Reduced airway levels of fatty-acid binding protein 4 in COPD: relationship with airway infection and disease severity.

BACKGROUND: For still unclear reasons, chronic airway infection often occurs in patients with Chronic Obstructive Pulmonary Disease (COPD), particularly in those with more severe airflow limitation. Fatty-acid binding protein 4 (FABP4) is an adipokine involved in the innate immune response against infection produced by alveolar macrophages (Mɸ). We hypothesized that airway levels of FABP4 may be altered in COPD patients with chronic airway infection. METHODS: In this prospective and controlled study we: (1) compared airway FABP4 levels (ELISA) in induced sputum, bronchoalveolar lavage fluid (BALF) and plasma samples in 52 clinically stable COPD patients (65.2 ± 7.9 years, FEV1 59 ± 16% predicted) and 29 healthy volunteers (55.0 ± 12.3 years, FEV1 97 ± 16% predicted); (2) explored their relationship with the presence of bacterial airway infection, defined by the presence of potentially pathogenic bacteria (PPB) at ≥103 colony-forming units/ml in BALF; (3) investigated their relationship with the quantity and proportion of Mɸ in BALF (flow cytometry); and, (4) studied their relationship with the severity of airflow limitation (FEV1), GOLD grade and level of symptoms (CAT questionnaire). RESULTS: We found that: (1) airway levels of FABP4 (but not plasma ones) were reduced in COPD patients vs. controls [219.2 (96.0-319.6) vs. 273.4 (203.1-426.7) (pg/ml)/protein, p = 0.03 in BALF]; (2) COPD patients with airway infection had lower sputum FABP4 levels [0.73 (0.35-15.3) vs. 15.6 (2.0-29.4) ng/ml, p = 0.02]; (3) in COPD patients, the number and proportion of Mɸ were positively related with FABP4 levels in BALF; (4) BALF and sputum FABP4 levels were positively related with FEV1, negatively with the CAT score, and lowest in GOLD grade D patients. CONCLUSIONS: Airway FABP4 levels are reduced in COPD patients, especially in those with airway infection and more severe disease. The relationship observed between Mɸ and airway FABP4 levels supports a role for FABP4 in the pathogenesis of airway infection and disease severity in COPD.

Impact of patient satisfaction with his or her inhaler on adherence and asthma control.

Background: Asthma guidelines recommend considering patient preferences for inhaler choice. However, few studies have assessed the impact of patient satisfaction with an inhaler on adherence and health outcomes. Objective: To assess the impact of patient satisfaction with an inhaler on adherence and health outcomes in asthma. Methods: In a cross-sectional, observational, multicenter study, 778 patients with moderate or severe asthma and who were treated with maintenance inhalers completed a number of scales and questionnaires: the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire, the Treatment Satisfaction Questionnaire for Medication, the Test of Adherence to Inhalers (TAI), the Morisky-Green questionnaire, and the Asthma Control Test (ACT). Results: The study population was categorized according to a median FSI-10 score as high (49.4%) and low (50.6%) satisfaction with their inhaler. Logistic regression analysis showed that high specific satisfaction with an inhaler was associated with the younger age group (odds ratio [OR] 0.976 [95% confidence interval {CI} 0.965-0.987]); male gender (OR 1.725 [95% CI 1.187-2.507]); controlled asthma: ACT score ≥ 20 (OR 1.664 [95% CI 1.133-2.445]); high general satisfaction with treatment (OR 4.861 [95% CI 3.335-7.085]); high adherence to inhaler: TAI score ≥ 46 (OR 1.546 [95% CI 1.025-2.332]); nonsevere asthma (OR 1.056 [95% CI 0.648-1.721]); and no trouble with inhaler use (OR 0.401 [95% CI 0.174-0.922]). Conclusion: High patient satisfaction with an inhaler, irrespective of received medication, was related to adherence and asthma control. Our results pointed out the relevance of inhaler choice in inhaled therapy; these results could be useful for designing new strategies targeted to increase adherence in patients with asthma.

[Is the introduction of clinical management programs for patients with chronic obstructive pulmonary disease useful? Comparison of the effectiveness of two interventions on the clinical progress and care received]. / ¿Es útil la implantación de programas de gestión clínica de los pacientes con enfermedad pulmonar obstructiva crónica? Comparación de la efectividad de dos intervenciones sobre la evolución clínica y la atención recibida.

