Transitions between COPD groups: A cross-sectional study in Turkey.

INTRODUCTION: Since GOLD 2017 separates spirometry results from 'ABCD' groups, there have been some changes to the stages of COPD patients. Our aim was to investigate the shifts in COPD groups after GOLD 2017. METHODS: COPD patients from outpatient clinics of 3 hospitals in Turkey were stratified into old and new ABCD groups according to exacerbation history, mMRC evaluation and spirometry results for both GOLD 2011 and 2017 assessments. Treatment protocols were also evaluated if they were suitable for both classifications. RESULTS: There were 578 patients (334 men, 244 women) with a mean age of 65.21±10.42. The distribution of patients from group A to D was 28%, 15%, 15%, 42% (GOLD 2011) and 36%, 22%, 7% and 35% (GOLD 2017) respectively. There were shifts from group C to A (53.4%) and D to B (18.4%). The treatment suitability was 66.3% in GOLD 2011 and 60.9% in GOLD 2017. The most common inappropriate treatment protocol was triple therapy. Presence of exacerbations in last year, mMRC score, FEV1 level (p < 0.01 for three parameters) and proportion of males (p = 0.029) were statistically significantly higher in groups C and D of GOLD 2017 compared with new patients in group A and B of GOLD 2017 (shifted from GOLD 2011's C-D groups). CONCLUSION: There were shifts from group C to A and D to B with GOLD 2017, which means some high-risk COPD patients were reclassified into low-risk groups. Despite guideline updates, there are still many COPD patients with overtreatment. To our knowledge, this is the first study examining transitions between COPD groups after GOLD 2017 in Turkey.

Plasma proteomics and lung function in four community-based cohorts.

BACKGROUND: Underlying mechanism leading to impaired lung function are incompletely understood. OBJECTIVES: To investigate whether protein profiling can provide novel insights into mechanisms leading to impaired lung function. METHODS: We used four community-based studies (n = 2552) to investigate associations between 79 cardiovascular/inflammatory proteins and forced expiratory volume in 1 s percent predicted (FEV1%) assessed by spirometry. We divided the cohorts into discovery and replication samples and used risk factor-adjusted linear regression corrected for multiple comparison (false discovery rate of 5%). We performed Mendelian randomization analyses using genetic and spirometry data from the UK Biobank (n = 421,986) to assess causality. MEASUREMENTS AND MAIN RESULTS: In cross-sectional analysis, 22 proteins were associated with lower FEV1% in both the discovery and replication sample, regardless of stratification by smoking status. The combined proteomic data cumulatively explained 5% of the variation in FEV1%. In longitudinal analyses (n = 681), higher plasma levels of growth differentiation factor 15 (GDF-15) and interleukin 6 (IL-6) predicted a more rapid 5-year decline in lung function (change in FEV1% per standard deviation of protein level -1.4, (95% CI, -2.5 to -0.3) for GDF-15, and -0.8, (95% CI, -1.5 to -0.2) for IL-6. Mendelian randomization analysis in UK-biobank provided support for a causal effect of increased GDF-15 levels and reduced FEV1%. CONCLUSIONS: Our combined approach identified GDF-15 as a potential causal factor in the development of impaired lung function in the general population. These findings encourage additional studies evaluating the role of GDF-15 as a causal factor for impaired lung function.

Pulmonary function of patients with 2019 novel coronavirus induced-pneumonia: a retrospective cohort study.

BACKGROUND: The aim of this study was to investigate the pulmonary function of patients with 2019 novel coronavirus (COVID-19)-induced pneumonia. METHODS: A retrospective analysis of 137 patients with COVID-19-induced pneumonia who were discharged from the Enze Hospital, Taizhou Enze Medical Center (Group) from January 31 2020 to March 11 2020 was conducted. Follow-up occurred 2 weeks after hospital discharge, during which patients underwent a pulmonary function test. RESULTS: Of the 137 patients who underwent a pulmonary function test 2 weeks after discharge, 51.8% were male, and the mean age was 47 years. Only 19.7% of the patients were identified as having severe COVID-19-induced pneumonia. The pulmonary function tests showed that for a small number of patients the forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC)/% values were <70%, and the mean forced inspiratory volume (IVC) and FVC values were 2.4±0.7 and 3.2±0.8 L, respectively. In severe cases, 88.9% of patients had an IVC <80% of the predicted value, and 55.6% of patients had an FVC <80% of the predicted value. The proportion of patients with maximum expiratory flow rate at 25%, 50% and 75% of the vital capacity (MEF25, MEF50, and MEF75) values <70% were 55.6%, 40.7%, and 25.9%, respectively. In the non-severe group, 79.1% of patients had an IVC <80% of the predicted value, and 16.4% of patients had an FVC <80% of the predicted value. The mean MEF25, MEF50, and MEF75 <70% values were 57.3%, 30%, and 13.6%, respectively. CONCLUSIONS: Our results demonstrated that the pulmonary function of patients with COVID-19-induced pneumonia predominantly manifested as restrictive ventilation disorder and small airway obstruction, which was increased in critically ill patients.

