Objective sputum colour assessment and clinical outcomes in bronchiectasis: data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: A 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. METHODS: We 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. RESULTS: 13 484 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. CONCLUSION: Sputum colour is a simple marker of disease severity and future risk of exacerbations, severe exacerbations and mortality in patients with bronchiectasis.

The cardiomyopathy of cystic fibrosis: a modern form of Keshan disease.

Introduction: We conducted a study to determine the prevalence of structural heart disease in patients with CF, the characteristics of a cardiomyopathy not previously described in this population, and its possible relationship with nutritional deficiencies in CF. Methods: We studied 3 CMP CF patients referred for heart-lung transplantation and a prospective series of 120 adult CF patients. All patients underwent a clinical examination, blood tests including levels of vitamins and trace elements, and echocardiography with evaluation of myocardial strain. Cardiac magnetic resonance imaging (CMR) was performed in patients with CMP and in a control group. Histopathological study was performed on hearts obtained in transplant or necropsy. Results: We found a prevalence of 10% (CI 4.6%-15.4%) of left ventricular (LV) dysfunction in the prospective cohort. Myocardial strain parameters were already altered in CF patients with otherwise normal hearts. Histopathological examination of 4 hearts from CF CMP patients showed a unique histological pattern of multifocal myocardial fibrosis similar to Keshan disease. Four of the five CF CMP patients undergoing CMR showed late gadolinium uptake, with a characteristic patchy pattern in 3 cases (p < 0.001 vs. CF controls). Selenium deficiency (Se < 60 µg/L) was associated with more severe LV dysfunction, higher prevalence of CF CMP, higher NTproBNP levels, and more severe pulmonary and digestive involvement. Conclusion: 10% of adults with CF showed significant cardiac involvement, with histological and imaging features resembling Keshan disease. Selenium deficiency was associated with the presence and severity of LV dysfunction in these patients.

Bronchiectasis and asthma: Data from the European Bronchiectasis Registry (EMBARC).

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.

The Association Between Bronchiectasis and Chronic Obstructive Pulmonary Disease: Data from the European Bronchiectasis Registry (EMBARC).

RATIONALE AND OBJECTIVE: Bronchiectasis and COPD are associated conditions but misdiagnosis is believed to be common. A recently published international consensus definition of bronchiectasis (BE) and COPD association: The ROSE criteria (radiological bronchiectasis(R), obstruction: FEV1/FVC ratio<0.7 (O), symptoms (S) and exposure:≥10 pack year smoking (E) allows objective diagnosis of the BE-COPD association. METHODS: Analysis of the EMBARC registry, a prospective observational study of patients with CT confirmed bronchiectasis from 28 countries. The ROSE criteria were used to objectively defined BE-COPD association. Key outcomes during up to 5-years follow-up were exacerbations, hospitalization and mortality. MEASUREMENT AND MAIN RESULTS: 16730 patients with bronchiectasis were included. 4336 had a co-diagnosis of COPD and these patients had more exacerbations, worse quality of life and higher severity scores. We observed marked overdiagnosis of COPD using the ROSE criteria: 22.2% of patients with a diagnosis of COPD did not have airflow obstruction and 31.9% did not have a history of ≥10 pack years smoking. Therefore the proportion meeting the ROSE criteria for COPD was 2157 (55.4%). Compared to patients without COPD, patients meeting ROSE criteria had increased risk of exacerbations and exacerbations resulting in hospitalisation during follow-up (IRR 1.25 95%CI 1.15-1.35 and 1.69 95%CI 1.51-1.90 respectively) but patients with a diagnosis of COPD who did not meet ROSE criteria also had increased risk of exacerbations. CONCLUSIONS: The label of COPD is often applied to bronchiectasis patients without objective evidence of airflow obstruction and smoking history. Patients with a clinical label of COPD have worse clinical outcomes.

[Safety and effectiveness of treatment with elexacaftor, tezacaftor and ivacaftor in adults with cystic fibrosis]. / Seguridad y efectividad del tratamiento con elexacaftor, tezacaftor e ivacaftor en adultos con fibrosis quística.