OBJECTIVE: To evaluate the effectiveness of two management programs on patients with chronic obstructive pulmonary disease (COPD). DESIGN: A study with a quasi-experimental design was used to evaluate the effectiveness of two interventions (I1, I2) for the care of patients with COPD after a mean follow-up of 31.2months. SETTING: Primary Care Centres in two Barcelona Health Areas and their referral hospitals. PARTICIPANTS: Patients with COPD selected by simple random sampling using any disease code corresponding to COPD. INTERVENTIONS: I1: Integrated management program that was optimised and coordinated the resources. Training was given, as well as quality control of spirometry. I2: Isolated interventions like a call-centre. Care circuits and computerised clinical notes were shared. MAIN MEASUREMENTS: Variables were recorded as regards lung function, severity, use of inhalers, lifestyles, quality of life, and exacerbations. RESULTS: Of the 393 patients evaluated at the beginning, 120 and 104 (I1 and I2, respectively) received the final evaluation. With I1, there was a reduction in patients who smoked (P=.034). Lung function and quality of life did not change significantly in either group, but shortness of breath was slightly worse. There was an increase in the correct use of inhalers, although it only reached 48% and 61% with interventions I1 and I2, respectively. The percentage of patients with exacerbations decreased with I1 compared to that of I2 (P<.001), and there were less hospital admissions due to exacerbations with I2 compared to I1 (P<.003]). CONCLUSIONS: Both interventions achieved significant improvements, and no overall worsening of a chronic and progressive disease as is COPD.

Expression of toll-like receptors 2 and 4 in subjects with asthma by total serum IgE level.

BACKGROUND: Emerging data suggest that innate immunity may play a role in asthma, particularly the toll-like receptors (TLRs). Some studies pointed to an involvement of TLRs 2 and 4 in the pathogenesis of allergic asthma, and other studies related TLRs to IgE. However, there are not any studies that have comprehensively evaluated the expression of TLRs 2 and 4 in inflammatory cells, in peripheral blood and induced sputum specimens from asthmatic patients, according to their total serum IgE. METHODS: We studied 44 asthmatic patients (15 with high total serum IgE and 29 with normal total serum IgE). On a single visit, all patients underwent: induced sputum, pulmonary function tests, determination of exhaled nitric oxide fraction, venipuncture for blood analysis and skin prick allergy tests. The induced sputum cellularity was analyzed by flow cytometry, where expression of TLRs 2 and 4 was studied using fluorochrome-conjugated monoclonal antibodies. RESULTS: Asthmatic patients with high total serum IgE showed, a higher percentage of macrophages expressing TLR4 (42.99 % ± 22.49) versus asthmatic patients with normal total serum IgE (28.84 % ± 15.16) (P = 0.048). Furthermore, we observed a correlation (but weak) between the percentage of macrophages expressing TLR4 in induced sputum and the total serum IgE level (R = 0.314; P = 0.040). CONCLUSION: Asthmatic subjects with high total serum IgE show increased macrophage expression of TLR4 in induced sputum. This outcome may result from a link between innate immunity and IgE-mediated, adaptive immune responses in asthma, and point to TLR4 as a potential therapeutic target.

Clinical and inflammatory features of asthma with dissociation between fractional exhaled nitric oxide and eosinophils in induced sputum.

BACKGROUND: Measurement of the fractional exhaled nitric oxide (FeNO) and eosinophils in induced sputum are noninvasive markers for assessing airway inflammation in asthma. The clinical usefulness of the correlation between raised FeNO and sputum eosinophilia is controversial. We aimed to examine dissociation between FeNO and sputum eosinophils in a clinical series of asthma patients and to determine whether dissociation between these noninvasive markers was associated with clinical and inflammatory differences in these patients. METHODS AND FINDINGS: A total of 110 patients with asthma were included in a cross-sectional study. All of them were on maintenance treatment for asthma. All patients underwent the following on the same day: FeNO, induced sputum, spirometry, serum total IgE levels and skin prick test. The level of asthma control was determined by the Asthma control Test Questionnaire. In 46 (41.8%) patients, a discrepancy between FeNO and sputum eosinophil count was observed, of those, 34 (73.9%) had a FeNO <50 ppb and high eosinophil count, and were characterized by having a predominance of nonallergic asthma with bronchial eosinophilic inflammatory phenotype. Also, 12 (26.1%) patients had FeNO ≥50 ppb and sputum eosinophilia within the normal reference values, and were characterized by having a predominance of atopy with a paucigranulocytic inflammatory phenotype. CONCLUSIONS: A high percentage of patients with dissociation between results of FeNO and sputum eosinophils was observed. These patients showed differential clinical and inflammatory features.