Maximum inspiratory and expiratory pressures in the pre and postoperative periods of patients with incisional abdominal hernia corrected by Lázaro da Silva technique.

OBJECTIVE: To verify the effect of longitudinal abdominal incisional herniorrhaphy on respiratory muscle pressure. METHOD: The technique of incisional herniorrhaphy used was proposed by Lázaro da Silva. To measure the pressure, we used a water manometer in 20 patients, median age 48.5 years (range 24 70). We analyzed the maximum inspiratory pressure at the level of residual volume (IP-RV) and functional residual capacity (IP-FRC) and the maximum expiratory pressure of functional residual capacity (EP-FRC) and total lung capacity (EP-TLC) in the preoperative and late postoperative (40 90 days) periods, in 13 patients with large incisional hernias and in 7 patients with medium incisional hernias. RESULTS: There was a significant increase in IP-FRC (p = 0.027), IP-RV (p = 0.011) and EP-TLC (p = 0.003) in patients with large incisional hernias. EP-FRC increased, but not significantly. In patients with medium incisional hernias, the changes were not significant. CONCLUSION: Surgical correction of large incisional hernias improves the function of the breathing muscles; however, surgery for medium incisional hernias does not alter this function.

Small airways in children with allergic rhinoconjunctivitis: the potential role of a multicomponent nutraceutical.

Allergic rhinitis and asthma are closely linked. A progression from rhinitis to overt asthma is common. FEF25-75 is a spirometry parameter that could reflect small airways patency and could reliably predict early bronchial involvement in allergic rhinitis patients. MEF50 very strongly correlates with FEF25-75. The aim of this study was to evaluate possible spirometry change in two groups of children suffering from AR over time. The first group took a course of a nutraceutical (Lertal®) before the observation (active group, AG); a second one was considered as control (control group, CG). The children were visited at baseline, at the end of the nutraceutical course, and after 1 year. FEV1, FVC, and MEF50 were the primary outcomes. After one year, children in AG had significantly higher MEF50 than CG children (p=0.009). In conclusion, the present study showed that a course with a multicomponent nutraceutical could prevent the MEF50 decline in children with allergic rhinoconjunctivitis.

Ratio of Maximal Inspiratory to Expiratory Flow Aids in the Separation of COPD from Asthma.

Patients who have chronic obstructive pulmonary disease (COPD) and bronchial asthma (BA) share symptoms such as, dyspnoea, cough and wheeze. Differentiating these diseases in the ambulatory setting can be challenging especially in older adult smokers who are being treated with a variety of medications. The objective of this study was to test the value of adding a maximal inspiratory manoeuvre to basic spirometry to differentiate COPD and BA. One hundred forty-three COPD patients and 142 BA patients had measurements of maximal inspiratory and expiratory flow during routine spirometry. Parameters from these tests were used to assess diagnostic accuracy using receiver-operating characteristic (ROC) analyses followed by logistic regression. The association of two independent parameters were analyzed using linear regression analyses. Results show that forced expiratory volume in one second/forced vital capacity (FEV1/FVC%) <62.4 was the best independent predictor to diagnose COPD. The combination of FEV1/FVC% <62.4 and the ratio of peak inspiratory flow/maximal expiratory flow at 50% FVC (PIF/MEF50) >3.06 significantly predicted COPD. Post-test probability for prediction of COPD was 82.0% when patients had both parameters. When asthmatic patients with a smoking history were compared with COPD patients, FEV1/FVC% <63.4 and PIF/MEF50 >3.29 were both independent predictors of COPD. The post-test probability for COPD was 94.4% when patients had both parameters. The association between FEV1/FVC% and PIF/MEF50 was significantly different between COPD and BA. In conclusion, the addition of the maximal inspiratory effort to routine pulmonary function measurements provides a simple test to help differentiate COPD and BA.

Age- and sex-dependent differences in patients with severe asthma included in the German Asthma Net cohort.