INTRODUCTION: Cystic fibrosis (CF) is a disease caused by mutations in the gene located on chromosome 7 that encodes the CF transmembrane conductance regulator protein. Several trials have demonstrated the efficacy and safety of the ELE/TEZ/IVA combination in patients who have at least one F508del mutation. The main objective of the study was to evaluate the safety at 3 and 6 months of treatment with ELE/TEZ/IVA in adult patients with CF. METHODS: This is a real-life, prospective, single-center, cross-sectional study that included adult patients from the CF multidisciplinary unit. The demographic and clinical characteristics of all patients were recorded. During the time of the study, 3 visits were carried out (baseline, at 3 and at 6 months). Side effects were recorded during the follow-up time. RESULTS: 3 months after the start of treatment, a statistically significant improvement was observed. of lung function, BMI, pulmonary exacerbations and energy level, as well as in all the categories of the CFQ-R questionnaire except in the digestive domain. This improvement was maintained, but not increased at 6 months in all variables, except BMI, where differences were observed between 3 and 6 months of treatment. CONCLUSIONS: In the cohort studied, treatment with ELE/TEZ/IVA has a good safety profile. and produces an early improvement in lung function, BMI, quality of life and the "energy level" of adult patients with CF, which is maintained at 6 months of treatment.

Peripheral Neutrophil-to-Lymphocyte Ratio in Bronchiectasis: A Marker of Disease Severity.

Most patients with bronchiectasis have a predominantly neutrophilic inflammatory profile, although other cells such as lymphocytes (as controllers of bronchial inflammation) and eosinophils also play a significant pathophysiological role. Easy-to-interpret blood biomarkers with a discriminative capacity for severity or prognosis are needed. The objective of this study was to assess whether the peripheral neutrophil-to-lymphocyte ratio (NLR) is associated with different outcomes of severity in bronchiectasis. A total of 1369 patients with bronchiectasis from the Spanish Registry of Bronchiectasis were included. To compare groups, the sample was divided into increasing quartiles of NLR ratio. Correlations between quantitative variables were established using Pearson's P test. A simple linear regression (with the value of exacerbations as a quantitative variable) was used to determine the independent relationship between the number and severity of exacerbations and the NLR ratio. The area under the curve (AUC)-ROC was used to determine the predictive capacity of the NLR for severe bronchiectasis, according to the different multidimensional scores. Mean age: 69 (15) years (66.3% of women). The mean NLR was 2.92 (2.03). A higher NLR was associated with more severe bronchiectasis (with an especially significant discriminative power for severe forms) according to the commonly used scores (FACED, E-FACED and BSI), as well as with poorer quality of life (SGRQ), more comorbidities (Charlson index), infection by pathogenic microorganisms, and greater application of treatment. Furthermore, the NLR correlated better with severity scores than other parameters of systemic inflammation. Finally, it was an independent predictor of the incident number and severity of exacerbations. In conclusion, the NLR is an inexpensive and easy-to-measure marker of systemic inflammation for determining severity and predicting exacerbations (especially the most severe) in patients with bronchiectasis.

Safety and tolerability of inhaled antibiotics in patients with bronchiectasis.