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.

Real World Evidence asthma and COPD inhaled treatment therapy in Spain.

Background: This study aimed to describe the use of pressured metered dose inhalers (pMDI) and dry powder inhalers (DPI) in Spanish patients in terms of socio-demographic, clinical, and functional characteristics in patients with asthma or COPD on maintenance treatment with inhaled therapy. Methods: A retrospective, descriptive, national, multicentre, and observational study using a database with 1.8 million patients from hospitals and primary care centers as a secondary information source. Results: The sample included 24,102 subjects with asthma on maintenance therapy (26.0% with pMDI, 54.9% with DPI, and 19.0% with a combination of DPI + pMDI inhalers) and 12,858 subjects with COPD on maintenance therapy (26.1% with pMDI, 38.7% with DPI and 35.2% with a combination of pMDI + DPI inhalers, mostly extemporary triple therapy). In proportion, subjects ≥ 75 years old use more pMDI than DPI, while younger subjects (40-64 years old) use more DPI. An inhalation chamber was prescribed in 51.0% of asthma subjects and 47.2% of COPD subjects treated with pMDI. The use of an inhalation chamber increases with the degree of airflow limitation by disease and age. In subjects with comorbidities, pMDI inhaler use increased in those ≥75 years old for asthma and COPD subjects. Switching from pMDI to DPI and vice versa was relatively common: 25.5% of asthma subjects and 21.9% of COPD subjects treated with pMDI had switched from DPI in the previous year. On the contrary, 14.1% and 11.7% of asthma and COPD patients treated with DPI had switched from pMDI the last year. Conclusions: The use of pMDI or DPI can vary according to age, both in asthma and COPD. Switching from pMDI to DPI and vice versa is relatively common. Despite the availability of dual and triple therapy inhalers on the market, a considerable number of subjects were treated with multiple devices.

Breath analysis using electronic nose and gas chromatography-mass spectrometry: A pilot study on bronchial infections in bronchiectasis.

BACKGROUND AND AIMS: In this work, breath samples from clinically stable bronchiectasis patients with and without bronchial infections by Pseudomonas Aeruginosa- PA) were collected and chemically analysed to determine if they have clinical value in the monitoring of these patients. MATERIALS AND METHODS: A cohort was recruited inviting bronchiectasis patients (25) and controls (9). Among the former group, 12 members were suffering PA infection. Breath samples were collected in Tedlar bags and analyzed by e-nose and Gas Chromatography-Mass Spectrometry (GC-MS). The obtained data were analyzed by chemometric methods to determine their discriminant power in regards to their health condition. Results were evaluated with blind samples. RESULTS: Breath analysis by electronic nose successfully separated the three groups with an overall classification rate of 84% for the three-class classification problem. The best discrimination was obtained between control and bronchiectasis with PA infection samples 100% (CI95%: 84-100%) on external validation and the results were confirmed by permutation tests. The discrimination analysis by GC-MS provided good results but did not reach proper statistical significance after a permutation test. CONCLUSIONS: Breath sample analysis by electronic nose followed by proper predictive models successfully differentiated between control, Bronchiectasis and Bronchiectasis PA samples.

Assessment of inhalation errors, training time and patient preference for DuoResp® Spiromax® and Symbicort® Turbuhaler® in patients with asthma and COPD.