BACKGROUND: Severe asthma affects less than 5% of asthmatics, but is associated with high costs and increased mortality. The aim of this study was to assess age- and sex-dependent differences in this patient group. METHODS: Retrospective analysis of 1317 children and adults with severe asthma who are included in the German Asthma Net registry. RESULTS: There were more adults than children in the registry and patients' mean age was 52. Apart from children <18 years, there were more women (57%) than men. The age of first diagnosis ranged from 0 to 76 years. 38% of patients had a positive bronchial reversibility after short acting bronchodilators. Quality of life, FEV1 and MEF 25 decreased with older age whereas treatment with oral steroids and monoclonal antibodies increased. An anti-eosinophil treatment was most frequently used in patients aged around 57 years, while an anti-IgE treatment was used in all age-groups including children. There were sex-dependent differences with lower values in men for FEV1, FVC, MEF 25 and DLCO. Yet, women were more frequently unable to work than men due to the disease. CONCLUSION: In patients with severe asthma, clinical characteristics, but also treatments differed between age groups and between the sexes, reflecting different phenotypes of the disease.

Maximum inspiratory and expiratory pressures in the pre and postoperative periods of patients with incisional abdominal hernia corrected by Lázaro da Silva technique / Pressões máximas inspiratórias e expiratórias no pré e pós-operatório de pacientes com hérnias incisionais abdominais corrigidas pela técnica de Lázaro da Silva

ABSTRACT Objective: To verify the effect of longitudinal abdominal incisional herniorrhaphy on respiratory muscle pressure. Method: The technique of incisional herniorrhaphy used was proposed by Lázaro da Silva. To measure the pressure, we used a water manometer in 20 patients, median age 48.5 years (range 24 70). We analyzed the maximum inspiratory pressure at the level of residual volume (IP-RV) and functional residual capacity (IP-FRC) and the maximum expiratory pressure of functional residual capacity (EP-FRC) and total lung capacity (EP-TLC) in the preoperative and late postoperative (40 90 days) periods, in 13 patients with large incisional hernias and in 7 patients with medium incisional hernias. Results: There was a significant increase in IP-FRC (p = 0.027), IP-RV (p = 0.011) and EP-TLC (p = 0.003) in patients with large incisional hernias. EP-FRC increased, but not significantly. In patients with medium incisional hernias, the changes were not significant. Conclusion: Surgical correction of large incisional hernias improves the function of the breathing muscles; however, surgery for medium incisional hernias does not alter this function.

RESUMO Objetivo: verificar o efeito da herniorrafia incisional abdominal longitudinal na pressão dos músculos da respiração. Método: a técnica de herniorrafia incisional utilizada foi a proposta por Lázaro da Silva. Para aferir a pressão foi utilizado manômetro de água, em 20 pacientes, idade mediana 48,5 anos (mínimo 24, máximo 70). Foram analisadas a pressão máxima inspiratória no nível do volume residual (PIVR) e da capacidade residual funcional (PICRF) e a pressão máxima expiratória da capacidade residual funcional (PECRF) e da capacidade pulmonar total (PECPT), no pré-operatório e pós-operatório tardio (entre 40 e 90 dias), em 13 pacientes com hérnias incisionais grandes e em 7 pacientes com hérnias incisionais médias. Resultados: houve aumento significante da PICRF (p=0.027), da PIVR (p=0.011), da PECPT (p=0.003) nos pacientes com hérnias incisionais grandes. A PECRF aumentou, porém de forma não significante. Nos pacientes com hérnias incisionais médias as alterações não foram significantes. Conclusão: a correção cirúrgica da hérnia incisional grande melhora a função dos músculos da respiração, porém a cirurgia da hérnia incisional média não altera a referida função.

Surfactant delivery in rat lungs: Comparing 3D geometrical simulation model with experimental instillation.

Surfactant Replacement Therapy (SRT), which involves instillation of a liquid-surfactant mixture directly into the lung airway tree, is a major therapeutic treatment in neonatal patients with respiratory distress syndrome (RDS). This procedure has proved to be remarkably effective in premature newborns, inducing a five-fold decrease of mortality in the past 35 years. Disappointingly, its use in adults for treating acute respiratory distress syndrome (ARDS) experienced initial success followed by failures. Our recently developed numerical model has demonstrated that transition from success to failure of SRT in adults could, in fact, have a fluid mechanical origin that is potentially reversible. Here, we present the first numerical simulations of surfactant delivery into a realistic asymmetric conducting airway tree of the rat lung and compare them with experimental results. The roles of dose volume (VD), flow rate, and multiple aliquot delivery are investigated. We find that our simulations of surfactant delivery in rat lungs are in good agreement with our experimental data. In particular, we show that the monopodial architecture of the rat airway tree plays a major role in surfactant delivery, contributing to the poor homogeneity of the end distribution of surfactant. In addition, we observe that increasing VD increases the amount of surfactant delivered to the acini after losing a portion to coating the involved airways, the coating cost volume, VCC. Finally, we quantitatively assess the improvement resulting from a multiple aliquot delivery, a method sometimes employed clinically, and find that a much larger fraction of surfactant reaches the alveolar regions in this case. This is the first direct qualitative and quantitative comparison of our numerical model with experimental studies, which enhances our previous predictions in adults and neonates while providing a tool for predicting, engineering, and optimizing patient-specific surfactant delivery in complex situations.

