospective and observational study from 43 centres in Spain derived from the Spanish Bronchiectasis Registry (RIBRON). Asthma and anti-eosinophil treatments were excluded. Patients with at least two yearly BEC measures (including the baseline measure) were included. Persistent eosinophilia (at least 300cells/mu L) or persistent eosinopenia (less than 100cells/mu L) were defined as the persistence in the same eosinophil group after three yearly measures (being the baseline the first measure). Results: Five hundred two patients with at least three BEC measures were included; 24.5% and 16.6% presented baseline eosinophilia or eosinopenia, respectively. Of these, 57.7% and 56.6% presented persistent eosinophilia and eosinopenia, respectively. Patients with persistent eosinophilia presented greater severity and a higher number/greater severity of exacerbations than those with non-persistent eosinophilia and those with persistent or non-persistent eosinopenia. Finally, patients with non-persistent eosinopenia presented more severity and a higher number/greater severity of exacerbations than those with non-persistent eosinophilia. Conclusion: When only the baseline BEC was taken into account, patients with eosinopenia presented greater severity than those with eosinophilia. However, patients with persistent eosinophilia presented greater severity than those with persistent eosinopenia. Monitoring the BEC seems to be important in bronchiectasis. (c) 2025 SEPAR. Published by Elsevier Espana, S.L.U. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Introduction:The use of intravenous antibiotic formulations delivered by inhalation is controversial. Tolerance can be an issue and some treatment guidelines discourage this route of administration if the same antibiotic is available in an inhalation formulation. Material and methods:This was a retrospective, observational, single-center study comparing tolerance to three antibiotics delivered by nebulization (intravenous formulations of ampicillin and gentamicin, and an inhalation formulation of colistimethate sodium) in patients with bronchial infection (BI), chronic bronchial infection (CBI), and/or recurrent respiratory infections. The study also aimed to identify factors potentially associated with tolerability. Results:A total of 330 antibiotic tolerance tests were performed in 135 patients (mean age 68 years; 48.9% female; mean post-bronchodilator FEV1% predicted 65.9%). Of these patients, 62.2% had bronchiectasis and 39.3% had chronic obstructive pulmonary disease (COPD). The best tolerated antibiotic was colistimethate. Overall, 89.6% of colistimethate doses were tolerated, compared to 69.5% of inhaled gentamicin doses (P < 0.001) and 69.1% of ampicillin doses (P < 0.001). Compared with colistimethate administration, the odds of intolerance were 5.69 times higher for gentamicin (P < 0.001) and 6.21 times higher for ampicillin (P < 0.001). In the univariate analysis, factors that may have been associated with antibiotic intolerance included smoking habit, worse post-bronchodilator FEV1% predicted and a diagnosis of COPD. In the multivariate analysis, after adjustment for antibiotic type, smoking habit, post-bronchodilator FEV1 and COPD diagnosis, the only factor influencing tolerance was the type of antibiotic used. Conclusion:In patients with BI and/or CBI and/or recurrent respiratory infections, inhaled sodium colistimethate is significantly better tolerated than intravenous formulations of gentamicin and ampicillin for the inhalation route. The only factor influencing tolerance is the type of antibiotic used.

Prevention of exacerbations is a key objective in chronic obstructive pulmonary disease (COPD) management. The adverse effects of an exacerbation include a negative impact on patient quality of life and symptoms, an accelerated rate of decline in lung function, hospital admissions, and increased mortality. Clinical guidelines related to COPD management recommend smoking cessation and inhaled therapy (bronchodilators with or without corticosteroids) as the mainstay for these patients. Apart from the above-mentioned treatment, other potential therapies, such as mucolytic agents, antibiotics (oral or inhaled), phosphodiesterase-4 inhibitors or vaccination, are available and have been shown to reduce the incidence of exacerbations. In this brief narrative review, we will examine the efficacy of various treatments for preventing COPD exacerbations, beyond the use of bronchodilator therapy and inhaled corticosteroids.

