Eder Mateus

Secreted mucins and airway bacterial colonization in non-CF bronchiectasis

Secreted mucins play a key role in antibacterial defence in the airway, but have not previously been characterized in non‐cystic fibrosis (CF) bronchiectasis patients. We aim to investigate the relationship between secreted mucins levels and the presence of bacterial colonization due to potentially pathogenic microorganisms (PPM) in the airways of stable bronchiectasis patients.

Airway Mucin 2 Is Decreased in Patients with Severe Chronic Obstructive Pulmonary Disease with Bacterial Colonization

RATIONALE Mucins are essential for airway defense against bacteria. We hypothesized that abnormal secreted airway mucin levels would be associated with bacterial colonization in patients with severe chronic obstructive pulmonary disease (COPD) Objectives: To investigate the relationship between mucin levels and the presence of potentially pathogenic micro-organisms in the airways of stable patients with severe COPD Methods: Clinically stable patients with severe COPD were examined prospectively. All patients underwent a computerized tomography scan, lung function tests, induced sputum collection, and bronchoscopy with bronchoalveolar lavage (BAL) and protected specimen brush. Patients with bronchiectasis were excluded. Secreted mucins (MUC2, MUC5AC, and MUC5B) and inflammatory markers were assessed in BAL and sputum by ELISA. MEASUREMENTS AND MAIN RESULTS We enrolled 45 patients, with mean age (±SD) of 67 (±8) years and mean FEV1 of 41 (±10) % predicted. A total of 31% (n = 14) of patients had potentially pathogenic micro-organisms in quantitative bacterial cultures of samples obtained by protected specimen brush. Patients with COPD with positive cultures had lower levels of MUC2 both in BAL (P = 0.02) and in sputum (P = 0.01). No differences in MUC5B or MUC5AC levels were observed among the groups. Lower MUC2 levels were correlated with lower FEV1 (r = 0.32, P = 0.04) and higher sputum IL-6 (r = -0.40, P = 0.01). CONCLUSIONS Airway MUC2 levels are decreased in patients with severe COPD colonized by potentially pathogenic micro-organisms. These findings may indicate one of the mechanisms underlying airway colonization in patients with severe COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01976117).

Usefulness of the Exhaled Breath Temperature Plateau in Asthma Patients

Background: Exhaled breath temperature (EBT) has recently been proposed as a noninvasive marker of bronchial inflammation in patients with asthma. However, the usefulness of EBT in everyday clinical practice is not well established. Results to date are contradictory and are mainly derived from small, pediatric populations. A comparison of results is further complicated by the use of different equipment and measurements. Objective: We performed a comprehensive study to determine whether EBT is related to asthma control, disease severity, bronchial obstruction, or bronchial inflammation. Methods: Sixty-nine patients on maintenance treatment for asthma were included in a cross-sectional study. At the same visit, we measured the EBT plateau (EBTp) using an X-halo Breath Thermometer (Delmedica, Singapore), the fraction of exhaled nitric oxide (FeNO), spirometry, and inflammatory cell count in induced sputum, and we administered the Asthma Control Test questionnaire. Results: No significant differences were found between EBTp measurements and the level of asthma control, disease severity, bronchial obstruction, FeNO levels, or inflammatory asthma phenotypes. We found a significant difference between EBTp and gender. The EBTp was 34.07°C (SD 0.74) in women and 34.38°C (0.46) in men (p = 0.038). We also found a significant correlation between EBTp measurements and the induced sputum eosinophil count (R = -0.348, p = 0.003). Conclusions: The results of this study do not support the usefulness of the EBTp in asthma management in routine clinical practice. Further research using standardized methods is needed to determine the potential use of the EBTp measurement in asthma management.

Variabilidad del fenotipo inflamatorio del asma en el esputo inducido. Frecuencia y causas

