Search

Background: Fragile COPD (f-COPD) associated with frequent hospital admissions have high morbidity, mortality and use of health resources. These patients should be managed in personalized integrated care models (ICM). Objectives: To evaluate the long-term effectiveness of a f-COPD ICM on emergency room (ER) visits, hospital admissions, days of hospitalization, mortality and improvement of health status. Methods: Prospective-controlled study with analysis of a cohort of f-COPD patients assigned to ICM and followed-up for maximally 7 years that were compared to a parallel cohort who received standard care. All patients had a confirmed diagnosis of COPD with a history of ≥2 hospital admissions due to exacerbations in the year before enrollment. The change in CAT score and mMRC dyspnea scale, hospital admissions, ER visits, days of hospitalization, and mortality were analyzed. Results: 141 patients included in the ICM were compared to 132 patients who received standard care. The ICM reduced hospitalizations by 38.2% and ER visits by 69.7%, with reduction of hospitalizations for COPD exacerbation, ER visits and days of hospitalization (p 17 was the strongest independent risk factor for mortality and hospitalization among ICM patients. Conclusions: An ICM for f-COPD patients effectively decreases ER and hospital admissions and improves health status, but not mortality.

The Caspian Sea hosts areas of high ecological value as well as industrial, leisure, and agricultural activities that dump into the water body different kinds of pollutants. In this complex context, a proper description of the origin and potential sources of pollution is necessary to address management and mitigation actions aimed at preserving the quality of the water resource and the integrity of the ecosystems. Here, we aimed at detecting sources of both nitrogen inputs, by N stable isotope analysis of macroalgae, and metals in macroalgae and sediments in two highly anthropized coastal stretches at the Iranian side of the Caspian Sea. Sampling was done near the mouth of rivers and canals draining agricultural and urbanized areas. In the westernmost waters, facing a port city, low macroalgal δ15N signatures indicated industrial fertilizers as the principal source of pollution. By contrast, in the central coastal waters, facing touristic areas, the high macroalgal δ15N indicated N inputs from wastewaters. Here the lowest dissolved oxygen concentrations in waters were associated with excess dissolved inorganic nitrogen. Metal concentrations varied largely in the study areas and were lower in macroalgae than in sediments. Localized peaks of Pb and Zn in sediments were observed in the central coastal sites as probable byproducts of mining activity transported downstream. By contrast, Cr and Ni concentrations were high in all sampling sites, thus potentially representing hazardous elements for marine biota. Overall, macroalgal δ15N coupled with metal analysis in macroalgae and sediments was useful for identifying the main sources of pollution in these highly anthropized coastal areas. This double approach in comprehensive monitoring programs could thus effectively inform stakeholders on major environmental threats, allowing targeted management measures.

Frequent-exacerbator COPD (fe-COPD) associated with frequent hospital admissions have high morbidity, mortality and use of health resources. These patients should be managed in personalized integrated care models (ICM). Accordingly, we aimed to evaluate the long-term effectiveness of a fe-COPD ICM on emergency room (ER) visits, hospital admissions, days of hospitalization, mortality and improvement of health status.Prospective-controlled study with analysis of a cohort of fe-COPD patients assigned to ICM and followed-up for maximally 7 years that were compared to a parallel cohort who received standard care. All patients had a confirmed diagnosis of COPD with a history of ≥2 hospital admissions due to exacerbations in the year before enrollment. The change in CAT score and mMRC dyspnea scale, hospital admissions, ER visits, days of hospitalization, and mortality were analyzed.141 patients included in the ICM were compared to 132 patients who received standard care. The ICM reduced hospitalizations by 38.2% and ER visits by 69.7%, with reduction of hospitalizations for COPD exacerbation, ER visits and days of hospitalization (p0.05) compared to standard care. Further, health status improved among the ICM group after 1 year of follow-up (p=0.001), effect sustained over 3 years. However, mortality was not different between groups (p=0.117). Last follow-up CAT score17 was the strongest independent risk factor for mortality and hospitalization among ICM patients.An ICM for fe-COPD patients effectively decreases ER and hospital admissions and improves health status, but not mortality.