Introducción los antibióticos inhalados se utilizan en el tratamiento de diversas enfermedades respiratorias, como la fibrosis quística (FQ), las bronquiectasias no relacionadas con FQ y la neumonía asociada a ventilación mecánica. Mientras que algunos de estos fármacos se comercializan listos para su administración, otros requieren manipulaciones previas, como su dilución o su reconstitución, procedimientos que a menudo carecen de estandarización. Además, ciertos antibióticos solo cuentan con autorización para su uso por vía intravenosa, lo que hace necesario establecer protocolos específicos para su preparación y administración por vía inhalada. Sus propiedades bioquímicas también pueden comprometer la seguridad y la tolerabilidad en los pacientes. El objetivo de este estudio fue analizar con qué frecuencia se describen en la literatura los métodos de preparación y los parámetros bioquímicos de las soluciones de antibióticos inhalados. Asimismo, se exploró su prevalencia de uso en nuestro país y se evaluaron sus características bioquímicas con el fin de valorar su tolerabilidad. Métodos se realizó una revisión bibliográfica en MEDLINE para identificar estudios que describieran las diluciones empleadas en la administración de antibióticos por vía inhalada. Además, se llevó a cabo una encuesta a nivel nacional con el objetivo de evaluar las diluciones utilizadas en la práctica clínica hospitalaria. Paralelamente, se realizaron análisis bioquímicos para determinar el pH, la osmolalidad y las concentraciones de iones sodio y cloruro de las soluciones empleadas. Los excipientes presentes en cada formulación se registraron según la información recogida en la ficha técnica del producto. Resultados la revisión bibliográfica identificó 533 publicaciones a texto completo, en las que se describían 737 mezclas diferentes de antibióticos inhalados. De estas, 476 carecían de estandarización. Solo 190 mezclas incluían instrucciones precisas de dilución, mientras que únicamente 31 proporcionaban datos sobre el pH y 28 sobre la osmolalidad. La encuesta nacional evidenció una alta prevalencia en el uso de antibióticos inhalados en los hospitales participantes, con 22 centros (64,7%) que reconocieron el empleo de formulaciones intravenosas administradas por vía inhalada. Los análisis de laboratorio revelaron que algunas de las diluciones evaluadas se encontraban fuera del rango considerado tolerable, especialmente aquellas correspondientes a reconstituciones de polvos secos o diluciones de presentaciones intravenosas concentradas. Conclusión se observó una escasa disponibilidad de información en la literatura científica sobre los métodos de preparación y las características bioquímicas de las soluciones de antibióticos administrados por vía inhalada. El uso fuera de indicación de formulaciones intravenosas para esta vía resulta generalizado, y algunas de las diluciones empleadas presentan parámetros bioquímicos fuera de los rangos recomendados de tolerabilidad, lo que podría comprometer la seguridad y la efectividad del tratamiento.

La fibrosis quística (FQ) es una enfermedad autosómica recesiva, causada por mutaciones en el gen que codifica para la proteína reguladora de la conductancia transmembrana (CFTR). La mayor morbimortalidad depende del deterioro progresivo que sufre el aparato respiratorio. El aumento de la esperanza de vida en esta patología en los últimos años, tiene una causa multifactorial, pero la principal de ellas es la generalización del uso de los moduladores del CFTR. Los moduladores del CFTR son pequeñas moléculas que restaurar parcialmente la funcionalidad del canal CFTR mutado. Existen 2 tipos, los potenciadores, correctores, y la combinación de ambos. La mayoría de los pacientes mayores de 2 años con al menos una mutación F508del van a poder beneficiarse de terapia moduladora de alta eficacia (ETI) que combina un corrector y dos potenciadores (elexacaftor/tezacaftor/ivacaftor). En la actualidad, todavía un 20-30% de los pacientes con FQ no son candidatos a estas terapias y por ello, se sigue investigando en distintas modalidades de terapia génica.