INTRODUCTION Recent studies have found variability in asthma inflammatory phenotypes determined by the inflammatory cells in induced sputum (IS). The aim of this study was to determine the frequency and factors affecting inflammatory phenotype variability in IS. METHODS Retrospective observational study that included 61 asthmatic patients who underwent at least two IS tests over a period of 5 years. They were classified according to their baseline inflammatory phenotype and subsequently grouped according to phenotype variability (persistent eosinophilic, persistent non-eosinophilic and intermittent eosinophilic). Demographic, clinical and functional data and factors potentially influencing IS variability were collected in all cases. RESULTS Of the 61 patients, 31 (50.8%) had a change with respect to baseline inflammatory phenotype. Of these, 16 (51.6%) were eosinophilic, 5 (16.1%) neutrophilic, 1 (3.2%) mixed and 9 (29.1%) paucigranulocytic. According to phenotype variability, 18 patients (29.5%) were classified as persistent eosinophilic, 17 (27.9%) non-persistent eosinophilic, and 26 (42.6%) intermittent eosinophilic. Smoking and recent asthma exacerbation were significantly associated with increased risk of variability of the IS inflammatory phenotype (OR=6.44; p=.013; 95% CI=1.49-27.80 and OR=5.84; p=.022; 95% CI=1.29-26.37, respectively). CONCLUSION Half of asthma patients, predominantly those with eosinophilic phenotype, present a change in IS inflammatory phenotype. This variability is associated with smoking and recent asthma exacerbation. Data suggest these factors can modify the classification of IS inflammatory phenotype in clinical practice.

Asthma with bronchial hypersecretion: expression of mucins and toll-like receptors in sputum and blood

Asthma with bronchial hypersecretion is a type of asthma that is poorly studied. Its pathogenesis is not well understood, but is probably related to innate impaired immunity, particularly with toll-like receptors (TLRs) and secretory mucins (MUC). Objectives 1) Define the clinical and inflammatory phenotype of asthma with bronchial hypersecretion of mucus. 2) Compare the type of mucin present in induced sputum (IS) of patients with and without bronchial hypersecretion. 3) Determine the expression of TLRs in IS and blood of asthmatics with and without bronchial hypersecretion. Materials and methods Cross-sectional study which included 43 non-smoking asthmatic patients without bronchiectasis, 19 with bronchiectasis, and 24 without bronchial hypersecretion. All patients underwent the following: IS, spirometry, fractional exhaled nitric oxide, prick test, total immunoglobulin E (IgE), and blood albumin. Analysis of mucins was determined by ELISA and expression of TLR2 and TLR4 by flow cytometry. The level of asthma control was determined by the Asthma Control Test (ACT) questionnaire and quality of life was assessed by the reduced version of the Asthma Quality of Life Questionnaire (mini-AQLQ). Results Asthmatics with bronchial hypersecretion were significantly older (62.6 years vs 48.5 years; p=0.02); had greater severity (persistent severe asthma 94.7% vs 29.2%; p=0.000); a higher proportion of nasal polyposis (36.8% vs 8.3%; p=0.022); less control of asthma (73.7% vs 8.3%; p=0,000); a higher proportion of asthma with negative prick test (68.4% vs 16.6%; p=0.001), and lower levels of IgE (113.4 IU/mL vs 448 IU/mL; p=0.007), compared with asthmatics without bronchial hypersecretion. Significant differences were observed neither in the expression of TLRs 2 and 4 in inflammatory cells of IS or peripheral blood, nor in the expression of mucins between both groups. Conclusion Asthma patients with bronchial hypersecretion have more severe and uncontrolled disease, with poor quality of life as well as a non-allergic inflammatory phenotype. Within the mechanisms involving these differences, it does not appear that mucins and TLRs play an important role.

Utilidad del esputo inducido en la práctica clínica habitual

OBJECTIVE To determine the general and specific utility in diagnosis and/or treatment of induced sputum (IS) inflammatory cell counts in routine clinical practice. METHODS Retrospective study of 171 patients referred for clinical sputum induction over a 1-year period in the pulmonology department of a referral hospital. Independent observers established whether the information provided by IS inflammatory cell count was useful for making diagnostic and therapeutic decisions. RESULTS The most frequent reasons for determination of IS inflammatory cell count were: asthma 103 (59.20%); uncontrolled asthma 34 (19.54%); chronic cough 19 (10.9%), and gastroesophageal reflux 15 (8.6%). In 115 patients (67.3%) it was generally useful for diagnosis and/or treatment; in 98 patients (57.3%) it provided diagnostic information and in 85 patients (49.7%) it assisted in therapeutic decision-making. In asthma, uncontrolled asthma, chronic cough and gastroesophageal reflux, the results were useful in 71.8%, 67.6%, 47.4% and 60%, respectively. CONCLUSION The information provided by IS inflammatory cell count is extremely useful in clinical practice, especially in asthma and chronic cough. These results may justify the inclusion of the IS technique in pulmonology departments and asthma units of referral centers.