INTRODUCTION: Bronchiectasis is typically treated with inhaled antibiotics in clinical practice. However, there is a striking lack of standardised procedures for the preparation of noncommercial solutions. We used biochemical parameters to analyse the safety and tolerability of inhaled antibiotics in patients with bronchiectasis, and determined potential associations between the inhaled antibiotics used and adherence to the medications and quality of life. METHODS: We conducted a literature review, biochemical testing, and a pilot study of patients admitted to our hospital with noncystic fibrosis bronchiectasis. The MEDLINE database was searched for studies involving inhaled antibiotics to treat bronchiectasis. We analysed the pH, osmolality, and sodium and chloride ion concentrations of the antibiotics used. The pilot study included patients receiving inhaled antibiotic treatment. Demographic data, adherence, and quality of life were recorded and assessed. We determined potential associations between the study variables. RESULTS: The literature review identified 429 articles: 106 included precise instructions for diluting antibiotics, and 18 reported data on the biochemical parameters analysed. Laboratory results showed that some antibiotic dilutions were outside the range of tolerability, especially those involving dry powders for intravenous infusion, which must be diluted for their inhalation. Adherence was good in more than 80% of the patients, and higher in men and older patients. Men reported better quality of life. No associations were found between the antibiotics used and the other variables. CONCLUSION: Regarding the biochemical parameters analysed, there is a lack of information on the tolerability and biochemical safety of noncommercial dilutions of inhaled antibiotics used to treat bronchiectasis.

Use of Hyaluronic Acid (HA) in Chronic Airway Diseases.

Hyaluronic acid (HA) is a key component of the extracellular matrix of the lungs. A unique attribute of HA is its water-retaining properties, so HA has a major role in the regulation of fluid balance in the lung interstitium. Hyaluronic acid has been widely used in the treatment of eyes, ears, joints and skin disorders, but in the last years, it has been also proposed in the treatment of certain lung diseases, including airway diseases, due to its anti-inflammatory and water-binding capacities. Hyaluronic acid aerosol decreases the severity of elastase-induced emphysema in murine models, prevents bronchoconstriction in asthmatics and improves some functional parameters in chronic obstructive pulmonary disease (COPD) patients. Due to the protection of HA against bronchoconstriction and its hydration properties, inhaled HA would increase the volume of airway surface liquid, resulting in mucus hydration, increased mucous transport and less mucous plugging of the airways. In addition, it has been seen in human studies that the treatment with nebulised HA improves the tolerability of nebulised hypertonic saline (even at 6% or 7% of concentration), which has been demonstrated to be an effective treatment in bronchial secretion management in patients with cystic fibrosis and bronchiectasis. Our objective is to review the role of HA treatment in the management of chronic airway diseases.

Consensus Document on the Diagnosis and Treatment of Chronic Bronchial Infection in Chronic Obstructive Pulmonary Disease. / Documento de consenso sobre el diagnóstico y tratamiento de la infección bronquial crónica en la enfermedad pulmonar obstructiva crónica.

Although the chronic presence of microorganisms in the airways of patients with stable chronic obstructive pulmonary disease (COPD) confers a poor outcome, no recommendations have been established in disease management guidelines on how to diagnose and treat these cases. In order to guide professionals, the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) has prepared a document which aims to answer questions on the clinical management of COPD patients in whom microorganisms are occasionally or habitually isolated. Since the available scientific evidence is too heterogeneous to use in the creation of a clinical practice guideline, we have drawn up a document based on existing scientific literature and clinical experience, addressing the definition of different clinical situations and their diagnosis and management. The text was drawn up by consensus and approved by a large group of respiratory medicine experts with extensive clinical and scientific experience in the field, and has been endorsed by the SEPAR Scientific Committee.

Nebulized hypertonic saline in noncystic fibrosis bronchiectasis: a comprehensive review.

Bronchiectasis occurs as a result of a vicious circle consisting of an impaired mucociliary transport system, inflammation, and infection and repair of the airways. Damage to the mucociliary system prevents secretion elimination and facilitates bacterial growth and bronchial inflammation. To facilitate mucociliary clearance, current guidelines recommend the use of hypertonic saline (HS) solutions in patients with bronchiectasis not secondary to cystic fibrosis (CF), although the evidence of efficacy in this pathology is sparse. A high percentage of patients with CF and bronchiectasis tolerate HS solutions, but often patients report cough, dyspnoea, throat irritation, or salty taste after inhalation. These adverse effects negatively impact adherence to treatment, which sometimes must be discontinued. Some studies have shown that the addition of hyaluronic acid increases the tolerability of HS solutions, both in patients with CF and in bronchiectasis of other etiologies. We aimed to review the benefits and safety of HS solutions in patients with bronchiectasis. The reviews of this paper are available via the supplemental material section.