Introduction: Limited studies have explored the impact of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators on glucose tolerance and insulin secretion in patients with CF, yielding varied results. This study aims to assess alterations in glucose metabolism and insulin secretion over 24 and 52 weeks following CFTR modulator initiation in a cohort of pediatric and adult patients with CF. Materials and Methods: A prospective longitudinal study conducting oral glucose tolerance test (OGTT) with C-peptide and insulin levels. The insulin secretion rate at 60 min (ISR60) and the insulinogenic index (IGI) were calculated during the first 60 and 30 min of the OGTT, respectively. Glucose metabolism status was categorized as normal (NGT), indeterminate (INDET), impaired glucose tolerance (IGT), or cystic fibrosis-related diabetes (CFRD). Additionally, continuous glucose monitoring (CGM) was performed for 14 days at each visit. We employed a repeated-measures general linear model to assess changes in insulin secretion and CGM metrics, with glucose tolerance status as the between-subjects factor and visit (baseline, 24 and 52 weeks) as the within-subjects factor. Results: The study comprised 25 patients (11 adults and 14 pediatrics). At baseline, 2 patients (8%) had NGT, 8 (32%) had INDET, 10 (40%) had IGT, and 5 (20%) had CFRD. Overall, there were no significant changes in insulin and C-peptide area under the curve (AUC), IGI and DI after 52 weeks. However, we observed an increase in ISR60 among NGT patients (mean change: 1.766; 95% CI: 1.414; 2.118, p < 0.001). Consistently, average glucose exhibited a significant decrease in NGT patients between 24 and 52 weeks (mean change: −5.645; 95% CI: −4.233; −10.866, p = 0.028). Conclusions: Treatment with CFTR modulators potentially enhances insulin secretion in patients with CF NGT. Early initiation of treatment, as evaluated through long-term prospective trials, is essential to further investigate whether decreased glucose control is preventable or reversible.

BackgroundA validated 4-point sputum colour chart can be used to objectively evaluate the levels of airway inflammation in bronchiectasis patients. In the European Bronchiectasis Registry (EMBARC), we tested whether sputum colour would be associated with disease severity and clinical outcomes.MethodsWe used a prospective, observational registry of adults with bronchiectasis conducted in 31 countries. Patients who did not produce spontaneous sputum were excluded from the analysis. The Murray sputum colour chart was used at baseline and at follow-up visits. Key outcomes were frequency of exacerbations, hospitalisations for severe exacerbations and mortality during up to 5-year follow-up.Results13 484 patients were included in the analysis. More purulent sputum was associated with lower forced expiratory volume in 1 s (FEV1), worse quality of life, greater bacterial infection and a higher bronchiectasis severity index. Sputum colour was strongly associated with the risk of future exacerbations during follow-up. Compared to patients with mucoid sputum (reference group), patients with mucopurulent sputum experienced significantly more exacerbations (incident rate ratio (IRR) 1.29, 95% CI 1.22–1.38; p<0.0001), while the rates were even higher for patients with purulent (IRR 1.55, 95% CI 1.44–1.67; p<0.0001) and severely purulent sputum (IRR 1.91, 95% CI 1.52–2.39; p<0.0001). Hospitalisations for severe exacerbations were also associated with increasing sputum colour with rate ratios, compared to patients with mucoid sputum, of 1.41 (95% CI 1.29–1.56; p<0.0001), 1.98 (95% CI 1.77–2.21; p<0.0001) and 3.05 (95% CI 2.25–4.14; p<0.0001) for mucopurulent, purulent and severely purulent sputum, respectively. Mortality was significantly increased with increasing sputum purulence, hazard ratio 1.12 (95% CI 1.01–1.24; p=0.027), for each increment in sputum purulence.ConclusionSputum colour is a simple marker of disease severity and future risk of exacerbations, severe exacerbations and mortality in patients with bronchiectasis.