Transitional waters are highly productive ecosystems, providing essential goods and services to the biosphere and human population. Human influence in coastal areas exposes these ecosystems to continuous internal and external disturbance. Nitrogen-loads can affect the composition of the resident community and the trophic relationships between and within species, including fish. Based on carbon (&delta, 13C) and nitrogen (&delta, 15N) stable isotope analyses of individuals, we explored the feeding behaviour of two ecologically and economically important omnivorous fish, the eel Anguilla anguilla and the seabream Diplodus annularis, in three neighbouring lakes characterised by different trophic conditions. We found that A. anguilla showed greater generalism in the eutrophic lake due to the increased contribution of basal resources and invertebrates to its diet. By contrast, the diet of D. annularis, which was mainly based on invertebrate species, became more specialised, focusing especially on polychaetes. Our results suggest that changes in macroinvertebrate and fish community composition, coupled with anthropogenic pressure, affect the trophic strategies of high trophic level consumers such as A. anguilla and D. annularis. Detailed food web descriptions based on the feeding choices of isotopic trophospecies (here Isotopic Trophic Units, ITUs) enable identification of the prey taxa crucial for the persistence of omnivorous fish stocks, thus providing useful information for their management and habitat conservation.

The dynamic and hierarchical structure of rivers, together with disruption of the natural river continuum by human activities, makes it difficult to identify and locate sources of nutrient pollution affecting receiving waters and observe its dispersion, thus impairing monitoring efforts. The identification of reliable indicators of anthropogenic nitrogen inputs in catchments is therefore key to achieving effective management of polluted rivers. We tested the capacity of N isotopic signatures (δ15N) of epilithon and snails to provide useful indications of organic and inorganic anthropogenic N inputs in three Mediterranean rivers differing in terms of surrounding land use and physicochemical conditions. We used a combined approach based on (i) analysis of nutrient concentrations in water, (ii) CORINE land cover classification and drainage patterns in catchments and (iii) isotopic analysis of river biota to verify whether isotopic variations were indicative of anthropic activities in the watershed, the associated alteration of water quality, and the consequent impact on snail abundance and diversity. Variation in the δ15N of epilithon within and between rivers reflected localised and diffuse N inputs from inorganic and organic sources. Negative epilithon δ15N values (

Marine coastal areas are highly productive due to the presence of various inputs of organic matter, including terrestrial material, which fuels food webs. However, the ecological mechanisms underlying the productivity of benthic and demersal fish species in estuarine areas are poorly understood. By means of C and N stable isotope analysis and Bayesian mixing models, we investigated the trophic niches of three common fish species: Citharus linguatula, Pegusa lascaris (flatfish) and Liza ramada (mullet) in the Gulf of Gaeta (Italy). Fish were collected from the north-western area and the south-eastern area of the Gulf of Gaeta, the latter affected by organic inputs from the Garigliano River. The results highlighted the riverine terrestrial origin of the organic matter at the base of the food web in the south-eastern area and marine autochthonous input in the north-western area. All fish species increased their trophic specialisation in proximity to the river mouth. L. ramada specialised on seston of terrestrial origin, reducing its niche overlap with C. linguatula and P. lascaris. Away from the river mouth, all species were characterised by longer individuals, increased intraspecific diet variability and higher interspecific similarity in resource use. Organic input from the river represented a complementary trophic niche axis that enabled lower interspecific niche overlap in the south-eastern area, where fish populations were found at higher densities. In conclusion, this study provided information about the effects of the flow of material from the basal compartment up to abundant fish species in areas enriched by organic matter of varying origin.

Background: Probe-based confocal laser endomicroscopy (pCLE) is a novel technique that provides in vivo microscopic imaging of the distal lung. We hypothesized that the intra-alveolar exudates characterizing Pneumocystis jirovecii pneumonia (PJP) can be identified by pCLE in vivo and help in its diagnosis. Objectives: We aimed to assess the usefulness of pCLE for the in vivo diagnosis of PJP. Methods: Thirty-two human immunodeficiency virus (HIV)-positive patients with new pulmonary infiltrates and fever were studied using pCLE. Real-time alveolar images were recorded during the bronchoscopy for off-line analysis by two independent observers. Bronchoalveolar lavage samples were also obtained and processed for microbiology and cytological evaluation, including Grocott stain for P. jirovecii. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of pCLE for the diagnosis of PJP in these patients were calculated. Results: Fourteen patients (44%) were confirmed to have PJP by cultures/staining. pCLE was well tolerated in all patients. It identified intra-alveolar exudates in 13 of them (41%), where 11 of them (85%) had positive Grocott stain for P. jirovecci, with 93% concordance between observers. Sensitivity, specificity, PPV and NPV of pCLE for the diagnosis of PJP were 79, 89, 85 and 84%, respectively. In smokers, these figures improved to be 92, 88, 85 and 94%. Conclusions: pCLE is a quick and safe procedure for on-site diagnosis of PJP in HIV+ patients with excellent specificity and sensitivity mainly in smokers.