While poor inhaler technique in asthma and chronic obstructive pulmonary disease (COPD) can compromise the effectiveness of inhaled medications, identifying and quantifying these errors may suggest ways to improve inhalation technique and patient outcomes. The objective of this international, multicentre care improvement programme was to investigate errors in inhaler use (handling errors and inhalation errors) made by patients in handling two dry powder inhalers; DuoResp® Spiromax® and Symbicort® Turbuhaler®. Patients with asthma or COPD aged between 18 and 80 years attending the allergology/pneumology departments of 14 hospitals in Spain and Portugal were included. All assessments were performed during one regular scheduled visit to the study clinic. Among 161 eligible patients (138 with asthma; 23 with COPD), inhalation errors were the most common type of error, with no significant difference between devices in overall total error rate, handling error rate or inhalation error rate. Significantly fewer total errors per patient (1.4 vs. 1.9; p < 0.001) and handling errors per patient (0.5 vs. 0.8; p < 0.001) were observed with DuoResp® Spiromax® compared with Symbicort® Turbuhaler®. The mean number of attempts for patients using DuoResp® Spiromax® to perform two correct procedures was 1.9 (0.6) compared with 2.1 (0.9) attempts for patients using Symbicort® Turbuhaler® (p = 0.016). Compared with Symbicort® Turbuhaler®, DuoResp® Spiromax® was found to be easy to learn how to use (p < 0.001), easy to prepare (p < 0.001), easy to use (p < 0.001), comfortable in terms of weight and size (p = 0.001), and patients felt that they were using the device correctly (p < 0.001). Overall, 79.5% of patients stated that they preferred DuoResp® Spiromax® as their first option over Symbicort® Turbuhaler®. The findings of this study may be useful in developing effective inhaler training programmes and thus improve outcomes in asthma and COPD.

Determinants and Differences in Satisfaction with the Inhaler Among Patients with Asthma or COPD.

BACKGROUND: Satisfaction with the inhaler is an important determinant of treatment adherence in patients with asthma and chronic obstructive pulmonary disease (COPD). However, few studies have compared these 2 groups to identify the factors associated with satisfaction with the inhaler. OBJECTIVE: To assess and compare satisfaction with the inhaler in patients with asthma or COPD and to determine the variables associated with high inhaler satisfaction. METHODS: A multicenter, cross-sectional study of 816 patients (406 with asthma and 410 with COPD) was conducted. Satisfaction was assessed with the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire. All participants completed the Test of Adherence to Inhalers and either the Asthma Control Test (ACT) or the COPD Assessment Test (CAT). RESULTS: Overall, the asthma group was significantly more satisfied with the inhaler (mean [standard deviation] FSI-10 scores: 44.1 [6.5] vs 42.0 [7.7]; P < .001) and more satisfied on most (7 of 10; 70%) items. Patients with asthma were significantly more satisfied with the inhaler regardless of the adherence level or the type of nonadherence pattern. Younger age, good disease control (ACT ≥20 or CAT ≤10), previous inhaler training, and absence of unwitting nonadherence were all independently and significantly associated with high inhaler satisfaction. CONCLUSIONS: Age, disease control, and training in inhalation technique all play a more significant role than the specific diagnosis in explaining satisfaction with the device in patients with asthma and COPD. These findings underscore the need to provide better training and more active monitoring of the inhalation technique to improve patient satisfaction, treatment adherence, and clinical outcomes.

The TAGA Study: A Study of Factors Determining Aortic Diameter in Families at High Risk of Abdominal Aortic Aneurysm Reveal Two New Candidate Genes.

A variety of disorders are known to be related with aortic geometry, among them abdominal aortic aneurysm (AAA). This work aims to present the main determinants of abdominal aortic diameter in a new cohort of families at high risk of AAA. The Triple-A Genomic Analysis (TAGA) study comprises 407 individuals related in 12 families. Each family was collected through a proband with AAA. We calculated heritability and genetic correlations between abdominal aortic diameter and clinical parameters. A genome-wide linkage scan was performed based on 4.6 million variants. A predictive model was calculated with conditional forest. Heritability of the abdominal aortic diameter was 34%. Old age, male sex, higher height, weight, creatinine levels in serum, and better lung capacity were the best predictors of aortic diameter. Linkage analyses suggested the implication of Epidermal Growth Factor Receptor (EGFR) and Betacellulin (BTC) genes with aortic diameter. This is the first study to evaluate genetic components of variation of the aortic diameter in a population of AAA high-risk individuals. These results reveal EGFR, a gene that had been previously implicated in AAA, as a determinant of aortic diameter variation in healthy genetically enriched individuals, and might indicate that a common genetic background could determine the diameter of the aorta and future risk of AAA.

Total and specific immunoglobulin E in induced sputum in allergic and non-allergic asthma.