Prognostic Value of Frequent Exacerbations in Bronchiectasis: The Relationship With Disease Severity.

INTRODUCTION: Bronchiectasis is a very heterogeneous disease but some homogeneous groups with similar clinical characteristics and prognosis have been identified. Exacerbations have been shown to have a negative impact on the natural history of bronchiectasis. The objective of this study was to identify the definition and characteristics of the "frequent exacerbator patient" with the best prognostic value and its relationship with the severity of bronchiectasis. METHODS: A historical cohort of 651 patients diagnosed with bronchiectasis was included. They had all received 5 years of follow-up since their radiological diagnosis. Exacerbation was defined as a worsening of the symptoms derived from bronchiectasis that required antibiotic treatment. The main outcome was all-cause mortality at the end of follow-up. RESULTS: The mean age was 48.2 (16) years (32.9% males). 39.8% had chronic infection by Pseudomonas aeruginosa. Mean BSI, FACED, and E-FACED were 7 (4.12), 2.36 (1.68), and 2.89 (2.03), respectively. There were 95 deaths during follow-up. The definition of the "frequent exacerbator patient" that presented the greatest predictive power for mortality was based on at least two exacerbations/year or one hospitalization/year (23.3% of patients; AUC-ROC: 0.75 [95% CI: 0.69-0.81]). Its predictive power was independent of the patient's initial severity. The clinical characteristics of the frequent exacerbator patient according to this definition varied according to the initial severity of bronchiectasis, presence of systemic inflammation, and treatment. CONCLUSIONS: The combination of two exacerbations or one hospitalization per year is the definition of frequent exacerbator patient that has the best predictive value of mortality independent of the initial severity of bronchiectasis.

Cost of Hospitalizations due to Exacerbation in Patients with Non-Cystic Fibrosis Bronchiectasis.

BACKGROUND: Knowing the cost of hospitalizations for exacerbation in bronchiectasis patients is essential to perform cost-effectiveness studies of treatments that aim to reduce exacerbations in these patients. OBJECTIVES: To find out the mean cost of hospitalizations due to exacerbations in bronchiectasis patients, and to identify factors associated with higher costs. METHODS: Prospective, observational, multicenter study in adult bronchiectasis patients hospitalized due to exacerbation. All expenses from the patients' arrival at hospital to their discharge were calculated: diagnostic tests, treatments, transferals, home hospitalization, admission to convalescence centers, and hospitals' structural costs for each patient (each hospital's tariff for emergencies and 70% of the price of a bed for each day in a hospital ward). RESULTS: A total of 222 patients (52.7% men, mean age 71.8 years) admitted to 29 hospitals were included. Adding together all the expenses, the mean cost of the hospitalization was EUR 5,284.7, most of which correspond to the hospital ward (86.9%), and particularly to the hospitals' structural costs. The adjusted multivariate analysis showed that chronic bronchial infection by Pseudomonas aeruginosa, days spent in the hospital, and completing the treatment with home hospitalization were factors independently associated with a higher overall cost of the hospitalization. CONCLUSIONS: The mean cost of a hospitalization due to bronchiectasis exacerbation obtained from the individual data of each episode is higher than the cost per process calculated by the health authorities. The most determining factor of a higher cost is chronic bronchial infection due to P. aeruginosa, which leads to a longer hospital stay and the use of home hospitalization.

Respiratory infections due to nontuberculous mycobacterias. / Infecciones respiratorias por micobacterias no tuberculosas.