Nitrogen inputs in aquatic ecosystems are increasing and climate change is likely to exacerbate cultural eutrophication. The recovery of aquatic ecosystem functionality requires strenuous efforts and entails considerable costs. Therefore, the development of early warning ecological indicators that can help arrest the phenomenon in its early stages is highly desirable. Stable isotope analysis of Nitrogen in algal primary producers has proved useful in determining the origins of Nitrogen inputs in several marine and freshwater ecosystems. Nitrogen signatures are often assigned to impact or non-impact classes by comparing the Nitrogen signature of samples with the Nitrogen signature ranges of potential sources, which can hinder objective ecological evaluation when sample signatures are close to the upper/lower boundaries of source ranges. To overcome this problem, we obtained the Nitrogen signatures of the epilithic associations collected in the littoral zone of Lake Bracciano (Central Italy), covering a pre-drought (2015–2016) and ongoing drought (2017–2019) period. The Bayesian Gaussian Mixture Model determined four probability distributions, each associated with a Nitrogen impact class, and assigned the observed epilithic signatures to the most appropriate classes. Application of the approach at various spatial and temporal scales allowed us to compare the pre-drought and ongoing drought Nitrogen input dynamics. At each spatial and temporal scale, we observed differences in the input dynamics arising from the side effects of the drought on human activities, which were reflected in changes in the probability of Nitrogen signatures belonging to one or the other impact class. Based on this probability, the proposed analytical protocol provided a useful tool for prioritizing specific management measures in areas affected by specific Nitrogen inputs. Moreover, with a few recalibrations, the model proposed for Lake Bracciano can be extended to other contexts.

Non‐native freshwater fish species can have adverse ecological impacts on native populations. However, the mechanisms determining the success or otherwise of their invasion and their role in invaded communities remain largely unknown. This is particularly true for the Mediterranean region, where endemic species characterised by restricted natural ranges may be at high risk of extinction. The largemouth bass (Micropterus salmoides) is native to North America but is invasive in the Italian Peninsula. The aim of this study was to explore the trophic position of M. salmoides, its diet and niche overlap with native fish species in the littoral areas of a Mediterranean lake. Our study was supported by analysis of stable C and N isotopes in the tissues of fish and their potential food sources, twenty years after the introduction of the largemouth bass to Lake Bracciano (Italy). Samples were collected in locations varying in terms of physical structure and resource availability at lower trophic levels in the food web, which was greater in the southern (hereafter: South) than in the northern (hereafter: North) area of the lake. These differences made it possible to explore the mechanisms linking environmental conditions and the role of alien predators in the invaded food web. The abundance of M. salmoides was higher, and the diversity of native fish species was lower, in North than South. In North, M. salmoides had a piscivorous diet and occupied a higher trophic position in the food web than in South, where invertebrates constituted an important part of its diet. As a consequence, trophic niche interference with other fish species at intermediate trophic levels was higher in South. In contrast, in North, M. salmoides showed stronger trophic interference with the percid Perca fluviatilis, a native top predator in the food web, but weaker interference with remaining fish species. Our results help to understand the role of alien species in the food webs of Lake Bracciano, which primarily depends on the habitat and the availability of prey across trophic levels. Physical and ecological variations in the habitat were associated with differences in predatory interactions among native and alien fish species. This suggests that a reduction in productivity and biodiversity at lower trophic levels in lake food webs may favour the success of opportunistic invasive fish species, given the ability of the invaders to maintain some of their characteristics silent, and to fully express their genotype under favourable environmental conditions.

The intensification of agricultural land use and urbanisation has increased nutrient loads in aquatic ecosystems. Nitrogen loads can alter ecosystem structure and functioning, resulting in increased algal productivity, algal blooms and eutrophication. The principal aim of the present paper is to extend the use of epilithic δ 15 N signatures to a lake ecosystem in order to evaluate the potential impact of anthropogenic nitrogen discharges (organic and inorganic) that can also reach coastal waters. Epilithic associations were collected from volcanic rocks in different seasons in shallow water along the entire perimeter of Lake Bracciano and analysed for their nitrogen stable isotope signatures. Furthermore, some stones were moved from an unpolluted site to a polluted one in order to verify the effect on the nitrogen signature of the epilithic association. The epilithon’s δ 15 N signatures provided strong evidence of the space-time variability of N inputs. The differing quality of nitrogen loads was reflected in high isotopic variation within the lake, especially at the beginning of summer (1.7‰ ≤ δ 15 N ≤ 13.3‰), while in winter, when anthropogenic pressure was lowest, the δ 15 N signature variation was less accentuated (3.1‰ ≤ δ 15 N ≤ 7.6‰). At all sampling times, spatial variability was found to be related to the various human activities along the lake shore (especially tourism and agriculture), while seasonal variation at all sampling sites was related to the intensity of anthropogenic pressures (higher in summer and lower in winter). Our results showed that epilithic algal associations and the physicochemical properties of the water did not influence the δ 15 N signature, which in contrast was strongly related to the site-specific effect of human activities around the lake. Thus, the distribution of δ 15 N across space and time can be used to direct nutrient reduction strategies in the region and can assist in monitoring the effectiveness of environmental protection measures.