BACKGROUND: Most patients with nonallergic asthma have normal serum immunoglobulin E (IgE) levels. Recent reports suggest that total and aeroallergen-specific IgE levels in induced sputum may be higher in nonallergic asthmatics than in healthy controls. Our objective is to compare total and dust-mite specific (Der p 1) IgE levels in induced sputum in allergic and nonallergic asthmatics and healthy controls. METHODS: Total and Der p 1-specific IgE were measured in induced sputum (ImmunoCAP immunoassay) from 56 age- and sex-matched asthmatics (21 allergic, 35 nonallergic) and 9 healthy controls. Allergic asthma was defined as asthma with a positive prick test and/or clinically-significant Der p 1-specific serum IgE levels. RESULTS: Patients with allergic asthma presented significantly higher total and Der p 1-specific serum IgE levels. There were no significant between-group differences in total sputum IgE. However, Der p 1-specific sputum IgE levels were significantly higher (p = 0.000) in the allergic asthmatics, but without differences between the controls and nonallergic asthmatics. Serum and sputum IgE levels were significantly correlated, both for total IgE (rho = 0.498; p = 0.000) and Der p 1-specific IgE (rho, 0.621; p = 0001). CONCLUSIONS: Total IgE levels measured in serum and induced sputum are significantly correlated. No significant differences were found between the differents groups in total sputum IgE. Nevertheless, the levels of Der p 1-specific sputum IgE levels were significantly higher in the allergic asthmatics, but without differences between the controls and nonallergic asthmatics. Probably due to the lack of sensitivity of the test used, but with the growing evidence for local allergic reactions better methods are need to explore its presence. The Clinical Trials Identifier for this project is NCT03640936.

Asthma patient satisfaction with different dry powder inhalers.

BACKGROUND: The preferences and opinions of patients are important when choosing the optimal inhaler device for asthma management. We compared patient satisfaction of three dry powder inhalers in patients with moderate to severe asthma. METHODS: We selected a group of patients treated with EasyhalerTM (n = 164) and a second group of patients treated with TurbuhalerTM (n = 100) or DiskusTM (AccuhalerTM) (n = 64) from the register of an observational, multicenter study. Data of patients were paired according to age, gender, and asthma severity. Patient satisfaction with the inhaler type was assessed with the specific 'Feeling of Satisfaction with Inhaler' (FSI-10) questionnaire. RESULTS: Specific satisfaction with inhaler was statistically significantly higher with EasyhalerTM, as well as the percentage of patients with high satisfaction with inhaler. (FSI-10 score ≥43). Scores for EasyhalerTM were also statistically significantly better for individual FSI-10 items such as learning how to use, inhaler preparation, inhaler use, weight and size, and portability. There were no significant differences in asthma control (ACT, Mini-AQLQ) and adherence (TAI global score). CONCLUSIONS: Specific satisfaction with inhaler was higher with EasyhalerTM in a homogeneous population of patients with moderate to severe asthma. However, the relationship between satisfaction with the inhaler and adherence and asthma control deserves more investigation.

[Knowledge of and attitudes and adherence to the Spanish Guidelines for Asthma Management (GEMA) among Spanish health care professionals: the GEMA test Project]. / Opinión, conocimientos y grado de seguimiento referidos por los profesionales sanitarios españoles de la Guía Española para el Manejo del Asma (GEMA). Proyecto GEMA-TEST.

OBJECTIVE: Health care professionals' adherence to asthma guidelines is believed to be low. The aim of the present study was to determine the knowledge, attitudes, and adherence of Spanish health care professionals with respect to the Spanish Guidelines for Asthma Management (GEMA). MATERIAL AND METHODS: A multiple choice test with 15 questions was constructed. Items assessed knowledge of and opinions and adherence to asthma guidelines in general and the GEMA in particular. Test completion was voluntary, individual, and anonymous. RESULTS: A total of 1,066 physicians and nurses took the test. The sample consisted of 241 (22.6%) respiratory medicine specialists and 244 (22.9%) nurses from the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), 221 (20.7%) pediatric pulmonologists from the Spanish Society of Pediatric Pulmonology (SENP), 220 (20.6%) general practitioners from the Spanish Society of Family and Community Medicine (semFYC), 181 (17%) general practitioners from the Spanish Society of Rural and General Medicine (SEMERGEN), and 38 (3.6%) others. Asthma guidelines were considered useful or very useful by 805 (76%), and 771 (72%) stated they were familiar with the GEMA. However, 388 (36%) admitted that they followed guidelines seldom or never. The level of adherence to the GEMA was poor for 243 (30.3%) respondents. The multivariate analysis revealed that low adherence was associated with the following characteristics: coming from the geographic center or south of Spain; being a primary care physician, unfamiliar with guidelines, or unconvinced of their utility; and not being a user of spirometry. CONCLUSIONS: Even though the majority of Spanish health care professionals surveyed seem to know of the GEMA, their adherence to those guidelines is very low. Educational programs that seek to improve knowledge of asthma guidelines should consider the profile of professionals with low adherence to the GEMA so as to include educational strategies that target them specifically.