Analysis of maximal expiratory flow-volume curves in adult survivors of preterm birth.

Adult survivors of very preterm (≤32 wk gestational age) birth without (PRE) and with bronchopulmonary dysplasia (BPD) have variable degrees of airflow obstruction at rest. Assessment of the shape of the maximal expiratory flow-volume (MEFV) curve in PRE and BPD may provide information concerning their unique pattern of airflow obstruction. The purposes of the present study were to 1) quantitatively assess the shape of the MEFV curve in PRE, BPD, and healthy adults born at full-term (CON), 2) identify where along the MEFV curve differences in shape existed between groups, and 3) determine the association between an index of MEFV curve shape and characteristics of preterm birth (i.e., gestational age, mass at birth, duration of oxygen therapy) in PRE and BPD. To do so, we calculated the average slope ratio (SR) throughout the effort-independent portion of the MEFV curve and at increments of 5% of forced vital capacity (FVC) between 20 and 80% of FVC in PRE (n = 19), BPD (n = 25), and CON (n = 20). We found that average SR was significantly higher in PRE (1.34 ± 0.35) and BPD (1.33 ± 0.45) compared with CON (1.03 ± 0.22; both P < 0.05) but similar between PRE and BPD (P = 0.99). Differences in SR between groups occurred early in expiration (i.e., 20-30% of FVC). There was no association between SR and characteristics of preterm birth in PRE and BPD groups (all P > 0.05). The mechanism(s) of increased SR during early expiration in PRE/BPD relative to CON is unknown but may be due to differences in the structural and mechanical properties of the airways.

Long-term observational study on the impact of GLP-1R agonists on lung function in diabetic patients.

INTRODUCTION: Preclinical research suggests a role of Glucagon Like Peptide-1 Receptors (GLP-1R) on the regulation of human bronchial tone. We investigated the effect of GLP-1R agonists on lung function of Type 2 Diabetes Mellitus (T2DM) population without co-existing chronic obstructive respiratory disorders. METHODS: This was a prospective cohort study that examined change in lung function measurements over two years of T2DM patients (n = 32) treated with metformin monotherapy (control cohort), metformin plus GLP-1R agonists (GLP-1R agonists cohort), or metformin plus insulin (insulin cohort). RESULTS: After 24 months of treatment, the forced expiratory volume in 1 s (FEV1) significantly (p < 0.05) increased from baseline in the GLP-1R agonists cohort (218 ml [95%CI 88-246]), but not in the control and insulin cohorts (94 ml [95%CI -28 - 216] and 26 ml [95%CI -174 - 226], respectively; p > 0.05 vs. baseline). The average increase in FEV1 in the GLP-1R agonists cohort was significantly greater than that in the control and insulin cohorts (delta: 110 ml [95%CI 18-202] and 177 ml [95%CI 85-270], respectively, p < 0.05). The forced vital capacity (FVC) also increased significantly more in the GLP-1R agonists cohort than in the control and insulin cohorts (overall delta FVC: 183 ml [95%CI 72-295], p < 0.05). The maximal expiratory flow at 50-75% significantly (p < 0.05) improved from baseline in the GLP-1R agonists cohort, but not in the control and insulin cohorts (p > 0.05). CONCLUSION: Our preliminary results suggest a potential new therapeutic perspective to treat airway disorders with GLP-1R agonists.

Distinctive lung function trajectories from age 10 to 26 years in men and women and associated early life risk factors - a birth cohort study.