Resumen Objetivo Evaluar la utilidad de diferentes caracteristicas ecograficas para diferenciar los ganglios linfaticos (GL) benignos y malignos mediante ecografia endobronquial (EBUS) y validar una puntuacion para una aplicacion clinica en tiempo real. Metodos Se analizaron 208 GL mediastinicos procedentes de 141 pacientes. Dos observadores evaluaron de manera independiente 6 criterios ecograficos diferentes (eje menor ≥ 10 mm, forma, margen, ecogenicidad y estructura hiliar central [EHC] y presencia de densidad hiperecogenica). Se genero una puntuacion simplificada en la que a la presencia de margenes bien definidos, la forma redondeada y el eje menor ≥ 10 mm se les asignaba una puntuacion de 1 y a la ecogenicidad heterogenea y la ausencia de EHC se les asignaba una puntuacion de 1,5. La puntuacion se evaluo prospectivamente para la aplicacion clinica en tiempo real en 65 GL durante la EBUS llevada a cabo por 2 operadores experimentados en 39 pacientes. Estos criterios se correlacionaron con los resultados histopatologicos, y se calcularon la sensibilidad, la especificidad y los valores predictivos positivo (VPP) y negativo (VPN). Resultados La heterogeneidad y la ausencia de EHC fueron los parametros que mostraron la maxima sensibilidad y VPN (≥ 90%) en la prediccion de la malignidad de los GL, con una coincidencia interobservadores aceptable (92 y 87%, respectivamente). En la aplicacion en tiempo real, la sensibilidad y la especificidad de la puntuacion > 5 fueron del 78 y del 86%, respectivamente; tan solo la ausencia de EHC, la forma redondeada y el tamano de los GL mostraron una asociacion significativa con la malignidad de estos. Conclusiones La combinacion de diferentes criterios ecograficos puede ser util en la prediccion de la malignidad de los GL mediastinicos y valida para una aplicacion clinica en tiempo real.

Objective To evaluate the utility of different ultrasonographic (US) features in differentiating benign and malignant lymph node (LN) by endobronchial ultrasound (EBUS) and validate a score for real-time clinical application. Methods A total of 208 mediastinal LNs acquired from 141 patients were analyzed. Six different US criteria were evaluated (short axis ≥10 mm, shape, margin, echogenicity, central hilar structure [CHS], and presence of hyperechoic density) by two observers independently. A simplified score was generated where the presence of margin distinction, round shape and short axis ≥10 mm were scored as 1, and heterogeneous echogenicity and absence of CHS were scored as 1.5. The score was evaluated prospectively for real-time clinical application in 65 LNs during EBUS procedure in 39 patients undertaken by two experienced operators. These criteria were correlated with the histopathological results and the sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated. Results Both heterogenicity and absence of CHS had the highest sensitivity and NPV (≥90%) for predicting LN malignancy with acceptable inter-observer agreement (92% and 87% respectively). On real-time application, the sensitivity and specificity of the score >5 were 78% and 86% respectively; only the absence of CHS, round shape and size of LN were significantly associated with malignant LN. Conclusions A combination of different US criteria can be useful for the prediction of mediastinal LN malignancy and valid for real-time clinical application.