BACKGROUND:Asthma is commonly reported in patients with a diagnosis of bronchiectasis. OBJECTIVE:The aim of this study was to evaluate whether patients with bronchiectasis and asthma (BE+A) had a different clinical phenotype and different outcomes compared with patients with bronchiectasis without concomitant asthma. METHODS:A prospective observational pan-European registry (European Multicentre Bronchiectasis Audit and Research Collaboration) enrolled patients across 28 countries. Adult patients with computed tomography-confirmed bronchiectasis were reviewed at baseline and annual follow-up visits using an electronic case report form. Asthma was diagnosed by the local investigator. Follow-up data were used to explore differences in exacerbation frequency between groups using a negative binomial regression model. Survival analysis used Cox proportional hazards regression. RESULTS:Of 16,963 patients with bronchiectasis included for analysis, 5,267 (31.0%) had investigator-reported asthma. Patients with BE+A were younger, were more likely to be female and never smokers, and had a higher body mass index than patients with bronchiectasis without asthma. BE+A was associated with a higher prevalence of rhinosinusitis and nasal polyps as well as eosinophilia and Aspergillus sensitization. BE+A had similar microbiology but significantly lower severity of disease using the bronchiectasis severity index. Patients with BE+A were at increased risk of exacerbation after adjustment for disease severity and multiple confounders. Inhaled corticosteroid (ICS) use was associated with reduced mortality in patients with BE+A (adjusted hazard ratio 0.78, 95% CI 0.63-0.95) and reduced risk of hospitalization (rate ratio 0.67, 95% CI 0.67-0.86) compared with control subjects without asthma and not receiving ICSs. CONCLUSIONS:BE+A was common and was associated with an increased risk of exacerbations and improved outcomes with ICS use. Unexpectedly we identified significantly lower mortality in patients with BE+A.

INTRODUCTION:Bronchiectasis is a very heterogeneous disease. This heterogeneity has several consequences: severity cannot be measured by a single variable, so multidimensional scores have been developed to capture it more broadly. Some groups of patients with similar clinical characteristics or prognoses (clinical phenotypes), and even similar inflammatory profiles (endotypes), have been identified, and these have been shown to require a more specific treatment.AREAS COVERED:We comment on this 'stratified' model of medicine as an intermediate step toward the application of the usual concepts on which precision medicine is based (such as cellular, molecular or genetic biomarkers, treatable traits and individual clinical fingerprinting), whereby each subject presents certain specific characteristics and receives individualized treatment.EXPERT OPINION:True precision or personalized medicine is based on concepts that have not yet been fully achieved in bronchiectasis, although some authors are already beginning to adapt them to this disease in terms of pulmonary and extrapulmonary etiologies, clinical fingerprinting (specific to each individual), cellular biomarkers such as neutrophils and eosinophils (in peripheral blood) and molecular biomarkers such as neutrophil elastase. In therapeutic terms, the future is promising, and some molecules with significant antibiotic and anti-inflammatory properties are being developed.

Objectives: The aim of this work was to apply shotgun metagenomics in CF sputum and fecal samples to determine the microbiota composition and the existence of antibiotic resistant genes (ARGs). Methods: Thirty-one youths and adults with CF (16 males, median age 36.8 years, range 15–66 years) were recruited in our Unit, each providing a sputum and a stool sample. Clinical data were collected, as well as the conventional microbiological cultures. Samples were kept at –80°C, DNA was obtained and submitted to mass sequencing on an Illumina NovaSeq platform. Raw Illumina reads were analyzed with GAIA (https://metagenomics.sequentiabiotech.com) as previously described (Paytuví et al., doi: 10.1101/804690). Results: At sample collection, chronic airway colonization occurred by Pseudomonas aeruginosa in 42%, and Staphylococcus aureus in 55% of the subjects, despite all of them were asymptomatic. Alpha diversity values were significantly higher in feces than in sputum. Beta diversity PCoA showed a vast dissimilarity in airway microbiota, whereas all feces clustered together. Viruses (Arenaviridae, Herpesviridae, Retroviridae and Siphoviridae) accounted for less than 5% of the airway microbiota and less than 0.05 in feces. Fungi (Malassezia) accounted for 25% of sputum samples. Pseudomonas abundance in metagenomic directly correlated with conventional cultures. A common microbiota core in lung and gut samples was detected, although each patient showed a particular composition. AGRs were more abundant and more diverse in feces (in order of frequency tetracyclines, aminoglycosides, beta-lactams and macrolides), than in sputum (macrolides, beta-lactams, tetracyclines). Conclusions: The shotgun strategy is suitable for characterizing the complete microbiome as the challenge of its bioinformatics analysis has been overcome. Low AGR diversity in lung microbiota may be related to high antibiotic exposure through inhaled therapies.