The most common infections caused by nontuberculous mycobacteria (NTM) are lung infections. The microorganisms causing these infections most frequently are Mycobacterium avium complex, Mycobacterium kansasii and Mycobacterium abscessus complex. Their incidence has increased in the last three decades. After identifying an NTM in the respiratory tract, clinical and radiological aspects must be considered to determine if isolations are clinically relevant. Predisposing conditions that could contribute to infection must also be investigated. Pulmonary disease due to NTM is presented in three clinical forms: a) pneumonitis due to hypersensitivity; b) fibrocavitary form; and c) nodular-bronchiectasic. The diagnosis of respiratory disease due to NTM does not make it obligatory to immediately initiate treatment. Before initiating the latter, other factors must be considered, such as age, comorbidities, life expectancy, due to the prolonged nature of treatments, with potential side effects and, in many cases, only a slight response to the treatment.

Latin America validation of FACED score in patients with bronchiectasis: an analysis of six cohorts.

BACKGROUND: The FACED score is an easy-to-use multidimensional grading system that has demonstrated an excellent prognostic value for mortality in patients with bronchiectasis. A Spanish group developed the score but no multicenter international validation has yet been published. METHODS: Retrospective and multicenter study conducted in six historical cohorts of patients from Latin America including 651 patients with bronchiectasis. Clinical, microbiological, functional, and radiological variables were collected, following the same criteria used in the original FACED score study. The vital status of all patients was determined in the fifth year of follow-up. The area under ROC curve (AUC-ROC) was used to calculate the predictive power of the FACED score for all-cause and respiratory deaths and both number and severity of exacerbations. The discriminatory power to divide patients into three groups of increasing severity was also analyzed. RESULTS: Mean (SD) age of 48.2 (16), 32.9% of males. The mean FACED score was 2.35 (1.68). During the follow up, 95 patients (14.6%) died (66% from respiratory causes). The AUC ROC to predict all-cause and respiratory mortality were 0.81 (95% CI: 0.77 to 0.85) 0.84 (95% CI: 0.80 to 0.88) respectively, and 0.82 (95% CI: 078-0.87) for at least one hospitalization per year. The division into three score groups separated bronchiectasis into distinct mortality groups (mild: 3.7%; moderate: 20.7% and severe: 48.5% mortality; p < 0.001). CONCLUSIONS: The FACED score was confirmed as an excellent predictor of all-cause and respiratory mortality and severe exacerbations, as well as having excellent discriminative capacity for different degrees of severity in various bronchiectasis populations.

The Multiple Faces of Non-Cystic Fibrosis Bronchiectasis. A Cluster Analysis Approach.

RATIONALE: The clinical presentation and prognosis of non-cystic fibrosis bronchiectasis are both very heterogeneous. OBJECTIVES: To identify different clinical phenotypes for non-cystic fibrosis bronchiectasis and their impact on prognosis. METHODS: Using a standardized protocol, we conducted a multicenter observational cohort study at six Spanish centers with patients diagnosed with non-cystic fibrosis bronchiectasis before December 31, 2005, with a 5-year follow-up from the bronchiectasis diagnosis. A cluster analysis was used to classify the patients into homogeneous groups by means of significant variables corresponding to different aspects of bronchiectasis (clinical phenotypes): age, sex, body mass index, smoking habit, dyspnea, macroscopic appearance of sputum, number of exacerbations, chronic colonization with Pseudomonas aeruginosa, FEV1, number of pulmonary lobes affected, idiopathic bronchiectasis, and associated chronic obstructive pulmonary disease. Survival analysis (Kaplan-Meier method and log-rank test) was used to evaluate the comparative survival of the different subgroups. MEASUREMENTS AND MAIN RESULTS: A total of 468 patients with a mean age of 63 (15.9) years were analyzed. Of these, 58% were females, 39.7% had idiopathic bronchiectasis, and 29.3% presented with chronic Pseudomonas aeruginosa colonization. Cluster analysis showed four clinical phenotypes: (1) younger women with mild disease, (2) older women with mild disease, (3) older patients with severe disease who had frequent exacerbations, and (4) older patients with severe disease who did not have frequent exacerbations. The follow-up period was 54 months, during which there were 95 deaths. Mortality was low in the first and second groups (3.9% and 7.6%, respectively) and high for the third (37%) and fourth (40.8%) groups. The third cluster had a higher proportion of respiratory deaths than the fourth (77.8% vs. 34.4%; P < 0.001). CONCLUSIONS: Using cluster analysis, it is possible to separate patients with bronchiectasis into distinct clinical phenotypes with different prognoses.