Resumen Introduccion Las unidades de cuidados respiratorios intermedios (UCRI) permiten la monitorizacion continua y la ventilacion mecanica no invasiva (VMNI) en los pacientes con insuficiencia respiratoria grave que habitualmente ingresan en unidades de cuidados intensivos (UCI). La utilidad de las UCRI en el manejo de las agudizaciones graves del asma nunca ha sido evaluada. Metodos Se recogieron de forma prospectiva y sistematica los datos clinicos de pacientes ingresados en la UCRI con el diagnostico principal de asma bronquial agudizada, se evaluo el fracaso terapeutico (intubacion o fallecimiento) y su evolucion hasta 6 meses tras el alta, comparada con un grupo de pacientes ingresados en planta de hospitalizacion convencional pareados por edad y sexo, con el mismo diagnostico principal. Resultados Se incluyeron un total de 74 pacientes asmaticos (37 ingresan en la UCRI y 37 en planta) con una edad media (± DE) de 58 ± 20 anos, predominantemente mujeres (67%), con diagnostico previo y tratamiento de asma persistente. La causa principal de ingreso en la UCRI fue insuficiencia respiratoria grave. Los pacientes que ingresaron en la UCRI presentaron mas afectacion radiologica (infiltrados alveolares) y tenian una pCO 2 significativamente mayor. Diez pacientes ingresados en la UCRI precisaron VMNI. No hubo diferencias entre ambos grupos en fracasos terapeuticos, ni en seguimiento a los 6 meses del alta. Conclusiones Los pacientes con agudizaciones graves del asma pueden ser atendidos en una UCRI, evitando ingresos en la UCI y con un pronostico similar a las agudizaciones mas leves que son ingresadas en una planta de hospitalizacion convencional.

a b s t r a c t Introduction: Intermediate respiratory care units (IRCU) provide continuous monitoring and non-invasive mechanical ventilation (NIMV) in patients with severe respiratory failure who are usually admitted to intensive care units (ICUs). The usefulness of IRCU in managing severe asthma exacerbations has never been evaluated. Methods: Clinical data were prospectively and systematically compiled from patients admitted to the IRCU with a principal diagnosis of bronchial asthma exacerbation. We assessed therapeutic failure (intu- bation or exitus) and patient evolution up until 6 months after discharge compared with a group of patients admitted to a conventional hospital ward, paired for age and sex, and with the same principal diagnosis. Results: A total of 74 asthma patients were included (37 admitted to IRCU and 37 to the hospital ward) with a mean age (±SD) of 58 ± 20, who were predominantly women (67%), with previous diagnosis of asthma and persistent asthma treatment. The main cause of admittance to the IRCU was severe respiratory failure. The patients who were admitted to the IRCU presented more radiological affectation (alveolar infiltrates) and had significantly higher pCO2. Ten patients admitted to the IRCU required non-invasive mechanical ventilation (NIMV). There were no differences between the two groups regarding either therapeutic failure or the 6-month follow-up after discharge. Conclusions: Patients with severe asthma exacerbations can be managed in an IRCU while avoiding hospi- talization in an ICU and demonstrating a prognosis similar to milder exacerbations treated in conventional hospital wards.

Background Histology is crucial for the multidisciplinary diagnosis of idiopathic interstitial pneumonias (IIP). Transbronchial cryobiopsy (TBC) has been demonstrated to be useful for obtaining lung parenchyma; however its experience in the diagnosis of IIP is limited. Objectives To describe the diagnostic yield and safety of TBC in the study of IIP. Method Prospective study of 23 outpatients of TBC. All cases had the typical clinical and radiological features of IIP. The endoscopic procedure was performed in the operating theatre using a flexible bronchoscope obtaining 3-5 biopsies of lung parenchyma with radiological control. Biopsies were reviewed by the reference pathologist. Results The patients were 65±10-year-old (57% men). The length range of biopsies was 2-7 mm. The sample was adequate (at least 20 alveolar spaces) in 20 patients (87%). The specific diagnosis (confirmed by Multidisciplinary discussion) was obtained in 12 patients (52%): usual interstitial pneumonia (UIP n=9) and nonspecific interstitial pneumonia (NSIP n=3). The complications were: pneumothorax in 2 patients (both required drainage), 4 patients showed significant bleeding (>100 ml), one of them severe with respiratory failure but the patient recovered 3 days after. In the remaining patients the diagnosis was reached by VATS (9 patients: UIP [n=5], unclassifiable interstitial pneumonia [n=2], NSIP [n=1] and respiratory bronchiolitis associated to interstitial pneumonia [n=1]), or by clinical and radiological parameters (1 organising pneumonia, 1 UIP). Conclusions In patients with suspected IIP, TBC is useful to obtain lung parenchyma with good yield and avoids in 52% of open biopsies in our population.