Errors in the Use of Inhalers by Health Care Professionals: A Systematic Review.

BACKGROUND: Inefficient inhaler technique (IT) compromises the optimal delivery of medication. However, the IT knowledge of health care professionals (HCPs) has received scant attention. OBJECTIVE: The objective of this study was to perform a systematic review of published reports assessing the IT proficiency of HCPs in using pressurized metered dose (pMDI) and dry powder (DPI) inhalers. METHODS: Studies published between 1975 and 2014 that directly assessed the IT skills of HCPs were selected according to predefined selection criteria. RESULTS: Data were extracted from 55 studies involving 6,304 HCPs who performed 9,996 tests to demonstrate their IT proficiency. Overall, the IT was considered correct in 15.5% of cases (95% confidence interval [CI], 12-19.3), decreasing over time from 20.5% (95% CI, 14.9-26.8) from the early period (defined as 1975-1995) to 10.8% (95% CI, 7.3-14.8) during the late period (1996-2014). The most common errors in the use of pMDIs were as follows: not breathing out completely before inhalation (75%; 95% CI, 56-90), lack of coordination (64%; 95% CI, 29-92), and postinhalation breath-hold (63%; 95% CI, 52-72). The most common errors using DPI were deficient preparation (89%; 95% CI, 82-95), not breathing out completely before inhalation (79%; 95% CI, 68-87), and no breath-hold (76%; 95% CI, 67-84). CONCLUSIONS: HCPs demonstrated inadequate knowledge of the proper use of inhalers. The poor understanding of the correct use of these devices may prevent these professionals from being able to adequately assess and teach proper inhalation techniques to their patients.

Identification of Pseudomonas aeruginosa and airway bacterial colonization by an electronic nose in bronchiectasis.

RATIONALE: Airway colonization by Potentially Pathogenic Microorganisms (PPM) in bronchiectasis is associated with worse clinical outcomes. The electronic nose is a non-invasive technology capable of distinguishing volatile organic compounds (VOC) in exhaled breath. We aim to explore if an electronic nose can reliably discriminate airway bacterial colonization in patients with bronchiectasis. METHODS: Seventy-three clinically stable bronchiectasis patients were included. PPM presence was determined using sputum culture. Exhaled breath was collected in Tedlar bags and VOC breath-prints were detected by the electronic nose Cyranose 320®. Raw data was reduced to three factors with principal component analysis. Univariate ANOVA followed by post-hoc least significant difference test was performed with these factors. Patients were then classified using linear canonical discriminant analysis. Cross-validation accuracy values were defined by the percentage of correctly classified patients. RESULTS: Forty-one (56%) patients were colonized with PPM. Pseudomonas aeruginosa (n = 27, 66%) and Haemophilus influenzae (n = 7, 17%) were the most common PPM. VOC breath-prints from colonized and non-colonized patients were significantly different (accuracy of 72%, AUROC 0.75, p < 0.001). VOC breath-prints from Pseudomonas aeruginosa colonized patients were significantly different from those of patients colonized with other PPM (accuracy of 89%, AUROC 0.97, p < 0.001) and non-colonized patients (accuracy 73%, AUROC 0.83, p = 0.007). CONCLUSIONS: An electronic nose can accurately identify VOC breath-prints of clinically stable bronchiectasis patients with airway bacterial colonization, especially in those with Pseudomonas aeruginosa.

Salivary immunity and lower respiratory tract infections in non-elite marathon runners.