Pre-bronchodilator lung function including forced vital capacity (FVC), forced expiratory flow in 1 second (FEV1), their ratio (FEV1/FVC), and forced expiratory flow 25-75% (FEF25-75) measured at age 10, 18, and 26 years in the Isle of Wight birth cohort was analyzed for developmental patterns (trajectories). Early life risk factors before the age of 10 years were assessed for the trajectories. METHOD: Members of the birth cohort (1989/90) were followed at age 1, 2, 4, 10, 18, and 26 years. Allergic sensitization and questionnaire data were collected. Spirometry tests were performed and evaluated according to the American Thoracic Society (ATS) criteria at 10, 18, and 26 years. To identify developmental trajectories for FVC, FEV1, FEV1/FVC, and FEF25-75 from 10 to 26 years, a finite mixture model was applied to the longitudinal lung function data, separately for males and females. Associations of early life factors with the respective lung function trajectories were assessed using log-linear and logistic regression analyses. RESULTS: Both high and low lung function trajectories were observed in men and women. FVC continued to grow beyond 18 years in men and women, whereas FEV1 peaked at age 18 years in female trajectories and in one male trajectory. For the FEV1/FVC ratios and FEF25-75 most trajectories appeared highest at age 18 and declined thereafter. However, the low FEV1/FVC trajectory in both sexes showed an early decline at 10 years. Lower birth weight was linked with lower lung function trajectories in males and females. Eczema in the first year of life was a risk factor for later lung function deficits in females, whereas the occurrence of asthma at 4 years of age was a risk factor for later lung function deficits in males. A positive skin prick test at age four was a risk for the low FEV1 trajectory in females and for the low FEV1/FVC trajectory in males. CONCLUSION: Men and women showed distinctive lung function trajectories and associated risk factors. Lower lung function trajectories can be explained by not achieving maximally attainable function at age 18 years and by a function decline from 18 to 26 years.

Asociación entre deterioro del flujo espiratorio máximo y prevalencia de enfermedades cardiovasculares y metabólicas en población adulta chilena: hallazgos preliminares de la Cohorte del Maule (MAUCO) / Peak expiratory flow and prevalence of cardiovascular and metabolic diseases in a Chilean adult population: preliminary findings from the Maule Cohort (MAUCO)

Introducción: La enfermedad respiratoria crónica determina alta morbimortalidad y frecuencia de comorbilidades cardiometabólicas. Evaluamos la asociación entre flujo espiratorio máximo (FEM) y algunas condiciones cardiometabólicas en adultos de una zona semirural, en la medición basal de la cohorte MAUCO (MAUle COhort). Material y Método: Estudio transversal (3.465 adultos, 40-74 años). Se midió el flujo espiratorio máximo (FEM) (mini-Wright, estándar ATS) utilizándose valores de Gregg y Nunn (FEM deteriorado ≤ 80% del teórico). Se obtuvo autorreporte/mediciones de hipertensión arterial (HTA), enfermedad cerebrovascular (ECV), infarto al miocardio (IAM), diabetes mellitus 2 (DM2), presión arterial, glicemia, colesterol, peso y talla. Actividad física y tabaquismo se evaluaron por encuesta, previa aprobación Ética. Se calcularon medidas de asociación, prevalencia y Odds Ratio (OR). Resultados: Muestra de 63,9% de mujeres edad media 55 (± 9) años, escolaridad media 9 (± 4) años. 84,7% tuvo exceso de peso, 81,5% inactividad física 29,4% fumadores actuales. Prevalencia de FEM bajo: 50,6% (IC 95% 48,9-52,3). El autorreporte fue: ACV 2,2% IAM 3,3, sospecha de hipertensión 24% y DM2 2,7%. Los OR crudos fueron significativos en mujeres que autorreportaron HTA, ECV, IAM y autorreporte/sospecha de DM2, y en hombres con autorreporte de ECV, sospecha de DM2 y autorreporte/sospecha de HTA. La asociación se mantuvo post-ajuste en mujeres para autorreporte de IAM y deterioro moderado (OR = 2,49) y severo del FEM (OR = 2,60) y en hombres para sospecha de DM2 y deterioro leve (OR = 5,24) y severo del FEM (OR = 6,19). Conclusiones: FEM resultó significativamente asociado con las enfermedades cardiometabólicas seleccionadas, con efecto sexo- específico para IAM (mujeres) y sospecha de DM2 (hombres). Se constata alta prevalencia de FEM alterado, y de enfermedades cardiometabólicas crónicas en la población estudiada.

Introduction: Chronic respiratory diseases determine high morbimortality and cardiometabolic comorbidities. We evaluated the association between peak expiratory flow (PEF) and cardiometabolic conditions in adults in a semi-rural area, in the baseline of MAUCO cohort (MAUle COhort). Material and Method: Cross-sectional study (3,465 adults, 40-74 years). Peak expiratory flow (PEF) (mini-Wright, ATS standard) was measured (Gregg & Nunn; impaired PEF ≤ 80% predicted). Self-reported/measured hypertension (HT), cerebrovascular disease (CVD), myocardial infarction (AMI), diabetes mellitus 2 (DM2), blood pressure, glycemia, cholesterol, weight and height were obtained. Physical activity and smoking were surveyed, after Ethical approval. Association's measures, prevalence and Odds Ratio (OR) were calculated. Results: Sample of 63.9% of women, mean age 55 (± 9) years, schooling 9 (± 4) years. 84.7% had overweight, 81.5%physical inactivity 29.4% smokers. Low PEF: 50.6% (48.9-52.3). Self-reported was: CVD 2.2% AMI 3.3%, suspicion of hypertension 24% and DM2 2.7%. Crude OR`s were significant for women by self-reported hypertension, stroke, AMI and self-reported/suspicion DM2; in men for self-reported CVD, suspected DM2 and self-reported/suspected hypertension. The association remained post-adjusted in women self-reported AMI -moderate deterioration (OR = 2.49) and severe PEF (OR = 2.60) and in men suspected DM2 and mild (OR = 5.24) and severe deteriorated PEF (OR = 6.19). Conclusions: PEF was significantly associated with cardiometabolic diseases; sex- specific findings for AMI (women) and suspicion of DM2 (men). High prevalence of altered PEF and chronic cardiometabolic diseases were detected among the studied population.