Introduction: The frequent exacerbator phenotype of COPD (fragile COPD) is associated with higher mortality, more exacerbations and greater resource consumption. A comprehensive care management program (CCMP) can be useful for the patient and the healthcare system. Objective: To evaluate the efficacy of a CCMP for patients with fragile COPD. Methods: Case-control study of patients with fragile COPD followed- up for at least 12 months. Cases were included in a CCMP consisting specialized medical evaluation, telephone and onsite monitoring by a case manager nurse and access to specialized care for early treatment of exacerbation. Controls received usual outpatient care. The number of admissions, emergency room (ER) visits, hospital days, number of treatments with steroids or antibiotics and survival rate were evaluated. Results: 36 cases and 36 controls matched for age and sex were studied. At baseline, cases had worse lung function and greater dyspnea than controls (FEV1 0.83 ± 0.26 vs 1.29 ± 0.54, p = 0.0001; mMRC 2.7 ± 0.88 vs 1.91 ± 0.85, p = 0.0018 respectively). However, during follow-up, cases had fewer hospital admissions (0.27 ± 0.57 vs 2.5 ± 1.96, p Conclusion: A CCMP for fragile COPD patients is effective in the prevention of hospitalizations and reduction of moderate exacerbations compared to usual care.

Probe-based confocal laser endomicroscopy (pCLE) is a novel technique that provides in vivo microscopic imaging of the distal lung. We hypothesized that the intra-alveolar exudates characterizing Pneumocystis jirovecii pneumonia (PJP) can be identified by pCLE in vivo and help in its diagnosis.We aimed to assess the usefulness of pCLE for the in vivo diagnosis of PJP.Thirty-two human immunodeficiency virus (HIV)-positive patients with new pulmonary infiltrates and fever were studied using pCLE. Real-time alveolar images were recorded during the bronchoscopy for off-line analysis by two independent observers. Bronchoalveolar lavage samples were also obtained and processed for microbiology and cytological evaluation, including Grocott stain for P. jirovecii. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of pCLE for the diagnosis of PJP in these patients were calculated.Fourteen patients (44%) were confirmed to have PJP by cultures/staining. pCLE was well tolerated in all patients. It identified intra-alveolar exudates in 13 of them (41%), where 11 of them (85%) had positive Grocott stain for P. jirovecci, with 93% concordance between observers. Sensitivity, specificity, PPV and NPV of pCLE for the diagnosis of PJP were 79, 89, 85 and 84%, respectively. In smokers, these figures improved to be 92, 88, 85 and 94%.pCLE is a quick and safe procedure for on-site diagnosis of PJP in HIV+ patients with excellent specificity and sensitivity mainly in smokers.

Chronic obstructive pulmonary disease and asthma are both highly prevalent inflammatory diseases characterized by airway obstruction with distinct pathogenic mechanisms and different degrees of response to antiinflammatory therapy. However, forms of presentation that show overlap between both diseases and which are not clearly represented in clinical trials are frequently encountered in clinical practice. These patients may show accelerated loss of pulmonary function and have a worse prognosis. Therefore their early identification is essential. Biomarkers such as bronchial hyperreactivity or nitric oxide in exhaled air have yielded discrepant results. Phenotypic characterization will allow treatment with inhaled corticosteroids to be individually tailored and optimized.

Fibred confocal fluorescence microscopy (FCFM) is a novel technology that allows the in vivo assessment and quantification during bronchoscopy of the bronchial wall elastic fibre pattern, alveolar and vessel diameters and thickness of the elastic fibre in the alveolar wall.To relate these structural characteristics with lung function parameters in healthy subjects, smokers with normal spirometry and patients with chronic obstructive pulmonary disease (COPD).We performed FCFM in 20 never smokers, 20 smokers with normal spirometry and 23 patients with COPD who required bronchoscopy for clinical reasons. The bronchial wall elastic fibre pattern was classified as lamellar, loose and mixed pattern, and later confirmed pathologically. Airspace dimensions and extra-alveolar vessel diameters were measured. Lung function measurements and pulmonary CT scans were obtained in all participants.Patients with COPD were characterised by a significantly higher prevalence of loose fibre bronchial deposition pattern and larger alveolar diameter which correlated inversely with several lung function parameters (forced expiratory volume in 1 s (FEV1) , FEV1/forced vital capacity ratio, maximum expiratory flow, carbon monoxide transfer factor and carbon monoxide transfer coefficient; p0.05). Increased alveolar macrophages were demonstrated in active smokers with or without COPD.This is the first FCFM study to describe in vivo microscopic changes in the airways and alveoli of patients with COPD that are related to lung function impairment. These findings open the possibility of assessing the in vivo effects of therapeutic interventions for COPD in future studies.