RATIONALE: Respiratory infections are common after strenuous exercise, when salivary immunity may be altered. We aim to investigate changes in salivary immunity after a marathon and its relationship with lower respiratory tract infections (LRTI) in healthy non-elite marathon runners. METHODS: Forty seven healthy marathon runners (28 males and 19 females) who completed the 42.195 km of the 2016 Barcelona marathon were studied. Saliva and blood samples were collected the day before the marathon and two days after the end of the race. Salivary IgA, antimicrobial proteins (lactoferrin, lysozyme) and chemokines (Groα, Groß, MCP-1) were determined using ELISA kits in saliva supernatant. Blood biochemistry and haemogram were analyzed in all participants. The presence of LRTI was considered in those runners who reported infectious lower respiratory tract symptoms during a minimum of 3 consecutive days in the 2 weeks after the race. RESULTS: Eight participants (17%) presented a LRTI during the 2 weeks of follow-up. Higher lysozyme levels were detected after the race in runners with LRTI when compared with those without infection. A decrease in salivary lysozyme, Groα and Groß levels after the race were observed in those runners who did not develop a LRTI when compared to basal levels. Salivary Groα levels correlated with basophil blood counts, and salivary lysozyme levels correlated with leukocyte blood counts. CONCLUSIONS: LRTI are common after a marathon race in non-elite healthy runners. Changes in salivary antimicrobial proteins and chemokines are related to the presence of LRTI and correlate with systemic defense cells, which suggest an important role of salivary immunity in the development of LRTI in non-elite marathon runners.

Palliative Care in Diffuse Interstitial Lund Disease: Results of a Spanish Survey. / Cuidados paliativos en la enfermedad pulmonar intersticial difusa: resultados de una encuesta de ámbito nacional.

INTRODUCTION: Interstitial lung diseases (ILD) and, in particular, idiopathic pulmonary fibrosis, may have a significant impact on patient survival. Recent studies highlight the need for palliative care (PC) in the management of ILD patients. The aim of this study was to determine the current situation of PC in patients in Spain. METHODS: A 36-question survey addressing the main aspects of PC in ILD patients was designed. The survey was sent via email to all members of the Spanish Society of Pulmonology and Thoracic Surgery. Participation was voluntary. RESULTS: One hundred and sixty-four participants responded to the survey. Ninety-eight percent said they were interested in PC, 46% had received specific training, and 44% reported being responsible for PC in their ILD patients. Symptom control and end-of-life stage were the most frequent reasons for referral to PC teams. Regarding end-of-life, 78% reported consensual agreement with patients on the limitation of therapeutic efforts, 35% helped prepare an end-of-life advance directive, and 22% agreed on the place of death. CONCLUSION: Despite the well-known need for PC in patients with ILD and the notable interest of the survey participants in this subject, there are clear formative and organizational gaps that should be addressed to improve care in this area in ILD patients in Spain.

The MEGA Project: A Study of the Mechanisms Involved in the Genesis and Disease Course of Asthma. Asthma Cohort Creation and Long-Term Follow-Up. / Estudio de los mecanismos implicados en la génesis y evolución del asma (proyecto MEGA): creación y seguimiento a largo plazo de una cohorte de pacientes asmáticos.

The general aim of this study is to create a cohort of asthma patients with varying grades of severity in order to gain greater insight into the mechanisms underlying the genesis and course of this disease. The specific objectives focus on various studies, including imaging, lung function, inflammation, and bronchial hyperresponsiveness, to determine the relevant events that characterize the asthma population, the long-term parameters that can determine changes in the severity of patients, and the treatments that influence disease progression. The study will also seek to identify the causes of exacerbations and how this affects the course of the disease. Patients will be contacted via the outpatient clinics of the 8 participating institutions under the auspices of the Spanish Respiratory Diseases Networking System (CIBER). In the inclusion visit, a standardized clinical history will be obtained, a clinical examination, including blood pressure, body mass index, complete respiratory function tests, and FENO will be performed, and the Asthma Control Test (ACT), Morisky-Green test, Asthma Quality of Life Questionnaire (Mini AQLQ), the Sino-Nasal Outcome Test 22 (SNOT-22), and the Hospital Anxiety and Depression scale (HADS) will be administered. A specific electronic database has been designed for data collection. Exhaled breath condensate, urine and blood samples will also be collected. Non-specific bronchial hyperresponsiveness testing with methacholine will be performed and an induced sputum sample will be collected at the beginning of the study and every 24 months. A skin prick test for airborne allergens and a chest CT will be performed at the beginning of the study and repeated every 5 years.

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.