Impact of burn contractures of chest wall and their surgical release on pulmonary function.

BACKGROUND: Extensive burn scars and contractures are likely to restrict the movements of the chest wall which may affect the pulmonary ventilation by restricting its expansion during inspiration. We designed this study to evaluate the effect of burn contractures of chest wall on pulmonary function and to estimate the effect of contracture release on pulmonary functions in patients with compromised PFT. METHODS: Pulmonary function tests (PFT) of 20 patients having chest wall contractures involving more than 50% of the chest circumference were studied. Restrictive lung disease was defined as forced vital capacity (FVC) value less than 80% of predicted normal for the age, weight, and height of that patient. Patients with a restrictive pattern on PFT were subjected to the surgical release of the contracture. PFT was repeated one month after the surgery which was compared with the initial report. RESULTS: Of the 20 patients included in the study, 5 (25%) patients had a restriction pattern on PFT. 1 patient had a mild restriction, 2 patients had moderate restriction and 2 patients had a severe restriction of pulmonary function. The mean duration of contracture was 58.2±15.75months in patients with a pulmonary restriction as compared to 29.87±6.21months in patients with a normal PFT (p=0.001). All patients having a restrictive pattern on PFT had contracture involvement of >75% of the chest wall circumference (p=0.0036). The mean forced vital capacity (FVC) increased from 1.94L preoperatively to 2.11L after surgical release of the contracture (p=0.047). However, the restriction pattern in PFT did remain. CONCLUSION: Long standing chest wall contractures and contractures involving >75% of the chest circumference are likely to cause a restrictive pattern on PFT. Any significant improvement of pulmonary function after surgical release of the contracture is unlikely.

Chemically modified hCFTR mRNAs recuperate lung function in a mouse model of cystic fibrosis.

Gene therapy has always been a promising therapeutic approach for Cystic Fibrosis (CF). However, numerous trials using DNA or viral vectors encoding the correct protein resulted in a general low efficacy. In the last years, chemically modified messenger RNA (cmRNA) has been proven to be a highly potent, pulmonary drug. Consequently, we first explored the expression, function and immunogenicity of human (h)CFTR encoded by cmRNAhCFTR in vitro and ex vivo, quantified the expression by flow cytometry, determined its function using a YFP based assay and checked the immune response in human whole blood. Similarly, we examined the function of cmRNAhCFTR in vivo after intratracheal (i.t.) or intravenous (i.v.) injection of the assembled cmRNAhCFTR together with Chitosan-coated PLGA (poly-D, L-lactide-co-glycolide 75:25 (Resomer RG 752 H)) nanoparticles (NPs) by FlexiVent. The amount of expression of human hCFTR encoded by cmRNAhCFTR was quantified by hCFTR ELISA, and cmRNAhCFTR values were assessed by RT-qPCR. Thereby, we observed a significant improvement of lung function, especially in regards to FEV0.1, suggesting NP-cmRNAhCFTR as promising therapeutic option for CF patients independent of their CFTR genotype.

Propuesta de ecuaciones predictivas de capacidad inspiratoria y flujo espiratorio máximo considerando mediciones torácicas: un estudio piloto / Proposal of predictive equations of inspiratory capacity and maximum spiratory flow considering thoracic measurements: a pilot study