Association of the relative change in weight and body mass index with lung function in teenagers and adults with cystic fibrosis: Influence of gender and diabetes.

BACKGROUND: Nutritional status is a prognostic factor in cystic fibrosis. Prevention of nutritional impairment and weigh loss are major clinical objectives because they are associated with worsening of lung function and increased mortality. OBJECTIVE: To identify a potential relationship of clinical nutrition parameters, and their relative changes, with lung function (FEV1%) in a cohort of adolescent and adult patients with CF. METHODS: A retrospective analysis of 64 patients older than 14years. Weight, height, BMI, and lung function data were collected at a period of disease stability, both in the year of the first abnormal oral glucose tolerance test (OGTT) and in the previous year. Relative changes in weight and BMI, and their relationship with FEV1%, were determined by linear regression and ANOVA tests; influence of gender and diabetes was also assessed. RESULTS: Mean age of the series (28 females and 36 males) was 26.8years. Normal glucose tolerance (NGT) was found in 26.7%, while 18.3% had diabetes without impaired fasting glucose (CFRD without FPG). Mean BMI was 20.32, with a mean weight of 53.53kg; 32.8% had BMI<18.5, and only 4.7% were overweight. Overall, a positive relative change in weight (≥6%) was associated with an increase in FEV1% (9.31%), as compared to those with a greater weight loss (at least 2%), who had a 12.09% fall in FEV1. Patients with CFRD without FPG had poorer lung function if they had a negative relative change in weight by at least 2% as compared to NGT. CONCLUSIONS: In patients with CF, a relative weight gain is positively associated to FEV1%, while a relative weight loss of at least 2% has a significant negative impact on lung function.

Insulin resistance, ß-cell dysfunction and differences in curves of plasma glucose and insulin in the intermediate points of the standard glucose tolerance test in adults with cystic fibrosis.

BACKGROUND: diabetes has become a co-morbidity with a negative impact on nutritional status, lung function and survival in cystic fibrosis. OBJECTIVE: To identify any changes in intermediate points after a 2-hour oral glucose tolerance test (OGTT), pancreatic ß-cell dysfunction, and insulin resistance in cystic fibrosis-related diabetes. METHODS: It was carried out a retrospective analysis in a cohort of 64 patients affected of cystic fibrosis, older than 14 years, using the first pathological OGTT. Peripheral insulin resistance was measured using the homeostasis model assessment for insulin resistance (HOMA- IR), and pancreatic ß-cell function was calculated according to Wareham. Time to maximum plasma insulin and glucose levels and area under the curve (AUC0-120) were also measured. RESULTS: Twenty-eight women and 36 men with a mean age of 26.8 years were enrolled, of whom 26.7% had normal glucose tolerance (NGT), 18.3% cystic fibrosis-related diabetes without fasting hyperglycemia (CFRD w/o FPG), 10% indeterminate (INDET), and 45% impaired glucose tolerance (IGT). HOMA-IR values were not significantly different between the diagnostic categories. Patients with any pathological change had worse ß cell function, with a significant delay in insulin secretion, although there were no differences in total insulin production (AUC0-120). Time to maximum glucose levels was significantly shorter in NGT patients as compared to other categories, with glucose AUC0-120 being higher in the different diagnostic categories as compared to NGT. CONCLUSIONS: In over half the cases, peak blood glucose levels during a standard OGTT are reached in the intermediate time points, rather than at the usual time of 120minutes. Patients with cystic fibrosis and impaired glucose metabolism have a delayed insulin secretion during the standard OGTT due to loss of first-phase insulin secretion, with no differences in total insulin production. Absence of significant changes in HOMA-IR suggests that ß-cell dysfunction is the main pathogenetic mechanism.