RESUMEN: El objetivo del siguiente estudio fue determinar si las mediciones de tórax provocan modificaciones en las ecuaciones predictivas de capacidad inspiratoria (CI) y flujo espiratorio máximo (FEM). Se evaluaron 24 sujetos de sexo masculino entre 18 y 26 años, todos estudiantes sedentarios de la Universidad Católica del Maule, Chile. Se les realizó antropometría corporal básica (peso y talla corporal) y específica de tórax, diámetro antero-posterior (DAT) y transverso (DTT) de tórax y perímetro mesoesternal (PME). Posterior a esto, se evaluó la función ventilatoria a través de pletismografía corporal. Para estimar las ecuaciones de regresión lineal se utilizó el método de mínimos cuadrados relacionando la CI y FEM. La comparación entre el valor predicho establecido y nuestra propuesta fue comparado utilizando la prueba t de student o U de Mann-Whitney según correspondiera, considerándose un nivel de significancia estadística de p<0,05. Los resultados indican que para la propuesta de la ecuación de FEM se consideró el DTT y PME, logrando diferencias significativas con los valores de Knudson et al. Por tanto, se concluye que las mediciones de DTT a VR y PME a CPT influyeron en la ecuación predictiva de FEM en estudiantes sedentarios.

SUMMARY: The aim of the following study was to determine if chest measurements cause changes in the predictive equations of inspiratory capacity (IC) and peak expiratory flow (PEF). Twenty- four male subjects between 18 and 26 years old, all sedentary students of the Universidad Catolica del Maule, Chile, were evaluated. They were subjected to basic body anthropometry (weight and body size) and chest specificity, anteroposterior diameter (APD) and transverse (TTD) of the thorax and mesosternal perimeter (MSP). After this, the ventilatory function was evaluated through body plethysmography. To estimate the linear regression equations, the least squares method were used, relating IC and PEF. The comparison between the established predicted value and our proposal was compared using the student t-test or Mann-Whitney U test as appropriate, considering a level of statistical significance of p <0.05. The results indicate that the TTD and MSP were considered for the proposal of the PEF equation, achieving significant differences with the values o f Knudson et al. Therefore, it is concluded that measurements of TTD to RV and MSP to TPC influenced the predictive equation of PEF in sedentary students.

Pulmonary function in patients with eosinophilic chronic rhinosinusitis.

OBJECTIVE: There is a close relationship between upper and lower respiratory tract diseases. Chronic rhinosinusitis patients frequently have lung diseases including asthma and chronic obstructive pulmonary disease. Eosinophilic chronic rhinosinusitis is considered a refractory and intractable subtype of chronic rhinosinusitis. However, there has been no report on pulmonary function in patients with eosinophilic chronic rhinosinusitis. The purpose of this study is to examine the pulmonary function in eosinophilic chronic rhinosinusitis patients and non-eosinophilic chronic rhinosinusitis patients, and evaluate clinical factors associated with the pulmonary function of these patients. METHODS: Pulmonary function was measured in 53 patients with eosinophilic chronic rhinosinusitis with asthma, 58 patients with eosinophilic chronic rhinosinusitis without asthma, and 30 patients with non-eosinophilic chronic rhinosinusitis. The diagnosis of chronic rhinosinusitis was based on the definition in the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2012. Eosinophilic chronic rhinosinusitis was diagnosed based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scoring system. The relationship between pulmonary function and clinical parameters was assessed. These parameters included radiographic severity of chronic rhinosinusitis, peripheral blood eosinophil percentage, serum total immunoglobulin E level, and eosinophilic infiltration in nasal polyps. RESULTS: The pulmonary function of the patients with eosinophilic chronic rhinosinusitis was significantly affected. The eosinophilic chronic rhinosinusitis patients had more peripheral airway obstruction as compared to the patients with non-eosinophilic chronic rhinosinusitis. CONCLUSION: Our findings indicated latent obstructive lung function changes in the eosinophilic chronic rhinosinusitis patients. The patients with eosinophilic chronic rhinosinusitis should be carefully monitored in order to detect lung diseases.

Flujo espiratorio máximo: caracterización en un estudio en población adulta chilena; resultados basales de la cohorte del Maule (MAUCO) / Peak expiratory flow rate: characterization study in Chilean adult population; baseline results of the Maule cohort (MAUCO)

Resumen Introducción: Las enfermedades respiratorias crónicas tienen alta prevalencia en países en desarrollo, en poblaciones rurales y deprivadas. El flujo espiratorio máximo (FEM) obtenido mediante espiración forzada tiene uso clínico y de investigación. Describimos valores de medición del FEM en la medición basal de un estudio de cohorte en curso (Cohorte del Maule-MAUCO). Material y Método: Diseño transversal en 3.465 adultos (40-74 años) con registros de FEM (ATS). (Flujómetro Mini-Wright), usando valores de Gregg y Nunn. Valores < 80% del predicho se consideraron disminuidos. Se obtuvo sexo, edad, nivel educacional, actividad física y tabaquismo; se calculó índice de masa corporal (IMC) usando mediciones antropométricas. Resultados: La muestra tuvo 63,9% de mujeres; edad media de 55 (± 9) años, escolaridad de 9 (± 4) años; sobrepeso y obesidad fueron 43,1% y 41,5%: 81,5% fueron inactivos y 29,4% fumadores actuales. El valor medio de FEM fue 330 (± 80) L/min (mujeres) y 460 (± 119) L/min (hombres): el FEM disminuido alcanzó el 50,6% ([48,9-52,3]) con diferencias según edad, educación, IMC y actividad física. Conclusiones: Se observó alta prevalencia de FEM disminuido con variaciones según sexo, edad, escolaridad, IMC e inactividad física. Como otros estudios latinoamericanos, los valores bajos también fueron altamente prevalentes, sugiriendo sobreestimación de valores predichos al usar valores de Gregg & Nunn. Estos resultados sugieren la conveniencia de estudiar factores ambientales locales.

Introduction: Chronic respiratory (CRD) diseases show high prevalence in developing countries, rural and deprived populations. Peak expiratory flow rate (PEFR) is a functional measurement obtained through forced expiratory used for clinical and research purposes. We described PEFR in a rural setting in an ongoing cohort study (Maule Cohort-MAUCO). Material and Method: Cross-sectional design in 3,465 adults (40-74 years) with PEFR ATS standard records (Mini-Wright flowmeter) using Gregg and Nunn values. PEFR ≤ 80% predicted were considered decreased. Sex, age, educational level, physical activity and tobacco smoking were obtained. Body mass index (BMI) was calculated based on anthropometrical measurements. Main Results: Sample had 63.9% of women; mean age of 55 (± 9) years, schooling of 9 (± 4) years. Overweight and obesity were 43.1% and 41.5%. Physical inactivity was 81.5% and 29.4% were current smokers. PEFR mean value was 330 (± 80) L/min (women) and 460 (± 119) L/min (men): Decreased PEFR was 50.6% ([48.9-52.3]) with significant differences by age, schooling, BMI and physical activity. Conclusions: High prevalence of decreased PEFR was observed: PEFR showed variations according to sex, age, schooling, BMI and physical activity. As other Latin-American studies show, low values were also highly prevalent, suggesting that Gregg & Nunn overestimated PEFR values. These results suggests the convenience of studying local environmental factors.

A 28-day, randomized, double-blind, placebo-controlled, parallel group study of nebulized revefenacin in patients with chronic obstructive pulmonary disease.

BACKGROUND: Revefenacin is a once-daily long-acting muscarinic antagonist (LAMA) in clinical development for the treatment of patients with chronic obstructive pulmonary disease (COPD). In a dose-ranging study, nebulized once-daily revefenacin had a long duration of action in patients after 7 days' administration of doses up to 700 µg. In this multiple-dose study, the bronchodilation efficacy and adverse events profile were characterized in patients administered nebulized revefenacin once daily for 28 days. METHODS: A total of 355 COPD patients (mean age 62 years, mean forced expiratory volume in 1 s [FEV1] 44% of predicted) were randomized in a double-blind, placebo-controlled parallel group study. Inhaled corticosteroids as well as short-acting bronchodilators were permitted. Once-daily treatments (44, 88, 175 or 350 µg revefenacin or matching placebo) were administered by a standard jet nebulizer, for 28 days. The primary endpoint was change from baseline in D28 trough FEV1, and secondary endpoints included weighted mean FEV1 over 0 to 24 h and rescue medication (albuterol) use. Safety evaluations included adverse events, laboratory assessments, electrocardiograms and 24-h Holter profiles. RESULTS: Revefenacin (88, 175 and 350 µg) significantly improved D28 trough FEV1 over placebo (187.4, 166.6 and 170.6 mL, respectively, all p < 0.001); 44 µg produced a sub-therapeutic response. At doses ≥88 µg, more than 80% of patients achieved at least a 100-mL increase from baseline FEV1 in the first 4 h post dose compared with 33% of placebo patients. For doses ≥88 µg, D28 24 h weighted mean differences from placebo for FEV1 were numerically similar to respective trough FEV1 values, indicating bronchodilation was sustained for 24 h post dose. Doses ≥88 µg reduced the average number of albuterol puffs/day by more than one puff/day. The 350 µg dose did not demonstrate additional efficacy over that observed with 175 µg revefenacin. Revefenacin was generally well tolerated, with minimal reports of systemic anti-cholinergic effects. CONCLUSIONS: These data suggest that 88 and 175 µg revefenacin are appropriate doses for use in longer-term safety and efficacy trials. Revefenacin offers the potential for the first once-daily LAMA for nebulization in patients with COPD who require or prefer a nebulized drug delivery option. TRIAL REGISTRATION: ClinicalTrials.gov NCT02040792 . Registered January 16, 2014.